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Documenti di Professioni
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CHEMISTRY
SECOND EDITION
BHUPINDER MEHTA
Associate Professor
Department of Chemistry
Swami Shraddhanand College
University of Delhi
and
MANJU MEHTA
Associate Professor
Department of Chemistry
Maitreyi College
University of Delhi
ORGANIC CHEMISTRY, Second Edition
Bhupinder Mehta and Manju Mehta
© 2015 by PHI Learning Private Limited, Delhi. All rights reserved. No part of this book may be
reproduced in any form, by mimeograph or any other means, without permission in writing from the
publisher.
ISBN-978-81-203-5126-4
The export rights of this book are vested solely with the publisher.
Published by Asoke K. Ghosh, PHI Learning Private Limited, Rimjhim House, 111, Patparganj
Industrial Estate, Delhi-110092 and Printed by Mohan Makhijani at Rekha Printers Private Limited,
New Delhi-110020.
To all our Family Members for their affection
and
our loving
daughter Ananta and son Sarthak
for being patient and supportive
Table of Contents
Preface
About the Cover Image
Acknowledgements
About the Authors
What This Book Is About
1. Organic Molecules: Structure, Bonding and Properties
1.1 ORGANIC CHEMISTRY—An introduction
1.2 Electronic structure and chemical bonding in organic compounds
1.3 LEWIS STRUCTURE and Chemical Bonds
1.3.1 Electronegativity
1.3.2 Ionic Bond
1.3.3 Covalent Bond
1.3.4 Atomic Radius, van der Waals Radius, Bond Length, and Bond
Angle
1.3.5 Formal Charge
1.3.6 Bond Polarity and Dipole Moment
1.4 Concept of Hybridization and Covalent Bonding
1.4.1 sp3 Hybridization
1.4.2 sp2 Hybridization
1.4.3 sp Hybridization
1.5 Writing the structural Formula for Organic Molecules
1.6 CONCEPT OF RESONANCE (Mesomerism)
1.7 INTERMOLECULAR FORCES (van der Waals Forces)
1.7.1 Melting Point and Boiling Point
1.8 Purification and Identification of Organic Compounds
1.9 Classification of Organic Compounds
1.10 ISOMERISM in Organic Molecules
1.10.1 Constitutional Isomers (Formerly Structural Isomers)
1.10.2 Resonance versus Tautomerism
1.11 ACIDS AND BASES
1.11.1 Bronsted and Lowry Definition
1.11.2 Lewis Definition
Exercises**
Answers to selected exercises
2. IUPAC Nomenclature of Organic Compounds
2.1 Introduction
2.2 IUPAC Nomenclature
2.2.1 Rules for Naming the Organic Compounds
2.3 Selected Examples Of Monofunctional And Polyfunctional
Organic Compounds
2.3.1 Writing the Structure of an Organic Compound from its IUPAC
Name
2.4 COMMON ERRORS IN WRITING IUPAC NAMES
Exercises*
Answers
3. Stereochemistry
3.1 INTRODUCTION
3.2 Configurational Isomerism
3.2.1 Concept of Chirality [Asymmetry]
3.2.2 Chirality in Organic Molecules: Enantiomers and
Diastereoisomers
3.2.3 Fischer Projection
3.2.4 Number of Stereoisomers of a Compound
3.3 Optical Activity
3.4 Absolute Configuration (R And S Configuration)
3.4.1 Assigning R and S Configuration
3.4.2 Relative Configuration (D- and L- Nomenclature)
3.4.3 Chirality in a Molecule with no Stereogenic (Chiral) Centre
3.5 GEOMETRICAL ISOMERISM
3.6 CONFORMATIONS
3.6.1 Conformations of Ethane
3.6.2 Conformations of Propane
3.6.3 Conformations of Butane
3.7 cycloalkanes: conformations and Geometrical Isomerism
3.7.1 Conformations of Cyclohexane
3.7.2 Conformations of Monosubstituted Cyclohexane
3.7.3 Conformations of Disubstituted Cyclohexane
Answers to selected exercises
4. Fundamentals of Organic Reactions
4.1 Electronic Displacements
4.1.1 Inductive Effect
4.1.2 Electromeric Effect
4.1.3 Resonance Effect [or Mesomeric Effect]
4.1.4 Hyperconjugation (No bond resonance)
4.2 REACTIVE INTERMEDIATES
4.2.1 Carbocations
4.2.2 Carbanions
4.2.3 Free Radicals
4.2.4 Carbene
4.2.5 Nitrene
4.3 ReAgent Types
4.3.1 Electrophiles and Nucleophiles
4.4 Types of Reactions
4.5 CHEMICAL ENERGETICS
4.5.1 Thermodynamics and Kinetics of Chemical Reactions
4.5.2 Chemical Equilibrium
4.5.3 Rate of Reaction
4.5.4 Energy Diagrams (or Energy Profile) of Chemical Reactions
4.6 STERIC EFFECT
4.7 Solvents in Organic Reactions
4.8 Organic Compounds as Acid and Bases
EXeRCISES
EXPLORE MORE (Set-I)
5. lkanes and Cycloalkanes
5A.1 Introduction
5A.1.1 Physical Properties
5a.2 Preparation of Alkanes
5A.2.1 Catalytic Hydrogenation of Alkenes and Alkynes
5A.2.2 From Haloalkanes (Alkyl halides)
5A.2.3 From Carbonyl Compounds (Aldehydes and ketones)
5A.2.4 From Sodium Salt of Carboxylic Acids
5A.3 Chemical Properties of Alkanes
5A.3.1 Halogenation
5A.3.2 Nitration
5A.3.3 Sulfonation
5A.3.4 Chlorosulfonation
5A.3.5 Oxidation Reactions
5A.3.6 Other Reactions
5A.4 Petroleum
5A.4.1 Petrochemicals
5A.4.2 Coal
5B.1 Introduction
5B.2 Strain in Ring Compounds: Baeyer’s Strain Theory
5B.3 Preparation of Cycloalkanes
5B.4 Chemical Properties Of Cycloalkanes
5B.4.1 Halogenation
5B.4.2 Catalytic Hydrogenation
5B.4.3 Effect of Heat
5B.4.4 Reaction with Hydrogen Halides
Selected Solved Examples
Exercises
6. Alkenes
6.1 Introduction
6.1.1 Physical Properties
6.2 Preparation Of Alkenes
6.2.1 Reduction of Alkynes: Formation of cis and trans Alkenes
6.2.2 Elimination Reactions [Saytzeff’s and Hofmann’s rule]
6.2.3 Other Methods
6.3 Chemical Properties of Alkenes
6.3.1 Stability of Alkenes
6.3.2 Electrophilic Addition Reactions
6.3.3 Free Radical Addition Reaction
6.3.4 Oxidation Reactions
6.3.5 Allylic Substitution Reactions
6.3.6 Polymerization
Selected Solved Examples
EXERCISES
7. Alkadienes
7.1 Introduction
7.2 Buta-1,3-Diene
7.2.1 Molecular Orbital Picture of Buta-1,3-diene
7.3 Preparation of Buta-1,3-diene
7.4 Chemical Properties of Buta-1,3-diene
7.4.1 Electrophilic Addition Reactions
7.4.2 Free Radical Addition Reactions
7.4.3 Diels–Alder Reaction [Cycloaddition Reaction]
7.4.4 Reduction and Oxidation Reactions
7.4.5 Polymerization
7.5 Isoprene (2-MethylButa-1,3-diene)
7.5.1 Preparation
7.5.2 Chemical Properties
7.6 Chloroprene (2-chlorobuta-1,3-diene)
Exercises
8. Alkynes
8.1 Introduction
8.1.1 Physical Properties
8.2 PREPARATION OF ALKYNES
8.3 CHEMICAL PROPERTIES OF ALKYNES
8.3.1 Addition of Hydrogen
8.3.2 Electrophilic Addition Reactions
8.3.3 Nucleophilic Addition Reactions
8.3.4 Reactions Involving Acetylenic Hydrogens
8.3.5 Polymerization Reactions
8.3.6 Isomerization (Acetylene Allene Rearrangement)
8.3.7 Oxidation Reactions
Selected Solved Examples
EXERCISES
9. Concepts of Aromaticity, Benzene and its Derivatives
A. Concepts of Aromaticity
9A.2 STRUCTURE OF BENZENE
9A.2.1 Kekule Structure
9A.2.2 Resonance Structure
9A.2.3 Orbital Picture of Benzene
9A.3 RESONANCE ENERGY: STABILITY OF BENZENE
9A.4 HUCKEL’S RULE AND AROMATICITY
9A.5 Aromaticity in BENZENE AND other CYCLIC systems
9A.5.1 Aromaticity and the Three Membered Ring Systems
9A.5.2 Aromaticity and Four Membered Ring Systems
9A.5.3 Aromaticity and Five Membered Ring Systems
9A.5.4 Aromaticity and Six Membered Ring Systems
9A.5.5 Aromaticity and Seven Membered Ring Systems
9A.5.6 Aromaticity and Eight Membered Ring Systems
9A.5.7 Aromaticity and Annulenes
9A.5.8 Aromaticity and Other Ring Systems
B. Benzene and its Derivatives
9B.1.1 Coal Tar: Source of Aromatic Hydrocarbons
9B.2 Nomenclature of aromatic compounds
9B.3 Physical properties of aromatic hydrocarbons
9B.4 PREPARATIONS AND CHEMICAL PROPERTIES OF
BENZENE
9B.4.1 Preparations
9B.4.2 Chemical Properties
9B.5 ARENES: Methylbenzene (Toluene) and styrene
9B.5.1 Methylbenzene
9B.5.2 Styrene
Selected Solved Examples
EXERCISES
10. Aromatic Electrophilic Substitution Reactions—Mechanism,
Orientation and Reactivity
10.1 INTRODUCTION
10.2 Mechanism Of Electrophilic Substitution Reactions Of Benzene
10.2.1 Halogenation
10.2.2 Nitration
10.2.3 Friedel–Crafts Alkylation
10.2.4 Friedel–Crafts Acylation
10.2.5 Sulfonation
10.3 ORIENTATION AND REACTIVITY IN Monosubstituted
Benzene: EFFECT OF SUBSTITUENTS ON ELECTROPHILIC
SUBSTITUTION REACTIONS
10.3.1 Nature of Groups
10.3.2 Effect of Group on the Reactivity
10.3.3 Effect of Groups on Orientation
10.4 ORIENTATION IN DISUBSTITUTED BENZENE
Selected Solved Examples
EXERCISES
EXPLORE MORE (Set-II)
11. Haloalkanes
11.1 INTRODUCTION
11.1.1 Physical Properties
11.2 PREPARATION OF HALOALKANES
11.3 CHEMICAL PROPERTIES of Haloalkanes
11.3.1 Nucleophilic Substitution Reactions: A General Discussion
11.3.2 Reactions of Haloalkanes
11.3.3 Elimination Reactions: A General Discussion
11.3.4 Substitution Versus Elimination
11.4 ORGANOMETALLIC COMPOUNDS –AN OVERVIEW
[Reaction of Haloalkanes with Metals]
11.4.1 General Characteristics
11.5 Allyl Chloride and Vinyl Chloride
11.5.1 Preparations
11.5.2 Chemical Reactivity of Vinyl and Allyl Halides
11.6 POLYHALOGENATED COMPOUNDS: A BRIEF ACCOUNT
11.6.1 Dihalogen Derivatives
11.6.2 Trihalogen Derivatives
Selected Solved Examples
EXERCISES
12. Haloarenes
12.1 INTRODUCTION
12.1.1 Physical Properties
12.2 PREPARATION of Haloarenes
12.3 CHEMICAL PROPERTIES of Haloarenes
12.3.1 Nucleophilic Substitution Reactions
12.3.2 Electrophilic Substitution Reactions
12.3.3 Reactions of Haloarenes with Metals
12.4 SIDE CHAIN HALOGEN SUBSTITUTED AROMATIC
COMPOUNDS
12.4.1 Preparations
12.4.2 Chemical Properties
Selected Solved Examples
EXERCISES
13. Monohydric Alcohols (Alkanols)
13.1 INTRODUCTION
13.1.1 Physical Properties
13.2 PREPARATION of Monohydric alcohols
13.3 CHEMICAL PROPERTIES of Monohydric Alcohols
13.3.1 Alcohols as an Acid as well as Base: A General Discussion
13.3.2 Reactions Involving the Acidic Characteristics of Alcohols
13.3.3 Reactions Involving the Basic Characteristics of Alcohols
13.3.4 Reactions involving the entire alcohol molecule
13.4 More about alcohols
Selected Solved Examples
Exercises
14. Ethers, Epoxides, Thiols and Thioethers
14A.1 Introduction
14A.1.1 Physical Properties
14A.2 PREPARATION OF ETHERS
14A.2.1 From Alcohols
14A.2.2 From Halo Compounds
14A.2.3 Alkoxymercuration–demercuration of Alkenes
14A.3 CHEMICAL PROPERTIES of Ethers
14A.3.1 Reactions due to Etheral Oxygen
14A.3.2 Reactions Involving Ether Linkage [Cleavage of Carbon–
Oxygen Bond]
14A.3.3 Other Reactions
14A.3.4 Common Uses of Ethers
14A.4 Crown ethers
14B.1 INTRODUCTION
14B.2 PREPARATION OF EPOXIDES
14B.3 CHEMICAL PROPERTIES of Epoxides
14B.3.1 General Mechanism for Ring Opening in Epoxides
14B.3.2 Ring Opening in Unsymmetrical Epoxides
14C.1 GENERAL INTRODUCTION—SULFUR COMPOUNDS IN
ORGANIC CHEMISTRY
14C.2 THIOLS [MERCAPTANS]
14C.2.1 Physical Properties
14C.3 PREPARATION OF THIOLS
14C.4 CHEMICAL PROPERTIES of Thiols
14C.5 THIOETHERS [ALKYL SULFIDES]
14C.6 PREPARATION OF THIOETHERS
14C.7 CHEMICAL PROPERTIES of Thioethers
Exercises
15. Polyhydric Alcohols (Diols and Triols)
15.1 INTRODUCTION
15.1.1 Physical Properties
15.2 ETHYLENE GLYCOL [ETHANE-1,2-DIOL]
15.2.1 Preparations
15.2.2 Chemical Properties
15.2.3 Uses of ethylene glycol
15.3 PINACOLS
15.3.1 Preparation of 2,3-dimethylbutane-2,3-diol
15.3.2 Pinacol–Pinacolone Rearrangement
15.4.1 Physical Properties
15.4.2 Preparations
15.4.3 Chemical Properties
Exercises
16. Phenols
16.1 INTRODUCTION
16.1.1 Physical Properties
16.2 PREPARATION OF PHENOLS
16.3 CHEMICAL PROPERTIES of Phenol
16.3.1 Acidic Nature of Phenol: A General Discussion
16.3.2 Reactions due to Acidic Nature of Phenol
16.3.3 Electrophilic Substitution Reactions of Phenols
16.3.4 Other Reactions
16.4 POLYHYDRIC PHENOLS
16.4.1 Dihydric Phenols
16.5 Quinones
Selected Solved Examples
Exercises
EXPLORE MORE (Set-III)
17. Aliphatic Carbonyl Compounds (Alkanals and Alkanones)
17.1 INTRODUCTION
17.1.1 Physical Properties
17.2 PREPARATION of ALiphatic Carbonyl Compounds
17.2.1 Formation of both Aldehydes and Ketones
17.2.2 Formation of Aldehydes
17.2.3 Formation of Ketones
17.3 CHEMICAL PROPERTIES of Carbonyl COmpounds
17.3.1 Reactivity of Carbonyl Group: A General Discussion
17.3.2 Nucleophilic Addition Reactions
17.3.3 Oxidation Reactions
17.3.4 Reduction Reactions
17.3.5 Reactions Involving α-Carbons of Carbonyl Compounds
17.3.6 Polymerization Reactions of Formaldehyde and Acetaldehyde
17.4 Reaction of α,β-Unsaturated carbonyl compounds
Selected Solved Examples
Exercises
18. Aromatic Aldehydes and Ketones
18.1 INTRODUCTION
18.1.1 Physical Properties
18.2 PREPARATION of Aromatic Aldehydes and Ketones
18.2.1 Oxidation Reactions
18.2.2 By Heating Calcium Salts of Carboxylic Acids
18.2.3 From Grignard Reagent
18.2.4 Electrophilic Substitution of Aromatic Hydrocarbons
18.2.5 Reactions Used for the Preparations of Aromatic Aldehydes
18.3 CHEMICAL PROPERTIES of Aromatic Aldehydes and Ketones
18.3.1 Reactivity of Carbonyl Group: A General Discussion
18.3.2 Nucleophilic Addition Reactions
18.3.3 Oxidation
18.3.4 Reduction
18.3.5 Typical Name Reactions of Aromatic Carbonyl Compounds
18.3.6 Electrophilic Substitution Reactions
Selected Solved Examples
Exercises
19. Aliphatic Carboxylic Acids and Their Derivatives
19.1 INTRODUCTION
19.2 PREPARATION of Aliphatic Carboxylic Acids
19.2.1 Oxidation Reactions
19.2.2 Hydrolysis
19.2.3 Carboxylation of Oganometallic Compounds (Carbonation)
19.2.4 Carbonylation Reactions
19.3 CHEMICAL PROPERTIES of Aliphatic Carboxylic Acids
19.3.1 Acidic Character of Carboxylic Acids: A General Discussion
19.3.2 Reactions Involving Acidic Hydrogen
19.3.3 Reactions Involving Replacement of –OH Group
19.3.4 Reactions Involving –COOH Group
19.3.5 Reactions Involving α-Carbon of Carboxylic acids
19.3.6 Some Typical Chemical Properties of Formic Acid
19.4 ACID DERIVATIVES
19.4.1 Acid Halides
19.4.2 Acid Anhydrides
19.4.3 Ketene—An Intramolecular Anhydride of Carboxylic Acid
19.4.4 Esters
19.4.5 Amides
19.4.6 Urea—A Derivative of Carbonic Acid
Selected Solved Examples
Exercises
20. Bifunctional Carboxylic Acids and Their Derivatives
INTRODUCTION
20A.1 DICARBOXYLIC ACIDS [Saturated and unsaturated]
20a.1.1 Preparations of Saturated Dicarboxylic Acids
20A.1.2 Preparation of Unsaturated Dicarboxylic Acids
20A.1.3 Chemical Properties
20A.2 Substituted Carboxylic Acids
20A.2.1 Hydroxy Acids
20A.2.2 Preparations of Hydroxy Acids
20A.2.3 Chemical Properties
20A.2.4 Halocarboxylic Acids
20A.2.5 Preparations of Halocarboxylic Acids
20A.2.6 Chemical Properties
20B.1 INTRODUCTION
20B.2 ETHYL ACETOACETATE
20B.2.1 Preparation
20B.2.2 Chemical Properties
20B.3 DIETHYL MALONATE
20B.3.1 Preparation
20B.3.2 Chemical Properties
Exercises
21. Aromatic Carboxylic and Sulfonic Acids
A. AROMATIC CARBOXYLIC ACIDS 729
21A.2 Preparation of Aromatic Carboxylic Acids
21A.3 CHEMICAL PROPERTIES of Aromatic Carboxylic Acids
21A.3.1 Acidic Character of Aromatic Carboxylic Acids: A General
Discussion
21A.3.2 Reactions Involving –OH Group: Nucleophilic Acyl
Substitution
21A.3.3 Reduction Reaction
21A.3.4 Reactions Involving –COOH Group
21A.3.5 Electrophilic Substitution Reactions
21A.3.6 Reactions of Some Important Substituted Carboxylic Acids
21B.1 INTRODUCTION
21B.2 PREPARATION of Aromatic Sulfonic Acids
21B.2.1 Electrophilic Substitution Reactions
21B.3 CHEMICAL PROPERTIES
21B.3.1 Acidic Character of Arenesulfonic Acid: A General
Discussion
21B.3.2 Electrophilic Substitution Reactions
21B.4 Aromatic Sulfonic Acid Derivatives
Selected Solved Examples
EXERCISES
Mini Essay I
A. LIPIDS—FATS, OILS, AND WAXES
B. SOAPS AND DETERGENTS
22. Aliphatic Nitrogen Containing Compounds [Amines, Nitro,
Nitriles, Isonitriles, Isocyanates and Thiocyanates]
A. AMINES [ALKANAMINES] 767
22A.2 PREPARATION of Alkanamines
22A.2.1 Reactions, which Yield Mixture of 1°, 2°, and 3° Amines
22A.2.2 Reactions Specific to the Individual Preparation of 1°, 2°, and
3° Amines
22A.3 CHEMICAL PROPERTIES
22A.3.1 Basicity of Amines: A General Discussion
22A.3.2 Reactions of Amines
22B.1 INTRODUCTION
22B.2 Preparation Of Nitroalkanes
Substitution reactions
22B.3 Chemical Properties Of Nitroalkanes
22B.3.1 Reactions at α-Carbon
22B.3.2 Reactions Involving Nitro Group
22B.3.3 Reactions Differentiating Nitroalkanes and Alkylnitrites
22C.1 Preparation and Properties
22D.1 INTRODUCTION
22D.2 Preparation Of Alkanenitriles
22D.2.1 Substitution Reactions
22D.2.2 Dehydration Reactions
22D.2.3 Other Reactions
22D.3 Preparation Of Isonitriles
22D.4 Chemical Properties Of Nitriles And Isonitriles
22E.1 INTRODUCTION
22E.2 Preparation Of Isocyanates
22E.3 Chemical Properties Of Isocyanates
22E.4 Preparation Of Isothiocyanates
22E.5 Chemical Properties Of Isothiocyanates
Selected Solved Examples
EXERCISES
23. Aromatic Nitrogen Containing Compounds (Nitro, Amines and
Diazonium Salts)
23A.1 INTRODUCTION
23A.2 Preparation Of Aromatic Nitro Compounds
23A.3 Chemical Properties Of Aromatic Nitro Compounds
23A.3.1 Nucleophilic Substitution Reactions
23A.3.2 Electrophilic Substitution Reactions
23A.3.3 Reduction
23B.1 INTRODUCTION
23B.2 CHEMICAL PROPERTIES OF AROMATIC AMINES
23B.2.1 Basicity in Aromatic Amines— A General Discussion
23B.2.2 Nucleophilic Substitution Reactions
23B.2.3 Electrophilic Substitution Reactions
23B.3 ARENEDIAZONIUM SALTS
23B.3.1 Chemical Properties of Diazonium Salts
Selected SOlved Examples
EXERCISES
24. Polynuclear Hydrocarbons
24.1 INTRODUCTION
24.2 NAPHTHALENE
24.2.1 Structure of Naphthalene
24.2.2 Aromaticity in Naphthalene
24.2.3 Preparations
24.2.4 Chemical Properties
24.3 DERIVATIVES OF NAPHTHALENE
24.3.1 Naphthols
24.3.2 Naphthylamines
24.3.3 Naphthoic Acids
24.3.4 Naphthoquinones
24.4 ANTHRACENE
24.4.1 Structure of Anthracene
24.4.2 Preparations
24.4.3 Chemical Properties of Anthracene
24.5 PHENANTHRENE
24.5.1 Preparation
24.5.2 Chemical Properties of Phenanthrene
EXERCISES
EXPLORE MORE (Set-IV)
25. Review Part I: Organometallic Compounds Part II: Oxidation–
Reduction Reactions
25.1 INTRODUCTION
25.2 ORGANOMAGNESIUM HALIDES—GRIGNARD REAGENT
25.2.1 Reactions of Grignard Reagent
25.2.2 Limitations
25.3 ORGANOLITHIUMS
25.3.1 Reactions of Organolithiums
25.4 Lithium dialkylcuprates—Gilman Reagent
25.4.1 Reactions of Lithium dialkylcuprates (Gilman Reagent)
25.5 Introduction
25.6 REDUCTION REACTIONS
25.6.1 Reduction by Catalytic Hydrogenation
25.6.2 Reduction by Metal Hydrides
25.7 OXIDATION REACTIONS
26. Heterocyclic Compounds
26.1 INTRODUCTION
26.2 FIVE MEMBERED HETEROCYCLIC COMPOUNDS
26.2.1 Pyrrole, Furan, and Thiophene
26.2.2 Structure and Aromaticity
26.2.3 Preparations of Pyrrole, Furan, and Thiophene
26.2.4 Chemical Properties of Pyrrole, Furan, and Thiophene
26.3 SIX-MEMBERED HETEROCYCLIC COMPOUND
26.3.1 Pyridine
26.3.2 Structure and Aromaticity
26.3.3 Basicity of Pyridine
26.3.4 Preparations of Pyridine
26.3.5 Chemical Properties of Pyridine
26.4 FUSED HETEROCYCLIC SYSTEMS
26.4.1 Quinoline and Isoquinoline
26.4.2 Preparations of Quinoline
26.4.3 Chemical Properties of Quinoline
26.4.4 Preparations of Isoquinoline
26.4.5 Chemical Properties of Isoquinoline
EXERCISES
27. Carbohydrates
27.1 INTRODUCTION
27.2 D- AND L-SUGARS: RELATIVE CONFIGURATION OF
SUGARS
27.3 D-(+)-GLUCOSE: Chemical Properties and Structure
27.3.1 Open Chain Structure
27.3.2 Cyclic Structure of Glucose
27.3.3 Mutarotation
27.3.4 Synthesis and Degradation of Aldoses
27.3.5 Epimerization and Ene–Diol Rearrangement
27.3.6 Osazone Formation: Reaction with Phenylhydrazine
27.3.7 Interconversion Involving Aldoses and Ketoses
27.3.8 Configuration of Glucose
27.3.9 Writing Haworth Formulae and Conformations for Sugars
27.3.10 Evidence for Cyclic Structure of Glucose
27.4 D(-) FRUCTOSE: Chemical Properties and Structure
27.4.1 Cyclic Structure of Fructose
27.5 DISACCHARIDES
27.5.1 Sucrose
27.5.2 Lactose
27.5.3 Maltose and Cellobiose
27.6 POLYSACCHARIDES
EXERCISES
28. Amino Acids, Peptides and Proteins
28.1 Introduction
28.2 Classification of Amino Acids
28.3 STEREOCHEMISTRY of AMINO ACIDS
28.4 PHYSICAL PROPERTIES
28.4.1 Electrophoresis
28.5 SYNTHESIS OF AMINO ACIDS
28.6 CHEMICAL PROPERTIES of Amino ACIDs
28.6.1 Reactions Due to Amino Group
28.6.2 Reactions Due to Carboxylic Group (–cooh)
28.6.3 Reactions Due to Both –Nh2 and –Cooh Groups
28.7 PEPTIDES and THeir Synthesis
28.7.1 Use of Protecting Groups in Synthesis of Polypeptides
28.7.2 Synthesis of Peptides Using Protected Amino and Carboxylic
Acid Ends
28.7.3 Solid Phase Polypeptide Synthesis
28.8 Determination of Sequence of Amino Acids in a Given
Polypeptide
28.8.1 End Group Analysis
28.8.2 Sequence Analysis
28.9 PROTEiNS
28.9.1 Structure of Proteins
28.9.2 Fibrous and Globular Proteins
28.9.3 Denaturation of Proteins
EXERCISES***
Answers to selected exercises
MINI ESSAY II
ENZYMES AND NUCLEIC ACIDS
Enzyme Action
B. NUCLEIC ACIDS
29. Drugs and Pesticides
A. DRUGS
29A.2 ANALGESICS, ANTIPYRETICS AND ANTI-
INFLAMMATORY DRUGS
29A.3 SULFA DRUGS—ANTIBACTERIAL AGENTS
29A.4 CHLORAMPHENICOL (CHLOROMYCETIN)—AN
ANTIBIOTIC
29A.5 CHLOROQUINE—ANTIMALARIAL DRUG
29A.6 ANTIHISTAMINES (Antihistaminics)
29B.1 INTRODUCTION
29B.2 INSECTICIDES
29B.2.1 Organochlorine Compounds
29B.2.2 Organophosphorous Compounds
29B.3 Herbicides
29B.4 Fungicides
EXERCISES
Pesticides
MINI ESSAY III
A. Alkaloids
B. TERPENes
C. Steroids
30. Dyes
30.1 Introduction
30.1.1 Theory of Dyeing
30.1.2 Classification of Dyes
30.2 COLOUR AND STRUCTURE
30.2.1 Witt Theory
30.2.2 Quinonoid Theory
30.2.3 Modern Theory
30.3 SYNTHESIS AND APPLICATION OF DYES
30.3.1 Azo Dyes
30.3.2 Triphenylmethane Dyes
30.3.3 Phthalein Dyes
30.3.4 Anthraquinone Dye
30.3.5 Indigotin Dye
EXERCISES
31. Synthetic Polymers
31.1 INTRODUCTION
31.2 Classification Of Polymers
31.3 PHYSICAL PROPERTIES AND CLASSIFICATION
31.3.1 Stereochemistry of Polymers
31.4 POLYMERIZATION REACTIONS
31.4.1 Addition Polymers
31.4.2 Condensation Polymers
31.5 RUBBERS
31.5.1 Natural Rubber
31.5.2 Vulcanization of Rubber
31.5.3 Synthetic Rubber
EXERCISES
32. Spectroscopy and Structure
32.1 INTRODUCTION
32.2 ULTRAVIOLET–VISIBLE SPECTROSCOPY
Woodward–Fieser rules
32.3 INFRARED SPECTROSCOPY
32.4 NUCLEAR MAGNETIC RESONANCE (NMR)
SPECTROSCOPY
32.5 MASS SPECTROMETRY—AN INTRODUCTION
EXERCISES
Glossary
Index
Preface
Audience
It has been more than ten years since this book was published in January,
2005. As an author there is always a temptation to include everything in a
book. But, we have to limit ourselves. Over the past decade our students,
friends and colleagues have been our best critics. In fact, these are the
people who have carefully gone through the text and appreciated the
contents and also made valuable suggestions and a few corrections.
Considering the scope of the book, an attempt has been made to incorporate
all important suggestions and necessary corrections. The most obvious
revision in the second edition is the introduction of a new set of problems to
enhance the conceptual vision on the various fundamental aspects of organic
chemistry. Further, there has been additions and modifications in the
contents of some of the chapters, wherever required.
The second edition of the book continues to provide the pedagogical
features with which it was written in the beginning. This helps students not
only to acquire a sound knowledge and understanding of organic chemistry,
but also makes their study interesting, stimulating and relevant as much as
possible. We conceived the idea of writing this book with the objective to
provide clarity on the core concepts of organic chemistry that will help
students in their studies and practice as well. The book presents a thorough
treatment of the principles in a new and exciting way that makes it easier for
students to learn and evokes interest of teachers to teach. The book also
introduces significant developments that have taken place in the field.
Organization of the Text
We have organized the text in a manner that the students develop interest in
this fascinating yet challenging subject. The book comprises:
Thirty-two chapters with abundance of solved examples throughout.
Four sets of especially designed solved problems named ‘Explore More’.
Three ‘Mini Essays’ for providing introductory knowledge of natural
products.
Chapters 1–4
Chapter 1 offers coherent presentation of fundamental aspects of chemical
bonding, structure and properties of molecules. It also covers the concept of
hybridization, resonance, isomerism, and intermolecular forces in organic
molecules. A brief discussion on the qualitative and quantitative analysis is
also incorporated.
IUPAC nomenclature has been discussed in Chapter 2 with latest
recommendations. Over 275 examples/solved problems are included with
suitable explanations. The rules for naming the organic compounds are
clarified by giving appropriate structures that are loaded with key points. In
this particular chapter we have endeavoured to share our classroom teaching
experience with the prospective readers of the book.
The treatment of stereochemistry in Chapter 3 is simple and illustrative. The
structures in this chapter are aesthetically drawn to give a feeling of real
three-dimensional visualization.
A brief explanation of the mechanisms of organic reactions and related
topics like reactive intermediates, electronic factors in organic reactions,
steric factors, role of solvents and chemical energetics has been offered in
Chapter 4.
A new problem set (Explore more-I) has been added after Chapter 4 in the
second edition to provide an in-depth view of fundamentals of organic
chemistry pertaining to
Chapters 1–4. The special emphasis is given to stereochemistry.
Chapters 5–24
The chemistry of hydrocarbons and functional groups has been dealt with in
detail in chapters 5 through 24. We have followed the strategy of discussing
a particular functional group, first for aliphatic compounds followed by that
for aromatic compounds. We feel that this strategy will help the students to
know the preparations and properties, which are different (or similar) in
nature. At the same time, utmost care has been taken to ensure that where
the underlying principles for both the aliphatic and aromatic compounds are
same, these are not repeated and instead bridged by appropriate tie-ins to
earlier material. This way a continuity is established and the overall text
stands simplified without diluting the quality of the contents.
Many new problems have been added to Explore More-II based on the
contents discussed in Chapters 5–10. Similarly, more problems have been
added in Explore More-III and IV as well.
Chapters 25—A Review
This chapter is one of the key features of the text. It presents an overall view
of major topics in two parts:
Part I: Organometallic Compounds
Part II: Oxidation-Reduction Reactions
The readers might wonder as to why we have only just given a review
instead of devoting a separate chapter to each of these topics. The simple
reason is to avoid repetition of the chemistry and at the same time
consolidate the much-scattered chemistry under one head, as almost all the
reactions pertaining to these topics are an integral part of the functional
group chemistry discussed in previous chapters.
Chapters 26–32
The topics like heterocyclic compounds, carbohydrates, amino acids,
peptides and proteins, drugs and pesticides, dyes, synthetic polymers,
spectroscopy and structure are discussed in chapters 26 through 32.
However, we have restricted our discussion to a level, generally covered in
the undergraduate curriculum.
In this edition some text has been added/modified in the chapters on
carbohydrates, amino acids, peptides and proteins, spectroscopy and
structure. Whereas in chapter 32 (Spectroscopy and Structure) Woodward-
Fieser rules along with a number of examples have been added to
Ultraviolet-Visible spectroscopy.
What is Notabilia?
It is an old English word which means, “things worthy of notice”. When we started writing this
book, we thought of putting some additional and important information under the head of
‘infobox’. However, it was creditable on the part of our editor to come up with a word that was not
only catchy but also went along completely and exactly with the contents. We overwhelmingly
accept this beautiful change.
Explore More
The four sets of ‘Explore More’ are a supplement to the text, designed to
provide in-depth knowledge in the form of some typical solved problems
(the number of problems included is 141).
Aim: Chemistry is taught to undergraduates at varying degrees of depth.
These four sets are a sort of bridging chapters for the students who wish to
explore the various aspects of the organic chemistry with a little more
attention to details. This material is based on the philosophy of ‘study or
skip’—students with chemistry as a major subject will find the problem sets
more meaningful. Other students studying organic chemistry as their
qualifying subject may ‘skip’ these problem sets.
Scope: The sets of ‘Explore More’ deal with the topics discussed in chapters
1 through 24. These problems (with solutions) are in addition to the
‘selected solved examples’ included at the end of various chapters. Each set
appears after a few chapters and contains the problems based on the
chemistry of the previous chapters.
Set I Set II Set III Set IV
Related to the text from chapters 1–4 5–10 11–16 17–24
Appears after chapter 4 10 16 24
Number of solved problems 1–31 32–71 72–98 99–141
Since problems are related to fundamental aspects of reactions, it is very
difficult to put the boundaries of chapters between the problems of each set.
The above division of problems must be considered in a broader sense
where the explanation for the problems may include the information given
in the earlier chapters. At appropriate places, section numbers are
incorporated for further reference.
Hope: We hope that our approach of adding these pages in the name of
‘Explore More’ will encourage students to learn more about chemistry, over
and above the text included in the chapters.
Mini Essays
A student of organic chemistry must have the knowledge of natural products
and related chemistry, for example, topics such as lipids (fats, oils and
waxes), nucleic acids, enzymes, terpenes, alkaloids and steroids. These
topics are taught to undergraduates only at an introductory level. We have
introduced these topics in the book in the form of three mini essays.
Mini Essay I Part A Lipids—Fats, Oils and Waxes
(After Chapter 21) Part B Soaps and Detergents
Mini Essay II Enzymes and Nucleic Acids
(After Chapter 28)
Mini Essay III Alkaloids, Terpenes and Steroids
(After Chapter 29)
In Mini Essay I, soaps and detergents are covered in Part B, because the
soaps are manufactured from fats/oils and detergents are complementary to
soaps.
Appendix and Glossary
In the appendix some important and useful data has been given in the form
of tables like characteristics of different solvents, energy data for homolytic
and heterolytic bond cleavage. The glossary includes ‘Name reactions’,
‘Reagents’ and some important terms so that the students can revise them at
a glance (page number(s) are also given for quick reference).
Finally
We hope that the students will find this second edition of the book
interesting, easy to read, and easy to learn from. We would very much
appreciate comments from both teachers and students to help us improve the
text further. Please draw our attention to any errors remained undetected that
you might discover.
BHUPINDER MEHTA
MANJU MEHTA
Acknowledgements
Dr. BHUPINDER MEHTA and Dr. MANJU MEHTA (husband and wife)
Enjoying the moments after accomplishing the venture of second edition.
Bhupinder Mehta received his bachelor’s degree in Chemistry (Honours) in
1981, Master’s degree in 1983 and Ph.D. in 1988, all from University of Delhi.
He was awarded National Merit Scholarship during his postgraduate studies and
later awarded fellowship by the Council of Scientific and Industrial Research,
New Delhi, for pursuing research. His main research work is in the field of
sulfur and nitrogen containing heterocyclic compounds.
He started his teaching profession in 1988 and at present is Associate professor
in Department of Chemistry, Swami Shraddhanand College, University of Delhi.
He has over twenty seven years of experience of teaching organic chemistry.
Manju Mehta, née Rawat received her bachelor’s degree in Chemistry
(Honours) in 1987, Master’s degree in 1989 and Ph.D. in 1993, all from
University of Delhi.
She was declared by the Central Board of Secondary Education, among the top
one per cent students (26th rank) in her Senior School Examination in 1984. She
was awarded Undergraduate Science Merit Award by University of Delhi and
later awarded fellowship by University Grants Commission, New Delhi, for
pursuing research. Her main research work is in the field of sulfur and nitrogen
containing heterocyclic compounds.
She started her teaching profession in 1993 and at present is Associate professor
in Department of Chemistry, Maitreyi College, University of Delhi. She has over
twenty two years of experience of teaching organic chemistry.
What This Book Is About
The synthesis of urea marked the beginning of a new era in organic chemistry,
thereby, starting off the process of identification of natural products and their
synthesis. Further, with the advancement in chemistry, a variety of new organic
compounds, catering the needs of mankind, were synthesized. This endless list
of compounds include plastic, rubber, fiber, medicines, dyes, agrochemicals, and
so on. The synthesis of natural and synthetic organic compounds has become a
continuous process and each day new compounds are added to the literature of
organic chemistry.
This development needed a new definition of organic chemistry, which is not
restricted only to the carbon compounds of living system but also includes, the
synthetic organic compounds under its umbrella. Thus, the simplest definition of
organic chemistry is the study of compounds that contain carbon, that is it is
chiefly, the study of compounds where carbon is covalently bonded to carbon,
hydrogen, halogens, oxygen, nitrogen and sulfur. The following text is devoted
to the study of structure, bonding and physical nature of these classes of organic
compounds.
1.2 ELECTRONIC STRUCTURE AND CHEMICAL
BONDING IN ORGANIC COMPOUNDS
1.3.1 Electronegativity
For example, the calculations using this formula (refer to Table 1.2 for
electronegativity) indicate that the covalent bond in HCl possesses 30% ionic
character.
Depending upon the number of shared electron pairs, the covalent bond may be
characterized as a single, double or triple covalent bond.
Atomic radius. The distance from the nucleus of the atom to the outermost
electrons is known as the radius of an atom. The atomic radius is the half of the
closest distance of the approach of the atoms in the structure of symmetrical
molecule. For covalent molecules such as H–H and Cl–Cl, the atomic radius is
often termed as covalent radius.
van der Waals radius. The distance from the nucleus of an atom beyond which
the approach of another atom causes repulsion is known as van der Waals radius
of that atom. If two atoms are brought closer than the sum of their van der Waals
radii, they repel each other and this phenomenon is known as van der Waals
repulsion.
Bond length. In a covalently bonded molecule, the distance between the nuclei
of the two atoms is known as bond length. Atomic radii and bond lengths are
measured in angstrom (1 Å = 10–10 m) units.
Bond angle. In a covalently bonded molecule having more than two atoms, the
bonds form an angle with each other, which is termed as bond angle.
Fig. 1.1 (a) Atomic radius and bond length in hydrogen; (b) van der Waals radii of atoms; (c) bond angles,
and bond lengths in methane and water molecule.
As an example, let us calculate the formal charge on oxygen in H3O+ and OH–.
The Lewis structure for these species are
The dipole moment is represented by $map$$, where head of the arrow is always
towards the more electronegative atom and tail is towards less electronegative
atom.
In a molecule, the dipole moment is the vector sum of all the individual bond
dipoles. The individual bond dipole may not be zero but their vector sum on the
whole may be zero since they cancel each other being vector quantities.
Dipole moment values give an idea about the structure of a molecule. A zero
dipole moment indicates that the molecule is symmetrical or linear.
1.4 CONCEPT OF HYBRIDIZATION AND
COVALENT BONDING
As mentioned earlier, an orbital describes the region in space which has the
maximum probability of finding the electrons. In accordance with the modern
theory of bonding, covalent bond formation between two atoms involves the
overlap of atomic orbitals. This overlap results in the formation of new orbitals
termed molecular orbitals.
As you already know that based on principal energy levels, the orbital may be s,
p, d, or f. In present text our emphasis will be on s and p atomic orbitals as
carbon (atomic number 6) involves atomic orbitals of second principal energy
level.
Fig. 1.2 Excitation and sp3 hybridization of the atomic orbitals of carbon.
The four atomic orbitals of carbon which differ in their energies (one 2s and
three 2p orbitals), undergo a sort of intermixing to form four new hybrid orbitals
having equivalent energies. The new hybrid orbitals are highly directional in
nature and are more effective in overlapping compared to pure atomic orbitals.
The four hybrid orbitals are arranged along the sides of a regular tetrahedron
(bond angle 109.5°) to have minimum electronic repulsions.
Fig. 1.3 Tetrahedral arrangement of four sp3 hybrid orbitals of carbon and formation of methane.
The four sp3 hybrid orbitals overlap with 1s orbital of four hydrogens to form
four carbon-hydrogen $sigma$$ bonds (sp3-s overlap) with same bond lengths
(1.09 Å) and same bond angle. The methane molecule is tetrahedral in shape.
Structure of ethane (C2H6)
In ethane, two carbons undergo sp3 hybridization. Each carbon has four sp3
hybrid orbitals arranged in tetrahedral manner, that is, in all, eight hybrid orbitals
are available. The overlap of two sp3 hybrid orbitals (one from each carbon)
results in the formation of a carbon-carbon $sigma$$ bond (sp3-sp3overlap).
The remaining six sp3 hybrid orbitals overlap with 1s orbitals of hydrogens to
form six carbon-hydrogen $sigma$$ bonds (sp3-s overlap).
Fig. 1.4 Structure of ethane showing overlap of sp3 hybrid orbitals of carbons.
1.4.2 sp2 Hybridization
Fig. 1.5 Excitation and sp2 hybridization of the atomic orbitals of carbon.
Each carbon has three planar sp2 hybrid orbitals, that is, in all six hybrid orbitals
are available. The sp2-sp2 overlap results in C–C $sigma$$ bond formation and
sp2-s overlap results in four C–H $sigma$$ bonds (1.08 Å).
Fig. 1.6 Structure of ethene showing formation of $sigma$$ and $pi$$ bonds.
Each carbon has a pure p orbital (does not participate in hybridization) and
overlap of these two p orbitals results in the formation of a $pi$$ bond. Since
$pi$$ bond is formed by collateral (sideways) overlapping of p orbitals of
carbon, it is relatively weaker than $sigma$$ bond.
Structure of formaldehyde (CH2O)
Carbon has three hybrid orbitals (each having single electron). Oxygen too, has
three hybrid orbitals (two having paired electrons and one with single electron).
The carbon-oxygen $sigma$$ bond is formed by the overlap of one of the sp2
orbitals of carbon and sp2 orbital of oxygen containing single electron. The
remaining two sp2 hybrid orbitals on carbon form two C–H $sigma$$ bonds by
overlaping with 1s orbitals of the two hydrogens. The hybrid orbitals of oxygen
contain two lone pairs of electrons. The overlap of pure p orbitals of carbon as
well as of oxygen forms a carbon–oxygen $pi$$ bond.
Fig. 1.7 Hybridization and formation of $sigma$$ and $pi$$ bond in formaldehyde.
1.4.3 sp Hybridization
The Lewis structure makes use of dots to represent bonding and nonbonding
electrons. Kekule proposed the simplest representation for organic molecules by
taking into consideration the valency of atoms. These chemical formulas were
represented by dash (—), which symbolizes bonding pair of electrons between
atoms and lone pair(s) of electrons is shown as pair of dots around the atom
concern in a molecule.
The lone pair(s) of electrons is not shown in the condensed and bond-line
formula unless or until it has a role to play in understanding the mechanistic
details in the reactions or explaining the other electronic factors associated with
concerned molecule.
1.6 CONCEPT OF RESONANCE (MESOMERISM)
The Lewis structure of a molecule or ion can be used for predicting the structural
properties and reactivity of that molecule. A number of molecules or ions can be
represented by more than one correct Lewis structures. For example, following
two Lewis structures can be written for nitrite ion (NO2–).
In accordance with these structures, the nitrite ion should have two different
nitrogen-oxygen bond lengths (N–O and N== ). Experimentally, it has been
observed that both nitrogen-oxygen bond lengths are same and their value lies
between that of a single and a double bond value. Any one of these Lewis
structures alone do not represent correctly the bonding in NO2– ion. The actual
structure is a hybrid of these two Lewis structures. The two Lewis structures are
known as resonance forms, resonance contributors, or contributing structures
and are represented by placing a double-headed arrow ($harr$$) between them.
These contributing structures are hypothetical structures. The actual resonance
hybrid structure cannot be represented by a Lewis structure and is shown by
placing dashes, which indicates delocalization of negative charge between two
oxygen atoms.
Here, the negative charge is delocalized among all the three oxygens.
Structure [I] and [II] are equivalent and contribute equally, however in structure
[III] the number of covalent bonds is three (less than [I] and [II] which have
four). Also, structure [III] has an electron deficient carbon with positive charge
and thus it is least contributing.
The concept of resonance provides an adequate explanation for electron
delocalization in certain molecules, ions and radicals. In general, delocalization
involves lone pair (non-bonding) of electrons and $pi$$-electrons (from multiple
bonds).
Delocalization of electrons during resonance is shown to occur in three ways:
1. Shifting of electrons from $pi$$ bond to adjacent bond.
In the following examples the shaded portion indicates the shifting of electrons
from $pi$$ bond to adjacent bond.
2. Shifting of electrons from $pi$$ bond to an immediately next placed atom.
In the following examples the shaded portion indicates the shifting of
electrons from $pi$$ bond to an immediately next placed atom.
Both ether and alcohol are polar in nature. However, alcohols have higher
boiling point compared to ether because of intermolecular hydrogen bonding.
The lower alcohols are soluble in water. This is due to hydrogen bonding among
alcohol and water molecules (Intermolecular hydrogen bonding). However, with
an increase in the nonpolar hydrocarbon chain of alcohols, the solubility in water
decreases.
Compared to other intermolecular forces, the hydrogen bonding occurs through
specific atoms, (having high electronegativity) on adjacent molecules, for
example, hydrogen with oxygen, hydrogen with nitrogen, hydrogen with
fluorine, and so on. Hydrogen bonding interactions are strong compared to ion-
dipole and dipole-dipole interactions.
London forces
The intermolecular interactions, which are observed in nonpolar molecules, are
known as London forces. The electrons are in continuous motion and induce
temporary polarization in one molecule, which in turn induces polarization in an
opposite direction in adjacent molecule. This momentary induction of dipole
results in attraction between otherwise nonpolar molecules (induced dipole
interaction). The London forces are very weak intermolecular forces. The
attraction among nonpolar molecules of alkanes is attributed to London
forces.
Sulfur, if present, gets converted into sodium sulfide, which on reaction with
lead acetate in acetic acid gives black precipitate.
The halogens, if present, in organic compounds are converted into corresponding
water-soluble sodium halides, which on reaction with silver nitrate give
corresponding silver halide precipitates.
Acyclic compounds
The linear or branched, open chain compounds of carbon are referred as acyclic
or aliphatic compounds. These compounds may be saturated (containing single
bonds) or unsaturated (containing double or triple bonds).
Cyclic compounds or ring compounds
These compounds have their atoms arranged in cyclic manner. They may be
divided into following two classes:
(a) Carbocyclic (or isocyclic) compounds. In these compounds, the ring
consists of carbon atoms only. This includes alicyclic and aromatic compounds.
Alicyclic compounds may be saturated, e.g. cycloalkanes or may be unsaturated,
e.g. cycloalkenes.
(b) Heterocyclic compounds. In these compounds, the ring consists of other
atoms in addition to carbon atoms such as, O, S, N, and so on which are referred
to as heteroatoms.
The replacement of one or more hydrogen atoms in a hydrocarbon with other
atoms or group of atoms gives rise to a characteristic structural unit known as
functional group. A functional group defines the class and reactivity of an
organic compound. Some of the functional groups are listed in Table 1.5.
1.10 ISOMERISM IN ORGANIC MOLECULES
The compounds having same molecular formula are called isomers. Earlier, we
have discussed that carbon is tetravalent in nature and it may form single,
double, or triple covalent bonds with other atoms. Different compounds of
carbon differ because of the way in which the constituent atoms are covalently
bonded to each other. At the same time, two compounds show different
properties even if they have same atoms or groups present and have same
covalent bonding. How can one account for these observations? Two important
aspects describe the structure of a molecule, namely.
Bond connectivity. It describes the sequence in which different atoms or groups
are bonded to each other in a molecule. The isomers that differ in their bond
connectivity are known as constitutional isomers (formerly *structural isomer).
Spatial arrangement. It describes the three-dimensional arrangement of atoms
or groups in a molecule, that is, configuration of a molecule. The branch of
chemistry dealing with the study of three-dimensional nature (spatial
arrangement) of molecules is known as stereochemistry. Chapter 3 is
completely devoted to stereochemistry which is one of the most important
aspects in the study of organic chemistry.
The isomers may be categorized as:
The discussion in this chapter is restricted to constitutional isomers only.
Functional isomers. These isomers have same molecular formula but they differ
in the nature of functional groups, for example, alcohols and ethers with same
molecular formula. Similarly, aldehydes and ketones with same molecular
formula are also functional isomers. Carboxylic acids and esters also represent
functional isomers.
Metamers. These isomers have same functional group but they differ in the
arrangement of alkyl groups around the functional group. For example,
Tautomers. These are the two forms of same compound, which arise due to
migration of a hydrogen atom in a compound. The two forms are readily inter-
convertible and exist in dynamic equilibrium with each other. This phenomenon
is known as tautomerism. For example,
(a) keto-enol tautomerism
A strong acid has a weak conjugate base and weak acid has a strong conjugate
base. Similarly, a strong base has a weak conjugate acid and a weak base has a
strong conjugate acid.
pKa and pKb values
The relative strength of acids or bases is expressed in terms of their dissociation
constant values Ka and Kb or in terms of pKa and pKb values.
For an acid HA, the dissociation constant, Ka is expressed as
Larger the value of Ka, the stronger is the acid, that is, Ka $prop$$ acidic
strength.
The negative logarithm of Ka is expressed as pKa.
pKa = –log Ka
Higher the value of pKa, lower is the strength of acid. This can be expressed
as
In a similar way, for a base B, the dissociation constant Kb is expressed as:
Larger the value of Kb, the stronger is the base, that is, Kb $prop$$ basic
strength
The negative logarithm of Kb is expressed as pKb
pKb = –log Kb
Higher the value of pKb, lower is the strength of base, i.e. weak base. This
can be expressed as
1. Draw the Lewis structures of the following molecules/ions and calculate the
formal charge on the atoms indicated in bracket.
(a) H2SO4 (sulfur)
(b) HSO4– (oxygen)
(c) NH4+ (nitrogen)
(d) NH2– (nitrogen)
(e) CO2 (carbon)
(f) CH3OH (carbon)
(g) CH3O– (oxygen)
(h) CH3COO– (oxygen)
2. In the following molecules, indicate the positive and the negative end of the
dipole using the symbol ($map$$ ).
(a) CH3Cl
(b) H2O
(c) CCl4
(d) CO2
3. In the following molecules, indicate the bond angle about the indicated atom.
2.1 INTRODUCTION
Each and every object in this universe is identified by its name. When organic
chemistry was in stage of infancy and not many compounds were known, the
compounds were named based on their sources or the name of their discoverer.
These names are called common or trivial names, a few such examples are listed
below in Table 2.1.
Prefix. The stem name may have certain groups or atoms attached to it which
are termed substituents. The names for these substituents are prefixed (added
before) to the stem name. Some of the substituents are listed in Table 2.3 and
Table 2.4. If a molecule contains more than one functional group than as per the
priority order, lower priority group is treated as substituent and written as a
prefix, as mentioned in the Table 2.5.
Suffix. A suffix denotes the functional group present in a compound and is
always added after the stem name (word root) as mentioned in Table 2.5.
2.2.1 Rules for Naming the Organic Compounds
IUPAC has laid down certain rules to be followed while naming different classes
of organic compounds. This subsection contains a detailed description of these
rules.
Alkanes
The procedural steps for the IUPAC nomenclature of alkanes are as follows:
1. For unbranched alkanes, nomenclature is done by adding suffix -ane to the
stem name. The stem name indicates the number of carbons in a compound
refer Table 2.2).
A few selected examples of the IUPAC names for some straight chain
(unbranched) alkanes are as follows.
CH4 Methane CH3(CH2)7CH3 Nonane
CH3CH3 Ethane CH3(CH2)8CH3 Decane
CH3CH2CH3 Propane CH3(CH2)9CH3 Undecane
CH3(CH2)2CH3 Butane CH3(CH2)10CH3 Dodecane
CH3(CH2)3CH3 Pentane CH3(CH2)18CH3 Eicosane
CH3(CH2)4CH3 Hexane CH3(CH2)19CH3 Heneicosane
CH3(CH2)5CH3 Heptane CH3(CH2)28CH3 Triacontane
CH3(CH2)6CH3 Octane CH3(CH2)98CH3 Hectane
For branched chain alkanes, the rules for naming are:
2. Longest possible continuous chain (parent chain) of carbon atoms is first
selected and the compound is named as a derivative of alkane
corresponding to the number of carbon atoms in the selected chain.
3. Selected chain is then numbered from the end which gives the lowest
number to the carbon atom carrying the alkyl group. For numbering, we use
Arabic numerals 1, 2, 3,… and so on.
4. The position of alkyl group in the chain is designated by the number given
to carbon in the chain, to which it is attached. The number (locant) is
written before the alkyl group. In this system, entire name is written as a
single word. A hyphen is used between a number and the word, and a
comma is used between two numbers. The use of n-, iso-, neo-, tert, sec-
and so on, is avoided as far as possible.
For example,
The wrong way of numbering of the carbon chain is indicated by encircled arabic numerals and the wrong
name given to organic compound is indicated by encircled ‘Not’ throughout the text.
5. The different alkyl groups, present in a compound, are written in an
alphabetical order, irrespective of their position in the carbon chain.
6. If two or more similar alkyl groups are present in a compound, the words
di, tri, tetra, and so on are used to specify the number of times these alkyl
groups appear in the chain. However, these prefixes themselves are not
considered for writing the alphabetical order. For example,
7. If two different alkyl groups are present at an equal distance from either end
of selected chain, the alkyl group which comes first in the alphabetical
order gets the lowest possible rank. For example,
8. If more than two alkyl groups are present and branching occurs at an equal
distance from either end, the numbering is done from the end which gives
minimum possible number to all the substituents. For example,
Alkenes
The basic rules for naming alkenes are similar to those for alkanes but include
the indication for position of double bonds. Additional rules pertaining to
alkenes can be summarized as follows:
1. The longest possible continuous carbon chain should include the carbons of
double bond.
2. The longest chain is given the name by replacing suffix -ane (in case of
alkanes) with
-ene.
3. The numbering is done in such a way that first carbon of double bond gets
the lowest number.
4. The carbon atoms of the double bond get the preference over the other
substituents present in the parent chain.
5. In an alkene, the position of double bond is indicated by placing the number
before the suffix -ene (refer Notabilia 3).
6. If more than one double bond is present, the location of each double bond is
indicated just before the suffix. The suffix used, for two double bonds is -
diene, for three double bonds it is -triene, and so on. The general name for
dienes is ‘Alkadiene’.
[Note: While naming the organic compounds, two vowels are never placed together.
But, in alkadiene and alkatriene vowel a is separated from ‘e’ (of -ene) by -di and -tri,
thus ‘a’ is retained in the name.]
Alkynes
1. In alkynes, the longest possible chain should include the carbons of triple
bond.
2. The naming of alkyne is done by replacing the suffix -ane of the
corresponding alkane with -yne.
3. Lowest numbering is given to first carbon of the triple bond.
Other rules are same as those for alkanes. A few examples of alkynes are as
follows.
5. If alkyl group has more number of carbon atoms than the cyclic structure,
the compound is named as cycloalkylalkane (cyclic structure becomes the
substituent). Otherwise the alkyl group is named as substituent of
cycloalkane.
Alkyl halides (RX)
1. Halogens are always treated as substituents and while naming, written as
prefix to the name of a compound.
2. The IUPAC name for alkyl halides is Haloalkane.
4. If different halogens are present at an equal distance from either end then
numbering is done according to their alphabetical order.
A few examples of mono and polysubstituted haloalkanes are as follows:
Alcohols (ROH)
1. The selected longest continuous chain of carbon atoms must include
hydroxy group.
2. The alcohols are named by suffixing -ol for the -e of the corresponding
alkane. Thus alcohols are named as Alkanols.
3. The carbon bearing the hydroxyl group gets the lowest possible numbering.
For example,
4. Alcohols containing two or more hydroxyl groups are commonly known as
polyhydric alcohols and in IUPAC system, suffixes -diol, -triol, and so on
are used instead of -ol, to indicate the number of hydroxyl groups. In such
cases the vowel ‘e’ of alkane is retained in the name (see note on p. 41).
