ISOMERISM

One of several species (or molecular entities) that have the same atomic composition
(molecular formula)but different line formulae or different stereo chemical formulae and
hence different physical and / or chemical properties is called isomer. The phenomenon
of existence of two or more compounds possessing the same molecular formula but
different properties is called isomerism.
Types of Isomerism
The isomerism is of two main types
a) Constitutional isomerism (formerly structural isomerism)
b) Stereo isomerism
a) Constitutional isomerism
The isomerism between structures differing in constitution and described by different
line formulae is called constitutional isomerism.
b) Stereo isomerism
Isomerism due to difference in the spatial arrangement of atoms without any
difference in connectivity or bond multiplicity between the isomers is called Stereo
isomerism.
The stereo isomerism is of three types
i) Geometrical isomerism
ii) Optical isomerism
iii) Conformational isomerism
Isomers

Constitutional Stereoisomers
(Structural isomers)

Conformational Configurational

Geometrical Optical
CONSTITUTIONAL ISOMERISM
Constitutional Structural isomerism can be further sub-divided as
I) Skeletal (or) Chain isomerism II) Position isomerism
III) Functional isomerism IV) Metamerism
V) Ring chain isomerism VI) Tautomerism

I) Skeletal (or) Chain isomerism

The compounds having same molecular formula but different arrangement of carbon
chain (skeleton) within the molecule are called chain isomers or skeletal isomers and
the phenomenon is termed as chain isomerism.
 ISOMERISM 117

The first three members of the alkane family  CH4 , C2H6 and C3H8  do not exhibit chain
isomerism.
Ex: 1. C 4 H10 2. C5 H12

Butane Isobutane Pentane Isopentane Neopentane

3. C 8 H10

Ethylbenzene 1,2-dimethylbenzen

Alkane C 4 H10 C5 H12 C 6 H14 C 7 H16 C 8 H18 C9H20 C10 H22

Chain Isomers 2 3 5 9 18 35 75

II) Position isomerism

The compounds which have the same molecular formula but differ in the position of
the functional group, carbon-carbon multiple bond or substituent group are called
position isomers and this phenomenon is termed as position isomerism.
Ex: 1)

2)

3)

2-methylpentane 3-methylpentane
118 ISOMERISM

4)

III) Functional isomerism

The compounds having same molecular formula but different functional groups in the
molecule are called functional group isomers and this phenomenon is termed as
functional group isomerism.
Ex: 1) Alkene cycloalkanes.

2) Alkynes dienes cycloalkenes bicycle.

3) Alcohols ethers

4) Aldehyde ketone unsaturated alcohol unsaturated ether

Cyclic alcohol

5) Acids esters
 ISOMERISM 119

6) Cyanide isocyanide
CH3 — CH2 — CN CH3 — CH2 — NC

7) Amide oxime nitroso

8) Phenol aromatic alcohols aromatic ethers

9) Nitroalkane alkyl nitrites

10) 1° amine 2° amine 3° amine

IV) Metamerism
The compounds having same molecular formula but different number of carbon atoms
(or alkyl groups) on either side of the functional group are called metamers and this
phenomenon is called metamerism.

Ex: 1) The two are metamers as well as position isomers.

A and B
2)  are metamers
A and C
B and C are not metamers but positional isomers since number of carbon
atoms are same on either side.
 120 ISOMERISM

3)
Both are metamers since nature of alkyl groups is changed.

4) B and C are metamers whereas

A and B
 are functional isomers
A and C
V) Ring Chain Isomerism
Ring-chain isomerism is the phenomenon shown by compounds having same
molecular formula but possessing open chain and closed chain structures. The
compounds showing this type of isomerism are known as ring-chain isomers.

Ex: 1) 2)

3)
Learn the skills:
1. Write the total number of structural isomers for molecular formulae C4H8?

Ans.

2. Draw the structural isomers of the formula C4H6.

Ans.

3. Draw all possible structures of C2H4O, C3H6O .

Ans. i)

ii)

4. How many cyclic compounds are possible with formula C 6 H12 and draw the structure?
 ISOMERISM 121

Ans. 12

5. How many substituted cyclohexanes are possible for the formula C 9 H18 and draw the
structure?
Ans. 12

Questions:
1. How many unsubstituted bicyclic compounds are possible with formula C 8 H14 ? Ans. 8.
2. How many chloro derivatives are possible for ethane? Ans. 2.
3. How many isomers possible for C7 H9N containing at least one benzene ring? Ans. 5.
4. How many mono bromo derivatives are possible for 2-methyl pentane? Ans. 5.

