RACEMISATIONAND

METHODS OF RESOLUTION

By: Sheikh Khalida Banu, K.J. Somaiya College of Sci. and Com.

Introduction Racemisation is the process when

the enantiomer is converted into racemic modification 

Resolution is the process when a racemic modification is separated into its constituent enantiomers.

Racemisation and Resolution are complementary to each other.

Formation of racemic modifications

Racemic (mixture,

compound, solid

solution)

By synthesis

By mixingBy

racemisation

Racemisation Enantiomers exist in 50:50

population. Thermodynamically favourable

process.  Reversible process.

form form

+

Mechanism of racemisation Involving carbanions Involving carbonium ions Involving free radicals Involving stable symmetrical intermediates Through rotation around bonds Configurational change in reactions

Mechanism involving carbanionsOH

OOH

C

CHCH

CH

CHCH C

C

HH O -

H 2 O

OH

O

C

C

CHCH

CH

CH CH

C-

H

H + c a n re c o m bin e fro m e ithe r s id e s

+/-

(+) isomer + (-) isomer racemic mixture

carbanion

Mechanism involving carbonium ions

Recombination of anion gives racemic mix.

R1

R2

C

R3

Cl R2

C+

R1

R3

-C l-

ac id

+/-

carbonium

Mechanism involving free radical

Free radical has a near planar structure and if a chiral centre is converted into a free radical pair by homolytic cleavage of a bond, the recombination of pair leads to racemic product

R1

R2

C

R3

+ ClR2

C

R1

R3

ClCl C

R3

R1

R2

Mechanism involving stable symmetrical intermediate

Enantiomers are interconverted through stable achiral intermediates and get racemised.

Mechanism through rotation around bonds

Configurational change in substitution reactions

Methods of resolution By crystallisation method Through formation of diastereomers By chromatography Through equilibrium asymmetric

transformation Through kinetic asymmetric

transformation By biochemical transformation Through inclusion compounds

Mechanical separation by crystallisation is based on solubility of enantiomers.

Resolution through formation of diastereomers

By chromatography

RESOLUTION IN FOUR WAYS : FORMATION OF DIASTEREOMERS AND

THEN SEPARATION DIRECT RESOLUTION USING CHIRAL

STATIONARY PHASE DIRECT RESOLUTION USING ACHIRAL

MOBILE PHASE DIRECT RESOLUTION USING ACHIRAL

STATIONARY PHASE MODIFIED BY CHIRAL REAGENT

Resolution through equilibrium asymmetric transformation

In this, resolution involve 2 steps:1. Epimerisation of diastereotopic

species2. Precipitation of the predominant

epimer This combination of epimerisation and precipitation is known as second order asymmetric transformation.

Resolution through kinetic asymmetric transformation

Resolution by biochemical transformation

Chiral reagents are replaced by microorganisms or enzymes which are stereoselective in their reactions.

It is mainly used in resolution in amino acids.

Through inclusion compounds

An inclusion compound is a complex in which one chemical compound (the "host") forms a cavity in which molecules of a second "guest" compound are located. 

If the spaces in the host lattice are enclosed on all sides so that the guest species is ‘trapped’ as in a cage, the compound is known as a clathrate. 

This method is of little practical use.