stereochemistry

1. Stereochemistry (study of stereoisomers)
Stereoisomers are the compounds with same molecular formula, and the same
structural formula but different arrangement of atoms in the three
dimensional space. This spatial arrangement of atoms or groups in the space is
called configuration.
Types of stereoisomers
1. Geometrical (cis-trans) isomers
2. Optical isomers – Enantiomers, and diastereomers
Geometrical (cis-trans) isomers
These are the stereoisomers that exist due to restricted rotation of atoms or
groups on double bonded carbon atoms or adjacent carbon atoms in a cyclic
molecule.
The independent rotation of atoms or groups in such condition is not possible,
and if we attempt to rotate them in opposite directions, the bond is broken.
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2. Criteria of existence of cis trans isomers
1. Same set of different groups on adjacent carbon atoms
2. Restricted rotation of these groups, connected to double bonded C atoms or adjacent
carbon atoms of cyclic molecule

4. 1. Trans isomer is more stable than cis isomer. It is because of high steric
repulsion between the similar groups on the same side in cis isomer.
2. We can get a mixture of cis and trans isomers starting from cis or trans isomer.
For this, we heat the isomer to cause breakage of π bond, so that there is
independent rotation of groups around the single bond with detached p
orbitals, and upon reformation or cooling, there is spatial rearrangement to
give both cis and trans isomers.

5. 3. Geometrical isomers differ in their chemical as well as physical properties
like m.pt., b. pt., solubility etc. So, they can be separated by conventional
physical methods like fractional crystallisation, fractional distillation,
recrystallization etc.
4. E and Z isomers are the special type of geometrical isomers. The E isomers
contain the groups of similar priority on opposite sides (E means entgegen
or opposite) and Z isomers contain the groups of similar priority on same
side ( Z means zussamen or together).

6. Optical Activity
An ordinary beam of light consists of radiations vibrating in all planes
in the three dimensional space. But, when it is passed through a nicol
prism or grating, the light emerged from it consists of radiations
vibrating in only one plane. Such a light with radiations vibrating in
only one plane is called plane polarized light.
An organic compound is said to be optically active if its solution can
rotate the plane polarized light either clockwise or anticlockwise. The
optical isomer which rotates the plane polarized light clockwise is
called dextrorotatory (+) and that which rotates such light
anticlockwise is called laevorotatory (-) isomer.
Optical activity is measured by polarimeter, in terms of optical rotation
in degree (°) (+) or (-).

7. Asymmetric Carbon atom
It is the carbon atom bonded with four different atoms or groups. Such
carbon atom is taken as optical or chiral centre.
Plane of Symmetry
It is the plane through which an object or a molecule can be divided into two
equal halves. Such a molecule is always superimposable with its mirror image,
and can not be optically active or chiral. It is always optically inactive or
achiral.

8. Criteria of optical activity
The only condition required for optical activity is non superimposability of a
molecule with its mirror image. Such a phenomenon which arises due to lack of
plane of symmetry in a molecule is called chirality or dissymmetry.
So, the molecule which lacks a plane of symmetry is called chiral or dissymmetric
molecule, and it shows optical activity.
1. A compound with only one asymmetric carbon is always chiral or dissymmetric,
or optically active. Eg. Lactic acid

9. 2. A compound with two or more asymmetric carbon atoms may be chiral or
achiral. Eg Tartaric acid

10. Types of optical isomers
Enantiomers:
When two stereoisomers are nonsuperimposable mirror images of
each other, the type of isomerism is called enantiomerism and these
isomers are referred to as enantiomers.
•Enantiomers are the stable and isolable compounds that differ in
their spatial arrangements in 3-D space.
•The exist as discreet pairs.
•The properties of enantiomers are identical. However, their
interaction with a plane of polarized light can vary.
•The direction in which they rotate the plane-polarized light is
different, that is, if one rotates in the right direction, the other rotates

11. Diastereomers:
When two isomers do not behave as mirror images of each other, they are called
diastereomers.
•A molecule with ‘n’ number of asymmetric carbon atoms can have up to ‘2n’
diastereomers.
•When two diastereomers differ at only one stereocenter, they are referred to as epimers.
•These isomers vary in physical properties and chemical reactivity.