Tautomerism (Kryptomerism/Desmotropism)
The phenomenon of two (or) more structurally distinct compounds that are in rapid
equilibrium is called tautomerism. Isomers of the general form
GYX  Z Y  XZG
where the isomers called tautomers are readily interconvertible.
If G is hydrogen it is called prototropy.
Tautomers differ both physically and chemically and can be “isolated”.
Diad System (1, 2–shift)

Triad System (1, 3–shift)

1. Keto-enol 2. Nitro-acinitro

3. Amide – iminol (imidic acid)

 122 ISOMERISM

4. Lactam – Lactim 5. Phenol – keto

6. Nitroso – oxime 7. Cyanide – ketimene

Simple esters don’t exhibit tautomerism due to lack of sufficient acidity to -hydrogen.
_______________________________________________________________________________________

Higher Systems

1, 5 – shift

1, 7 - shift

Ring – chain tautomerism

Valence Tautomerism
Tautomerism in which single and/or double bonds are rapidly formed and ruptured without
migration of atoms (or) groups.
 ISOMERISM 123

3-bonds 2-bonds, 1 bond

Keto-enol tautomerism
Requirement
Presence of -hydrogen preferably bonded to sp3-carbon atom.
Reason
-hydrogen of carbonyl compounds is acidic due to resonance stabilization of their conjugate
base (carbon ion (or) enolate ion).

Factor influencing the enol content

I) Presence of active methylene group
A methylene group surrounded by two carbonyl groups is called active methylene
group.
Active methylene H-atoms are more acidic than normal -H atoms because the
conjugate base formed by deprotonation of active methylene H-atoms is stabilized by
resonance of two-carbonyl groups.
Any group that increases the acidity of active methylene H-atoms increases the enol
content.
If alkyl groups are connected to carbonyl carbons, they decrease the + on the carbon
by “electron releasing effect (+I effect)” and thus decrease the acidity of methylene H-
atoms.
Alkoxy groups involve in resonance with carbonyl carbon, thus decreasing its
availability to stabilize the conjugate base after deprotonation.
Phenyl groups attached to carbonyl groups provide extended conjugation in the enol
form, this enhances its enol content

Aceto acetic ester (EAA) Diethyl malonate (or)

Malonate ester (DEM)
Note
124 ISOMERISM

II) Aromaticity
Introduction of aromaticity stabilizes the enol to a larger extent than keto form which
makes phenols to exist almost 100% in enol form (resonance energy of benzene is
36 kcal/mol)

Ex: 1)

2)

3)
III) Bridge head
In a non-zero bridged bicycle compound, bridged head carbon cannot have a double
bond if the ring size is less than 8-carbons (Bredt’s rule).
Ex:

IV) Rings
Simple cyclic ketones have higher enol content than simple acyclic ketones.
Cyclic ketones have restricted rotation of their bonds and hence adding a double bond
does not make much difference to the entropy of system.
In case of acyclic ketones, there will be appreciable decrease in entropy due to
restricted rotation caused about C = C in the enol form.
Ex:

V) Steric relief
 ISOMERISM 125

Dimesityl acetaldehyde on moving from keto to enol form enjoys a steric relief of 10°
32' (theoretically) between two mesityl groups. This results in a very high enol
content.

Ex:

VI) Effect of -carbonyl group

i)

ii)
In (i), the dipoles of carbonyl groups align “anti” to each other to minimize the
repulsion between partial charges on oxygen.
The rigidity of the ring does not permit such an alignment, in the (ii). Thus it has no
other option but to enolise and stabilise via chelation.

VII) Excessive -substitution by fluorine

Excessive substitution of fluorine on -carbon favours keto form. In case of penta
flouro acetone, enol form can be prepared and it is quite stable at room temperature,
however on standing for longtime (or) heating it changes to thermodynamically more
stable keto form.

VIII) Effect of solvent

 126 ISOMERISM

Polar protic solvents have H than can involve in H-bond.

Ex: H2O, C2H5 OH, NH3 , etc.
Polar aprotic solvents do not have H-atoms that can involve in H-bonding.

Polar protic solvents solvate keto form forming hydrogen bonds with carbonyl oxygen,
hence increase in polarity of solvents shifts the equilibrium towards keto form.

Gaseous phase – 92 %
n – hexane solvent – 92 %
Liquid phase – 76 %
CH3CN – 58 %
H 2O – 15 %
IX) Effect of temperature
High temperature shift the equilibrium towards keto form.

Questions:
5. Which of the following show tautomerism?
A) CH3 COOH B) CH3COCl C) CH3COOEt

D) E) CH3CONH2
6. Arrange in order of enol content.
A)  HCO3 CH B)  CH3CO3 CH C)  i Pr CO3 CH3 D)  t  BuCO3 CH
Ans. A>B>C>D

Mechanism of enolisation

Acid catalysed enolisation

Mechanism
 ISOMERISM 127

Base catalysed enolisation

Mechanism

Ex: 1)

2)
Learn the skills:
6.

Ans. Mechanism

CONFORMATIONAL ISOMERISM
Conformations are different spatial arrangements of atoms (or) groups in a molecule that are
interconvertible by free rotation about single bond (or) flipping of rings.
Rotamers/conformers are conformations corresponding to minimum potential energy.
Conformers cannot be isolated as they convert rapidly but are detected spectroscopically.
They do not differ in physical properties and chemical properties.
Specific conformations are made use while proposing certain reaction mechanism.
128 ISOMERISM

For conformers to exist there must be two polyvalent atoms connected by single bond.
Ex: Ethane.

As there is a carbon-carbon single bond, rotation about the bond results in many
spatial arrangements called conformations.
Saw Horse Projection

Newmann Projections
In Newman projections the observer looks at the C—C bond head on. The three lines
emanating from the center of the circle represent the bonds coming from the front carbon,
with respect to the observer.