Thus, the general name for an alkane containing two hydroxyl groups is
Alkanediol.
Ethers (ROR′)
1. The general IUPAC name for ethers is alkoxyalkane.
2. The longest continuous carbon chain is named as alkane, whereas the chain
with lesser number of carbon atoms is named alkoxy and is always written
as substituent with the number specifying its position. For example,
3. The cyclic ethers are named in two ways. That is,
(i) Using epoxy as a prefix, which is commonly used for 3-membered cyclic
ethers.
(ii) As heterocyclic compounds. This is commonly used for higher membered
cyclic ethers. For example,
Naming the three membered cyclic ethers
Aldehydes (RCHO)
1. The longest continuous carbon chain contains —CHO group and the carbon
of —CHO group gets the lowest number.
2. The aldehydes are named by suffixing -al in place of -e of the
corresponding alkane. Thus in general, an aldehyde is named as Alkanal.
3. The chain is numbered from the aldehydic carbon but the position of the
aldehyde is not specified by number ‘1’, as it is understood that aldehydic
carbon is the terminal carbon.
4. Compounds with two aldehydic groups are named Alkanedial and so on,
where vowel ‘e’ of alkane is retained (p. 41).
5. The unsaturated aldehydes are named Alkenal (ene + al) and Alkynal (yne
+ al).
Rest of the rules for naming substituents remain the same as mentioned already.
For example,
Ketones (RCOR′)
1. The longest continuous carbon chain must contain ketonic group.
2. The ketones are named by suffixing -one in place of -e of the corresponding
alkane. Thus, the name Alkanone.
3. The carbon chain is numbered in such a way that ketonic group gets the
lowest number.
4. Further, numbering the positions of the substituents is carried out and these
are placed as prefix according to the rules explained earlier.
5. The compounds containing two ketonic groups are termed as Alkanediones
along with the position number of groups. The vowel ‘e’ of the alkane is
retained in this case.
6. The unsaturated ketones are called Alkenones (ene + one) or Alkynones
(yne + one). For example,
Carboxylic acids (RCOOH)
1. The longest continuous carbon chain must contain the carboxylic group
which gets the lowest number.
2. The naming of carboxylic acids is done by adding the suffix -oic acid in
lieu of -e of the corresponding alkane. Thus, the name Alkanoic acid.
3. The name of carboxylic acid is written as two words (unlike others, written
as single word).
4. The general name for the family of unsaturated carboxylic acids is
Alkenoic acid and Alkynoic acid.
5. In case of dicarboxylic acids, the longest chain should include both
carboxylic groups. The numbering starts from one carboxylic group and
terminates at the other. Thus, names of dicarboxylic acids are Alkanedioic
acid. It is written without specifying the position of the carboxylic group.
A few examples of carboxylic acids are as follows:
Acid derivatives (RCOCl, (RCO)2O, RCOOR′, RCONH2)
The acid derivatives are named in the following manner:
1. Acid halides are named as Alkanoyl halides.
2. Acid anhydrides are termed Alkanoic anhydrides.
3. Esters are named as Alkyl alkanoates, where alkyl refers to alcoholic part
and alkanoate refers to carboxylic part of the molecules.
4. Acid amides are named as Alkanamides.
5. The names of acid halides, acid anhydrides and esters are written as two
words, whereas the names for acid amides are written as a single word.
Some illustrative examples of IUPAC names for the acid derivatives are:
Nitroalkanes (RNO2)
1. The nitro group is always treated as substituent and written as prefix along
with its position on the longest continuous carbon chain. For example,
Amines (RNH2)
1. The longest continuous carbon chain includes the carbon attached to –NH2
group.
2. Amines are named by suffixing -amine in place of -e of the corresponding
alkane. Thus, the general IUPAC name for amines is Alkanamine.
3. While numbering the parent chain, the lowest possible number is given to
the carbon attached to –NH2 group. For example,
4. In case of secondary amines, the longer chain is selected as a parent chain.
The other alkyl group is named as prefix and written as N-alkyl before the
parent chain. Thus, they are named N-alkylalkanamines.
5. In case of tertiary amines, the longest chain is selected as a parent chain and
other two alkyl groups are written as prefixes as N,N-dialkyl (if both alkyl
groups are the same) or as N-alkyl-N-alkyl (if both are different).
The examples of secondary and tertiary amines are as follows.
Thioalcohols (R-SH)
1. The IUPAC name for thioalcohol is Alkanethiol.
2. The lowest possible number is given to the carbon bearing the –SH group.
For example,
Organometallic compounds
The organometallic compounds are generally named by writing organic groups
as prefixes followed by the name of the metal without leaving space in between
the group and metal. In case anionic ligands are present in organometallic
compounds, they are named by writing the organic group followed by the name
of metal and then name of anion. The anion is written as a separate word. For
example,
2.3 SELECTED EXAMPLES OF
MONOFUNCTIONAL AND POLYFUNCTIONAL
ORGANIC COMPOUNDS
In this section, some typical examples are discussed that will help in applying
the rules studied for IUPAC nomenclature of organic compounds.
The general guidelines to be followed are as follows:
1. Select the longest possible carbon chain where the lowest possible number
is assigned to the principal functional group.
2. If more then one functional groups are present, select the principal
functional group in accordance with the preference order given in Table 2.5.
The other functional groups present are treated as substituents and these
functional groups are written as prefixes as given in Table 2.5.
3. The IUPAC name is always written in an alphabetical order irrespective of
the position of substituents.
Selected examples are given to explain the rules studied and wherever
neccessary suitable remarks are given along with.
Example 1
Remarks. When both the double bond and triple bonds are equidistant from both
the ends (Example 1b), preference is given to the double bond.
Remarks. Preference is given to triple bond as it is nearer to one end [refer (a)
and (b)] but name is always written as -enyne with their respective number
indicating positions.
Example 2. The following are the examples of bifunctional compounds, where
in accordance with the priority order (see Table 2.5), one of the functional group
is selected as principal functional group and the other functional group is treated
as a prefix (here indicated by shaded portion in the structure and name).
Example 3
Remarks.
(1) The prefix oxo is used when carbon of aldehyde group is a part of the
longest chain (Example 3a).
(2) The prefix formyl is used when –CHO cannot be included in the longest
continuous chain (Example 3b).
Remarks
(1) Numbering is undesirable as two carboxylic groups are always at terminal.
(2) Vowel ‘e’ is retained in the name as ‘e’ and ‘o’ (of oic) are separated by di.
Example 5
Remarks. It is not possible to include all the three carboxylic groups in the
longest continuous chain. Since all the three carboxylic groups are the principal
functional groups, so naming one of the carboxylic groups as a prefix ‘carboxy’
would be wrong. In such a situation, an alternative
suffix (refer Table 2.5, column II) ‘carboxylic acid’ is used for all the three
groups, where
carbons of three carboxylic groups are not a part of the parent chain yet they are
the principal functional groups.
Remarks. Explanation for Examples 5(b) and 5(c) is similar to that given for
Example 5(a).
Example 6. In cyclic compounds the principal functional group can not be
included in the carbon chain and they are named by using alternative suffixes
(Table 2.5).
Example 7
Remarks. All the three –CN groups can not be expressed as principal functional
groups,
hence prefix cyano is used for one of the –CN groups as it cannot be included in
the longest continuous chain. The same explanation holds true for Example –7b
[compare with Examples
5(b) and (c)].
Example 8
Remarks. In Example 8(c), Iodo and methyl are equidistant, so numbering is
done from the end nearer to iodo, as iodo has alphabetical precedence over
methyl. [Compare with Examples 8(a)
and (b)].
Example 9
Remarks
(1) Similar groups are attached to nitrogen (N,N-) as well as carbon (C-3). So
the prefix used is N,N,3-trimethyl.
(2) Branched chain substituent present on nitrogen is written in bracket
[Example 9(b)].
Step 2. The principal functional group is then identified and placed as indicated
by the name. In this case the principal functional group is alcohol (–OH), present
at third carbon.
Step 3. Rest of the substituents are placed at the indicated positions. In this case
the substituents are -chloro and -methyl, present at positions 4 and 5
respectively, on the carbon skeleton.
Step 4. Now, hydrogen(s) are placed to satisfy valency of the carbon skeleton.
Thus, the structure of organic compound can be written as:
Student’s answerbook
Correct name: 4-Ethyl-2,2-dimethylhexane
Given structures (2)
Student’s answerbook
Correct name: 3-Bromo-5-chloro-2,4-dimethyl-2-nitrohexane
Given structure (4)
Student’s answerbook
2.
3. Correct name (In brackets, hints for error rectification)
(a) Pent-1-yne
(Hint: Lowest number to triple bond.)
(b) 2-Bromo-3-Chlorobutane
(Hint: Numbering and naming as per alphabetical order.)
(c) Propenal
(Hint: Numbering is undesirable.)
(d) Methoxymethanol
(Hint: Parent compound is an alcohol with ether linkage as substituent.)
(e) Hexa-1,5-diene
(Hint: Carbons bearing double bonds get lowest possible numbers.)
(f) N-ethyl-N-methylpropanamine
(Hint: Named as a derivative of longest carbon chain.)
(g) 3-Oxopropanoic acid
(Hint: Aldehydic carbon is a part of longest carbon chain.)
(h) Pent-3-en-2-one
(Hint: Lowest number to the ketonic functional group.)
(i) Pentanedioic acid
(Hint: Numbering is undesirable.)
(j) 2,3,5-trimethyl-4-propylheptane
(Hint: Longest chain must include maximum number of substituents.)
(k) 5-Bromo-2-chloro-9-hydroxy-7-iodo-6-methyl-3-nitro-8-oxononanoic acid
(Hint: Name to be written in alphabetical order.)
* Answers to the exercises are given at the end. It is suggested that the readers first try themselves then
check the answers. Use prefixes and suffixes carefully (as given in tables in the text) and apply the rules
systematically.
Chapter3
Stereochemistry
3.1 INTRODUCTION
The isomers which have same bond connectivity but different arrangement of
groups or atoms in space are termed stereoisomers. The branch of chemistry
dealing with the study of three-dimensional nature (spatial arrangement) of
molecules is known as stereochemistry. Living organisms, their metabolic
activities, natural syntheses, and drug synthesis incorporate various aspects of
stereochemistry. Let us learn some facts about stereoisomers of different
compounds.
• D-glucose is metabolized by animals and fermented by yeast unlike L-
glucose.
• (–) Adrenaline has more hormonal activity than (+) adrenaline.
• (–) Nicotine is more poisonous than (+) nicotine.
• One stereoisomer of Caravone has caraway (spice similar to cumin seeds;
Jeera in Hindi) flavour while other isomer has flavour of spearmint.
• One stereoisomer of Limonene has smell of lemon while the other smells
like oranges.
• Of the several possible isomers of BHC, only one isomeric form has
insecticidal property, that is, gamma–BHC (or Lindane).
• All naturally occurring fatty acids have cis-configuration.
• One stereoisomer of monosodium glutamate (MSG) is used as an active
flavour enhancer (in Chinese recipes such as chowmein).
These facts clearly indicate that a difference in spatial arrangement may affect
the properties of isomers drastically.
The various aspects of stereoisomers will be discussed in context of their
following classification:
3.2 CONFIGURATIONAL ISOMERISM
The carbon is tetravalent in nature and the non-planar tetrahedral geometry in
carbon compounds gave birth to the concept of stereochemistry. The four atoms
(or groups) attached to a carbon are present in different planes as shown in Fig.
3.1 through the dashed-wedged-line structure, and ball and stick model. The
arrangement of different groups or atoms in space is termed as configuration.
Fig. 3.1 (a) Ball and stick model and (b) corresponding dashed-wedged-line structures for a tetrahedral
carbon atom joined to four different group.
Fig. 3.5 The different representations for dashed-wedged-line structure [A] as shown by the ball and stick
model [B] and its equivalent structure [C]. The orientation of groups as shown in [C] are direct
representation of 2-Dimensional Fischer Projection [D].
The Fischer projection of a compound with more than one chiral centre can be
written in the same way using more than one horizontal lines. This is illustrated
through the Fischer projection of 2-bromo-3-chlorobutane as follows:
Step 3. A Fischer projection can be rotated through 180° in the plane of the paper
since this does not change the configuration, that is, spatial arrangement of
groups around chiral carbon. In this manner, same stereoisomer can be
represented in different ways. A rotation by 180° does not involve the
interchange between horizontal and vertical lines as visible in the Fig. 3.7.
Fig. 3.7 Rotation of Fischer projection by 180° does not change the configuration of stereoisomer. The
Fischer projection IA and IB (of lactic acid) represent the same stereoisomer. Similarly, IIA and IIB
(of 2-hydroxypropanal) represent the same stereoisomer.
Specific rotation
Specific rotation [α], is the rotation caused by a sample at a concentration of 1.0
g/mL in a sample tube of length 1.0 dm (10.0 cm). The value of specific rotation
depends on the concentration of sample, its structure, wavelength of light source,
temperature, length of the sample tube, and solvent. The temperature t (in oC)
and wavelength λ of light source are indicated as superscript and subscript
respectively while writing the specific rotation.
Racemic mixture
A mixture containing equal amounts of a pair of enantiomers is termed as
racemic mixture (also called racemic modification). A racemic mixture is
optically inactive. As the enantiomers exhibit same specific rotation in opposite
directions, the specific rotation values of two isomers cancel each other,
resulting in zero optical activity. The racemic mixture is denoted by (+). For
example, (+) lactic acid.
The chiral carbon is attached to –CH3, –NH2, –OH, and an H atom. The groups
–CH3, –NH2, and –OH are attached through C, N, and O atoms respectively.
The atom with the highest atomic number is assigned the highest priority (1) and
the atom with lowest atomic number is assigned the lowest priority (4).
The priority order to the groups, attached through similar atoms, is assigned as
follows:
Rule 4. In case of groups having multiple bond, for assigning priority order a
multiple bond (double or triple) is considered to be bonded to an equivalent
number of similar atoms through single covalent bonds. For example, two
carbons attached through a double bond and considered as if each carbon is
joined through two single covalent bonds to two carbons. The priority order is
then decided in accordance with the above discussed rules.
The priority order of different groups with multiple bonds is assigned as follows:
For (b): The priority order of attached groups and atoms to the chiral carbon is
Now converting the given molecule to Fischer projection (refer Fig. 3.6)
Now bringing the lowest priority group vertically downwards by even number of
interchanges (p. 79) will give the configuration, which is as follows:
For (c): The priority order of attached groups to the chiral carbon is assigned as
mentioned earlier (p. 78)
Thus, the configuration of above molecule is 2S, 3S (since at C2 and C3, the
configurations are S and S repectively) and this stereoisomer will be named (2S,
3S)-2,3-Dibromopentane.
Illustrative Example 3. Assign the R and S configuration to the following
molecule
Similarly, in substituted biphenyl, the two phenyl rings are not present in same
plane. The substituents present adjacent to bond joining two benzene rings
restrict the rotation around this bond and the molecule is said to be
conformationally locked. The molecules are highly strained and cannot achieve
symmetry because of the steric hindrance or strained structure. Thus, the
substituted biphenyls exist in enantiomeric forms, which are optically active.
3.5 GEOMETRICAL ISOMERISM
The compounds having similar molecular formulae but different arrangement of
atoms or groups in space around the double bond are called geometrical isomers
and the phenomenon is known as geometrical isomerism. The geometrical
isomerism arises due to restricted rotation about a carbon–carbon double bond.
A complete rotation around carbon–carbon double bond causes the breaking of π
bond (refer Notabilia 4).
Necessary and sufficient condition for geometrical isomerism
An alkene of the type abC==Cxy exhibits geometrical isomerism if a ≠ b and x ≠
y. In an alkene, if either of the double bonded carbons is attached to two
identical groups or atoms, no geometrical isomerism will exist.
There are three different ways in which groups a, b, x, and y can be arranged
around carbon–carbon double bond. The configuration of the geometrical
isomers is designated by
• Cis–trans system
• E–Z system
Cis–trans system
This system is used for designating the alkenes in which the two olefinic carbons
have at least one similar group or atom present on them. For example, the
alkenes of the type abC==Cab and abC==Cax exhibit cis–trans isomerism. It is
to be noted that
(i) the term cis- is used when two similar atoms or groups are present on same
sides across the double bond and
(ii) the term trans- is used when two similar atoms or groups are present on
opposite sides across the double bond.
The cis- and trans- isomers differ in their physical properties. In general,
trans- isomers are more stable compared to cis- isomers. In cis- isomers, the
groups present on the same side experience van der Waals repulsive forces due
to steric factors.
Dipole moment values can be used effectively for distinguishing cis- and
trans-isomers. The trans-isomers have zero dipole moment as the bond dipole on
opposite sides cancel each other.
E–Z system
The alkenes of the type abC==Cxy exhibit geometrical isomerism but they
cannot be classified as cis- or trans- isomers, as all the substituents attached to
olefinic carbons are different. The configuration about any carbon–carbon
double bond is specified using E–Z system. The sequence rules as discussed
earlier (see Sec. 3.5) are used for this purpose.
• The atoms or groups attached to each olefinic carbon are given priority as
per sequence rules described earlier.
• If higher priority groups are present on same sides across the double bond, the
geometrical isomer is said to have Z-configuration [German: Zusammen—
same side].
• If higher priority groups are present on opposite sides across the double bond,
the geometrical isomer is said to have E-configuration [German: Entegegen
—opposite side].
All geometrical isomers (including cis- and trans-) are designated by E–Z
system.
NOTABILIA
3.6 CONFORMATIONS
In alkanes, the carbon atoms are connected through single bonds. The atoms
connected by a single bond can rotate about that bond without breaking it and
the energy required for this rotation is very low. Molecules possess kinetic
energy due to a state of continuous motion. The energy is transferred among
molecules during collisions and is sufficient to bring about rotation about single
bond and for this reason the rotation is termed free rotation. Different three-
dimensional arrangements of atoms that result due to free rotation about carbon–
carbon single bond are known as conformations. The individual structures
arising due to free rotation are known as conformers or conformational isomers.
A free rotation about carbon–carbon single bond does not change the basic
skeleton of the molecule.
Fig. 3.11 Ball and stick model showing C–C free rotation in Ethane.
Representation of conformations
Sawhorse and Newman projections better represent the staggered and eclipsed
conformations of ethane besides dashed-wedged-line structure or ball and stick
model.
Sawhorse projection. In sawhorse projection, the two carbons attached through
σ bond are represented by points where four lines intersect. The bond through
which two carbons are joined is considered in the plane whereas the atoms (or
groups) attached to carbons may be above (shown by thick lines) or below the
plane (shown by dotted lines).
Newman projection. In Newman projection, a dot and a circle represent the two
carbons, attached through σ bonds. The dot represents the front carbon whereas
circle represents the rear carbon. The represents the two carbons attached
through σ bond. The three bonds attached to front carbon are represented as full
lines , whereas the three bonds attached to rear carbon are represented by line
arising from the surface of the circle .
Thus, the staggered and eclipsed forms of ethane can be represented as shown in
the following structures. In a staggered conformation, if we hold the front carbon
and rotate the rear carbon through an angle of 60° around carbon–carbon axis, it
results in an eclipsed conformation; a further rotation by 60° will result in a
staggered conformation.
Sawhorse projection
Newman projection
The study of the energy associated with different conformations is known as
conformational analysis. A plot between energy (along Y-axis) and angle of
rotation (along X-axis) depicts that in the energy diagram the lowest energy
conformations are staggered conformations. The maximum energy is associated
with eclipsed conformations. The difference in energy between the most stable
staggered and least stable eclipsed conformation is referred to as torsional strain
of the molecule. For ethane, the torsional strain is 3.0 kcal mol–1.
The energy required to overcome torsional strain is known as energy of
activation (Ea) and is supplied by molecular collision. The lower the value of
Ea, faster is the rotation about carbon–carbon single bond.
Fig. 3.13 Conformational analysis of ethane.
However, the torsional strain in propane is a little higher (3.3 kcal mol–1) than
ethane due to steric hindrance caused by methyl group in eclipsed conformation.
In the eclipsed conformation of propane, van der Waals repulsion occurs
between the methyl group and hydrogen.
Fig. 3.14 Conformations in propane and its conformational analysis.
If we view the molecule of butane through C2–C3 bond, each carbon is seen
attached to one methyl group and two hydrogens. A rotation about C2–C3 bond
results in the formation of a number of conformations. The Newman projections
(I-VI) for different conformers of butane, as obtained through 60° rotation
around C2–C3 bond, are as follows:
In a planar cyclic structure, all the hydrogens are eclipsed which leads to
torsional strain. The more the number of ‘eclipsed hydrogens’, higher is the
torsional strain. Thus, cyclobutane and cyclopentane with a planar structure will
have considerable torsional strain. Acquiring non-planar structure relieves this
torsional strain. A non-planar structure however causes an increase in angle
strain but this increase in angle strain is compensated by the decrease in torsional
strain.
The non-planar cyclopentane ring has a negligible angle strain and is therefore
more stable compared to cyclobutane and cyclopropane.
cis, trans isomerism in cycloalkanes
As discussed earliar in the chapter, cis-, trans-isomerism arises due to restricted
rotation in double bonds. Cyclic compounds can also have cis-, trans-isomerism
because the cyclic system prevents free rotation about single bond. In a cyclic
compound, if the substituents are present on the same side of the ring, it is said
to be cis isomer and if substituents are present on opposite sides of the ring it is
termed as trans isomer. The substituted cycloalkanes posses chiral centre and
exist as enantiomers. Some of the isomers posses the plane of symmetry as
shown in the figure below and thus, do not exist as enantiomers.
Chair conformation
This is the most stable conformation of cyclohexane as it is free from torsional
strain. All the twelve hydrogens are in staggered state as evident form Newman
projection. The bond angle is nearly 109.5° and thus, it is free from angle strain
also.
Boat conformation
Twisting about carbon–carbon single bond of the chair form results in the
formation of boat conformation. Boat conformer is free from angle strain.
However, in boat conformation the hydrogens are in eclipsed state, which causes
torsional strain in the molecule. Along with this the hydrogen at C1 and C4 are
close to each other and experience van der Waals repulsion known as flagpole
interaction. The torsional strain and flagpole interaction make boat conformation
less stable compared to chair conformation.
Chair conformation >> twist boat conformation > boat conformation > half chair
conformation
In the above conformations, (a,a) and (e,e) represent trans- isomers, whereas
(a,e) or (e,a) represent cis- isomers.
1,3-Dimethylcyclohexane
Different chair conformations possible for 1,3-dimethylcyclohexane are:
In these conformations, (a,a) and (e,e) represent cis- isomers, whereas (a,e) or
(e,a) represent trans- isomers.
1,4-Dimethylcyclohexane
Different chair conformations possible for 1,4-dimethylcyclohexane are as
follows:
In the conformations above, (a,a) and (e,e) represent trans-isomer whereas (a,e)
or (e,a) represent cis-isomers.
Stability of conformers in dimethylcyclohexanes
In 1,2-, 1,3- and 1,4-dimethylcyclohexane, the stability of conformers is decided
on the basis of the following:
(i) The (e,e) conformer is the most stable and the most preferred conformation
because of the absence of 1,3-diaxial interactions.
(ii) The (a,a) conformer is the least stable because of 1,3-diaxial interactions
that are experienced by both methyl groups.
(iii) The (a,e) or (e,a) conformers are more stable than (a,a) but less stable
than (e,e) because one of the methyl group at axial position experiences
1,3-diaxial interactions.
Exercises*
1. Classify the following as ‘chiral’ and ‘achiral’.
(a) Scissors
(b) Shoe
(c) Hammer
(d) Nail
(e) Screw
(f) T-shirt
(g) Foot
(h) Fork
(i) Nose
2. In the following compounds, indicate the stereogenic (or chiral) centre by
putting an asterisk mark over it.
(a) CH3CH(Br)CH2OH
(c) CH3CH(Cl)CH(Br)CH3
(b) C6H5CH(OH)CH3
(d) CH3CH2CH(Cl)CH(CH3)CH3
3. What are stereoisomers?
4. Define the terms enantiomers and diastereomers.
5. Comment on the physical and chemical properties of enantiomers and
diastereomers.
6. What is optical activity? What is the necessary condition for a molecule to be
optically active?
7. What are meso compounds? Are the meso compounds optically active or
inactive? Explain your answer through a suitable example.
8. What is general formula for determining the number of stereoisomers
possible for a given compound? Indicate the number of stereoisomers
possible for each of the following:
(a) CH3CH(NH2)COOH
(b) CH3CH2CH(OH)CH2CH3
(c) CH3CH2CH(Br)CH(Cl)CH3
(d) CHOCH(OH)CH(OH)CH(OH)CH2OH
9. Draw the Fischer projections for all possible stereoisomers of:
(a) C6H5CH(NH2)COOH
(b) HOOCCH(CH3)CH(CH3)CH2OH
10. In accordance with the sequence rules, assign the decreasing order of
priority to following groups/atoms.
(a) –CH3, –OH, –NH2, Cl
(b) –Br, –CH2Br, –CH2CH3, —SH
(c) –Cl, –Br, –F, –CH2I
(d) –CH==CH2, –CH2CH==CH2, —CH2CH2CH3, —COOH
(e) –Cl, –COCH3, CONH2, COCl
(f) –COOH, –CH2COOH, –CH(Cl)COOH, —CH3
(g) –OCH3, –OH, –NH2, –F
(h) –H, –D, –CH3, –T
(i) –CH2CH3, –CH3, –CH2OH, –H
(j) –CH2OH, –CH2COOH, –CH3, –H
11. Assign the R and S configuration to the following:
(f)
22. (a) E (b) E (c) E (d) Z (e) Z
* Answers to selected exercises are given at the end.
Chapter4
Fundamentals of Organic Reactions
Being a temporary effect, it does not affect the physical properties of a molecule.
[Delocalization of π electrons]
In Chapter 1, we have discussed the concept of resonance in detail (refer section
1.6). The resonance effect (or mesomeric effect) is a permanent effect which
involves delocalization of π electrons in a system. The electrons involved in
delocalization may be π-electrons of a double bond, or π electrons of the
aromatic system (as in benzene), or lone pair of electrons present on an atom.
In other words, delocalization may involve
(1) Overlap of p orbitals involved in the formation of π bonds (π–π overlep)
or
(2) Overlap of p orbital of an atom (vacant or filled) with p orbitals involved
in π bond formation (p–π overlap)
Delocalization of π electrons through π–π overlap
Delocalization of π electrons through π–π overlap occurs in conjugated systems,
that is, a system where π bonds are separated by one σ bond only. For example,
in buta-1,3-diene, each carbon is sp2 hybridized and thus each carbon has a p
orbital. These four p orbitals overlep with each other to form π bonds. The π
bonds are not localized between two carbons (C1 and C2, or C3 and
C4) rather π electrons are delocalized (or distributed equally) over all the four
carbons. This delocalization of π electrons makes all the carbon–carbon bond
lengths in buta-1,3-diene same and the value of carbon carbon bond length in
butadiene lies in between that of carbon–carbon single bond and carbon–carbon
double bond length (refer also section 7.2). The delocalization lowers the
resonance energy (more appropriately delocalization energy—refer section 1.6
for this terminology) and thus stabilizes the system.
Similarly in benzene, the π electrons are delocalized over all the six carbons of
the ring (refer Chapter 9 for details).
The groups containing π bonds such as
and so on when attached directly to benzene ring withdraw electrons from ring
by participation in delocalization through π–π overlap. The π bonds of such
groups are in conjugation with π electrons of the benzene ring system. Such
groups are said to exhibit minus resonance effect or minus mesomeric effect
(–R or –M effect).
The delocalization further explains the low reactivity of vinyl chloride and
chlorobenzene due to strengthening of carbon–chlorine bond. The +R effect in
chlorobenzene and vinyl chloride results in the development of a double bond
character between carbon and chlorine, which provides the extra stability to this
bond (refer Sections 11.5.2 and 12.3.1).
Further in p–π overlap, the delocalization of π-electrons may occur through
vacant or half filled p orbitals. This explains the stability of carbocations and
free radicals through resonance effect and is discussed later in this chapter.
4.2.1 Carbocations
Heterolytic cleavage in an organic molecule where carbon donates the shared
pair of electrons to the leaving group results in the formation of carbocation,
where, carbon carries positive charge. The carbocation is the general term used
for the positively charge carbon. Based on the type of structure and type of
hybridization involved in the formation of carbocation some other terms used for
the purpose are carbenium ion and carbonium ion (refer Notabilia 5).
Carbocations are formed as a consequence of heterolytic cleavage. For example,
in case of haloalkanes, the removal of halide ion results in formation of
carbocation. Similarly, alkenes and alcohols in acidic medium result in the
formation of carbocation.
In a carbocation, carbon is bonded to three atoms or groups (trivalent) and has
only six electrons (sextet) so it behaves as an electron deficient species. A
carbocation is sp2 hybridized with a vacant p orbital and has a planar geometry.
A carbocation once formed may undergo reaction with an electron rich species
i.e. nucleophile, or may undergo deprotonation to form an alkene, or may
undergo rearrangement (you will come across a number of reactions where
carbocations are formed and the reactions carbocations undergo, at various
places throughout the text).
Stability of carbocations
A carbocation is classified as 1o, 2o, or 3o depending upon the number of
carbons (1, 2 or 3 respectively) attached to positively charged carbon. Further,
the carbocations may be categorised as alkyl, allyl, benzyl or vinyl cations. For
example
Both are primary (1o) carbocations but are highly stable. The stability of these
carbocations
is attributed to the resonance effect. In both the cases, the vacant p orbital on
carbon
bearing positive charge is in conjugation with π bonds and thus delocalization
occurs through
p-π overlap.
In allyl cation, delocalization occurs through resonance effect (–R effect) and it
is a resonance hybrid of two contributing structures. Since, in general, resonance
effect dominates inductive effect, the carbocation which involves delocalization
through resonance effect are more stable than those where inductive effect
causes the delocalization.
In benzyl cation, the positive charge on carbon is in conjugation with π electrons
of benzene ring and undergoes a –R effect. Both, allyl and benzyl cations are
stabilized by resonance but benzyl cation is more stable compared to allyl
cation because in benzyl cation, the number of contributing structures are more
as compared to allyl cation (Recall more the number of contributing structures,
more is the stability).
In benzyl cation, the replacement of hydrogen by phenyl group results in the
formation of diphenyl and triphenylmethyl cations.
The order of stability of these resonance stabilized cations is [C] > [B] > [A]. In
[A], the positive charge is delocalized over one benzene ring while in [B] and
[C], the positive charge is delocalized over two and three benzene rings
respectively. The number of contributing structures is maximum for [C] i.e. nine
while it is six and three for [B] and [A] respectively.
The carbocations are reactive intermediates which are short lived. One of the
most stable carbocation, namely the ‘tropylium ion’ has been extensively
studied. The stability of tropylium ion (cycloheptatrienyl cation) is attributed to
extensive delocalization.
The allyl and benzyl cations which are substituted at carbon carrying positive
charge are found to be more stable than 3° alkyl cations.
4.2.2 Carbanions
In an organic molecule heterolytic cleavage of a bond where carbon retains the
shared pair of electrons, results in the formation of carbanion. In this case,
carbon carries negative charge. In general, carbanions are formed by the removal
of hydrogen from a carbon in presence of a strong base. The formation of
carbanion is facilitated if the carbanion is attached to an electron withdrawing
group. For example,
The negative charge delocalization occurs in allyl and benzyl anions through
resonance effect
(+R effect). The resonance effect contributes towards the stability of these
anions. A benzyl anion is more stable compared to allyl anion because of
more number of contributing structures.
Similarly, the diphenylmethyl anion and triphenylmethyl anion are more stable
compared to benzyl anion. In diphenyl methyl anion the negative charge is
delocalized over two benzene rings whereas in triphenylmethyl anion the
negative charge is delocalized over three benzene rings. The order of stability of
phenylsubstituted methyl anions is thus,
Due to resonance effect, the allyl and benzyl radicals are more stable than 1o,
2o, or 3o alkyl free radicals. Thus, we can summarize the stability order of free
radicals discussed so far, as follows:
Benzylic > allylic > 3o > 2o > 1o > C•H3
4.2.4 Carbene
The neutral species which have divalent carbon with an unshared electron pair
are termed Carbenes. In carbenes, carbon has six electrons (sextet) and hence,
carbenes are electron deficient in nature. The carbene carbon may be sp2 or sp
hybridized.
The carbene with sp2 hybridized carbon has planar shape. The hybridized carbon
has a vacant p orbital and electron pair is present in sp2 hybrid orbital. Thus,
ground state of a planar carbene has a singlet state.
The carbene with sp hybridized carbon has a linear shape. The hybridized carbon
has two pure p orbitals each of which carries an unpaired electron. Thus, ground
state of a linear carbene has triplet state.
One of the most familiar reaction, that is, Reimer Tiemann reaction involves
carbene as a reactive intermediate.
4.2.5 Nitrene
Nitrene can be considered as the nitrogen analogous of carbene. Nitrene is
monovalent and has two unshared pairs of electrons on nitrogen. In nitrene, six
electrons (sextet) are present and it is electron deficient. Nitrene is an important
reactive intermediate in Hofmann degradation and other related reactions.
4.3 REAGENT TYPES
and
are not electrophiles as positive charge on oxygen is due to higher
valency.
Nucleophiles are electron rich species and in general any nucleophile bears
atleast one lone pair of electrons. The nucleophiles may be negatively charged or
neutral molecules. In a reaction, they always seek a site to which electrons can
be donated, that is, nucleophiles get bonded to electron deficient centres.
Electrophiles and nucleophiles can be classified under two categories, namely
charged and neutral. The classification of electrophiles and nucleophile has been
summarized in Table 4.1.
Electrophilicity describes the relative strength of electrophiles, that is, the speed
with which they react during a reaction while nucleophilicity is the term used for
describing the relative strength of nucleophiles, that is, the swiftness with which
a nucleophile reacts during a reaction.
4.4 TYPES OF REACTIONS
Chemical reaction basically involves the cleavage of existing bonds and
formation of new bonds. As we have already discussed the structure of molecule,
their reactive sites, electronic displacements, reactive intermediates, and type of
reagents (electrophiles and nucleophiles), now we are in a position to classify the
general organic reactions into the following categories:
1. Substitution reactions
2. Addition reactions
3. Elimination reactions
4. Rearrangement reactions
5. Oxidation and reduction reactions
Here we are giving a brief introduction to the different types of reactions
mentioned above. The chemistry of functional groups which has been discussed
in subsequent chapters is mainly the study of the reactions of these categories. A
detailed discussion on these reactions is dealt separately at appropriate places
through out the text.
Substitution reactions
These reactions involve the displacement of an atom or a group by another atom
or group. Substitution occurs in highly stabilized systems. For example, it takes
place at
(i) sp3 hybridized carbons as in alkanes, haloalkanes, and alcohols.
(ii) sp2 hybridized carbons of benzene and its homologous aromatic
compounds.
These reactions may further be classified as free radical, electrophilic, or
nucleophilic substitution reactions.
Addition reactions
These reactions occur in unsaturated systems where
(i) sp2 hybridized centre gets converted into sp3 hybridized centre
(ii) sp hybridized centre gets converted to sp2 or sp3 hybridized centre.
A number of reactions in alkenes, alkadienes, alkynes, carbonyl compounds etc.
fall in this category. Further, these reactions may be categorised as free radical,
electrophilic or nucleophilic addition reactions.
Elimination reactions
These reactions involve removal of two atoms or groups from a molecule. The
elimination of two atoms (or groups) may occur from same atom or different
atoms in molecules and accordingly the elimination reactions may be classified
as
(i) α-Elimination or 1,1-elimination: For example formation of carbene from
chloroform in presence of a base involves a 1,1-elimination of HCl from
chloroform molecule.
In this rate equation, ‘a’ is order of reaction with respect to reactant ‘A’ and ‘b’
is the order of reaction with respect to reactant ‘B’. The overall order of this
reaction is ‘a + b’.
In a multi-step reaction, the slowest step is the rate determining step. The
collision of reactant molecules results in the formation of products. The number
of reactant species colliding in a rate determining step determines the
molecularity of a reaction. If only one species reacts, the reaction is
unimolecular; if two species collide and react in the rate determining step it is
bimolecular. The factors affecting the rate of reaction are:
(a) Energy of activation, Ea: Lower the value of energy of activation, Ea,
higher is the rate of reaction.
(b) Concentration of reactants: The higher the concentration of reactants in
the rate determining step, higher is the rate of reaction.
(c) Temperature, T: The rate of reaction increases with an increase in
temperature.
(d) Nature of solvent: Rate of the reaction may increase or decrease depending
upon the type of solvent used.
(e) Use of catalyst: A catalyst provides an alternate path for a reaction with
lower Ea value and thus, increases the rate of reaction.
Fig. 4.1 (a) Energy change in a chemical reaction; energy profile of exothermic (b) and endothermic (c)
reactions.
Fig. 4.2 Energy profile of a Fast (low Ea) and slow (high Ea) reaction.
Fig. 4.3 Energy profile for two step reactions showing transition states (T.S. I and T.S. II) and the
intermediate.
4.6 STERIC EFFECT
The presence of groups or atoms in close proximity of each other causes van der
Waal repulsions and this phenomenon is termed steric effect (also known as
steric hindrance). Steric effect largely depends upon the size (bulkiness) of the
group or atom and arises from their arrangement in reacting species.
This effect has a marked impact on the rate of reaction, its nature and the extent
to which a reaction proceeds under a given set of conditions. Even if the reaction
conditions are favourable, there may be a change or inhibition of reaction due to
steric effect. Similarly, steric effect may also alter the acidic and basic strengths
of organic molecules.
The stability of molecules their chemical reactivity and few of the physical
properties (like acidity and basicity) are greatly influenced by steric effect and
some common examples are tabulated in Information Chart-II.
4.7 SOLVENTS IN ORGANIC REACTIONS
A homogeneous mixture of two or more components (a solute and a solvent) is
known as solution. In organic chemistry, almost all the reactions are carried out
in an appropriate solvent. In a solution, solvent molecules surround the
molecules or ions and their interaction is known as solvation. The nature of
solvent plays an important role in carrying out a reaction. Solvents are broadly
classified into two categories, namely
(a) Protic and aprotic solvents, and
(b) Polar and non-polar solvents.
Protic solvent
A solvent which contains a hydrogen attached to an electronegative atom such as
nitrogen and oxygen, is termed protic solvent. For example,
Aprotic solvent
A solvent in which hydrogen is not attached to an electronegative atom such as
nitrogen and oxygen, is termed aprotic solvent. For example,
Polar solvents
The solvents having dielectric constant, ε value of 15 and above are termed as
polar solvents. A polar solvent may be protic or aprotic in nature. For example,
Non-polar solvents
The solvents which possess dielectric constant ε value below 15 are termed non-
polar solvents. For example,
The solubility follows the thumb rule ‘like dissolves like’, that is, a polar
substance is soluble in polar solvent and non-polar substance is soluble in non-
polar solvent. A solvent may solvate either the reactants or reaction
intermediates and thereby, cause an increase or decrease in the rate of reaction.
4.8 ORGANIC COMPOUNDS AS ACID AND
BASES
In Chapter 1 (Sec. 1.10) two concepts are explained for defining the compounds
as acid and base. One is Bronsted and Lowry concept according to which an acid
is a proton donor and base is proton acceptor. The second is Lewis concept
according to which an acid is an electron pair accepter and base is an electron
pair donor. The organic compounds like carboxylic acids, phenols, alcohols
show acidic character where as amines, amides etc. exhibit basic character.
Further terminal alkynes, active methylene compounds, α-hydrogen containing
nitrile and nitro compounds also exhibit acidic character.
These factors are discussed at appropriate places in the text along with the
chemistry of concerned functional groups in the subsequent chapters.
EXERCISES
1. What is the hybridization state of carbon in carbocation, carbanion and free
radical?
2. Write short note on heterolytic and homolytic cleavage.
3. How does inductive effect differs from electromeric effect?
4. What is hyperconjugation? How does it differ from resonance?
5. Explain the stability of following carbocations in terms of inductive effect
and hyperconjugation.
13. Name the category (type) of reaction to which the following belong.
Problem 1. Which of the following compounds are related as constitutional
isomers? Write also IUPAC names for these isomers.
Problem 3. Using curved arrows draw the contributing structures for the
following. Indicate which structure is more contributing and why?
Solution.
Problem 4. Classify the following as Lewis acid, Lewis base or neither:
Solution. Lewis acid is an electron deficient species that accepts an electron pair
to form a covalent
bond. A Lewis base on the other hand donates a pair of electron during the
formation of covalent bond. Thus, among the given examples the Lewis acids
and bases are as follows:
Problem 5. 2,4-dinitrophenol has pKa = 4.1 and nitromethane has pKa = 10.2.
Which one is a stronger acid? Also explain whether reaction given below will go
to right or left?
The given reaction will go to left to form weak acid and weak base from strong
acid and strong base (on right side)
Problem 6. Give the IUPAC nomenclature for the following bridged
hydrocarbons.
Solution. The bicyclic bridged compounds have two or more carbon atoms
common to both the rings. The common atoms are designated as bridgeheads.
These are named as bicyclo [x.y.z] alkanes, where x, y and z are the number of
carbons in each of the three bridges connecting the bridgeheads. The following
steps are considered for naming the bridged molecules in accordance with the
IUPAC system:
(1) The total number of carbon atoms in all the rings including bridge atoms
is counted from which the parent name of the compound is derived.
(2) Further the total number of cyclic systems present in the molecule is
located and the system is designated as bicyclo, tricyclo, and so on
depending on the number of cyclic systems.
(3) Now the number of carbon atoms, around the bridged carbon atoms, is
counted individually. Then these numbers are written in the decreasing
order inside a square bracket.
(4) The numbering starts from one of the bridgehead and proceeds through
the larger ring to other bridgehead.
Keeping these steps in consideration, the IUPAC nomenclature of structure (i)
can be done as:
The total number of carbon atoms in the rings is six and it is an alkane. Hence,
its parent name is hexane. Further the number of carbon atoms in a skeleton
around the bridged carbons are 2, 2, and 0 respectively and it is bicyclic. Thus,
its IUPAC name is bicyclo[2.2.0]hexane.
Similarly, The IUPAC name for structure (ii) and (iii) can be written as
The IUPAC name for (iv) is bicyclo[2.2.1]heptane, already given for structure
(ii), (Only the structure is written in a different way).
Problem 7. Give the IUPAC name for the following spiral compounds
Solution. The spiral compounds are bicyclic compounds that have single carbon
common to both the rings. This common carbon is designated as spiro atom.
These compounds are named as
spiro [x. y] alkane. The x and y are the number of carbon atoms in each ring
joining the spiro atom and are written in square bracket followed by the parent
name derived from the total number of carbons in a system.
The numbering of such systems starts from the ring atom next to spiro atom
and proceeds from this ring through spiro atom to another ring.
If spiro compound is substituted then numbering starts from the ring carrying
the substituent and continues further to other ring.
Thus, spiro compounds [I] and [II] can be given the IUPAC names as follows:
If two rings are of different size than numbering starts next to spiro atom and
proceeds around the smaller ring first then through the spiro atom proceeds
around the second bigger ring.
If this type of spiro compound is substituted, even then numbering starts from
the smaller ring and continues further to other ring. The position of
substituent is numbered accordingly.
Thus, spiro compounds [III] and [IV] can be given the IUPAC names as follows:
Solution.
Hydrogen attached to double bonded (olefinic) carbon is termed vinylic
Hydrogen attached to carbon present next to double bonded (olefinic) carbon
is termed allylic
Hydrogen attached to the carbon directly attached to benzene ring is termed
benzylic
Number of allylic, benzylic and vinylic hydrogens present in the given structures
are indicated below.
Each allylic hydrogen is indicated by grey screen, vinylic hydrogens are circled
and hydrogens with square around them indicate benzylic hydrogens.
Problem 9. Indicate whether the following two structures are identical or related
to each other as enantiomers? Can the stereoisomers of a molecule with one
chiral centre (stereogenic centre) be related as diastereomers?
Solution. The three dimensional structure (i) is first written in the Fischer
projection form. Further the priority is assigned to the group/atoms according to
sequence rule (see section 3.4). The decreasing order of priority is Br > CH3 > D
> H.
Now configuration is assigned to both structures (i) and (ii) by writing the
Fischer projection in such a way that least priority H atom lies at a vertically
downward position (see section 3.4.1).
The configuration of (i) is S and for (ii) is R. Hence, they are related as
enantiomers.
It should be noted that the molecules with one chiral centre can have only two
possible, stereoisomeric forms which are mirror images of each other. Thus, they
always exist as enantiomers and not as diastereomers.
Problem 10. Write the Fischer projection for (a) R-2,3-dihydroxypropanal
(glyceraldehyde)
(b) S-2-chloropropanoic acid.
Solution. To draw the Fischer projection from the given name of compound,
with desired configuration, proceed as follows:
Step 1: Write the structure of compound
Step 2: Identify the stereocentre
Step 3: Identify the four groups/atoms attached to the stereocentre and assign the
priority order in accordance with CIP rules (refer p. 75)
Step 4: Draw a cross (+) for Fischer projection and write the least priority group
vertically downward
Step 5: Now place the top three priority groups in clockwise manner (for R) or
in an anti-clockwise manner (for S) as desired
For “R” configuration
Groups/atoms can be arranged in the following manner across the vertical and
horizontal line on a cross.
(a) Following the steps mentioned above, the Fischer projection for R-2,3-
dihydroxypropanal (glyceraldehyde) can be written as
(b) Following the steps mentioned above, Fischer projection for S-2-
chloropropanoic acid can be written as
Problem 12. Give the R and S configuration, and their IUPAC names, for the
following compounds:
Solution. Assigning configuration at each stereocentre in (a):
The compound (a) has two stereocentres and procedure for assigning the
configuration at these stereocentres is as follows:
Thus the IUPAC name for compounds (a to d) along with configuration around
stereocentre are as follows:
(a) (1R, 2S)-1,2-dimethylcyclohexane (c) (1S, 2R)-1-bromo-2-
chlorocyclohexane
(b) (1R, 2R)-1,2-dimethylcyclohexane (d) (3R)-3-methylcyclopentene
Problem 13. In the above problem (no. 12) the compound (a) is named as (1R,
2S)-1,2-dimethyl-cyclohexane. Can it be named as (1S, 2R)-1,2-
dimethylcyclohexane?
Solution. The answer is NO.
In compounds when the same substituents are present at different stereocentres,
in such a way that in IUPAC the lowest possible number can be on either of the
carbon then the configuration decides the numbering for nomenclature.
In 1,2-dimethylcyclohexane numbering can start from either of the carbon
carrying methyl substituent. However, once configuration is assigned at these
carbons (stereocentre) then carbon having ‘R’ configuration gets preference in
numbering over carbon having ‘S’ configuration. The numbering can start only
from carbon with ‘R’ configuration and not from carbon with ‘S’ configuration.
Thus, the compound (a) is named as (1R, 2S)-1,2-dimethylcyclohexane and not
as (1S, 2R)-1,2-dimethylcyclohexane.
Solution. The sawhorse representations are written in a form where CH3 groups
are in the eclipsed position. The structure with eclipsed methyl group are then
written directly in Fischer projection form, which indicates that the two
structures are related as enantiomers in the manner as shown here.
The Fischer projections clearly indicate that the two forms (i) and (ii) are
diastereomers.
Problem 17. (i) Name the molecule and indicate the carbon-carbon bond around
which free rotation is occurring as depicted by the Newman projection given
below.
(ii) Which of the following does not represent a conformer of C5H12?
Identify the molecules and indicate the carbon-carbon bond around which
free rotation occurs as depicted by following Newman projections?
Solution. (i) The given Newman projection indicates the presence of four
carbons (molecular formula C4H10) and thus, the molecule is butane. The
Newman projection represent the rotation around C1-C2 bond of butane as
shown:
(ii) As explained in the earlier problem, the given Newman projections (a-d)
indicate the presence of five carbons (molecular formula C5H12) whereas
the Newman projection
(e) indicates the presence of four carbons (molecular formula C4H10).
The Newman projections (a-d) represent conformers of isomeric pentanes.
Their structures and the carbon-carbon bond around which free rotation
occurs are given as follows:
The Newman projection (e) represents conformer of butane (section 3.6.7) and
indicates the rotation around C2-C3 bond of butane as shown:
Problem 18. What will be the Newman projection for the following:
Solution. In case of alkenes the rotation around C–C bond is restricted due to
double bond. More over the molecule has the planar structure because of sp2
hybridization. Thus, there is only one Newman projection possible for each of
the given alkenes.
Newman projections
Problem 19. How many staggered conformations are possible for 1,2-
dichloroethane? Why does dipole moment of this compound increase with
temperature?
Solution. 1,2-dichloroethane has three staggered conformations, namely anti
(staggered) conformation [I] (μ = 0), and gauche (skew staggered) conformations
[II] and [III] (μ ≠ 0). Here μ refer to the dipole moment of the molecule.
As temperature increases, the molecules gain energy and move from lower
energy (most stable) conformation [I] to higher energy (less stable)
conformations [II] and [III] and thus, the dipole moment of molecule increases
with increasing temperature.
Problem 20. Draw structures of given dimethylcyclobutanes and indicate which
one will be optically active ?
(a) 1,1-dimethylcyclobutane
(b) Cis-1,2-dimethylcyclobutane
(c) Trans-1,2-dimethylcyclobutane
(d) Cis-1,3-dimethylcyclobutane
(e) Trans-1,3-dimethylcyclobutane
Solution. Only (c) is optically active.
Structures of all dimethylcyclobutanes (a-e) are as follows:
Problem 25. A sample of aspartic acid has specific rotation +4.5° mL/g.dm. If
αobs = 0.9°, when taken in cell of pathlength 0.8 dm, calculate the concentration
of sample.
Problem 28. Arrange the following in the order of their increasing acidic
strength:
Solution. The acidic strength of these compounds can be explained on the basis
of stabilities of their corresponding conjugate base. A compound with most
stable conjugate base is most acidic.
The loss of proton (H+), in these cases, result in the formation of corresponding
carbanions (a conjugate base). The triphenylmethyl carbanion (Ia) is much more
stabilized as delocalization involves three benzene rings. In case of
diphenylmethyl cabanion (IIa) the delocalization of electron involves the two
benzene rings and in methylbenzene (IIIa) it involves only one benzene ring (see
p. 124). Thus the stability of conjugate base follows the order:
Thus, the acidic strength follows the order as
I > II > III
Problem 29. Give the decreasing strength of following species as a base:
Solution. All the three species are derived from triphenylmethane, that is,
triphenylmethyl
anion (I), triphenylmethyl radical (II) and triphenylmethyl cation (III). All these
species I, II, and III, are equally stabilized through delocalization. Thus the
Lewis acid and base concept explain the basicity, which states that the
availability of electrons is directly related to the basic strength of that species. A
carbanion, I has a pair of electron and hence most basic in the given examples.
Free radical, II and carbocation, III are electron deficient species. However, free
radical-II is a stronger base (because of the presence of an electron) as compared
to carbocation (III), which is electron deficient. In other words carbanion, I can
accept the H+ readily and thus is a strong base. A positively charged species has
least affinity for accepting a proton.
Thus, the basic strength follows the order as
I > II > III
Problem 30. Identify each of the given carbocations as primary (1º), secondary
(2º), or tertiary (3º) along with their vinylic or allylic nature (wherever possible).
Also give the IUPAC names for these carbocations.
Comment, if for these carbocations one writes corresponding carbanion or free
radicals, will their nature as primary, secondary, or tertiary will change or will
remain the same?
Solution.
(a) A primary carbocation is one in which the carbon bearing the positive
charge, is attached to one carbon.
(b) A secondary carbocation is one in which the carbon bearing the positive
charge is attached to two carbons.
(c) Likewise, a tertiary carbocation is one in which the carbon bearing the
positive charge is attached to three carbons.
Carbocation II is 2º in nature, the oxygen donates its lone pair and stabilizes
carbocation through delocalization.
A. ALKANES
5A.1 INTRODUCTION
Alkanes belong to the class of hydrocarbons where all the carbons present in the
molecule are linked through single bonds (σ bonds) only and thus, referred as
saturated hydrocarbons. Alkanes follow the general formula CnH2n+2. The first
member of this class is methane (CH4). The carbon in alkanes is in sp3 hybrid
state and thus, has 4 hybrid orbitals. These hybrid orbitals of carbon overlap with
‘s’ orbital of hydrogen to form carbon–hydrogen σ bond or hybrid orbital on one
carbon may overlap with hybrid orbital on another carbon (sp3–sp3 overlap) to
form carbon–carbon σ bond. The sp3 hybridization of carbon in alkane provides
a tetrahedral shape to molecule (see Section 1.4.1).
Due to saturation, the alkanes are highly stable and show little reactivity, thus,
they are popularly known as paraffins (Latin: Para means little, affins means
affinity).
1°, 2°, 3° carbons. In alkanes (C3 and onwards), all the carbons are not
equivalent and are referred as primary (1°), secondary (2°), or tertiary (3°)
carbons depending upon the number of carbons attached.
The hydrogens attached to 1o, 2o, 3o carbons are referred to as 1°, 2°, 3°
hydrogens respectively.
The IUPAC nomenclature of alkanes has been discussed in detail in Chapter 2.
Few representative examples of alkanes are as follows.
Isomerism
Alkanes exhibit chain isomerism as well as stereoisomerism (conformations).
The conformations of alkanes have already been discussed in Chapter 3. Alkanes
containing four or more carbon atoms show chain isomerism. For example, the
chain isomers of C4H10 and C5H12 hydrocarbons are:
Isomeric alkanes of molecular formula C4H10
For example,
The
Lithium dimethylcuprate can further be used for preparation of ethane
(symmetrical) or propane (unsymmetrical) as follows
Via alkyllithiums
Alkyllithiums react with compounds containing active hydrogen such as water,
alcohol, and so on, to give corresponding alkane. These reactions of
alkyllithiums are similar to that of Grignard reagent (p. 173). For example
Further, the preparation and various reactions of alkylithium are also discussed
in Chapter 25.
By hydrolysis of alkylboranes
Alkenes on reaction with borane form trialkylborane, which on hydrolysis with
acetic acid give corresponding alkane. For example,
5A.3 CHEMICAL PROPERTIES OF ALKANES
This section discusses various chemical properties of alkanes including free
radical substitution reactions (halogenation, nitration, sulfonation,
chlorosulfonation), oxidation reactions, aromatization, isomerization, and
pyrolysis reactions.
5A.3.1 Halogenation
The alkanes react with halogens, at high temperature or in presence of light, to
form haloalkanes.
The highly reactive chlorine radical can react with chloromethane to abstract a
hydrogen radical similar to reaction (1) above. The presence of electronegative
chlorine in CH3Cl makes the abstraction of hydrogen much easier as compared
to methane.
The abstraction of hydrogen from dichloromethane and trichloromethane is even
easier compared to chloromethane. This is because of the introduction of more
number of electronegative chlorine atoms.
The peroxides are known to be good free radical generators. They contain a
weak
oxygen–oxygen single bond, which gets homolytically cleaved to produce
radicals. Benzoylperoxide undergoes homolytic cleavage to produce phenyl
radicals as follows:
The phenyl radical combines with chlorine molecule to give chlorobenzene and
chlorine radical. The chlorine radical so generated reacts with methane leading
to chain propagation.
6
Reactions involving peroxides proceed through a free radical mechanism and
this clearly supports a free radical mechanism for reaction of methane and
chlorine in presence of light since in both the cases, same product is obtained.
NOTABILIA 6
The reaction can be made to halt at the chloromethane stage by taking higher
amount (concentration) of methane compared to chlorine. Similarly, chlorination
of ethane gives chloroethane.
The propagation step of the radical mechanism explains the formation of two
products as
The Lower the Ea value, more readily the reaction occurs to form free radical.
Surprisingly, the Ea value for chlorine is ‘maximum’ and as the data suggests,
the radical formation occurs relatively faster in case of fluorine and iodine. At
the same time, a free radical
once formed (irrespective of the ease with which it is formed) is sufficient to
carry out further reaction.
Thus, the Ea values in chain initiation step are not the only factor, which govern
the proceeding of halogenation reaction. So, along with Ea, we have to consider
the heat of reaction, ΔH involved in chain propagation.
Calculation of ΔH for chlorination of methane during chain propagation step
In chain propagation,
5A.3.2 Nitration
The reaction of alkanes with nitric acid results in the formation of nitroalkanes.
Nitration may be carried out at a high temperature of 400–500°C (vapour phase
nitration) or it may be carried out at a low temperature of 150°C (liquid phase
nitration).
Higher alkanes (C6 onward) undergo sulfonation which generally occurs at the
second carbon atom.
5A.3.4 Chlorosulfonation
The chlorosulfonation of alkanes results in the formation of alkanesulfonyl
chloride. The two reagents used for carrying out sulfonation are:
(a) Chlorosulfonic acid
(b) Mixture of chlorine and sulfurdioxide (Cl2 + SO2) in presence of light or
peroxide at a temperature of 40°–60°C.
5A.3.5 Oxidation Reactions
Combustion
Complete combustion of alkanes in the presence of air results in the formation of
carbondioxide and water as the final products. A general formula for combustion
of hydrocarbons is
Oxidation in presence of oxidizing agents
(i) Catalytic oxidation: In lower alkanes, a selective oxidation may result in the
formation of alcohol, aldehyde/ketone, or carboxylic acid. Specific reagents are
used for this purpose.
For example, methane results in the formation of methanal on oxidation with
MoO2 (at 400°C) and oxidation with Cu (at 200°C) results in the formation of
methanol in the following manner:
5A.3.6 Other Reactions
Insertion of carbene to alkanes
The alkanes undergo reactions with carbene (a reactive intermediate, section
4.2.4), and in the process C–H bond of alkane is converted into C–CH3 bond,
that is, insertion of carbene occurs at C–H bonds of alkane. The insertion of
carbene leads to the formation of a higher alkane and the reaction occurs
readily in a tert. hydrogen containing C–H bond.
The ease of insertion of carbene to C–H bonds follows the order 3° > 2° > 1°.
