The document discusses racemization and resolution of enantiomers. Racemization is the process where an enantiomer converts to a racemic mixture. Resolution separates the enantiomers of a racemic mixture. Various mechanisms of racemization are described, including those involving carbanions, carbonium ions, free radicals, and stable symmetrical intermediates. Methods of resolution discussed include crystallization, formation of diastereomers, chromatography, equilibrium asymmetric transformations, kinetic asymmetric transformations, biochemical transformations, and inclusion compounds.
2. 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.
7. Mechanism involving carbonium ions
Recombination of
anion
gives racemic mix.
R
1
R
2
C
R
3
Cl R
2
C
+
R
1
R
3
-Cl-
acid
+/-
carbonium
8. 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
R
1
R
2
C
R
3
+ Cl
R
2
C
R
1
R
3
Cl
Cl C
R
3
R
1
R
2
12. 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
15. 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
16.
17. Resolution through equilibrium
asymmetric transformation
In this, resolution involve 2 steps:
1. Epimerisation of diastereotopic species
2. Precipitation of the predominant epimer
This combination of epimerisation and
precipitation is known as second order
asymmetric transformation.
19. 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.
20. 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.