Newmann representation

Staggered Eclipsed
Dihedral Angle (Torsional Angle)
The angle of torsion, which is a dihedral angle, is the angle between the X—C—C and the
C—C—Y planes, as shown

Angle between the XCC and CCY plane is dihedral angle.

Conformations in Open Chain system

 ISOMERISM 129

1) Conformations of Ethane
The conformation in which torsional angle is 0° (or) 120° (or) 240° is called as Eclipsed
conformation.

Eclipsed Eclipsed
2) The conformation in which the torsional angle is 60° (or) 180° (or) 300° is called as
staggered conformation.

Staggered Staggered
3) Any conformation other than Staggered and Eclipsed are called Skew conformations.
There are infinite numbers of conformations possible for ethane.
The most stable conformation of ethane is the staggered conformation and the least
stable is eclipsed conformation.
The energy difference between the most stable conformation and the least stable
conformation is 12 kJ.
The low stability of eclipsed form is attributed to torsional strain.
At ordinary temperatures enough rotational energy is present for the ethane molecule
rapidly to rotate, though it still spends most of its time at or near the energy
minimum. Groups larger than hydrogen cause larger barriers. When the barriers are
large enough, as in the case of suitably substituted biphenyls, rotation at room
temperature is completely prevented and only configurational isomerism is exhibited.

Torsional Strain
It is the repulsion between electron clouds of bonds on adjacent atoms. It is maximum when
 = 0 and is minimum (or) zero in staggered form.

Conformations of Butane
n-butane is treated as 1,2-disubstituted ethane for which there are four extremes a fully
staggered conformation called anti, trans, or antiperiplanar another staggered conformation
called gauche or synclinal and two types of eclipsed conformations called synperiplanar and
anticlinal.
130 ISOMERISM

Energy diagram

The fully eclipsed is the least stable form due to van der Waals strain (steric repulsion) in
additional to torsional strain)
If the electron clouds of the pair of atoms (or) group of atoms (such as methyl group) are too
close to each other, then there is a destabilization due to the electrostatic repulsion of the
electron clouds called van der Waals strain.
In syn conformation (eclipsed) the distance between the methyl groups (210 pm) is less than
the sum of van der Waals radii of two hydrogen atoms (240 pm).
Repulsion between two methyl groups in gauche conformation is called “Gauche repulsion”.
Potential energy barrier between least and most stable conformation of butane is 25 kJ/mol.

Glycol and Related Compounds

Gauche form is more stable than anti form due to hydrogen bond.
 ISOMERISM 131

Generalization

1, 2-dihalo ethanes
Conformational equilibrium in 1, 2-dihalo ethanes shift from prefentially anti in the chloro,
bromo and iodo compounds, to “gauche” for the diflouride.

Conformation in Propanal
All the conformations so far discussed have involved rotation about sp3  sp3 bonds. Many
studies were also made of compounds with sp3  sp2 bonds. For example, propanal (or any
similar molecule) has four extreme conformations, two of which are called eclipsing and the
other two bisecting. For propanal the eclipsing conformations have lower energy than the other two,
with ‘P’ favored over ‘Q’ by ~1kcal mol
1
 4 kJ mol  .
1

P Q

CONFORMATIONS OF CYCLOALKANES
Baeyer’s strain theory
Baeyer assumed cycloalkanes as planar molecules and calculated the deviation of C—C—C (bond
angle) from original tetrahedral bond angle.
According to him lesser the deviation from the original angle, more is the stability.

Expected bond angles  10928 ' 10928 ' 10928 ' 10928 '
Assuming planar
structure bond angle  60 90 108 120
Deviation  4928' 1928 ' 128 ' 1052'
Angle strain  2444' 944' 44 ' 526'
Expected stability order
132 ISOMERISM

1
Angle strain = 109°28' —  bond angle assuming planar 
2
Heat of combustion and stability
For isomeric hydrocarbons, stability is inversely proportional to heat of combustion.

Ex: is more stable than .

Cycloalkane Heat of combustion per CH2 groups (in xJ/mol)

Cyclopropane 697
Cyclobutane 681
Cyclopentane 658
Cyclohexane 653
Cycloheptanes 657
Cyclooctane 658
Cyclononane 659
From the above data, the actual stability order of cycloalkanes.
Cyclopropane < Cyclobutane < Cyclopentane < Cyclohexane.
I) Conformations of Cyclohexane
Odd Hassel (1969 Noble Laureate) established that most stable conformation of cyclo
hexane “Chair conformation”.
In chair conformation, C—C—C bond angle and hence it is almost free from angle
strain.
As all the bonds are staggered, it is free of torsional strain.

II) Boat conformation

In boat conformation of cyclohexane ‘van der Waals stain’, ‘torsional strain’ are
present and angle strain is absent.

The C—C—C bond angle is 111° which makes it almost free from angle strain.
 ISOMERISM 133

Boat is de-stabilised by van der Waals strain involving two flag pole hydrogens which
are at a distance of 180 pm.
Also there is a torsional strain between the eclipsed bonds of four carbon atoms.
Boat is less stable than chair form by 27 kJ/mol.
III) Twist boat conformation
The torsional and van der Waals strain are reduced by rotation by C—C bonds to give
skew boat (or) twist boat conformation on which it is slightly more stable than boat
form.

