BITS Pilani

Pilani Campus

CHEM F111 General Chemistry

Lecture 29
Dr. Ajay K. Sah
BITSPilani, Pilani Campus

Stereochemistry
Without looking at the structures, label each
pair as either enantiomers or diastereomers.
a) (2R,3R)-2,3-hexanediol & (2S,3S)-2,3hexanediol

Both change, enantiomers

b) (2R,3S,4R)-2,3,4-hexanetriol &
(2S,3R,4R)-2,3,4-hexanetriol
2 change, one stays the same, diastereomers
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Stereochemistry
Configurational stereoisomers of
Alkenes (Geometrical isomerism )
Q: Which is the simplest alkene in which
this isomerism can be expected?
Ans: Butene.
Is it expected in all butenes ?
No, not in all three isomeric butenes ( viz., 1butene, isobutene and 2-butene).

But, only in but-2-ene.

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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.
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Geometrical isomerism

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Stereochemistry

Configurational stereoisomers
of cycloalkanes

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Stereochemistry
Chiral compounds without
asymmetric atoms
Conformational Enantiomerism
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.
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Atropisomers

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Atropisomers
trans - cyclooctene
H
H

H
H

This molecule has no stereocenters, but it

is chiral.
The enantiomers have either a righthanded or a left-handed twist.
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Atropisomers: Allenes
Contains sp hybridized carbon with adjacent
double bonds: -C=C=C End carbons must have different groups.

Allene is achiral.
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Atropisomers: Allenes

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Physical Properties

Enantiomeric molecules differ in the direction in

which they rotate plane polarized but their
other common physical properties are the
same.
Diastereomers have a complete set of different
physical properties.
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13

Optical activity
Light possesses certain properties that
are best understood by considering it to be
a wave phenomenon in which the vibrations
occur at right angles to the direction in
which the light travels.

There are infinite number of planes

passing through the line of propagation, and
ordinary light is vibrating in all these planes.
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Plane polarized light

Plane polarized light is light whose
vibrations take place in only one of these
possible planes.
Ordinary light is turned into plane
polarized light by passing it through a
prism made up of the material known as
Polaroid or more traditionally through
pieces of calcite (a crystalline form of
CaCO3) so arranged as to constitute Nicol
prism.
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Plane polarized light

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Plane polarized light

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Optically active substance

An optically active substance is one that
rotates the plane of polarized light.
If the rotation of the plane is in clockwise
direction the substance is said to be
dextrorotatory and the rotation is labeled
d or (+).
If the rotation is in counterclockwise
direction then substance is said to be
laevorotatory and the rotation is labeled
l or (-).
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Optically active substance

Two enantiomers rotate plane-polarized
light to an equal extent but in opposite
directions.
No relationship exists between R and S
prefixes and the (+) and (-) designations
that indicate optical rotation.
The optical activity of a compound is
determined by an instrument called
polarimeter.
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Polarimeter

It is an instrument that allows

polarized light to travel through a
sample tube containing an organic
compound. It permits the measurement
of the degree to which an organic
compound
rotates
plane-polarized
light.
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With achiral compounds, the light that exits the

sample tube remains unchanged. A compound
that does not change the plane of polarized
light is said to be optically inactive.
Polarizer
Sample tube

Ordinary light
Plane polarized light

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With chiral compounds the plane of the

polarized light is rotated through an angle .
The angle is measured in degrees (), and is
called the observed rotation.
Plane of polarization has changed

Plane polarized light

Exiting Plane
polarized light

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Specific rotation
Standardized physical constant for
the amount that a chiral compound rotates
plane-polarized light.
It is the number of degrees of rotation
observed if a 1-dm tube is used, and the
compound being examined is present to the
extent of 1g/ml.

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Specific rotation
This
is
usually
calculated
from
observations with tubes of other lengths
and at different concentrations by means
of the equation:
Temp

(observed)
[] D =
cl

c is concentration in g/mL
l is length of path in decimeters.
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Specific rotation

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Racemic Mixtures
An equimolar mixture of two enantiomers
is called a racemic form (either a
racemate or a racemic mixture).
Notation: (d,l) or ()
It does not show any rotation of plane
polarized light.