14. Meso compound
A compound which has more than one asymmetric carbon (more than one chiral center) and has a plane of
symmetry and hence optically inactive is called meso compound. In such a compound, optical rotation of
one half of the molecule is cancelled by equal and opposite rotation of another half of same molecule.
A meso compound is one whose molecules are superimposable on their mirror images even though they
contain chiral centers.
Examples:

15. Racemic mixture (Racemate or Racemic modification)
A mixture of equal amounts of two enantiomers is called racemic mixture or racemic
modification or racemate. In other words, it is a 50:50 mixture of two enantiomers. Such a
mixture is optically inactive (can not rotate plane polarized light) because two compounds rotate
the plane polarized light equally but in opposite direction and cancel one another. The net
rotation becomes zero. It is denoted by ±.
Examples: ± Lactic acid , ± Tartaric acid.

16. Optical Resolution
The separation of a racemic mixture into its (+) and (—) components is called optical
resolution. Since the optical isomers have identical physical properties, they cannot be
separated by conventional physical methods such as fractional crystallization or fractional
distillation. So, they are separated by special techniques called optical resolution.
Ways of Optical Resolution
1. Chemical Resolution
2. Biochemical Resolution
3. Mechanical Resolution

17. Chemical resolution (Pasteur, 1858)
In chemical resolution, the racemic mixture is made to combine with another optically active compound to form
diastereomers. Thus, the principle of this method is that diastereomers have different physical properties such as
melting point, boiling point, solubility etc. and they can be easily separated using conventional techniques like
fractional crystallization, solvent extraction etc. When, separated components are treated with suitable reagent, (+)
and (—) isomers are resolved.
Conditions essential for effective chemical resolution
a) Produced diastereomers should be easily separated.
b) There should be an easy method to convert the so separated diastereomers into original isomers using suitable
reagents.
c) The optically active compound to be used should be cheap and recovered easily.
d) It must have suitable functional group to produce the diastereomers that can be easily separated.
Examples: Acids
+ Tartaric acid, Maleic acid, Mandelic acid etc.
Bases:
Strychnine, Brucine etc.

19. Biochemical resolution (Pasteur, 1858)
When certain bacteria or moulds are added to the racemic mixture, one of the enantiomers is consumed (decomposed) and
another can be isolated. So, we get only one type of isomer by this method.
Disadvantages of biochemical method:
i) One of the enantiomers is scarified.
ii) It cannot be applied to (±) mixtures of poisonous substances which are
incapable of acting as food for organisms.
Example:

20. Mechanical resolution (Pasteur, 1848)
This method is applicable only to solid which form well defined crystals. Frequently, the
racemic mixtures consist of two types of crystals which have different shapes, being the
mirror images of each other. The two varieties of crystals can be separated with the aid of
a magnifying lens and a small forceps. This method is too tedious for practical purposes
and is now of historical interest only because it was the first method which Pasteur
employed for the separation of the tartaric acids.

21. Racemization
The process of converting an optically active compound (+) or (-) isomer into racemic
mixture (±) is known as racemization. The (+) and (-) forms of most of the compounds are
capable of racemization under the influence of heat, light or chemical reagents. The process
involves the change of half of the active compound to the isomer of the opposite rotation, thus
resulting in the racemic mixture.

23. E and Z configurations of Geometrical Isomers
E and Z isomers are the special type of geometrical isomers. The E isomers contain the
groups of similar priority on opposite sides (E means entgegen or opposite) and Z isomers
contain the groups of similar priority on same side ( Z means zusamen or together).
The priority order of groups around the adjacent carbon atoms is determined on the basis
of sequence rules.
Sequence rules
1. Higher the atomic number, higher the priority of the atom (The atom directly attached
to the doubly bonded carbon). Example

24. 2. In the case of groups, the priority order is decided based on atomic number of the
first atom attached to the doubly bonded carbon. Example
3. If the priority order of the group cannot be decided based on atomic number
of first atom, then second atom’s atomic number of the group or subsequent
group is considered. Example