Energy diagram of cyclohexane conformations

Stability order of cyclohexane conformations

Chair > twist boat > Boat > Half chair (skew)

Substituted cycloalkanes
I) Mono substituted cyclohexane
Ex: Methyl cyclohexane

Reason

A substituent in cyclohexane prefers equatorial position to avoid 1, 3-diaxial

repulsion.

As the size of the substituent increases, the preference of equitorial position increases.
Me < Et < iPr < t-Br
F < Cl < Br < I

II) Disubstituted cyclohexane

Disubstituted cyclohexane can be of cis isomer or trans isomer.
1) 1, 2-disubstituted
Configuration-Cis (axial and equitorial)
Configuration-Trans (aa (or) ee)
134 ISOMERISM

Ex: 1, 2-dimethylcyclohexane

Cis isomer

Trans isomer

2) 1, 3-disubstituted
Configuration - Cis (aa/ee)
Configuration-Trans (ae)
Ex: 1, 3-dimethylcyclohexane

Cis isomer Trans isomer

Ex: 1, 3-cyclo hexanediol

Due to H-bonding (aa) is more stable.

3) 1, 4-disubstituted
Configuration-Trans (aa/ee); Configuration-Cis (ae)
Ex: 1,4-cyclohexanediol
 ISOMERISM 135

Ex: 1, 4-di t-butyl cyclohexane

Cis isomer
Twist boat is more stable compared to chair form as both t-butyl bulky groups occupy
equatorial position in twist boat form.

Cyclobutane
Has lesser angle strain than cyclo propane and minimizes the torsional strain by adopting a
“puckered” conformation.

In case of 1,3-dimethyl cyclobutane, Cis-1, 3-dimethyl cyclobutane is more stable than trans-
1, 3-dimethyl cyclobutane.
Cyclopentane
In planar structure, angle strain is negligible but torsional strain exists. There are two non-
planar conformations with lesser torsional strain namely (“half chair” and “envelope form”
both have same energy).

Envelope Half-chair

GEOMETRICAL ISOMERISM
Geometrical isomerism is exhibited by a wide variety of compounds and they may be
classified into three groups
I) Compounds containing a double bond: C  C, C  N, N  N .
II) Compounds containing a cyclic structure — homocyclic, heterocyclic and fused ring
systems.
III) Compounds which may exhibit geometrical isomerism due to restricted rotation about
a single bond.
Geometrical isomers cannot be inter converted without breakage of bond and they have
different physical and chemical properties. These compounds do not rotate plane polarized
unless they also happen to be chiral.

I) Geometrical isomerism in compounds containing double bond

In alkenes the two carbon atoms of a C  C double bond and the four atoms directly
attached to them are all in the same plane and that rotation around the double bond
136 ISOMERISM

is prevented. So in the case of molecule WXC  CYZ , stereoisomerism exists when

W  X and Y  Z. There are two and only two isomers each superimposable on its
mirror image unless one of the groups happens to carry a chiral centre.

When W = Y, isomer (i) is called cis and isomer (ii) is called trans.
There is no easy way to apply this method when the four groups are different. The
newer method which can be applied to all cases is based on the Cahn-Ingold-Prelog
system the two groups at each carbon are ranked by the sequence rules. Then the
isomer with the two higher ranking groups on the same side of the double bond is
called Z isomer (for the German word zusammen meaning together); the other is E (for
entgegen meaning opposite) The Z isomer is not necessarily the one that would be
called Cis.

Ex:

Absolute Configuration of Geometrical Isomers

Cahn – Ingold – Prelog system : (E-Z nomenclature) priority rules
1) Assign priorities as (1) and (2) to the atoms or groups bonded to the same carbon of
the double bond depending on the atomic number of atom connected to carbon higher
atomic number gets lower number) (more priority).
2) If the first atom attached is same proceed in the chain, till the point of difference is
founded.
3) In case of isotopes, higher priority to higher mass number.
4) A multiple bond is considered as both atoms being bonded multiple times.

Ex:
5) A bond pair gets higher priority over lone pair.
 ISOMERISM 137

Ex:
6) cis gets higher priority over trans

Ex:
7) If the group cannot be regarded as cis (or) trans then E gets higher priority over Z.
8) If like priorities are on the same side of the axis of the double bond it is given a
configuration ‘Z’.
9) If like priorities are on opposite side of the axis of double bond, it is given a
configuration ‘E’.
Ex:

In the case of other double bond such as C  N,N  N or even C  S only two or three
groups are connected to the double-bond atoms. In case of imines, oximes and other
C  N compounds, if W = Y.

Azo compounds
In azo compounds, regardless nature of W and Y, if W and Y are same side it is ‘syn’ isomer
and if W and Y are opposite side then it is ‘anti’ isomer.
E and Z system also can be used.
138 ISOMERISM

Ex: 1)

2)

3)

Geometric isomerism in cumulenes

Cumulenes with odd number of double bonds exhibit geometrical isomerism if terminal
carbons are connected to different groups.
Ex:

Spiranes having even number of rings do not show geometrical isomerism, but
spiranes with odd number of rings exhibits geometrical isomerism
Ex:

(does not show Geometrical isomerism)

Geometrical isomerism in cyclo alkanes

The E, Z system is not used for cyclic systems.

