First Year Organic Chemistry

Theory Autumn Semester

Wednesday 8.0-9.55 AM, F142
Thursday 10-10.55 AM, F142
15 Lectures

Tutorial
Monday 10-10.55 AM, F131, F132
Monday 3.0-3.55 AM, F233, F234

Teacher
Dr. Santanu Panda
spanda@chem.iitkgp.ac.in

Organic Chemistry:Clayden,Greeves,
Warren, Wothers

Stereochemistry of Carbon Compounds

Eliel

A Guide Book to mechanism

in Organic Chemistry
P. Sykes
Life Is Organic Chemistry

origin of life
CH4, CO2, H2O, NH3, H2
electric discharges
(like lightning)

highly reactive species

amino acids, HCHO, HCN, purines, pyrimidines

Organic Chemistry; Miracle Drug
Organic Chemistry; Vitamin B12
 Topics

 Stereochemistry
Conformational Analysis
Pericyclic Reactions
Stereochemistry of Nucleophilic
Substitution at saturated carbon
Stereochemistry of Elimination reaction
 Chiral The word chiral comes from the Greek
word cheir, which means hand

Chirality is a property of an object which is non-superimposable

with its mirror image. Most objects in the environment are chiral. In
chemistry this term applies to molecules, specific conformations of
molecules, as well as to macroscopic objects such as crystals.
 Enantiomers and Chirality
O -
CN HO CN
R R
H H

How many products are formed ?

O
NC OH

R R
H H

A B
CN
Approach from front face of the carbonyl

What is the relation between A & B?

HO
NC OH CN

A&B are non superimposable mirror images R R

H H

A B
A&B are chiral and Enontiomers (Mirror images)
 What happens when cyanide is added to acetone

HO CN HO Plane of symmetry runs

CN
Me through central carbon, OH,
Me Me CN
Me
Acetone Cyanohydrine

So, any structure that has no plane of symmetry can exist as two mirror-image forms
(enantiomers)

Now we will learn about the point groups and symmetry elements

Element Operation
Rotation axis, Cn n-fold rotation
Improper rotation axis, Sn n-fold improper rotation
Plane of symmetry,  Reflection
Center of symmetry, i Inversion
Identity, E
C2
 plane of symmetry
O
 H
H
H H
H H
H H
C6 h
H H H
H
H
H
A B A
H H
H
H

60
Symmetry Elements & Operation (IV)

Center of symmetry (i)

CH3 H

Cl H

H Cl

H CH3
 Dissymmetric vs Asymmetric

A dissymmetric molecule may have one axis or more axes of symmetry (Cn).
On the other hand, the chiral or dissymmetric molecules which lack even Cn
axis (save C1 axis) is termed asymmetric.

Asymmetric molecule

Chiral molecule having C2 symmetry

Problem: Which of the following are chiral and why?

Me
Me

Me Me Me Me Me Me

Me Cl Me
Me Cl Me
Cl Cl

Cl Me Cl
Me Me Cl Me
 Bromochlorofluoromethane is chiral

Cl Cl
Br Br
H H

F F
Chemical Properties of Enantiomers
 Enantiomers have different biological property
Me
*
COOH

Ibuprofen

500 mg of one tablet contains only half of its as active drug

Me
Me
COOH
COOH

S is active R is inactive
Problem: Feist's acid (C6H6O4) is a cyclopropane based natural product and having two
stereocenter. The compound is chiral. Based on this information predict its correct structure?
 CO2 H CO2 H
Hint:

CO2 H HO2C CO2 H CO2 H

X X

HO2C CO2 H HO2C CO2 H

right structure
Discuss the stereochemistry of the following compounds and
mention about their optical activity with good diagrams.
OH
NHCO2 Me
O
Ph
Me
O
SMe O SMe

N
H
Representation of a (Chiral) Molecule
Projection of a tetrahedral molecule onto a planar surface.

Visualizing a Fischer projection.

 Fisher Projection of Chiral Molecule
Representation of 3D structure of chiral compound in 2D

H
H H3C H
H3C

H3C C2H5
C2H5 OH
C2H5 OH OH

COOH
H COOH
H OH
HO
HO HO H
H COOH
COOH
Rule of rotation in Fisher Projection
 Sawhorse projection
The C-C bond is viewed at an angle.

View

This projection is difficult to use with acyclic molecules but is most popular for
representation of cyclic molecules e.g. saturated six-membered rings.
 Newman projection
The molecule with two tetrahedral centers is viewed along the C-C axis.
The atom in front is represented as a three-way branch, the atom in the back as
a circle with three outgoing bonds.

DH2C-CH2D

This projection is most useful to understand steric relations between ligands

linked to adjacent tetrahedral centers and is most popular
 Flying Wedge Projection

1. Flying Wedge Formula : To write flying wedge formula, the following conventions are
followed;
a. A tetrahedral molecule is viewed in such a way that two groups are in the plane of the
paper and two groups below it.
b. A bond coming towards US (viewer) out of the plane of the paper is represented by a solid
wedge
c. A bond going away from us (viewer) behind the plane of the paper is represented by a
broken wedge 
d. A bond lying in the plane of the paper is represented by ordinary line.

