Recap: Stereochemistry

(i) Introduction

(ii) Importance

(iii) Historical Origin

(iv)Chiral racemic, chiral non-racemic

(v) Chiral term “Cheir”

 mirror
plane
OH OH

H CH3 CH3 H
HO 2C CO 2H

(S)(+) lactic acid (R)(-) lactic acid

observed rotation
rotation of pure enantiomer x 100 = enantiomeric
fromexcess
muscle(e.e.)tissue
o
from milko
[] = +13.5o [ ] = -13.5
observed rotation = +109
109.0
e.e. = 123.0 x 100

= 88.6% e.e.
H H
88.6% (+)
(S)-(-) Limonene (R)(+) Limonene 11.4% racemic
o o
[=  [] = +123.0 actually 94.3% (+)
from lemons from oranges
d-asparagine : Sweet taste but

l- asparagine is tasteless

l-aspartame is sweet but

d-isomer is better

Used in flavored cookies

 low: < 60 kJ/mol
High: > 100 kJ/mol

These values are quite arbitrary

Isomers: Substances/compounds that have the same
composition & molecular weight but differ in structures
and properties.
On molecular level it means: difference in structural
arrangement.

Isomers are of two types: Constitutional & stereoisomers

?
configurational
&
conformational

classification based on energy criterion

Configurational Isomers: Isomers differing in configuration
(separated by a high energy barrier)

Means the fixed relative arrangement of atoms in space of a

molecule of defined constitution

HOOC-CH=CH-COOH has two stereoisomers

* Does not include those arrangement in space of a molecule that can be

achieved by rotation of the part of the molecule about one or more single
bonds
Conformational Isomers:
(separated by a comparatively low energy barrier)
Stereoisomers that can be interconverted by the mechanical processes
without breaking & making of bonds (chemical process).

*Mechanical processes include rotations around single bonds or twisting of

bonds

Rotation

Twisting
 An alternative subdivision of stereoisomers
Enantiomers & diastereomers
Enantiomers are pairs of isomers related as an object to its mirror
image (must be isomers as well as mirror images)

Enantiomers may differ in configuration or only in conformation

Examples

CO2H O2N
NO2 HO C
2

NO2 HO C
2
CO2H O2N
One can draw many structures which bear a mirror- image relationship but,

upon rotation of the entire model (rigid rotation) around an appropriate axis,

turn out to be superposable; such structures are identical not enantiomorphic.

H H
Me H H Me

Me
Me = Me
Me
H H 90o
Me H H Me

H
Me H
Me
Me
H
Me H
 COOH COOH COOH
H OH
HO CH 3 H 3C OH
H H
CH 3 wedge r epr esen t at ion
(R )-Lact ic acid
 Facts about enantiomers
Not permitted are interchanges of two groups and 90o rotations of the
formula (mainly in Fisher projection).

Two successive exchanges of two groups are permitted

Experiment carried out by Fisher-Brauns (1914) to demonstrate that

interchange of two groups converts one enantiomer into another enantiomer
& that configuration of chiral center is responsible for the direction of
optical rotation.
CONH2 CONH2 CO2H

CH2N2 HNO2
H CH(CH3)2 H CH(CH3)2 H CH(CH3)2

CO2H CO2CH3 (-) CO2CH3

(+)-dextrorotatory (+)

NH2NH2

COOH COOH COOH

NH3 HNO2
H CH(CH3)2 H CH(CH3)2 H CH(CH3)2

CONH2 CON3 CONHNH2

(-)-levorotatory (-) (-)
 OH o H CH3 o
90 o
90 CO2H
90
H CO2H CH3 OH HO2C H HO CH3
CH3 CO2H OH H
(S) (R)
(R) (S) (R)
(S) (S) (R)
 Both are Meso
CH3 CH3 CH3 CH3

CH3 CH3 CH3 CH3

Br Br
Br Br
Br Br

A B
1(R),2(S) cis 1,2-dibromocyclohexane
nonsuperimposible but A flips into B Meso
Early 1960’s (146 country)
Germany majorly

THE THALIDOMIDE TRAGEDY

Diastereomers

Stereoisomers which do not bear a mirror – image relation

to each other
Diastereomers may differ in configuration (or conformation) at several
sites in the molecule
CO2H Br Br O2N
H CO2H HO2C H

OH OH H OH

HO2C H HO CO2H
NO2 I I HO2C
CO2H O N
2

NO2 CO2CH(CH3)C2H5
 Key points……….

The term enantiomers and diastereomers relate to

molecules as a whole

Stereoisomers are either related as mirror images or not

The differentiation can be made without specifying any

part of the molecule but in viewing and specifying
enantiomers & diastereomers one often focuses on
particular sites in the molecule

namely……….. Chiral center or axis of chirality

NO2 HO C
2

B
D
A CO2H O2N
The existence of enanatiomers is usually, but not invariably,
associated with at least one chiral center or chiral torsion
axis

Diastereomers often contain two or more chiral centers,

chiral torsion axes, or a combination of the two

But sometimes diastereomers are neither chiral nor contain

chiral centers
Cl H
Cl Cl Cl H
Cl Cl
* * Stereogenic
axis
* H * Cl
H H H Cl

H H
Stereogenic centres may or may not be chiral,
Stereogenic center However, all chiral centers are stereogenic
Enantiomers are chemically alike because they have identical
connectivity of atoms along with identical relative spatial
arrangements of atoms with respect to distance and dihedral
angles.

Therefore, same achiral reagent will react identically with them

under same conditions.

Two enantiomers, therefore, are isometric to each other in simila

conditions.

Diastereomers, are chemically different because, in spite of their

identical connectivity of atoms, they have different relative
spatial arrangements of atoms with respect to distances and
dihedral angles.

Therefore, diastereomers are anisometric.

 Concept of residual stereoisomers CH3

Cl H

2-chlorobutane generally has two forms C2H5

H3C Cl H CH3
Cl H

CH3 H CH3 Cl
CH3 CH3
Diastereomers

H H H H D F
H H
A Enantiomers
H3C H Cl CH3 H Cl

CH3 Cl CH3 H CH3 CH3

H H
E
H H B H H C
Relation of E and F?

There are six stereoisomers (A-F): two categories: A-D-F/ C-B-E

* Rapid interconversion, as energy barrier is very low 20 kcal/mol (84 kJ/mol)

On the laboratory time scale, only two Residual enantiomers
CH3 CH3

H Cl Cl H

C2H5 C2H5

S R

Residual stereoisomers may be defined as those of the total

set of stereoisomers that can be distinguished and isolated
under specified condition by a given technique.

One is usually interested in residual stereoisomerism, and

therefore disregards events that are rapid on the time scale
of the experiments
Degenerate cases
H H

O O

O O O O

H H H
H
(mp: 170 oC)
Instead of 4 there are only three isomers
Two chiral center but only three isomers (one degenerate)
(mp: 140 oC, less dense)