I) Cyclo propane

II) Cyclobutane
 ISOMERISM 139

III) Cyclopentane

IV) Cyclohexane
1,2-disubstituted

1,3-disubstituted 1,4-disubstituted

V) Cycloalkenes

All cyclo alkenes having less than 8 carbons atoms don’t show geometrical isomerism.
140 ISOMERISM

Cis form is more stable than trans form because in trans form there is trans-annular
repulsion between hydrogens.

Stability order

Decaline

Geometrical isomerism due to restricted rotation about a single bond

Due to steric repulsion the outer rings will be in the same plane and inner will be
perpendicular to others.

Physical properties of geometric isomers

1)

Dipole moment () – A > B

Stability – A < B (steric repulsion between – CH3 groups)
Melting point – A < B (effective packing in B)
Boiling point – A > B
Solubility in H2O – A > B

2)
 ISOMERISM 141

Dipole moment () – A < B

Stability – A < B
Melting point – A < B
Boiling point – A < B
Solubility in H2O – A < B

3)

Dipole moment () – A>B

Stability – A<B
Melting point – A<B
Boiling point – They decompose before boiling

Number Of Geometrical Isomers

In polyenes, the number of geometrical isomers can be calculated as

Case-I If the ends are not identical CHX  CH  CH  CHY

2n , where n is number of double bonds.

Case-II If the ends are identical CHX  CH  CH  CHX

n
2n1  2p1 , where ‘n’ is number of double bonds and p  when ‘n’ is even and
2
p
 n  1 when ‘n’ is odd.
2
Questions:
7. How many stereoisomers are possible for C2FClBrI ?
Ans. 6 isomers

8. Name the following compounds.

 142 ISOMERISM

Ans. (a) (3Z)-3-ethynyl-4-methyl hexa-1, 3-diene

(b) (1E)-1-cyclohexyl-2-isopropyl-1-phenyl buta-1, 3-diene
(c) (2Z, 4E)-hepta-2, 4-diene
_______________________________________________________________________________________________
OPTICAL ISOMERISM
Optical activity and chirality
Any material that rotates the plane of plane polarized light is said to be optically active. The
isomer that rotates the plane to the left (counter clockwise) is called the levoisomer (l) and is
designated (–), while the one that rotates the plane to the right (clockwise) is called the dextro
isomer (d) and is designated (+). If a pure compound is optically active, the molecule is
nonsuperposable on its mirror image. If a molecule is superposable on its mirror image, the
compound does not rotate the plane of plane polarized light it is optically inactive. The
property of nonsuperposable of an object on its mirror image is called chirality. If a molecule
is not superposable on its mirror image it is chiral. If it is superposable on its mirror image it
is achiral. The relationship between optical activity and chirality is absolute. So the necessary
and a sufficient condition for a molecule to be optically active is chirality (nonsuperposability
on the mirror image). If a molecule is nonsuperposable on its mirror image, the mirror image
must be a different molecule, since nonsuperposability is the same as identity.
Plane Polarized Light (PPL)
Light that propagates only in one plane

PPL is made up of two circularly polarized beams one propagating clockwise and the other
anti-clockwise.
Polarizer
Crystal used in (or) to polarize unpolarized light.
Ex: 1) Nicol prism which is made up of calcite crystal.
2) Tourmaline Prism.
Specific Rotation []
The amount of rotation ‘’ is not a constant for a given enantiomer it depends on the length
of the sample vessel, the temperature, the solvent and concentration (for solutions), the
pressure (for gasses), and the wavelength of light. Of course, rotations determined for the
same compound under the same conditions are identical. The length of the vessel and the
concentration or pressure determine the number of molecules in the path of the beam and 
is linear with this. Therefore, a number is defined, called the specific rotation [], which is
 ISOMERISM 143

 
  for solutions   for pure compounds
lc ld
Where  is the observed rotation, l is the cell length in decimeters, c is the concentration in
grams per millilitre and d is the density in the same units. The specific rotation is usually
given along with the temperature and wavelength, in this manner:   T .


ELEMENTS OF SYMMETRY
For optical activity, although the ultimate criterion is, of course, nonsuperposability on the
mirror image (chirality), other tests may be used that are simpler to apply. One such test is
the presence of elements of symmetry.
I) Axis of symmetry (Cn)
360
A molecule is said to have n-fold axis of symmetry in a rotation of along an axis
n
gives the same representation in space.

Ex:

II) Plane of symmetry / Mirror plane

Plane passing through on object such that the part on one side of the plane is the
exact reflection of the part on other side (the plane acting as the mirror).
Ex:

III) Centre of symmetry (inversion centre) (Ci)

A point within an object such that a straight line drawn from any part (or) element of
the object to the centre and extended an equal distance on the other side encounters
an equal part (or) element.

