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
 2.12 Isomerism.

Organic compounds having same molecular formula but differing from each other at least in
same physical or chemical properties or both are known as isomers (Berzelius) and the
phenomenon is known as isomerism.

For example,

Ethyl alcohol (C2H6O) Dimethyl ether (C2H6O)

CH3 − CH2 − OH CH3 − O− CH3

 

It is liquid. It is a gas.

Its boiling point is 78°C Its boiling point is - 24°C.

It reacts vigorously with sodium and evolves It does not react with sodium.

hydrogen.

It reacts with HI and forms ethyl iodide, C2H5I . It reacts with HI and forms methyl iodide,

CH3I .

The difference in properties of isomers is due to the difference in the relative arrangements of
various atoms or groups present in their molecules. Isomerism can be classified as follows:

Isomerism

Constitutional or structural isomerism Configurational or stereo isomerism

Without referring to space, the isomers differ in the The isomerism arises due to different arrangement of atoms or
arrangement of atoms within the molecule is called groups in space. It deals with the structure of molecules in three
structural isomerism. Thus structural isomers have:
dimensions. Thus stereoisomers have:
• Same molecular formula
• Same molecular formula
• Same empirical formula
• Same empirical formula
• Same molecular weight
• Same molecular weight
• Different properties
• Different properties
• Different structural formula
• Different orientation of atoms or molecules in space

Chain Position Ring chain Functional Metamerism Tautomerism Geometrical Optical Conformational


2.13 Constitutional or structural isomerism.
(1) Chain, nuclear or skeleton isomerism :
This type of isomerism is arises due to the difference in the nature of the carbon chain (i.e.,
straight or branched) which forms the nucleus of the molecule.
Examples :
(i) C4H10 : CH3 − CH2 − CH2 − CH3 , CH3 − CH − CH3
n −Butane |
CH3
Isobutane

CH3
|
(ii) C5H12 : (Three) CH3 − CH2 − CH2 − CH2 − CH3 , CH3 − CH − CH2 − CH3 , CH3 −C− CH3
n −Pentane | |
CH3 CH3
Isopentane Neopen tan e

(iii) C4H8 : CH3 − CH2 − CH = CH2 , CH3 − C = CH2

−butylene |
CH3
Isobutylene

(iv) C5H8 : HC  C − CH2 − CH2 − CH3 , HC  C − CH2 − CH3

1-Pentyne |
CH3
2−Methyl - 1 - butyne

4 3 2 1 2 3
(v) C4H7N : CH3 − CH2 − CH2 − CN CH3 − CH − CH3
Butane nitrile |
CN
1
2−Methyl propane nitrile

DRC :  Except alkynes chain isomerism is observed when the number of carbon atoms is four
or more than four.
 Generally Chain isomers differ in the nature of carbon chain, i.e., in the length of carbon chain.
 The isomers showing chain isomerism belong to the same homologous series, i.e., functional
group, class of the compound (Cyclic or open) remains unchanged.
 Chain and position isomerism cannot be possible together between two isomeric compounds. If
two compounds are chain isomers then these two will not be positional isomers.
(2) Position isomerism :


It is due to the difference in the position of the substituent atom or group or an unsaturated linkage
in the same carbon skeleton.
Examples :
OH
|
(i) C4 H10 O : CH3 − CH − CH2 − OH , CH3 − C − CH3
| |
CH3 CH3
Isobutylalcohol t −Butyl alcohol

(ii) C3 H6 Cl2 :
CH3 − CCl2 − CH3 , CH3 − CH2 − CH − Cl2 , CH3 − CH− CH2 , CH2 − CH2 − CH2
2,2−Dichloro propane, 1,1−Dichloro propane | | | |
Cl Cl Cl Cl
1,2−Dichloro propane 1,3−Dichloro propane
[Gem-two, vic-one and  , -one]

(iii) C4 H8 : CH3 − CH2 − CH = CH2 , CH3 − CH = CH − CH3

1−Butene 2−Butene

(iv) C4 H6 : CH3 − CH2 − C  CH , CH3 − C  C − CH3 , CH2 = C = CH − CH3 , CH2 = CH − CH = CH2

1−Butyne 2−Butyne 1,2−Butadiene 1,3−Butadiene

(v) C3 H6 O2 : CH3 − CH− CHO , CH2 − CH2 − CHO

| |
OH OH
2−Hydroxy propanal 3−Hydroxy propanal

(vi) C7 H7 NO2 (Three aromatic) :

CH3 CH3 CH3
NO2
NO2

o - Nitrotoluene m - Nitrotoluene
NO2
p - Nitrotoluene

(vii) C8 H10 (Three aromatic) :

CH3
CH3 CH3
CH3
CH3 CH3
o - Xylene m - Xylene p - Xylene

(viii) C6 H3 (OH)3 (Three aromatic) :