H
H

H H
H H
H
H

H H
H H
Inter conversion between

Flying wedge projection/

Wedge-dash projection

to Fisher Projection

to Flying wedge projection to Fischer projection

180o 1 4
CH3
Br H H3C CH3
syn-2-chloro-
1 C2-C3 2 3
H Cl
H3C 2
3-bromo-butane 3 CH3 H Br Br H
4 Cl H
Cl H eye eye CH3
or
1 4
anti-2-chloro- H Br H3C CH3 CH3
1 2 3
3-bromo-butane H3C 2
3 CH3 H Cl
Cl H
4 H H Br
Cl H Br
eye
eye CH3
Inter conversion between

Flying wedge projection to Sawhorse Projection

to Newman Projection
 D, L-Nomenclature
Fisher introduced this nomenclature for different enantiomer of sugar and amino acids
In the standard fisher projection if the functional group on the horizontal axis
lies on the left side we name it as L or (-) (Laevorotatory, rotate the plane of polarized light
Left or counterclockwise) and D or (+) (Dextrorotatory, rotate the plane of polarized light
right or clockwise).

However, the (+) and (-) sign not always go with D or L

CHO CHO CHO CHO

H OH = H OH HO H = HO H

CH2OH CH2OH CH2OH CH2OH

D-Glyceraldehyde L-Glyceraldehyde
Both are enantiomer of each other

CHO CHO

COOH
H OH HO H

H2N H
HO H H OH

HO H
CH3
H OH
L-Alanine
H OH HO H

CH2OH CH2OH

D-Glucose L-Glucose
Stereogenic Centers
 Cahn-Ingold-Prelog rules
Cahn, Ingold and Prelog introduced this systematic notation during the period 1951-1956.
The notation allows us to define in an unambiguous manner the absolute configuration of a
drawn stereogenic centre by assigning it as either (R) or (S).

1. Assign priority sequence to the four groups attached to a stereogenic carbon

following sequence rule
2. Observe the stereogenic centre from a direction opposite to the group
of lowest priority
3. Trace the path from 1 to 2 to 3.

If clockwise R (rectus, right)

If anti clockwise S (sinister, left)
 Sequence rules
1. Priority is first assigned on the basis of the atomic number of the atom
that is directly attached to the stereo centre.
CH3 ?

I > Br > Cl > F > O > N > C > H (1) HO H (4)

CH2 ?
2. When a priority cannot be assigned on the basis of atomic number of
CH3
FIRST ATOM, then the next set of atoms/groups are examined.

(3) CH3 H, H, H
3. Groups containing double or triple bonds are assigned (1) HO H (4)
as if both atoms were duplicated and triplicated.
CH2 H, H
H
(2)
H CH3 C
C C C C H
H (C) (C)

(C) (C)
Alkyne > Alkene > Alkyl
C C H C C H

(C) (C)
4. In case of isotopes, isotope with higher atomic number get higher priority

3H (tritium) > 2H (deuterium) > 1H (hydrogen)

5. When the difference between substituents is in configuration then (R) takes precedence
over (S).
6. Sometime it is difficult to visualize the molecule from the backside of lowest
Priority, In that case finish the priority based on sequence rule, if 4th priority group is
Is in the front then the then it reverses the priority R to S and S to R
We can also do single swap of atom and bring the 4th priority group back,
making sure that we will end-up getting the enantiomer

1 Cl 1 OH

1
3 2 NH2
S
3
2 H S 3

Atom with priority 4 (H) formed an hasch bond so

the pririty S will change to R
(1S,2S)-2-amino-1,2,3,4-tetrahydronaphthalen-1-ol
(R)-3-chlorohexane
Atom with priority 4 (H) formed an hasch bond so
the pririty R will change to S
3 2

OH
1

(R)-3-methylhexan-3-ol
Atom with priority 2 (n-Pr) formed an wedge bond so
the pririty S will change to R
 Cl

Br Br
OH (R)-3-chlorohexane
(R,E)-hept-4-en-3-ol Cl
(R)-3-(bromomethyl)-2,3- HO
dimethylpentane
(S)-3-(bromomethyl)-1-chloropentan-3-ol

OH
F3C OH

NH2
HS
CO2H
(S)-1-(anthracen-9-yl)ethanol (R)-2-amino-3-mercaptopropanoic acid
(R)-1-(anthracen-9-yl)-2,2,2-trifluoroethanol

OH
NH2
CHO
(R)-3,7-dimethyloct-6-enal
(1R,2S)-2-amino-1,2,3,4-tetrahydronaphthalen-1-ol

HN
O
OH
S

(S)-furan-2-yl(1H-pyrrol-2-yl)(thiophen-2-yl)methanol
Absolute configuration in Fischer Projection
 Assign a configuration, R or S to each of these compounds

Br
Cl

Cl
OH HO
Br

R OH
NH2
HS CHO
CO2 H

R = Me; CF3
 Z/E Geometry of Double Bonds

CIP rules used to geometrical isomers of olefinic compounds

Precedence of ligands at both X & Y of the double bonds is determined pairwise.
If both higher precedence ligands are
on the same side of the double bond the configuration is Z,
if on the opposite sides the configuration is E.