IV) Alternating Axis of symmetry – (Sn)

An alternating axis of symmetry of order ‘n’ is an axis such that when an object
containing such an axis is rotated by 360 °/n about the axis and then reflection is
144 ISOMERISM

effected across a plane at right angles to the axis, an new object is obtained that is
indistinguishable from the original one. This is also called “improper axis of
symmetry”.
Condition for molecule to be optically active
For a molecule to be optically active it should be dissymmetric i.e., it should not have
i) Centre of symmetry
ii) Plane of symmetry
iii) Alternating axis of symmetry
An old but commonly used word to describe the condition for optical activity is asymmetric.
It is commonly used for carbon atoms connected for four different substituents.
Enantiomer
One of a pair of molecular entities which are mirror images of each other and non-
superposable is called enantiomer.
Ex:

H3C  CH  CH  C2H5
| |
OH Cl

3-Chloro pentan-2-ol Enantiomers (dl pair)

Enantiomers have identical physical and chemical properties except in two important
aspects.
1. They rotate the plane of plane polarized light in opposite directions, though in equal
amounts. Because they differ in this property they are often called optical antipodes.
2. They react at different rates with other chiral compounds. These rates may be so close
together that the distinction is practically useless, or they may be so far apart that one
enantiomer undergoes the reaction at a convenient rate while the other does not react
at all. This is the reason that many compounds are biologically active while their
enantiomers are not. Enantiomers react at the same rate with achiral compounds.
In general, it may be said that enantiomers have identical properties in a symmetrical
environment, but their properties may differ in an unsymmetrical environment.

Racemic mixture/recemate/form
Mixtures of equal amounts of enantomers are optically inactive since the equal and opposite
rotations cancel out. Such mixtures are called racemic mixture or recemate.
Diastereomers
Two non-superposable configurational units that correspond to the same constitutional unit
and if they are not mirror images are called diastereomers.
They have different physical as well as chemical properties they can be separated by
fractional distillation (or) crystallization and chromatography.
Ex: 1
 ISOMERISM 145

(A, B), (A, B'), (A', B), (A', B') — diastereomers.

(A, A'), (B, B'), — enantiomers
Ex: 2
Cis and trans isomers are diastereomers

Meso compound
Meso compound is the compound with chiral centres but is optically inactive due to
symmetry in it.
It is a term for achiral member(s) of a set of diastereo isomers which also includes one or
more chiral members.
Ex:

Classification of optically active compounds

1. Compounds with chiral carbon atom
If there is only one such atom, the molecule must be optically active. This is no matter
how slight the differences are among the four groups.
Ex: Optical activity is present in

Optical activity has been detected even in cases such as 1-butanol-1-d, where one
group is hydrogen and another deuterium.

2. Compounds with other quadrivalent chiral atoms

Any molecule containing an atom that has four bonds pointing to the corners of a
tetrahedron will be optically active if the four groups are different. Among atoms in
this category are Si, Ge, Sn and N (in quaternary salts or N-oxides). In sulfones the
sulfur bonds tetrahedrally, but since two of the groups are always oxygen, no chirality
146 ISOMERISM

normally results. However, the preparation of an optically active sulfone (i) in which
one oxygen is 16 O and the other 18 O illustrates the point that slight differences in
groups are all that is necessary. This has been taken even further with the preparation
of the ester (ii), both enantiomers of which have been prepared. Optically active chiral
phosphates (iii) have similarly been made.

3. Compounds with tervalent chiral atoms

Atoms with pyramidal bonding might be expected to give rise to optical activity if the
atom is connected to three different groups, since the unshared pair of electrons is
analogous to a fourth group, necessarily different from the others.
For example, a secondary or tertiary amine where X, Y and Z are different

would be expected to be chiral and thus resolvable. Many attempts have been made to
resolve such compounds, but until 1968 all of them failed because of pyramidal
inversion, which is a rapid oscillation of the molecule into its enantiomer. For
ammonia there are 2  1011 inversions every second. The inversion is less rapid in
substituted ammonias (amines, amides etc.). Two types of nitrogen atom invert
particularly slowly,
1) A nitrogen atom in a three-membered ring
2) A nitrogen atom connected to another atom bearing an unshared pair.
Even in such compounds, however, for many years pyramidal inversion proven too
rapid to permit isolation of separate isomers. This goal was accomplished only when
compounds were synthesized in which both features are combined: a nitrogen atom in
a three-membered ring connected to an atom containing an unshared pair.

Ex: The two isomers of 1-chloro-2-methyaziridine were separated and do not interconvert
at room temperature.

In suitable cases this barrier for inversion can result in compounds that are optically active
solely because of a chiral tervalent nitrogen atom.
Ex: The following compound has been resolved into its separate enantiomers. In this case
too, the nitrogen is connected to an atom with an unshared pair.
 ISOMERISM 147

Phosphorus inverts more slowly and arsenic still more slowly. Non bridgehead phosphorus,
arsenic, and antimony compounds have also been resolved.
Ex:

Sulfur exhibits pyramidal bonding in sulfoxides, sulfinic esters, sulfonium salts and sulfites.
These compounds have been resolved.
Ex:

Biphenyls
Biphenyls with bulky groups at ortho positions face large steric repulsions which force both
the rings perpendicular to each other, this hinders (or) greatly lowers the free rotation about
the C – C bond connecting the rings and makes molecules dissymmetric. Isomers that can be
separated only because rotation about single bonds is prevented or greatly slowed are called
atropisomers.
Ex:

Similarly if t-butyl and mesityl groups are present even H-atom forces it out of plane.