The mixture may have different b.p. and

m.p. from the enantiomers!
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Optical Purity
A sample of an optically active substance
that consists of a single enantiomer is
said to be enantiomerically pure.

Optical purity is specified for

a
mixture that is neither optically pure nor
racemic
(Observed specific rotation) X 100
o.p. = -------------------------------------------------Specific rotation of the pure enantiomer
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Enantiomeric excess
Denoted by the symbol ee.
Amount of pure enantiomer in excess
of the racemic mixture.

ee = % of one enantiomer - % of the other

% ee =

enantiomer
(Moles of one enantiomer - Moles of
other enantiomer) X 100
---------------------------------------------Total moles of both enantiomers
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Enantiomeric excess
If observed specific rotation of an
enantiomeric solution is +6.760 and
specific rotation of the pure enantiomeric
solution is +13.520 then
+6.760 X 100
% ee = ----------------------------------- = 50 %
+13.520
What does this 50% mean?
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Enantiomeric excess
It means, 50% of the mixture consists of
the (+)enantiomer (the excess) and the
other 50% consists of the racemic form.

Hence, the mixture contains 75% of

one enantiomer and 25% of the other

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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.
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Resolution
A common reaction for
resolution is salt formation

chemical

After separation of the diastereomers,

the enantiomerically pure compounds are
recovered.
+
:B
RCOOH
(R,S)-Carboxylic (R)-Bas e
acid

RCOO HB
(R,R)-Salt + (S,R)-Salt)

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Resolution

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Chiral Column Chromatography

Solution of
(+) and (-)
Chiral column
packing

(-) enantiomer
(+) enantiomer

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Stereoselective Reaction
Reactions that lead to a preponderance 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.
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Stereoselective Reaction
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.
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Reactions involving stereoisomers

(a) Conversion of an achiral molecule into
a chiral molecule, with the generation of a
chiral center.
h
n-butane + Cl2
sec-butyl chloride
+
n-butyl chloride
One of the products of chlorination of nbutane is sec-butylchloride which can
exist as two enantiomers, as it has a
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stereocenter in it.

Stereochemistry
Reactions involving stereoisomers
CH

CH

Cl
C2H5

(S)-(+)-secbutylchloride

and

Cl

H
C2H5

(R)-(-)-secbutylchloride
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Stereochemistry

C2H5

C2H5

C2H5

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Reactions involving stereoisomers

H
Attack from bottom side

H3C

OH
CH2CH3

O
H3C

CH2CH3
Attack from top side

HO
H3C

H
CH2CH3
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Stereochemistry
Reactions involving stereoisomers
Synthesis of chiral compounds from
achiral reactants always yields the
racemate.

This is simply one aspect of the more

general rule:
Optically inactive reactants yield optically
inactive products.
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Stereochemistry
Reactions involving stereoisomers
(b) Reaction of a chiral molecule where
bonds to the chiral center are not broken.

*
CH3CH2CHClCH3 + Cl2

*
CH3CH2CHClCH2Cl
+
other products
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Stereochemistry
Reactions involving stereoisomers
We focus our attention on one of these
products,1,2-dichlorobutane.

CH3
Cl
H

Cl

CH2
Cl
H

C 2H 5
(S)-sec-butylchloride

C 2H 5

Cl2

CH2Cl
Cl
H
C 2H 5

(R)-1,2-dichlorobutane
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Stereochemistry
Reactions involving stereoisomers
In the above reaction since we break
no bond to the stereocenter in either step,
we say configuration is retained.
An axiom of stereochemistry is :

A reaction that does not involve the

breaking of a bond to a stereocenter
proceeds with retention of configuration
about that stereocenter.
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Stereochemistry
Relative configuration

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Stereochemistry
Relative configuration

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Fischer Rosanoff convention

D-L system
Correlate to D- and
L-glyceraldehyde
D-erythrose is
mirror image of
L-erythrose

the

Now only used for

sugars and amino
acids
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