CM134-1 CO1 - Alcohols and Phenols (Updated) PDF

CM134-1 ORGANIC CHEMISTRY 2 LECTURE
Course Outcome 1: (Part 1)

ALCOHOLS AND PHENOLS
CM134-1 Prof. UREAH THEA A. SEVILLA, Ph.D.

Organic Chemistry 2 Lecture School of Chemical, Biological, and Materials
Engineering and Sciences
Topic Outline
• Structure and Properties of Alcohols
• Acidity of Alcohols and Phenols
• Preparations of Alcohols
• Protection of Alcohols
• Reactions of Alcohols:
• Substitution Reaction
• Elimination Reaction
• Oxidation Reaction
utasevilla@mapua.edu.ph 1
Structure and Properties of Alcohols

• Alcohols possess a hydroxyl group (-OH)
• Hydroxyl groups are extremely common in natural compounds

• Hydroxyl groups in natural compounds

• Phenols possess a hydroxyl group directly attached to an aromatic ring

• Like halides, alcohols are often classified by the type of carbon they
are attached to
• When an –OH group is attached to a benzene ring, the parent name

is phenol
What is the name of the molecule?

• Name the molecule:
• Draw the most stable chair conformation for (cis)-1-isopropyl-1,2-

cyclohexanediol

• Methanol (CH3OH) is the simplest alcohol
• With a suitable catalyst, about 2 billion gallons of methanol is made
industrially from CO2 and H2 every year
• Methanol is poisonous, but it has many uses
1. Solvent
2. Precursor for chemical syntheses
3. Fuel

• Ethanol (CH3CH2OH) has been produced by fermentation for
thousands of years. HOW?
• About 5 billion gallons of ethanol is made industrially from the acid-
catalyzed hydration of ethylene every year
• Ethanol has many uses
1. Solvent, precursor for chemical syntheses, fuel
2. Human consumption – ethanol suitable for drinking is heavily taxed. Ethanol
used for purposes other than drinking is often denatured. WHY?
• Is it poisonous?

• Isopropanol is rubbing alcohol. Draw its structure
• Isopropanol is made industrially from the acid-catalyzed hydration
of propylene
• Isopropanol is poisonous, but it has many uses
1. Industrial solvent
2. Antiseptic
3. Gasoline additive
Physical Properties of Alcohols

• The –OH of an alcohol can have a big effect on its physical
properties
• Compare the boiling points below
• Explain the differences

• Because they can H-bond, hydroxyl groups can attract water
molecules strongly
• Alcohols with small carbon chains are miscible in water (they mix in
any ratio). WHY?
• Alcohols with large carbon chains do not readily mix with water

• Do hydrophobic groups repel or attract water?
• WHY are molecules with large hydrophobic groups generally

insoluble in water?
• Alcohols with 3 or less carbons are generally water miscible
• Alcohols with more than 3 carbons are not miscible, and their
solubility decreases as the size of the hydrophobic group increases

• An alcohol’s potency as an anti-bacterial agent depends on the size
of the hydrophobic group
• To kill a bacterium, the alcohol

should have some water
solubility. WHY?
• To kill a bacterium, the alcohol
should have a significant
hydrophobic region. WHY?

• Hexylresorcinol is used as an antibacterial and as an antifungal
agent
• It has a good combination of hydrophobic and hydrophilic regions

• It has significant water solubility
• Its nonpolar region helps it to pass through cell membranes
Acidity of Alcohols and Phenols

• The conjugate base of an alcohol is
called an alkoxide ion, and it
exhibits a negative charge on an
oxygen atom.
• A negative charge on an oxygen
atom is more stable than a negative
charge on a carbon or nitrogen
atom but less stable than a
negative charge on a halogen, X.
Acidity of Alcohols and Phenols

• Alcohols are more acidic than amines and alkanes but less acidic than
hydrogen halides
Reagents for Alcohol Deprotonation
Factors Affecting Acidity of Alcohols and Phenols
This resonance-stabilized anion

is called a phenolate, or
phenoxide, ion.