Allenes
In allenes, the central carbon is sp bonded. The remaining two p-orbitals are perpendicular
to each other and each overlaps with the p-orbital of one adjacent carbon atom, forcing the
two remaining bonds of each carbon into perpendicular planes.
148 ISOMERISM

Like biphenyls, allenes are chiral only if both sides are unsymmetrically substituted.

These cases are completely different from the cis–trans isomerism of compounds with one
double bond. In the latter cases, the four groups are all in one plane, the isomers are not
enantiomers, and neither is chiral, while in allenes the groups are in two perpendicular
planes and the isomers are a pair of optically active enantiomers.
When three, five, or any odd number of cumulative double bonds exist, orbital overlap causes
the four groups to occupy one plane and cis–trans isomerism is observed. When four, six, or
any even number of cumulative double bonds exist, the situation is analogous to that in the
allenes and optical activity is possible.
Among other types of compounds that contain the system illustrated in the below examples
are similarly chiral, if both sides are dissymmetric are spiranes and compounds with
exocyclic double bonds.

The Fischer projection

For thorough understanding of stereochemistry it is useful to examine molecular models.
However, this is not feasible when writing on paper or a blackboard. In 1981 Emil Fischer
greatly served the interests of chemistry by inventing the Fischer projection, a method of
representing tetrahedral carbons on paper.
By this convention
1) The model is held so that the two bonds in front of the paper are horizontal and those
behind the paper are vertical.
2) It should be remembered that they are projections and must be treated differently
from the models in testing for superposability. Every plane is superposability on
its mirror image; hence with these formulas there must be added the restriction that
they may not be taken out of the plane of the blackboard or paper. Also they may not
be rotated 90°, though 180° rotation is permissible.

3) It is also permissible to keep any one group fixed and to rotate the other three
clockwise or counter-clockwise (because this can be done with models).
 ISOMERISM 149

However, the interchange of any two groups results in the conversion of an enantiomer
into its mirror image (this applies to models as well as to the Fischer projections).
With these restrictions Fischer projections may be used instead of models to test
whether a molecule containing asymmetric carbons is superposable on its mirror
image. However, there are no such conventions for molecules whose chirality arises
from anything other than chiral atoms; when such molecules are examined on paper,
three-dimensional pictures must be used. With models or three-dimensional pictures
there are no restrictions about the plane of the paper.
Note: Fischer projection represents eclipsed conformation of the molecules.
Ex:

Absolute configuration of optical isomers

R, S configuration
Assign priorities for four different atoms or groups bonded to the chirality centre using Cahn
Ingold Prelog (CIP) rules. If the molecule is in wedge dash projection view the molecule in the
way that the lowest priorities group is away from you. Moving from 1 to 2 to 3 if it is
clockwise, it is given a configuration R, if it is anticlockwise, it is given a configuration S.

1  2  3 Clockwise direction
Least priority group is away from observer so configuration is R.
If the molecule is in Fischer projection the following rules are used.
If lowest priority group is in vertical line
123 Clockwise R.
Anti-clockwise S.
If lowest priority group is in horizontal line
123 Clockwise S.
Anti-clockwise R.
Ex:

(2R, 3R) — 2,3-dihydroxy butanoic acid.

150 ISOMERISM

(2E, 5Z, 4S) – hepta – 2,5-dien -4-ol.

R and S do not indicate dextro or leavo however, if R of a compound is dextrorotatory

(+) and its mirror image (S) would be Levorotatory (–).

Molecules with more than one chiral center

Four is the maximum possible isomers when the compound has two chiral centers.
Some compounds have fewer.
When the three groups on one chiral atom are the same as those on the other, one of the
isomers (called a meso form) has a plane of symmetry and hence is optically inactive even
though it has two chiral carbons.
Ex: Tartaric acid.

The three stereoisomers of tartaric acid

I,II are enantiomers
I,III and II,III are diastereomers
In most cases with more than two chiral centers, then number of isomers can be calculated
from the formula 2n , where n is the number of chiral centers, although in some cases the
actual number is less than this, owing to meso forms.
Ex: 2,3,4-pentanetriol

(III, IV) are enantiomers

(I,II), (I,III), (I,IV), (II,III), (II,IV) are diastereomers
Number of Optical isomers
Molecules having ‘n’ chiral centers
Case-I If molecule is not divisible into two identical halves
Number of optically active forms = 2n  a
a
Number of enantiomeric pair 
2
 ISOMERISM 151

Case-II If molecule is divisible into two identical halves (meso compound)

a) If number of chiral centers is even
Number of optically active forms = a  2n1
a
Number of enantiomeric pairs 
2
n
Number of meso forms = m  2 p 1 where p 
2
b) If number of chiral centers is odd
Number of optically active forms = a  2n1
a
Number of enantiomeric pairs 
2
Number of meso forms = m  2 p 1 where p 
 n  1
2

D,L-System (Relative configuration)

Used to give configuration to carbohydrates and aminoacids or their derivaties.
The simplest chiral carbohydrates with (glyceraldyhyde) the following arrangement in Fischer
projection is given a configuration D.

