Stereochemistry: an introduction

Origins

Etienne Louis Malus

(1775-1812). French physicist,
Conducted experiments (1809) to verify Christian
Huygens work.
French astronomer,
mathematician, and
physicist.
The stereochemistry of 2,3-dibromobutane
The possible stereoisomers of 1,2,3,4-tetrabromobutane are as follows:

CH2Br CH2Br

Figures 1 & 2, represent

H Br Br H
the same(identical) molecule
H Br Br H
because Fig.2 is superimposable
CH2Br CH2Br on Fig.1 and vice-versa.

1 2
CH2Br CH2Br

Br H H Br The possible stereoisomers of

1,2,3,4-tetrabromobutane are
H Br Br H
as follows:

CH2Br CH2Br
3 4
 Diastereomers
Superimposability check based on Fisher’s Restrictions:
1) Slide (movement without taking the molecule out of the plane
of projection) mirror image projection over the original.
At this stage if you find superimposability then our conclusion is
that the mirror image is representing identical molecule. Hence
the structure is achiral even though stereocenters are present.

CH2Br CH2Br

H Br Br H

H Br Br H

CH2Br CH2Br
 Diastereomers
2) If you find after the first step, the mirror image is non
superimposable then we should rotate the mirror image through
180o while keeping it within the plane of projection.
If we now find it to be superimposable then our conclusion is that
the mirror image is representing identical molecule. The structure
is therefore achiral even though stereocenters are present in it.
CH2Br CH2Br
1800
Br H H Br

Br H H Br

CH2Br CH2Br

Superimposable
 Enantiomers
CH2Br CH2Br
(R) (S)
Br H H Br
(R) (S)
H Br Br H

CH2Br CH2Br
3 4
Testing the superimposability of 4 on 3 as before we find they
are non superimposable.
Therefore, figures 3 and 4 represent a pair of enantiomers as
they are non-superimposable mirror image stereoisomers.
 MESO and diastereomer
CH2Br
In Figure 1, there are two
(S)
stereocenters but we found it to be
H Br achiral.
This is an example of a meso
H Br
(R) compound.
It is achiral since it has a plane of
CH2Br symmetry.
CH2Br CH2Br
This is an example of a
(S) (R)
H Br Br H diastereomeric
(R) (R) relationship between 1
H Br H Br
and 3. Neither mirror
1
3 image nor superposable
CH2Br CH2Br
 The stereochemistry of 1,2,3,4-tetrabromobutane
The stereochemistry of 1,2,3,4-tetrabromobutane can be
summarized as:
Maximum number of stereoisomers = 3
Number of Meso compound = 1
Number of enantiomeric pairs = 1
Number of diastereomeric relationships = 2
How many stereoisomers?
maximum number of stereoisomers = 2n
where n = number of structural units capable of stereochemical variation

structural units include chirality centers and cis and/or trans double bonds

number is reduced to less than 2n if meso forms are possible

How many stereoisomers? 3-Penten-2-ol
E E Z R Z S
R S
H OH
H HO H
HO H OH
 How to recognise a meso structure?

• Check if there is an inherent plane of symmetry.

• If you cannot visualise the plane of symmetry in the
structure, do the following:-
 Both chiral centres must have identical substituents.
 Both chiral centres must have opposite configuration.

Is the adjacent compound

Meso or not?
 Diastereomers
Look at different isomers of 2-bromo-3-chlorobutane

(i) & (iii) represents a diastereomeric pair

(ii) & (iv) represents a diastereomeric pair
(i) & (iv) represents a diastereomeric pair
(ii) & (iii) represents a diastereomeric pair
The possible stereoisomers of 1,2,3,4-tetrabromobutane are as follows:

CH2Br CH2Br

Figures 1 & 2, represent

H Br Br H
the same(identical) molecule
H Br Br H
because Fig.2 is superimposable
CH2Br CH2Br on Fig.1 and vice-versa.

1 2
CH2Br CH2Br

Br H H Br The possible stereoisomers of

1,2,3,4-tetrabromobutane are
H Br Br H
as follows:

CH2Br CH2Br
3 4
 Diastereomers
Superimposability check based on Fisher’s Restrictions:
1) Slide (movement without taking the molecule out of the plane
of projection) mirror image projection over the original.
At this stage if you find superimposability then our conclusion is
that the mirror image is representing identical molecule. Hence
the structure is achiral even though stereocenters are present.