Dehydrogenation
Lower alkanes (upto C5), on heating in presence of catalysts such as Al2O3,
ZnO, or V2O5, undergo dehydrogenation to produce alkenes.
Aromatization
Straight chain alkanes (C6 and onwards), on heating in presence of Al2O3 and
Cr2O3 at 500oC–600oC, result in cyclization followed by dehydrogenation. The
reaction results in aromatization of alkanes.
For example, n-Hexane undergoes aromatization to give benzene.
Similarly, n-heptane gives toluene under identical conditions. The reaction is
shown as
Cracking or pyrolysis
The cracking process involves thermal decomposition of an alkane into fractions
of lower molecular weight by fission of C–C and C–H bonds. The cracking
process is widely used in petroleum industry. Cracking may be of the following
types:
(i) Thermal cracking: Cracking is carried out at high pressure and high
temperature
(> 500°C).
(ii) Catalytic cracking: This process involves the use of catalysts such as
SiO2, Al2O3, and natural or synthetic aluminium silicate zeolites. The
process improves both quality and quantity of gasoline.
(iii) Hydro cracking: This process is a combination of both catalytic cracking
and hydrogenation and is used to produce gasoline in high yields.
(iv) Steam cracking: Cracking process carried out in presence of steam by
heating at
700–900°C followed by rapid cooling is termed steam cracking.
For example,
Isomerization
Isomerization of alkanes (C4 and onwards) occurs in presence of HCl/AlCl3 or
HBr/AlBr3 at a temperature of 300°C.
5A.4 PETROLEUM
Petroleum is a decomposed product of the remains of marine organisms and
plants formed over the ages, under high pressure and temperature conditions. It
is a dark viscous oil found in interstices in rocks under high pressure. Petroleum
along with natural gas serves as a major source of alkanes (upto C50–C70),
cycloalkanes, and aromatic hydrocarbons along with organosulfur compounds.
Natural gas is always found along with petroleum.
Natural gas
The chief constituent of natural gas is methane (95%) though along with this a
little fraction of ethane (~4%), propane, butane and isobutene are also present.
The uses of natural gas can be summarized as follows:
(i) It is used as fuel and is commercially supplied as CNG (compressed natural
gas).
(ii) Incomplete combustion of natural gas results in the formation of carbon
black which is a fine powder. Carbon black is used as a pigment in ink,
paints, shoe polish and also as a filler in rubber tyres to increase their
strength.
Petroleum refining
Crude petroleum is a viscous mixture of number of hydrocarbons. Refining is
the process to obtain useful products of commercial and industrial importance
from crude petroleum. This involves fractional distillation, which separates the
mixture into a number of fractions in increasing order of boiling point and
molecular mass. In refineries, the mixture is introduced into tall fractionating
column and heated which results in the separation of different fractions. More
volatile fractions with lower boiling point are collected at the top of the column
whereas the less volatile fractions having higher boiling point get collected at the
bottom of the column. The residue of this refining is bitumen, which is used as a
binding material for road surfaces and also as a roofing material.
Table 5.5 enlists different fractions along with their composition and uses.
Octane number
One of the commercially important fractions of petrol refining is gasoline (or
petrol). The efficiency of gasoline as a fuel depends upon its octane number. The
higher the octane number, the better is the fuel.
The octane number of a fuel is taken to be the percentage of isooctane in a
mixture of isooctane and n-heptane, which has the same knocking property as
the fuel. For example, if knocking of a fuel is same as the knocking of the
mixture having 15% n-heptane and 85% of isooctane, then the octane number of
the fuel is 85.
In an internal combustion engine as the piston moves down the cylinder, a
mixture of fuel and air is introduced. The mixture gets compressed during the
return stroke of the piston. At the point of high compression, the mixture is
ignited by a spark plug and a smooth burning of fuel takes place. If premature
ignition of fuel occurs in the engine, that is, the fuel–air mixture explodes during
compression itself without any ignition from the spark plug, it results in the
knocking (cracking sound) of engine. Knocking decreases the efficiency of fuel
besides damaging the engine.
Branched chain hydrocarbons exhibit good antiknock properties, whereas
straight chain hydrocarbons exhibit poor antiknock properties. For rating a fuel,
an arbitrary reference scale has been chosen in which 2,2,4-trimethylpentane
(isooctane) is assigned an octane number 100 and
n-heptane is assigned an octane number 0 (zero).
Tetraethyllead (TEL) has good antiknock properties and is added to petrol for
increasing its octane number. Addition of 3.0 g of TEL per gallon of petrol may
raise the octane number by
15–20 units. However, due to environmental hazards of lead, unleaded petrol is
used now a days. The octane number of unleaded petrol is enhanced by addition
of a mixture of benzene, toluene, and xylene (BTX). Aromatic hydrocarbons also
show good antiknock properties.
5A.4.1 PETROCHEMICALS
These are the compounds obtained from fractions isolated from petroleum by
using different processes such as distillation, cracking, reforming, and
isomerization. Petrochemicals are major sources of industrially important
chemicals. These are used chiefly in the production of polymers, aromatic
hydrocarbons solvents, plastics detergents, alcohols, and so on.
Cracking (pyrolysis)
Higher fractions of petroleum refining which constitute less volatile or solid
hydrocarbons are heated at high temperature resulting in the formation of small
chain hydrocarbons including lower alkanes and alkenes as discussed earlier (pp.
194–95).
Uses of cracking:
1. Cracking process is used in the industries to obtain gasoline from higher
fractions of petroleum.
2. The alkenes obtained during cracking are used commercially for production of
(i) Isooctane (2,2,4-trimethylpentane) by alkylation (p. 235)
(ii) Alcohols and glycols.
(iii) Polymers, for example polyethene (Chapter 31).
Reforming and Isomerization
Reforming is the conversion of straight chain compounds to cyclic and aromatic
compounds. This process is used for the production of fuels with high octane
rating. For example hexane and heptane having, low octane number, on
aromatization form benzene and toluene (having high octane number)
respectively (pp. 193–94).
Isomerization of lower alicyclic hydrocarbons to higher ones followed by
dehydrogenation (aromatization) results in the formation of aromatic
compounds.
The xylenes obtained from isomerization of cyclooctane derivatives have the
immense importance in chemical industries. As these are oxidized to produce
benzenedicarboxylic acids (phthalic, isophthalic, terphthalic acids) which are
further used for the synthesis of various organic compounds.
5A.4.2 Coal
Coal is an important source of alkane and other hydrocarbons which are of
commercial importance. Different processes which are used to prepare synthetic
fuels from coal are discussed here.
Bergius process. Destructive hydrogenation of coal under high temperature and
high pressure conditions results in the formation of alkanes.
This process is used for the production of gasoline (synthetic fuel). The
reduction of synthesis gas (obtained from coal) results in the formation of
alcohol, which may be used as a fuel.
B. CYCLOALKANES
5B.1 INTRODUCTION
Cycloalkanes are the simplest type of alicyclic compounds. The general formula
for cycloalkanes is CnH2n. The first few members of the series are
The boiling points of alicyclic hydrocarbons increase regularly as the ring size
increases. Cyclic structures are rigid thus boiling points of cycloalkanes are
higher than the corresponding alkanes. Table 5.6 compares the boiling points of
a few cycloalkanes with correspoinding alkanes.
Although Baeyer’s theory explained the instability of three and four membered
ring systems, it failed to explain the stability associated with some larger rings.
Sachse suggested non-planar structure for cyclohexane (chair and boat form),
which was further supported by E. Mohr. The Sachse Mohr theory confirms the
existence of cycloalkanes as non-planar (puckered) strain free rings. This is
evident from the experimental data, cyclohexane ring is the most stable system
and the larger ring systems such as C12, C13, and so on show considerable
stability. Strain in cycloalkanes can be calculated quantitatively by comparing
the heat of combustion values per CH2 group. The unusual stability of
cyclohexane due to non-planar structure, has already been discussed in Chapter
3.
5B.3 PREPARATION OF CYCLOALKANES
Some important methods of preparation of cycloalkanes are discussed as the
subject matter of this section.
By the addition of carbene to alkenes
Carbenes are neutral, divalent species. Their electrophilic addition to alkenes
results in the formation of cyclopropane derivatives.
The use of diethylmalonate in the synthesis of alicyclic compound has also been
discussed in Chapter 20.
By Dieckmann condensation
The esters of dicarboxylic acids (C6, C7, or C8) in presence of a base such as
sodium ethoxide undergo an intramolecular condensation to give cyclic β-
ketoesters (Dieckmann condensation), which by a series of reactions may be
converted to cycloalkanes. The reaction is used for the preparation of
cyclopentane, cyclohexane, and cycloheptane. For example, diethyladipate is
used for the preparation of cyclopentane as follows.
Diels–Alder reaction
The thermal or photochemical addition of alkenes to buta-1,3-diene produces
cyclohexene. It is a 1,4- cycloaddition reaction involving a 4 π-system (diene)
and an unsaturated compound having 2-π-system (dienophile) to give a cyclic
adduct. This is one of the best methods for the preparation of cyclohexane
derivatives (for details refer section 7.4.3).
5B.4.1 Halogenation
Photohalogenation
Cycloalkanes react with halogens in presence of light to produce corresponding
halocycloalkanes.
Catalytic halogenation
The halogenation in presence of a catalyst or at high temperature results in ring-
opening of cyclopropane and cyclobutane to yield dihaloalkanes.
5B.4.2 Catalytic Hydrogenation
Cyclopropane and cyclobutane on catalytic hydrogenation undergo ring-opening
to give propane and butane respectively. Cyclopentane and cyclohexane are
stable even at high temperature conditions and do not undergo ring-opening.
6.1 INTRODUCTION
The class of hydrocarbons containing a carbon–carbon double bond is termed
alkenes. Alkenes, the unsaturated hydrocarbons, have the general formula
CnH2n.They contain two hydrogens less than corresponding alkanes with same
number of carbon atoms. The first member of this series is, H2C=CH2, ethene
commonly known as ethylene. The alkenes are also called olefins (Latin: oleum
means oil and fiant means producing).
The carbons in ethene are sp2 hybridized. The sp2-sp2 orbital overlap results in
carbon–carbon σ bond formation while sp2-s overlap results in carbon-hydrogen
σ bond formation. The pure p orbitals on each carbon overlap to form carbon–
carbon π bond. Ethene has a planar structure (see details in section 1.4.2)
The branching in alkenes lowers the boiling point compared to isomeric linear
alkenes (Table 6.2). Alkenes are less denser than water. Alkenes are insoluble in
water but soluble in non polar solvents. In comparison to alkanes which are non
polar, the alkenes show slight polarity due to presence of weakly held electrons
in the π-bond.
6.2 PREPARATION OF ALKENES
In nature, alkenes do not occur in free form. Commercially, the lower alkenes are
obtained by cracking of petroleum. The higher alkenes have little difference in
their boiling points and cannot be separated by fractional distillation, thus,
cracking cannot be used for the preparation of higher alkenes. The various
methods are used for the preparation of alkenes. Some important methods are
reduction of alkynes and elimination reactions of haloalkanes, alcohols and
quaternany ammonium hydroxides. This section offers an explicit discussion on
various preparative methods of alkenes.
Saytzeff’s rule: This rule states that whenever there is a possibility of formation
of two alkenes by elimination, the formation of more substituted alkene is
favoured. In other words, the hydrogen is removed from β-carbon having lesser
number of hydrogen(s).
Dehalogenation of dihaloalkanes
The vicinal dihaloalkanes undergo dehalogenation in presence of zinc and
methanol to produce alkenes. The other dehalogenating agents used for this
purpose are Zn–Cu couple, magnesium etc.
General Mechanism
The first step of reaction is protonation of alcohol which forms an oxonium ion.
The second step involves cleavage of carbon-oxygen bond that result in removal
of a water molecule and formation of carbocation as an intermediate. The third
step is deprotonation of carbocation to form an alkene. The loss of proton occurs
from the β-carbon of carbocation. The overall mechanism can be represented as
follows:
The details and mechanism of the reaction is discussed in Chapter 17 (pp. 582–
83).
Kolbe’s electrolytic method
The concentrated aqueous solution of alkali salts of dicarboxylic acids on
electrolysis results in the formation of an alkene at anode. For example
6.3 CHEMICAL PROPERTIES OF ALKENES
This section disucsses various chemical properties of alkenes such as
Electrophilic addition reactions, free radical addition reactions, oxidation
reactions, isomerization, polymerization,
Diels-Alder cycloaddition reactions and allylic substitution reactions.
As an example,
In case of an unsymmetrical alkene like propene, reaction with HCl may result in
the formation of two products, namely 1-chloropropane or 2-chloropropane.
However, it is 2-chloropropane which is produced selectively.
Markovnikov’s rule: The addition of polar reagents like HX to unsymmetrical
alkenes follows Markovnikov’s rule, which states that the negative part of the
addendum (polar reagent) adds to that carbon of double bond which has
minimum number of hydrogen(s).
This method cannot be used for the preparation of 1o alcohols, except in case of
reaction with ethene, which yields ethanol. Further, during the reaction the
carbocation rearrangement may occur through 1,2-hydride shift and 1,2-methyl
shift.
Addition of water (Formation of alcohol)
The acid catalyzed reaction of water with alkenes results in the formation of
alcohol. The addition follows Markovnikov’s rule.
General reaction
Mechanism
For example,
Step 2. Demercuration
It’s a highly regioselective reaction and occurs readily even at room temperature
to give alcohol (more than 90% yield).
Similarly,
Oxidation:
Similarly,
The hydroboration-oxidation reaction is carried out readily and results in high
yields of the product.
For example,
The reaction of alkene with alkaline KMnO4 is known as
Baeyer’s test and is used to test unsaturation. Unsaturated
compounds react with alkaline KMnO4 (purple in colour) to form
diols (colourless). Thus, decolourization of KMnO4 by an organic
compound indicates the presence of double bond therein.
With OsO4
Alkenes react with osmiumtetroxide to form an osmate ester, which on
hydrolysis produces cis-diols.
Similarly
Olefinic carbon with no hydrogen attached to it gets oxidized only upto ketones,
which are very difficult to be oxidized further to carboxylic acids.
Ozonolysis
Ozone exhibits the electrophilic character and reacts rapidly with alkene in
presence of a solvent (such as carbon tetrachloride or light petrol) to produce
cyclic peroxide known as ozonide.
The reaction of ozone with alkene results in the cleavage of carbon-carbon
double bond.
The ozonide being explosive in nature are not isolated as such. Further the
decomposition of ozonide is carried by reduction (known as reductive
ozonolysis) or by oxidation (known as oxidative ozonolysis).
• The reductive ozonolysis with Zn, H2O results in the formation of aldehydes
and/or ketones.
• The oxidative ozonolysis with H2O2 results in the formation of carboxylic
acids and/or ketones.
The oxidation reactions discussed above are summarized in Fig. 6.2, which
depicts the fate of various olefinic carbons during oxidation process.
The HBr released reacts with NBS to produce low concentration of bromine.
6.3.6 Polymerization
Polymerization is the process of joining of small molecular units (known as
monomers) to form large molecules (called polymers) with high molecular
weight.
Alkenes can form large molecules by repetitive addition where monomer units
are joined together without loss of any atom(s). Such a process is termed
Addition polymerization. For example, a number of ethene molecules may join
together to form polyethene.
Sequence 2
7.1 INTRODUCTION
The class of hydrocarbons containing two carbon–carbon double bonds are
termed dienes and possess a general formula, CnH2n–2. These have the same
molecular formula as alkynes and are thus, isomeric with alkynes. Based on the
relative position of the two double bonds, dienes can be classified as isolated
dienes, conjugated dienes, and cumulated dienes.
Isolated dienes. The two double bonds are separated by at least one sp3
hybridized carbon. For example,
Conjugated dienes. The double bonds are present alternatively, i.e. a double
bond followed by a single bond and then the other double bond. For example,
Cumulated dienes. The two double bonds are present on same carbon. These
dienes are popularly known as Allenes.
Stability of dienes
Earlier we have discussed in Chapter 6 that stability of alkenes are determined
form their heat of hydrogenation values. The comparsion of heat of
hydrogenation (Table 7.1) values of different diene systems indicate the order of
stability of dienes as follows:
Conjugated diene > Isolated diene > Cumulated diene
Table 7.1 Heat of hydrogenation for some diene systems
In buta-1,3-diene, all the four carbons are sp2 hybridized and each carbon has a
p orbital (with single electron). The four p orbitals are present in same plane. A p
orbital has two lobes with opposite signs (+ and –) that represent opposite phases
of wave function. In general a lobe with + sign is represented as shaded lobe and
a lobe with – sign as an empty lobe. The lobes with same phase overlap to give
bonding molecular orbitals (π) while the overlap of opposite phase lobes give
antibonding orbitals (π*). In case of overlap of opposite phase lobes there is a
node which represents region of zero electron density, that is, at the node the +
and – lobes exactly cancel each other. The bonding molecular orbitals (π) are
lower in energy than the antibonding molecular orbitals (π*). The total number
of molecular orbitals formed are always equal to the number of p atomic orbitals
that partici-pate in bond formation. For example, in case of ethene there are two
p orbitals that overlap and result in the formation of two molecular orbitals one
bonding and one antibonding. The electrons are first filled in lower energy
bonding molecular orbitals and then to higher energy antibonding molecular
orbitals. In case of ethene there are two electrons thus they are filled in bonding
molecular orbital, π, whereas the antibonding molecular orbital, π*, is empty.
Thus π is the Highest-Occupied Molecular Orbital (HOMO) of ethene and π* is
the Lowest Unoccupied Molecular Orbital (LUMO) of ethene. The molecular
orbital picture of ethene is represented in Fig. 7.1
Now, in case of Buta-1,3-diene there are four p orbitals with single electron each
and their overlap results in the formation of four molecular orbitals. The two
molecular orbitals of butadiene are bonding molecular orbitals (π1 and π2) and
two are antibonding molecular orbitals (π3* and π4*).
For a molecular orbital πn, the number of nodes are (n –1). Thus π1, π2, π3, π4
molecular
orbitals have 0, 1, 2 and 3 nodes respectively. The molecular orbital picture of
buta-1,3-diene (Fig. 7.2) is as follows.
NOTABILIA 8
7.3 PREPARATION OF BUTA-1,3-DIENE
The various methods used for preparation of buta-1,3-diene are discussed as
follows:
From Cyclohexene
Cyclohexene on heating in the presence of nickel chrome wire results in opening
of the ring which yields buta-1,3-diene and ethene.
(a) The reaction of allyl carbocation and bromide ion to form 1,2- addition
product involves low Ea while that of allyl carbocation and bromide ion to
form 1,4- addition product involves high Ea.
(b) At low temperature, 1,2- addition occurs more readily due to low
activation energy, Ea. As high activation energy is required for 1,4-
addition, only a small fraction of molecules undergo this reaction.
(c) At low temperature, the product formation is an irreversible process. At
low temperature sufficient energy is not available for products to revert
back, through high energy barrier, to allyl cation. Thus, 1,2- addition
reaction dominates at low temperature and is said to be kinetic or rate
controlled.
(d) At high temperature, sufficient energy is available and even 1,4- addition
(high Ea) is feasible.
(e) 1,4- addition product is more stable compared to 1,2- addition product.
(f) At high temperature, 1,2- addition occurs (because of low Ea) but since
1,4- addition product is more stable, 1,2- addition product reverts back to
form allyl carbocation and bromide ion (reversible reaction is possible only
at high temperature) and forms a more stable 1,4- addition product.
(g) The conversion of 1,2- addition product to 1,4- addition product is
energetically favoured.
(h) The 1,4- addition reaction dominates at high temperature and is said to be
thermodynamic or equilibrium controlled.
Mechanism
Step 1. Chain initiation (generation of free radical).
Peroxides are good free radical generators as they undergo homolytic cleavage to
produce radicals readily. The radical captures a chlorine radical from chlorine
molecule and in turn generates a chlorine radical.
Mechanism
Step 1. Chain initiation
Fig. 7.4 Symmetry allowed 4 + 2 cycloaddition (Diels–Alder reaction) in 1,3-butadiene and ethene. In (I)
overlap of HOMO of 1,3-butadiene occurs with LUMO of ethene. In (II) overlap of LUMO of 1,3-
butadiene occurs with HOMO of ethene.
7.4.5 Polymerization
Polymerization of buta-1-3-diene occurs in the presence of organic peroxide or
in the presence of sodium to give a rubber like product. The polymer formed in
the presence of sodium is popularly known as Buna rubber. The product may be
linear or a branched chain polymer.
7.5.1 Preparation
From isopentane or isopentene (by dehydrogenation)
Isopentane (2-methylbutane) or isopentene (3-metylbut-1-ene) on heating with
alumina and chromium oxide at a temperature of about 600°C undergo
dehydrogenation to form isoprene.
From acetone
The reaction of acetone with sodamide and then with acetylene, in a series of
reactions is used to synthesize isoprene as follows:
7.5.2 Chemical Properties
Isoprene follows the same addition reactions as buta-1,3-diene though the
ozonolysis and polymerization products are different. Reactions of isoprene can
be summarized as follows:
Addition reactions
Ozonolysis
The ozonolysis of isoprene results in the formation of methanal (2 moles) and 2-
oxopropanal (dicarbonyl compound).
Polymerization
Polymerization of isoprene is carried out in the presence of an organic peroxide
and follows a free radical mechanism (refer Chapter 31).
The polymer of isoprene having cis- configuration at all the double bonds is
known as natural rubber. The polymer of isoprene having trans- configuration
at all the double bonds is known as synthetic rubber or gutta percha.
Vulcanization of rubber: The natural and synthetic rubbers are associated with a
drawback that they become sticky during hot weather and become hard in cold.
To overcome this and also to increase the strength, the rubber is heated with 5–
10% of sulfur and this process is known as vulcanization of rubber. Sulfur forms
a cross-link between the linear polymer chains thereby giving a compact
structure, which strengthens the polymer.
7.6 CHLOROPRENE (2-CHLOROBUTA-1,3-
DIENE)
Chloroprene is a liquid which boils at 60oC. Chloroprene can be synthesized
from acetylene as follows:
.
The reactions which chloroprene undergoes are similar to buta-1,3-diene and
isoprene. The polymerization product of chloroprene is popularly known as
neoprene rubber.
EXERCISES
1. Explain the following terms with suitable examples:
(a) Isolated dienes
(b) Cumulated dienes
(c) Conjugated dienes
2. What is conjugation? How can the greater stability of conjugated dienes be
explained?
3. Discuss molecular orbital structure of buta-1,3-diene and the way it can
explain the stability of conjugated dienes systems.
4. Describe the methods of preparation of buta-1,3-diene.
5. Explain with mechanism, the addition of bromine to buta-1,3-diene. Why
buta-1,3-diene undergoes both 1,2- and 1,4- additions?
6. Discuss the mechanism of addition of HBr to buta-1,3-diene.
7. Discuss the effect of temperature on 1,2- and 1,4- addition in buta-1,3-diene.
8. Explain the free radical addition mechanism in butadiene.
9. Write a short note on Diels–Alder reaction.
10. What is the difference between synthetic and natural rubber?
11. Write short notes on
(a) Vulcanization of rubber
(b) Buna-S
(c) Buna-N
12. Give the reductive ozonolysis products of buta-1,3-diene and penta-1,3-
diene.
Chapter8
Alkynes
8.1 INTRODUCTION
The class of organic compounds containing a carbon–cabon triple bond are
called alkynes. Alkynes have the general formula CnH2n-2. Alkynes do not
occur free in nature but are produced during cracking of petroleum. Commonly,
the members of alkyne family are termed acetylenes. The first member of the
series is ethyne or acetylene.
In ethyne, each carbon is sp hybridized and sp–sp overlap results in the
formation of carbon-carbon σ bond while sp-s overlap results in carbon–
hydrogen σ bond. Also, each carbon has two pure p orbitals which are
orthogonal (perpendicular) to each other. Overlap of these p orbitals results in
the formation of two π bonds. Ethyne has a linear structure.
From methane. On heating the mixture of methane and oxygen (1:1 by volume)
at 1500oC, acetylene is obtained. Higher members of the alkyne family can be
conveniently prepared by acetylene.
For example
Addition of halogens
The addition of one equivalent of halogen to alkynes results in the formation of
haloalkenes. However 2 equivalents of halogens add on to alkynes to form
tetrahaloalkane derivatives.
For example,
Iodine is less reactive and only one mole of it adds to alkyne to form
diiodoalkene.
For example,
The reaction of alkyne with HBr in the presence of a peroxide follows anti-
Markovnikov’s rule.
Thus, hydration of alkynes gives ketones except for ethyne, which on hydration
forms an aldehyde, that is acetaldehyde.
Reaction with hypohalous acid
[Addition of Halogen and water]
The reaction of alkynes with Hypohalous acid result in the formation of geminal
dihalocarbonyl compounds. The mechanism does not involve the addition of
HOX as such to alkyne rather it is the addition of halogen (behaves as
electrophilic part of reagent) followed by reaction of water (behaves as
nucleophilic part of reagent).
Thus, net result is addition of HO–X+ to alkynes. For example
Vinylborane can undergo oxidation with hydrogen peroxide and NaOH to yield
carbonyl compounds while hydrolysis of a vinylborane in acidic medium
(protonolysis) gives cis- alkenes.
For example,
For example,
For example,
Cyclic polymerization
Alkynes polymerize when passed over a red hot tube to form cyclic (at times
aromatic)
compounds. For example, three molecules of acetylene undergo cyclic
polymerization to produce benzene. In a similar manner, three molecules of
propyne undergo cyclic polymerization to produce 1,3,5-trimethylbenzene
popularly known as mesitylene. The polymerization of four molecules of ethyne
in presence of catalyst results in the formation of cyclooctatetraene.
8.3.6 Isomerization (Acetylene Allene Rearrangement)
Terminal alkynes may be converted to non-terminal alkynes and vice versa
through an acetylene allene rearrangement. For example, but-1-yne is converted
to but-2-yne using ethanolic potassium hydroxide. However, but-2-yne can be
converted to but-1-yne (again through an allene intermediate) by using NaNH2.
Ozonolysis of alkynes
Alkynes on treatment with ozone at low temperature in CCl4 solvent, followed
by hydrolysis result in the formation of carboxylic acids.
Structure Determination of Alkynes
The ozonolysis–hydrolysis of alkynes results in the cleavage at
triple bond. The cleaved parts contain carboxylic groups at the
carbon atoms, which were initially joined through triple bond. The
ozonolysis–hydrolysis products of alkynes are used for determining
the structure of alkyne.
For example, the ozonolysis–hydrolysis of an alkyne gives
propanoic acid and ethanoic acid. To determine the structure of
alkyne, we write the products side by side with their carboxylic
groups facing each other and instead of carboxylic groups, place
carbon–carbon triple bond to determine the structure of alkyne.
Oxidative coupling
This reaction is undergone by terminal alkynes (except ethyne). Terminal
alkynes react with cuprous chloride and ammonium hydroxide to give copper
alkynides which can be coupled together by oxidation to form dialkynes. The
oxidation is carried out in presence of oxygen and acetic acid.
For example,
Solution
Example 4. How will you distinguish hex-1-yne from hex-3-yne?
Solution. Cu2Cl2 and Ag(NH3)OH can be used to distinguish hex-1-yne (an
terminal alkyne) from hex-3-yne. Hex-1-yne gives red precipitate with Cu2Cl2
and white precipitate with Ag(NH3)2OH while hex-3-yne does not react.
Example 5. Complete the following sequence of reactions.
Solution
A. But-2-ene
B. 2,3-Dibromobutane
C. But-2-yne
D. Butanone
Example 6. Carry out the following conversions (for preparation of
corresponding alkynes).
(a) Pent-2-ene to pent-2-yne
(b) But-1-ene to but-2-yne
(c) 1-Bromo-4-methylpentane to 4-methylpent-1-yne
Solution
A. CONCEPTS OF AROMATICITY
9A.1 Introduction
In earlier days of organic chemistry, the term ‘Aromatic’ was used for
compounds associated with certain aroma or fragrance. Benzene is the
representative member of the class of aromatic organic compounds which was
isolated in 1825 by Michael Faraday. The term aromatic has been widely used
for benzene and its derivatives since many of them are associated with a distinct
odour. However, there are other organic compounds which are known to be
associated with some odour but are not classified as aromatic. Thus, the
classification of organic compounds as aromatic is not only based on aroma but
on structure and reactivity of the compounds. To study the characteristics of
aromatic compounds and the criteria for aromaticity, let us first study the
structure of benzene.
9A.2 STRUCTURE OF BENZENE
Benzene has a molecular formula C6H6 that suggests a high degree of
unsaturation. However, it does not undergo the usual reactions of unsaturated
compounds such as addition, oxidation, and reduction. It does not decolourize
bromine water or potassium permanganate solution, which is the characteristic
of unsaturated compounds. In fact, benzene undergoes substitutions reactions.
Reaction of benzene with bromine in presence of ferric bromide catalyst results
in the formation of only one compound i.e. C6H5Br. This suggests that all
hydrogens in benzene are equivalent. This unusual behaviour of benzene is
attributed to its structure.
Although Kekule structure satisfied the structural features of benzene and also
explained the equivalent nature of hydrogen, it was not able to account for the
unusual behaviour of benzene. However, the Kekule structure of benzene was a
giant step forward and for this reason, the structure is still used but at present,
the explanation for the structure and reactivity of benzene is given in an entirely
different manner.
The actual hybrid structure has lower energy compared to either of the
contributing structures alone. This decrease in energy of the hybrid structure
stabilizes the molecule and is known as resonance energy. The resonance
energy is also termed as delocalization energy (see Notabilia 2). Benzene has
high resonance energy. In general, all aromatic compounds show high resonance
energy.
Fig. 9.1 Molecular orbital model of bonding in benzene. (a) C–C sigma bonds are a result of sp2–sp2
orbital overlap, C–H sigma bonds are a result of sp2-1s orbital overlap. The six 2p orbitals, each
containing one electron also combine (b) π-cloud formation due to six 2p orbital overlap.
It is evident that double bonds are not localized between any two carbons rather,
there is a continuous delocalization of π electrons. This delocalization causes all
the six carbon–carbon bond lengths to be same (1.39 Å). This value lies in
between a pure C–C bond length 1.54 Å and C=C bond length (1.33 Å).
Benzene is thus, represented as a hexagon with a circle inscribed, where the
circle represents delocalized π electrons.
For benzene, the calculated value is –358.8 kJ mol–1 while the experimentally
observed value is
–208 kJ mol–1. Thus, benzene is stabilized due to lowering of energy by 150.8
kJ mol–1 (i.e.
358.8–208). This difference of energy between the observed heat of
hydrogenation for actual molecule and the one calculated from the hypothetical
structure is known as resonance energy (or delocalization energy). Thus,
benzene has a resonance energy of 150.8 kJ mol–1.
Characteristics of Benzene
The discussion above explains the unusual characteristics of benzene, which is
also known as its aromatic character.
Benzene is a cyclic planar molecule. All the carbons are sp2 hybridized and the
p orbital available on each carbon contributes towards continuous delocalization
of π electrons. This provides stability to benzene and imparts it high resonance
energy. To retain the resonance energy and thereby the stability, benzene
undergoes substitution reactions. As a result, benzene does not behave as an
unsaturated system and does not undergo addition reactions.
9A.4 HUCKEL’S RULE AND AROMATICITY
In 1931, Huckel gave a rule for monocyclic compounds, which states that the
cyclic compounds containing (4n + 2) delocalized π electrons exhibit aromatic
character. Here, n can be zero or a whole number. For example, for n = 0 the
value of (4n + 2) is 2 and for n = 1, the (4n + 2) is 6 and so on. This means that
systems containing 2, 6, 10, 14, 18, 22, and so on, delocalized π electrons show
aromatic behaviour.
Thus, cyclopropene is not aromatic as all the conditions are not simultaneously
satisfied. The condition of continuous delocalization is not followed.
Cyclopropenyl cation
Characteristics of cyclopropenyl cation are as follows
(i) It is cyclic
(ii) It is planar
(iii) It exhibits continuous delocalization. All the carbons of cyclic system are
sp2 hybridized, and thus p orbitals are available for delocalization.
(iv) Does not obey Huckel’s rule, as the number of delocalized π electrons is
four.
Thus, cyclopropenyl anion is not aromatic, as all the conditions are not
simultaneously satisfied.
Thus, cyclobutadiene is not aromatic as all the conditions are not satisfied
simultaneously. The condition of Huckel’s rule is not followed.
Cyclopentadienyl Ions
The sp3 hybridized carbon in cyclopentadiene is not involved in
delocalization. Removal of a hydrogen (either as a proton (H+) or as a
hydride (H–)) from this carbon results in the formation of an anion or
a cation where all the carbons are sp2 hybridized and thus, continuous
delocalization of π electrons takes place.
Cyclopentadienyl anion
Characteristics of cyclopentadienyl anion are as follows
(i) It is cyclic
(ii) It is planar
(iii) It exhibits continuous delocalization. All the carbons of cyclic system are
sp2 hybridized, and thus p orbitals are available for delocalization.
(iv) Obeys Huckel’s rule, as number of delocalized π electrons is six.
Thus, cyclopentadienyl cation is aromatic, as all the conditions are satisfied
simultaneously.
Cyclopentadienyl cation
Characteristics of cyclopentadienyl cation are as follows
(i) It is cyclic
(ii) It is planar
(iii) It exhibits continuous delocalization. All the corbons of cyclic system are
sp2 hybridized and thus p orbitals are available for delocalization.
(iv) Does not obey Huckel’s rule, as number of delocalized π electrons is four.
Thus, cyclopentadienyl cation is not aromatic, as all the conditions are not
satisfied simultaneously. The condition of Huckel’s rule is not followed.
Cycloheptatrienyl Ions
The sp3 hybridized carbon in cycloheptatriene is not involved in
delocalization. Removal of a hydrogen (either as a proton (H+) or as a
hydride (H–)) from this carbon results in the formation of an anion or
a cation, where all the carbons are sp2 hybridized and thus,
continuous delocalization of π electrons takes place.
Cycloheptatrienyl cation (Tropylium ion)
Characteristics of cycloheptatrienyl cation are as follows
(i) It is cyclic
(ii) It is planar
(iii) It exhibits continuous delocalization. All the carbons of cyclic system are
sp2 hybridized, and thus p orbitals are available for delocalization.
The [10]annulene due to small size of ring cannot accomodate the hydrogens
present at the centre of the ring and this steric hindrance prevents it to attain
planarity. However in [14]annulene and other higher annulenes, due to large size
of ring the hydrogens at the centre are easily accomodated and annulenes attain a
nearly planar structure.
More on the aromatic character in annulenes
A compound is more often said to be aromatic if it is a planar system with
continuous delocalization of electrons and obeys Huckel’s rule.
In any system the delocalization of electrons occurs effectively, if the overlap of
p orbitals is effective. The overlap of p orbitals can occur effectively only when
these orbitals are in the same plane. Any deviation from planarity in a molecule
(system) will retard the delocalization process in it and that will reduce the
aromatic character of the system. Thus, planarity is an essential factor to
describe the aromatic character.
As explained earlier that [10]annulene (structure-I) in spite of obeying Huckel’s
rule, does not exhibit aromatic character because of deviation from planar
structure. The hydrogens present at position 1 and 6 in the ring system prevent it
from attaining a planar structure because of steric hindrance and thus, interfere
in the overlap of orbitals.
However the aromaticity in this molecule can be introduced by eliminating the
interaction of hydrogens (at C1 and C6). One of the best strategy is to bridge 1
and 6 positions as shown in structure-II. The bridging replaces the hydrogens
and prevents the steric hindrance thereby, providing sufficient overlap of
orbitals. This provides aromatic character to bridged molecule.
Azulene
Azulene is a nonbenzenoid fused ring system unlike naphthalene,
anthracene and phenanthrene that are benzenoid systems
(containing fused benzene rings). In azulene a seven and five
membered ring systems are fused together. Azulene is an aromatic
system and readily undergoes electrophilic substitution reactions.
All the above heterocyclic compounds are aromatic. The carbons as well as
nitrogen, oxygen, and sulfur are sp2 hybridized which give a planar structure. In
each case, the total number of delocalized π electrons is six, that is, Huckel’s rule
is followed. In pyrrole, furan, and thiophene, a lone pair of electrons present in p
orbital of nitrogen, oxygen, and sulfur respectively participates in delocalization
with p orbital of sp2 hybridized carbons. In pyridine, the lone pair of electrons
on nitrogen does not participate in delocalization. (For further details on
aromaticity, see Chapter 26 on Heterocyclic Compounds).
If two different alkyl groups are present, they are numbered in alphabetical order
as in the following case.
9B.4.1 Preparations
From sodium salt of benzoic acid
Sodium salt of benzoic acid on heating with soda-lime undergoes
decarboxylation to give benzene.
From phenol
Distilling phenol over zinc dust results in the formation of benzene.
By Grignard reagent
The Grignard reagent, phenylmagnesium bromide on hydrolysis results in the
formation of benzene.
Nitration
Benzene on reaction with fuming nitric acid (HNO3 + H2SO4) results in
formation of nitrobenzene. Sulfuric acid acts as a catalyst and helps in
generating the electrophile (NO2+).
Friedel–Crafts alkylation
Benzene reacts with haloalkanes in presence of a catalyst (AlCl3) to give
alkylbenzenes. The catalyst AlCl3, a Lewis acid helps in generation of
electrophile (alkyl carbocation). For example
Friedel–Crafts acylation
Benzene reacts with acid chloride in presence of aluminum chloride as catalyst
to give aryl ketone as the final product. The reaction can also be carried out with
acid anhydride.
Sulfonation
Benzene reacts with fuming sulfuric acid to give benzene sulfonic acid. The
electrophile in sulfonation reaction is sulfur trioxide. It is a reversible reaction
and desulfonation occurs readily in aqueous acidic medium.
Addition reactions
Addition of hydrogen
In presence of nickel catalyst at a temperature of 200oC, benzene undergoes
hydrogenation to produce cyclohexane. The Birch reduction of benzene gives
cyclohexa-1,4-diene.
Addition of chlorine
In the presence of sun light, the addition of chlorine to benzene gives
benzenehexachloride (BHC, Lindane, or gammaxene). BHC is extensively used
as an insecticide.
Oxidation reactions
With oxygen
Benzene, on heating with oxygen in presence of a catalyst vanadium pentaoxide
(V2O5) at 500oC results in the formation of maleic anhydride. In the process,
carbon dioxide and water are evolved.
With ozone
Benzene adds on three molecules of ozone to form a triozononide, which on
reductive cleavage results in the formation three molecules of glyoxal.
9B.5 ARENES: METHYLBENZENE (TOLUENE)
AND STYRENE
9B.5.1 Methylbenzene
Preparations
Wurtz–Fittig reaction
Reaction of chlorobenzene and chloromethane with sodium metal in presence of
dry ether as solvent results in the formation of methylbenzene (toluene).
Sulfonation
The reaction of toluene with fuming sulfuric acid results in the formation of o-
and p- toluenesulfonic acids. The electrophile in sulfonation reaction is sulfur
trioxide.
Side chain reactions
Halogenation
Reaction of toluene with chlorine in presence of light (without catalyst) results in
substitution in the side chain (–CH3). The reaction is similar to substitution
reactions in alkanes. The product formed in the reaction is benzyl chloride that
undergoes further substitution to give benzal chloride and finally
trichloromethylbenzene. The reaction follows a free radical mechanism.
Oxidation
Toluene on oxidation with sodium dichromate in acidic medium or on oxidation
with potassium permanganate results in the formation of benzoic acid.
Oxidation. Oxidation of styrene with hydrogen peroxide and formic acid results
in hydroxylation of side chain to produce 1-phenylethane-1,2-diol. However,
strong oxidizing agents like KMnO4 results in the oxidation of styrene to
benzoic acid.
SELECTED SOLVED EXAMPLES
Example 1. Complete the following sequence of reactions.
Solution
(a) It is Friedel–Crafts alkylation using benzylchloride as the alkylating agent.
The product A is Diphenylmethane, i.e.
Note: The mechanism and details of these reactions are discussed in Chapter 10.
Chapter10
Aromatic
Electrophilic Substitution Reactions
—Mechanism, Orientation and
Reactivity
10.1 INTRODUCTION
One of the most important and characteristic reactions of benzene as well as of
other aromatic systems are electrophilic substitution reactions. Aromatic systems
have delocalized π electrons and this availability of π electrons makes them
susceptible to the attack of electron deficient species called electrophiles.
Benzene is the representative member of the class of aromatic compounds. The
high resonance energy provides stability to benzene (refer Chapter 9). The
addition of electrophile causes a loss in aromaticity and hence, a loss in the
resonance energy of benzene as delocalization of electrons is discontinued. Thus,
benzene prefers to undergo electrophilic substitution reactions as during
electrophilic substitution the aromaticity is retained and so is the resonance
energy.
Fig. 10.1 Comparing the electrophilic addition and electrophilic substitution in benzene.
The present chapter deals with various aspects of electrophilic substitution
reactions of benzene and substituted benzenes. The mechanisms of the
substitution reactions and the impact of substituents on the orientation and
reactivity of substituted benzenes are discussed in detail under the heads as
tabulated in Information Chart I.
10.2 MECHANISM OF ELECTROPHILIC
SUBSTITUTION REACTIONS OF BENZENE
Benzene undergoes electrophilic substitution reactions such as halogenation,
nitration, sulfonation, alkylation, acylation, and so on in presence of a catalyst.
Substitution results in the formation of a monosubstituted benzene as the only
product.
10.2.1 Halogenation
Benzene reacts with chlorine or bromine in the presence of Lewis acids like
AlCl3, FeCl3, FeBr3 etc. as catalysts to give chlorobenzene or bromobenzene.
The catalyst initiates the reaction by generating the electrophile, that is,
chloronium (Cl+) or bromonium (Br+) ions.
However, it is also belived that from complex the chlorine may get transferred
directly to the benzene ring.
Step 2. Attack of chloronium ion on π-electron rich aromatic system (formation
of arenium ion)
Aromaticity is lost at this stage as one of the carbons becomes sp3 hybridized.
Formation of arenium ion is an endothermic process. The four π-electrons in
arenium ion are delocalized among five sp2 hybridized carbons.
10.2.2 Nitration
Benzene, on treatment with fuming nitric acid (or mixture of conc. HNO3 and
H2SO4) results in the formation of nitrobenzene. Concentrated sulfuric acid acts
as a catalyst which helps in generation of electrophile, that is, nitronium ion.
The sulfuric acid protonates the nitric acid, which on loss of water molecule
gives nitronium ion, a strong electrophile.
NOTABILIA 9 π
10.2.3 Friedel–Crafts Alkylation
Haloalkanes react with benzene in presence of a Lewis acid, as catalyst (AlX3,
FeX3) to produce alkylbenzenes. The reactivity of haloalkanes increases with an
increase in the polarity of C–X bond. Thus, order of reactivity of RX is RF >
RCl > RBr > RI.
Mechanism
Step 1. Generation of electrophile (alkyl carbocation)
The Lewis acid enhances the electrophilic character on carbon of alkyl group in
the complex.
Continuous delocalization ceases as one of the carbon becomes sp3 hybridized,
this results in loss of aromaticity in arenium ion. The four π-electrons are
delocalized among five sp2 hybrid carbons of the ring.
The other Lewis acids can also be used in Friedel–Crafts alkylation namely BF3,
HF, SnCl4 or acids (as in above examples).
Although –NH2, –NHR, and –NR2 are electron-releasing in nature, they form
a complex with AlCl3 (a Lewis acid). The development of positive charge
on nitrogen makes them behave as electron-withdrawing groups.
However, this step is not so important as SO3 may react directly with benzene.
Step 2. Attack of sulfurtrioxide on benzene π-electron cloud (formation of
arenium ion)
A number of reactions have been studied by the chemists, and based on this a
generalization has been put forward for the effect of substituents on electrophilic
substitution reactions.
As an example, let us compare the nitration reaction of methylbenzene,
nitrobenzene, and benzene.
The nitration of methylbenzene takes place more readily compared to nitration
of benzene and nitro-group gets substituted preferably at ortho and para
positions. On the other hand, the nitration of nitrobenzene takes place less
readily compared to nitration of benzene and nitro- group prefers to be
substituted at meta position.
Thus electron releasing groups are termed as ring activators and electron
withdrawing groups are termed as ring deactivators. A list of some activator and
deactivator groups is given in Table 10.1.
10.3.3 Effect of Groups on Orientation
Ortho, para directors
Electron-releasing groups activate the ring and direct the electrophile towards
ortho and para positions. The group may release the electrons through Inductive
or Resonance effect.
Let us consider the case of methylbenzene. The attack of electrophile may occur
at ortho, meta, and para positions. The most favourable site of attack is decided
and understood from the stability of the carbocation formed in each case.
In all the three cases, each carbocation is a hybrid of three contributing
structures. The carbocations formed by the attack at ortho and para positions are
relatively more stable, as one of the contributing structures in these cases is
associated with extra stability. In case of meta attack, no such extra stability is
provided to the carbocation. Thus, attack occurs more readily at ortho and para
positions.
The alkyl groups attached to benzene ring, release electrons through inductive
effect as well as through hyperconjugation (p. 113).
As an example, consider the chlorination of methylbenzene (toluene).
Mechanism
Step 1. Generation of chloronium ion (Electrophile)
Step 2. Attack of chloronium ion at ortho- and para- positions of toluene
(formation of arenium ion)
Ortho attack:
para attack:
The release of electrons can occur through resonance effect and this is
observed in case of atoms or groups where lone pair is present on the atom
through which group is attached to benzene ring.
Nitrogen, oxygen, and halogens are electronegative in nature and withdraw
electrons through inductive effect (–I effect), but presence of lone pair on these
atoms makes them participate in an extended delocalization with the π-electrons
of the benzene ring. Due to this strong resonance effect, they behave as electron-
releasing groups towards benzene ring.
Consider, the case of phenol. The electrophile may attack at ortho, meta and
para positions. The most favourable site of attack is decided from the stability of
the carbocation formed in each case.
In case of ortho and para attack the carbocations are hybrid of four contributing
structures, one of which is associated with extra stability. In case of meta attack,
the carbocation is a hybrid of only three structures. More the number of
contributing structures, more is the stability of carbocation and faster is the
reaction. Carbocations formed by ortho and para attack are more stabilized
compared to those formed by meta attack. Thus, in phenol substitution of
electrophile occurs preferably at ortho and para position.
To conclude, electron-releasing groups activate the ortho and para positions to
greater extent (i.e. electron-releasing effect is observed maximum at ortho and
para positions) as compared to meta and therefore, direct the electrophile
towards ortho and para positions. The –NH2, –NHR, –NR2, –OR, –OCOR, –
NHCOR, –O– and –X are electron releasing groups and behave in a similar
manner as shown in case of phenol.
Meta directors
Electron-withdrawing groups deactivate the ring and direct the electrophile
towards meta position. The group may withdraw electron through inductive or
resonance effect.
Let us consider the case of nitrobenzene. The attack may occur at ortho, meta
and para positions. The most favourable site of attack can be decided from
stability of carbocations formed by ortho, meta, and para attack as follows.
Fig. 10.5 Attack of eletrophile on m-nitrophenol (–OH group directs the postion of entering group).
Fig. 10.6 Attack of eletrophile on p-methylphenol (–OH group directs the position of entering group being
a strong ring activator over –CH3 group).
Fig. 10.7 Attack of eletrophile on o-nitrobenzaldehyde and p-nitrobenzonitrile (–NO2 group directs the
position of entering group).
Case study IV(a) (Both the substituents are either strong activating or weak
activating)
(a) When both the substituents are either strong activating or weak activating
then all the possible products are formed. This means that the products are
obtained with respect to the directive influence of each substituent.
Fig. 10.8 Attack of electrophile at ortho and para to both the substituents.
Case study IV(b) (Both the substituents are either strong deactivating or
weak deactivating)
(b) Similarly, when both the substituents are either strong deactivating or
weak deactivating then all possible products are formed. The products
obtained are formed by substitution of electrophile at positions that are meta
with respect to each group individually.
Now, benzylchloride acts as an alkylating agent and reacts with second molecule
of benzene to form diphenylmethane.
Groups like methoxy (OCH3) and chloro (Cl) groups are electron-releasing and
thus compound III and VI will undergo the Friedel–Crafts alkylation. The
products formed are:
Example 8. In the following disubstituted benzenes, indicate the position(s)
where nitration reaction will occur. Also indicate the expected major product.
Solution. The possible positions where nitration will occur are indicated by
arrows. A thick arrow indicates the position where the substituent attaches to
form the major product.
Both –COOH and –NO2 groups are deactivating in nature. The orientation of
electrophile (Br+) is governed by strong deactivating –NO2 group and thus,
bromine enters at a less sterically hindered meta position with respect to nitro
group.
EXERCISES
1. Give the detailed mechanism of electrophilic substitution reaction in benzene
by taking nitration and sulfonation as examples.
2. Write a note on the following reactions in benzene:
(a) Friedel–Crafts alkylation
(b) Friedel–Crafts acylation
(c) Halogenation
3. How does the nature of a substituent affect the reactivity of aromatic ring
system towards electrophilic substitution reactions? Explain on the basis of
inductive and resonance effects.
4. Explain the directive influence of amino and methyl groups in electrophilic
substitution reactions.
5. Halogens are electron-withdrawing in nature yet they direct the incoming
electrophile to ortho and para positions. Explain.
6. Explain the deactivating and meta directing nature of nitro group towards
electrophilic aromatic substitution.
7. What are σ– and π–complexes?
8. What products will be obtained on the nitration of methylbenzene? Explain
the underlying mechanism.
9. What will be the orientation of an entering electrophile in a disubstituted
benzene when
(a) one substituent is activating and the other is deactivating.
(b) one substituent is strong activating and the other is weak activating.
(c) both the substituents are strong deactivating.
(d) both the substituents are strong activating.
10. Discuss the limitations of Friedel–Crafts alkylation?
11. Arrange the following compounds in decreasing order of reactivity towards
bromination.
12. Indicate the position of the entering electrophile NO2+ in the following
compounds:
SET-II
Problem 32. Coupling of two methyl radicals result in formation of ethane.
However, coupling of two triphenylmethyl radicals does not form the expected
hexaphenylethane but results in the formation of another dimer known as
Gomberg dimer. Explain the formation of dimeric product.
Solution. The coupling of two triphenylmethyl radicals does not form
hexaphenylethane due to high steric strain imposed by presence of bulky phenyl
rings. The triphenylmethyl radical (I) undergoes delocalization to give
contributing structure –II. It is the free radical centre generated at carbon of one
of the phenyl ring in II, that undergoes coupling with another triphenylmethyl
radical (I) to produce “Gomberg dimer”.
The dimer looses aromatic stabilization from one of the phenyl ring but still its
formation is energetically more favourable compared to formation of highly
strained hexaphenylethane.
Thus, this is an example where aromaticity is sacrificed to overcome steric
strain to form the stable product “Gomberg dimer”.
Problem 34. What product (s) will be obtained from the Grignard reagents,
obtained from the isomeric monobromo derivatives of 2-methylbutane, if they
are hydrolyzed by (i) water and
(ii) heavy water, that is, D2O?
Solution. The possible four isomers of monobromo derivatives of 2-
methylbutane on treatment with Mg in dry ether will result in the formation of
corresponding Grignard reagent.
These Grignard reagents on hydrolysis with water will result in the formation
of same alkane that is 2-methylbutane (refer for details Sec. 5A.2.2).
But these four Grignard reagents will lead to the formation of different
products on hydrolysis with deuterated water, that is, isomeric deuterated
2-methylbutanes. The reactions are as follows:
Problem 35. How will you carry out the synthesis of (2H1) cyclohexane (that is,
deuterated cyclohexane)?
Solution. Synthesis of deuterated cyclohexane can be carried out by reaction of
Grignard reagent with deuterated water. The overall synthesis starting from
cyclohexene is as follows:
Problem 36. The chlorination of methane is favoured through pathway (a) and
not (b) as given. Explain this proposition by making use of the bond dissociation
energy (DE) values from
Table 5.2 (p. 184).
Solution. The favourable step for chlorination (in general, halogenation) can be
determined by calculating the values of ΔH (heat of reaction) as:
ΔH = (dissociation energy (DE) of bonds broken) – (dissociation energy (DE) of
bonds formed)
In Pathway (a)
The C–H bond breaks (DE = 435 kJmol–1) and H–Cl bond is formed (DE = 431
kJmol–1)
Thus, ΔH = 435 – 431 = +4 kJmol–1
In Pathway (b)
The C–H bond breaks (DE = 435 kJmol–1) and H3C–Cl bond is formed (DE =
352 kJmol–1)
Thus, ΔH = 435 – 352 = +83 kJmol–1.
Since, pathway (b) is highly endothermic (+83 kJmol–1) it is not favoured over
pathway (a).
Problem 37. Determine which of the following reactions can occur during the
bromination of ethane?
Solution. The occurrence of a reaction can be determined from its ΔH value (as
in the previous problem). For bond dissociation energy values refer to Table 5.2
(p. 184).
ΔH for (A) = 368 kJmol–1 – 293 kJmol–1 = +75 kJmol–1
ΔH for reaction (B) = 410 kJmol–1 – 368 kJmol–1 = +42 kJmol–1
This shows that cleavage of C–C bond as in reaction (A), is relatively more
endothermic and therefore does not occur.
Problem 38. The reaction of 2-methylbutane (iso-pentane) and chlorine in
presence of light gives a mixture of monochloro derivative constituting 50% of
1°, 28% of 2°, and 22% of 3° chloro derivatives. What is the relative reactivity
of primary, secondary, and tertiary C–H bonds? What inference can be drawn
from these values?
Solution. In 2-methylbutane there are nine primary, two secondary, and one
tertiary C–H bonds.
The relative reactivity of C–H bonds is therefore given by 1°: 2°: 3° = 5.5:14:22
It clearly indicates that tertiary hydrogen can be substituted much more readily
as compared to secondary and primary hydrogens.
Problem 39. Calculate the percentage of isomers formed during the
monobromination of 2,3-dimethylbutane. The relative reactivity values for
tertiary, secondary, and primary hydrogens are 1600, 82, and 1 respectively.
Solution. In 2,3-dimethylbutane there are twelve primary and two tertiary
hydrogens.
Problem 43. The addition of bromine to isomeric but-2-ene (that is cis- and
trans-) results in the formation of different stereoisomers of 2,3-dibromobutane.
Explain.
Solution. But-2-ene exhibits geometrical (cis- and trans-) isomerism. The
addition of bromine to alkenes is a stereospecific reaction (see section 6.3.2, p.
223) and occurs in a trans- manner. The trans- addition of bromine to cis-but-2-
ene results in the formation of racemic mixture of 2,3-dibromobutane whereas
trans- addition of bromine to trans-but-2-ene results in the formation of meso-
2,3-dibromobutane.
The trans-addition of bromine to cis-but-2-ene can be represented using
sawhorse projections as follows:
Problem 45. Stating the reasons, name the products formed when bromine reacts
with ethene in the presence of lithium chloride in methanol?
Solution. When bromine is added to ethene in the presence of LiCl in CH3OH,
the reaction first involves the attack of electrophile, Br+ (refer sec. 6.3.2, p. 224).
The next step is the attack of the nucleophile and in this case besides Br–, the
other nucleophiles are also available namely Cl– (from LiCl) and –OCH3 (from
CH3OH). This results in the formation of three products, namely 1,2-
dibromoethane, 1-bromo-2-chloroethane, and 1-bromo-2-methoxyethane.
Problem 46. What will be the decreasing order of reactivity of the following
alkenes, towards the addition of HBr?
(a) CH2=CH2
(b) CH3CH2CH=CHCH3
(c) CH3C(CH3)=C(CH3)CH3
(d) CH3CH2CH=CH2
Solution. As mentioned earlier (Problem 42), alkenes with more number of alkyl
substituents undergo electrophilic addition readily as compared to less
substituted alkenes. Thus, the decreasing order of reactivity of the given alkenes
towards the addition of HBr is:
(c) > (b) > (d) > (a)
Problem 47. In the addition of hydrogen halides to the alkenes, the ease of
addition to the double bond follows the order HI > HBr > HCl. Explain.
Solution. The addition of electrophile (H+) is the rate-determining step in the
electrophilic addition reactions. The higher the acidic strength of hydrogen
halide, the faster is the addition of H+.
A hydrogen halide, which is more acidic in nature, furnishes H+ (electrophile)
more easily to the alkenes and the addition reaction is therefore quicker.
Thus, the ease of addition is directly related to the acidic strength of hydrogen
halides thereby explaining the order of reaction ease:
HI > HBr > HCl
Problem 48. Keeping in view the electrophilic addition mechanism, give the
product obtained by the addition of iodine chloride (ICl) to propene.
Solution. Since chlorine is more electronegative than iodine, iodine behaves as
an electrophile and addition occurs in accordance with Markovnikov’s rule to
give 2-chloro-1-iodopropane as the product.
Pathway-II
Problem 50. In each of the given set of carbocations (a) and (b) indicate which
one is more stable, along with explanation.
Solution.
(a) Carbocation I is more stable than II.
Carbocation I (Cyclobutylmethylium) is a primary carbocation but it is
more stable than carbocation II (1-methylcyclobutylium) which is tertiary
carbocation.
Carbocations are sp2 hybridized with bond angle 120°. The four membered
cyclic system have bond angle of 90° and high angle strain does not favour
the formation of
1-methylcyclobutylium [carbocation II].
(b) Carbocation IV is more stable than III.
The carbocation III (cyclohexylmethylium) is a primary carbocation while
carbocation IV (1-methylcyclohexylium) is tertiary in nature. The
cyclohexane ring systems do not exhibit significant angle strain. Thus
Carbocation IV, a tertiary carbocation, is more stable than III, a primary
carbocation.
Problem 51. What product(s) will be formed on addition of HCl to
(i) methylenecyclobutane and
(ii) methylenecyclohexane
Solution. Addition of HCl to alkene is an electrophilic addition and follows
Markovnikov’s rule.
(Recall: Addition proceeds via the formation of more stable carbocation and
products are formed accordingly, refer pp. 226–28).
(i) Although tertiary carbocations are more stable than primary but in this case
tertiary is unstable due to angle strain (see explanation in previous problem
no. 50).
(ii) Six membered ring systems are free from angle strain, so in this case
tertiary carbocation is formed readily(see explanation in previous problem
no. 50).