D(+) glyceraldehyde
To assign configuration of their carbohydrates their Fischer projection is drawn with the
longest C-chain in vertical line and the most oxidised one at the top (aldehyde or ketone). If
OH group at the farthest chiral centre form CHO or C = O group is at the right, it is given
configuration ‘D’, if it is left ‘L’ configuration.

Similarly when amino acids are drawn in Fischer projection —COOH group up and the alkyl
residue down. If NH2 group is on the right it is given D-configuration or else L.

Erythro and Threo configuration

In a compound containing more than one chiral center, if similar groups are on same side
then it is known as erythro isomer and similar groups are on opposite side then that is
known as threo isomer.

Optical isomerism in cyclic compounds

Mono substituted cycloalkanes are optically active.
152 ISOMERISM

1) Cyclopropane

Optically active

When a = b the cis isomer is optically inactive due to plane of symmetry whereas
trans isomer is optically active.
2) Cyclobutane
1, 2 - disubstituted

Cis isomer optically active Trans isomer optically active

If a = b cis isomer is optically inactive whereas trans isomer is optically active.

1, 3 - disubstituted

Cis isomer optically inactive Trans isomer optically inactive

3) Cyclopentane
1,2-disubstituted

1,3-disubstituted

If a = b cis isomer is optically inactive where as trans isomer is optically active.

4) Cyclohexane
1,2-disubstituted
 ISOMERISM 153

If a = b cis isomer is optically inactive not due to plane of symmetry but to a rapid
interconversion of the molecule and its mirror image.

1,3-disubstituted

1,4-disubstituted

1,4-disubstituted cis and trans isomer of cyclo hexanes are optically inactive
irrespective of nature of the substitutions.
Enantiomeric excess (Optical purity)
If the value of [] for the pure material    
max
is known, the purity of the sample can be
determined by measuring its rotation. For example, if max is +80° and our (+) enantiomer
contains 20 % of the (–) isomer, [] for the sample will be +48°.
observed
Optical purity   100
max  Pure enantiomers 
Assuming a linear relationship between [] and concentration, which is true for most cases,
the optical purity is equal to the percent excess of one enantiomer over the other

Optical purity  pecent enantiomeric excess 

R   S 100  d  l   100
R   S d  l 
Questions:
9. A sample of butan-2-ol has an observed rotation of +9.72°. The optical rotation of pure leavo
isomer is –13.5°. Calculate the % composition of the mixture.
Ans. 86 % d, 14 % l.

RESOLUTION
Resolution is the process whereby a recemic modification is separated into its two
enantiomers.
Method of resolution
1) Mechanical separation
This method is also known as spontaneous resolution by crystallization, and was
introduced by Pasteur (1848). It depends on the crystallization of the two forms
separately, which are then separated by hand. The method is applicable only for
recemic mixtures where the crystal forms of the enantiomers are themselves
enantiomerphous. Pasteur separated sodium ammonium recemate in this way. The
transition temperature of sodium ammonium recemate is 28 °C; above this
154 ISOMERISM

temperature the recemic compound crystallizes out, and below this temperature the
recemic mixure. Now Pasteur crystallized his sodium ammonium recemate from a
concentrated solution at room temperature, which must have been below
28 °C, since, had the temperature been above this, he would have obtained the
recemic compound, which cannot be separated mechanically. Actually, Staedel (1878)
failed to repeat Pasteur’s separation since he worked at a temperature above 28 °C.

2) Preferential crystallization by inoculation

A supersaturated solution of the recemic modification is treated with a crystal of one
enantiomer (or an isomorphous substance), whereupon this form is precipitated. The
resolution of glutamic acid by inoculation has been perfected for industrial use.

3) Biochemical separation (Pasteur, 1858).

Certain bacteria and moulds, when they grow in a dilute solution of a recemic
modification, destroy one enantiomer more rapidly than the other, e.g., Penicillium
glaucum (a mould), when grown in a solution of recemic ammonium tartrate, attact
the (+)-form and leaves the (–).
This biochemical method of separation has some disadvantages:
a) Dilute solutions must be used, and so the amounts obtained will be small.
b) One form is always destroyed and the other form is not always obtained in
50 percent yield since some of this may also be destroyed.
c) It is necessary to find a micro-organism which will attack only one of the
enantiomers.

4) Conversion into diastereoisomers (Pasteur, 1858).

The method, which is the best of all the methods of resolution, consists in converting
the enantiomers of a recemic modification into diastereoisomers the recemic
modification is treated with an optically active substance and thereby produced are
separated by fractional crystallization.
Ex: If the recemic mixture to be resolved contains a carboxyl group (and no strongly basic
group), it is possible to form a salt with an optically active base. Since the base used
is, say, the S form, there will be a mixture of two salts produced having the
configurations SS and RS. Although the acids are enantiomers, the salts are
diastereomers and have different properties and can be separated.

Resolution can also be done by chromatographic techniques.

Asymmetric induction
Introduction of chiracity center in an achiral compound.
 ISOMERISM 155

Enantiotropic hydrogens

 Ha , Hb  – enantiotropic hydrogens.
Diastereobropic hydrogens

 H, Hb  – diastereotropic hydrogens.

Prochiral centre
Atom which turns chiral during reaction.

Ex: