The document discusses various methods for resolving a racemic mixture into its pure enantiomers, including: 1) Mechanical separation, which separates crystal forms of enantiomers 2) Preferential crystallization, which seeds a solution with a pure enantiomer to induce crystallization 3) Biochemical separation using microorganisms that metabolize one enantiomer more quickly 4) Chromatographic separation exploiting differences in how enantiomers adsorb to a chiral support 5) Kinetic methods using reactions that proceed at different rates for each enantiomer 6) Precipitation of one enantiomer through reaction with a reagent 7) Formation of diastereomers with an opt

1. RESOLUTION OF RACEMIC MIXTURE
BY
IQRAR AHMAD ABRAR AHMAD
Department Of Pharmaceutical Chemistry
M.Pharm First Year(Sem 1)
RCPIPER,shirpur
1

2. ENANTIOMERS:
 Isomers which are nonsuperimposable mirror images of each
other are called enantiomers.
 These are distinguished by
 1)+/-
 2)D/L
(l/-)-enantiomer
(anticlockwise rotation)
(dl/±)-racemate
(no overall effect)
(d/+)-enantiomer
(clockwise rotation)
2

3.  RACEMIC MIXTURE: A equimolar(50/50) mixture of the two
enantiomers is called a racemic mixture or a racemate.
 Enantiomers have identical chemical and physical properties,
except:Their effect on plane polarised light.
 RESOLUTION: the process of seperation of pure enantiomer from
their racemic modification is called resolution.
3

4. NEED FOR RESOLUTION OF RACEMIC
MIXTURE:
CETRIZINE
levocetirizine has been found to be less sedating than
cetirizine
4

5. LEVODOPA
levodopa (L-dopa) is used in treatment of Parkinson’s disease, its
D-form causes serious side effects,such as granulocytopenia
5

6. RESOLUTION
OF RACEMIC
MIXTUR
MECHANIC
AL
SEPERATIO
N
PREFRENTI
AL
CRYSTALLIZ
ATION
BIOCHEMIC
AL
SEPERATIO
N
BY
DIASTEREO
MERS
PRECIPITATI
ON
CHROMATO
GRAPHIC
SEPERATIO
N
KINETIC
METHOD
6

7. 1.MECHANICAL SEPARATION OR
SPONTANEOUS RESOLUTION:
 This invoved mechanical separation of the crystal of one enantiomers
from the other in racemic mixture based on difference in their shapes
 Crystal of the two forms have different shapes separated by
magnifying lens and forceps
 This method first used by pasteur for he resolutiuon of sodium
ammonium tartarate which crystallise out in the form of racemic
mixture below 27 degree
 This methods is time consuming and every compound can not be
crystallized at room temperature
7

8. 2.PREFERENTIAL CRYSTALIZATION BY
INOCULATION:
 This method involve seeding of a saturated solution of the racemic
mixture with a pure crystal of one the two enantiomers.
 The soluition now become suppersaturated with respect to the added
enantiomers
 It begins to crystallise out
 Eg. Harda obtained free from amino acid by adding corresponding
d/l isomers of amino acid
8

9. 3.BIOCHEMICAL SEPARATION:
 It was introduced by PASTEUR in 1858.
 This method is based on fact that when certain micro organisms like
bacteria,fungi,yeast,moulds,etc are grown in dilute solution of racemic
mixture,they eat up one enantiomer rapidly than other.
 Example: the mould penicillium glaucum preferentially destroys the
(+) isomer of racemic ammonium tartarate leaving (-) ammonium
tartarate in solution.
9

10. 4.CHROMATOGRAPHIC SEPERATION:
 The racemic mixture can be separated by chromatography on an
optically active support.
 The diastereomeric adsorbates which are formed have different
stabilities.
 Thus one enantiomer will be held more tightly than the other and
would be eluted first.
10

11. 5.KINETIC METHOD :
 This method is based on the fact that one of the enantiomer of racemic
mixture reacts faster than other with optically active compound.
 menthol reacts faster with (+) mandelic acid than with (-) mandelic
acid.
 Thus with difference in kinetics of reaction,racemic mixture can be
seperated.
11

12. 6.PRECIPITATION:
 This method is based on formation of precipitate by reaction between
any reagent and racemic mixture.
 Example: (+) & (-) narcotine when dissolved in HCL ,precipitates
(+) narcotine.
12

13. 7.BY DIASTEREOMERS:
 When racemic mixture is allowed to interact with optically active
material, it give a diastereomeric derivatives.
 Diastereomer have different physical properties and hence can
easily separated into two component by fractional crystallisation
13

14. REFRENCES:
 1. O.P Agrawal, “Organic Chemistry Reaction And Reagent”
Goel Publication Fourty Eight Edition 2012 Page No.137-143
 2.Ernest L Eliel, “Stereochemistry Of Carbon Compound”
Tata Mc Graw-hill Page No.47-75
 3.Jerry March, “Advance Organic Chemistry” Fourth Edition
Page No.120-124
 4 Morrison Boyd, “Organic chemistry”, edition-6,page-133
14

15. 15