Step 3 The product formed in step-2 reacts with sodamide to form corresponding
alkyne (refer
pp. 275, 276)
Problem 54. Name the products obtained on selective addition of one mole of
bromine to the following alkadienes:
Solution. The given alkadienes are the example of isolated dienes (that is,
double bonds are not conjugated). One mole of bromine can attack either of the
double bonds, however it attacks selectively at the double bond, which is
substituted with more number of alkyl groups (also refer Problem 42).
More the number of electron releasing groups (+I effect) attached to C=C, much
easier is the addition of electrophile (in this case, Br+). Thus, electrophilic
addition of bromine occurs preferably at the double bond which is substituted
with more number of alkyl groups.
Problem 55. Giving the mechanism, explain the formation of product(s) when:
(i) Cyclopenta-1,3-diene is treated with 1 mole of HBr.
(ii) Cyclopenta-1,3-diene is treated with 1 mole of Br2.
(iii) 1,4-diphenylbuta-1,3-diene is treated with 1 mole of Br2.
Solution. In all the above three cases (i-iii), the reactants are conjugated dienes,
which on reaction with one mole of reagent undergo electrophilic addition to
give 1,2- and 1,4- addition products (refer section 7.4.1). In general formation of
1,4-addition product is favoured due to thermodynamic stability.
(i) Cyclopenta-1,3-diene is treated with 1 mole of HBr. In this case, 1,2- and
1,4- addition of HBr to cyclopenta-1,3-diene results in the formation of
same product. Thus, Cyclopenta-1,3-diene with 1 mole of HBr gives only
one product, that is, 3-bromocyclopentene.
(ii) Cyclopenta-1,3-diene is treated with 1 mole of Br2. The reaction of
cyclopenta-1,3-diene with 1 mole of Br2 gives two products, that is,
3,4-dibromocyclopentene (1,2- addition product) and
3,5-dibromocyclopentene (1,4- addition product)
Problem 61. Indicate which of the stereoisomers (cis- or trans-) will be obtained
as products in the following addition reactions:
Solution.
(a) The catalytic hydrogenation is a stereospecific reaction where addition of
hydrogen occurs in a syn manner to give cis-alkene (section 6.2.1).
(b) The addition of bromine to an unsaturated system is a stereospecific
reaction. The reaction follows an electrophilic addition mechanism where
addition of bromine occurs in an anti manner to yield a trans-
dibromoalkene.
Problem 62. What product(s) will be obtained by the reaction of (i) H2O/Hg2+,
H2SO4 and (ii) HCl (one mole) with the following alkynes?
(a) Hex-2-yne (b) Hex-3-yne
Solution. The electrophilic addition to alkyne proceeds via the formation of vinyl
cation as intermediate (section 8.3.2).
The acid catalyzed hydration of alkyne is catalyzed by Hg2+ and results in
the formation of carbonyl compound.
Further the addition of one mole of HCl to alkyne results in the formation of
corresponding vinyl chloride derivatives.
In the given examples, these reactions can be explained as follows:
(a) Hex-2-yne is an unsymmetrical alkyne and there is a possibility of
formation of two types of carbocations (I and II) during the electrophilic
addition reactions.
These carbocations may lead to the formation of different products. Thus, in the
given set of reactions
(i) The hydration of hex-2-yne will result in the formation of two types of
carbonyl compounds
(ii) Addition of HCl will also result in the formation of two types of vinyl
chloride derivatives.
(b) Hex-3-yne is a symmetrical alkyne and it will lead to the formation of only
one type of carbocation (I) during the electrophilic addition reactions. Thus
electrophilic addition to symmetrical alkynes will result in the formation of
one product only.
Thus, reactions of hex-3-yne with (i) H2O/Hg2+, H2SO4 and (ii) HCl (one
mole) are as follows:
Similarly,
Problem 65. The following species (A-F) as such are not aromatic. Identify
which of these species
(a) Have contributing structures (resonance contributor) that exhibit aromatic
character.
(b) Have tautomers that exhibit aromatic character.
Solution. All the species A-F as such are not aromatic as they do not follow
Huckel’s rule of
(4n + 2) delocalized π-electrons in a cyclic conjugated system.
(a) Contributing structures (resonance contributor) that exhibit aromatic
character:
The species D, E and F are delocalized (conjugated) systems but this extended
conjugation is not a part of cyclic system. These species undergo resonance
and in their contributing structures the electrons get delocalized in the
cyclic system and satisfy the condition of (4n + 2) π-electrons (Huckel’s
rule). Thus contributing structures of D, E and F, exhibit aromatic
character, as shown below:
(b) Tautomers that exhibit aromatic character: The species A, B and C are
delocalized (conjugated) systems but this extended conjugation is not a part
of cyclic system. These species exhibit tautomerism and their tautomeric
forms are highly stable aromatic species, as they follow all the criteria of
aromaticity, as shown below:
(b) The nitrating agent in nitration reaction is nitronium ion (+NO2) (refer
section 10.2.2).
(i) The nitric acid alone produces a low concentration of nitronium ion as nitric
acid is ionized to a very little extent (~ 4%) and equilibrium lies to left:
The product formed in the above reactions clearly indicates that chloropropane
cannot be used for preparation of propylbenzene as carbocation rearrangement
occurs and isopropylbenzene is formed as the product.
Solution.
(a) In biphenyl, the phenyl group behaves as electron releasing group due to
resonance. Thus phenyl group activates the ortho and para positions of
other phenyl ring towards electrophilic aromatic substitution
Problem 70. Explain, in brief, Birch reduction along with its important aspects.
Solution. Birch reduction: The reduction of aromatic rings by sodium (or Li or
K) in liquid ammonia, in presence of alcohol, is known as Birch reduction. The
1,4-addition of hydrogen in aromatic ring result in the formation of non-
conjugated cyclohexa-1,4-diene derivatives. This is an example of dissolving
metal reduction.
Mechanism:
The alkali metal Na (or Li or K) provide an electron to system whereas
alcohol provides proton (H+) during reduction.
Ammonia is less acidic compared to alcohol and thus cannot provide proton.
Solution.
Above two reactions are the examples of Birch reduction.
In reaction (a) electron withdrawing group is attached to phenyl ring and in
reaction (b) the electron releasing group is attached to phenyl ring. Nature of
groups largely effects the reduction products as they stabilize/destabilize the
radical anion formed during the course of reaction.
The reactions are as follows:
(a) The nitro group is electron withdrawing in nature and Birch reduction
results in the formation of product as explained below:
(b) The methoxy group, in methoxybenzene, is electron releasing in nature
and Birch reduction results in the formation of product as explained below:
Chapter11
Haloalkanes
11.1 INTRODUCTION
Haloalkanes are the halogen derivatives of hydrocarbons with general formula
CnH2n+1X and are represented as R–X where R is an alkyl group and X
represents halogen. In haloalkanes the carbon–halogen bond is formed by sp3-p
overlap. Being more electronegative compared to carbon, halogens impart a
polar character to C–X bond where halogens acquire a negative charge and
carbon acquires a positive charge.
Depending upon the number of carbons attached to the carbon to which halogen
is attached, haloalkanes may be classified as primary (1°), secondary (2°), or
tertiary (3°).
(b) Solubility and state of matter: Haloalkanes are insoluble in water but
soluble in organic solvents. Lower molecular mass haloalkanes are gases at
room temperature while higher molecular mass haloalkanes are liquid at
room temperature.
(c) Boiling point: Boiling point of haloalkanes is higher compared to
corresponding alkanes due to dipole–dipole interaction. With an increase in
molecular mass, there is an increase in boiling point. For the same alkyl
group the boiling point increases from fluoroalkane (R–F) to iodoalkane
(R–I). Iodine has a larger surface area and outer electrons are loosely
bound. This makes iodine a highly polarizable atom. A polarizable atom has
increased London forces of attraction (section 1.7), which causes an
increase in boiling point. The branched chain haloalkanes follow a similar
increasing order of boiling points.
(d) Density: The densities of haloalkanes increase with atomic mass of the
halogen and decrease with increasing size of the alkyl group. In
monohaloalkanes, iodomethane (CH3I) has the maximum density.
The general characteristics of monohaloalkanes can be enumerated as follows:
(a) Fluoro and chloroalkanes are less dense than water whereas bromo and
iodoalkanes are denser than water.
(b) Monofluroalkanes are unstable and on heating, H–F is eliminated to
produce alkene.
(c) Bromo and iodoalkanes are generally photosensitive and are stored in
brown opaque bottles. Otherwise, they liberate free bromine and iodine
respectively.
11.2 PREPARATION OF HALOALKANES
The various methods used for the preparation of haloalkanes are discussed in this
section. Some of the methods for the preparation of haloalkanes are already
discussed in details in other chapters as the chemical properties of other
functional groups from which these are derived. Such reactions are indicated at
appropriate places in the present text.
By halogenation of alkanes
Direct Halogenation of alkanes in presence of light (photohalogenation), heat
(thermal halogenation), or catalyst (catalytic halogenation) results in formation
of haloalkanes. The reaction proceeds through a free radical substitution
mechanism. For example,
Note:
(i) Order of reactivity of halogens is F > Cl > Br > I
(ii) Ease of abstraction of hydrogen from alkanes by halogens is 3° > 2° > 1°
By addition of hydrogen halides to alkenes
The electrophilic addition of hydrogen halides to alkenes (Section 6.3.2; p. 225)
results in the formation of haloalkanes. The reaction is regioselective and follows
Markovnikov’s rule.
The addition of HBr in presence of a peroxide results in the formation of 2°
haloalkane (Kharasch effect). A free radical mechanism is followed in presence
of peroxide. For example,
From alcohols
(i) By reaction with HCl or HBr
Reaction of alcohol with HCl in presence of anhydrous ZnCl2 results in the
formation of a chloroalkane. The reagent, HCl combined with anhydrous ZnCl2,
is known as Lucas Reagent and is used for distinguishing 1°, 2° & 3°alcohols.
Similarly, reaction of alcohols with HBr in presence of H2SO4 results in the
formation of bromoalkanes. For example,
Depending upon the nature of substrate and to some extent on the nature of
reagent and reaction conditions, the course of the nucleophilic substitution
reactions may follow the following mechanisms (or pathways):
(a) Substitution Nucleophilic Unimolecular mechanism (referred as SN1
mechanism)
(b) Substitution Nucleophilic Bimolecular mechanism (referred as SN2
mechanism)
(c) Substitution Nucleophilic Internal mechanism (referred as SNi
mechanism)
(The SNi mechanism is discussed thoroughly in section 13.3.3; p. 466)
The rate determining step involves interaction of two species, namely the
haloalkane and the nucleophile. Thus, rate is dependent upon the concentration
of these two species and is referred as bimolecular reaction, which follows
second order kinetics. It is to be noted that the mechanism is favoured in
presence of strong nucleophiles.
The order of reactivity of haloalkanes is dependent on the stability of
transition state. The stability of the transition state is governed by the following
factors:
(i) A primary haloalkane preferably undergoes SN2 mechanism because of
least steric hindrance in the transition state, which makes the transition state
more stable.
(ii) A bulkier group attached to carbon, makes the transition state unstable
because of steric interactions. More the number of bulkier alkyl groups,
more is the steric hinderance and lesser will be the stability of transition
state. This in turn causes a slow rate of reaction.
Hence, the order of reactivity of haloalkanes is CH3X > 1° > 2° > 3°.
The effect of substituents on the stability of transition state in SN2 reaction is
illustrated as follows:
SN 2 reactions
In SN2 mechanism, the reactants in rate determining step involve both
haloalkane and nucleophile (a charged species). A polar protic solvent interacts
with nucleophile and solvolyzes it. As solvent molecules surround the
nucleophile, its approach towards electrophilic carbon gets hindered and the rate
of nucleophilic substitution reaction decreases.
Thus, the SN2 reaction rate is decreased in presence of polar protic solvents and
to increase the rate of SN2 reactions, polar aprotic solvents are used. Polar
aprotic solvents provide a polar medium but do not inhibit the approach of
nucleophile towards electrophilic carbon, as they do not solvolyze the
nucleophile.
11.3.2 Reactions of Haloalkanes
Nucleophilic substitution reactions
1. Reaction with oxygen nucleophiles
The nucleophilic species which attack the electrophilic carbon of haloalkane
through oxygen are termed as oxygen nucleophiles. For example, –OH,
–OC H , RCOO–, and (CH ) S=O.
2 5 32
(i) Reaction of haloalkane with aq. NaOH, aq. K2CO3, or moist silver oxide
(AgOH) results in the formation of alcohol.
(ii) Reaction of haloalkanes with sodium alkoxide or dry silver oxide results in
the formation of ether.
(iii) Reaction of haloalkanes with dimethylsulfoxide results in the formation
of carbonyl compounds. For example,
5. Ambident nucleophiles
The nucleophiles which can attack a substrate through two possible sites are
termed as ambident nucleophiles. For example, a cyanide ion can attack as a
nucleophile through carbon as well as through nitrogen. Similarly, nitrite can
attack as a nucleophile through oxygen and nitrogen.
In general Ag+ ions promote SN1 reaction as they can pull the
leaving group effectively and helps in generating the carbocation.
Thus, with silver salts nucleophilic attack occurs mainly through
more electronegative atom in the nucleophilic substitution
reactions.
The tertiary haloalkanes do not undergo this substitution reaction and instead
undergo an elimination to form alkenes.
(ii) Reaction of haloalkanes with alcoholic solution of AgCN results in the
formation of alkaneisonitrile (via SN1 mechanism). The attack of
nucleophile in this case occurs through nitrogen.
(iii) The reaction of sodium nitrite with primary or secondary haloalkanes (via
SN2 mechanism) result in the formation of nitroalkanes. The ambident
nucleophile (nitrite ion) attacks through less electronegative atom (i.e.
nitrogen).
Fig. 11.1 Synthetic utility of nucleophilic substitution reactions of haloalkanes: Functional group
transformations from haloalkanes using oxygen, sulfur, nitrogen and carbon nucleophiles.
In haloalkanes, the reaction with an electron rich species (Nu–) may either be a
nucleophilic substitution reaction or an elimination reaction. In fact, the
substitution and elimination reactions compete with each other. The reaction of
haloalkanes with aqueous sodium or potassium hydroxide results in the
formation of alcohol (substitution reaction). However, the reaction of
haloalkanes with alcoholic potassium hydroxide results in dehydrohalogenation
to produce an alkene (elimination reaction).
In general elimination reaction occurs: (i) in the presence of a strong and/or
bulkier base;
(ii) at high temperature; and (iii) with bulkier haloalkanes.
The alcoholic KOH results in the formation of a strong base, ethoxide ion (
–OC H ). The much stronger ethoxide ion abstracts a proton to form an alkene.
2 5
• The rate determining step involves only the haloalkane. Thus, it’s a
unimolecular reaction and follows first order kinetics.
• The stability of carbocation governs the rate of reaction. The order of
stability of carbocations and hence, the order of reactivity of haloalkanes
towards elimination reactions is 3° > 2° > 1° > CH3X.
• The reaction involves a carbocation intermediate. Therefore, there is a
possibility of carbocation rearrangement.
Step 2. Abstraction of β-proton of the carbocation by strong base: formation of
an alkene
The rate determining step (only step) involves the base as well as the haloalkane
so it’s called a bimolecular reaction, which follows a second order kinetics. It
should be noted that
(i) A more substituted alkene is favoured during the reaction.
(ii) An E-2 mechanism involves anti elimination, that is, removal of β-
hydrogen and halide ion occurs from opposite sides.
In general, elimination reactions favour bimolecular (E-2) mechanism, as it does
not involve carbocation rearrangement. The following table (Table 11.2)
compares the E-1 and E-2 mechanism.
E1cB (Elimination, unimolecular, conjugate base) mechanism
The presence of electron-withdrawing substituents on β-carbon of haloalkane
favours E1cB mechanism. This is a step wise mechanism where first step is fast
and involves loss of β-hydrogen of haloalkane, in presence of a base, to give a
carbanion. The loss of halide ion from carbanion intermediate, is a slow, rate
determining step that results in the formation of an alkene.
(c) A more electropositive metal forms a more ionic carbon–metal bond and
the electropositive character of metals follows the order: Li > Mg > Cu
(d) The preparation and reactions of organometallic compounds are carried
out in suitable inert solvents like ethers, under anhydrous conditions. In
general, the ethers used are diethyl ether, dimethoxyethane (DME), and
cyclic ethers such as Tetrahydrofuran (THF) and dioxane.
(e) The ethers solvate the organometallic compounds easily, that is, they
remain in dissolved form and generally exist as etherates.
11.5.1 Preparations
Vinyl chloride [Chloroethene]
Reaction of ethyne (acetylene) with one mole of HCl results in the formation of
vinyl chloride (chloroethene). It is an electrophilic addition reaction (Section
8.3.2).
Allyl bromide is prepared by the reaction of propene with NBS (Section 6.3.5)
NOTABILIA 10
SELECTED SOLVED EXAMPLES
Example 1. Of the following nucleophilic subsititution reactions, which one will
be faster and why?
Solution. Reaction (ii) is faster compared to recation (i) because acetate ion is a
better nucleophile compared to water. In both the cases the attacking site of
nucleophiles is oxygen. A negatively charged ion is more nucleophilic than
corresponding neutral species (refer pp. 402–03). Thus, CH3COO– has more
nucleophilicity than H2O.
Example 2. Arrange the haloalkanes in the following series in an increasing
order of reactivity towards SN1 reations:
(i) CH3CH2CH2CH2Br; CH3CH2CH(Br)CH3; (CH3)3C–Br
(ii) (CH3)2CHBr; (CH3)2CHCl; (CH3)2CHI
Solution. In series (i), all the compounds are bromoalkanes and hence the rate of
reaction will depend upon the stability of carbocations formed by loss of
bromide ions in the first step. The carbocations formed are:
Solution
Reactions (i) and (ii) are carried out in the presence of same base, i.e. sodium
ethoxide. In
reaction (i), the substrate is a primary haloalkane which undergoes preferably a
substitution reaction. In reaction (ii), the substrate is a tertiary haloalkane which
undergoes preferably an elimination reaction.
The substitution and elimination reations compete with each other. In presence
of same base, the bulkier haloalkane (3°) undergoes elimination. If the substrate
is same but reation is carried out with different bases, a strong base favours
elimination (see pp. 415–16)
Example 6. Why in the reaction of (CH3)3CCl with –OH, there is no formation
of (CH3)3C–OH?
2. Write the structure and IUPAC names for all isomeric chlorobutanes
(C4H9Cl) and bromopentanes (C5H11Br).
3. How are the haloalkanes prepared from alkanes and alkenes? What type of
mechanism is involved in these preparations?
4. Give the convenient method for the synthesis of the following haloalkanes.
Name the type of reaction mechanism involved and also indicate the name
reaction(s), if any?
(a) 2-Chloropropane from alkene
(b) 1-Iodobutane from 1-Chlorobutane
(c) 2-Bromobutane from but-1-ene
(d) 1-Bromobutane from but-1-ene
(e) Bromoethane from carboxylic acid
(f) tert. Butylbromide from tert. butyl alcohol
5. Giving a suitable explanation, arrange the following haloalkanes in increasing
order of boiling points:
(a) CH3Br, CH3Cl, CH3I, CH3F
(b) n-butyl bromide, isobutyl bromide, 2° butyl bromide, and 3° butyl
bromide
6. Giving examples, explain the following terms:
oxygen nucleophiles, nitrogen nucleophiles, sulfur nucleophiles, and carbon
nucleophiles.
7. What product(s) will be obtained when 1-bromobutane is treated with
(a) Aqueous KOH
(b) Alcoholic KOH
(c) Na/ether
(d) Mg/ether
(e) NaI/acetone
(f) NaCN
(g) AgCN
(h) C2H5ONa
8. How will you distinguish between haloalkane, alkenes, and terminal alkynes?
9. How will you distinguish between chloroethane and vinyl chloride?
10. How will you distinguish between chloroform and carbon tetrachloride?
11. Explain, why
(a) Vinyl chloride is less reactive than ethyl chloride.
(b) Allyl chloride is more reactive than vinyl chloride.
12. Discuss and compare the mechanism of SN1 and SN2 reactions of
haloalkanes.
13. Comment on the stereochemical aspects involved in the bimolecular
nucleophilic substitution reactions?
14. Explain the term nucleophilicity by taking suitable examples.
15. Define the role of solvents in nucleophilic substitution reactions.
16. What are leaving groups? Explain with examples.
17. Define ‘elimination reactions’ and explain the conditions under which they
compete with substitution reactions.
18. Give the detailed mechanism of the reaction of bromomethane and 2-bromo-
2-methylpropane with aqueous NaOH.
19. What are organometallic compounds and how are they prepared?
20. What is the effect on the polarity of alkyl group in haloalkane after its
reaction with metal?
21. What are haloforms? Give industrial method of preparation of chloroform.
22. Why is ethanol added to bottles during storage of chloroform?
23. How are geminal and vicinal dihalides prepared from unsaturated
hydrocarbons?
Chapter12
Haloarenes
12.1 INTRODUCTION
The aromatic halogen compounds can be classified into two categories, namely
(i) the compounds where halogen is directly attached to benzene ring called
halobenzenes or haloarenes and (ii) the compounds where halogen is attached to
the side chain of benzene ring. A few examples of both the categories along with
their IUPAC names are given here. This chapter describes the chemistry of
haloarenes in detail.
(iii) SN2 reactions are stereospecific where attack of nucleophile occurs from
the back (rear side) to form a product with inversion of configuration. In
halobenzenes, the steric hindrance due to aromatic ring shields the back
side attack of nucleophile.
In benzyne, sp2 orbitals lie in the plane of the ring and do not interact with the p
orbitals of the aromatic system. The two sp2 orbitals are in same plane but the
overlap is not effective due to improper orientation and thus, they form a very
weak bond. For this reason, the benzyne intermediate is highly unstable and thus
highly reactive.
Addition–elimination mechanism
The presence of electron-withdrawing groups on benzene ring of haloarenes
enhances the rate of nucleophilic substitution reactions as evident from the
following reactions. For example, the formation of 2-nitrophenol from 2-
chloronitrobenzene occurs in alkaline medium at about 135°C. On the contrary
2,4,6-trinitrophenol (picric acid) can be prepared from 2,4,6-
trinitrochlorobenzene in alkaline medium at room temperature.
Thus, more the number of electron-withdrawing groups present at ortho- and
para- positions, faster is the nucleophilic substitution reaction.
In the presence of electron-withdrawing groups the reaction follows addition–
elimination mechanism. The nucleophile in the first step adds on to electrophilic
carbon of C–X bond. This is a slow step, which results in the formation of an
anion. The anion is stabilized by delocalization. The delocalization occurs in
presence of electron-withdrawing groups and occurs effectively if the electron-
withdrawing groups are present at ortho- and para- positions.
The mechanisms for these electrophilic substitution reactions have already been
discussed in details in Chapter 10.
12.4.1 Preparations
This section describes the various methods used for the preparation of aromatic
compounds with halogens attached to the side chain.
Direct halogenation
The reaction of toluene with halogens in presence of sunlight or ultraviolet light,
results in its substitution at side chain rather than, at the hydrogen of the
aromatic ring.
The halogenation of side chain occurs by the free radical mechanism, similar to
alkanes via the formation of benzyl free radical.
By the action of N-bromosuccinimide
The reaction of toluene with N-bromosuccinimide (NBS) in the presence of
organic peroxide results in side chain bromination to form benzyl bromide.
Blanc reaction
The reaction of benzene with formaldehyde and HCl in presence of zinc chloride
or aluminium chloride results in the formation of benzyl chloride. This is a
typical electrophilic substitution reaction, which involves the introduction of
chloromethyl group (–CH2Cl) directly to the nucleus (aromatic ring). The
reaction is commonly known as chloromethylation.
From benzaldehyde
Benzaldehyde on reaction with phosphorous oxychloride results in the formation
of benzal chloride.
Wurtz reaction
Benzyl chloride reacts with sodium metal to form dibenzyl. Similarly with
haloalkanes in presence of sodium metal, it forms alkylbenzene.
Reduction
On reduction with lithium aluminium hydride benzyl chloride results in the
formation of toluene.
The benzyne intermediate can undergo addition at either carbon to give two
carbanions. A more stable carbanion of the two results in the formation of final
product.
EXERCISES
1. Give the structure and IUPAC names for all isomers possible for
(a) C7H7Br and
(b) C6H4Cl2.
2. Under what conditions, the chlorination of benzene results in the formation of
chlorobenzene?
3. In toluene, chlorination can occur at the aromatic ring as well as at the side
chain. Give the reaction conditions for the formation of both.
4. How can chlorobenzene and bromobenzene be synthesized from benzene
diazonium salt?
5. Why is chlorobenzene less reactive than haloalkanes towards nucleophilic
substitution reactions?
6. How can chlorobenzene be converted into
(a) phenol
(b) aniline
(c) toluene
(d) benzene
(e) phenyllithium
Give, if any, name reaction(s) involved in above conversions.
7. What is the effect of electron-withdrawing group(s), present in
chlorobenzene, towards its nucleophilic substitution reaction?
8. How can picric acid be prepared from chlorobenzene?
9. Explain why 2,4,6-trinitrochlorobenzene is easily hydrolyzed with water but
chlorobenzene is not.
10. Give the electrophilic substitution reactions of chlorobenzene.
11. Chlorobenzene acts as an ortho and para director for electrophilic
substitution reactions but is a weak ring deactivator. Explain.
12. Giving evidence for the formation of benzyne intermediate, discuss the
elimination–addition mechanism for the nucleophilic aromatic substitution
reactions.
13. How can the side chain aromatic halogen compounds be prepared?
14. Give some nucleophilic substitution reactions of side chain aromatic halogen
compounds. Are these nucleophilic reactions different for side chain aromatic
halogen compounds than those for haloalkanes?
15. How can the benzyl chloride be converted into
(a) benzyl amine
(b) benzaldehyde
(c) benzyl alcohol
(d) toluene
(e) diphenylmethane
(f) benzoic acid
Give, if any, name reaction(s) involved in these conversions.
16. What is the directive influence of –CH2Cl in benzyl chloride towards
electrophilic substitution reactions? Give the products for halogenation,
nitration, and sulfonation reactions of benzyl chloride.
17. Which product will be obtained by the reaction of benzyl chloride with
(a) chloromethane in presence of sodium.
(b) benzene in presence of anhydrous AlCl3.
(c) chlorine in presence of sunlight followed by hydrolysis.
18. Give the oxidation reactions of benzyl chloride.
19. How is benzyl chloride converted into benzal chloride and benzotrichloride.
20. How will you distinguish between 2-methylbromobenzene and benzyl
bromide?
Chapter13
Monohydric
Alcohols (Alkanols)
13.1 INTRODUCTION
The class of organic compounds in which hydroxy (–OH) group is attached to a
hydrocarbon is termed as alcohols. Alcohols may be considered as the hydroxy
derivatives of hydrocarbons and have a general formula CnH2n+1OH. The
formula represents a monohydric alcohol, that is, one which contains only one
hydroxyl group. Similarly, alcohols containing two or three hydroxyl groups are
called dihydric or trihydric alcohols and are collectively termed as polyhydric
alcohols. The carbon–oxygen bond in alcohol is formed by sp3–sp3 overlap. An
alcohol may be classified as primary (1°), secondary (2°), or tertiary (3°)
depending upon the number of carbons attached to carbon bearing hydroxyl
group.
According to the IUPAC nomenclature, the alcohols are named as alkanols. The
rules for naming alcohols have already been discussed in detail in Chapter 2. A
few examples of alcohols are
13.1.1 Physical Properties
Alcohols exhibit considerable dipole moment due to the presence of
electronegative oxygen. The alcohol molecules form intermolecular hydrogen
bonds readily. The intermolecular association of alcohol molecules through
hydrogen bonding is responsible for higher boiling point of alcohols as
compared to that of corresponding hydrocarbons and haloalkanes. Generally, the
boiling point increases with an increase in molecular mass. Though methanol
has low molecular mass compared to corresponding haloalkanes, it still exhibits
a high boiling point due to intermolecular hydrogen bonding. In case of
haloalkanes, no such hydrogen bonding occurs and thus they have low boiling
points.
As the number of carbon atoms in the chain in alcohol increases (C4 and above),
its solubility in water decreases. This is because in higher alcohols the large
alkyl groups cause an enlargement of the nonpolar hydrocarbon part, which
decreases their solubility in water (a polar solvent). The higher order alcohols
are soluble in organic solvents. In general, the monohydric alcohols have lower
density compared to water.
13.2 PREPARATION OF MONOHYDRIC
ALCOHOLS
Alcohols can be prepared conveniently by a number of different methods, some
of which have already been discussed, in previous chapters. In this section
various methods used for the preparation of monohydric alcohols are discussed
and the reference of the section numbers is given for methods which have been
discussed earlier.
From alkenes
The preparation of alcohols from alkenes can be carried out through various
reactions, which have already been discussed in section 6.3.2. These reactions
are —
(a) Addition of water–Hydrolysis of alkenes (p. 229)
(b) Addition of concentrated H2SO4 to alkenes followed by hydrolysis (p.
228)
(c) Oxymercuration–demecuration process in alkenes (p. 230)
(d) Hydroboration oxidaton in alkenes (p. 232)
These reactions can be summarized as
From haloalkanes
The hydrolysis of haloalkanes with aqueous sodium or potassium hydroxide, or
carbonates, or moist silver oxide results in the formation of alcohols. These
nucleophilic substitution reactions have already been discussed in details in
Chapter 11. For example,
In general, hydrolysis is not preferred for preparation of
alcohols from haloalkanes in the presence of strong bases.
• The use of strong base (such as NaOH) may cause elimination (as a
side reaction) in haloalkanes to form an alkene along with the
usual substitution to form alcohol.
• Moist silver oxide and sodium carbonate are mild bases compared to
alkali metal hydroxides. Thus, the use of AgOH or Na2CO3
minimizes the possibility of elimination reaction.
FROM ORGANOMETALLIC COMPOUNDS
Reactions of Grignard reagent
(a) With carbonyl compounds. One of the most convenient and versatile
method for preparation of alcohols involves the reaction of Grignard Reagent
with aldehydes or ketones.
In Grignard reagent (an organomagnesium halide), the alkyl group behaves as a
nucleophile (electron rich) and gets added to electrophilic carbon (electron
deficient) of aldehyde or ketone to give an addition product. Hydrolysis of this
addition product results in the formation of alcohol.
(c) With esters. The reaction of Grignard reagent with esters may result in the
formation of secondary or tertiary alcohols.
(i) Reaction with formate esters (formation of 2° alcohols). Grignard reagent on
reaction with ethylformate results in the formation of aldehyde, but the aldehyde
produced reacts further with another molecule of Grignard reagent to produce 2°
alcohol as the final product. For example,
(ii) Reaction with esters other than formate esters (formation of 3° alcohols).
The alkyl alkanoates (other than alkyl formate) on reaction with Grignard
reagent result in the formation of ketones which further react with another
molecule of Grignard reagent to produce 3° alcohols. For example,
(d) With acid chlorides (formation of 3° alcohols). The acid chlorides (other
than formyl chloride, HCOCl, which is not stable) on reaction with Grignard
reagent result in the formation of ketone which immediately reacts with another
molecule of Grignard reagent to form 3° alcohol. For example,
Reactions of alkyllithiums
Alkyllithiums are organometallic compounds which are prepared by the reaction
of haloalkanes with lithium using ether as a solvent (Section 11.4). In
alkyllithium, the alkyl group behaves as a nucleophile (electron rich) and reacts
readily with electrophilic carbon (electron deficient). The reactions of
alkyllithiums leading to the formation of alcohols are similar to Grignard
reagent. However, alkyllithiums are more reactive in comparison to
Grignard reagent. By selecting an appropriate alkyllithium, any type of 1°, 2°,
or 3° alcohols can be prepared. The concerned reactions are summarized as
follows:
By reduction
The aldehydes, ketones, carboxylic acids, acid chlorides, esters, and acid
anhydrides, on reduction
result in the formation of corresponding alcohols. Different types of reducing
agents are used for reduction of these classes of organic compounds.
The common methods used for the reduction of aldehydes and ketones to
alcohols are
(i) Bouveault–Blanc Reduction (Na/alcohol)
(ii) Meerwein–Ponndorf–Verley Reduction (Aluminium isopropoxide in
isopropyl alcohol)
(iii) Catalytic Reduction (H2/Pt, Pd or Ni)
Besides, Zn/acetic acid or alkali and Na–Hg/alcohol are also used as reducing
agents.
The reducing agents just mentioned cannot reduce carboxylic acids and their
derivatives. The metal hydrides such as LiAlH4 can be conveniently used for
reducing not only the carbonyl compounds to alcohols but also for reduction of
carboxylic acids and their derivatives to corresponding alcohols. For example,
(Replacement of hydrogen)
When a proton is removed from an alcohol, it results in the formation of
alkoxide ion. The alcohol then behaves as an acid. The acidic strength of
alcohols depends upon the following factors:
(a) Number of alkyl groups. More the number of alkyl groups (+I effect)
attached to carbon, the lesser is the stability of alkoxide ion and lesser will
be acidic strength of alcohol.
(b) Solvation. Alkoxide ion formed is stabilized through hydrogen bonding
with solvent molecules and this is known as solvation. In 3° alcohols, the
alkoxide ion is destabilized as steric factors inhibit the solvation. Thus,
steric hindrance reduces the acidic strength and as a consequence, the 3°
alcohols are least acidic.
Thus, order of reactivity of alcohols when they behave as acids is 1° > 2° > 3°.
Reaction of alcohol with metal (formation of alkoxides)
The alcohols react with active alkali metals like sodium to form corresponding
sodium alkoxides with the release of nascent hydrogen. For example,
The order of reactivity of alcohols is 3° > 2° > 1° and the order of reactivity of
hydrogen halides is HI > HBr > HCl.
Reaction with Lucas reagent (HCl + anhydrous ZnCl2)
[Test for distinguishing 1°, 2°, and 3° alcohol]
The reaction of alcohol with HCl in the presence of anhydrous ZnCl2 (called
Lucas reagent) results in the formation of corresponding chloroalkanes. The
alcohols are soluble in Lucas reagent whereas the chloroalkanes formed are
insoluble. The formation of chloroalkane is indicated by the cloudiness, which
appears in the reaction mixture. The time taken for the appearance of cloudiness,
by an alcohol is a measure of its reactivity. Thus, the reaction of alcohols with
Lucas reagent
(HCl/ZnCl2) is used as a test to distinguish between 1° , 2° and 3° alcohols. This
can be done by observing that
(i) in case of 3° alcohols, cloudiness appears immediately.
(ii) in case of 2° alcohols, cloudiness appears after a few minutes.
(iii) in case of 1° alcohols, no cloudiness appears.
Mechanisms
3. At 170°C (Ethene)
Reaction of ethanol with sulfuric acid (in excess) at 170° results in the formation
of ethene.
Mechanism
Victor Meyer test
This test is used for distinguishing 1°, 2°, and 3° alcohols. The alcohols are
converted to corresponding iodoalkanes, which are further treated with silver
nitrite to form corresponding nitroalkanes. The reaction of nitroalkanes with
nitrous acid followed by treatment with aqueous alkali gives following results
which distinguishes the 1°, 2°, and 3° alcohol.
(i) The nitroalkane from 1° alcohol on reaction with nitrous acid gives nitrolic
acid, which dissolves in aqueous alkali to give a red coloured solution.
(ii) The nitroalkane from 2° alcohol on reaction with nitrous acid gives
pseudonitrol, which is insoluble in aqueous alkali and gives blue colour.
(iii) The nitroalkane from 3° alcohol does not react with nitrous acid.
Iodoform reaction
Alcohols on oxidation result in the formation of carbonyl compounds. Alcohols
containing a CH3CH(OH)– group on reaction with iodine in presence of alkali
result in the formation of a yellow crystalline solid, iodoform along with sodium
salt of a carboxylic acid. In the first step, the
CH3CH(OH)– group is oxidized by sodium hypoiodite, NaOI (from NaOH + I2)
to group.
This group undergoes iodination at α-position in presence of a base to form a
triiodocarbonyl compound, which on alkaline hydrolysis forms iodoform.
In alcohols, the iodoform reaction is given by:
(i) Ethanol, the only primary alcohol that gives reaction.
(ii) Secondary alcohols having CH3CH(OH)– group (methyl secondary
alcohols).
Thus, iodoform reaction is used for distinguishing ethanol from other 1°
alcohols and also to distinguish CH3CH(OH)– (methyl secondary alcohols)
from other alcohols (except ethanol).
13.4 MORE ABOUT ALCOHOLS
1. Methyl alcohol or methanol, CH3OH, is also known as wood alcohol
because it was earlier obtained from the destructive distillation of hard
wood in the absence of air. Its common name methyl alcohol can also be
linked with the traditional process of its manufacturing since in Greek
methe means wine and hyle means wood. However now methanol is
manufactured in large scale by reduction of carbon monoxide with
hydrogen. Industrially methanol is used to manufacture formaldehyde and is
a precursor for many other chemicals.
2. Ethanol is also known as grain alcohol. It is obtained from the fermentation
of sugars
and starches by yeast. This process provides alcohol for beverages and
industrial
purposes. Fermentation process produces an aqueous solution of 12–15%
ethanol
because at this concentration of alcohol, yeast cells stop reproducing due to
its antiseptic action.
Example 4. Prepare the following alcohols using propene as the intial reactant:
(i) Pent-4-en-2-ol
(ii) Allyl alcohol (Prop-2-en-1-ol)
Solution
Example 5. Complete the following sequence of reactions:
Solution
Example 10. How will you convert tert. butyl alcohol to 2-Methylpropan-1-ol.
Solution. The conversion of 3° alcohol to 1° alcohol can be carried out as
follows:
EXERCISES
1. Give the IUPAC name for the following alcohols:
2. How many isomeric alcohols are possible for C4H10O. Write the structural
formula and IUPAC names for all the isomeric alcohols.
3. Explain, why alcohols have higher boiling points than alkanes and
haloalkanes of comparable mass.
4. How is ethanol manufactured from molasses or starch?
5. Give the product(s) formed when propan-1-ol reacts with following:
(a) Na
(b) PCl5
(c) Conc. H2SO4
(d) SOCl2
(e) K2Cr2O7/H+
(f) Conc. HBr
6. What are the different products obtained by the treatment of ethanol with
concentrated H2SO4 at 110°, 140°, and 170°C?
7. Give the oxidation products of 1°, 2°, and 3° alcohols.
8. Discuss the acid catalyzed mechanism for the dehydration of alcohol.
9. What happens when:
(a) Ethanol is treated with iodine in a strong alkaline medium.
(b) tert. butanol is passed over the heated copper at 300°C.
(c) Ethanol is treated with ethanoic acid in presence of conc. H2SO4.
10. How are methanol and ethanol manufactured commercially?
11. Complete the following sequence of reactions.
12. Which of the alcohol will give the positive iodoform test?
A. ETHERS
14A.1 INTRODUCTION
Ethers belong to class of oxygen containing organic compounds that can be
considered as derivatives of alcohols where an alkyl or aryl group replaces
hydroxy hydrogen. Structurally they may be considered as dialkyl (or aryl)
derivatives of water. Ethers are isomeric with alcohols but like alcohols they do
not posses replaceable active hydrogen. They may also be regarded as
anhydrides of alcohols as they can be derived by the elimination of water
molecule from two alcohol molecules. If the two groups attached to oxygen are
same in ethers, they are known as symmetrical ethers however if two groups are
different, they are termed as mixed or unsymmetrical ethers. Ethers are further
classified as open chain, cyclic, saturated, unsaturated, and aromatic ethers
depending on the nature of groups attached to oxygen.
Most of the ethers are known by their common names where while naming, the
alkyl or aryl groups attached to oxygen are prefixed before the word ether.
Cyclic ethers are named as oxides or epoxy compounds. In the IUPAC system,
ethers (refer Chapter 2) are considered as alkoxy derivatives of alkanes and
named accordingly as alkoxyalkanes. In case of unsymmetrical ethers, larger
alkyl group is chosen as parent hydrocarbon and the smaller alkyl group is
considered as alkoxy group. The IUPAC names of few ethers are as follows
(with the common names written in parentheses).
Isomerism
Ethers exhibit functional isomerism and metamerism.
(i) Functional isomerism. Ethers are isomeric with alcohols as both have same
general formula (CnH2n+2O).
(ii) Metamerism. Ethers having four or more number of carbons exhibit
metamerism because with same molecular formula they can have different
alkyl groups attached to oxygen atom. Thus, the molecular formula
C4H10O represents three isomeric ethers or metamers as
The reaction occurs by SN2 mechanism and involves the attack of alkoxide ion
(a nucleophile) on polar carbon–halogen bond of haloalkane. The reaction is
most suitable for preparing mixed or unsymmetrical ethers.
14A.2.3 Alkoxymercuration–demercuration of
Alkenes
The reaction of alkenes with mercuric trifluoroacetate and alcohol in the
presence tetrahydrofuran as solvent results in the formation of alkoxyalkyl
mercury compounds (alkoxy mercuration). The reduction of these compounds
with sodium borohydride (demercuration) results in the formation of ether.
Ethers behave as Lewis bases and form coordination complexes with Lewis
acids, such as BF3, AlCl3, and the like, popularly known as etherates. Because
of the ability of etheral oxygen to coordinate with the electron deficient species,
they are used as solvents in preparations of organaometallic compounds like
Grignard reagent.
Formation of peroxides
On exposure to air in the presence of light, ethers slowly undergo spontaneous
auto-oxidation and form peroxide derivatives.
In case of mixed ethers, halogen attaches itself to smaller of the two alkyl groups
of ether. For example,
This can be explained on the basis of the fact that halide ion (a nucleophile) will
attack readily on a less hindered carbon with high electrophilic character. The
overall mechanism for the reaction of mixed ether with HI is as follows:
Other hetero atoms may replace the oxygen in the crown ethers. In 1987,
Pederson, Cram and Lehn received Nobel Prize for development of crown
ethers. The crown ethers have the unique property of forming strong complexes
with metal ions. These complexes are known as Cryptates and crown ethers
themselves are known as Cryptands. The complex exhibit a Host-Guest
relationship where crown ether plays the part of host for its guest that is metal
ion. The ability to bind the metal ion depends on the size of crown ether and that
of metal ion. For example,
[12]-crown-4 binds Li+ strongly (in other words Li+ forms strong cryptate
with
[12]-crown-4)
[15]-crown-5 binds Na+ strongly (in other words Na+ forms strong cryptate
with
[15]-crown-5)
[18]-crown-6 binds K+ strongly (in other words K+ forms strong cryptate
with
[18]-crown-6)
Because of their property to bind with metal ions they are used as phase transfer
catalysts. The ionic reagents do not dissolve in organic solvents. To carry out the
reaction of organic substrate more effectively with ionic reagents, in a
homogeneous medium, the crown ethers are used. Crown ethers basically behave
as a phase transfer catalysts, which form complex with metal ions and transport
the anion from aqueous phase to organic phase as an ion pair. The anion reacts
with the organic substrate more efficiently in this process.
B. EPOXIDES
14B.1 INTRODUCTION
In general, cyclic ethers with three membered heterocyclic ring (one of the
carbon is replaced by oxygen, hetero atom) are known as epoxides. Carbons and
oxygen are sp3 hybridized in epoxides. These three membered cyclic ethers are
also known as ethylene oxides or oxiranes. Another name of cyclic ethers is
oxacycloalkanes where oxa- indicates replacement of a CH2 group in the ring by
oxygen. Commonly, the cyclic ethers are referred to as epoxyalkanes. A few
examples of epoxides are:
The general mechanism for acid catalyzed and base catalyzed ring opening
reactions are as
follows:
Acid catalyzed ring opening in unsymmetrical epoxides:
This chapter discusses two most important classes of sulfur compounds, namely
thiols (or thioalcohols) and thioethers.
14C.2 THIOLS [MERCAPTANS]
Thiols may be considered as alkyl derivatives of hydrogen sulfide, are analogous
to alcohols, and thus termed as thioalcohols. Since they react with mercuric
oxides to form mercuric salts they are also called alkyl mercaptans (mercurium =
mecury; captans = catching) or simply mercaptans. The
–SH group is known as sulfhydral or mercapto group. The IUPAC nomenclature
of thioalcohols is done by suffixing thiol to the parent alkane with the lowest
possible numbered position for thiol. Thus, the name becomes alkanethiol. Few
examples of thiols are given here.
From alcohols
Thiols can be prepared from alcohols either by heating with phosphorous
pentasulfide or by the reaction with hydrogen sulfide in the presence of a
catalyst.
From alkyldisulfides
The reduction of alkyldisulfides with zinc in the presence of acid results in the
formation of thiols as
From Grignard reagent
Reaction of sulfur with Grignard reagent forms an adduct, which on subsequent
hydrolysis yields corresponding thiol.
14C.4 CHEMICAL PROPERTIES OF THIOLS
The low polarity of –SH bond makes it a weak bond, which contributes to high
acidic character of thiols compared to alcohols. The alkane thiolate ion (RS–)
formed by loss of a proton is stabilized to a greater extent due to delocalization
of negative charge over larger sulfur atom. Thus, thiols are stronger acids
compared to alcohols. In their reactions, the thiols are more nucleophilic
compared to alcohols.
Reaction with alkali metals and alkali
Thiols on reaction with alkali metals forms mercaptides with the evolution of
hydrogen.
Thiols behave as weak acids and thus dissolve readily in alkalis also to form
mercaptides. For example,
Oxidation
Thiols are oxidized to disulfides with mild oxidizing agents such as hydrogen
peroxide and, sodium hypochlorite. But with strong oxidizing agents like nitric
acid or potassium permanganate, they are oxidized to corresponding sulfonic
acids.
14C.5 THIOETHERS [ALKYL SULFIDES]
Thioethers are the sulfur analogues of ethers. The C–S–C bond angle in thioether
is nearly 105°. In IUPAC nomenclature, symmetrical thioethers are named as
dialkyl sulfides whereas in unsymmetrical thioethers, both the alkyl groups are
written before the suffix sulfide.
From ethers
Ethers on reaction with phosphorous pentasulfide form thioethers.
From thiols
(i) Thioethers are formed when vapours of thioalcohols are passed over heated
catalysts at 300°C.
(ii) The addition of thiols to an olefin in the presence of peroxide produces
thioethers. For example,
2. Write the structures and names for all the isomeric compounds with molecular
formula C5H12O.
3. Why do ethers have low boiling points compare to isomeric alcohols?
4. Explain, with mechanism, how can ethers be synthesized by following
methods.
(a) Williamson synthesis
(b) Alkoxymercuration–demercuration of alkenes
5. Why are 3° haloalkanes not used in Williamson ether synthesis?
6. How can Grignard reagent be used for the preparation of higher ethers?
7. Why are ethers less reactive compared to alcohols?
8. Why are ethers stored in dark coloured bottles?
9. How are peroxides formed in ethers solution destroyed?
10. What will be the product formed in the following reaction.
11. Why, in the reaction of HBr and HI with unsymmetrical ethers, does the
smaller group form the haloalkane?
12. How will you convert methoxymethane to (i) methanol, (ii) methylacetate,
and (iii) bromomethane?
13. What is Zeisel’s method for the estimation of alkoxy groups?
14. Following methods are basically the methods used for the preparations of
some commercially important ethers. Complete the reactions and identify the
ether formed in each case.
15. Complete the following reactions:
16. What is the product formed when bromoethane reacts with excess of sodium
hydrogen sulfide?
17. Why do thiols have lower boiling points compared to alcohols?
18. Compare the acidic strength of alcohols with thiols.
19. How can diethyl sulfide (C2H5SC2H5) be prepared from a Grignard
reagent?
20. What are the products obtained by oxidation of (a) thiols and (b) thioethers,
with mild oxidizing agents?
Chapter15
Polyhydric Alcohols
(Diols and Triols)
15.1 INTRODUCTION
Polyhydric alcohols contain two or more hydroxy groups present on different
carbons of the hydrocarbon chain. Depending upon the number of hydroxy
groups they are termed as di-, tri-, tetra-, or pentahydric alcohols. The
compounds that contain two hydroxy groups attached to the same carbon atom
are highly unstable and readily eliminate a water molecule to form more stable
carbonyl compounds.
In polyhydric alcohols, the relative position of the –OH group in the molecule
is designated by 1,2-, 1,3-, or 1,2,3- and so on. In IUPAC nomenclature system,
the longest carbon chain containing –OH groups is selected and the hydroxy
groups get the minimum possible number. The dihydric alcohols are termed as
alkanediols (commonly known as glycols) and in a similar manner trihydric
alcohols are called alkanetriols (refer Chapter 2). A few examples of polyhydric
alcohols are as follows:
In the present chapter we shall discuss dihydric and trihydric alcohols taking
Ethylene glycol (ethane-1,2-diol ), pinacols, and glycerol (propane-1,2,3-triol) as
the representative examples of this family of compounds.
15.2 ETHYLENE GLYCOL [ETHANE-1,2-DIOL]
It is the first member of the series of alkanediols and is also known as glycol.
Ethylene glycol is a colourless, viscous liquid (boiling point 197°C). It is
hygroscopic in nature and is miscible with water and ethanol in all proportions.
It is sweet in taste but a toxic compound. It forms low freezing mixture with
water.
15.2.1 Preparations
Ethylene glycol may be prepared by the following methods:
From ethene
There are three different methods by which ethylene glycol (ethane 1,2-diol) can
be synthesized from ethene.
(i) Oxidation. The reaction of ethene with cold, dilute alkaline KMnO4 solution
or osmium tetraoxide (OsO4) results in cis-hydroxylation to form ethane-1,2-
diol as the final product.
From ethane-1,2-diamine
In general, reaction of aliphatic amines with nitrous acid results in the formation
of corresponding alcohol. By a similar analogy, the reaction of ethane-1,2-
diamine gives ethylene glycol.
(ii) With dicarboxylic acids. The reaction of ethylene glycol with dicarboxylic
acid generally results in the formation of condensation polymers. For example,
its reaction with terphthalic acid forms a well-known polymer called terylene
(also known as decron or terene), which is extensively used as a fiber.
Oxidation
Ethane-1,2-diol contains two primary alcoholic groups. The oxidation results in
the formation of different products depending on the nature of the oxidizing
agent.
(i) Oxidation of ethane-1,2-diol with nitric acid results in the formation of
oxalic acid via a series of other oxidation products.
(ii) Ethane-1,2-diol on oxidation with periodic acid, or lead tetraacetate, or
sodium bismuthate results in the carbon–carbon bond cleavage of glycol
producing carbonyl compounds. In case of ethylene glycol, the product
formed is formaldehyde.
Dehydration
Ethylene glycol undergoes dehydration under different conditions to form
different products. For example:
(i) Heating ethylene glycol up to 500°C results in dehydration to form
ethylene oxide.
(ii) Heating with anhydrous zinc chloride results in the formation of
acetaldehyde.
(ii) Two molecules of ethylene glycol condense in the presence of
concentrated H2SO4 to form cyclic ether known as dioxane.
• In this example, the migratory aptitude of the groups governs the formation
of product. In Step 3 of mechanism, the migration of an aryl group is
preferred over an alkyl group. In general the migratory aptitude of different
groups follows the order
–Ph > –C(CH3)3 > –CH2CH3 > –CH3 > H
15.4.2 Preparations
Glycerol is prepared by the following methods:
From fats and oils
As already mentioned, fats and oils are triesters of glycerol (glycerides).
The hydrolysis of glycerides forms glycerol and fatty acids. The fats and oils are
hydrolyzed either with alkali (in soap industry) or by superheated steam (in
candle industry) and glycerol is obtained as a by-product.
(i) From soap industry. In the soap industry fats and oils are hydrolyzed with
sodium hydroxide and the hydrolysis results in the formation of sodium salt
of fatty acids (known as soap) and glycerol is obtained as a by-product.
Soap is salted out (or precipitated) by adding sodium chloride to the reaction
product. The soap is filtered and the filtrate is known as spent lye. It contains
approximately 3–5% glycerol. Spent lye is then allowed to settle in tanks where
most of the suspended impurities settle down. These impurities are then filtered
off, filtrate is distilled under vacuum and futher purified with activated charcoal.
It is again subjected to vacuum distillation, which gives glycerol of 90–95%
purity. Further distillation under reduced pressure yields pure glycerol (specific
gravity 1.26).
(ii) From candle industry. Higher fatty acids like stearic acid are mixed with
paraffin wax in the manufacture of candles. The fatty acids required for this
purpose are obtained by the hydrolysis of fats and oils with superheated
steam using dilute sulfuric acid as catalyst. The fatty acids are usually solids
and can be removed by filtration. Water is evaporated from the filtrate under
vacuum and further redistillation is done to obtain pure glycerol.
By fermentation of sugars
Glycerol is formed as a by-product during fermentation of sugars to obtain
ethanol. Better yields are obtained by adding small amount of sodium sulfite
along with yeast.
(ii) Heating glycerol at 260°C with oxalic acid result in the formation of
glyceryl dioxalate which undergoes decarboxylation at high temperature to
give allyl alcohol as the final product.
Oxidation
Glycerol contains two 1° and one 2° alcoholic groups and undergoes oxidation to
yield a variety of products. The type of product formed is dependent on the
nature of oxidizing agent.
16.1 INTRODUCTION
The class of organic compounds where hydoxy group (–OH) is directly attached
to benzene ring is termed as phenols. The carbon–oxygen bond in phenols is
formed by sp2–sp3 overlap. Most of the phenolic compounds are better known
by their common name. The IUPAC names of some phenolic compounds along
with their common name and physical characteristics (boiling and melting
points) are as follows:
16.1.1 Physical Properties
Phenols are generally colourless solids at room temperature. On exposure to air,
phenol becomes reddish in colour. Phenols are polar in nature and form strong
hydrogen bonding, which is reflected by high boiling point compared to
hydrocarbons of same molecular mass.
The substitution of phenol with amino, nitro, or hydroxy groups results in an
increase in melting point. Phenols are slightly soluble in water and their
solubility increases with an increase in temperature. Phenol is also known as
carbolic acid. Generally phenols are toxic but they exhibit antiseptic property.
Liquid phenol is a mixture of 90% phenol and 10% water. Phenols are weakly
acidic in nature.
16.2 PREPARATION OF PHENOLS
Various preparative methods of phenols as follows:
Dow’s process
Heating chlorobenzene with concentrated NaOH solution at 300°C under high
pressure results in the formation of sodium salt of phenol, which in acidic
medium liberates free phenol. The reaction proceeds through an elimination–
addition mechanism via benzyne intermediate (Section12.3.1). The presence of
electron withdrawing group in chlorobenzene enhances the rate of substitution
reaction and the reaction follows an addition-elimination mechanism via
Meisenheimer complex formation as an intermediate.
Mechanism
Step 1. Friedel–Crafts alkylation
Relatively less stable contributing structures for phenoxide ion as negative charge is delocalized
over electropositive carbon of the aromatic ring.
More stable contributing structures for carboxylate ion as negative charge delocalized over
electronegative oxygens.
The sodium salt of phenol is highly reactive and as a result, most of the reactions
of phenols are carried out as reactions of sodium phenoxide and not that of free
phenol.
Phenols react only with strong bases but not with weak bases
such as sodium carbonate or sodium bicarbonate. This reaction is
often used to distinguish between aromatic carboxylic acid and
phenol.
Reaction with acid chlorides and acid anhydrides (formation of esters)
Phenols react with acid chlorides and acid anhydrides in presence of bases to
form phenyl esters. The reaction and reaction mechanism are illustrated here.
Mechanism
The reaction forms same products in the presence of light, using ethanol as a
solvent (and without catalyst) and is then termed as Photo Fries rearrangement.
Mechanism. The fries rearrangement is an electrophilic substitution reaction that
may proceed through an inter- or intramolecular rearrangement. These
rearrangement mechanisms are individually discussed here.
Intermolecular rearrangement
Step 1. Complex formation (phenolic ester) with Lewis acid AlCl3 (formation of
acyl cation, an electrophile)
Step 2. Attack of electrophile at ortho and para positions of the ring & resonance
stabilization of arenium ion
Reimer–Tiemann reaction
Sodium phenoxide, on reaction with chloroform in alkaline medium, results in
the formation of
o-hydroxybenzaldehyde (salicylaldehyde) and p-hydroxybenzaldehyde.
The reaction is an electrophilic substitution reaction where the electrophile
involved is dichlorocarbene. Dichlorocarbene is generated by the reaction of
chloroform and sodium hydroxide. The attack of dichlorocarbene at strongly
activated ortho- and para- positions in phenoxide ion results in formation of
ortho and para products. Salicylaldehyde is formed as a major product due to
intramolecular hydrogen bonding. The details of reaction mechanism are as
follows:
Step 1. Generation of electrophile (1,1-elimination)
Step 3. Hydrolysis
In a similar manner, the electrophile can react at para position of phenoxide ion
to give
p-hydroxybenzaldehye as the minor product.
Nitrosation
Phenol reacts with nitrous acid to form p-nitrosophenol along with a small
amount of o-nitosophenol. The product p-nitrosophenol exhibits tautomerism
and thereby forms yellow crystals of
p-benzoquinone monoxime.
Azo-dye formation
The aryldiazonium salt behaves as an electrophile and couples with phenols at
strongly activated para- position to form azo dyes. The reaction occurs in
alkaline medium and is referred to as azo-coupling. In case p-position in phenol
is already occupied by a substituent, the coupling occurs at ortho position.
16.3.4 Other Reactions
Reduction
(i) Phenol on distillation over zinc dust results in the removal of the hydroxy
group and forms benzene.
(ii) Hydrogenation of phenol in presence of metal catalyst like nickel results in
the formation of cyclohexanol.
Oxidation
The oxidation of phenol results in the formation of various products depending
upon the nature of oxidizing agent used. For example, oxidation with hydrogen
peroxide gives a mixture of di- and trihydric phenols.
In the presence of stronger oxidizing agents, the breakdown of ring may occur.
Strong oxidizing agents may also cause the coupling of several benzene rings,
which results in the formation of tarry materials. The oxidation occurs through
the formation of phenoxy radical.
Ammonolysis of phenol
Phenol, when heated with ammonia in presence of zinc chloride as catalyst,
results in the formation of aniline.
