Molecular symmetry and Chirality

 A molecule can have only one mirror image

 If superimposable - Achiral
 If not superimposable – Chiral and enantiomers are formed

 Enantiomers give rise to stereoisomerism - Enantiomerism

Enantiomers of Lactic acid
 Stereoisomerism – Definition and Classification

 Depending on bonding connectivity and configuration isomers

are formed
 Isomers are separated by energy barrier and differ in their
physical and chemical properties

 Molecules with same molecular formula but differing in bonding

Connectivity are called constitutional isomers
 Molecules with same molecular formula but differing in the
orientation of atoms in space are called stereoisomers

 Stereoisomers having same bonding connectivity but different

configurations are often called configurational isomers

 Stereoisomers resemble only in functional group properties

 Stereoisomers differ substantially in physical, chemical and

biochemical properties
 Most of the natural products and biologically important molecules
occur in specific stereoisomeric forms and their biochemical
behaviour are regulated by their molecular architecture

Molecular representation of an asymmetric(Chiral) carbon

 Stereochemistry refers to molecules in three dimension

There are different modes of representations of three

dimensional molecules on two dimensional plane
Flying Wedges Flying Wedges

Fischer Projection
Fischer Projection Sawhorse Newman
Classification of stereoisomers based on symmetry criteria

Mislow (1965) suggested this new system of

classification

If two isomers are related to each other as object and

mirror image which are not superimposable they are
called enantiomers Kurt M Mislow

If two isomers are not related to each other as object and

mirror image which are not superimposable they are
called diastereomers
Compounds Enantiomers Diastereomers

A,B --

F,G E,F
E,G

-- K,L
Distinctive features of Enantiomers and Diastereomers

Enantiomers are mirror images of each other and are related

by symmetry elements. Diastereomers are not related by symmetry
elements

Enantiomers can exist only in pairs on the other hand a molecule

can have any number of diastereomers
No two stereoisomers can be enantiomers and diastereomers at the
same time (Mutually exclusive)

Diastereomers include all stereoisomers (except enantiomes) such as

optically active diastereomers, geometrical isomers and cis-trans
isomers
Enantiomers are isometric ie they have same

Melting point/Boiling point

Density
Solubilities
Refractive indices
Dipole moments

Reactivity towards achiral reagents

Diasteremers are anisometric ie they differ in properties

Classification of stereoisomers based on Energy criteria

Isomers can be classified on the basis of energy barrier and

kinetic stability
Configurational Isomers

Stereoisomers separated by high energy barrier (› 100 kJ/mol)

are stable and can be isolated at room temperature

Conformational Isomers or Conformers

Stereoisomers separated by low energy barrier (‹ 60 kJ/mol)

and are easily interconvertible at room temperature
Examples of confornational enantiomers and diastereomers

Configuration Enantiomers Diastereomers

O P Q

R S T

U V
Classification of stereoisomers based on symmetry & energy criteria
 Points to be remembered

The standard energy barrier is 2.58 kJ/mol (RT at room

temperature) below which two species may be considered as
homomers
The energy barrier separating two stereoisomers depends on
the mechanism of interconversion
Enantiomers of lactic acid have high energy barrier since the
interconversion involves a σ bond breaking. Hence they
represent configurational enantiomers

In the isomerism of cis and trans-2-butene a π bond is

disrupted which requires appreciable amount of energy. Hence
they are configurational diastereomers
 Points to be remembered

Rotation around single bond is easy and leads to conformational

isomerism. eg. n-butane, dichlorobromofluoroethane

Ring inversion is a facile process and leads to conformational

isomers.

Inversion in nitrogen compounds is facile and give

conformational isomers known as invertomers.

In some crowded molecules rotation about a single bond may be

restricted to give stable and isolable isomers known as
atropisomers
 Biphenyl derivatives and atropisomerism

In biphenyl two phenyl groups are joined by a single bond

(sp2-sp2) called the pivotal bond

If the phenyl groups are dissymmetrically substituted two

planar diastereomers (cis and trans) are formed.
 Biphenyl derivatives and atropisomerism

If bulky groups are introduced in the ortho positions the planar

conformations are destabilized due to steric repulsion.
 Energy profile diagram of biphenyls

A double minimum in energy around 90° and 270° indicates that

the two phenyl planes are approximately but not exactly
perpendicular to each other.
The isomerism which owes its existence to restricted rotation
around a single bond is known as atropisomerism and the isomers
are called atropisomers.

The bulkier the ortho substituents are, the higher is the energy
barrier separating the enantiomers and when it exeeds 100
kJ/mol the stereoisomers may be separable at room
temperature.