Meso compound

Meso compound Plane of symmetry Superimposable

Optically inactive

Internal plane of symmetry Internal plane of symmetry

Optically inactive Point of inversion or
center of symmetry
Optically inactive
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Disubstituted cyclic molecules
• Consider 1,3-dibromocyclopentane. Since it has two stereogenic
centers, it has a maximum of four stereoisomers.

• A disubstituted cycloalkane can have two substituents on the

same side of the ring (cis isomer, A) or on opposite sides of the
ring (trans isomer, B). These compounds are stereoisomers but
not mirror images.

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Disubstituted cyclic molecules

• The cis isomer is superimposable on its mirror image, making the

images identical. Thus, A is an achiral meso compound.

• The trans isomer is not superimposable on its mirror image,

labeled C, making B and C different compounds.
• B and C are enantiomers. 3
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Disubstituted cyclic molecules
Rotate

Conformational

Two can not be separated, optically inactive.

Optically active Rotate

Non-superimposable
mirror image

If the contributing conformations average out to an achiral conformation, then the

molecule is considered achiral and If a chiral conformation prevails over the others,
then the molecule is considered chiral and it will show optical activity. 4
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Chirality without chiral center
Atropisomers: If a molecule is bulky or highly strained and
can not easily convert from its original conformation to the
mirror image conformation. The molecule becomes
conformationally locked and enantiomers generated so are
called atropisomers.

H H

H H

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Allenes

Allene is achiral.
Allenes can be Chiral
H H
H H
C C C C C C
Cl Cl
CH3 CH3

For allenes to be chiral, end carbons must have different groups.

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Geometrical isomerism

Cahn-Ingold-Prelog convention
• If the higher priority groups are on the same
side the stereoisomer is called as ‘Z’.
• If the higher priority groups are on the opposite
side the stereoisomer is called as ‘E’. 7
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Resolution
• The separation of enantiomers from a racemic
mixture is called resolution.
• Convert the pair of enantiomers into two
diastereomers.
• Diastereomers are different compounds and
have different physical properties so can be
separated by crystallisation, distillation etc.
• A common reaction for chemical resolution is
salt formation
• After separation of the diastereomers, the
enantiomerically pure compounds are recovered. 8
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Resolution

• A common reaction for chemical

resolution is salt formation
• After separation of the diastereomers,
the enantiomerically pure compounds are
recovered.

+ - +
RCOOH :B RCOO HB
(R,S)-Carboxylic (R)-Bas e (R,R)-Salt + (S,R)-Salt)
acid

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Resolution and Chiral Chromatography
COOH
COO NH3
NH2
H CH3
HO H CH3 H
HO H3C
(R)-2-hydroxypropanoic acid
H
H3C An R, R salt
They are diastereomers
Have different physical and
COOH
COO NH3
chemical properties
Can be seperated
HO CH3
H HO CH3 H
H H3C
(S)-2-hydroxypropanoic acid

Racemic mixture An S, R salt

Solution of (+) & (-)

Chiral column (-) enantiomer

packing (+) enantiomer

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Stereoselective Reaction
• Reactions that lead to a predominance of one stereoisomers
over other stereoisomers that could possibly be formed.
• Enantioselective reaction: one of the two enantiomers is
produced in excess whenever possibility of the formation of
both exists.
• Diastereoselective reaction: one of the two diastereomers is
produced in excess whenever possibility of the formation of
both exists.
• For a reaction to be steroselective, a chiral reagent, chiral
solvent, or chiral catalyst must assert an influence on the
course of the reaction.
• In nature, where most reactions are enantioselective, the
chiral influences come from protein molecules, called
enzymes. 11
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Reactions involving stereoisomers
Conversion of an achiral molecule into a chiral
molecule, with the generation of a chiral center.
n-butane + Cl2 hν sec-butylchloride + n-butylchloride

One of the products of chlorination of n-butane is sec-

butylchloride which can exist as two enantiomers, as it has
a stereocenter in it.
CH3 CH3

H Cl Cl H

C2H5 C2H5
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Reactions involving stereoisomers

C2H5 C2H5 C2H5

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Reactions involving stereoisomers

H OH
Attack from bottom side
H3 C CH2CH3
O

H 3C CH2CH3
HO H
H 3C CH2CH3
Attack from top side 14
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Reactions involving stereoisomers
• Synthesis of chiral compounds from achiral
reactants always yields the racemate.
Optically inactive reactants yield optically
inactive products.
Reaction of a chiral molecule where bonds to the
chiral center are not broken.
Chlorination of (S)-2-chlorobutane
CH3 CH2 CH2Cl
Cl Cl
Cl2
H Cl H H Cl
C 2H 5 C2H5 C 2H 5
(R)-1,2-dichlorobutane
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Reactions involving stereoisomers

A reaction that does not involve the breaking of a bond

to a stereocenter proceeds with retention of
configuration about that stereocenter.

(S)-2-Methyl-1-butanol (S)-1-Chloro-2-methylbutanol

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