• Resonance stabilization of the phenoxide ion explains why phenol is eight orders
of magnitude (100,000,000 times) more acidic than cyclohexanol.
• Phenol does not need to be deprotonated with a very strong base like sodium
hydride. Instead, it can be deprotonated by hydroxide.
The ethoxide ion is not sterically

hindered and is therefore easily solvated
(stabilized) by the solvent, while tert-
butoxide is sterically hindered and is less
easily solvated.
The conjugate base of compound A will

be more stable than the conjugate base
of compound B. Therefore, compound
A will be more acidic.
Preparation of Alcohols via Substitution or Addition
• Substitution Reactions
• Addition Reactions Acid-catalyzed hydration proceeds with

Markovnikov addition. The hydroxyl group is
installed at the more substituted position. It is a
useful method if the substrate is not susceptible
to carbocation rearrangements.
In a case where the substrate can possibly

rearrange, oxymercuration-demercuration
can be employed. It can also proceeds via
Markovnikov addition, but it does not involve
carbocation rearrangements.
Hydroboration-oxidation is used to
achieve an anti-Markovnikov addition of water.
Markonikov’s Rule:
The rule states that with the addition of a protic acid HX to an
asymmetric alkene, the acid hydrogen (H) gets attached to the carbon
with more hydrogen substituents, and the halide (X) group gets
attached to the carbon with more alkyl substituents.
• The Nu- adds to the more substituted carbon.

• The hydrogen goes to the less substituted carbon.
• "hydrogen rich" gets "hydrogen richer"
Preparation of Alcohols via Addition Reaction

ACID-CATALYZED HYDRATION REACTION

• Predict the product:
(Markonikov)
Preparation of Alcohols via Reduction
• The reaction requires a reducing agent, which is itself oxidized as a result of the
reaction.
Although rarely used for synthesis, ketones or aldehydes

are converted to alcohols through hydrogenation in the
presence of metal catalyst under more forcing conditions
(higher temperature and pressure).

• Sodium borohydride (NaBH4) is a common reducing agent that can be used to
reduce ketones or aldehydes.
Sodium borohydride functions as a
source of hydride (H: –)
Solvent functions as the source
of a proton (H+)

• Lithium aluminum hydride (LiAlH4) is another common reducing agent
LiAlH4 is more
reactive that
NaBH4

• LiAlH4 reacts with a carboxylic acid or an ester to produce an alcohol.
It occurs in a 2-step reaction.

• Predict the product of the following:
Preparation of Diols
• Diols can be prepared from diketones via reduction using any of the reducing
agents
Alternatively, diols can be made via dihydroxylation of an

alkene.
Preparation of Alcohols via Grignard Reagents

• A Grignard reagent is formed by the reaction between an alkyl halide and
magnesium.
A Grignard reagent is characterized by the presence of a C−Mg
bond.
Carbon is more electronegative than magnesium, so the carbon
atom withdraws electron density from magnesium via induction.
This gives rise to a partial negative charge (δ−) on the carbon
atom.
Grignard reagents are carbon nucleophiles capable of attacking a

wide range of electrophiles, including
the carbonyl group of ketones or aldehydes
Step 1:
Identify the carbon where OH is directly attached.
Step 2:
Identify the three groups connected to the α position.
Step 3:
Show how each group could have been
installed via a Grignard reaction.
Protection of Alcohols
• Addition of protecting group enables desired Grignard reaction for
alcohols.
Steps:
1. Protect the hydroxyl group by removing its proton and converting the
hydroxyl group into a new group, called a protecting group, that is compatible
with a Grignard reagent.
2. Form the Grignard reagent and perform the desired Grignard reaction.
3. Deprotect, by converting the protecting group back into a hydroxyl group.
• Protecting group OTMS - conversion of the hydroxyl group into a
trimethylsilyl ether
The trimethylsilyl ether is formed via the

reaction between an alcohol and trimethylsilyl
chloride, abbreviated TMSCl.
• Mechanism: SN2-like
reaction(backside attack on Si)
• After the desired Grignard

reaction has been performed,
the trimethylsilyl group can be
removed easily with either
H3O+ or fluoride ion.
A commonly used source of fluoride ion is
tetrabutylammonium fluoride (TBAF).
Preparation of Phenols
• Phenol is prepared industrially via a multistep process involving the formation
and oxidation of cumene.
antioxidant food additives
Reactions of Alcohols: Substitution Reaction

• Tertiary alcohols will undergo a SN1 when treated with a hydrogen halide.