 OH OH OH
OH OH
OH
OH OH
OH
Paragallol 1,2,4 - Trihydroxybenzene Phloroglucinol

(ix) C6 H3 X2Y (Six aromatic) :

X X X X X X
X X Y Y
Y X
X Y X
Y Y X

(x) C6 H3 XYZ (Ten aromatic) :

X X X X X X
Y Y Y Z Y Z
Z Y
Z Y
Z Z
X X X X
Z Z

Z Y Y Z
Y Y

(xi) C6 H14 : CH3 − CH − CH2 − CH2 − CH3 , CH3 − CH2 − CH − CH2 − CH3
| |
CH3 CH3
2− Methylpentane 3− Methylpentane

(xii) C4 H11 N : CH3 − NH − CH2 − CH2 − CH3 CH3 − NH − CH − CH3

N−Methyl-1-propaneamine |
CH3
N−Methyl-2-propaneamine

DRC :  Aldehydes, carboxylic acids (and their derivatives) and cyanides do not show position
isomerism.
 Monosubstituted alicylic compounds and aromatic compounds do not show position isomerism.
 Structural isomers which differ in the position of the functional group are called regiomers. For
example, (i) CH3 − CH2 − CH2 − OH (ii) CH3 − CH − CH3
|
OH


(3) Functional isomerism :
This type of isomerism is due to difference in the nature of functional group present in the
isomers. The following pairs of compounds always form functional isomers with each other.
Examples :
(i) Alcohols and ethers (Cn H2n+2O)
C2H6O : CH3 − CH2 − OH ; H3C − O − CH3
Ethyle alcohol Dimethylether

C3H8O : CH3 − CH2 − CH2 − OH ; C2H5 − O − CH3

n − propyl alcohol Ethyl methylether

C4H10O : CH3 − CH2 − CH2 − CH2 − OH ; C2H5 − O − C2H5

n −Butyl alcohol Diethyl ether

(ii) Aldehydes, ketones and unsaturated alcohols …etc. (Cn H2nO)

O
||
C3H6O : CH3 − CH2 − CHO ; CH3 − C − CH3 ; CH 2 − CH − CH 3 ; CH2 = CH − CH2OH
Propionaldehyde Acetone Allyl alcohol
O
1,2 −Epoxy propane

(iii) Acids, esters and hydroxy carbonyl compounds …etc. (Cn H2nO2)
C2H4O2 : CH3COOH ; HCOOCH3
Acetic acid Methyl formate

O
||
C3H6O2 : CH3 − CH2 − COOH ; CH3COOCH3 ; CH3 CHCHO ; CH3 − C − CH2 − OH
Propionic acid Methyl acetate | 1− Hydroxy propan-2-one
OH
2− Hydroxy propanal

(iv) Alkynes and alkadienes (Cn H2n-2)

C4H6 : CH3 − CH2 − C  CH ; H2C = CH − CH = CH2 ; CH3 − C  C − CH3 ; H2C = C = CH − CH3
1− Butyne 1,3− Butadiene 2−Butyne 1,2− Butadiene

(v) Cyanides and isocyanides ( −CN and −NC )

C2H3N : CH3CN ; CH3NC

Methylcyanide Methyle isocyanide

(vi) Nitro alkanes and alkyl nitrites ( −NO2 and −O − N = O )

O
C2H5NO2 : C2H 5 − N ; C2H5 − O − N = O
Ethyl nitrite
O
Nitro ethane

(vii) Amines (Primary, secondary and tertiary)


 H
C3H9N : CH3 − CH2 − CH2 − NH2 ; CH3 − CH2 − N
Propan-1-amine
CH3
N−Methyl ethanamine

CH3
CH3 − CH − CH3 ; CH3 − CH2 − N
|
NH2 CH3
N,N−Dimethyl methanamine
Propan -2- amine

(viii) Alcohols and phenols

CH2OH OH
CH3
C7 H8 O ;

Benzyl alcohol o-Cresol

(ix) Oximes and amides

O
||
C2H5NO : CH3 − CH = NOH ; CH3 − C− NH2
Acetaldoxime Acetamide

(x) Thio alcohols and thio ethers

C2H6S : C2H5SH ; CH3 − S − CH3
Ethyl thioalcohol Dimethyl thioether

(4) Ring-chain isomerism : This type of isomerism is due to different modes of linking of carbon
atoms, i.e., the isomers possess either open chain or closed chain sturctures.
Examples :
CH2
(i) C3H6 : CH3 − CH = CH2 ; H C − CH
2 2
Propene Cyclopropane

CH3
H2C — CH2 |
CH
(ii) C4H8 : CH3 − CH2 − CH = CH2 ; | | ;
1− Butene H2C − CH2
H2C — CH2
Methyl cyclopropane
Cyclobutane

H2
C
H2C CH2 CH − CH
(iii) C6H12 : | | ; | 2 2
CHCH3 ; CH3CH2CH2CH2CH = CH2
H2C CH2 C H2 − CH2 1−Hexene
Methyle cyclopentane