12. What is the directive influence of –OH group in phenol towards electrophilic
substitution reactions?
13. Why is nitration of phenol carried out with dilute HNO3 and not with
concentrated HNO3 and H2SO4 mixture?
14. What will be the bromination product of phenol under following reactions
conditions? Explain the formation of product.
Problem 73. What is the most convenient route for the synthesis of neopentyl
iodide from neopentyl chloride.
Solution. Normally the iodides are conveniently prepared by the halide
exchange reaction known as Finkelstein reaction (Sec. 11.2, p. 396). Neopentyl
chloride (2,2-dimethyl-1-chloropropane) is a 1° haloalkane but has a bulky alkyl
group, so the substitution reactions (both SN1 and SN2) are very slow.
Synthesis of neopentyl iodide from neopentyl chloride using Grignard reagent
(from neopentyl chloride) is the most convenient method. The conversion takes
place as follows:
Problem 74. The hydrolysis of primary cholroalkanes is much faster in the
presence of iodide ions. Explain.
Solution. Hydrolysis of primary chloroalkanes follows SN2 mechanism to form
alcohols. The chloride ion is a poor leaving group and thus, its hydrolysis is
slow.
Iodide ion is a strong nucleophile as well as a good leaving group (p. 404) and
thus, catalyzes the hydrolysis of chloroalkane.
Problem 75. In an attempt to prepare Grignard reagent from 3° haloalkane, a
side reaction occurs frequently. Explain the formation of the side product by
taking as an example, the reaction of
2-chloro-2-methylpropane with magnesium in dry ether.
Solution. The reaction of 2-chloro-2-methylpropane with magnesium in dry
ether results in the formation of tert-butylmagnesium chloride. Since a 3°
haloalkane is used, it may simultaneously undergo dehydrohalogenation to give
2-methylpropene as the side product.
Problem 77. In the given series of anions, identify the strongest base and the
strongest nucleophile.
(a) CH3O–, CH3COO–, HO–
(b) HO–, Cl–, CH3O–, I–
Solution. (a) If the attacking atom is the same, nuclophilicity of an anion is
directly related to the basicity of the anion (p. 402). Basicity is the ease of
availability of electrons on a species that can further participate in a reaction.
More is the availability of electrons in an anion, higher is its basicity. As the
increasing order of the basicity of the anions is CH3COO– < HO– < CH3O–, the
same order is followed for nucleophilicity. The nucleophilic centre in all these
anions is same, namely oxygen.
(b) The nucleophilicity order of anions containing different nucleophilic centres
is directly related to the polarizability of anions. An anion with a larger size is
more polarizable and hence will be a strong nucleophile. The iodide ion because
of its largest size will behave as the strongest nucleophile. But at the same time,
the larger size of iodine makes it least basic due to dispersal of negative charge.
The CH3O– is the strongest base as +I effect of –CH3 group increases the
availability of electrons on oxygen.
Problem 78. Of the following pair of anions, indicate which one will be a
stronger nucleophile and why?
(a) CH3O– and CH3S–
(b) CF3COO– and CH3COO–
(c) C6H5O– and CH3O–
Solution. The nucleophilicity is directly related to basicity if different species
have the same attacking nucleophilic atom. However, if nucleophilic atoms are
different, polarizability is taken into consideration (refer Problem 77). Thus,
(a) CH3S– is a stronger nucleophile than CH3O– because sulfur being larger
in size is more polarizable and is a better nucleophile than oxygen.
(b) CH3COO– is a stronger nucleophile than CF3COO– as the presence of
electron withdrawing fluorine decreases the basicity and hence the
nucleophilicity of the anion.
(c) CH3O– is a stronger nucleophile than C6H5O–. In case of C6H5O–, the
negative charge on oxygen participates in delocalization with phenyl ring
that decreases the basicity and hence its nucleophilicity.
Problem 79. Are SN2 reactions stereospecific or stereoselective?
Solution. The SN2 reactions are stereospecific. It proceeds with a rear side
attack of nucleophile to form a substituted product with an inversion of
configuration (refer text). Thus, each stereoisomer of the initial reactant forms a
specific stereoisomer of the product.
Problem 80. Explain, why in an SN2 reaction the rate of reaction of
bromopropane in acetone is much higher than that of 2-bromo-2-methylpropane
(tert.butyl bromide) under similar conditions?
Solution. As already explained in the text (for details, refer to sec 11.3.1), the
formation of highly unstable transition state (as in case of tert.alkyl halides)
slows down the reaction rate in an SN2 reaction. In general, transition state in
SN2 is more stable when lesser number of alkyl groups are attached (as in case
of primary alkyl halides) as it causes lesser steric hindrance.
Thus, in 2-bromo-2-methylpropane (tert.butyl bromide), steric hindrance inhibits
it from undergoing SN2 reactions.
Problem 82. Explain, what is/are the product(s) formed in the following reaction
if SN1 mechanism is followed?
Problem 84. Explain, why are the compounds CH3CHF2 and CH3CF3 not
reactive towards nucleophilic reagents?
Solution. Fluorine has a strong –I effect. The presence of more number of
fluorine atoms should increase the electrophilicity of the carbon. However, the
fluorine atoms present on same carbon
atom decreases the polarity of molecule as the dipole moment of C–F bonds
oppose each other. This causes a net decrease in the electrophilic character of the
carbon attached to two or more fluorine atoms. Thus, the compounds CH3CHF2
and CH3CF3 are not reactive towards nucleophilic reagents due to reduced
electrophilicity of the carbon.
Problem 85. Complete the following reactions and indicate, giving reasons,
which of the reactions will be faster?
Both reactions are SN2 type. The sulfur atom being larger in size is more
polarizable and hence, more nucleophilic compared to oxygen (refer also
Problem 78). Thus, the rate of reaction in 2, is much faster due to higher
nucleophilicity of the anion CH3CH2CH2CH2S– as compared to
CH3CH2CH2CH2O– anion.
Problem 86. Giving a suitable explanation, arrange the following species in
order of their increasing strength as dehydrohalogenating agents.
Problem 88. Which is the possible geometrical isomeric alkene formed during
dehydrbromination of 2-bromopentane in alcoholic KOH?
Solution. Dehydrobromination of 2-bromopentane results in the formation of
trans-2-pentene. The reaction follows E2 mechanism (see Section 11.3.3) where
trans- (or anti-) elimination occurs and results in the formation of a more stable
alkene.
Problem 89. Carry out the synthesis of the following alcohols from
ethylmagnesium bromide:
(a) 2,3-Dimethylpentan-2-ol
(b) Pentan-1-ol
Solution. In both the cases, parent chain in alcohol is having five carbon atoms.
Grignard reagent, that is, ethylmagnesium bromide supplies two carbons and
therefore, the other reactant must supply three carbon atoms.
(a) Synthesis of 2,3-dimethylpentan-2-ol: Its synthesis involves the reaction of
ethylmagnesium bromide with substituted epoxy compound (oxacyclopropane
derivative). The ring opening takes place from the less hindered site and the
reaction occurs as follows:
The activation of ortho- and para- positions decreases with an increase in the
electronegativity of halogen, which results in a relative increase in the yield of
meta- product.
The –I effect of –OCH3 group stabilizes the negative charge at ortho position
more effectively as compared to negative charge at meta position. This results in
the formation of
m-phenylmethoxybenzene as the final product.
Problem 92. The reaction of ketones with Grignard reagent is a convenient
method for the preparation of 3° alcohols. However, one fails to synthesize a
sterically hindered 3° alcohol by a similar reaction as shown here:
Explain the reason and suggest an alternative method for the preparation of
sterically hindered 3° alcohols.
Solution. The reaction of organometallic compounds with ketones is used as a
tool for synthesizing alcohols. The reaction involves the attack of nucleophlic
alkyl group on electrophilic carbon of keto group. Higher the electropositive
character of metal, faster is the reaction with ketones.
The carbonyl group in the given ketone (2,4-dimethylpentan-3-one) is sterically
hindered. The relatively less electropositive character of magnesium inhibits the
attack of alkyl group of Grignard reagent on the sterically hindered carbonyl
carbon. Thus, Grignard reagent fails to give any reaction with sterically hindered
ketones.
Alkyllithiums are relatively more reactive than organomagnesium compounds
(Grignard reagent) due to high electropositive character of lithium compared to
magnesium. The highly electropositive lithium increases the carbanion character
of alkyl group and as a result alkyllithium reacts readily, even with sterically
hindered ketones to form 3° alcohol.
Problem 93. Give a suitable explanation for the following results obtained
during substitution reactions of 3°butyl alcohol.
The increasing order of stability of carbocation is: [II] < [I] < [III] < [IV]
The carbocations are stabilized through resonance. More the number of phenyl
rings attached to carbon with positive charge, more is the delocalization of the
charge and higher will be the stability. The p-nitrobenzyl cation is more stable
than benzyl carbocation due to delocalization of positive charge by –NO2 group.
Thus, order of reactivity is the same as the order of stability of carbocations.
Problem 97. The reaction of methoxybenzene (methylphenyl ether) with
concentrated aqueous HI solution at ~100°C results in the formation of phenol
and iodomethane. However, diphenyl ether under similar conditions (and even at
higher temperature), gives no reaction. Explain.
Solution. In phenolic ethers it is very difficult to cleave the phenolic C–O bond.
The mechanism for the reaction of methoxybenzene with concentrated HI
solution is as follows:
In diphenyl ether, the protonation of oxygen occurs but there is no sp3 carbon
which can be attacked by nucleophile I– to carry out further reaction.
Problem 98. What product will be obtained from following pinacols on heating
them in acidic medium? Explain with mechanism.
(a) 2,3-Diphenylbutane-2,3-diol
(b) 2-Methyl-1,1-diphenylpropane-1,2-diol
Solution. The heating of pinacols in acidic medium results in a rearrangement
reaction to form pinacolone (pinacol–pinacolone rearrangement). The important
steps in pinacol–pinacolone rearrangement (Section 15.3.2) are:
(i) Formation of a stable carbocation by removal of one of the –OH group in
acidic medium.
(ii) Migratory aptitude of groups during 1,2-shift of alkyl/aryl group.
(a) 2,3-Diphenylbutane-2,3-diol (a symmetrical pinacol) in acidic medium
undergoes pinacol–pinacolone rearrangement to produce 3,3-diphenylbutanone.
A symmetrical pinacol can lose either of the –OH group as it leads to the
formation of same carbocation. However during 1,2-shift, a phenyl group
migrates preferably over alkyl group.
Mechanism
(b) 2-Methyl-1,1-diphenylpropane-1,2-diol (an unsymmetrical pinacol) in acidic
medium undergoes pinacol–pinacolone rearrangement to produce 3,3-
diphenylbutanone. In unsymmetrical pinacol, the loss of –OH group occurs from
that carbon atom which results in the formation of stable carbocation. In this
case, the removal of –OH group occurs from carbon atom carrying two phenyl
groups. During 1,2-shift, either of the methyl group can migrate to give the
product.
The Pinancol-pinacolone rearrangement in some cases may
lead to ring expansion or ring contraction of the cyclic system.
Refer Problem 99 of Explore More Set-IV.
Chapter17
Aliphatic
Carbonyl Compounds
(Alkanals and Alkanones)
17.1 INTRODUCTION
The aldehydes and ketones belong to the class of oxygen containing organic
compounds that have a C=O group. Therefore, they are termed as carbonyl
compounds. In carbonyl group, the carbon and oxygen are sp2 hybridized. In
aldehydes, the three sp2 hybrid orbitals of the carbon form three σ-bonds,
namely the bonds with alkyl group (sp2–sp3 overlap), hydrogen (sp2–s overlap),
and oxygen (sp2–sp2 overlap). The p orbitals on carbon and oxygen overlap to
form a carbon–oxygen π-bond. The bond angle is 120° and carbonyl compounds
have planar structure. Aldehydes and ketones have the following general
structure:
In accordance with IUPAC nomenclature, the aldehyde and ketones are named as
alkanals and alkanones respectively. The carbonyl carbon is included in the
longest possible carbon chain and is given the lowest possible number. The
nomenclature of carbonyl compounds has already been discussed in detail in
Chapter 2. A few selected examples follow along with their IUPAC
nomenclature (common names in parentheses).
17.1.1 Physical Properties
The carbonyl compounds are polar in nature as the electronegativities of carbon
and oxygen differ a lot, and oxygen being more electronegative has a greater
electron density around it compared to carbon.
Hydroboration–oxidation of alkynes
Hydroboration of alkynes with borane results in the formation of vinyl
organoboranes, which on oxidation with alkaline hydrogen peroxide forms an
enol that tautomerizes rapidly to corresponding carbonyl compound (p. 282).
While terminal alkynes result in the formation of aldehydes, non-terminal
symmetrical alkynes result in the formation of ketones. However, non-terminal
unsymmetrical alkynes on hydroboration–oxidation result in the formation of a
mixture of ketones.
The vinyl organoborane has a double bond, which may undergo addition of a
second molecule of borane (as in the case of alkenes) to give a mixture of other
side products. Thus to prevent further addition, a bulkier hydroborating agent is
used which is popularly known as 9-BBN (9-Borabicyclo [3.3.1] nonane).
(ii) Stephen reaction. The reaction of alkanenitrile with HCl in the presence of
anhydrous stannous chloride (SnCl2) yields aldimine complex as an
intermediate, which on hydrolysis results in the formation of aldehyde. The main
reducing species is tetrachlorostannic acid, H2 [SnCl4], which is formed by
action of HCl and SnCl2. This is illustrated in the following reaction:
(iii) Reduction of acid chloride with Lithium tri-t-butoxyaluminohydroxide.
The reagent is prepared by treating LiAlH4 with three moles of tert-butyl
alcohol. Treating the acid chloride with this reagent in the presence of diglyme
(CH3OCH2CH2OCH2CH2OCH3) as a solvent results in the reduction of acid
halide to aldehyde.
17.2.3 FORMATION OF KETONES
From Dialkylcadmium
Reaction of acid chloride with dialkylcadmium results in the formation of
ketones. Dialkylcadmium is prepared by treating alkylmagnesium halide
(Grignard reagent) with cadmium chloride.
For example, preparation of butanone using Gilman reagent may be carried out
in the following two ways:
17.3 CHEMICAL PROPERTIES OF CARBONYL
COMPOUNDS
The carbonyl compounds undergo various types of chemical reactions which
include reactions involving the carbonyl ( C=O) group (nucleophilic addition
reactions), oxidation and reduction reactions, reactions involving α-carbon of
carbonyl compounds, and polymerization reactions of aldehydes. The reactions
which have already been discussed are also given in brief, along with the
reference of previous section numbers.
(ii) Wittig reaction. The Wittig reaction is used for the synthesis of alkenes by
reaction of carbonyl compounds with phosphorous ylides. Phosphorous ylide is
prepared by reaction of triphenylphosphine with haloalkane (methyl, 1° or 2°).
This reaction results in the formation of phosphonium salt which on treatment
with strong base (such as PhLi, BuLi, NaOC2H5 ) undergoes deprotonation to
form the phosphorous ylide. The reaction of phosphorous ylide with carbonyl
group results in the formation of betaine, which undergoes elimination to
produce an alkene. The synthesis of alkene (for example, propene) through this
reaction involves the following steps:
Step 1. Preparation of phosphorous ylide
Phosphorous ylide is a resonance hybrid of two structures and the structure with
positive and negative charge on adjacent atoms is the major contributing
structure.
Step 2. Reaction of phosphorous ylide with carbonyl compounds
Oximes have planar structure ( C=N) and they exhibit geometrical isomerism.
One of the important reactions of oxime is Beckmann rearrangement which is
discussed in
Chapter 18.
(c) With hydrazine (formation of hydrazone)
(d) With phenylhydrazine (formation of phenylhydrazone)
The reaction does not require any acid catalyst and the nucleophile in this
reaction is SO32–. Sulfur is a more powerful nucleophile compared to oxygen
and therefore the attack is preferred through sulfur.
All aldehydes but not all ketones give bisulfite adduct. This
bisulfite addition product is formed by all aldehydes and only by
methyl ketones. The other ketones due to decrease in electrophilicity
of carbonyl carbon and also because of steric factors due to alkyl
groups, do not react with sodium bisulfite.
This reaction is used for the purification of aldehydes and ketones
because aldehydes and ketones may be recovered from their bisulfite
adducts by warming them up with sodium carbonate solution.
(ii) Reaction with thiols. Thiols are more acidic as compared to alcohols and
thiolate salts behave as powerful nucleophiles. The acid catalyzed addition of
thiols to carbonyl compounds results in the formation of thioacetals. In general,
the catalysts used in this reaction are Lewis acids such as BF3 in diethyl ether or
ZnCl2. For example,
Aldehydes are oxidized much more readily compared to ketones and as a result,
aldehydes are able to reduce even mild oxidizing agents as discussed in the
subsequent parts of this section.
Oxidation reactions of ketones
Ketones are fairly resistant to oxidation. The oxidation of ketones occurs
under drastic conditions and requires strong oxidizing agents like acidified
K2Cr2O7 solution or alkaline KMnO4 solution. The oxidation of ketones results
in the formation of carboxylic acid with lesser number of carbon atoms. The
cleavage occurs at carbonyl carbon and hydrocarbon chain and one of the
hydrocarbon parts is oxidized to carbon dioxide and water. Oxidation of
cyclohexanone in presence of concentrated nitric acid results in the formation of
adipic acid.
In case of unsymmetrical ketones, during oxidation the cleavage can occur on
either side of carbonyl group to give a mixture of carboxylic acids.
Mechanism
It should be noted that these reagents are selective reducing agents, which reduce
only carbonyl group in a molecule. The double bond, if any, is not reduced by
these reducing agents.
Meerwein–Ponndorf–Verley reduction
Aldehydes and ketones are reduced to alcohols by treating them with a solution
of aluminium isopropoxide in isopropanol. The reaction is reversible in nature
and the reverse reaction is known as Oppenauer oxidation. However, oxidation
is carried out preferably using aluminium tert butoxide in tert butanol as a
catalyst.
Wolff–Kishner reduction
Wolff–Kishner reduction involves hydrazine as the reducing agent and reduces
carbonyl group of aldehydes and ketones to methylene group ( CH2). Aldehyde
or ketone is heated with hydrazine in presence of base such as potassium tert.
butoxide, potassium hydroxide, or potassium ethoxide, which results in the
reduction of the carbonyl compound to corresponding alkane. For example.
The aldehydes and ketones containing at least one α-hydrogen exhibit keto-enol
tautomerism.
The enolate ions are involved in a number of reactions of aldehydes and ketones.
Some of these reactions are popular and happen to be important name reactions.
These are discussed as follows:
Aldol condensation
Two molecules of aldehyde containing α-hydrogen undergo condensation in the
presence of a base to produce β-hydroxy aldehyde known as aldol and the
reaction is known as Aldol reaction. The acetaldehyde (ethanal) molecules
condense in the presence of a base like sodium hydroxide to produce 3-
hydroxybutanal (β-hydroxybutanal). Other bases such as barium hydroxide or
calcium hydroxide may also be used.
Mechanism
Step 1. Abstraction of α-hydrogen of aldehyde by base (formation of enolate
ion):
The α-hydrogen, being acidic, is abstracted by base to produce carbanion.
The mesityl oxide may be condensed with another molecule of acetone to form
phorone.
Claisen–Schmidt reaction
The aldol reaction may occur between an aldehyde and a ketone. In a crossed
aldol condensation if one of the component is ketone having α-hydrogen and the
other is an aldehyde with no α-hydrogen, the reaction is called Claisen–Schmidt
reaction.
In general, the reactivity of aldehydic carbonyl group is more compared to the
carbonyl group of ketone. Thus, attack of carbanion occurs on carbonyl carbon
of aldehyde.
Cannizzaro’s reaction
In the presence of alkali, the aldehydes with no α-hydrogen, undergo
intermolecular oxidation and reduction (auto oxidation–reduction or dismutation
of aldehyde). In this case, one molecule of aldehyde is oxidized to sodium salt of
carboxylic acid and the other is reduced to an alcohol.
Mannich reaction
The aldehydes and ketones containing α-hydrogen undergo condensation with
formaldehyde and ammonia (or primary and secondary amines) to produce β-
aminocarbonyl compounds. This condensation reaction is known as Mannich
reaction. The reaction may be acid or base catalyzed. For example,
Tischenko reaction
The aldehydes (with or without α-hydrogen) in presence of aluminium alkoxide
or magnesium alkoxide undergo auto oxidation and reduction. In the process,
one molecule of aldehyde is oxidized to carboxylic acid and the other aldehyde
molecule is reduced to alcohol, which results in the formation of an ester as the
final product of the reaction. For example,
Darzen glycidic ester synthesis
The reaction of a carbonyl compound with an α-hydrogen containing α-haloester
in the presence of a base like sodamide (NaNH2), to produce an α,β-epoxy ester
(known as glycidic ester) is termed as Darzen glycidic ester synthesis. This is an
aldol type condensation reaction and proceeds through an internal nucleophilic
substitution reaction.
Mechanism
Step 1. Abstraction of α-hydrogen from α-haloester by sodamide (formation of
carbanion)
All the α-hydrogens present in the carbonyl compound may be replaced easily
by halogens.
As discussed earlier in Section 13.3.4, p. 472, the iodoform reaction is also given
by ethanol and secondary alcohols which have CH3CH(OH)– group. In the first
step, the CH3CH(OH)– group is oxidized by sodium hypoiodite, NaOI (from
NaOH + I2) to CH3CO– group and then the reaction proceeds as it does with
carbonyl compounds.
Mechanism. The presence of CH3CO– group is necessary for iodoform reaction.
The >C=O group is an electron withdrawing group which makes the α-
hydrogens (CH3– group) acidic in nature.
Step 1. Abstraction of α-hydrogen by base (formation of carbanion)
Due to resonance, during the addition of polar reagent the electrophilic part of
the reagent add to carbonyl oxygen and nucleophilic part to β-carbon. The β-
carbon is electrophilic due to electron withdrawing carbonyl group.
The reactions of α,β-unsaturated carbonyl compounds are summarized below by
taking the examples of propenal (R=H) and but-3-enone (R=CH3)
If the polar reagent has H+ as electrophile part, then 1,4-addition results in enol
that rapidly tautomerizes to give a keto product, which is a 1,2-addition product.
For example,
Solution. The polar compounds have higher boiling point compared to nonpolar
compounds. Thus, CH3CH2CH2CH3 will have the lowest boiling point.
Alcohol (CH3CH2CH2OH) will have
the highest boiling point due to hydrogen bonding. Carbonyl compounds have
higher boiling points compared to ethers (refer Section 17.1.1). Therefore, the
increasing order of boiling
points is:
Thus, sodium butanoate and iodoform will be obtained from the following
carbonyl compound.
Example 8. Give the structure of the carbonyl compound which on reaction with
iodine and sodium hydroxide followed by hydrolysis gives iodoform and sodium
salt of 3,4-dimethylpentanoic acid.
Solution. The structure of carbonyl compound can be written by writing the
structure of products side by side & replacing the marked part by –CH3 as
shown here:
Example 9. What are the reactions which distinguish aldehydes from ketones?
Solution. The following reactions distinguish aldehydes and ketones (refer
Section 17.3 for details):
(1) Aldehydes reduce Tollens reagent and thus precipitate silver (silver mirror
test).
(2) Aldehydes reduce Fehiling’s solution and Benedict’s solution. Aldehydes
give a red precipitate on reaction with these reagents.
Ketones do not give reactions (1) and (2)
(3) Aldehydes, on oxidation, readily give carboxylic acids with the same
number of carbon atoms.
Ketones are very difficult to oxidize. Oxidation of ketones under drastic
conditions result in formation of carboxylic acids with lesser number of
carbon atoms.
(4) In general, the nucleophilic addition reactions occur at a faster rate with
aldehydes compared to ketones.
(5) Ketones do not form simple addition products with ammonia.
(6) Sterically hindered ketones do not undergo sodium bisulfite addition.
(7) Ketones do not show polymerization. Aldehydes may polymerize to give
different products.
Example 10. Identify the following name reactions and write the products
formed in each case:
Solution. (i) This is an example of Aldol reaction. The reaction occurs as
follows:
(ii) This is an example of crossed aldol condensation where one aldehyde has
no α-hydrogen and other is a ketone with α-hydrogen. The reaction is
known as the Claisen–Schmidt reaction.
2. Give the structures and IUPAC names of the isomeric carbonyl compounds
that have the molecular formula C5H10O.
3. Why do the carbonyl compounds have
(a) higher boiling points than alkanes of comparable molecular mass?
(b) lower boiling points compared to alcohols of comparable molecular
mass?
4. How will you prepare the following carbonyl compounds using suitable
Grignard reagents?
(a) Butanal
(b) Pentan-3-one
(c) Pentan-2-one
5. Name the carbonyl compounds obtained by the reductive ozonolysis of
(a) 3-Methylhex-1-ene
(b) 2,3-Dimetylbut-2-ene
(c) Penta-1,3-diene
6. Name the reagent used for the selective oxidation of alcohols to aldehydes.
7. Give the commercial method for the manufacture of formaldehyde and
acetaldehyde.
8. What is formalin?
9. Write the chemical equation and name the product(s) obtained by the
hydrolysis of
(a) But-1-yne
(b) 2,2-Dichlorobutane
(c) 1,1-Dichlorobutane
10. How can aldehydes and ketones be prepared by (a) hydroboration–oxidation
of alkynes and (b) pyrolysis of calcium salts of carboxylic acids?
11. Give the two ‘name reactions’ used for the preparation of aldehydes only.
12. Why dialkylcadmium is preferred over Grignard reagent for preparation of
ketones from acid chloride?
13. Using lithium dialkylcuprate (Gilman reagent), how will you prepare
acetone?
14. Arrange the following carbonyl compounds in the increasing order of their
reactivity towards nucleophilic addition reactions.
HCHO, CH3COCH3, CH3CHO, CH3CH2CHO, CH3CH2COCH3
15. Give the general mechanism for the nucleophilic addition reactions in
carbonyl compounds.
16. What are phosphorous ylides?
17. Giving suitable examples, explain Wittig reaction.
18. Using ethylmagnesium bromide, how will you prepare
(a) Propan-1-ol
(b) Butan-1-ol
(c) 2-Methylbutan-2-ol
(d) Pentan-3-ol
19. Complete the following reactions:
18.1 INTRODUCTION
Aromatic aldehydes and ketones belong to the class of oxygen containing
organic compounds where –CHO or –COR (where R may be alkyl or aryl) group
is directly attached to benzene ring system so they are termed as aromatic
carbonyl compounds. In the carbonyl group carbon and oxygen are sp2
hybridized and carbonyl carbon is bonded to benzene ring through sp2–sp2
overlap. The simplest aromatic aldehyde is benzaldehyde. An aromatic aldehyde
does not contain α-hydrogen. Aromatic ketones may contain alkyl or aryl group.
Di-aryl ketones do not contain α-hydrogen. The nomenclature of aromatic
carbonyl compounds has already been discussed in detail in Chapter 2.
Etard reaction
The oxidation of aromatic hydrocarbons to get better yields of aromatic
aldehydes makes use of chromyl chloride as an oxidizing agent and the reaction
is known as Etard reaction.
The reaction results in the formation of an intermediate, which on hydrolysis
gives quantitative yield of aldehyde.
The oxidation of –CH3 group of the aromatic hydrocarbon to aldehyde (–CHO)
group cannot be carried out easily, if oxidizable groups like –OH and –NH2 are
present on the ring system.
Oxidation of aromatic alcohols
Benzyl alcohol, on oxidation with acidified potassium dichromate results in the
formation of benzaldehyde. The oxidation of secondary aromatic alcohols under
similar conditions results in the formation of aromatic ketones.
Mechanism
The modified Gattermann aldehyde synthesis use Zn(CN)2 and and HCl which
makes the reaction easy to carry out.
Gattermann–Koch reaction versus Gattermann aldehyde
synthesis
(a) The Gattermann–Koch reaction does not occur in case of phenol,
phenolic ethers and nitrobenzene.
(b) The Gattermann aldehyde synthesis can be carried out in case of
phenols and phenolic ethers but not with nitrobenzene (or any
other deactivating group).
Reimer–Tiemann reaction
The reaction of phenol with chloroform in presence of sodium hydroxide results
in the formation of o- and p-hydroxybenzaldehydes and the reaction is known as
Reimer–Tieman reaction. This is an electrophilic substitution reaction and
proceeds via the formation of dichlorocarbene as electrophile. Salicylaldehyde
(o-hydroxybenzaldehyde) is the major product of Reimer–Tieman reaction
because of the stabilization that occurs through intramolecular hydrogen bonding
(p. 543).
Friedel–Crafts reaction
One of the most widely used reaction for the preparation of aromatic ketones is
the Friedel–Crafts reaction (Section 10.2.4). Benzene reacts with acetyl chloride
in the presence of AlCl3 (as catalyst) to form acetophenone. This reaction is
known as Friedel–Crafts acylation reaction. Use of benzoyl chloride instead of
acetyl chloride results in the formation of benzophenone.
One of the most economical and frequently used methods for the preparation of
benzophenone involves reaction of two molecules of benzene with
carbontetrachloride in the presence of AlCl3 catalyst.
Fries rearrangement
Phenolic esters, on heating with aluminium chloride, undergo rearrangement to
form phenolic ketones (p. 540).
Hoesch condensation
Reaction of polyhydric phenols with alkanenitriles in presence of HCl and
anhydrous ZnCl2 in ether as solvent results in the formation of ketones. For
example, reaction of 1,3,5-trihydroxybenzene (phloroglucinol) with
methanenitrile results in the formation of 2,4,6-trihydroxyacetophenone.
Sommelet reaction
Benzyl chloride on reaction with hexamethylenetetramine, using alcohol as
solvent followed by acid hydrolysis, results in the formation of benzaldehyde.
Hydrolysis of benzal chloride (gem dihalide)
Chlorination of toluene in the presence of sunlight results in the formation of
benzal chloride. The hydrolysis of benzal chloride in alkaline medium then
forms benzaldehyde.
Rosenmund reduction
Benzoyl chloride on catalytic reduction in the presence of Pd/BaSO4 results in
the formation of benzaldehyde.
Stephen reaction
The aromatic nitriles on reduction with stannous chloride in presence of HCl
produce aldimine complex. The main reducing species is tetrachlorostannic acid,
H2[SnCl4], which is formed by reaction of HCl and SnCl2. The hydrolysis of
aldimine complex results in the formation of aromatic aldehyde.
18.3 CHEMICAL PROPERTIES OF AROMATIC
ALDEHYDES AND KETONES
The aromatic carbonyl compounds undergo various types of chemical reactions
which include
(i) reaction involving carbonyl ( C=O) groups, namely the nucleophilic addition
reactions, oxidation reactions, and reduction reactions, (ii) reactions involving α-
carbon of carbonyl compounds, (iii) some typical reactions of aromatic
aldehydes, and (iv) electrophilic substitution reactions. The various reactions are
discussed as follows:
with acetophenone:
with benzophenone:
with benzophenone:
In aryl aldehydes, at times after the hydrolysis, elimination occurs and the
product is an α,β-unsaturated ester.
with acetophenone:
with benzophenone:
(ii) Addition of thiols. The reaction of carbonyl compound with thiols is much
faster compared to reaction with alcohol due to high nucleophilicity of sulfur
compared to oxygen. Acid catalyzed addition of thiols to carbonyl compounds
results in the formation of thioacetals. Thioacetals are used for the protection of
carbonyl group in multi-step organic synthesis. The reduction of thioacetals with
raney nickel results in the formation of hydrocarbons.
Beckmann rearrangement
The reaction of ketones with hydroxylamines results in the formation of
ketoximes. The ketoximes (R2C=NOH) in presence of acidic catalysts such as
PCl5 in ether, H2SO4, P2O5, BF3, SOCl2, SO3, and so on undergo
rearrangement to form N-substituted amides. This reaction is known as
Beckmann rearrangement. The reaction was first observed by Beckmann in case
of benzophenone oxime.
18.3.3 Oxidation
Aromatic aldehydes are less susceptible to oxidation compared to aliphatic
aldehydes. Aromatic aldehydes can reduce Tollens reagent to metallic silver salt
and give positive silver mirror test.
18.3.4 Reduction
The reduction of aromatic carbonyl compounds results in the formation of
different products depending upon the type of reducing agent used.
Catalytic reduction
The hydrogenation of aromatic carbonyl compounds in the presence of metal
catalyst results in the formation of alcohol.
Meerwein–Ponndorf–Verley reduction
Aromatic carbonyl compounds on treatment with a solution of aluminium
isopropoxide in isopropyl alcohol get reduced to alcohols.
This reagent does not reduce other groups, namely the double bond, triple bond,
and the nitro group present in compound. For example,
Clemmensen reduction
The carbonyl ( C=O) group of aromatic aldehydes and ketones can be reduced to
methylene ( CH2) group by zinc amalgam in a manner similar to aliphatic
carbonyl compounds. This reaction is used for reducing carbonyl compounds,
which are sensitive to alkali.
Wolff–Kishner reduction
The carbonyl group ( C=O) of aromatic aldehydes and ketones can be reduced to
methylene ( CH2) group by reaction with hydrazine followed by hydrolysis with
sodium or potassium ethoxide as in the case of aliphatic carbonyl compounds.
The method is used for the reduction of carbonyl compounds that are sensitive to
acids.
Reduction to pinacols
Aliphatic aldehydes do not form pinacols unlike aromatic aldehydes and ketones
that form pinacols (di-tert 1,2-diols) on reduction. The reducing agent used in
the process is zinc in acetic acid. Further in the presence of light and isopropanol
as a solvent, benzophenone yields benzopinacol. The reaction is termed as
photochemical reduction of benzophenone. The reaction with different aromatic
carbonyl compounds are as follows:
with benzaldehyde:
with acetophenone:
with benzophenone:
Step 2. Removal of hydride ion and its shift to second molecule of benzaldehyde
(with no
α-hydrogen)
Claisen–Schmidt reaction
The reaction of benzaldehyde with α-hydrogen containing ketone in presence of
a base results in the formation of a β-hydroxy ketone. This reaction is known as
Claisen–Schmidt reaction. The aromatic aldehydes cannot undergo Aldol
condensation due to lack of α-hydrogen. However, they participate in crossed
Aldol condensation reactions (p. 601), where one aldehyde does not contain α-
hydrogen (as in aromatic aldehydes) and the other is a α-hydrogen containing
ketone.
Generally, the dehydration of hydroxy compound takes place to form α, β-
unsaturated carbonyl compounds.
Mechanism. This is a base catalyzed reaction. The step wise Mechanism of the
reaction is as follows:
Step 1. Abstraction of α-hydrogen (formation of carbanion)
In alkaline medium, carbonyl compound containing α-hydrogen looses a proton
and forms an enolate ion (carbanion).
Benzoin condensation
Aromatic aldehydes, in the presence of cyanide ion condense to form α-hydroxy
ketones. In case of benzaldehyde, the condensation in the presence of cyanide
ion as a catalyst results in the formation of benzoin.
Mechanism
Step 1. Attack of nucleophile (cyanide ion) on the aromatic aldehyde
The –CN is a good nucleophile, which attacks the carbonyl carbon of the first
molecule of benzaldehyde. The –CN is a good electron withdrawing group and
increase the acidic character of C-H bond. This results in the removal of proton,
which is rapidly transferred to oxygen. The cyanide group helps in stabilization
of carbanion thus formed.
Mechanism
Step 1. Attack of nucleophile (base –OH) on carbonyl carbon
Mechanism
Step 1. Abstraction of α-hydrogen of acid anhydride by base (formation of
carbanion)
The anion of the acid acts as a base and removes α-hydrogen from the anhydride.
The aromatic aldehydes and ketones undergo usual halogenation, nitration, and
sulfonation reactions to produce corresponding m-halo, m-nitro, and m-
substituted sulfonic acid derivatives (for mechanism and detailed discussion,
refer Chapter 10).
Being electron withdrawing in nature, the aromatic aldehydes and ketones do not
undergo Friedel–Crafts reaction.
SELECTED SOLVED EXAMPLES
Example 1. Identify the following name reactions and write the product(s)
formed in each case:
5. Discuss two name reactions, which are used for the preparation of aromatic
aldehydes only.
6. Arrange the following carbonyl compounds in increasing order of their
reactivity towards nucleophilic addition reactions.
11. Why do aromatic ketones not form addition product with sodium bisulfite?
12. Complete the following reactions:
13. Give the reduction product of following carbonyl compounds in the
presence of indicated reducing agents:
14. Complete the following by substituting appropriate reagent needed for the
reactions to take place.
15. Identify the name reactions and the final products formed in the following
reactions:
16. How will you distinguish between the following carbonyl compounds:
19.1 INTRODUCTION
Aliphatic carboxylic acids belong to the class of oxygen containing organic
compounds having a caboxyl group. In a carboxyl functional group, a hydroxy
group is attached to carbonyl group. The general formula of carboxylic acids is
CnH2n+1COOH. In general, many of the compounds with this general formula
are obtained by hydrolysis of fats and for this reason carboxylic acids are also
termed as fatty acids. The carboxylic acids have a planar structure due to planar
carbonyl group.
The carboxylic acids in IUPAC system are termed as alkanoic acids (refer
Chapter 2). The common and much familiar names are derived from the source
of these acids and are widely accepted. A few examples of IUPAC name for
carboxylic acids are given in Table 19.1.
Physical properties. The carboxylic acids exhibit high polarity because of the
presence of carbonyl (–CO–) and hydroxy (–OH) group, and are thus able to
form hydrogen bonds with other polar molecules.
The carboxylic acids generally exist in dimeric form where the hydroxy group of
one carboxylic acid molecule is hydrogen bonded to carbonyl oxygen of the
second molecule of carboxylic acid. In a similar manner, the hydroxy group of
second molecule is hydrogen bonded to carbonyl oxygen of the first molecule.
Thus, carboxylic acid molecules are held together strongly through
intermolecular hydrogen bonding in solid, liquid, and in some cases even
gaseous phase. Due to this reason, carboxylic acids have high melting and
boiling points compared to hydrocarbons and alcohols of comparable mass.
Branching in the alkyl chain of carboxylic acids decreases the boiling point.
Boiling points (°C) of a few monocarboxylic acids are given in Table 19.1.
In a similar manner, carboxylic acid molecules can form hydrogen bonding with
alcohol and water. The lower members of carboxylic acids (C4 and below) are
thus, soluble in water. This is depicted in the following structure.
19.2 PREPARATION OF ALIPHATIC
CARBOXYLIC ACIDS
This section discusses various methods used for preparation of monocarboxylic
acids. Some of the methods have already been discussed in details in other
chapters and for such reactions only the section numbers are given for reference.
The following oxidation methods for preparation of carboxylic acids have been
discussed in details in previous chapters and their references are as follows:
• Oxidation of alkanes (Section 5A.3.5)
• Oxidative cleavage of alkenes with hot KMnO4 (Section 6.3.4)
• Oxidation of monohydric alcohols (Section 13.3.4)
• Oxidation of aldehydes and ketones (Section 17.3.3)
19.2.2 Hydrolysis
Alkaline hydrolysis of trihaloalkanes
Trihaloalkanes on treatment with alkali solution (aq NaOH or KOH) undergo
nucleophilic substitution to form gem. triols which readily undergo elimination
of water molecule to form carboxylic acids. For example,
Hydrolysis of alkanenitriles
The hydrolysis of alkanenitriles in hot acidic or alkaline medium results in the
formation of carboxylic acid with liberation of ammonia. This is one of the
convenient and preferred methods for the introduction of carboxylic functional
group. For example,
Hydrolysis of esters
The hydrolysis of esters results in the formation of alcohols and carboxylic
acids. The hydrolysis may be carried out in acidic or alkaline medium. The
hydrolysis in alkaline medium is termed as saponification reaction. This has been
shown as follows:
In both the cases, carboxylic acid produced contains one carbon more than the
alkyl group present in organometallic compounds.
Mechanism
Step 1. Formation of carbocation
In presence of an acid, the alkene undergoes protonation to yield a stable
carbocation.
Step 2. Attack of carbon monoxide on carbocation
Step 3. Addition of water to electrophilic carbon
All these steps are shown in the following reaction sequence:
Industrial methods for preparation of formic acid and acetic acid by
carbonylation reactions
Heating carbon monoxide with sodium hydroxide under pressure results in the
formation of sodium formate, which on hydrolysis yields formic acid.
Haloform reactions
The reader may refer to Section 17.3.5; p. 606 for a detailed discussion on
haloform reactions, as this reaction involves the formation of carboxylic acids
along with haloform (CHX3).
19.3 CHEMICAL PROPERTIES OF ALIPHATIC
CARBOXYLIC ACIDS
The carboxylic acids show acidic as well as basic properties. The important
reactions of carboxylic acids involve the reactions due to carboxylic group,
hydroxy group, carbonyl group, and the alkyl part of the carboxylic acid
depicted as follows:
Due to delocalization in carboxylate ion, both the C–O bond lengths are same.
However in carboxylic acids, these two C–O bond lengths are different.
Effect of substituents on acidic strength
The presence of electron withdrawing group increases the acidic strength of
carboxylic acids. This effect is more pronounced if electron withdrawing group
is present on α-carbon which is close to carboxylic group. The electron
withdrawing group/atom (–I effect) delocalizes the negative charge thereby
stabilizing the carboxylate ion. For example, chloroacetic acid is more acidic
than acetic acid.
It should be noted that the electron withdrawing nature of halogens (–I effect)
decreases due to decrease in electronegativity and follows the order F > Cl > Br
> I. Thus, in α-haloacetic acids the decreasing order of acidic strength is as
follows:
The presence of electron releasing groups (+I effect) decreases the acidic
strength. This happens as these groups increase or intensify the negative charge
thereby destabilizing the carboxylate ion. As a result, acetic acid is more acidic
than propanoic acid. Similarly, more alkyl groups attached to acetic acid, further
decrease the acid strength. Thus, for alkylated acetic acids the decreasing order
of acidic character is as follows:
19.3.2 Reactions Involving Acidic Hydrogen
Reaction with bases
The carboxylic acids show considerable acidic character and form salts even
with mild alkalis. For example,
The reaction of carboxylic acids with sodium bicarbonate is
used as a qualitative test for detection of carboxylic functional group
in an organic compund. Carboxylic acids on reaction with aqueous
sodium bicarbonate solution produce brisk effervescence. The sodium
salts of carboxylic acids are highly soluble in water.
Also the acids react with metals to form metallic salts with the liberation of
hydrogen.
Machanism
(ii) By dehydration of carboxylic acids. The acid anhydrides are also prepared
by heating carboxylic acid at high temperature in the presence of dehydrating
agents such as phosphorous pentoxide or sodium ammonium hydrogen
phosphate. For example,
Reaction with alcohols: formation of esters
The reaction of carboxylic acid with alcohols in acidic medium results in the
formation of an ester and this is known as Fischer’s esterification. For example
During ester formation, the elimination of water occurs where the removal of –
OH occurs from carboxylic acid and the removal of H occurs from alcohol.
Mechanism
Step 1. Addition of ammonia (or amine) to carbonyl carbon. Ammonia (or
amines) act as a nucleophile and attacks the carbonyl carbon.
Step 2. Proton transfer. The loss of proton occurs from nitrogen and this proton
is transferred to oxygen of hydroxyl group.
Step 3. Elimination of water (formation of amide)
Examples
(b) Formic acid, on mild heating with sulfuric acid forms carbon monoxide
and water.
While at a higher temperature (160°C), it results in the formation of carbon
dioxide and hydrogen.
(c) Oxidation: Formic acid due to its structure, gets oxidized with even mild
oxidizing agents and acts as a strong reducing agent.
Formic acid reduces Tollens reagent, Fehling’s solution, and
potassium permanganate. Thus, it is the only monocarboxylic acid,
which gives positive silver mirror test (Tollens test) and a reddish
brown precipitate with Fehling’s solution. Therefore, these reactions
are used for distinguishing formic acid from other carboxylic acids.
with Tollens reagent
These groups are collectively known as acid derivatives. All these derivatives on
hydrolysis result in the formation of carboxylic acid. In view of this, the nitriles
(–C≡N) are also sometimes considered as derivatives of carboxylic acids.
Nitriles and isonitrites are discussed separately in Chapter 22.
Table 19.2 enlists the IUPAC names, general formulae and common names (in
parentheses) of some carboxylic acids and their corresponding derivatives.
19.4.1 Acid Halides
Acid chlorides are the most common and widely studied acid halides, being
convenient to prepare as compared to acid bromides and acid iodides. This
section therefore focusses on the reactions and properties of acid chlorides only.
Acid chlorides are liquid and have lower boiling point compared to
corresponding carboxylic acids. This decrease in the boiling point is due to the
replacement of –OH of carboxylic acids by –Cl in acid chlorides causing the loss
of hydrogen bonding.
The acid chlorides react rapidly with water (hydrolyzed) to
produce carboxylic acid and hydrochloric acid. This rapid reaction of
acid
chlorides with water makes them Lachrymatory, that is, producing
tears in the
eyes as these react with moisture in eyes to form hydrochloric acid,
which acts as an irritant.
Preparation
(i) Ketene is prepared by the dehydration of carboxylic acid at a high
temperature in the presence of triethylphosphate.
(ii) Ketene is also prepared by the pyrolysis of acetone at a high temperature
in the presence of catalysts.
(iii) The substituted ketene, say, diphenylketene can easily be prepared by the
reaction of substituted acid chloride with organic base
(dehydrohalogenation).
Except methanamide, other unsubstituted amides are all solids. These are
colourless, crystalline compounds and have higher melting points in comparison
to parent carboxylic acids. The high melting point of amides is attributed to the
fact that amide molecules are highly associated through intermolecular hydrogen
bonding.
In case of N-substituted amides, the boiling and melting points decrease as the
sites for hydrogen bonding diminish with increasing number of alkyl
substituents. Amides are less basic compared to aliphatic amines. They exhibit
resonance where the lone pair on nitrogen participates in delocalization with
oxygen of carbonyl group. This reduces the availability of electrons on nitrogen
thereby decreasing the basicity.
The introduction of double bond character between carbon and nitrogen reduces
the C–N bond length to less than the usual C–N single bond. Amides due to
resonance, show a planar geometry with restricted rotation around the C–N
bond. In nature, amide linkages are found in proteins.
Amides are least reactive of all acid derivatives because of delocalization which
reduces the electrophilicity of carbon (of CONH2). The electron releasing –OR
group in esters decreases the electrophilicity of carbon (of –COOR). In acid
chlorides the highly electronegative chlorine increases the electrophilicity of
carbon (of COCl) thereby making them the most reactive.
Based on electronic factors, the order of reactivity of acid derivatives towards
nucleophilic reaction is as follows:
The reactions of amides are generally slow and require prolonged heating or
catalysts (acid or base) for them to take place. A few reactions of amides are
19.4.6 Urea—A Derivative of Carbonic Acid
Urea is a diamide of carbonic acid.
Urea is a stronger base than amides. In urea, the two –NH2 groups are present
that form the amide linkage. In acid amides, the lone pair on nitrogen
participates in delocalization with carbonyl group. However in urea, at a time
only one of the lone pair on nitrogen participates in delocalization while the lone
pair on other nitrogen is free to interact with other species. Thus, the basicity of
urea is high as compared to acid amides.
Urea is widely used as a fertilizer and is also used in the manufacture of polymer
resin, for example, urea formaldehyde.
The reactions of urea can be classified in two categories, namely general
reactions and those leading to the formation of heterocyclic compounds.
(a) General reactions
NOTABILIA 13
SELECTED SOLVED EXAMPLES
Example 1. Write the chemical reactions and products formed, when
calciumbutanoate is
(i) heated alone
(ii) heated after the addition of conc. sulfuric acid
(iii) heated along with calcium formate.
Solution.
(i) Heating calcium salt of carboxylic acid results in the formation of ketone in
the following manner.
2. Why boiling points of carboxylic acids are much higher than alcohols of
comparable mass?
3. Why do
(a) Acid chlorides have lower boiling points compared to the corresponding
carboxylic acids?
(b) Acid amides have high melting points compared to parent carboxylic
acids?
(c) Acid anhydrides have high boiling point compared to parent carboxylic
acids?
4. Give Wacker’s process for synthesis of acetic acid.
5. Name the carboxylic acids formed by the hydrolysis of:
(a) 1,1,1-Trichlorobutane in alkaline medium
(b) Acetonitrile in acidic medium
(c) Ethyl propanoate in alkaline medium
6. Complete the following reactions:
7. Give the industrial method of the preparation of formic and acetic acid by the
carbonylation reaction.
8. In carboxylic acids, there are two different C–O bond lengths, however the
carboxylate ion has the same C–O bond lengths, explain.
9. How will you prepare methyl ester of ethanoic acid without using alcohol as a
reagent?
10. Give the mechanism for the alkaline hydrolysis of an ester.
11. Give the mechanism for the acid catalyzed nucleophilic acyl substitution in
carboxylic acids.
12. Why do acid amides show less basicity compared to amines?
13. Why does the presence of base catalyze the nucleophilic acyl substitution in
carboxylic acids?
14. Giving example, explain the synthesis of mixed anhydrides.
15. Give the mechanism for acid catalyzed esterification process.
16. Explain with mechanism Hell–Volhard–Zelinsky reaction in carboxylic
acids.
17. Why are acid chlorides more reactive towards nucleophilic substitution
reactions compared to alkyl chloride?
18. Why does formic acid give a positive Tollens test (Silver mirror test)?
19. How do you explain the lachrymatory nature of acid chlorides?
20. Why is C–N bond length in amide shorter than C–N bond in amines?
21. Complete the following reactions:
22. What is trans-esterification?
23. Giving suitable explanation, arrange the acid derivatives (acid chlorides,
esters, acid anhydrides, and amides) in increasing order of reactivity towards
nucleophilic substitution reaction.
24. Why is urea a stronger base compared to acid amides?
25. Carry out the following conversions:
(a) Urea to Semicarbazide
(b) Ketene to Methanamine
(c) Urea to Thymine
(d) Ethyl acetate to tert. Butyl alcohol
(e) Propanoic acid to Propanenitrile
(f) Urea to Barbituric acid.
Chapter20
Bifunctional
Carboxylic Acids and
Their Derivatives
INTRODUCTION
The organic compounds in general may contain more than one functional group,
which may not be same. The compounds with two functional groups exhibit the
characteristics of each functional group and at same time undergo some typical
reactions that depict a characteristic influence of one functional group over
another. The section A of present chapter deals with the chemistry of
Dicarboxylic and substituted carboxylic acid. The section B is devoted to
chemistry of reactive methylene compounds. This chapter gives an in-depth
analysis of the bifunctional carboxylic acids and their derivatives as tabulated in
Information Chart I.
A. DICARBOXYLIC ACIDS AND
SUBSTITUTED CARBOXYLIC ACIDS
20A.1 DICARBOXYLIC ACIDS [SATURATED AND
UNSATURATED]
The aliphatic dicarboxylic acids are named in IUPAC as alkanedioic acids. Most
of the dicarboxylic acids are better known by their common names. The
unsaturated dicarboxylic acids exhibit geometrical isomerism and named as E-
or Z-alkenedioic acids.
The most important reaction is the action of heat where different products may
be obtained depending upon the structure of dicarboxylic acid.
Action of heat on dicarboxylic acids
The dicarboxylic acids on heating may undergo one of the two important
reactions, namely
(i) decarboxylation and (ii) dehydration.
(i) Decarboxylation. Oxalic acid (ethanedioic acid), malonic acid, and other
dicarboxylic acids where two carboxylic groups are present on same carbon, on
heating, undergo removal of carbon dioxide to produce monocarboxylic acids.
The mechanism of decarboxylation is as follows:
(ii) Dehydration. Dicarboxylic acids where two carboxylic groups are separated
by two or three carbon atoms, on heating, undergo elimination of water molecule
to form acid anhydrides. For example,
(iii) Simultaneous decarboxylation and dehydration. Dicarboxylic acids
where two carboxylic groups are separated by four or five carbon atoms undergo
simultaneous removal of carbon dioxide and water to form cyclic ketones. This
is depicted in the following reactions:
Oxidation reactions
The oxidation of oxalic acid with KMnO4 or K2Cr2O7 results in the formation
of carbon dioxide and water.
Maleic and fumaric acid on reaction with alkaline KMnO4 or OsO4 forms
tartaric acid. Maleic acid gives the meso tartaric acid while fumaric acid gives a
racemic mixture of tartaric acid.
The hydroxy acids on heating may undergo following reactions, namely (i)
intermolecular esterification, (ii) intramolecular esterification, and (iii)
dehydration.
α-Hydroxycarboxylic acids. Two molecules of an α-hydroxy acid, on heating,
undergo intermolecular esterification and result in the formation of cyclic
diesters known as lactides.
B. REACTIVE METHYLENE
COMPUNDS
[Chemistry of Enolate ions]
20B.1 INTRODUCTION
The hydrogens in methane practically do not exhibit acidic character. However
when two of the hydrogens are replaced by electron withdrawing groups, the rest
of the hydrogens become acidic in nature. The electron withdrawing groups
present on both sides attract the electrons towards themselves and thus, weaken
the C–H bond of methylene ( CH2) group. It results in the easy release of
hydrogen as a proton (H+). Thus a methylene group, which is sandwiched
between two electron withdrawing groups, exhibits acidic character and is
known as reactive methylene group.
It is to be noted that in ethyl acetoacetate the ester group does not participate in
enolization as it results in the decrease of the resonance energy of the system. On
these grounds, it is quite clear that the percentage of enol form will be lower in
case of ethyl acetoacetate and diethyl malonate compared to acetyl acetone. The
order of the percentage of enol form in reactive methylene compounds is as
follows:
Further the polar solvents increase the keto content whereas the non-polar
solvents increase the enol content.
Acidic character of reactive methylene compounds. In reactive methylene
compounds, the presence of electron withdrawing groups facilitates the removal
of proton from methylene group. In presence of a base, the loss of proton from a
reactive methylene compound results in the formation of a carbanion. The
resonance stabilization of this carbanion accounts for the high acidic strength of
reactive methylene compounds.
The chemistry of enolate ions is of immense importance as these can be used for
the synthesis of a number of organic functional groups. Here we will be
discussing the chemistry of two important reactive methylene compounds,
namely ethyl acetoacetate and diethyl malonate.
20B.2 ETHYL ACETOACETATE
(IUPAC name: Ethyl 3-oxobutanoate); [CH3COCH2COOC2H5]
Ethyl acetoacetate (commonly referred as acetoacetic ester) is a colourless liquid
(b.p. 181°C) with pleasant smell and is sparingly soluble in water. Although it is
neutral to litmus, it is soluble in sodium hydroxide solution. It partially
decomposes on strong heating and is therefore distilled much below its boiling
point under reduced pressure.
20B.2.1 Preparation
Two molecules of α-hydrogen containing esters condense in presence of a base
to form β-keto esters and this reaction is known as Claisen condensation. The
Claisen condensation of ethyl acetate in the presence of sodium ethoxide results
in the formation of ethyl acetoacetate (acetoacetic ester).
(ii) Higher dicarboxylic acids. Higher dicarboxylic acids such as glutaric acid,
adipic acid, pimelic acid, and the like, are prepared by reaction of two molecules
of the sodium salt of ethyl acetoacetate with dihaloalkanes (having halogen at
the terminal carbons) followed by acid hydrolysis. This is shown in the
following reaction:
(c) Synthesis of keto acids. The reaction of sodium salt of ethyl acetoacetate
with α-haloesters followed by ketonic hydrolysis results in the formation of keto
acids as the final product.
20B.3.1 Preparation
Diethyl malonate (malonic ester) is prepared by heating a solution of potassium
cyanoacetate in ethanol with concentrated hydrochloric acid.
(ii) Higher dicarboxylic acids. Higher dicarboxylic acids such as glutaric acid,
adipic acid,
pimelic acid, and so on are prepared by reaction of two molecules of the sodium
salt of malonic ester with dihaloalkanes (having halogen at the terminal carbons)
followed by hydrolysis and decarboxylation.
(c) Synthesis of keto acids. The reaction of sodium salt of malonic ester with
acid chloride followed by hydrolysis and decarboxylation results in the
formation of keto acids as the final product.
The oxidation cannot be carried out if groups like –OH and NH2 are present on
aromatic ring as they are highly susceptible to oxidation.
2. Oxidation of primary aromatic alcohol. The oxidation of benzyl alcohol
with acidified sodium dichromate or potassium permanganate results in the
formation of benzoic acid.
Hydrolysis reactions
1. Hydrolysis of trihaloalkyl benzenes. The chlorination of toluene in the
presence of ultraviolet light results in the formation of trichloromethyl benzene.
The alkaline hydrolysis of this product gives benzoic acid.
The hydrolysis can occur in both acidic or alkaline media (the mechanism has
already been discussed in Section 19.2.2; p. 658 with aliphatic carboxylic acids).
Other methods
1. Carboxylation of organometallic compounds. In organometallic compounds
such as Grignard reagent and phenyllithium, the aryl group behaves as a
nucleophile, which adds carbon dioxide (a weak nucleophile) to form
carboxylate salts. The acidic hydrolysis of addition product results in the
formation of aromatic carboxylic acids.
2. Haloform reaction of acetophenone. The acetophenone is an aryl methyl
ketone, which reacts with halogen in the presence of sodium hydroxide to form
haloform and sodium benzoate.
The high acidic strength of p-nitrobenzoic acid is due to both –I and –R effects
of nitro group.
The formation of acid derivatives, namely acid chlorides, acid anhydrides, esters,
and amides are the examples of nucleophilic substitution reactions occurring
through addition–elimination mechanism. The mechanism for all these reactions
is similar to that discussed in the aliphatic carboxylic acids (Section 19.3.3).
Preparation of aromatic carboxylic acid derivatives
(i) Acid chlorides. Reaction of carboxylic acid with thionyl chloride is one of
the best methods for preparation of acid chlorides.
(ii) Acid anhydride. Heating aromatic carboxylic acid and acid chloride
together results in the formation of acid anhydride and this method is used
widely for the synthesis of anhydrides.
(iii) Esters. The reaction of aromatic carboxylic acids with alcohol in acidic
medium results in the formation of esters.
(iv) Amides. Aromatic carboxylic acids react with ammonia or amine to form
amides through an addition–elimination mechanism. The ammonia (or amine)
behaves as a nucleophile in the reaction.