• Primary alcohols will react with HBr via an SN2 process.
• This reaction works well for HBr but does not work well for HCl. To replace the
hydroxyl group with chloride, ZnCl2 can be used as a catalyst.

• Primary and secondary alcohols
react with SOCl2 or PBr3 via an SN2
process.

• Reaction with PBr3
• Reagents to form alkyl halides: • Chemical test to differentiate 1°, 2°

• HBr or PBr3 and 3° alcohols: LUCAS TEST
• HCl or PCl3 or SOCl2 Lucas reagent: HCl + ZnCl2
• HI or PI3
(+)result: cloudy solution 3°> 2°> 1°

Sample problems:
1. Isobutanol + HCl →
2. Cyclohexanol + PBr3 (+pyridine) →
3. Cyclohexanol + SOCl2 (+pyridine) →
4. n-butanol → butylmethylether (butoxymethane)
5. 3-methyl-2-butanol + HBr →
Reactions of Alcohols: Elimination Reaction

• Elimination reaction in alcohols involve dehydration to generate
alkene by heating the alcohols in the presence of a strong acid.

Zaitsev Rule:
• Formally, the rule is that an elimination will occur such that a
hydrogen is removed from the “β-carbon” with the fewest hydrogens.
• The alkene formed in the greatest amount is the one that correspond
to the removal of hydrogen from the β-carbon having the fewest
hydrogen substituent.

• Tertiary alcohols follows an E1 mechanism:
Elimination reaction generally favors

the more substituted alkene.
alkyloxonium ion

• Primary alcohols undergo bimolecular elimination E2:
Oxygen donates two electrons to a proton from sulfuric acid H2SO4, forming an alkyloxonium ion.
Then the nucleophile HSO4– back-side attacks one adjacent hydrogen and the alkyloxonium ion
leaves in a concerted process, making a double bond.

a) 3-methyl-2-butanol → 2-methyl-2-butene + 2-methyl-1-butane
b) .
c) .
Reactions of Alcohols: Oxidation

• Oxidation products of alcohol depends on the type alcohol:
• For 1° alcohols:

• 2° alcohols form ketone:
• 3° alcohols cannot be further oxidized:

A common oxidizing reagent is chromic
acid (H2CrO4), which can be formed either
from chromium trioxide (CrO3) or from
sodium dichromate (Na 2Cr2O7) in aqueous
acidic solution.

• Primary alcohol is oxidized with chromic acid, a carboxylic acid is obtained. It is
generally difficult to control the reaction to produce the aldehyde.
When a secondary alcohol is treated

with a chromium oxidizing agent
(whether chromic acid or PCC), the
alcohol is oxidized to give a k etone:
In order to produce the aldehyde without further oxidation
Comparison of E1 and E2 Reactions
Comparison of Substitution with Elimination Reaction
The Swern oxidation uses dimethyl sulfoxide (DMSO) and oxalyl chloride, (COCl)2, as
shown:

• The Swern oxidation can also be used to convert primary alcohols into aldehydes:
Under these conditions, the aldehyde is not further oxidized to a carboxylic acid. The by-products of
the Swern oxidation are volatile (low-boiling), so they can be easily separated from the reaction
mixture.

• Dess–Martin periodinane (DMP) oxidation, much like the Swern oxidation, will
also convert primary alcohols into aldehydes, and secondary alcohols are
converted into ketones:
Both the Swern and DMP-based oxidations are “greener” alternatives to chromium-based oxidations,
however both processes have very poor atom efficiency. Also, the Swern oxidation produces a very
foul-odored by-product (dimethyl sulfide, DMS), and DMP is shock sensitive (explosive).