CH2Br CH2Br

H Br Br H

H Br Br H

CH2Br CH2Br
 Diastereomers
2) If you find after the first step, the mirror image is non
superimposable then we should rotate the mirror image through
180o while keeping it within the plane of projection.
If we now find it to be superimposable then our conclusion is that
the mirror image is representing identical molecule. The structure
is therefore achiral even though stereocenters are present in it.
CH2Br CH2Br
1800
Br H H Br

Br H H Br

CH2Br CH2Br

Superimposable
 Enantiomers
CH2Br CH2Br
(R) (S)
Br H H Br
(R) (S)
H Br Br H

CH2Br CH2Br
3 4
Testing the superimposability of 4 on 3 as before we find they
are non superimposable.
Therefore, figures 3 and 4 represent a pair of enantiomers as
they are non-superimposable mirror image stereoisomers.
 MESO and diastereomer
CH2Br
In Figure 1, there are two
(S)
stereocenters but we found it to be
H Br achiral.
This is an example of a meso
H Br
(R) compound.
It is achiral since it has a plane of
CH2Br symmetry.
CH2Br CH2Br
This is an example of a
(S) (R)
H Br Br H diastereomeric
(R) (R) relationship between 1
H Br H Br
and 3. Neither mirror
1
3 image nor superposable
CH2Br CH2Br
 The stereochemistry of 1,2,3,4-tetrabromobutane
The stereochemistry of 1,2,3,4-tetrabromobutane can be
summarized as:
Maximum number of stereoisomers = 3
Number of Meso compound = 1
Number of enantiomeric pairs = 1
Number of diastereomeric relationships = 2
How many stereoisomers?
maximum number of stereoisomers = 2n
where n = number of structural units capable of stereochemical variation

structural units include chirality centers and cis and/or trans double bonds

number is reduced to less than 2n if meso forms are possible

How many stereoisomers? 3-Penten-2-ol
E E Z R Z S
R S
H OH
H HO H
HO H OH
 How to recognise a meso structure?

• Check if there is an inherent plane of symmetry.

• If you cannot visualise the plane of symmetry in the
structure, do the following:-
 Both chiral centres must have identical substituents.
 Both chiral centres must have opposite configuration.

Is the adjacent compound

Meso or not?
 Diastereomers
Look at different isomers of 2-bromo-3-chlorobutane

(i) & (iii) represents a diastereomeric pair

(ii) & (iv) represents a diastereomeric pair
(i) & (iv) represents a diastereomeric pair
(ii) & (iii) represents a diastereomeric pair
 Diastereomers - Properties
• Diastereomers have different physical properties: m.p.,
b.p and hence can be separated easily either by
crystallisation, distillation etc.
• They have different physical and chemical properties in
any type of environment.
COOH COOH

HO H HO H

H OH HO H

bp 0.90C bp 3.70C
COOH COOH
trans-2-butene cis-2-butene
mp 171-1740C mp 146-1480C
Diastereomers of tartaric acid
 Properties of Diastereomers and enantiomers
• Diastereomers have different physical properties: m.p., b.p.
• They can be separated easily.
• Enantiomers differ only in reaction with other chiral molecules and
the direction in which polarized light is rotated.
• Enantiomers are difficult to separate.
Important information on Fischer Projections
o
OH o H o CH3 90 CO 2 H
90 90
H CO 2 H CH3 OH HO 2 C H HO CH3

CH3 CO 2 H OH H
(S) (R) (S) (R)

Even number of exchanges at the same chiral centre would lead to

identical molecule.

Odd number of exchanges at the same chiral centre would lead to

the enantiomers.
 Optical activity, plane polarized light
• Most of the light which we see is unpolarized light,
vibrating randomly in all directions.
• Plane polarized light is composed of waves that vibrate
in only one plane.
• Ordinary light is turned into plane polarized light by
passing it through polarizing filter made up of the
material known as Polaroid or calcite (a crystalline form
of CaCO3).
• The direction of vibration is called the axis of filter.
• Rotation of plane polarized light is called optical
activity and an optically active substance is one that
rotates the plane polarized light.
Plane polarized light
Chiral compounds are optically active; they rotate the
plane of polarized light.

Clockwise (+) Counterclockwise (-)

Different from R,S configuration

Achiral compounds do not rotate the plane of polarized

light. They are optically inactive.
 Plane polarized light
Plane polarized light is obtained
as a superposition of a left circularly
polarized (LCP) & a right circularly
polarized (RCP) light wave, whose
amplitude is identical.
Translation and rotation are occuring at the
same time

Enantiomorphic helical light wave http://www.enzim.hu/~szia/cddemo/edemo8.htm

Behaviour of polarized light in chiral medium Diastereoisomeric

Interaction:
Chiral molecules
refract one helical
electrical vector
more than the other
For optically active compounds
refractive index is different for
left and right circularly polarized
light.
speed of light is different
for the two polarizations