These reactions that lead to the formation of aromatic carboxylic acid derivatives
are summarized as follows using benzoic acid as one of the reactants.
21A.3.3 Reduction Reaction
The reduction of carboxylic acids is carried out in the presence of strong
reducing agents like lithium aluminium hydride. The reaction involves the
hydride transfer and reduces the carboxylic acid to alcohol.
(ii) Hunsdiecker reaction. Silver salt of benzoic acid is heated with bromine to
yield bromobenzene with the evolution of carbon dioxide.
Thus, the carboxylic acid group behaves as a ring deactivator and meta director
towards electrophilic substitution reactions such as halogenation and nitration.
Aromatic carboxylic acids do not undergo Friedel–Crafts reaction. [Note:
Friedel–Crafts reaction does not occur in presence of electron withdrawing
groups]
(iii) Nitration of [I] will give two mononitro derivatives (at positions indicated
by arrows). Similarly, compounds [II] will also produce two mononitro
derivatives. A single mononitro derivative will be formed in case of p-
isomer. Thus, the structure of [A] is:
Fatty acids obtained from the triglycerides of plant or animal origin (few are
listed in Table 2) have some common characteristics that can be summarized as
follows:
(1) Most fatty acids in nature are unbranched and have even number of carbon
atoms (although exceptions are known).
(2) If unsaturation, is present in fats, all the double bonds are cis- (or Z) in
nature and are never conjugated.
(3) Saturated fatty acids have high melting points and fully extended carbon
chain.
(4) Unsaturated fatty acids have low melting points and have rigid bent
structure due to presence of double bond.
Dissimilarities between fats and oils
(i) Oils contain a much higher percentage of unsaturated fatty acids in
triglycerides whereas fats contain high percentage of saturated acids.
(ii) Fats are solid at room temperature (~20°C) and are called “oils” if they are
liquid at the same temperature.
(2) Waxes
Waxes are esters of long chain linear fatty acids and long chain linear alcohols.
In nature, waxes are present as protective coating on leaves , feathers of birds,
and animal fur. The fatty acids and alcohols present in waxes are:
Soaps
When a oil or fat is heated with alkali, the triglyceride is converted to glycerol
and salts of fatty acids. The salts (usually sodium salts) of long-chain fatty acids
are referred to as soaps.
Detergents
Synthetic detergents (sometimes called syndets) today dominate the market and
have taken over ordinary soaps. The development of syndets was a response to
two problems associated with the use of ordinary soaps. First being salts of weak
acids, soaps give rather alkaline solutions in water, due to partial hydrolysis and
alkalis can be harmful to certain fabrics. The ordinary soap cannot function well
at low pH (that is in acid) because the long chain fatty acids precipitate in the
solution. The second disadvantage of soaps is that they form insoluble salts with
calcium, magnesium, or ferric ions that may be present in hard water.
The first detergents to be introduced were sodium salts of alkyl hydrogen
sulfonates, such as lauryl hydrogen sulfate.
Lauryl hydrogen sulfate is an excellent detergent. Being salt of a strong acid, its
solutions are nearly neutral. Its calcium, magnesium and iron salts are water-
soluble. With similar properties, the detergents are effective in hard water also
and their cleaning action is not affected. At present, the most widely used
detergents are straight chain alkylbenzenesulfonates.
It is important that in detergents, the alkyl chain should be linear as these are
biodegradable. The chains can be degraded by microorganisms and do not
accumulate in the environment.
The detergents which have branched alkyl chains are non-biodegradable and
cause environmental contamination. Especially, such detergents are a threat to
aquatic species and pollute the water of ponds and rivers to the extent that it
becomes non-usable.
Washing Action of Soap and Detergents
The cleansing action of soaps and detergents is due to an important property of
being an emulsifying agent. The fabric with dirt/oil is dipped in a solution of
soap or detergent. The oil, dirt, or stains are insoluble in water. The nonpolar end
of soap and detergent molecule surrounds the oil (dirt) while the polar end,
which is hydrophilic remains suspended in water. The aggregates of a number of
such molecules with their non-polar segments (lypophilic) surrounding the oil or
dirt and polar part suspended in water are known as micelles. The micelles so
formed dissolve the dirt, which is washed away when fabric is rinsed thoroughly
with water.
Chapter22
Aliphatic Nitrogen
Containing Compounds
[Amines, Nitro, Nitriles, Isonitriles,
Isocyanates and Thiocyanates]
A. AMINES [ALKANAMINES)
22A.1 INTRODUCTION
Nitrogen is one of the essential components of our living system as well as of
our atmosphere. The nitrogen containing organic compounds are of immense
importance. Amines may be considered as organic derivatives of ammonia
where alkyl groups replace the hydrogen atoms of ammonia. Depending upon
the number of alkyl groups directly attached to nitrogen, the amines may be
classified as 1°, 2°, or 3° amines. In addition to this, tetra-substituted nitrogen
derivatives are also known and are termed as quaternary ammonium salts. The
general formulae for these types of amines are:
The boiling points of primary, secondary, and tertiary amines of the same
molecular mass follow the order 1° > 2° > 3°. The primary and secondary
amines form intermolecular hydrogen bonding through their hydrogens while
there is no hydrogen bonding in tertiary amines since hydrogen is absent. More
the number of hydrogens directly attached to nitrogen, stronger is the hydrogen
bonding. Thus, primary amines show strong hydrogen bonding relative to
secondary amines and thus, have higher boiling point compared to 2° and 3°
amines.
The low molecular mass amines are soluble in water due to the formation of
intermolecular hydrogen bonding with water molecules as shown below.
22A.2 PREPARATION OF ALKANAMINES
Amines can be prepared by a number of methods. The discussion on the various
preparatory methods can be classified under two heads, namely (1) reactions,
which yield mixture of 1°, 2° and 3° amines and (2) reactions specific to the
individual preparation of 1°, 2°, and 3° amines.
If ammonia is used in excess, one gets primary amine as the major product.
However, excess of haloalkane results in the formation of 3° amine as the major
product.
(b) Reaction of alcohol with ammonia. The reaction of 1° alcohol with
ammonia in presence of Al2O3 or ThO2 at 360°C results in the formation of a
mixture of 1°, 2°, and 3° amines.
The mixture of amines formed by these two reactions is separated into different
amines by two important methods namely Hofmann’s method and Hinsberg
method.
Separation of mixture of 1°, 2°, and 3° amines
Hofmann’s method
The mixture of amines is treated with diethyl oxalate and the following results
are obtained
(i) The 1° amine reacts with diethyl oxalate to form oxamide (a solid
compound)
(ii) The 2° amine reacts with diethyl oxalate to form oxamic ester (a liquid
compound).
(iii) While 3° amine does not react with diethyl oxalate.
The mixture is then distilled, the solid residue is oxamide (from 1° amine) while
the distillate gives two fractions; the low boiling fraction which separates out is
pure 3° amine (because it does not react) while the high boiling fraction contains
oxamic ester (from 2° amine).
The 1° and 2° amines are then recovered from the separated derivatives by
hydrolyzing them with potassium hydroxide solution. The hydrolysis of oxamide
gives 1° amine while hydrolysis of oxamic ester gives 2° amine.
The following flowchart gives an overview of the Hofmann’s method which is
used for the separation of amines.
Extracting the mixture with ether, using a separating funnel, is then used to carry
out the separation. The upper ether layer contains insoluble sulfonamide (from
2° amine) and the unreacted 3° amine. The lower aqueous layer contains water-
soluble sulfonamide salt from 1° amine. The lower layer is separated and ether
layer is distilled. The residue of distillation contains insoluble sulfonamide from
2° amine and the distillate contains 3° amine.
Recovery of 1°and 2° amines. The recovery of primary and secondary amines
is carried out by treating the soluble sulfonamide salt (having 1° amine) with
HCl, followed by treatment with alkali, which releases pure 1° amine. Similarly,
acidification of insoluble sulfonamide followed by treatment with alkali gives 2°
amine.
The overall separation process is illustrated with the following flowchart:
(iii) Acid amides on reduction with LiAlH4 form amine. This is one of the
widely used methods for the synthesis of amines since good yields are
obtained with this method without any side products. For example,
(iv) Oximes are formed by reaction of carbonyl compounds with
hydroxylamine. These oximes on reduction with LiAlH4 or Na/C2H5OH or
NaBH4 or H2/catalyst, result in the formation of amines.
Mechanism. The mechanism involves a 1,2-migration of the alkyl group and the
reaction therefore is a rearrangement reaction, which proceeds through an
isocyanate intermediate. The reaction at times is referred as Hofmann
rearrangement. For example the mechanism of Hofmann degradation in case of
propanamide is as follows:
Step 1. Reaction with bromine (formation of N-bromoamide)
Now, we describe some reactions namely Curtius, Lossen, and Schmidt reactions
which are related to Hofmann reaction in the sense that all these proceed through
formation of isocyanate intermediate.
(4) Lossen rearrangement. The hydroxamic acid on heating in the an inert
solvent in the presence of acetic anhydride undergoes loss of water to form an
acetyl derivative that rearranges, through migration of alkyl group, to form
alkylisocyanate. The hydrolysis of isocyanate results in the formation of 1°
amine.
(5) Curtius reaction. Curtius reaction involves the pyrolysis of acid azide to
form isocyanate which produces 1°amine on hydrolysis. The formation of
isocyanate involves migration of alkyl group.
(6) Schmidt reaction. The reaction of carboxylic acid with hydrazoic acid
(HN3) in the presence of an acid catalyst (H2SO4) results in the formation of 1°
amine through an isocyanate intermediate. The formation of isocyanate involves
migration of alkyl group.
Mechanism
(iii) The reaction of aldehydes or ketones with primary amines result in the
formation of Schiffs bases which on reduction form secondary amines.
(2) Hydrolysis of substituted cyanamides. One of the useful and convenient
method for preparation of pure 2° amines involves the reaction of calcium
cyanamide (CaNCN) with haloalkane to form disubstituted cyanamide. This
disubstituted cyanamide on hydrolysis followed by decarboxylation yields 2°
amine.
(3) From aniline. The reaction of aniline with haloalkane results in formation of
N-N-disubstituted aniline. Treating N-substituted aniline with nitrous acid
followed by hydrolysis results in the formation of 2°amine.
TERTIARY AMINES
(1) Reduction
(i) The reduction of dialkyl substituted amides with LiAlH4 results in the
formation of 3°amines in the following manner:
In other words, the presence of three alkyl groups (+I effect) in 3° amines
increases the electron density on nitrogen but the crowding due to the presence
of three bulkier alkyl groups hinders the ability of nitrogen to make these
electrons available to other species (like solvent molecules). Thus, the steric
hindrance in 3° amines makes them less basic compared to 2° amines. Thus, in
aqueous solution the order of basicity is (CH3)2NH > CH3NH2 > (CH3)3N.
The basicity of 2° and 3° amines can also be explained through solvation effect.
In aqueous solution, the amines form the ammonium ions. The basicity is
directly related to the stability of ammonium ions (conjugate acid). The
ammonium ions undergo solvation (association with water molecules). Higher
the solvation of ammonium ion, higher is the basicity of amine. In a 3° amine
because of the steric crowding and the availibilty of only one N–H bond (R3N+–
H), the solvation is less compared to that in a 2° amine.
However, in the absence of solvation effect (in non-aqueous medium), that is, in
gaseous phase the order of basicity is (CH3)3N > (CH3)2 NH > CH3NH2.
The basicity of amines is more compared to water.
The mineral acids react with amines and convert them to their respective
ammonium salts.
The amines can be recovered from their salts by treatment with strong alkali
such as hydroxide ion. The hydrochloride salts of amines on heating eliminate
chloroalkane to give the following products:
22A.3.2 Reactions of Amines
(1) Alkylation of amines. The amines react with haloalkanes to form substituted
amines.
(2) Reaction with acid chlorides (formation of amides). The reaction of acid
chlorides (aliphatic or aromatic) or sulfonyl chlorides with 1° and 2° amines
results in the formation of N-substituted and N,N-disubstituted amides. This is a
nucleophilic substitution reaction where amines behave as nucleophiles and react
at carbonyl carbon of acid chlorides. The 3° amines do not react with acid
chlorides.
The reaction of amines with benzoyl chloride in the presence of sodium
hydroxide solution is referred to as Schotten-Baumann reaction. Besides acid
chloride, the amide formation takes place with acid anhydrides also.
(3) Reaction with nitrous acid. Primary and secondary aliphatic amines react
with nitrous acid to give different products whereas 3° amines do not react with
it. The nitrous acid is produced in situ by reaction of sodium nitrite and
hydrochloric acid. The reactive species in this case is nitrosonium ion
(electrophile), which attacks the nucleophilic nitrogen of amines and replaces
proton (H+).
The reaction of 1° amines with nitrous acid yields unstable diazoniumion ion,
which decomposes with expulsion of nitrogen to give alcohol as the main
product along with traces of alkene.
The isothiocyanates are used for the preparations of thiourea derivatives. This
occurs in the following manner:
Secondary amines react with carbon disulfide to produce N-substituted
dithiocarbamic acid but do not form isothiocyanate with HgCl2. It should be
noted that tertiary amines do not react with CS2.
Mechanism
Step 1. Formation of electrophile
In alkaline medium, chloroform eliminates an HCl molecule to form
dichlorocarbene, an electron deficient species.
Depending upon the number of hydrogen atoms present on the carbon to which
nitro group is attached, these are classified as 1°, 2°, or 3° nitro compounds. In
IUPAC nomenclature, they are named as nitroalkanes (refer Chapter 2 also). A
few examples are
Physical properties. As evident from their structure, the nitro compounds are
polar in nature and exhibit high dipole moment. Due to dipole-dipole
interactions, nitroalkanes have high boiling points. Most of the nitroalkanes are
colourless liquids, have pleasant smell, and are sparingly soluble in water.
The primary and secondary nitroalkanes exhibit tautomerism (nitro and aci
forms) as illustrated with the following examples.
22B.2 PREPARATION OF NITROALKANES
Substitution reactions
(1) Nitration of alkanes. Alkanes react with concentrated nitric acid and result
in the formation of nitroalkanes. The reaction occurs in vapour phase at high
temperature and follows free radical substitution mechanism. All possible
mononitroalkanes are produced in the reaction (refer
Section 5A.3.2).
(2) Reaction of haloalkanes with nitrite ion. The primary and secondary
haloalkanes (generally bromides and iodides) on reaction with sodium nitrite
undergo nucleophilic substitution reaction to produce nitroalkanes (refer p. 411).
Oxidation reactions
(1) Oxidation of primary amines. The 1° and 2° alkyl groups containing 1°
amine are oxidized with peracids to nitro compounds. However, a 3° alkyl group
containing 1° amine is oxidized with KMnO4 to give excellent yields of
corresponding nitroalkane. For example,
(1) Reaction with alkali (formation of salt). The acidic character (due to –I
effect of nitro group) is exhibited in reaction with strong alkalis, where salt
formation takes place.
(4) Reaction with nitrous acid [Test for distinguishing 1°, 2°, and 3°
nitroalkanes]. The 1° and 2° nitroalkanes react with nitrous acid to form nitrolic
acid and pseudonitrol respectively. The 3° nitroalkanes do not react with nitrous
acid. The reaction forms the basis of Victor Meyer’s test for distinguishing 1°,
2°, and 3° alcohols. Nitrous acid is produced in situ from sodium nitrite and
hydrochloric acid.
22B.3.2 Reactions Involving Nitro Group
(1) Reduction (formation of amine and hydroxylamines). The nitroalkanes on
reduction result in the formation of amines or hydroxylamine depending on the
nature of the reducing agent. Reduction of nitroalkane in presence of metal
catalyst (H2/Pt or Pd or Ni or Zn/HCl or SnCl2/ HCl) results in the formation of
amines. On the other hand, reduction of nitroalkane in neutral medium using
Zn/NH4Cl results in the formation of hydroxylamine. The reactions can be
illustrated as:
(2) Action of heat. The primary and secondary nitroalkanes on heating at 300°C
undergo elimination of nitrous acid (HNO2) to produce alkenes.
(3) Hydrolysis of nitroalkanes (formation of carbonyl compounds). The
acidic hydrolysis of sodium salt of 1° or 2° nitroalkanes results in the formation
of aldehyde or ketone. This is known as Nef reaction. For example,
The reactions, which distinguish the isomeric nitroalkanes and alkylnitrites can
be compared as follows:
C. DIAZOMETHANE [CH2N2]
22C.1 PREPARATION AND PROPERTIES
Diazomethane (CH2N2) is a toxic, yellow gas (b.p. –23°C). It is highly
explosive. The structure of diazomethane is the resonance hybrid of following
contributing structures.
Physical properties
(i) Alkanenitriles have a pleasant smell while alkaneisonitriles have offensive
odour.
(ii) Lower alkanenitriles are soluble in water (form hydrogen bonding with
water) but alkaneisonitriles are insoluble in water because of no hydrogen
bonding.
(iii) Alkanenitriles have higher boiling points in comparison of corresponding
isonitriles.
(iv) Alkanenitriles are less toxic compared to isonitriles
22D.2 PREPARATION OF ALKANENITRILES
(2) From alkali salts of sulfonic acid. The potassium alkylsulfate on heating
with potassium cyanide results in the formation of alkanenitrile. Some iosnitrile
is also produced during reaction.
(2) From Grignard reagent. The Grignard reagent on reaction with cyanogens
chloride results in the formation of alkanenitrile. This method is used for the
preparation of 3° alkanenitriles.
22D.3 PREPARATION OF ISONITRILES
(1) From haloalkanes. Iodoalkane on heating with silver cyanide in aqueous
ethanolic solution undergoes nucleophilic substitution to form alkaneisonitrile
(Section 11.3.2).
This reaction is used for distinguishing the primary amines from secondary and
tertiary amines in the qualitative analysis and the reaction is popularly known as
carbylamine test (or reaction).
22D.4 CHEMICAL PROPERTIES OF NITRILES
AND ISONITRILES
(1) Hydrolysis. The hydrolysis of alkanenitrile in acidic or alkaline medium
results in the formation of carboxylic acid. The hydrolysis of alkaneisonitrile
results in the formation of amine and formic acid. Isonitriles can be hydrolyzed
only in acidic medium.
(3) Addition of hydrogen halides. The nitriles and isonitriles undergo reaction
with HX to form corresponding addition products.
(4) Reaction with Grignard reagent. Alkanenitriles on reaction with Grignard
reagent followed by hydrolysis result in the formation of ketones. This is the best
method for the preparation of ketones. The alkane isonitriles on reaction with
Grignard reagent result in the formation of amines and aldehydes. For example,
E. ISOCYANATES AND
ISOTHIOCYANATES
22E.1 INTRODUCTION
The isocyanates are nitrogen derivatives of carbonic acid whereas
alkylisothiocyanates are considered as esters of isothiocyanic acids.
Alkylisocyanates are liquids with pungent smell and are toxic in nature. The
isothiocyanates are liquids with pungent odour having strong mustard smell and
are insoluble in water. They are lachrymatory and cause blisters on skin.
22E.2 PREPARATION OF ISOCYANATES
Alkaneisonitriles on oxidation with HgO result in the formation of isocyanates
(refer Section 22D.4). Alkaneisocyanates are also formed as intermediates in
reactions such as Claisen, Hofmanm, and Loosen reaction in decomposition of
amides, azides, and hydroxamic acids. Besides this, isocyanates can be
synthesized by the following methods:
(1) Dimethyl sulfate on heating with potassium cyanate in the presence of
sodium carbonate results in the formation of methylisocyanate.
(2) The reaction of primary amines with phosgene results in the formation of
isocyanates. It is an process used for the synthesis of methyl isocyanate
(MIC; refer Notabilia 15) in the industries.
22E.3 CHEMICAL PROPERTIES OF
ISOCYANATES
Isocyanates are highly reactive compounds due to the cumulated double bond
system present. They react readily with nucleophiles such as water, alcohol,
ammonia, and amines.
(1) Hydrolysis. The alkyl isocyanates on hydrolysis form primary amine and
carbon dioxide. This is a highly exothermic reaction.
(2) Reaction with alcohols or phenols (formation of esters). The isocyanates
react readily with alcohols or phenols to form solid esters (urethanes).
(3) Reaction with ammonia. Isocyanates react readily with ammonia to yield
N-substituted
urea.
(4) Trimerization. In presence of bases, the isocyanates trimerize to form
cyanuric acids.
All these reactions are summarized as follows:
22E.4 PREPARATION OF ISOTHIOCYANATES
1. Hofmann mustard oil reaction (p. 786)
2. Reaction of isonitrile with sulfur (p. 800)
3. Reaction of primary amines with carbondisufide. The reaction of primary
amines with carbondisulfide in the presence of alkali (NaOH) results in the
formation of N-alkyldithiocarbamide, which reacts with ethyl chloroformate to
form alkyl isothiocyanate as
22E.5 CHEMICAL PROPERTIES OF
ISOTHIOCYANATES
The characteristic reactions of isothiocyanates are
(1) Hydrolysis. The alkylisothiocyanates are hydrolyzed on heating in acidic
medium to yield primary amines.
(2) Chlorination. Addition of chlorine to isothiocyanates results in the
formation of isocyanidedichloride.
(3) Reaction with amines. Isothiocyanates on reaction with primary or
secondary amines form corresponding thiourea. Tertiary amines do not react
with isothiocyanates.
These reactions are summarized taking the example of methylisothiocyanate.
SELECTED SOLVED EXAMPLES
Example 1. Giving suitable explanation, arrange the following in increasing
order of basicity.
The guanidine accepts a proton readily, to form a cation. The cation undergoes
delocalization and is thus highly stabilized. Higher the stability of cation, higher
is the basicity of corresponding neutral molecule.
Example 5
(i) But-1-ene to Pentan-1-amine
(ii) Butanal to Butan-1-amine
(iii) Butan-1-ol to Propan-1-amine
(iv) Propanone to Propan-2-amine
(v) Propan-2-amine to Propanone
(vi) 2-Methylpropanoic acid to Propan-2-amine
Solution
2. Write all the possible isomers of C5H13N and give their IUPAC names.
3. Amines attached to different alkyl groups do not show optical activity, why?
4. Why do amines have lower boiling points compared to alcohols?
5. Arrange the following in increasing order of their boiling points.
(CH3CH2)3N , CH3CH2CH2NH2, (CH3CH2)2NH
6. Describe Hofmann’s and Hinsberg’s methods for separation of 1°, 2°, and 3°
amines?
7. What product will be obtained by reduction of CH3CH2CONH2 with
LiAlH4?
8. Give mechanism for the Hofmann degradation reaction.
9. How do Loosen rearrangement, Curtius reaction, and Schmidt reaction result
in the formation of amines?
10. Complete the following reactions:
Physical properties. The nitro compounds are polar in nature and the dipole-
dipole interactions impart them high boiling points. Nitrobenzene has a dipole
moment 3.9 D and is a high boiling pale yellow liquid, which has a characteristic
bitter almond odour. Nitrobenzene is denser than and insoluble in water,
however, it dissolves in organic solvents. The substituted nitro derivatives are
generally solids. The melting and boiling points of aromatic nitro compounds
generally increase with an increase in the number of nitro groups.
23A.2 PREPARATION OF AROMATIC NITRO
COMPOUNDS
The different methods of preparation of aromatic nitro compounds are as
follows:
(1) Nitration of aromatic ring. The nitration of benzene is carried out with a
mixture of
nitric acid and sulfuric acid, known as nitrating mixture at ~50°C, which results
in the
formation of nitrobenzene. At higher temperature (~100°C), one more nitro
group is
introduced resulting in the formation of m-dinitrobenzene. It is an electrophilic
substitution
reaction where nitronium ion (+NO2) acts as an electrophile (for mechanism,
refer
Section 10.2.2).
The nitration in aromatic systems may also be carried out with acetyl nitrate or
NaNO2/CF3COOH.
(2) From arenediazonium salts. The aromatic amines can be converted to nitro
compounds via diazonium salts. The first step involves reaction of aromatic
amines with nitrous acid in the presence of BF4– and the second step involves
the treatment of diazonium salt with sodium nitrite in the presence of copper
catalyst.
The nitro group deactivates the aromatic ring towards electrophilic substitution
reactions and thus, behaves as a meta-director in these reactions. However, this
deactivation leads to nucleophilic substitution reaction in nitro compounds at
ortho and para positions.
In nitrobenzene, the ring is highly deactivated. As a result, nitrobenzene is stable
towards oxidation by different reagents and is generally used as a solvent in
oxidation reaction of other organic compounds.
The important reactions of nitro compounds include (i) nucleophilic substitution
reactions,
(ii) electrophilic substitution reactions, and (iii) reduction reactions. A discussion
of these reactions is as follows:
23A.3.3 Reduction
The reduction of aromatic nitro compounds is a complex process and involves
the production of many intermediate products before the final stage—formation
of aromatic amine, is reached.
(a) The reduction of nitrobenzene in acidic or neutral solution results in the
formation of nitrosobenzene, which on reduction yields
phenylhydroxylamine. Further reduction of phenylhydroxylamine results
in the formation of aniline as the final product.
A proper choice of reducing agent and conditions may result in the formation of
most of the above reduction products. The following reaction series summarizes
all these reduction reactions.
Also, an aromatic amine such as aniline exhibits a resonance effect (+R effect),
due to which the lone pair on nitrogen participates in delocalization with π-
electrons of benzene ring system and is less available to be shared with other
species.
The order of basic strength of amines is as follows:
With an increase in the number of phenyl groups, the delocalization of lone pair
increases. Further, steric hindrance is also increased due to the presence of
phenyl groups and these two factors together reduce the availability of lone pair
of electrons on nitrogen thereby decreasing the basicity. Diphenylamine is a
weaker base than aniline while triphenylamine completely lacks basicity.
Effect of substituents on basicity of aromatic amines
In aromatic amines, the presence of electron releasing group on benzene ring
enhances the electron density on nitrogen and thus, increases the basicity.
However, the presence of electron withdrawing groups decreases the basicity of
amines. The order of basicity of different substituted amines is as follows:
The quaternary ammonium halide on treatment with silver oxide results in the
formation of quaternary ammonium hydroxide with precipitation of silver halide.
Heating the quaternary ammonium hydroxide results in the formation of 3°
amine and an alkene. This reaction is known as Hofmann elimination (p. 217).
(2) Reaction with acid chlorides (formation of amides)
The nucleophilic substitution of aromatic amines with acid chlorides results in
the formation of
N-substituted amides. The reaction of amines with benzoyl choride is carried out
in alkaline medium. This benzoylation reaction is popularly called Schotten-
Baumann reaction.
Mechanism
Step 1. Attack of aniline on carbonyl carbon of benzoyl chloride
Step 2. Loss of proton
Step 3. Removal of HCl (formation of benzamide)
In a similar manner, the reaction of aromatic amines with aliphatic acid chlorides
(or aliphatic acid anhydride) results in the formation of amides. The acetylation
reaction is best carried out with acetic anhydride rather than acetyl chloride.
Sulfanilic acid exists as a dipolar or zwitter ion. The acidic character due to
sulfonic acid group is increased as it is present in the form of sulfonate ion
whereas basic character is reduced due to anilinium ion.
It should be noted that amides of sulfanilic acids are known as sulfanilamides.
These compounds are used as potential sulfa drugs.
Reaction with nitrous acid
Nitrosation reaction. One of the most important electrophilic substitution
reactions is the nitrosation reaction, which occurs in the presence of nitrous acid.
This reaction can differentiate 1°, 2°, and 3° amines as they yield different
products with nitrous acid. The nitrous acid is produced insitu by reaction of
sodium nitrite and hydrochloric acid.
Primary aromatic amines react with nitrous acid to form aromatic diazonium
salts (arenediazonium salts). Unlike their aliphatic counterparts, the aromatic
diazonium salts are stable. Formation of diazonium salts and their further
reactions are of immense importance and are discussed in detail in the next
section.
The 2° amines on reaction with nitrous acid yield yellow oily N-nitroso
compounds.
The 3° aromatic amines react with nitrous acid and the nitrosation occurs at p-
position of the ring. The ring substitution by nitrosonium ion (an electrophile)
results in the formation of 4-nitroso-N,N-disubstituted aniline.
The nitrosonium ion is a weak electrophile and thus attacks at an electron rich
site. In primary amines, the electron rich site is nitrogen.
For 2° amine: In 2° amines the electron rich site is again nitrogen, which is
attack by +NO, and a proton is displaced. Reaction occurs till the N-nitroso
compound is formed.
Solution
Example 4. Carry out the following conversions:
(i) Benzene to metanilic acid (3-aminobenzenesulfonic acid)
(ii) Toluene to m-chlorotoluene
Solution
EXERCISES
1. Give IUPAC names of the following compounds:
2. Write the structure for all isomeric aromatic amines with molecular formula
C8H11N.
3. Why do aromatic amines have higher boiling point compared to aromatic
hydrocarbons?
4. Comment on the basic strength of aromatic amines with respect to aliphatic
amines.
5. Select the stronger base in the following pairs (Justify your answers with
reasons).
6. What is Hofmann elimination reaction?
7. What product is formed when aniline reacts with benzoyl chloride in alkaline
medium? Name the type of reaction involved and give suitable mechanism.
8. Although, in aniline the –NH2 group exhibits +R effect, direct nitration gives
meta- nitroaniline instead of expected ortho and para nitro product, explain.
9. What products are formed by reaction of the following amines with nitrous
acid?
24.1 INTRODUCTION
The class of aromatic hydrocarbons containing more than one aromatic ring are
known as polynuclear hydrocarbons. The polynuclear hydrocarbons in which
two or more aromatic rings are fused together (generally through ortho carbons)
are referred to as condensed polynuclear compounds or fused ring hydrocarbons.
For example,
The present chapter includes the structure elucidation, preparation, and chemical
properties of fused ring system such as naphthalene, anthracene and
phenanthrene.
24.2 NAPHTHALENE
Naphthalene is one of the constituents of coal tar, which is also its industrial
source. Naphthalene is the simplest fused ring system. It is a colourless
crystalline solid (m.p. 80°C) and sublimes on heating. It has a characteristic
odour. It is insoluble in water but soluble in alcohol, ether, and benzene.
Naming the positions in naphthalene: The rings in naphthalene are designated
individually as A and B and are numbered using Arabic numerals or Greek
letters as follows:
This is to further add that benzene ring containing an –NH2 group is highly
activated and is more susceptible to oxidation whereas benzene ring containing –
NO2 group is deactivated and does not undergo oxidation. These two factors
explain the product formation already discussed in (b) and (c) above.
Thus, naphthalene comprises two benzene ring systems fused at ortho position
and is a condensed polynuclear hydrocarbon. The reactions discussed so far can
be summarized as follows:
24.2.2 Aromaticity in Naphthalene
In naphthalene, the two benzene rings are condensed at ortho carbons where
each carbon is sp2 hybridized. It contains a delocalized π-electron system with
ten π-electrons [Fig. 24.1(a)] and follows Huckel’s (4n + 2) rule. Thus,
naphthalene is an aromatic system (Section 9A.4).
Figure 24.1 (a) Overlap of p-orbitals in naphthalene (hydrogens not shown in the figure); (b) resonance in
naphthalene; and (c) hybridization and bond lengths in naphthalene.
Benzene has resonance energy 36 kcal mol–1. Since in naphthalene the two
benzene rings are fused together, the resonance energy of 2 × 36 = 72 kcal mol–1
is expected. In reality, naphthalene has a resonance energy of 61 kcal mol–1. The
two benzene rings share a pair of electrons and therefore the total number of π-
electrons available for delocalization is not twelve but ten. This means that
delocalization energy per ring is decreased. This decrease in the resonance
energy (delocalization energy) reduces the aromaticity and for this reason, in
general, condensed polynuclear hydrocarbons have relatively less aromatic
character, which is evident from their high chemical reactivity. Naphthalene is a
hybrid of three contributing structures [Fig. 24.1(b)].
In case of naphthalene, the C1–C2 bond length is shorter than the C2–C3 bond
length
[Fig. 24.1(c)].
In two of the contributing structures (I and II in Fig. 24.1(b)), a double bond
character develops between C1 and C2 whereas in C2–C3 bond, it is only in one
of the contributing structure III. Thus, overall double bond character in C1–C2 is
more than that in C2–C3 bonds and this attributes to the shortening of C1–C2
bond.
NOTABILIA 16
24.2.3 Preparations
Naphthalene can be prepared by the following methods:
(i) Haworth synthesis. The Friedel–Crafts acylation of benzene with succinic
anhydride gives
3-benzoylpropanoic acid (I), which on Clemmensen reduction forms 4-
phenylbutanoic acid (II). Heating this product in presence of concentrated
H2SO4 results in ring closure by elimination of water molecule to form α-
tetralone (III). The Clemmensen reduction of α-tetralone gives
tetrahydronaphthalene [tetralene (IV)] which on dehydrogenation with selenium
results in the formation of naphthalene.
Reduction of naphthalene
Naphthalene on reduction (addition of hydrogen) by different methods results in
the formation of number of products.
(i) Reduction of naphthalene with sodium and ethanol results in the formation
of 1,4-dihydrodialin (1,4-dihydronaphthalene).
(ii) Reduction of naphthalene with isopentanol (isoamyl alcohol) and sodium
results in the formation of tetralin (1,2,3,4-tetrahydronaphthalene).
(iii) Catalytic reduction (Formation of trans and cis-decalin). Naphthalene on
catalytic reduction with H2/Ni results in the formation of tetralin, which is
further reduced to yield trans-decalin. On the other hand, the catalytic
reduction of naphthalene with H2/Pt results in the formation of cis-decalin.
Trans-decalin is more stable than cis-decalin due to less strained structure.
These reduction reactions of naphthalene are summarized as follows:
Addition of halogens
The addition of chlorine to naphthalene results in the formation of naphthalene
dichloride, which is a 1,4-dichloro addition product. Further addition of chlorine
results in the formation of naphthalene tetrachloride, which is a 1,2,3,4-tetra
addition product. Bromine also results in the formation of di- and tetra-bromides.
In the addition of halogens, all the atoms (of chlorine or bromine) add to the
same ring of naphthalene.
(iii) Friedel–Crafts Alkylation. The fused ring compounds are highly reactive
and are attacked by the catalyst AlCl3 under vigorous conditions. As a result,
poor yields are obtained in Friedel–Crafts reaction. For better yields, the
Friedel–Crafts alkylation of naphthalene is carried out at low temperature (mild
conditions). The Friedel–Crafts alkylation of naphthalene with iodomethane
results in the formation of 1-methylnaphthalene as a major product along with 2-
methylnaphthalene as a minor product. However, Friedel–Crafts alkylation with
bromoethane results in the formation of 2-ethylnaphthalene as the only product.
The reaction of naphthalene with bromopropane yields 2-isopropylnaphthalene
as the propyl cation formed during reaction rearranges to a more stable isopropyl
cation (p. 336).
24.3.1 Naphthols
Preparations
(i) 1-Naphthol and 2-naphthol (α-naphthol and β-naphthol) occur in small
quantities in coal tar. The industrial preparation of naphthol involves fusion
of corresponding naphthalene sulfonic acid with sodium hydroxide.
Chemical properties
The chemical reactions of naphthols are similar to phenols. Formation of esters
and ethers with naphthols is much faster as compared to phenols since naphthols
are more acidic than phenols. The increased acidic strength in case of naphthols
is attributed to the stabilization of naphthoxide ion due to more delocalization as
compared to phenoxide ion. In naphthoxide ion, the delocalization involves both
the rings as shown below:
Naphthols undergo coupling reactions with benzene diazonium salts and this
reaction is used for preparation of azo dyes. 1-Naphthol undergoes coupling at
C4 whereas 2-naphthol undergoes coupling at C1.
With ferric chloride solution, 1-naphthol (α-naphthol) gives violet colour and 2-
naphthol
(β-naphthol) gives green colour. This reaction is used for the qualitative
detection of α- and
β-naphthols.
24.3.2 Naphthylamines
Preparation
Bucherer reaction. Naphthylamines are prepared from naphthols by Bucherer
reaction. This involves heating of naphthols with aqueous solution of
ammonium hydrogen sulfite and ammonia. In the process, 1-naphthol results in
the formation of 1-naphthylamine and 2-naphthol yields 2-naphthylamine.
Mechanism
Chemical properties
1-Naphthylamine on diazotization forms naphthalene-1-diazonium salt,
24.3.4 Naphthoquinones
There are three types of possible naphthoquinones depending upon the position
of the two carbonyl groups. The two carbonyl groups in naphthoquinones may
be present in the same ring or different rings. The naphthoquinones are yellow
coloured crystalline solids. It should be noted that
(a) 1-Amino-2-naphthol is synthesized by coupling of 2-naphthol and benzene
diazonium chloride, followed by reduction. 1-amino-2-naphthol on
oxidation results in the formation of 1,2-naphthoquinone.
Aromaticity in anthracene
In anthracene, all the carbons are sp2 hybridized and the three fused rings lie in
the same plane, which gives a flat structure to anthracene. The ring has fourteen
π-electron delocalized system (obeys Huckel’s rule) and is aromatic in nature.
The structure of anthracene is a hybrid of following contributing structures:
24.4.2 Preparations
The anthracene can be prepared by Friedel–Crafts reaction in the following
manner:
(a) The acylation of benzene with phthalic anhydride in presence of AlCl3
results in the formation of 2-benzoylbenzoic acid which is converted into a
cyclic compound in presence of concentrated sulfuric acid to form
anthraquinone. The distillation of anthraquinone over zinc dust gives
anthracene.
The carbons in phenethrene are sp2 hybridized but unlike anthracene, the three
benzene rings are fused in angular manner. Similar to anthracene, it is a fourteen
π-electron delocalized system and is aromatic in nature.
The numbering in phenanthrene is carried out as follows:
24.5.1 Preparation
Haworth synthesis: Friedel–Crafts acylation of naphthalene with succinic
anhydride results in the formation of 3-(1-naphthoyl)propanoic acid (I). The
Clemmensen reduction of this acid gives 4-(1-naphthyl)butanoic acid (II) which
undergoes cyclization at 2-position of naphthalene to give a cyclic ketone (III).
The ketone III, on Clemmensen reduction followed by dehydrogenation with
selenium or Pd-C results in the formation of phenanthrene.
Solution
(i) Dieckmann condensation (ii) Dieckmann condensation
(Intramolecular Claisen condensation)
Solution. The above compounds are examples of dicarbonyl compounds, that is,
two carbonyl groups are present in the same molecule. These dicarbonyl
compounds do not contain an α-hydrogen. In presence of base, these dicarbonyl
compounds undergo an intramolecular Cannizzaro’s reaction.
The mechanism is similar to what has been discussed in Cannizarro’s reaction
(refer text). In intramolecular reaction, the hydride transfer occurs to second
carbonyl group present within the same molecule to form hydroxy carboxylic
acids.
[Note: However, if polarity of C=C is enhanced considerably, it may undergo attack by Grignard reagent.
(refer problem 113)]
Problem 113. The reaction of pent-3-en-2-one with methylmagnesium iodide
(molar ratio 1:1) followed by hydrolysis results in the formation of two products
—a 3°alcohol (as expected) and a minor amount of saturated ketone
(unexpectedly). Write the reactions involved and explain the formation of
saturated ketone.
Solution. The addition of Grignard reagent at the carbonyl group of the
unsaturated ketone followed by hydrolysis results in the formation of unsaturated
alcohol (shown as [I] in the reaction). This reaction is similar to the reaction of
saturated ketone with Grignard reagent.
Although Grignard reagent does not attack C=C (as explained in previous
problem) but in pent-3-en-2-one, the carbon–carbon double bond is in
conjugation with the carbonyl group. Due to this conjugation, the delocalization
of electrons takes place that enhances the polarity of olefinic bond. Thus,
olefinic carbon with enhanced electrophilic nature is attacked readily by
Grignard reagent (Section 17.4) to form saturated ketone (shown as [II] in the
reaction).
Problem 118. The cis-cinnamic acid has a relatively high acidic strength
compared to trans-cinnamic acid. Explain.
Solution. The cis-cinnamic acid has phenyl ring and carboxylic group on the
same side of the double bond. The steric hindrance from phenyl group makes
carboxylic group to be in a plane different from the double bond. As a result, no
delocalization of electrons takes place between the double bond and carboxylic
group, which enhances the acidic strength.
Problem 119. Among succinic acid (butanedioic acid) and malonic acid
(propanedioic acid), which will undergo thermal decarboxylation most readily?
Solution. The carboxylic acids having electron withdrawing group (–I effect) at
α-position undergo decarboxylation most readily. Thus, among the given two
dicarboxylic acids, malonic acid will undergo decarboxylation more easily
compared to succinic acid.
In malonic acid, carboxylic group (having –I effect) is at α-position to the other
carboxylic acid. Succinic acid undergoes dehydration to form succinic anhydride
(refer text) rather than decarboxylation.
Problem 120. Which of the carboxylic acid of the following pairs will undergo
decarboxylation readily?
(i) O2NCH2COOH O2NCH2CH2COOH
(ii) CH3COCH2COOH CH3CH2CH2COOH
(iii) CH3CH2COOH CH3CH(Cl)COOH
(iv) CCl3COOH CH2ClCOOH
Solution. As mentioned in the previous problem, carboxylic group having
electron withdrawing group at α-position undergoes decarboxylation more
readily. Thus,
(i) O2NCH2COOH will undergo decarboxylation more readily (–NO2 at α-
position) as compared to O2NCH2CH2COOH (–NO2 at β-position).
(ii) CH3COCH2COOH will undergo decarboxylation more readily (CH3CO
at α-position) as compared to CH3CH2CH2COOH (no electron
withdrawing group is present).
(iii) CH3CH(Cl)COOH will undergo decarboxylation more readily (Cl at α-
position) as compared to CH3CH2COOH (no electron withdrawing group
is present).
(iv) Both the acids have –Cl atom at α-position but in case of CCl3COOH, three
–Cl atoms are present at α-position (enhanced –I effect) as compared to
CH2ClCOOH (only one –Cl at α-position, –I effect is less). Thus,
CCl3COOH will undergo decarboxylation more readily.
Problem 121. Arrange the following diazonium ions in increasing order of
reactivity towards coupling reactions.
Solution
(a) Add Br2 water; the alkene [ii] and alkyne [iii] will decolorize it but alkane
[i] will not decolorize the bromine water. Further the alkyne [iii] (being a
terminal alkyne) gives white precipitate with Tollens reagent, Ag(NH3)2+,
or red precipitate with Cu(NH3)2+ .
(b) These three can be distinguished with AgNO3. 1-Bromobut-2-ene [i] gives
the precipitate of AgBr immediately.1-Bromobutane [ii] gives precipitate on
heating while 1-bromobut-1-ene [iii] does not react.
Remarks: Reason lies with the position of bromine in these compounds that is in
[i] it is allylic, in [ii] it is at primary carbon and [iii] it is vinylic which is
least reactive.)
(c) Acid [i] would give effervescence with NaHCO3 solution (due to
liberation of CO2) and will dissolve in it. Aldehyde [ii] and ketone [iii] both
will give the positive test (yellow/orange ppt.) with 2,4-
dinitrophenylhydrazine (DNP reagent). In addition to this only aldehyde [ii]
gives silver mirror with Tollens reagent and red precipitate with Fehling’s
solution.
Problem 124. How the following set of organic compounds (a–e) can be
distinguished?
Solution
(a) Only ether [ii] is soluble in sulfuric acid
Remarks: it results in the formation of oxonium salts
(b) Phenol [ii] will give violet colour with FeCl3 (a characteristic reaction of
phenols).
Alternatively,
Only Phenol [ii] would dissolve in sodium hydroxide solution.
Remarks: phenol forms sodium phenoxide while alcohol [i] does not react with
sodium hydroxide.
(c) On adding AgNO3 solution the ethanoyl chloride (acetyl chloride; [i]) will
give white precipitate of AgCl immediately.
Remarks: acetyl chloride will liberate HCl with water, which will form
precipitate with AgNO3.
(d) Only Aniline [i] decolorizes the bromine water (because of the formation
of tribromoaniline) Alternatively,
On addition of NaNO2 in HCl at 0°C; Cyclohexylamine [ii] will give
effervescences as the N2 will bubble off from the solution.
Remarks:
• Both [i] and [ii] will give carbylamine test as these are 1° amines
• Aromatic amine forms diazonium salt while aliphatic amine forms mainly
alcohol with the evolution of N2 from the solution.
(e) cis-Cyclopentane-1,2-dicarboxylic acid [ii] on heating will undergo
dehydration to form corresponding anhydride.
Remarks: carboxylic groups are on the same side so the dehydration will occur
readily which is not possible in case of its trans isomer [i].
Problem 125. How the following set of organic compounds [a and b] can be
distinguished?
Solution
(a) Acid [i] would give effervescences with NaHCO3 solution and will
dissolve in it. Aldehyde [ii] and ketone [iii] both will give the positive test
(yellow/orange ppt.) with
2,4-dinitrophenylhydrazine (DNP reagent). But in addition to this only
aldehyde [ii] will give silver mirror with Tollens reagent and red precipitate
with Fehling’s solution.
Remarks:
• Formic acid (methanoic acid) also gives the silver mirror test with Tollens
reagent. So first acid has to be distinguished as mentioned above to
avoid confusion between [i] and [ii].
• Both aldehyde [ii] and ketone [iii] will also give the iodoform test.
Further to add these tests not only confirm the type of functional group but also
confirms the compound, that is
• Aldehyde giving iodofrm test must be ethanal (acetaldehyde)
• Acid responding to Tollens test must be methanoic acid (formic acid).
(b) Amide [i] and urea [iii] liberate ammonia on heating with sodium
hydroxide solution. However only urea will give biuret test.
Compound [ii] is an amino acid and will give violet colour with ninhydrin
(ninhydrin test).
Strategies in organic synthesis (126–137)
Problem 126. How will you carry out the conversion of benzene to p-
methylbenzaldehyde?
Solution
[C]:
Gilman reagent (lithium dialkylcuprate) is used to introduce the alkyl group
(here it is ethyl group) at β-position of α,β-unsaturated carbonyl
compounds. It does not affect the –CHO group (unlike the other
organometallic compounds such as Grignard reagent and Organolithiums
refer Chapter 25).
Problem 130. Carry out the following conversion only in two steps and justify
the each step involved in it.
Solution. The reaction sequence and the comments on each step are as follows:
The Gilman reagent is prepared from vinyl bromide, CH2=CH–Br (refer for
general preparation; (Chapter 25).
Problem 131. What product(s) will be obtained by the reaction of p-
acetylbenzoic acid with
(1) NaBH4 (2) LiAlH4 and (3) with SOCl2 followed by reaction with
(CH3)2CuLi? Give the comments associated with the specific use of these
reagents.
Solution. The reaction of p-acetylbenzoic acid with the given reagents along
with comments is as follows:
Problem 132. How will you carry out the following transformations starting
from
3-oxocyclohexanecarbaldehyde[X]?
Solution. Aldehydes are more reactive as compared to ketones. In a compound
containing aldehyde and keto group, the reaction occur at –CHO preferentially.
In these transformations selective protection of aldehydic group is carried out
through acetal formation. The reaction of aldehyde with ethylene glycol is
carried out with catalytic amount of acid. However use of excess acid results in
deprotection. The reactions are then carried out selectively at keto group and in
the final step deprotection of aldehydic group is carried through acidic
hydrolysis.
The general reaction of selective protection of aldehyde group is as follows:
The first step in all these transformation is protection of aldehyde group using
ethylene glycol. Further these reactions are shown from protected 3-
oxocyclohexanecarbaldehyde.
Transformation to hydroxy compounds [A] and [B]
The IUPAC names of the products formed in the above sequences of reactions
are as follows:
Cyclohexanecarbaldehyde [C],
Cyclohexanecarboxylic acid [D],
Bromocyclohexane [E],
Cyclohexanecarbonyl chloride [F],
Cyclohexylethanone [G, common name:cyclohexylmethylketone],
Methylcyclohexane [H]
Problem 133. How will you synthesize the following compound using Friedel–
Crafts reaction?
Solution. The immediate solution, which comes to the mind involving Friedel–
Crafts reaction is benzoylation of nitrobenzene (because –NO2 group is electron
withdrawing group and meta-directing) using benzoyl chloride in the presence of
AlCl3. But, this reaction cannot be carried out since Friedel–Crafts acylation
does not occur in case of aromatic systems containing electron withdrawing
group (Section 10.2.4). In fact, nitrobenzene is generally used as a solvent for
Friedel–Crafts acylation reactions.
Problem 137. How will you carry out the conversion of nitrobenzene to o-
nitroaniline?
Solution. This conversion involves the use of a protecting group as well as a
blocking group simultaneously in the following manner:
Solution. The given mixture contains benzoic acid, aniline and biphenyl. These
three can be separated by the following procedure:
Problem 139. How can the mixture of following organic compounds be
separated by extraction and acid-base method?
Solution. The given set of mixture of phenol, benzyl alcohol, and benzoic acid
can be separated by scheme as follows:
Problem 140. How can the mixture of following organic compounds be
separated? The separation by extraction procedure may involve acid-base
method and/or chemical transformation.
Solution. Phenol and benzoic acid are acidic components of the mixture and are
separated from basic components like aniline and N, N-dimethylaniline using
acid-base reactions. The separation of mixture of amines is carried out using
chemical transformation that is Hinsberg method. Benzene is a neutral
compound in this case. The separation scheme is as follows:
Problem 141. How can the mixture of pentanal and pentan-3-one be separated in
pure form?
Solution. Both pentanal and pentan-3-one are carbonyl compounds. So they are
separated by the chemical method indicated as follows:
Chapter25
Review
Part I: Organometallic Compounds
Part II: Oxidation–Reduction
Reactions
AIM
To offer consolidated information about above mentioned topics which have been
discussed under different functional groups interspersed throughout the text. Also
provides additional information (if any) which could not be accomodated earlier to
avoid loss of focus of the targetted topic.
.
SCOPE
To correlate and condense the scattered information under one roof and help
comprehend the vast field of organic chemistry with a broader outlook yet an integrated
approach.
.
HOPE
The unified and organized approach throughout the review will help the reader to
understand the topics in a simple and easily digestable manner.
LOOKING GLASS The review is thoroughly and regularly connected with the
text in the book by corresponding section number(s)[denoted as sec], page
number(s) [denoted as pp.] and solved problems from explore more
[Mentioned as EM followed by problem number] as and where they appear
throughout the book.
Further, key points and additional information (wherever needed) is also
incorporated along with reactions. Appearance of symbol star (↔) in the review
indicates the reactions and informations not discussed earlier in the text.
PART I: ORGANOMETALLIC
COMPOUNDS
25.1 INTRODUCTION
The high reactivity of organometallic compounds makes them a versatile tool to
synthesize a variety of functional groups. In Part I of this review chapter, a
summary of the general characteristics, preparations, reactions, and limitations
related to these compounds is given. Since most of the reactions have already
been discussed in the text in respective chapters, only key information is referred
to.
The organometallic compounds, prepared from organic halides, that are
discussed in this chapter include (in the same order:)
(1) Organomagnesium halides—Grignard Reagent
(2) Organolithium Compounds
(3) Lithium dialkylcuprates–Gilman Reagent
General characteristics (Section 11.4)
The organometallic compounds contain carbon-metal bond. Due to high
electropositive character of metals, the carbon bears a negative charge, that is,
the carbanion character develops at the organic moiety. Therefore, higher the
electropositive character of metal, higher is the ionic character of the carbon–
metal bond in organometallic compound.
The electropositive character of different metals follows the order: Li > Mg > Cu.
Similarly,
• Ar–Cl and CH2=CH–Cl (vinyl chloride) generally do not react readily with
magnesium. However CH2=CH–Br, Ar–I and Ar–Br react with magnesium under
normal conditions to form Grignard reagent.
• In case of Dihaloarenes, if both chlorine and bromine are present, the Grignard
reagent is formed by the replacement of bromine (refer Section 12.3.3 ).
• The preparation of Grignard reagent from tertiary haloalkanes is frequently
accompanied by dehydrohalogenation as the side reaction, that results in the
formation of alkene as a side product (refer EM problem 75).
25.2.2 Limitations
The high reactivity of Grignard reagent also poses some limitations in the
preparations of organomagnesium compounds. The organic halide used for the
preparation of Grignard reagent should be selected carefully because
(a) Grignard reagent cannot be prepared from an organic halide having an
acidic/active hydrogen containing functional groups such as –OH, –SH, –
NH2, –COOH, –SO3H. In the preparation of Grignard reagent from such
functional group containing halides, the Grignard reagent formed
decomposes immediately under reaction conditions only (refer reaction 1 of
this section).
(b) Grignard reagent cannot be prepared from organic compounds containing
groups such as carbonyl, epoxy, ester, nitrile, and acyl chloride as Grignard
reagent is reactive towards these functional groups (To get a good
understanding, the reader may refer to all the reactions of Grignard reagents
discussed).
25.3 ORGANOLITHIUMS
General preparation
Organolithium compounds are prepared by the reaction of lithium with organic
halides using dry ether, THF, or hexane as a solvent.
Lithium dialkylcuprates (Gilman reagent) are also used for the formation of
carbon–carbon bond. It is the most versatile and selective reagent used for the
preparation of unsymmetrical alkanes (Corey–House synthesis) thus overcoming
the limitation of Wurtz synthesis (which cannot be used to synthesize
unsymmetrical alkanes, refer Section 5A.2.2). Besides this, it reacts with organic
halides, acid chlorides, epoxy compounds and α, β-unsaturated carbonyl
compounds.
The reactions of Gilman reagent (Lithium dialkylcuprates) have been
summarized in this section. All reactions are discussed taking lithium
dimethylcuprate as the representative example:
(1) Reaction of lithium dimethylcuprate with halogenated organic
compounds. Lithium dialkylcuprates readily couple with halogenated
compounds and replace the halogen with alkyl group (from reagent). This
coupling reaction as well as the low reactivity towards carbonyl compounds is
used extensively to prepare higher alkanes, higher acids, unsaturated
compounds, and ketones. The reactions are as follows:
General characteristics
(i) LiAlH4 is a dark grey solid (m.p. 125°C, density 0.917 g/cc) and is highly
inflammable. It is soluble in ether. It is highly reactive towards water and
protonated solvents like alcohols.
(ii) The reaction of water with LiAlH4 is highly exothermic and the liberated
hydrogen may catch fire. Thus, LiAlH4 is stored away from water and its
reactions are carried out in perfectly anhydrous conditions.
Reactions of LiAlH4
The reduction reactions of LiAlH4 are summarized as follows:
(1) Reduction of oxygen containing functional groups
General reactions:
(2) Reduction of nitrogen containing functional groups
General reactions
Selective reduction of nitrile to aldehyde
DIBAL (diisobutylaluminium hydride) adds only one hydride to nitrile to
give imine derivative, which on hydrolysis results in the formation of
aldehyde.
General characteristics
(i) It is less reactive than LiAlH4. It is a colourless solid (m.p. 400° C, density
1.074 g/cc).
(ii) It is soluble in water but gets decomposed by water with liberation of heat
to form diborane gas.
(iii) It is a mild reducing agent and selectively reduces the compounds by
hydride transfer. Similar to LiAlH4, it behaves as a nucleophilic reagent.
(iv) The reactions of sodium borohydride are generally carried out in alcohol as
a solvent unlike LiAlH4 where alcohol cannot be used as solvent.
Reactions of NaBH4
The reduction reactions of NaBH4 are summarized in this section. Functional
groups, which cannot be reduced by NaBH4 have also been listed.
General characteristics
(i) Boron hydride (BH3) exists as a more stable dimeric structure and is
known as diborane (B2H6).
(ii) It is highly reactive and is stored in ethers like tetrahydrofuran (THF). Its
reactions are carried out in nitrogen atmosphere.
• Unlike LiAlH4 or NaBH4, diborane behaves as an electrophilic reagent.
Reactions of B2H6
In the reactions, the reagent is written as BH3 and its reactions are generally
carried out in inert solvents like THF. The reduction reactions of B2H6 are
summarized as follows along with the list of functional groups, which cannot be
reduced by B2H6.
Functional groups not reduced by BH3
Jones reagent (solution of chromic acid and sulfuric acid in water) is also used to
oxidize
1° alcohols to acid and 2° alcohols to ketone. The oxidation of alcohol is indicated by a
change in the colour of the solution from orange to green.
26.1 INTRODUCTION
The cyclic organic compounds where one or more carbon atoms of the ring are
replaced by other atoms (referred to as hetero atom) such as those of nitrogen,
oxygen, sulfur, and so on are classified as heterocyclic compounds. Nitrogen
heterocyclic compounds are most commonly found in nature and are involved in
several biological functions in plants and animals.
The heterocyclic compounds generally have five or six membered rings with one
or more hetero atom(s). Further, heterocyclic compounds may have fused ring
structure with other cyclic organic compounds and are known as condensed
heterocyclic compounds. The heterocyclic compounds may exhibit aromaticity
depending on the structure. Some important heterocyclic compounds are better
known by their common names and are widely accepted in IUPAC system. In
IUPAC nomenclature, the heterocyclic compounds are named in accordance with
the size of ring and the hetero atom present in the ring system (Table 26.1). For
example, In case of 5-membered heterocyclic ring system for nitrogen, sulfur,
and oxygen the prefixes used are aza-, thio- and oxa-, respectively. In case of
more than one hetero atom, the priority order followed while naming is oxa >
thio > aza. When used as suffix, the names of the compounds are written so that
they end with -ole. A few illustrative examples are as follows:
Numbering the position in heterocyclic compounds. The numbering in
heterocyclic compounds begins from the hetero atom in a molecule. The 2-
position is also referred to as α-position and similarly 3-position as β-position.
The numbering in pyrrole, furan, thiophene, pyridine, quinoline, and
isoquinoline is as follows:
26.2 FIVE MEMBERED HETEROCYCLIC
COMPOUNDS
In pyrrole, the carbon and nitrogen atoms are sp2 hybridized. Nitrogen utilizes
its sp2 hybrid orbitals in making two N–C bonds (sp2-sp2 overlap) and one N–H
bond (sp2–s overlap). The p-orbital of nitrogen carries a lone pair of electron.