Predict the product:
Oxidation of Phenols
• Phenol is observed to undergo oxidation even more readily than primary and
secondary alcohols. The product is benzoquinone.
• Quinones are important because they are readily converted to hydroquinones.
Reduction-Oxidation Reactions
• Summary
• Redox reactions in the cell:
• Redox reactions in the cell:
A map of reactions for interconversion between alkanes, alkenes,

alkynes, alkyl halides, alcohols, and ketones/aldehydes.
References:
• Klein, David. Organic Chemistry 3rd Edition, John Wiley and Sons, Inc.
2017.
• Solomons, T. W. Graham, Craig B. Fryhle, Organic Chemistry, 10th

edition, John Wiley and Sons, 2011.

CM134-1 CO1 - Alcohols and Phenols (Updated) PDF

Caricato da

Informazioni sul documento

Titolo originale

Copyright

Formati disponibili

Condividi questo documento

Condividi o incorpora il documento

Opzioni di condivisione

Hai trovato utile questo documento?

Questo contenuto è inappropriato?

Copyright:

Formati disponibili

CM134-1 CO1 - Alcohols and Phenols (Updated) PDF

Caricato da

Copyright:

Formati disponibili

CM134-1 ORGANIC CHEMISTRY 2 LECTURE

Course Outcome 1: (Part 1)

CM134-1 Prof. UREAH THEA A. SEVILLA, Ph.D.

Structure and Properties of Alcohols

• Hydroxyl groups are extremely common in natural compounds

Structure and Properties of Alcohols

Structure and Properties of Alcohols

Structure and Properties of Alcohols

• When an –OH group is attached to a benzene ring, the parent name

What is the name of the molecule?

Structure and Properties of Alcohols

• Draw the most stable chair conformation for (cis)-1-isopropyl-1,2-

Structure and Properties of Alcohols

Structure and Properties of Alcohols

Structure and Properties of Alcohols

Physical Properties of Alcohols

• Explain the differences

Physical Properties of Alcohols

Physical Properties of Alcohols

• WHY are molecules with large hydrophobic groups generally

Physical Properties of Alcohols

• To kill a bacterium, the alcohol

Physical Properties of Alcohols

• It has a good combination of hydrophobic and hydrophilic regions

Acidity of Alcohols and Phenols

Acidity of Alcohols and Phenols

Reagents for Alcohol Deprotonation

Factors Affecting Acidity of Alcohols and Phenols

This resonance-stabilized anion

Factors Affecting Acidity of Alcohols and Phenols

Factors Affecting Acidity of Alcohols and Phenols

Factors Affecting Acidity of Alcohols and Phenols

The ethoxide ion is not sterically

Factors Affecting Acidity of Alcohols and Phenols

The conjugate base of compound A will

Preparation of Alcohols via Substitution or Addition

Preparation of Alcohols via Substitution or Addition

• Addition Reactions Acid-catalyzed hydration proceeds with

In a case where the substrate can possibly

Preparation of Alcohols via Substitution or Addition

• The Nu- adds to the more substituted carbon.

Preparation of Alcohols via Addition Reaction

Preparation of Alcohols via Addition Reaction

Preparation of Alcohols via Addition Reaction

Preparation of Alcohols via Addition Reaction

Preparation of Alcohols via Substitution or Addition

Preparation of Alcohols via Reduction

Although rarely used for synthesis, ketones or aldehydes

Preparation of Alcohols via Reduction

Preparation of Alcohols via Reduction

Preparation of Alcohols via Reduction

Preparation of Alcohols via Reduction

Preparation of Alcohols via Reduction

Alternatively, diols can be made via dihydroxylation of an

Preparation of Alcohols via Grignard Reagents

Grignard reagents are carbon nucleophiles capable of attacking a

Preparation of Alcohols via Grignard Reagents

Preparation of Alcohols via Grignard Reagents

Preparation of Alcohols via Grignard Reagents

Preparation of Alcohols via Grignard Reagents

The trimethylsilyl ether is formed via the

• After the desired Grignard

antioxidant food additives