Z (zusammen, together) E (entgegen, opposite)

H H Br 1 F

1 1
H3C CH3 1
H Cl
(Z)-2-butene
Or cis-2-butene (E)-2-bromo-1-chloro-1-fluoroethene
 H CH3
Br CH2CH3
H3C

CH3
Cl H
H CH3

(Z)-1-bromo-1-chloro-1-butene (Z,4S)-3,4-dimethyl-2-hexene

Et CH2CH2CH3

H3C CH2CH2CH2CH3

(E)-3-methyl-4-propyl-3-octene
(2E),(4E)-2-chloro-2,4-hexadiene
 Summary for today’s class

1. Types of Isomerism: Structural isomerism, stereo isomerism

2. What is enantiomer?
3.
 Nitrogen chirality center

The inversion barrier is only 6 kcal/mol for R= alkyl

Ammonia: inverts 2X1011 times per second

Inversion is very fast and difficult to separate

 Inversion becomes slow when
•N is in three-membered ring

 N cannot achieve a 1200 bond

angle in a 3-membered ring
 The two enantiomers can be
separated

•N-atom is connected to atom which has unshared lone pair of electrons

CH3
Cl Me Me Cl N

N N N

H3C
Tröger’s base
Me Me

Two enantiomers has been separated Nitrogen at bridgehead position,

Pyramidal inversion prevented, chiral
Phosphorus chirality center

P
C(CH3)3
CH3 CH3
P C(CH3)3

inversion barrier 32.7 kcal/mol

P
H3C
H2C=HCH2C

[]D = 16.80
S-enantiomer
 Nitrogen, Phosphorus, Sulfur attached to four different groups

CH3
CH3
Br
Br H N
N H
CH2CH2CH3
H3CH2CH2C CH2CH3 H3CH2C

a pair of enantiomers
O O

H P
P H
H3CH2CO OCH2CH3
OCH3 H3CH2CO

16 O
a pair of enantiomers
O18

a pair of enantiomers
H3C
Diastereomers
•Diastereomers are stereoisomers that are not mirror images.
•Two diastereomers are different compounds and have different
relative stereochemistry.
Diastereomers may be chiral (have no plane of symmetry):
Ar CO2Me Ar CO2Me

O O

Diastereomers may be achiral

OH OH

plane of symmetry
 Compounds with no stereogenic centres

The presence of chiral atom is neither a

necessary nor a sufficient condition to be
optically active

Me H H3C H
H Me
C
C C C C
H Me Me H
H H
achiral
These mirror images are not superimposable - enantiomers
biphenyls

has been resolved

half-life for racemization
is 78 min at 118oC
Biphenyl atropisomerism
Optically active di- and mono-substituted biphenyls
Relative Configurations in Compounds with Multiple Chiral Centers.

•The use of CIP nomenclature requires assignment of R,S descriptors

for every center. The quicker way (older and a more ambiguous one) is
by using threo/erythro nomenclature.
•Threo/erythro It requires vertical projection of main chain.
•threo-compounds are defined as those that have two groups of higher
precedence on each carbon atom on the opposite sides of the chain.
•erythro on the same side.
CH3 CH3
CH3 CH3
* * H OH HO H
H3C CH CH CH3 HO H
H OH
H Cl Cl H
Cl OH Cl H H Cl
CH3 CH3 CH3
CH3
3-Chloro-2-butanol
A B D
C
erythro enantiomers
threo enantiomers

A&C
diastereomers A&D
B&C
B&D
 Tartaric acid
HOOC-CH(OH)-CH(OH)-COOH 22 = 4 stereoisomers ?

OH OH

R HO2C R S
HO2C R
CO2H CO2H

OH diastereomers OH
?
enantiomers
OH OH

S HO2C S R
HO2C S
CO2H CO2H

OH OH

HO2C CO2H
R S
COOH COOH HO OH COOH
H OH HO H
H OH
HO H H OH
H OH
COOH COOH
COOH
pair of enantiomers
meso compound
 Stereochemistry
Meso Compounds
 Indicate wheather each of the following pairs of compounds
are identical or enantiomers, diastereomers or constitutional isomers.

H Me Me Et
a. Et CH2OH and H Et b. HO H HO H
Me CH2OH and
H Cl H Cl
Et Me

Me Me
HO H H OH
c. and d. and Cl
H Cl Cl H
Me Me
Cl Cl H Cl

e. H H H Cl Cl H H Cl
and f. and

Cl Cl Cl H H Cl Cl H

Br H
CH2Cl Et H Br
g. h. and
Et Me and Me CH2Cl
H Br
H H Br H

i. H
j. and
and Br H Br