Similarly, the p-orbital of each carbon carries a single electron. The five p-
orbitals (one of nitrogen and four of carbon) being in the same plane overlap
with each other, resulting in the delocalization of six π-electrons (1 lone pair + 4
single electrons = 6 π-electrons) in the cyclic ring system. This sextet of
delocalized π-electrons follows Huckel’s rule (4n + 2 delocalized π-electrons;
refer Section 9A.4) and imparts aromatic character to pyrrole.
In furan, the carbons and oxygen are all sp2 hybridized. Oxygen utilizes its sp2
hybrid orbitals in making two O–C bonds (sp2–sp2 overlap) while the third sp2
hybrid orbital carries an unshared pair of electrons. The pure p-orbital on
oxygen is in the same plane as p-orbitals of carbon and carries a pair of
electrons. Thus, overlap of five π-orbitals results in delocalization of six π-
electrons (1 lone pair + 4 single electrons = 6 π-electrons). The sextet of
delocalized π-electrons follows Huckel’s rule (4n + 2 delocalized π-electrons;
refer Section 9A.4) and imparts aromatic character to furan. In furan, the sp2
hybrid orbital of oxygen carrying unshared pair of electrons is orthogonal
(perpendicular) to the plane of p orbitals and does not participate in
delocalization.
In thiophene, the aromaticity is explained in a similar manner as furan. The
carbons and sulfur are all sp2 hybridized. Sulfur uses sp2 hybrid orbitals to form
two S–C bonds (sp2–sp2 overlap) and the third sp2 hybrid orbital carries an
unshared pair of electrons. The p-orbital of sulfur carries two electrons. The p-
orbitals on sulfur and on each carbon are in the same plane and their overlap
causes delocalization of six π-electrons and follows Huckel’s rule (4n + 2
delocalized π-electrons; refer Section 9A.4). Thus, thiophene exhibits aromatic
character. The sp2 hybrid orbital of sulfur carrying unshared pair of electrons
does not participate in delocalization since it is orthogonal (perpendicular) to p-
orbitals of carbons.
Fig. 26.1 Various contributing structures of pyrrole I(a–e), furan II(a–e), and thiophene III(a–e).
26.2.3 Preparations of Pyrrole, Furan, and Thiophene
From 1,4-dicarbonyl compounds (general method)
Pyrrole, furan, and thiophene can conveniently be synthesized using 1,4-
dicarbonyl compounds (as the initial reactant) as follows:
(i) Heating 1,4-dicarbonyl compounds in presence of ammonium carbonate
results in cyclization to form pyrrole (Paal–Knorr Synthesis).
(ii) Heating 1,4-dicarbonyl compounds in the presence of phosphorous
pentoxide (P2O5) results in the formation of furan.
(iii) Heating 1,4-dicarbonyl compounds in the presence of phosphorous
trisulfide (P2S3) results in the formation of thiophene.
These reactions can be summarized as follows:
This method can also be used for the preparation of number of alkyl derivatives
of pyrrole, furan, and thiophene by taking suitable 1,4-dicarbonyl compound.
Preparations of pyrrole
Following methods are used for the preparation of pyrrole.
(i) Pyrrole is obtained by distillation of succinimide over zinc dust.
(iii) Heating a mixture of furan, ammonia, and steam over alumina catalyst
results in the formation of pyrrole.
Preparations of furan
(i) The catalytic decomposition of 2-formylfuran popularly known as furfural
(or furfuraldehyde) in steam, in the presence of calcium oxide as a catalyst,
yields furan.
Furfural is prepared by distilling pentoses (carbohydrates) with dilute sulfuric
acid.
(ii) Dry distillation of mucic acid forms furoic acid. Decarboxylation of furoic
acid using copper and quinoline results in the formation of furan.
Preparations of thiophene
(i) The reaction of butane and sulfur at 600°C results in the formation of
thiophene.
The high reactivity of pyrrole is due to the ease with which nitrogen
accommodates the positive charge compared to oxygen and sulfur, which results
in an increase in the electron density of the ring. Thus, the nucleophilic
character of the ring increases and electrophile readily attacks it. In case of
thiophene the sulfur utilizes its 3d orbitals in delocalization and as a result, the
ring bears positive charge (Fig. 26.2) and the reactivity towards electrophile
decreases.
Attack of electrophile (E+) is preferred at C2. The electrophile can attack
either at C2 or at C3 of the heterocyclic ring. In general, the electrophilic
substitution occurs preferably at C2.
(i) Also, C2 is relatively electron rich as evident from the contributing
structures I (c–d),
II (c–d), and III (c–d), which are more stable, compared to I (b and e), II (b
and e), III (b
and e) (Fig. 26.1).
(ii) The intermediate carbocation formed by the attack of electrophile at C2, is
more resonance stabilized (three contributing structures) compared to
carbocation formed by attack of electrophile at C3 (two contributing
structures).
The nitration of thiophene is carried out with fuming nitric acid in the presence
of acetic anhydride.
(2) Sulfonation. The sulfonation of pyrrole, furan, and thiophene also occurs at
C2 position of the heterocyclic ring to yield corresponding sulfonic acids.
The sulfonation of pyrrole and furan is carried out with sulfur trioxide in
pyridine.
Reaction of thiophene with benzoyl chloride in the presence of tin (IV) chloride
results in the formation of 2-benzoylthiophene (a phenyl ketone).
The mercury group can be easily replaced by halogen and acyl group and is
therefore used as an intermediate to prepare 2-substituted derivatives.
(6) Formylation. Formylation is carried out using Vilsmeier–Haack reaction
where dimethylformamide (DMF) in presence of phosphorous oxychloride
(POCl3) is used as the formylating reagent. The formylation reaction with
pyrrole, furan, and thiophene results in the formation of corresponding 2-formyl
derivatives.
Formylation can also be carried out using Gatterman reaction in the presence of
Zn(CN)2/HCl.
(8) Reaction with diazonium salts. Pyrrole couples with diazonium salts in
weakly acidic medium to give azo compounds. The coupling occurs at 2-
position. In alkaline solution, it couples at 2- and 5-positions to give bis-azo
compounds.
Furan reacts with diazonium salts in alkaline medium and undergoes substitution
to give
2-arylderivative. The reaction involves the replacement of diazo group and is
known as Gomberg’s reaction.
Reduction reactions
Pyrrole and furan on reduction with hydrogen (hydrogenation) in presence of Ni
(at 200–300°C) form corresponding tetrahydro derivatives.
But thiophene on reduction with hydrogen and nickel results in the opening of
the ring to form butane. Tetrahydrothiophene is formed by the hydrogenation of
thiophene in the presence of palladium (Pd) as a catalyst. In this method, catalyst
Pd is used in relatively large amounts to overcome the poisoning effect of sulfur
of thiophene.
Some other reactions
(i) Salt formation and Kolbes—Schmitt reaction in pyrrole: Pyrrole is a weak
base. The lone
pair of electrons on nitrogen is not available for reaction as it is a part of the
aromatic sextet
(Section 26.2.2). Pyrrole shows a weakly acidic character and reacts with
potassium hydroxide to form a potassium salt. The loss of proton from nitrogen
is favoured as pyrrolyl anion is resonance stabilized. Due to this acidic character,
its potassium salt readily undergoes Kolbes–Schmitt reaction (similar to phenol)
to form pyrrole -2-carboxylic acid.
26.3.1 Pyridine
Pyridine is obtained from coal tar. It is a six membered heterocyclic compound
containing one nitrogen atom. Its molecular formula is C6H5N and a boiling
point 115°C.
In pyridine, five carbon atoms and one nitrogen atom are all sp2 hybridized.
Nitrogen utilizes its sp2 hybrid orbitals in making two N–C bonds (sp2–sp2
overlap) and the third hybrid orbital carries a lone pair of electrons. The p-
orbital of nitrogen carries a single electron. Similarly, the p-orbital of each
carbon carries a single electron. The p-orbital of nitrogen lies in the same plane
as the
p-orbital of five carbons. The six p-orbitals (one of nitrogen and five of carbon)
overlap with each other, resulting in the delocalization of six π-electrons (1
electron of nitrogen + 5 single electron of carbons = 6 π-electrons) in the cyclic
ring system. This sextet of delocalized π-electrons follows Huckel’s rule (4n + 2
delocalized π-electrons; refer Section 9A.4) and imparts aromatic character to
pyridine.
The lone pair of electrons on nitrogen does not participate in delocalization as
the sp2 hybrid orbital of nitrogen carrying the lone pair of electrons is
orthogonal (perpendicular) to the plane of the p-orbitals of carbon.
Pyridine can be represented as a resonance hybrid of the following structures:
(i) Chichibabin reaction. Pyridine when heated with sodamide results in the
formation of
2-aminopyridine and the reaction is known as Chichibabin reaction.
Oxidation reactions
The oxidation of pyridine with hydrogen peroxide or peroxybenzoic acid results
in the formation of pyridine-N-oxide.
Reduction reactions
The reduction of pyridine under different reaction conditions results in the
formation of different products. Such as,
(i) The catalytic hydrogenation of pyridine using nickel results in the
formation of piperidine.
(ii) Reduction of pyridine with lithium aluminiumhydride gives 1,2-
dihydropyridine.
(iii) Reduction of pyridine with sodium in liquid ammonia (Birch reduction)
gives 1,4-dihydropyridine.
(iv) Pyridine on reduction with hydrogen iodide at 300°C results in ring
opening to form pentane and ammonia.
These reactions are summarized as follows:
26.4 FUSED HETEROCYCLIC SYSTEMS
27.1 INTRODUCTION
Carbohydrates, also termed as saccharides, one of the basic components of
food, are composed of carbon, hydrogen, and oxygen. Structurally, they are
polyhydroxy aldehydes or polyhydroxy ketones. Lower molecular weight
carbohydrates are known as sugars and their names generally end in
characteristic ose. Some examples are sucrose (cane sugar), lactose (milk sugar),
glucose (also known as dextrose), and fructose (levulose).
Classification
Carbohydrates are divided into four major groups–monosaccharides,
disaccharides, oligosaccharides, and polysaccharides.
(i) Monosaccharides. These are the simple sugars, which cannot be hydrolyzed
further into simpler forms and they have a general formula CnH2nOn.
Monosaccharides can be further sub-classified in accordance with
(i) the number of carbon atoms in continuous chain. A three-carbon
monosaccharide is termed as triose; one with four carbons—a tetrose; one
with five carbons—a pentose; and that with six carbons—a hexose.
(ii) the aldehyde (–CHO) or ketone (–CO) group present in the saccharide.
The saccharides containing an aldehyde group are called aldoses while
those with a ketone group are referred to as ketoses.
All aldoses can be prepared by a complex series of reactions from one of the
enantiomeric glyceraldehydes. The overall procedure involves adding carbons
one at a time. By this method, the glyceraldehyde is converted to an aldotetrose;
the aldotetrose can in turn be used to synthesize an aldopentose. Further,
aldopentose can be used to synthesize aldohexose, and so on. When
glyceraldehyde is converted to a tetrose, the carbon atom of the aldehyde group
of glyceraldehyde is reduced, thus, becoming a new-asymmetric carbon atom.
The added carbon atom becomes the aldehyde group of aldotetrose produced.
Thus, two aldotetroses are formed from D-glyceraldehyde and two from L-
glyceraldehyde. Consequently, there are four aldotetroses (as would be predicted
by the formula 2n for the number of stereoisomers, where n is the number of
asymmetric carbon atoms; refer Section. 3.2.4). The relationship of the four
possible aldotetroses to D- and L-glyceraldehydes is shown in Fig. 27.1.
Fig. 27.1 The four aldotetroses and their relationship with enantiomeric glyceraldehyes. Aldotetroses (i and
ii) are derived from D-glyceraldehyde whereas (iii and iv) are derived from L-glyceraldehyde.
Note that the original asymmetric carbon atom of glyceraldehyde now becomes
the asymmetric carbon farthest from the aldehyde group in new aldose. This
asymmetric carbon atom is shown as shaded in Fig. 27.1. All aldoses in which
the –OH group of the asymmetric carbon farthest from the aldehyde group
is written on the right of the Fischer projection formula are said to be
related to D-glyceraldehyde and are known as D-sugars. Similarly the aldoses
where asymmetric carbon farthest from the aldehyde group has –OH group on
the left are termed as L-sugars. This is known as relative configuration of
sugars. The D-threose and L-erythrose (ii and iii) and D-erythrose and L-threose
(i and iv) in Fig. 27.1 are enantiomeric pairs while the other combinations are
diastereomers.
In a similar manner, ketoses exist as enantiomeric pairs, that is, D and L sugars.
Most of the naturally occurring monosaccharides are members of the D-family.
The D-family of aldoses is depicted in Fig. 27.2.
This chapter discusses monosaccharides through the study of glucose (aldose)
and fructose (ketose) as representative examples.
27.3 D-(+)-GLUCOSE: CHEMICAL PROPERTIES
AND STRUCTURE
Glucose is the most common and perhaps the most abundant naturally occurring
organic compound. In nature, it occurs in fruits, honey and in blood (as blood
sugar). Glucose is a monosaccharide and it belongs to the D-family of the
carbohydrates. It is an optically active compound, which is dextrorotatory and
also known as dextrose (+ Glucose). This is a white crystalline solid (melting
point 146°C) which is highly soluble in water. Commercially it is prepared by
hydrolysis of starch under high temperature and pressure conditions in acidic
medium.
The various chemical reactions that support an open chain structure of glucose
are discussed as follows:
(i) Reduction. In presence of H2/Ni, the reduction of glucose results in the
formation of sorbitol (C6H14O6) which on heating with hydrogen iodide
completely reduces glucose to yield n-hexane. Reduction to sorbitol can also be
carried out using LiAlH4 or NaBH4.
This clearly indicates that the six carbon atoms in glucose are in a straight
chain.
(ii) Reactions with
(a) Hydroxylamine and phenylhydrazine. The reaction of glucose with
hydroxylamine results in the formation of oxime. On the other hand, the reaction
with one mole of phenylhydrazine yields glucose phenylhydrazone. This
indicates the presence of a carbonyl group in glucose.
(b) HCN. Glucose reacts with HCN to produce a cyanohydrin, which on
hydrolysis followed by treatment with HI yields heptanoic acid, thus indicating
the presence of a carbonyl group in glucose as an aldehyde.
(iii) Acetylation of glucose. Glucose on reaction with acetic anhydride gives a
very stable pentaacetyl derivative.
The penta-acetyl derivative indicates that it contains five hydroxyl groups and
since the derivative is very stable, it indicates that five hydroxyl groups must be
present on different carbons.
(iv) Oxidation
(a) With bromine water. This results in the formation of gluconic acid
(C6H12O7). Bromine water is a mild oxidizing agent, which oxidizes an
aldehyde group to carboxylic acid.
(b) With concentrated nitric acid. This gives a glucaric acid (a dicarboxylic
acid), which contains the same number of carbon atoms as glucose. Nitric acid is
a strong oxidizing agent, which oxidizes not only the aldehyde group but also
any 1° alcoholic group present in the molecule to carboxylic acid.
(c) With periodic acid (HIO4). Glucose consumes five moles of periodic acid
(HIO4) to yield formic acid (five moles) and formaldehyde (one mole). The
periodic acid cleaves the carbon–carbon bond containing –OH groups.
(d) With Fehling’s solution and Tollens reagent. Glucose reduces both
Fehling’s solution as well as Tollens reagent similar to aldehydes and itself gets
oxidized to gluconic acid.
(v) Reaction of glucose with excess of phenyl hydrazine (formation of
osazone). Glucose reacts with phenyl hydrazine to form phenylhydrazone.
However, the reaction occurs further and alcoholic group adjacent to aldehyde
group gets oxidized to a carbonyl group, which reacts with phenyl hydrazine to
form osazone. The overall process involves the consumption of three moles of
phenyl hydrazine (The mechanistic details of the reaction is discussed later in
this chapter).
Fig. 27.3 Open chain and cyclic hemiacetal forms of D-glucose (Fischer projection).
27.3.3 MUTAROTATION
Glucose is an optically active compound. However, a solution of glucose in
water undergoes a gradual change in its initial specific rotation till a constant
specific rotation is achieved. This phenomenon of change in specific rotation is
known as mutarotation.
Explanation. The D (+)-glucose exists in two isomeric forms, namely α-D-
glucose and β-D-glucose (that is, α-D-glucopyranose and β-D-glucopyranose)
having the following physical characteristics:
(b) In the presence of alkali, D-glucose looses the α-hydrogen (at C2) to form
an enolate ion, which is resonance stabilized. The enolate ion may undergo
protonation at oxygen to form an ene–diol intermediate, which in presence
of alkali forms an enolate ion. The rearranged enolate ion on protonation
forms D-fructose as
Thus, interconversion of aldose and ketose may be carried out in alkaline
medium through an ene–diol intermediate. As all the steps involved are
reversible, one can easily write down interconversion of D-glucose, D-mannose,
and D-fructose (aldose to ketose and also ketose to aldose) as follows:
All monosaccharides are reducing sugars.
Oxidation with Tollens and Fehling’s reagent
The sugars, which reduce Tollens and Fehling’s reagent, are known as
Reducing sugars. Both aldoses and ketoses reduce Fehling’s solution
and Tollens reagent. Aldoses contain aldehyde group, which reduces
the Fehling’s solution and Tollens reagent and in turn, aldoses are
oxidized to carboxylic group containing compounds (Aldonic acids).
Fructose (a ketose) is a reducing sugar because of enolization property
of the ketonic group. In the open chain form, fructose forms an enol
by movement of α-hydrogen (on C1). When the enol reverts to
carbonyl form, an aldose (glucose) may be formed. Thus, ketoses (the
α-hydroxyketones), in presence of alkali undergo ene–diol
rearrangement to aldoses and hence, reduce Fehling’s and Tollens
reagents.
In general, all monosacchsarides are reducing sugars irrespective of
aldose or ketose.
Why does the reaction stop beyond C2, that is, why does
secondary alcoholic group at C3 not react with phenylhydrazine?
This has been explained by ‘Fieser’ that osazone is stabilized through
chelation which prevents further reaction at C3.
The osazones, on hydrolysis in acidic medium, form osones (α-ketoaldehydes).
Alternatively, heating osazone with benzaldehyde can carry out its conversion to
osone. Benzaldehyde phenylhydrazone is highly stable which facilitates the
formation of osone as depicted in the following reaction:
Applications of osazone:
(1) Monosaccharides have a tendency to form syrups. The osazones have
characteristic crystalline strctures with sharp melting points. Being solids,
they are easily isolated and purified. Thus, identification of
monosaccharides can be carried out through osazones.
(2) Osazones are helpful in determining configuration of monosaccharides.
For example, hexose sugars, glucose, mannose, and fructose yield same
osazone with phenylhydrazine. Since osazone formation involves C1 and
C2 of aldose or ketose, these hexose sugars have same configuration at C3,
C4, and C5 stereocentres.
(3) Epimeric aldoses (which differ in their configuration at C2) also give same
osazones.
(4) An aldose can be converted to a ketose easily through osazone formation.
It contains four stereogenic (chiral) centres. Thus, the first task is to assign
configuration to four stereocentres. For glucose, sixteen stereoisomers are
possible (2n, where n is the number of stereogenic centres and for glucose it is
24 = 16), which means eight pairs of enantiomers. [Fischer established the
configuration of glucose for which he received the Nobel prize.]
Fischer arbitrarily retained the structure for only those isomers, which had –OH
group on the right hand side. The configuration was established on the basis of
an aldopentose, i.e. arabinose.
In arabinose, four stereoisomers were retained that had –OH on right side (on
chiral centre farthest from –CHO).
Fig. 27.4 Diagramatic representation of writing Haworth formula from Fischer projection for D-sugars.
The various reactions discussed above are summarized in the reaction sequence
shown in Fig. 27.5.
Fig. 27.5 Reactions of fructose.
(v) Reaction of fructose with excess of phenylhydrazine (formation of
osazone)
Fructose reacts with excess phenylhydrazine to form osazone, which is same as
the osazone formed with glucose. Thus, fructose has the same configuration at
C3, C4 and C5 carbons as that of glucose.
Since the configuration of glucose has already been discussed, the configuration
of fructose can be written on the same lines as follows:
27.5.1 Sucrose
Sucrose is the most common and familiar disaccharide (C12H22O11), also
known as table sugar. Commercially, sucrose is obtained from sugar cane and
sugar beets. It is also present in varying concentrations in most fruits, flowers,
seeds, and roots. On hydrolysis, sucrose gives a molecule of D-glucose and D-
fructose each.
Sucrose has α-D-glucopyranose ring attached through its C1 to C2 of β-D-
fructofuranose. It is a non-reducing sugar (1–2 linkage) and does not undergo
mutarotation.
Invert Sugar
Invert sugar is a mixture of glucose and fructose in equal amounts
resulting from the hydrolysis of sucrose. Sucrose is dextrorotatory
having specific rotation, αD= +66.5°. while its constituent
monosaccharides have specific rotation αD= +53° (for D-glucose) and
αD= –92° (for D-fructose). Since D-fructose has higher specific
rotation than D-glucose, the resulting mixture obtained by the
hydrolysis of sucrose rotates plane-polarized light to the left
(laevorotatory; opposite from the direction of rotation of sucrose).
Due to this, the mixture is known as invert sugar.
27.5.2 Lactose
Lactose is a disaccharide found solely in milk of mammals and is commonly
known as milk sugar. On hydrolysis, it yields D-glucose and D-galactose. The
D-galactose is present as β-D-galactopyranose and D-glucose as D-
glucopyranose. The lactose has β-D-galactopyranose ring attached through its
C1 to C4 of D-glucopyranose (α or β anomer). It is a reducing sugar.
BARFOED’S TEST
Distinguishing Between Monosaccharides and Reducing
Disaccharides.
Monosaccharides and reducing disaccharides can be distinguished by
Barfoed’s test. This test takes the advantage of the fact that copper (II)
ions are weaker oxidizing agents in acid solution than in basic
solution. The test solution is prepared by dissolving copper (II) acetate
in acetic acid. Monosaccharides yield a red precipitate of Cu2O
within 10 minutes of warming in the solution.
On the other hand, reducing disaccharides do not react under normal
conditions of Barfoed test. Upon prolonged heating, they produce a
positive test because of hydrolysis that yields monosaccharides in
acidic solution.
27.6 POLYSACCHARIDES
A polysaccharide consists of a number of monosaccharide units joined through
glycosidic linkages. The monosaccharide units may be same
(homopolysaccharides) or different (heteropolysaccharides). A polysaccharide
consisting of glucose units only is known as glucan. Few important examples of
polysaccharides are starch, cellulose, and glycogen.
Starch is one of the important polysaccharides, which is present in the roots ,
seeds, and tuber of plants. It is made of a number of D-glucose units and on
hydrolysis, results in the formation of amylose and amylopectin
(polysaccharides). In amylose, the C1 of one glucopyranoside ring is attached to
C 4 of another glucopyranoside ring. In this manner, thousands of
glucopyranosides rings are joined together linearly to form a compact molecule
(Fig 27.7a). Amylopectin also contains a number of glucopyranoside rings
joined through 1,4-linkage as in case of amylose. However, in this case
branching takes place between C1 and C6 of different glucose units (Fig. 27.7b).
In general, the branching occurs at an interval of 20 glucose units. The
hydrolysis of starch can be represented as follows:
NOTABILIA 17
EXERCISES
1. What are carbohydrates? Give their classification.
2. Many carbohydrates are known by their common names. Give the name of
the carbohydrates whose common names are given below:
(a) Cane sugar
(b) Grape sugar
(c) Fruit sugar
(d) Malt sugar
(e) Milk sugar
(f) Table sugar
3. What are D- and L-sugars?
4. Define reducing and non-reducing sugars?
5. What is mutarotation?
6. How will you establish the structure of glucose?
7. Carry out the following conversions:
(a) Glucose to n-hexane
(b) Glucose to fructose
(c) Arabinose to glucose
(d) Glucose to sorbitol
(e) Arabinose to erythrose
(f) Glucose to mannose
8. Explain the following:
(a) Unlike aldehydes, glucose does not form a bisulfite addition product with
NaHSO3.
(b) Sucrose, a disaccharide is a non-reducing sugar while maltose (also a
disaccharide) is a reducing sugar.
(c) The penta-acetylated product of α-D-glucopyranose does not give Tollens
test.
(d) Glucose, fructose, and mannose yield the same osazone in excess phenyl
hydrazine.
(e) Glucose reacts with one mole of CH3OH to form an acetal.
(f) Starch does not reduce Benedict’s solution.
9. Complete the following:
10. Give the chemical reactions that support the fact that glucose has a cyclic
structure.
11. What is the difference between epimers and anomers. Explain with
examples.
12. What are glycosides? Describe a glycidic linkage?
13. Write the Haworth projections for the sugars whose Fischer projections is
given as follows:
14. How can one determine the configuration of glucose? How is the
configuration of D-glucose related to that of D-glyceraldehyde?
15. What is ‘invert sugar’?
16. How can one establish the structure of fructose?
17. Why do both glucose and fructose give positive Tollens and Fehling tests?
18. Write the structure, using Haworth formula, for
(a) α-D-glucopyranose
(b) β-D-glucopyranose
(c) α-D-fructopyranose
(d) β-D-fructopyranose
(e) α-D-fructofuranose
(f) β-D-fructofuranose
19. In sucrose, fructose is present as fructopyranose or fructofuranose?
20. Disaccharide ‘trehalose’ is found in mushrooms and has the following
structure.
28.1 INTRODUCTION
Amino acids are carboxylic acids having an amino group. The naturally occuring
prevalent amino acids are α-amino acids. These are the carboxylic acids where
‘amino’ functional group is present at α-carbon.
In general, all amino acids have an amino (–NH2) group*, carboxylic (–COOH)
group, and a hydrogen atom attached to carbon along with an side chain. Amino
acids differ in their side chains. The variation in the nature of side chain imparts
characteristic properties to amino acids. Amino acids form polymers known as
peptides and proteins.
Amino acids can be represented by the general formula RCH(NH2)COOH as.
Though a large number of amino acids (more than 500) exist in nature, however,
proteins in all living organisms mainly consist of twenty amino acids. A protein
molecule may contain several hundreds or thousands of amino acid units joined
in different combinations. As an amino acid contains an amine* and carboxylic
group, it exhibits both acidic as well as basic behaviour.
28.2 CLASSIFICATION OF AMINO ACIDS
Amino acids may be classified
(1) Based on the chemical reactions they undergo in solution form as
(i) acidic, (ii) basic, and (iii) neutral
(2) Based on their nutritional importance as
(i) essential, (ii) semi-essential, and (iii) non-essential
Table 28.1 enlists the natural amino acids along with their classification,
structure, and abbreviations (three letter and one letter code).
Table 28.1 Natural animo acids
Classification based on the chemical nature
Acidic amino acids. These amino acids contain, in their side chain, a carboxylic
or carboxamide group. Examples are—aspartic acid, glutamic acid, glutamine,
and asparagine.
Basic amino acids. These amino acids contain, in their side chain, a basic group
such as an amino or an imidazole ring (a heterocyclic group). Examples are—
arginine, lysine, hydroxylysine, and histidine.
Neutral amino acids. The largest number of amino acids belong to neutral
amino acids. These neutral amino acids are further classified as:
(i) Aliphatic neutral amino acids. The side chain of these amino acids
contains either hydrogen, or an alkyl group, or hydroxyalkyl group.
Examples of aliphatic neutral amino acids are glycine, alanine, valine,
leucine, isoleucine, serine, and threonine.
(ii) Aromatic neutral amino acids. The side chain of these amino acids
contains an aromatic ring. For example, phenylalanine, and tyrosine.
(iii) Sulfur containing neutral amino acids. The side chain of these amino
acids contains thiol group (–SH) such as in cysteine or methylthio group (–
SCH3) such as in methionine, or a disulfide linkage such as in cystine.
(iv) Heterocyclic neutral amino acids. The side chain of these amino acids
contains a heterocyclic group such as indole or pyrrolidine. For example,
tryptophan, proline, and hydroxypyroline. In fact, proline and
hydroxyproline are α-imino acids.
Classification based on nutrition importance
(i) Essential amino acids. The amino acids that are not synthesized by body and
are required to be taken externally through diet are termed as essential amino
acids. Valine, leucine, isoleucine, phenylalanine, threonine, tryptophan,
methionine, and lysine, are some of the essential amino acids.
The amount of these amino acids required by our body is 1.1–0.25 g per day.
These amino acids are synthesized industrially and added to foodstuff.
(ii) Semi-essential amino acids. These amino acids are not synthesized in
human body in sufficient amount during growth. However, these are essential in
pregnant woman, lactating mothers, and in growing children. These amino acids
have an important role as growth promoting nutrients. Arginine and histidine fall
under this category.
(iii) Non-essential amino acids. These amino acids can be synthesized by
human body from other materials through a series of biochemical reactions. It is
therefore, not necessary that they are consumed through diet. Ten amino acids
(see Table 28.1) have been classified under this category.
28.3 STEREOCHEMISTRY OF AMINO ACIDS
Except glycine, all amino acids contain a stereocentre (chiral centre) and are thus
optically active.
The amino acids may be dextro (+) or laevo (–) rotatory depending upon the pH
of the solution and nature of the side chain. Except glycine, rest of the amino
acids may occur in D and L forms.
Natural amino acids occur in L-form. The natural proteins obtained from
animals and plants, in general, contain L-amino acids. Bacteria contain D-amino
acids. The L-amino acids exhibit
S-configuration.
Exceptions to this are cystine and cysteine, where sulfur is present in the side
chain (R) and thus in assigning the configuration, the side chain (containing
sulfur) gets higher priority over –COOH group, (R > COOH).
28.4 PHYSICAL PROPERTIES
Zwitterions and Isoelectric Points
Amino acids exhibit the following properties:
(a) These are high melting, colourless crystalline substances.
(b) Highly soluble in water as compared to other polar solvents.
(c) Large dipole moment and high dielectric constant value.
Thus, they resemble ionic compounds. This occurs by an internal, self-
neutralization reaction so highly favoured that amino acids exist in the zwitterion
form or inner salt (Zwitterion: a compound containing equal numbers of positive
and negative charges).
In strong acidic solutions (low pH), the amino acid exists as ammonium
carboxylic acid. In strong basic solutions (high pH), amino acids exist as amino
carboxylate ions.
In zwitterion form, the molecule has no net charge and is said to be isoelectric.
Zwitterion formation is dependent on the pH of the solution. The pH at which
an amino acid exists in its zwitterion form is called the isoelectric point
(symbolized as pI) for that amino acid. Thus, each amino acid has a
characteristic isoelectric point depending upon the nature of its side chain.
28.4.1 Electrophoresis
Electrophoresis is a method used for the separation and analysis of amino acids.
The method is based on pH control and electric charge. The amino acids differ in
their isoelectric points. The mixture of amino acid is placed on the centre of a
paper strip (cellulose acetate) at certain pH. The pH is maintained by saturating
the paper strip with the buffer solution. The paper strip is attached to two
electrodes. On passing electric current through the strip, amino acids migrate
towards electrodes depending upon the net charge present on them. For example,
a mixture of lysine, alanine, and glutamic acid at pH = 6.0, when placed on a
paper strip, on passing current results in the movement of glutamic acid towards
anode and of lysine towards cathode. The alanine has no net charge and
therefore does not move (Fig. 28.1). The amino acid with isoelectric point
greater than the buffer pH gains a proton and becomes positively charged
(Lysine, pI = 9.7) and thus moves towards cathode. On the other hand, the amino
acid with isoelectric point lower than the buffer pH looses a proton and becomes
negatively charged (Glutamic acid, pI = 3.2) and thus, moves towards anode.
The amino acid with isoelectric point comparable to buffer pH does not migrate
towards any electrode, such as Alanine, pI = 6.0.
Fig. 28.1 Separation of amino acids by electrophoresis. (a) At pH = 6.0, Glutamic acid is negatively
charged and moves towards anode. Lysine at this pH is positively charged and moves towards
cathode. Alanine remains at the same position, as at pH = 6.0 it has no net charge (b) Separation of
mixture of amino acids after electrophoresis.
28.5 SYNTHESIS OF AMINO ACIDS
The amino acids can be synthesized by a number of methods. However, a single
method cannot be used for preparation of all amino acids. The different methods
used extensively for preparation of different kinds of amino acids are as follows:
(1) Direct ammonolysis of α-haloacids. The carboxylic acids can be converted
to α-chloro or
α-bromo acids by Hell–Volhard–Zelinsky method (HVZ reaction) using chlorine
or bromine in the presence of red phosphorous. The α-bromo or α-chloro acids
on treatment with excess of ammonia result in the substitution of chlorine or
bromine by –NH2 to give α-amino acid.
Glycine, alanine, valine, leucine, and aspartic acid can be prepared by this
method.
The reaction is used for estimation of amino acids by direct titration with alkali.
This method is known as Sorensen’s Formol Titration Method. The direct
titration of amino acid with alkali cannot be carried out because of the presence
of free –NH2 group. Reaction with formaldehyde converts amino acid to
methylene amino acid, which is a strong acid and can be titrated directly with an
alkali.
(v) Oxidation. Potassium permanganate or hydrogen peroxide oxidizes the
amino group to imino group. The hydrolysis of imino acid, so produced, results
in the formation of a α-keto acid. In this process, ammonia is evolved.
(iii) Chelation with copper. The salts of amino acids with heavy metals are
chelate compounds. An aqueous solution of glycine on heating with copper
oxide form deep blue colour chelate compound.
(iv) Reduction. The α-amino acid on reduction with lithium aluminium hydride
undergoes reduction of carboxylic group to alcohol group. The product of
reduction is an amino alcohol.
28.6.3 Reactions Due to Both –NH2 and –COOH
Groups
(i) Effect of heat. Two molecules of α-amino acids, on heating undergo
intermolecular
dehydration to form 2,5-diketopiperazine derivatives. For example, glycine on
heating yields
2,5-diketopiperazine.
(ii) Ninhydrin reaction. This reaction is used for the identification of amino
acids as amino acids on reaction with ninhydrin give a blue violet colour.
Ninhydrin is a hydrate of indane-1,2,3-trione. The steps involved in the reactions
are as follows:
(iii) Reaction with isocyanates (formation of hydantoin). The reaction of α-
amino acids with isocyanates results in the formation of substituted urea
derivatives (carbamides), which on heating in acidic medium result in the
formation of hydantoin derivative.
28.7 PEPTIDES AND THEIR SYNTHESIS
The interaction of amino group of one amino acid with carboxylic acid group of
another amino acid results in the formation of an amide linkage. A number of
amino acid units are joined with each
In peptide formation:
• There is a free amino group at one end of the molecule known as N-
terminal end and a free carboxylic acid group at another end
known as C-terminal end.
• It is a convention to name a polypeptide starting from the N-
terminal amino acid to be followed by the sequence of other
amino acids and ending with the C-terminal amino acid.
• While writing the structure of a polypeptide, the N-terminal is
written at the left and C-terminal at the right.
Let us consider the synthesis of peptides by taking example of combination of
glycine and valine (without repetition of either amino acid) which can result in
the formation of two different dipeptides.
(a) Carboxylic group of glycine reacting with amino group of valine, that is,
amino group of glycine (as N-terminal) is free and carboxylic group (as C-
terminal) of valine is free. The dipeptide thus formed is named as
Glycylvaline.
(b) Carboxylic group of valine reacting with amino group of glycine, that is,
amino group of valine (as N-terminal) is free and carboxylic group (as C-
terminal) of glycine is free. The dipeptide thus formed is called as
Valylglycine.
In a similar manner, three different amino acids—alanine (Ala), valine (Val), and
leucine (Lys) can form six different tripeptides (without repetition of any amino
acid), which are as follows:
(iii) Phthaloyl group. The phthaloyl group is introduced into amino acid (for
blocking —NH2 group) by the reaction of amino acid with phthalic anhydride.
The deprotection of phthaloyl group is carried out using hydrazine follwed by
treatment with HCl.
Protection of carboxylic group (–COOH)
Ester groups, for example methyl, ethyl, allyl, or benzyl ester protect the
carboxylic end of amino acids.
Treating the protected amino acid with base (aq. NaOH) carries out deprotection
at the carboxylic group. The benzylic esters are deprotected by catalytic
hydrogenolysis (H2/Pd) to give toluene and free carboxylic group.
(ii) Dansyl method. In this method the reaction of peptide chain with 5-
dimethylaminonaph-thalene-1-sulfonylchloride (Dansyl chloride) occurs at the
N-terminal (amino end). The hydrolysis of peptide chain results in the formation
of Dansyl amino acid. This Densyl amino acid on irradiation with UV light
shows fluorescence. Thus, the N-terminal is identified. This method is 100 times
more sensitive than DNP method in detection of the N-terminal.
(iii) Edman degradation. One of the most important and widely used method
which depends on the selective removal of N-terminal amino acids from
polypeptide chain (proteins) is the Edman degradation. The method removes N-
terminal amino acid and leaves the rest of the polypeptide chain intact. Thus, the
method can be used repeatedly to identify the N-terminal of shortened peptide
chain.
Pehr Edman of Max Planck institute of biochemistry, Munich, introduced this
method. It involves treatment of polypeptide with phenylisothiocyanate. The N-
terminal of the polypeptide reacts with phenylisothiocyanate to form substituted-
thiourea, that on mild hydrolysis results in the selective separation of N-terminal
amino acid as phenylthiohydantoin, which is identified by HPLC (High
Performance Liquid Chromatography). The rest of the polypeptide chain remains
intact (of course with one N-terminal amino acid less). The method can be
repeated on this new N-terminal and the process may be repeated.
The automation of above process has enhanced the efficiency of this method to
continue sequencing the amino acids in polypeptides. The repeated Edman
degradation can be used for identification of polypeptides containing 50 or even
more amino acids. This method is not applicable for high polypeptide chains due
to accumulation of impurities (that is, amino acids) in each hydrolysis step.
C-terminal analysis
The C-terminal analysis is carried out even more efficiently by enzymatic
methods rather than chemical methods. The enzyme carboxypeptidase, cleaves
selectively the peptide linkage adjacent to C-terminal (free carboxylic group) in
polypeptide chain. The removal of C-terminal residue results in the formation of
shortened polypeptide chain, which can be treated with the carboxypeptidase
enzyme to determine the new C-terminals.
28.8.2 Sequence Analysis
The end group or terminal analysis can be used for selective removal of terminal
groups. However, it is a difficult process to identify a polypeptide chain by
stepwise continuous removal of the terminal residues. The sequence of amino
acids is identified by carrying out partial hydrolysis of the polypeptide chain.
Partial hydrolysis breaks the chain selectively into smaller fragments that can be
identified further. Specific enzymes are used which cleave the polypeptide at
specific sites only. The smaller fragments can then be identified by Edman
degradation.
Reagents/Enzymes Specific site of cleavage in polypeptide chain
Cynogen bromide Cleaves at carboxy end of methionine (Met)
Clostripain Cleaves at carboxy end of arginine (Arg)
Trypsin Cleaves at carboxy end of arginine (Arg) and lysine (Lys)
Chymotrypsin Cleaves at carboxy end of phenylalanine (Phe), tyrosine
(Tyr) and tryptophan (Trp)
Pepsin Cleaves at carboxy end of aspartic acid (Asp), glutamic acid
(Glu), leucine (Leu), phenyalanine (Phe), tyrosine (Tyr), and
tryptophan (Trp)
The sequence of amino acid, in pentapeptide, using one letter code can be
written as F-G-V-A-P.
Illustrative Example 3. A heptapeptide on reaction with DNFB followed by
hydrolysis produces N-DNP valine. The hydrolysis of peptide by
carboxypeptidase enzyme releases glutamic acid. The partial hydrolysis of
peptide gives the following fragments:
(i) Pro – Leu – Val (ii) Ala – Tyr – Pro (iii) Leu – Val – Glu (iv) Val – Ala (v)
Val - Glu
Identify the sequence of amino acids in the heptapeptide.
Solution. The formation of N-DNP valine in DNB method indicates that N-
terminal of peptide is valine (Val). The hydrolysis of peptide by
carboxypeptidase enzyme releases glutamic acid, which indicates that C-
terminal of peptide is glutamic acid (Glu).
Now the two fragments have valine (Val) as N-terminal, that is, Val-Ala and
Val-Glu. But the fragment with glutamic acid (Val-Glu) cannot be N-terminal as
glutamic acid is C-terminal of the heptapeptide.
Thus, aligning the different fragment obtained by hydrolysis keeping the Val-
Ala at N-terminal and Val-Glu at C-terminal gives the sequence as:
Amino acid sequence using one letter code can be written as V-A-Y-P-L-V-E.
Illustrative Example 4. Metenkephalin, a brain peptide, on Edman degradation
gives phenylthiohydantoin derivative of tyrosine. The hydrolysis of same peptide
with carboxypeptidase enzyme releases methionine. The second, third, and
fourth Edman degradation yields glycine, glycine and phenylalanine
respectively. What will be sequence of amino acid in metenkephalin?
Solution. The carboxypeptidase enzyme releases the C-terminal amino acid of
the peptide chain. Thus, methionine (Met) is the C-terminal of Metenkephalin
peptide. The Edman degradation releases the N-terminal amino acid of a peptide
as phenylthiohydantoin derivative leaving the rest of the polypeptide chain
intact. The repeated Edman degradation of the remaining peptide chain releases
the successive N-terminal amino acids as phenylthiohydantoin derivative. The
first Edman degradation releases tyrosine (Tyr) as phenylthiohydantoin
derivative, which indicates the
N-terminal of metenkephalin peptide to be tyrosine (Tyr). The successive
Edman degradation yields glycine (Gly), glycine (Gly) and phenylalanine (Phe)
respectively. Thus the sequence of amino acids in metenkephalin peptide is:
Tyr–Gly–Gly–Phe–Met
Amino acid sequence using one letter code can be written as Y-G-G-F-M.
28.9 PROTEINS
The nitrogenous macromolecules composed of several amino acid units are
referred to as proteins. The name is derived from the Greek word pre-eminent, as
proteins are the most important and fundamental structural components of the
body.
Functions. Proteins perform a variety of functions in the body. Proteins are the
only source, which supply nitrogen and sulfur to the body. Nitrogen is lost from
body in the form of urea through urine. Enzymes, responsible for catalyzing
various biochemical reactions are proteineous in nature. Proteins, also known as
immunoglobins or antibodies protect the body against bacterial and viral
infections. They provide mechanical support to body being the major
components of skin, muscles, and bones. Proteins perform the role of receptors
(bind vitamins and hormones) and transporters (carry small molecules and ions
within the system), and aid in storage. Proteins exert osmotic pressure and thus,
help in maintaining the electrolyte concentration and water balance in the body.
Secondary structure
The secondary structure involves the determination of spatial arrangement of
polypeptide chains. The peptide linkage is a rigid bond. However, free rotation is
possible between C–C single bonds and C–N single bonds in amino acid side
chain. This results in different conformations of polypeptide chains referred to as
secondary structure of the proteins.
Examples. The amino acids which commonly form β-pleated sheet are—
alanine, methionine, valine, and isoleucine. The β-keratin protein, which occurs
in spider’s web and reptilian claw, is a fully extended chain of β-pleated sheet.
The silk fibroin protein (occurs in silk worms) is also rich in β-pleated sheet
structure.
β-bend structure. In proteins, the polypeptide chains may change their direction
and result in the formation of a loop. The loop is stabilized by hydrogen bond
formation between carbonyl oxygen and amide hydrogen (of the third amino
acid residue).
Examples. The amino acids that are found in β-bends are glycine, aspargine and
proline.
Tertiary and quaternary structures
The polypeptide chain with secondary structure may be present as folded
structures that have the hydrophilic groups on the exterior and hydrophobic
groups on the interior of the polypeptide chains. This lowest energy
conformation is known as the tertiary structure. The tertiary structure of a
protein is its biologically active conformation and is also known as native
conformation.
The major stabilizing force responsible for compact three-dimensional (3-D)
form of tertiary structure is hydrophobic interactions between non polar side
chains of amino acids. Besides this, the polar side chains undergo hydrogen bond
formation and ionic interactions. Folding in tertiary structures of proteins bring
the amino acid residues close together compared to primary structure.
Example. Enzyme carbonic anhydrase exhibits tertiary structure of proteins.
A protein that consists of two or more polypeptide chains held together by non-
covalent forces or covalent bonds, is referred to as the quaternary structure of
protein.
The assembly of many polypeptide chains is known as oligomer and the
individual polypeptide chains are termed monomer units.
The monomeric units can be identical or different in their primary, secondary,
and tertiary structures.
Example. Haemoglobin has a quaternary structure and consists of four folded
polypeptide chains. Enzyme creatine phophokinase has two polypeptide chains.
A substrate can attach to a specific site at the enzyme. This is the reason that
enzymes show specificity to reactions, that is, an enzyme catalyzes only a
particular reaction and not other reactions (even closely related).
A small portion of an enzyme area which is responsible for its catalytic activity
is termed as the active site.
Factors influencing enzyme action
Different factors that affect the activity of an enzyme are:
(i) Temperature. For each enzyme, there is a specific temperature at which the
activity of enzyme is maximum. This is termed as the optimum temperature of
enzyme. In general, the enzymes in human system have an optimum temperature
in the range 35–40°C.
(ii) pH. The pH at which an enzyme has maximum activity is termed as its
optimum pH. For most of the enzymes, the optimum pH ranges from 4–9.
(iii) Enzyme concentration. The rate of an enzymatic reaction increases with an
increase in the concentration of enzyme.
(iv) Concentration of product. An increased product concentration lowers
down the enzymatic reaction. The products formed may either inhibit the active
site of enzyme or can make the reaction proceed in backward direction.
B. NUCLEIC ACIDS
Nucleic acids are macromolecules present in the living organisms. Nucleic acids
control the synthesis of proteins and are also responsible for storing the complete
description of living organism (genetic information) and passing the information
from one generation to another. The two nucleic acids that are found in living
organisms and are of much importance are:
1. Deoxyribonucleic acid (DNA)
2. Ribonucleic acid (RNA)
Structure of nucleic acids
The structural units of nucleic acids are nucleotides. Nucleic acids, on complete
hydrolysis, produce heterocyclic base (nitrogenous base), sugar residues and
phosphoric acid. The basic structure of nucleic acids consists of a polymer chain
(polyester) where phosphoric acid forms an ester linkage with sugar. In other
words, polyester chain has alternate phosphoric acid and sugar residues. To each
sugar residues, one group of nitrogenous base is attached.
For DNA:
Sugar is D-2-deoxyribose and correspoinding nitrogen bases can be thymine, cytosine, adenine, or guanine
For RNA:
Sugar is D-ribose and corresponding nitrogen bases can be uracil, cytosine, adenine or guanine
Fig. 1 Schematic representation of nucleic acids.
The heterocyclic bases are pyrimidine and purine derivatives. The pyrimidine
derivatives include cytosine, uracil, and thymine while adenine and guanine are
purine bases. In deoxyribonucleic acids (DNA), adenine, guanine, thymine and
cytosine are present. In ribonucleic acid (RNA), thymine is replaced by uracil.
Sugar in nucleic acids is a pentose sugar, which may be either D-ribose (in
which case, nucleic acid is called ribonucleic acid; RNA) or D-2-deoxyribose
(the nucleic acid is called deoxyribonucleic acid, DNA).
Figure 2 depicts the structures of nitrogen bases and sugars in nucleic acids.
Nucleosides
A sugar is attached to a heterocyclic base through a glycosidic linkage and this
whole unit constitutes a nucleoside.
In a pyrimidine nucleoside, the C1 of sugar is attached directly to N1 of
pyrimidine base.
In a purine nucleoside, the C1 of sugar is attached to N9 of purine base.
The naming of nucleosides is done based on the type of sugar and bases present.
Thus, adenosine (ribose + adenine), deoxyadenosine (deoxyribose sugar +
adenine), cytidine (ribose + cytosine), deoxycitidine (deoxyribose + cytosine),
uridine (ribose + uracil); deoxythymidine (deoxyribose + thymine) are some
examples of nucleosides.
Nucleotides
A nucleoside which is attached through its sugar to phosphoric acid group is
termed as a nucleotide. It should be noted that
(i) A deoxyribose sugar of nucleoside can attach to phosphoric acid through
free –OH present at C3 or C5 to form ester linkage.
(ii) A ribose sugar in a nucleoside can attach to phosphoric acid through free –
OH groups at C2, C3, or C5 to form an ester linkage.
The structures of nucleosides and nucleotides are as follows:
Deoxryribonucleic acid (DNA)
Watson and Crick postulated that this nucleic acid has a double helical structure.
In DNA, the sugar is a deoxyribose sugar and heterocyclic bases are Adenine
(A), Guanine (G), Thymine (T), and Cytosine (C). The nucleotide chain in DNA
has alternate sugar and phosphate ester residues. The phosphoric acid on one
side forms ester linkage with 3′ –OH of one sugar and on other side it forms
ester linkage with 5′–OH of another sugar residue.
The helix are held together by hydrogen bonds between the bases on one strand
and those on the other. The bases in one strand are attached to complementary
bases on other strand through hydrogen bonding. Adenine pairs with thymine
while cytosine pairs up with guanine. The adenine and thymine base pairs have
two hydrogen bonds between them while cytosine and guanine base pairs have
three hydrogen bonds between them. Thus, two strands can fit together as a helix
properly only if given base in one chain has only a specific base as its nearest
neighbour in the other chain.
During cell division, the double helix of DNA unwinds into two strands each
acting as a template on which its complementary strand may be constructed.
This replication is the key to inheritance of character (genetic information). A
gene is a portion of DNA molecule.
Ribonucleic acid (RNA)
This nucleic acid exists as a single stranded helix. The structure of RNA is
similar to that of DNA except that the sugar in it is ribose sugar and uracil is
present instead of thymine as a heterocyclic base. There are three types of RNA,
namely messenger (m-RNA), transfer (t-RNA), and ribosomal
(r-RNA).
The DNA and RNA are involved in protein biosynthesis, which involves two
important processes of transcription and translation.
Transcription. The genetic information contained in DNA is incorporated into
m-RNA by this process. The DNA strands uncoil and the m-RNA having a
nucleotide sequence complementary to that of uncoiled DNA strand is
assembled. For example, for DNA strand with sequence A-T-G-C-T-A-C, the
complementary m-RNA assembly is U-A-C-G-A-U-G.
The sequence of three heterocyclic bases in m-RNA is known as codon and each
codon specifies the amino acids to be used in protein synthesis. For example, the
codons for glycine are GGG, GGA, GGC, and GGU.
Translation. It is the process by which the nucleotide sequences in m-RNA
(formed by transcription) are identified by t-RNA and accordingly the order of
amino acid in the protein being synthesized is determined. For each amino acid,
there is at least one specific t-RNA. The t-RNA serves as an amino acid carrier
as the well as the interpreter of genetic code.
Chapter29
Drugs and Pesticides
A. DRUGS
29A.1 Introduction
Drug is defined as any substance or product that is used or is intended to be
used, to modify or explore physiological systems or pathological states, for the
benefit of the recepient. In medicine, drugs are used for diagnosis, prevention,
treatment/cure of diseases. The origin of word drug can be traced to the French
word drogue which means a dry herb. The treatment of infections (or diseases)
with specific drugs that destroy the harmful organisms with minimal or no toxic
effects on the cells of the host is known as chemotherapy. Drugs are mainly
classified on the basis of their action and it is difficult and rather meaningless to
include all the classifications in this book. Here, we discuss only those categories
which are general in nature and are of common concern.
Analgesics
A drug that selectively relieves pain by acting on the central nervous system
(CNS) and on peripheral (external) pain mechanisms without significantly
altering consciousness is referred to as an analgesic. For example, aspirin,
ibuprofen, phenylbutazone, and morphine (a drug obtained from opium).
Remarks: Analgesics relieve pain only as a symptom, without treating its cause.
Antipyretics
A drug, which reduces body temperature in fever but does not lower the normal
body temperature is called an antipyretic. Examples of antipyretics are
paracetamol and aspirin.
Antibiotics
These are the substances produced by microorganisms which suppress the
growth of or kill other microorganisms. For example, penicillin,
chloramphenicol, and tetracycline. The first antibiotic was discovered by
Alexander Fleming in 1929, which was procured from penicillium mould, and he
named the substance as penicillin.
Other categories of drugs include antimalarials (for cure and prevention of
malaria such as chloroquine), antihistamines (as antiallergics), hypnotics (for
inducing and maintaining sleep such as diazepam), sedatives (to reduce
excitement without inducing sleep, though drowsiness is caused. Examples,
derivatives of barbiturates), tranquilizers (to reduce mental tension, for example,
reserpine—an alkaloid). Derivatives of barbiturates are also used as hypnotics
and tranquilizers.
The action of the drugs on bacteria may be (a) bacteriostatic, that is, inhibiting
the growth of bacteria without killing them. Chloramphenicol and sulfonamides
are two of the bacteriostatic drugs; (b) bacteriocidal, that is, inhibiting the
growth of bacteria by killing them. For example, penicillin and streptomycin.
Some primarily static drugs may become cidal at higher concentrations such as
sulfonamides. On the other hand, some cidals may only be static under certain
circumstances. For example, streptomycin.
Effects of drugs
Drugs can affect the functioning of the body through side effects, secondary
effects, and toxic effects.
Side effects. These effects are unwanted but often unavoidable that occur at
therapeutic doses (means prescribed doses). For example, some of the anti-
allergic drugs may produce sedation (drowsiness).
Secondary effects. These effects are indirect consequences of a primary action
of the drug. For example, antibiotics kill the friendly bacteria along with harmful
bacteria.
Toxic effects. These effects are the result of excessive pharmacological action of
the drug due to over dosage or prolonged use. For example, over dosage of
paracetamol causes liver damage.
(2) Phenacetin
Chemically, phenacetin is 4-ethoxyacetanilide. It can be synthesized from p-
nitrophenol using two routes discussed as follows:
(a) In the first method, p-nitrophenol is converted into p-aminophenol, which
on acetylation with acetic anhydride yields p-hydroxyacetanilide
(paracetamol). It is then converted into sodium salt, which on reaction with
bromoethane results in the formation of phenacetin.
(b) In the second method, p-nitrophenol is converted into ethyl ether by
treating with sodium ethoxide and iodoethane (or bromoethane), which
results in the formation of p-ethoxynitrobenzene. Reduction of p-
ethoxynitrobenzene yields p-phenetidine, whose acetylation results in the
formation of phenacetin.
(4) Phenylbutazone
Chemically, phenylbutazone is 4-butyl-1,2-diphenylpyrazolidine-3,5-dione. It is
synthesized by the condensation of diethyl butylmalonate and hydrazobenzene in
the presence of sodium ethoxide.
(2) Sulfaguanidine
In the synthesis of sulfaguanidine, first two steps are the same as in the synthesis
of sulfanilamide. This means that up to the formation of p-
acetamidobenzenesulfonyl chloride the reaction process is the same. Thereafter
the reaction of guanidine and p-acetamidobenzenesulfonyl chloride followed by
acid hydrolysis results in the formation of sulfaguanidine. The reactions
involved in the process are as follows:
(3) Sulfadiazine
Chemically, this drug is 2-(4-aminobenzenesufonamido)pyrimidine. It is
synthesized by the condensation of 2-aminopyrimidine with p-
acetamidobenzenesulfonyl chloride. Synthesis of 2-aminopyrimidine is carried
out by the reaction of guanidine with ethyl 3-oxopropanoate (ethyl ester of
formyl acetic acid). The reactions are as follows:
(i) Synthesis of 2-aminopyrimidine
Histamine dilates the blood vessels, contracts smooth muscles, increases gastric
secretion besides behaving as a neurotransmitter.
The drugs that competitively neutralize or oppose (antagonize) the action of
histamine at the receptor site are known as antihistamines. For example,
diphenhydramine (benadryl), promethazine (phenergan), cetrizine, etc. The
structure of benadryl is as follows:
NOTABILIA 19
Besides the drugs discussed so far, the alkaloids and steroids are another class
of compounds which are of immense medicinal use. The physiological
importance of some alkaloids and steroids is discussed in ‘Mini Essay III’
subsequently.
B. PESTICIDES
29B.1 INTRODUCTION
Agrochemicals can be broadly defined as the class of chemicals, which are used
to increase the yield of the crops. This class includes fertilizers and pesticides.
Fertilizers increase the crop yield by supplying the nutrients and pesticides
protect the crop.
Pesticide is the broader term used for the chemicals, which are used to combat
the attack of various pests to the crops. The application of pesticides can be
further broadened and is not just restricted to the crops but also includes the
chemicals used to eradicate the community pests such as cockroaches,
mosquitoes, rats, flies, and so on. Pesticides can be classified into three major
classes—insecticides, fungicides, and herbicides (or weedicides). Besides this,
there are also acaricides (to kill mites), molluscicides (to kill snails),
nematocides (to kill microscopic worms), and rodenticides (to kill vertebrate
pests such as rats).
Further on, pesticides may be categorized under the classes—contact, systemic
(or stomach), and fumigants. Contact pesticides are those, which kill insects
primarily by contact. For example DDT, HCH, Pyrethrum, and so on. Systemic
pesticides kill the pests by entering into their biological system. Parathion is one
such pesticide. Fumigants are easily vaporizable chemicals with insecticidal
properties that easily spread over a large area when used. For example, methyl
bromide (boiling point 4.5° C) is used for fumigation of grains, fruits, and
vegetables.
In the present chapter, we will discuss the synthesis of some selected
insecticides, herbicides, and fungicides.
29B.2 INSECTICIDES
Insecticides are defined as the chemicals, which are used to destroy the insects.
The chemical class of insecticides mainly includes organochlorine,
organophosphorous and carbamate compounds.
On the other hand, commercial DDT is a mixture of various isomers along with
the desired one. For example, ~80% of para isomer along with ~20% ortho-para
isomer and some impurities (due to intial reactants) Purified DDT is a white
crystalline solid having a melting point 108°C.
Uses of thiram. It is used for the protection of lettuce and strawberry. It is also
used to prevent seeds (by seed dressing) from soil fungi.
5. How does the side effect of drug differ from its toxic effect?
6. What are sulfa drugs? What is their general mode of action?
7. Carry out the following syntheses:
(a) Sulfaguanidine from aniline
(b) Chloroquine from Novaldiamine
(c) Chloroamphenicol from benzaldehyde and nitroethanol
(d) Phenacetin from p-ethoxynitrobenzene
(e) Phenylbutazone from diethylmalonate.
8. How many stereoisomers are possible for chloroamphenicol? Write their
structures?
9. How would you differentiate between an antiseptic and a disinfectant?
10. Giving suitable explanation, differentiate among following terms:
(a) Toxic effect of drugs
(b) Secondary effect of drugs
(c) Side effect of drug
11. Penicillins are β-lactam ring containing compounds. Give general structure
of penicillins and indicate the β-lactam portion of the structure by encircling
it.
12. To what class of drugs do the following compounds belong?
(a) Aspirin
(b) Barbiturates
(c) Chloroquine
(d) Reserpine
(e) Paracetamol
(f) Phenylbutazone
(g) Sulfadiazine
(h) Penicillin
PESTICIDES
1. What are pesticides?
2. Define the following terms:
(a) Contact pesticides
(b) Systemic pesticides
(c) Fumigants
3. What are insecticides and how are they categorized into different chemical
classes?
4. Give the synthesis of DDT and methoxychlor. Why is methoxychlor a
preferred choice over DDT?
5. How many stereoisomers are possible for HCH? Which isomer of HCH
exhibits insecticidal properties?
6. How is HCH (formally BHC) synthesized?
7. Write the conformation of gammexane (i.e. Lindane).
8. To which class of chemical compounds do malathion and parathion belong?
Give their structures and uses.
9. Name one natural insecticide and its source. Discuss its insecticidal
properties.
10. Give an example (along with its structure) of an insecticide that belongs to
carbamate class of compounds.
11. What are herbicides and fungicides? Explain giving one example of each.
12. What are toxic effects of pesticides?
13. Name the class of pesticides to which the following compounds belong:
(a) HCH
(b) Cypermethrin
(c) 2,4-D
(d) Allethrin
(e) Thiram
(f) DDT
(g) Malathion
(h) Methylbromide
MINI
ESSAY III
ALKALOIDS TERPENES, AND STEROIDS
A. ALKALOIDS
Alkaloids are naturally occurring nitrogen compounds that are generally
obtained from plants. These naturally occurring amines exhibit basicity and for
this reason, they are termed alkaloids which means ‘alkali like’. The main
structural feature of alkaloids is that they contain one or more nitrogen
heterocyclic ring. The alkaloids have marked physiological impact in living
organisms. A majority of alkaloids are excellent pharmaceutical agents and are
widely used as medicine since ancient times.
The alkaloids are extracted from dry plant material by boiling in methanol
followed by acidification and extraction from ether. The addition of base to this
extracted acidic solution results in crystallization of alkaloids. The water soluble
alkaloids are extracted from a suitable solvent. The alkaloids are then purified
and their structure is determined from their synthesis.
Classification: Alkaloids are broadly classified on the basis of their structural
features, as derivatives of phenyl alkyl amine, pyrrolidine, piperidine pyridine,
quinoline, isoquinoline, condensed heterocyclic systems, and so on.
Without delving into the details of such vast field of naturally occurring
compounds, we list (Table 1) some selected and well-known alkaloids and their
physiological importance. There after follow the structures of these compounds.
B. TERPENES
The fragrance of rose, jasmine, lilies, lavender, camphor, sandalwood, and the
like and the flavour of orange, lemon, peppermint, cloves and so on, are ones we
all are well familiar with. The volatile compounds responsible for such flavours
and fragrances are associated with certain parts of the plants (flower, leaves,
fruits, and so on) and are known as terpenes. Terpenes are also the major
constituents of the essential oils, which are the oils distilled from plants and are
generally associated with such fragrance/flavour.
The term ‘terpene’ has originated from one of the constituents (isomeric
C10H16) of turpentine. Terpenes were initially defined as compounds containing
isoprene unit (2-methylbuta-1,3-diene). In a terpene, more than two isoprene
units may be present and for this reason they are also termed as isoprenoids.
Terpenoid is another more appropriate term used for these compounds in wider
sense and includes open chain or cyclic compounds having C5 skeleton units
(isoprene units). These may contain oxygen containing functional groups such as
–OH, C=O and so forth. Thus, the term terpenoids includes a wide range of
natural compounds from terpenes to steroids. Terpenes generally occur in plants,
however, some of the higher terpenes occur in animals too, for example,
lanosterol, and β-carotene.
Isoprene Rule
The relation of terpenes to isoprene (molecular formula C5H8) characterizes all
the members of this very large group of molecules. The isoprene rule initially
postulated by Wallach states that in terpenes a number of isoprene units are
joined together. Later on, Ingold suggested that these isoprene units are joined in
head–tail arrangement. Now instead of head–tail linkage, the term used is 1-4
linkage. In other words, C1 of one isoprene unit (head) is joined to C4 of another
isoprene unit (tail).
Limitations of isoprene rule. In some cases, the isoprene rule is not followed.
For example, in carotenes there is tail–tail linkage of isoprene units.
In accordance with the number of isoprene units in a compound, the terpenes are
classified into some categories, each one of which may contain open chain or
cyclic compounds. The classes of terpenes are summarized in Table 2.
Monoterpenes
Monoterpenoids have ten-carbon atom skeleton and are the simplest terpenes.
These are dimers of isoprene. The monoterpenes are further sub-classified as (a)
acyclic monoterpenes, (b) monocylic monoterpenes, and (c) bicylclic
monoterpenes. A few selected examples of monoterpenes along with sources and
linkages between them are given in Fig. 1.
Fig. 1 Some examples of common monoterpenes (along with their source) and type of linkages of two
isorene units.
Sesquiterpenes
Sesquiterpenes have three isoprene units and have fifteen carbon atoms in their
skeleton. The sesquiterpenes may have acyclic, monocyclic, bicyclic, and
several other structures. A few of the representative sesquiterpenes along with
the linkages of isoprene units are shown in Fig. 2.
Fig. 2 Representative examples of sesquiterpenes (along with their common source) and linkages of three
isoprene units in their structure.
• The terpenes and steroids resemble in their molecular make up. Surprisingly,
in their biosyntheses isoprene is not the biological precursor.
The biosynthesis of steriods involves isopentylpyrophosphate and
dimethylallylpyrophosphate as precursors. In presence of enzymes, the repetitive
combinations of these units results in the formation of mono-, sesqui-, di-,
triterpenes and so on. Squalene (C30H50) acts as a precursor for steroids. It
undergoes cyclization to form lanosterol which through enzymatic reaction is
converted to cholesterol. The steroids are classified into five major categories:
1. Sterols: These steroids are characterized by the presence of an alcoholic
group and are found in plant oils and animal fat, for example cholesterol.
2. Sex hormones: Unlike hormones sex hormones are not secreted by ductless
gland. But are produced in gonads (testes of male and ovaries of female).
These are termed as steroidal hormones and are classified in these major
categories:
(a) Androgens: Male hormones e.g. testosterone
(b) Oestrogens: Female hormone e.g. oestrone
(c) Gestogens: Corpus Luteum hormone e.g. progesterone
3. Cardiac glycoside: These steroids are extracted from plants and are used
for cardiac therapy, for example, digitoxigenin.
4. Bile acids: These are the organic compounds present in bile. The bile is a
liquid secreted by liver and is stored in gall bladder and is essential for
digestion.
5. Sapogenins: These are present in the plant glycosides and their colloidal
solution in water form foam similar to soap (Latin sapo means soap). Their
solutions are highly toxic as they destroy the red blook cells.
The structures of some commonly found steroids are:
Chapter30
Dyes
30.1 INTRODUCTION
Dyes are organic compounds, which impart colour to the fibre. It not only
adheres to the surface of the fibre but also penetrates deep into it. For it to be a
good dye, the colour of a dye should be resistant towards heat, light, moisture,
dilute acids, washing soaps, and so on. A dye that permanently fixes on the
surface of the fibre is known as a fast dye where as a dye that fades out, or is
washed off is known as a fugitive dye.
There is no definite procedure for the nomenclature of dyes and these are
commonly known by their commercial names, as given by the manufacturer.
This is the disadvantage since the same dye may have different names. Thus,
‘Society of Dyes and Colourists’ has proposed a colour index and each dye is
given a colour index number (abbreviated as C.I.No.).
(vi) Azo dyes (or ingrain or developed). These are applied directly on the fibre.
The process includes the diazotization and the coupling reaction at low
temperature on the fibre itself.
(vii) Sulfur dyes. These are complex water insoluble dyes containing sulfur. But
these dyes are soluble in sodium sulfide (Na2S) solution and thus the dyeing
process is carried out in Na2S solution. These dyes are generally used for dyeing
cotton fibre.
Chemical structure of dyes
Due to the variation in the structures of dyes, no distinct classification can be
given but roughly their classification can be given depending on their chemical
constitution. Some selected chemical classes of dyes are listed here as follows:
(i) Azo dyes (v) Anthraquinone dyes
(ii) Diphenylmethane dyes (vi) Indigoid dyes
(iii) Triphenylmethane dyes (vii) Phthalocyanine dyes
(iv) Phthalein dyes (viii) Nitro and nitroso dyes
30.2 COLOUR AND STRUCTURE
An organic compound appears coloured only if it absorbs the radiations in the
visible part of the electromagnetic spectrum. The visible region extends from
400–800 nm. The white light in the visible region consists of seven colours,
namely Violet, Indigo, Blue, Green, Yellow, Orange, and Red (VIBGYOR).
When the white light falls on an object, it may be:
(1) totally reflected back, and in such a case the object appears white.
(2) totally absorbed, and in such case the object appears black.
(3) a part of light is absorbed and the rest is reflected back, and in such case,
the object appears coloured.
Now consider case (3). The colour of the object depends upon the waevlength of
the light reflected back (that is, not absorbed). For example, a substance appears
red if it absorbs all the light waves except that with wavelength λ = 700 nm, that
is, it reflects the light which appears red to eyes.
However, if the substance absorbs light of a particular wavelength, our eyes
perceive the complementary colour. For each colour in the visible region there is
a complementary colour. For example, a substance that absorbs light of
wavelength 700 nm basically absorbs the red colour from white light and reflects
the rest. Thus, it appears blue-green. For this reason, we consider colours blue-
green and red to be complementary.
The colours and complementary colours perceived by eyes for the wavelength of
light reflected or absorbed by the substance have been summarized in Table
30.1.
The different theories that have been proposed for correlation of colour and
structure of organic compounds are as follows:
Auxochromes. These groups are not responsible for colour but when present
along with chromophore groups are responsible for deepening of the colour.
These are electron-donating groups. Some examples of auxochrome groups are:
It is used for direct dyeing of silk, wool, leather, and acetate rayon fibres. It can
also be used for dyeing cotton after mordanting it with tannins.
(2) Rosaniline [mode of application: basic dye]
[Other names: Fuschine, Magenta]
Rosaniline is synthesized by the condensation of an equimolar mixture of
aniline, o-methylaniline (o-toluidine), and p-methylaniline (p-toluidine) in the
presence of an oxidizing agent (nitrobenzene in presence of iron). This results in
the formation of leuco base, which on oxidation with lead oxide (PbO2) in acidic
medium gives a colour base. The colour base on treating with excess of HCl
gives rosaniline as dye salt [I].
It is a white solid, which in alkaline solution gives red colour and is colourless in
acidic solution. In alkaline medium, it exists as a disodium salt, which exhibits a
quinonoid structure that undergoes resonance in the manner as shown:
In strong alkaline solution, the red colour of the dye disappears due to formation
of a trisodium salt (loss of the quinonoid structure) that cannot undergo
resonance. Phenolphthalein is used as an indicator in acid–base titrations.
(2) Fluorescein [mode of application: acid dye]
Fluorescein is synthesized by condensation of phthalic anhydride with resorcinol
in the presence of concentrated sulfuric acid as:
Alizarin exists as yellow flakes and in aqueous alkali gives violet colour. It is a
mordant dye and in presence of different metallic mordants, it produces different
colours. Table 30.2 gives the list of various colours imparted by alizarin in
presence of different mordants.
Following figure shows the interaction of alizarin with a fibre in the presence of
a mordant.
The alizarin with aluminium and iron mordants is used for dyeing and printing
cotton while with aluminium and chromium mordants, it is used for dyeing
wool.
31.1 INTRODUCTION
A polymer (Greek poly means many, and meros means parts) is defined as a
large molecule of high molecular weight formed by combination of a number of
one or more types of molecules of low molecular weight. Being molecules of
high molecular weight, they are also known as macromolecules. The smaller
molecules, which occur as repeating units to make up a polymer, are known as
monomers.
In other words, a polymer may be defined as a number of repeating chemical
units (monomers) held together by covalent bonds. The process by which
monomers combine to form a polymer is known as polymerization. The extent to
which the number of monomer units combines to form a polymer is known as
degree of polymerization and is represented by ratio of the average molecular
weight of polymer to molecular weight of the monomer.
31.2 CLASSIFICATION OF POLYMERS
Polymers are classified in a number of ways depending upon their source,
structure, physical properties, and type of polymerization reaction. These are:
(1) On the basis of source. On the basis of source, the polymers are classified
as:
(a) Natural polymers. These polymers are obtained from natural resources.
For example, proteins, cellulose, starch, rubber, and so on.
(b) Synthetic polymers. These polymers are synthesized by chemical
reactions. For example, polyethylene, teflon, nylon, and so on.
(2) On the basis of structure. The structure of a polymer depends upon (i) the
composition of basic polymer unit and (ii) the arrangement of the polymer
chains. Polymers can be classified as follows under these categories:
[i] Based on the composition of basic polymer unit, polymers are classified as
(a) Homopolymers. These polymers are made from only one type of
monomer unit. For example, polyethylene is synthesized by the
polymerization of a single monomer, namely ethylene (IUPAC name—
ethene).
(b) Copolymers. These polymers comprise two or more monomers. An
example is synthetic rubber, which is a copolymer of two monomers—
styrene and 1,3-butadiene.
[ii] Based on the arrangement of the polymer chains, polymers can be
classified as:
(a) Linear polymers. These are also known as one-dimensional polymers where
monomer units are held together in a long chain without any lateral
linkage or branching.
(b) Cross-linked polymers. In these polymers, different linear chains of
monomer units are cross-linked with each other through covalent bonds.
They may be further categorized into
• Sheet polymers. These are also known as two-dimensional polymers
where linear chains of monomer units are joined with each other in such
a manner that the length of the chain is more than its width.
• Three-dimensional polymers. In these, the linear chains are cross-linked
to form a huge network, which results in the formation of a thick
polymer product, for example, bakelite.
The schematic diagrams for classification of polymers based on composition and
arrangement of polymer chains are depicted in Figs. 31.1 and 31.2 respectively.
Fig. 31.1 Schematic diagrams of (a) homopolymer; (b) Branched polymer, (c) cross-linked polymer; and
(d) copolymer (P and Q indicate different monomer units).
Fig. 31.2 Schematic diagrams of (a) linear polymer; (b) sheet polymer and (c) three-dimensional polymer.
31.3 PHYSICAL PROPERTIES AND
CLASSIFICATION
Polymers may be classified on the basis of their properties as crystalline and
amorphous polymers.
Crystalline polymers. Due to the arrangement of polymer chains in a linear
regular pattern, the polymer exists as a crystalline solid. The crystalline
polymers being hard can be drawn into fibres.
Amorphous polymers. In Amorphous polymers, there is an irregular
arrangement of polymer chains (coiled or random) and they exist as amorphous
solids. Amorphous solids may exhibit elasticity and such polymers are known as
elastomers, for example, rubber. The amorphous solids, which do not exhibit
elasticity, are termed as plastics.
Depending upon the structure of a polymer and its behaviour at different
temperatures, the polymers may be classified as thermoplastics and
thermosetting plastics.
Thermoplastics. These polymers soften on heating and can be moulded into
different shapes. They become hard on cooling and regain their physical
properties. The process of heating and cooling can be repeated a number of times
without causing any change in their physical properties. For example
polyethylene, polyvinyl chloride (PVC), and nylon.
Thermosetting plastics. These polymers can be moulded into different shapes
by heating and they become hard when heated. The heat treatment is given only
during the preparation of various articles from these polymers. Once solidified
and set, they cannot be softened or remoulded on heating. Bakelite and
melamine are two such thermosetting plastics.
31.3.1 Stereochemistry of Polymers
In the formation of a polymer, there may be generation of stereocentres (chiral
centres) depending upon the structure of monomer units. In general,
monosubstituted vinyl compounds on polymerization result in the formation of a
polymer where alternate carbons in the chain are chiral in nature. The
arrangement of atoms or groups at these stereocentres affects the physical
properties of polymers. Depending upon the configuration at stereocentres, the
polymers can be classified as atactic, syndiotactic and isotactic.
(a) Isotactic polymer. In these polymers, all the stereocentres in the chain have
same configuration. This regular arrangement results in the formation of an
extremely fine quality polymer.
(b) Syndiotactic polymer. In these polymers, the configuration of stereocentre
alternates, for example, R, S, R, S... This orderly arrangement results in the
production of a good quality polymer.
(c) Atactic polymer. In these polymers, the stereocentres have a random
configuration. This disorderly arrangement results in a very poor quality
polymer.
While isotactic and syndiotactic polymers are generated through Ziegler–Natta
polymerization, atactic polymers are produced in the presence of peroxides. As
an example, the stereoisomeric forms of polypropylene are illustrated in Fig.
31.3.
Fig. 31.3 Stereoisomeric forms of polypropylene.
31.4 POLYMERIZATION REACTIONS
(1) Addition polymerization. Addition polymerization occurs in monomer units
having double or triple bonds. It involves the combination of a large number of
monomer units by addition reaction. In general, compounds containing
(Z is substituent) undergo addition polymerization which is popularly known as
vinyl polymerization as shown in Table 31.2). This polymerization is also known
as chain growth polymerization. The monomer units may be joined in a head–
tail arrangement, or a head–head and tail–tail arrangement, or it may be a
random arrangement. The most favourable arrangement is head–tail
arrangement.
Mechanism. The catalyst has a complex structure. The alkyl titanium bond
undergoes insertion of monomer units. The π-electrons of monomer are
coordinated to a vacant site on metal (This being the reason that it is known as
coordination polymerization). The coordinated monomer then inserts into
titanium–carbon bond and the process goes on to form a polymer. Since titanium
is attached to different ligands, the coordination of monomer units follow a
stereoregular pattern. The various steps of reaction mechanism are given
schematically in Fig. 31.4, as follows:
Fig. 31.4 Ziegler–Natta polymerization: schematic and simplified representation of (a) formation of
polyethylene (b) polypropylene formation (further simplified); (c) mechanism for the formation of
polyethylene.
Some of the vinyl polymers, along with their monomer units and common uses
are listed in
Synthesis of monomers of some vinyl polymers
1. Polyvinyl chloride (PVC). Vinyl chloride is a monomer of polyvinyl chloride
and is synthesized industrially from ethene or acetylene as follows:
3. Polyesters
(i) Dacron [terylene]. Dacron, a copolymer, is prepared by the condensation of
methyl ester of terphthalic acid with ethylene glycol. The condensation involves
loss of a methanol molecule, which results in the formation of a number of ester
linkages (polyester).
This polyester can be fabricated into a strong film, which is known by the name
Mylar. It is a light weight, high strength, transparent film, which is used for
protection of artwork and important documents.
(ii) Polycarbonates. These are polyesters formed by condensation of derivatives
of phenol and carbonic acid. For example, condensation of bis-phenol A with
phosgene results in the formation of a polycarbonate, known by the name of
lexan. The reaction takes place as follows:
4. Polyurethanes. The reaction of an isocyanate and alcohol results in the
formation of a carbamate, which is known as urethane.
General reaction
Polyurethanes are copolymers and are prepared by the reaction of alkyl or aryl
diisocyanates with diols. In general, the diol used in the preparation is a
copolymer of ethylene glycol and adipic acid, which has free hydroxy (–OH)
end groups. The commonly used diisocyanate is toluene-2,4-diisocyanate
The polymerization in the presence of water results in the
formation of polyurethane foam. Water reacts with the isocyanate
group to produce carbamic acid, which spontaneously looses carbon
dioxide. The carbon dioxide thus generates bubbles (giving porosity to
polymer) to yield polyurethane foam. The density of foam is
dependent on the amount of carbon dioxide evolved during the
process.
Some condensation polymers along with their monomer units and common uses
are listed in
Table 31.3.
31.5 RUBBERS
Natural rubber is a soft and sticky solid and is often associated with a peculiar
smell. It has low elasticity and low tensile strength. It softens in hot weather and
gets hardened in cold weather. It is soluble in organic solvents such as carbon
disulfide, petrol, ether, and so on. The properties of natural rubber are improved
by introducing cross linkages in polymer chains by heating rubber with sulfur.
This process is known as vulcanization. A polymer of isoprene (from natural
sources) that has trans-configuration at the double bonds is known as Gutta-
Percha.
32.1 INTRODUCTION
Throughout this textbook, the chemistry of various functional groups of organic
compounds has been discussed. In every reaction, one functional group is
transformed into another. The reactions are the indication of the chemical nature
of functional groups and sometimes the characteristic chemical tests are
employed for the confirmation of the structural features of organic compounds.
But it is a difficult and cumbersome task to identify the structure of organic
compounds through these chemical reactions or tests alone. This problem of
identification of the structure of organic compounds aggravates in case of
isomeric compounds or when compounds are virtually unknown.
The identification of compounds through chemical reaction may include the
following steps:
(1) Purification
(2) Detection of elements
(3) Estimation of elements
(4) Calculation of empirical formula
(5) Molecular formula
(6) Assigning of structure, which involves (a) functional group determination;
(b) degradation (mainly for unknown compounds) to simple compounds
and their characterization, through which structure is established; and (c)
confirmation of structure by synthesis.
These are the conventional methods for the determination of the structure of
organic compounds. A substantial amount of pure compound is required for
carrying out the analysis, and practically compounds are not recovered as all
methods are destructive in nature.
The purpose of this chapter is to show how information about the presence or
absence of a particular functional group or arrangement of groups and atoms in a
skeleton of an organic molecule, can be obtained using spectroscopy.
The spectral methods have the four major advantages over most of chemical
tests:
(1) Spectral analyses are easier and take very little time.
(2) Spectral analyses require very small quantity of compound (~1 mg or less).
(3) Spectral analyses generally provide more detailed and reliable information
about molecular structure, which makes the task of determining the
structure easy and less time consuming.
(4) Spectral analyses are nondestructive (that is, have no effect on the sample)
and the sample can be recovered, if required.
All organic compounds interact with electromagnetic radiations, that is, they
absorb energy. Spectroscopy is a technique based on the absorption of radiations
by molecules. Different molecules absorb different amounts of radiations and
this difference in absorption is used for the analysis and identification of
molecules. In the present chapter, we briefly introduce the three important
spectroscopic techniques, namely (i) Ultraviolet–visible spectroscopy, (ii)
infrared spectroscopy, and (iii) nuclear magnetic resonance.
In discussing any type of spectroscopy, it is necessary to have an idea of some
facts about the interaction of all types of electromagnetic radiation with
molecules.
Electromagnetic radiations
The various types of electromagnetic radiation or light (ultraviolet light, visible
light, infrared, microwaves, X-rays, radio waves, and so on) can be described in
one simple way, by assuming that electromagnetic radiations have a dual
character (of a wave as well as that of a particle). The light consists of small
packets of energy called photons and the energy of a mole of photon, is related
to the frequency of light by equation:
E = hν
Since frequency and wavelength are inversely proportional and are related by ν =
c/λ,
Thus,
The other important unit frequently used in spectroscopy is wave number ,
that is, the number of wave cycles per centimetre, which is the reciprocal of
wavelength and is expressed in cm–1.
The infrared absorption frequencies are generally reported in wave numbers. The
energy of light wave is directly related to its frequency. This means that higher
the frequency of radiation, higher is its energy. A summarized data of
wavelengths, frequencies, and energies of electromagnetic spectra is as follows:
The Woodward–Fieser rules, for calculating λmax for conjugated dienes, are
summarized in
Table 32.1.
Few examples of conjugated dienes, implementing Woodward–Fieser rules, for
the calculation of λmax, are given below:
2. α, β-unsaturated carbonyl compounds
The Woodward-Fieser rules, for calculating λmax for α, β-unsaturated carbonyl
compounds, are summarized in Table 32.2.
The Woodward–Fieser rules, for calculating λmax for aromatic compounds, are
summarized in Table 32.3.
Few examples of Aromatic compounds, implementing Woodward-Fieser rules,
for the calculation of λmax, are given below:
Further it has been noted that steric hindrance also has an impact on λmax value.
For example, cis-stilbene has lower λmax value than trans-stilbene. The π – π*
transition requires higher energy in cis-form compared to that in trans-form. The
steric hindrance of aromatic hydrogens in cis-stilbene prevents the coplanarity of
the molecule and disturbs the delocalization of π-electrons.
32.3 INFRARED SPECTROSCOPY
The detection of the type of bonds and functional groups present in a molecule is
carried out easily with the help of infrared or IR spectroscopy. It deals with the
region of electromagnetic spectrum that lies in the frequency range 500–6670
cm–1. For organic chemists, the important region of IR spectroscopy is 700–
5000 cm–1. The infrared frequency is expressed in units of wave number. A
molecule of a compound is made up of large number of atoms, which
continuously undergo vibration and rotation. The exposure of the compound to
IR radiations results in an increase in the already existing vibrations and
rotations. A very little energy (2–12 kcal/mol) is required to bring about such
vibrational excitations. A particular vibration absorbs
IR radiations of particular frequency and this absorption occurs only when there
is a change in the dipole moment. The vibrations can be of two types, namely (i)
bond stretching and
(ii) bond bending. The following figure depicts such vibrations for tetrahedral
carbon:
Fig. 32.2 Different vibrations around tetrahedral carbon: (a) stretching and (b) bending.
Stretching of a bond requires higher energy and thus, absorption occurs at high
frequency region (1500–5000 cm–1). The bond stretching vibrations are
generally recorded and are useful for interpretations. For recording the IR
spectra of a compound, the compound is taken in Nujol (liquid paraffin) to make
film or mixed with potassium bromide and used as KBr pallet. Each functional
group shows a characteristic band in this region of band stretching vibrations and
appears in the same range irrespective of the structure of molecule.
For example, the C=O bond shows a stretching band in the range of 1680–1750
cm–1 irrespective of whether this bond is present in an aldehyde, ketone, acid, or
ester molecule. The infrared frequencies of some bonds are listed in Table 32.4.
Table 32.4 Characteristic infrared absorption frequencies for some important covalent bonds of various
structural units of organic molecules and some typical carbonyl stretching frequencies of
different functional groups
The bending of a bond requires less energy and thus, absorption occurs in low
frequency region (700–1500 cm–1), which is known as fingerprint region. The
bands obtained due to bending vibrations are difficult to interpret. The
fingerprint region is used for establishing the identity of two compounds. Each
compound shows unique bands in this region and if two compounds are
identical, they have same bands in fingerprint region.
The stronger bonds generally show absorption in the high frequency region due
to higher energy required for stretching. For example, the absorption band for
N–H bonds in amines appears in the frequency range 3300–3500 cm–1 whereas
the relatively stronger O–H bond shows absorption in 3600–3650 cm–1 (refer
Fig. 32.3). Although the functional groups have a characteristic absorption value,
a shift in the values may be observed due to presence of conjugation or hydrogen
bonding in a molecule. The hydrogen bonding in a molecule causes lengthening
of bonds and thus decreases the stretching frequency. Thus, the hydrogen bonded
–OH group appears at low frequency compared to free –OH groups. The
intermolecular hydrogen bonding is affected by dilution. In dilute solutions, the
hydrogen bonds between the molecules break and thus absorption for O–H
stretching appears at high frequency as in the case of free –OH groups. However,
the intramolecular hydrogen bonding does not break even in dilute solutions.
Fig. 32.3 A comparison of IR absorption frequencies in the region of 3000–3600 cm–1; (a) Hexan-1-ol
(O–H stretching), (b) Butanoic acid (hydrogen bonded O–H stretching) (c) Propan-2-amine (N–H
stretching or 1° amines), besides other characterisitics stretching frequencies are also encircled.
The following illustrative examples explain the use of IR spectroscopy in
identification of functional group(s) present in a compound:
Illustrative Example 1. How will you distinguish between the following pairs
of compounds using IR spectra (for values, refer Table 32.4)
Solution:
(a) In case of ketones, a strong absorption band for C=O appears around
1705–1725 cm–1 but in case of ethers no absorption is observed in this
region. In ethers, C–O– stretching band appears at ~1100 cm–1.
(b) In case of benzoic acid, the –OH of carboxylic group is hydrogen bonded
(exists as dimer; intermolecular hydrogen bonding) and thus the absorption
band for O–H appears at ~3000 cm–1 and the carboxylic acid also shows
the absorption band (for C=O ) around 1700–1725 cm–1. On the other
hand, in case of p-hydroxyacetophenone, the hydroxy group is not hydrogen
bonded and therefore its absorption band appears at ~3500–3700 cm–1.
Another absorption band is observed (for C=O) at 1705–1725 cm–1. Thus,
the absorption values for hydroxy group help in differentiating between the
two compounds.
Illustrative Example 2. How will you distinguish between the following pairs
of compounds using IR spectroscopy (for values, refer Table 32.4)
Solution
(a) An absorption band around 3000 cm–1 appears in case of acetic acid (in
general, carboxylic acids) due to hydrogen bonded –OH stretching. No such
band is possible in case of ethyl acetate (in general, esters).
(b) The 3° and 2° amines can easily be distinguished by IR spectra. The band
around
3300–3500 cm–1 appears for –N–H stretching which is possible only in
case of 2°
amines.
32.4 NUCLEAR MAGNETIC RESONANCE (NMR)
SPECTROSCOPY
Nuclear magnetic resonance (NMR) involves absorption of radiations in the
radio frequency region. This spectroscopy is generally used for the
determination of the type and the number of protons present in a molecule. The
nuclei of certain elements behave like spinning charges, for example, 1H, 13C,
15N, 19F, and 31P. A spinning charge creates a magnetic field and therefore
behaves as a tiny magnet. (Fig. 32.4). The spinning nuclei generate a magnetic
field on exposure to an external magnetic field. If an external magnetic field is
applied, spinning nuclei can get oriented in two ways:
(i) The magnetic field due to nuclei is in the same direction as the external
field. In this case, the nuclei are said to be in a low energy spin state.
(ii) The magnetic field due to nuclei is in the opposite direction as the external
magnetic field. In this case, the nuclei are said to be in a high–energy spin
state.
By applying radiation in radio frequency range, the nuclei can be excited from
lower energy spin state to higher energy spin state. The energy required for this
change in spin state (known as flipping) depends on the strength of external
magnetic field. Higher the external magnetic field, higher is the energy (or
frequency) required for excitation. It is a general practice to supply a constant
radio frequency and vary the strength of external magnetic field.
Fig. 32.4 (a) Spining charge develops a magnetic field along the axis of spin and (b) behaves as a tiny
magnet. (c) In presence of applied magnetic field, hydrogen nucleus absorbs electromagnetic
radiations and shows transition from low energy state to high energy state.
Fig. 32.5 Chemical shift with respect to TMS as the reference peak.
For example, if a proton appears 360 Hz downfield from the TMS peak, and the
spectrum is taken at a radio frequency of 60 MHz, the chemical shift δ is given
as:
δ = (position of peak) – (position of TMS/radio frequency)
= 360 – (0.0/60 × 106) = 6.0 ppm
Recording the NMR spectrum. The sample is dissolved in deutrated solvent
like CDCl3 (chloroform-d3), CD3COCD3 (acetone-d6), and (CD3)2SO
(DMSO-d6). As a characteristic, the deutrated solvents do not show any peak in
the spectra and are thus non-interfering in spectral study of the given sample. For
the reference peak (δ = 0), TMS is added to the deutrated solvent. The sample is
then introduced into spectrometer and the NMR spectrum is recorded on a paper
as a plot between intensity of absorption and the chemical shift (δ). A peak or
signal is obtained when nuclei absorb energy.
Interpretation of NMR spectrum
The different peaks obtained in a NMR spectrum need to be considered in terms
of the following observations:
(i) Number of signals. The total number of signals obtained in a spectrum is a
direct indication of the number of different types of protons present in a
molecule. Same types of protons (present in the same environment) are known
as equivalent protons and give only one signal or peak. Non-equivalent protons
(present in different environments) give different signals.
(ii) Position of signals. Protons that are present in different chemical
environments have different δ values. There is a standard chart that predicts the δ
values for representative protons (refer
Table 32.5). Highly shielded protons appear at low δ values (or upfield). The
presence of electron withdrawing groups or atoms on a carbon makes the protons
attached to that carbon less shielded and these protons appear at high δ value (or
downfield). For example, CH3CH2CH2CH3 has two types of protons and shows
two signals in the spectrum—one signal for CH3 protons and the other for CH2
protons. Similarly, CH3CH2CH2Cl has different types of protons and shows
three signals—one signal for CH3 protons, one for CH2, and one for CH2
(attached to Cl) protons.
Table 32.5 Chemical shifts (approximate values) of representative types of protons relative to TMS
(iii) Intensity of signals. The intensity of a signal gives an idea of the relative
number of equivalent protons that are responsible for the signal. The intensity of
a signal is measured electronically and in a spectrum, it appears as a stepped
curve over each signal.
(iv) Splitting of peak (spin–spin coupling). The signals in an NMR spectrum
may appear as
singlets (a single peak), abbreviated as ‘s’
doublets (signal split into two peaks), abbreviated as ‘d’
triplets (signal split into three peaks), abbreviated as ‘t’
quartets (signal split into four peaks), abbreviated as ‘q’, and so on.
This multiplicity (splitting) of a signal arises due to the presence of non-
equivalent neighbouring, protons. In general, the signal for a proton on a
carbon splits into (n + 1) number of peaks where n is the number of protons
present on the adjacent carbon(s). The equivalent protons have same δ
value and do not cause splitting of each other’s signal.
The multiplicity of a signal basically arises due to spin–spin coupling. For
example, signals for protons Ha and Hb present on adjacent carbons appear each
as a doublet in the NMR spectrum.
As discussed earlier, a proton behaves as a magnet and has two spin orientations.
In the presence of an external field, a proton may exist either in a low or high
energy spin state. Thus, Ha proton appears both in low energy spin state and in
high energy spin state. The same is true for Hb proton.
(a) Proton (Ha) can have its spin opposite to Hb and thus Ha decreases the net
magnetic field experienced by Hb. The signal for Hb appears at high
magnetic field strength (upfield, low δ value).
(b) Proton Ha can have its spin aligned with Hb and in this case, Ha increases
the net magnetic field experienced by Hb. The signal for Hb appears at low
magnetic field strength (downfield, high δ value).
(c) As a result, the Hb observes resonance twice and its signal appears as a
doublet (split into two). In a similar manner, Ha also splits into two signals.
Figure 32.6 illustrates the NMR spectra of some compounds.
This phenomenon is known as spin–spin coupling. The distance (in Hz) between
the individual peaks in a doublet is known as coupling constant (J). The value of
coupling constant remains same even if there is a change in strength of external
magnetic field. Spin–spin coupling can occur between hydrogens present on
adjacent carbons (vicinal coupling) or between hydrogens present on the same
carbon (geminal coupling).
The following illustrative examples explain the application of NMR
spectroscopy in the identification of organic compounds.
Fig. 32.6 NMR (1HNMR or PMR) spectra of (a) 1,1-dichloroethane (b) phenylmethyl ethanoate [or benzyl
acetate] and (c) methyl propanoate. (Integral and splitting patterns are mentioned for 1,1-
dichloroethane.)
Illustrative Example 3. Assign the number of signals (peaks) that will be
observed in the NMR spectra (or PMR) of the following compounds:
Solution
(a) One signal—Because all the hydrogens on methyl groups are chemically
equivalent; (CH3)4C.
(b) Two signals—One signal for the hydrogens on three methyl groups
(chemically equivalent (CH3)3C–) and one for methylene group (–CH2–
Cl) hydrogens.
(c) Three signals—As the hydrogens on each carbon are chemically non-
equivalent
(CH3–CH2–; –CH2–O-; –O–CH3).
(d) One signal—All the hydrogens are chemically equivalent; (CH3)2C=O.
Illustrative Example 4. Give the splitting pattern of the signals for the
hydrogen(s) in the PMR spectra of following compounds:
Solution
(i) a = singlet; b = quartet (splitting due to three adjacent hydrogens on methyl
group ‘c’); c = triplet (splitting due to two neighbouring protons of ‘b’).
(ii) a = triplet (splitting due to two protons of ‘b’); b = quartet (splitting due to
three protons of ‘a’); c = singlet (the proton on oxygen i.e. hydroxy group is
a labile proton and does not affect the splitting pattern of ‘b’).
(iii) a = triplet ; b = quartet; c = singlet
(iv) a = singlet ; b = doublet; c = sextet (actually said to be multiplet due to
complexity of signal); e and f = both are in the same chemical environment
and give single peak as doublet.
Illustrative Example 5. Give the splitting pattern of the signal(s) for the
hydrogen(s) in the PMR spectra of the following:
Solution
(i) The signal for benzene appears as a singlet.
(ii) Two signals are observed—one signal for three hydrogens of the methyl
group (as singlet) and one for five hydrogens of the aromatic ring (a broad
peak appears).
(iii) In case of 1,3,5-trimethylbenzene, only two signals (as singlets) appear—
one signal for all the nine hydrogens of three methyl groups and another for
three hydrogens of the aromatic ring.
(iv) In case of 4-methylphenol, the three signals appear as follows:
— one singlet for methyl group.
— one doublet each for two sets of ortho protons.
— the phenolic –OH appears as a broad singlet.
Illustrative Example 6. How will you distinguish between the following pairs
of compounds using PMR spectroscopy. Give the splitting pattern, intensity of
the signal and approximate chemical shift values (δ) refer Table 32.5.
It is a convention to write NMR spectra as for example: (triplet for 3H, CH3) and not as: (triplet for three
hydrogens for CH3 group). Further to add, the more correct way of writing is by using abbreviation. For
splitting patterns (e.g. singlet as ‘s’ doublet as ‘d’, triplet as ‘t’ and so on). But it is more often used in
specialized books.
32.5 MASS SPECTROMETRY—AN
INTRODUCTION
Mass spectrometry is an important physical technique, which is used for
measuring the masses of atoms and molecules with great accuracy. It differs
from the other spectroscopic techniques that have been discussed so far, in the
sense that, it does not involve the absorption of radiation. It is based on the
principle that the charged particles (ion) moving in magnetic field follow curved
paths and in this process heavy ions are deflected the least while light ions are
deflected the most.
In a mass spectrometer, the vapours of organic compounds are bombarded with
beam of high-energy electrons (70 eV) that makes the neutral molecule loose an
electron and converts it to a radical cation known as molecular ion. Some of the
molecular ions in the process break into all types of possible fragments. The
molecular ions of varying mass (m) to charge (e) ratio are generated in the
process.
The molecular ions are then passed through an electric field, which accelerates
their velocity. These high velocity molecular ions are subjected to magnetic field
where they follow a circular or curved path depending on their mass to charge
ratio. A highly sensitive detector then detects the molecular ions. When a
molecular ion reaches the detector, it is automatically recorded on paper as a
line. The height of the line is proportional to the number of ions (abundance)
reaching the detector. The resulting mass spectrum is thus, obtained as a discrete
series of lines with increasing m/e values. The molecular ion peak with greatest
m/e value is called the parent ion and is used to find the relative molecular mass
of the original molecule. As an example the mass spectrum of butane is shown in
Fig. 32.7.
Fig. 32.7 Mass spectrum of butane (schematic representation).
This data makes it clear that the compound is an ester – –O– with a phenyl ring
(C6H5),
a –CH2– group, and a –CH3 group and can have three possible structures (I, II,
and III as shown here). Out of the three structures, the structure III is correct, as
it does not show any splitting pattern
and chemical shift values are in accordance with the given data. (see its NMR
spectrum in
Fig. 32.6b).
Illustrative Example 8. An oxygenated organic compound shows the molecular
ion peak (parent ion) at 72 m/e. Its IR spectrum shows strong absorption at 1070
cm–1 but no absorption is observed at 1600 cm–1. In its NMR spectra, it shows
peaks at δ 1.8 and δ 3.7 each corresponding to a triplet (intensity ratio 1:1).
Identify the structure of the compound.
Solution. The given compound is not an alcohol or carbonyl compound as
evident from its IR absorption patterns. But the absorption at 1070 cm–1
indicates that it could be an ether (see
Table 32.4). The splitting pattern in its NMR spectra indicates that it contains
structural unit
–CH2–CH2–, where both the –CH2– groups are not chemically equivalent (δ1.8
and δ3.7 each). That means one of the –CH2 groups is attached to oxygen.
Further the mass spectrum of the compound reveals that its molecular mass is 72
and since it is an ether, the molecular formula must be C4H8O. This molecular
formula suggests that the compound is a cyclic ether with four carbons, namely
tetrahydrofuran.
EXERCISES
1. Define the term molecular spectroscopy.
2. Give the units in which spectral information is reported for the following:
(a) UV–visible spectroscopy (b) IR spectroscopy (c) NMR spectroscopy
3. What type of molecular transitions occur by the absorption of the following:
(a) Ultraviolet–visible radiations
(b) Infrared radiations
(c) Radiofrequency radiations
4. Arrange the following:
(a) Ultraviolet–visible radiations
(b) Infrared radiations
(c) Radiofrequency radiations
in order of their (i) increasing wavelength, (ii) increasing frequency, and (iii)
increasing energy.
5. How can one distinguish the following pairs of compounds using IR
spectroscopy?
8. Which of the compounds (given in Exercise-7) will show single peak in their
1HNMR spectra?
9. Predict the splitting pattern using n + 1 rule in each set of chemically
equivalent protons in the following molecules:
10. How is 1HNMR spectroscopy helpful in distinguishing between the
following isomers?
11. How many signals will be obtained from the 1HNMR spectra of the
following:
12. What is the principle of mass spectrometry? How is it different from other
spectral techniques?
* Solvent correction (source): “Applications of absorption spectroscopy of organic compounds”–John R.
Dyer,
p. 14 (1991), Prentice-Hall of India Private Limited.
Octa-1,3,5,7-tetraene
Glossary
Fats, 759
Fats and oils, analysis of, 762
Fatty acids, 759
Fehling’s test, 595, 673, 875–878
Fenton’s reagent, 524, 707, 966
Fermentation, 472
Ferrocene, aromaticity in, 302
Fibrous Proteins, 1025
Ficher-Tropsch process, 198
Finger print region, 1123
Finkelstein reaction, 396, 556
Fischer projection, 67–68, 148–150, 155–157
from dashed-wedged-line structure, 69, 154, 155
from Newman and Sawhorse projection, 154–157, 369–371
of carbohydrates, 958, 963, 977–980
Fischer-Speier method, 463
Fischer-Tropsch synthesis, 198
Fittig’s synthesis, 851
Fluorescein, 1081
Fluoroacetic acid, 663
Fluoroalkanes, preparation of, 397, 561
Fluorobenzene, preparation of, 433, 834
Food preservatives, 182
Formal charge, 6
Formaldehyde (see aldehydes),
polymers of, 546, 608, 1101–1103
reactions, 444, 455, 603, 647
synthesis, 192, 574
Formalin, 574, 609
Formic acid,
characteristics, 672–673
industrial preparation, 661
Formylation,
Gatterman reaction, 938
in aromatic system, 624
Vilsmeier–Haack reaction, 938
2-Formylfuran (see furfural)
Free radical addition reactions, 237–239, 263–264
Free radical inhibitors, 182
Free radical substitution reactions,
energy calculation, 184
of alkanes, 179–191, 366, 367
of alkenes, 244–245
proof for, 181
Free radicals, formation, stability and structure of, 124–127, 166
Friedel–Crafts alkylation, 313, 321, 333, 354, 441, 446, 855
alkylating agents in, 335, 390, 391
comparison with Friedel-Crafts acylation,
338
limitations of, 335, 357
Friedel–Crafts acylation, 314, 337, 387, 855, 893
synthetic applications of, 339
Friedlander’s synthesis, 949
Fries rearrangement, 540
-D-Fructofuranose, 986
-D-Fructopyranose, 986
Fructose (levulose), 955, 983
D(-) Fructose,
conversion to D-glucose, 973
cyclic ketal form, 986
cyclic structure, 985
furanose and pyranose form, 986
open chain structure, 983
reactions of, 983–985
sweetness value, 956
Fumaric acid, 696, 698, 699
Fuming nitric acid, 331
Fuming sulfuric acid, 339
Functional groups, 26, 27
Functional isomers, 29, 142
Fungicides, 1055
Furan,
aromaticity, 307, 929
Diels-Alder reaction, 942
electrophilic substitution reactions, 933–938
mercuration, 937
orbital picture, 929
physical properties of, 928
preparations of, 931–933
reaction with diazonium salts, 940
reaction with organometalic compounds, 939
reactivity, 933, 934
reduction reactions, 940–941
resonance and contributing structures, 930
structure, 929
Furfural,
Cannizzaro’s reaction, 939
Claisen condensation, 939
furil furilic acid rearrangement, 939
furoin condensation, 939
Perkin reaction, 939
preparations of, 932, 938
Furfuraldehyde (see furfural)
Furil-furilic acid rearrangement, 939
Furoic acid, 933
Furoin condensation, 939
Haemoglobin, 1025
Halide ions,
as leaving group, 404, 426
basicity, 404
comparison of basicity and nucleophilicity of, 403
nucleophilicity, 403
Haloalkanes,
bond strength, 393
classification of, 392
nomenclature, 43, 393
physical properties, 393
preparation of, 394–397
Hunsdiecker reaction, 396
Finkelstein reaction, 396
Via Grignard reagent, 396
reactions of, 397–417, 556 (see also, nucleo-philic substitution reactions, Elimination reactions)
structure of, 392
Haloarenes,
electrophilic substitution reactions, 440–441
nomenclature, 431
nucleophilic substitution reactions, 434–440
a comparision with SN1 and SN2
addition-elimination mechanism, 438
elimination-addition mechanism, 435, 447, 448
physical properties, 432
preparation of, 432–434
reactions of, 434–442
reactivity, comparison with haloalkanes, 434
resonance in, 434
structure of, 431
Halocarboxylic acids, preparations and reactions of; -,- and -halocarboxylic acids, 708–709
-Halo esters, reaction of, 584
-Haloester, 604
Haloform, 422
Haloform reaction (see also Iodoform reaction), 606–608
Halogenated hydrocarbons (see haloalkane), 396
Halogenation, of alkane, 179
energy calculation, 184
of aromatic compounds, 316, 345, 537, 647, 741, 749, 818, 827, 828, 855
of benzene, 313, 329
-halogenation, 599, 712, 790
of heterocyclic compounds, 937, 945, 949, 952
reactivity and selectivity, 186–188, 208
Halogens, as ortho, para director, 348
Halohydrins, 229
Halon, 426
Hantzsch synthesis, 944
Haworth projection formulae, for sugars, 976–980
Haworth synthesis, 850, 868
HCFC’s, abbrev. of hydrochlorofluorocarbons, 425
HCH; abbrv. of hexachlorocyclohexane, 1050
–HCH (see lindane)
Heat of combustion, 220
Heat of hydrogenation, 219, 250, 297, 368
Heavy oil, 196
-Helix, 1034
-Helix, 1034
Hell-Volhard-Zelinsky reaction (HVZ reaction), 671
Hemiacetal; forms of sugars, 977
Henna, 1072
n-Heptane, dehydrogenation, 194
Herbicides, 1053
Heterocyclic compounds, nomenclature, 926–927
numbering the position, 927
Heterocyclic compounds, five membered, 928–942 (see pyrrole, furan and thiophene)
Heterocyclic compounds, fused, 948–952
(see quinoline and isoquinoline)
Heterocyclic compounds, six membered, 942–948 (see pyridine)
Heterolytic bond cleavage, 115
Heumann synthesis, 1083
1,2,3,4,5,6-Hexachlorocyclohexane (see HCH)
Hexamethylenediamine, 1103
Hexamethylenetetramine; use of, 628
n-Hexane, dehydrogenation, 193
Hexaphenylethane, 363
HFC’s (see hydrofluorocarbons)
Hinsberg method, 772–774, 900
Hinsberg reagent, 777
Hippuric acid, 1006
Histidine, 999
Hoesch condensation, 627
Hofmann degradation reaction, 776
Hofmann elimination/rule, 217
Hofmann mustard oil test, 786
Hofmann rearrangement, 776
Hofmann’s exhaustive methylation, 781
Hofmann’s method, 771
HOMO (highest occupied molecular orbital), 255
Homolytic bond cleavage, 115
Homopolymers, 1087
Huckel’s rule, 298
Hund’s rule, 2
Hunsdiecker reaction, 396, 892
Hydrates, of carbonyl compounds, 585, 872
Hydration reactions, 229–233, 281, 585, 872
Hybridization, 7
effect on bond length and bond strength, 12, 13
hybrid orbitals, 9
sp hybridization, 11
2
sp hybridization, 10
3
sp hybridization, 8
Hydantoin, 1009
Hydrazine; use in reduction, 597, 639
Hydrazobenzene, 820
Hydrazoic acid, 778
Hydrazone derivatives, of carbonyl compounds, 591, 635
Hydride shift (see Cannizzaro’s reaction and also 1,2-Hydride shift)
1,2-Hydride shift, 216, 227
Hydroboration oxidation, of alkynes, 577
Hydrocyanic acid, 796
Hydrofluorocarbons, 425
Hydrogen bonding, 20, 452, 528, 534, 572, 655, 730, 782, 538, 1036
Hydrogenation of,
alkenes, 172
alkynes, 172
coal; destructive, 198
-Hydrogens; reactivity in,
aldehydes, 599
esters, 712
ketones, 599
nitroalkanes, 790
Hydrolysis of,
acetals and ketals, 586
acid anhydrides, 677
acid halides, 676, 882
active methylene compounds, 659
amides, 681
cynamides, 780
epoxides, 495, 496
esters, 460, 488, 658, 733
ethers, 460
geminal halides, 575, 628, 732
isonitriles, 776
neopentyl halide, 559
nitriles, 656, 657, 732
tert. butyl chloride, 562
trialkylborane, 179
triglycerides, 519, 760
2-Hydroxybenzaldehyde (see salicylaldehyde)
2-Hydroxybenzoic acid (see salicylic acid)
2-Hydroxybutanedioic acid (see malic acid)
-Hydroxycarboxylic acids, 644
-Hydroxyketone, 643
2-Hydroxypropane-1,2,3-tricarboxylic acid (see citric acid)
2-Hydroxypropanoic acid (see lactic acid)
2-Hydroxypyridine, 946
-Hydroxysuccinic acid (see malic acid)
-Hydroxy esters; formation of, 584
-Hydroxyaldehyde (see aldol),
-Hydroxyketone, 599, 601, 639
o-Hydroxybenzaldehyde (see salicylaldehyde )
o-Hydroxybenzoic acid (see salicylic acid)
Hydroquinone, 547, 548
Hydroxamic acid, 777
Hydroxycarboxylic acids (see also citric acid, lactic acid, malic acid, tartaric acid)
action of heat, 706
IUPAC names of, 700
oxidation, 706
physical properties, 700
preparations, 701–702
reactions of, 702–708
reduction, 707
Hydroxylamine, 960
Hydroxylation reactions, 239, 240
Hyperconjugation, 112–115, 119, 125
isovalent, 113
sacrificial, 113
Hypsochromic shift, 1070, 1111
Indane-1,2,3-trione; 1009
Indigo, 1083–1084
Inductive effect, 107, 561, 564
in acidic strength, 462, 662, 663, 693
in basicity, 781
in decarboxylation, 883, 884
in esterification, 881, 882
in reactivity of carbonyl compounds, 580, 598, 599
in reactivity of diazonium salts, 884
in stability of carbanions, carbocations, free radicals, 118, 123, 125
in stability of hydrates, 872
Infrared (IR) spectroscopy, 1120–1124
problems based on, 1123–1124
characteristics stretching frequencies, 1121
Inner salt (see Zwitterions)
Insecticides, 1049
Intermolecular forces, 19–22
Internal Cannizzaro’s reaction, 602
Intramolecular cyclization, 951
Invert sugar, 989, 994
Iodine value, of fats and oils, 762
Iodoalkanes; preparation of, 396, 556
Iodoform reaction, 422, 472, 606–608, 646
2-Iodopropane, 521, 522
Ion–Exchange resins, 1107
Ion-dipole interaction, 19
Ionic bond, 3
Ipso-substitution, a definition, 440
IR spectra, 1122
Isobutane, 170
Isobutene, 211, 234, 235
Isocyanates, 776–778, 801–803
nomenclature, 801
Iodoacetic acid, 663
Isoelectric point (symbolized as pI), 998, 999, 1002
Isolated dienes, 253
Isoleucine, 998
Isomerism, 27–30
constitutional isomers, 28, 141
stereoisomers, 28, 70
Isonitriles (see alkaneisonitrile)
Isooctane, 197
Isopentane, 170
Isophthalic acid, 319
Isoprene,
preparation of, 269
reactions of, 270–271
rule, 1060
Isoquinoline, 948, 951, 952
Isotactic polymer, 1088
Isothiocyanates, 786, 801–804
Isothiocyanic acid, 801
Isoxazolone, 721
IUPAC nomenclature, 36
common errors in writing names, 56–59
organometallic compounds, 51
polyfunctional organic compounds, 38, 51–55
principal functional groups, suffixes and prefixes, 36–38, 51
recommendations, 42
rules for naming functional groups, 36–51 (see also individual functional groups like alcohols and ethers
etc.)
Kerosene, 196
Ketals, cyclic, 524, 586, 891, 892
Ketenes, 677–678, 796
Ketones (aliphatic and aromatic), (see carbonyl compounds)
preparations of, 573–579, 622–624, 626, 627
reactions of, 579–594, 596–598, 627–640, 646, 647
Ketoses, definition of, 955
-Ketoester, 712, 932
Ketoximes, 635
Kharasch effect, 238
Kieselguhr (a clay type), 522
Killiani-Fischer synthesis, 964
Kjeldahl method, 24
Knocking, of engine, 197
Knoevenagel reaction, 696, 725
Knorr-Paal synthesis, 932
Koch reaction, 660
Kolbe’s electrolytic process, 178, 218, 277
Kolbe-Schmitt reaction, 542, 941
Tabun, 684
Tannins, 1066
Tartaric acid, 641, 707, 708, 984
meso tartaric, 699
racemic mixture, 699
stereochemistry, 72, 702
Tartronic acid, 523, 524, 707
Tautomerism
amido-amidol, 30
keto-enol, 29, 141, 142
nitro-aci, 30
Tautomers, 28, 29, 384
Teflon, 247, 1096, 1097
TEL (abbrev. of tetraethyllead), 197
antiknocking agent, 197
environmental hazard, 197
Terminal alkynes, 290
Terpenes, 1059, 1063
Terphthalic acid, 319
Terylene (see polyester)
Testosterone, 1064
Tetrafluoroethene (see teflon)
Tetrahydrofuran, 941
Tetrahydrothiophene, 941
Tetralin, 851, 852
Tetraterpenes, 1062–1063
Thermocole, 1098
Thermoplastic plastics, 1088
Thermosetting plastics, 1088
Thioacetals, 501
Thioacids, 498
Thioalcohol (see thiols)
Thioaldehydes, 498
Thioethers,
bond angle, 503
nomenclature, 503
physical properties, 503
preparation of, 503–504
reactions of, 504–505
Thioketals, 501
Thioketones, 498
Thiols,
acidic strength, 500
detection of, 502
nomenclature, 498
physical properties, 499
preparation of, 499–500
reactions of, 500–502
Thiophene,
aromaticity, 307, 929–931
electrophilic substitution reactions, 933–938
mercuration, 937
orbital picture, 929
physical properties of, 928
preparations of, 931, 933
reaction with organometalic compounds, 939
reactivity, 933, 934
reduction reactions, 941
resonance and contributing structures, 930
structure, 929
Thiram, 1055
Threo (as prefix), 72, 370, 371
Threonine, 999
Thymine, 1035, 1036
Tischenko Reaction, 604
TMS (tetramethyl silane; (CH3)4Si), 1126
Tollens Reagent/test, 594, 673, 875–878, 887
Toluene, 446
preparation of, 194, 315–316
reactions of, 316–320, 628
p-Tolunesulfonates, 748
Toluic acids (o-, m-, p), 316
Torsional strain, 92
Tosylates (see p-toluenesulfonates)
Trans-addition, 222, 225
Transannular strain, 99
Transesterification, 679
Triacetin, 522
Tricresylphosphate (see plasticizer)
Trifluoroacetic acid, 1015
Trihaloalkanes, preparations and reactions, 422–424
2,2,4-Trimethylpentane (see isooctane)
Triols (see glycerol)
Trioxane, 609
Triphenylmethane; carbanions, carbocations, free radicals of, 121, 124, 127, 166, 568
Triphenylmethane dyes, 1075–1080
Triphenylmethyl radicals, 363
Triterpenes, 1062
Tropylium ion, 121, 303
Trypsin, 926
Tryptophane, 998
Turmeric, 1072
Tyrosine, 999
Valine, 998
van der Waals forces (see intermolecular forces)
van der Waals radius, 5
Vat dyes, 1066, 1083
Veronal (see barbitone)
Victor Meyer test, 471
Vinyl acetate, 1096, 1097
Vinyl chloride, as monomer, 1097, 1096
Vinyl halides, 418–419, 561
Vinylic hydrogens, 146
Vinyl polymers, 1095–1097
Vinylic borane, 282, 283
Vinylidine chloride (1,1-dichloroethene), 1096
Vitamin-A, 1062
Vulcanization, 1104
Wacker’s process, 656
Wagner-Meerwein rearrangement, 216, 227, 567
Walden inversion, 400
Walnut shell, 1072
Washing action of soap and detergents, 765
Water gas reaction, 199
Wave number, 1110
Waxes, 762
Williamson ether synthesis, 484, 485
Witt theory, 1066, 1068, 1069
Wittig Reaction, 218, 582, 631
Wohl’s degradation, 966
Wolff-Kishner reduction, 177, 597, 639, 892
Wood alcohol, 472
Woodward Fieser rules, 1113
Wurtz reaction, 174, 207, 442, 446
Wurtz-Fittig reaction, 315, 323, 442
Xanthins, 1062
Xylenes (o-, m-, p), 198, 310, 319
Ylides, 582