C
H2
Cyclohexane


 DRC : Ring – chain isomers are always functional isomers.
(5) Metamerism :
This type of isomerism is due to the difference in the nature of alkyl groups attached to
the polyvalent atoms or functional group. Compounds like ethers, thio-ethers ketones, secondary
amines, etc. show metamerism.
Examples :
(i) C4H10O : C2H5 − O − CH3 ; C3H7 − O − CH3
Diethylether Methyl propylethers

(ii) C5H10O : C2H5 − CO − C2H5 ; C3H7 − CO − CH3

Diethyl ketone Methyl propyl ketone

(iii) C4H11N : C2H5 − NH − C2H5 ; C3H7 − NH − CH3

Diethylamine Methyl propyl amine

CH3 C2 H 5
(iv) C5H13N : C3H7 − N ; C2 H 5 − N CH 3
CH3
Dimethyl propyl amine Diethyl methyl amine

(v) C6H15N : C3H7 − NH − C3H7 ; C2H5 − NH − C4H9

Dipropylamine Ethyl butyl amine

DRC :  If same polyvalent functional group is there in two or more organic compounds, then
never write chain or position isomerism, it will be metamerism e.g.,
(a) CH3 − C− CH2 − CH2 − CH3 ; CH3CH2 − C− CH2CH3 are metamers and not position isomers.
|| ||
O O
(Pentan −2−one) (Pentan −3−one)

(b) CH3 − C− CH2CH2CH3 ; CH3 − C− CH − CH3 are metamers and not chain isomers.
|| || |
O O CH3
(Pentan −2−one) (3-Methylbutan-2-one)

 Alkenes does not show metamerism.

Number of structural isomers

Molecular formula Number of isomers

Alkanes

C4H10 Two

C5H12 Three

C6H14 Five


C7H16 Nine

C8H18 Eighteen

C9H20 Thirty five

C10H22 Seventy five

Alkenes and cycloalkanes

C3H6 Two (One alkene + one cycloalkane)

C 4H8 Six (Four alkene + 2 - cycloalkane)

C5H10 Nine (Five alkenes + 4 – cycloalkanes)

Alkynes

C3H4 Two

C 4 H6 Six

Monohalides

C3H7 X Two

C 4H9 X Four

C5H11 X Eight

Dihalides
C2H4 X 2 Two

C3H6 X 2 Four

C4H8X2 Nine

C5H10 X 2 Twenty one

Alcohols and ethers

C2H6O Two (One alcohol and one ether)

C3H8O Three (Tow alcohols and one ether)

C4H10O Seven (Four alcohols and three ethers)

C5H12O Fourteen (Eight alcohols and six ethers)


 Aldehydes and ketones
C3H6O Two (One aldehyde and one ketone)

C4H8O Three (Two aldehydes and one ketone)

C5H10O Three (Four aldehydes and three ketone)

Monocarboxylic acids and esters

C2H4O2 Two (One acid and one ester)

C3H6O2 Three (One acid and two esters)

C4H8O2 Six (Two acids and four esters)

C5H10O2 Thirteen (Four acids and nine esters)

Aliphatic amines
C2H7N Two (One 1°-amine and one 2°-amine)

C3H9N Four (Two 1°-amines, one 2°-amine and one 3°-amine)

C4H11N Eight (Four 1°-amines, three 2°-amines and one 3°-amines)

Aromatic compounds
C8H10 Four

C9H12 Nine

C7H8O Five

(6) Tautomerism :
(i) The type of isomerism in which a substance exist in two readily interconvertible different
structures leading to dynamic equilibrium is known as tautomerism and the different forms are
called tautomers (or tautomerides).
The term tautomerism (Greek: tauto = same; meros = parts) was used by Laar in 1885
to describe the phenomenon of a substance reacting chemically according to two possible
structures.
(ii) It is caused by the wandering of hydrogen atom between two polyvalent atoms. It is also
known as Desmotropism (Desmos = bond and tropos = turn). If the hydrogen atom oscillates
between two polyvalent atoms linked together, the system is a dyad and if the hydrogen atom
travels from first to third in a chain, the system is a triad.


 (a) Diad system : Hydrocyanic acid is an example of dyad system in which hydrogen
atom oscillates between carbon and nitrogen atoms. H − C  N ⇌ C = N − H
(b) Triad system
Keto-enol system : Polyvalent atoms are oxygen and two carbon atoms.
Examples :
O H OH
|| | |
− C− C ⇌ − C = C−
| |
(Keto) (Enol)

O
||
Acetoacetic ester (Ethyl acetoacetate) : CH 3 − C − CH 2COOC2H 5 ⇌
Keto form

OH
|
CH 3 − C = CHCOOC2 H 5
Enol form

Acetoacetic ester gives certain reactions showing the presence of keto group
(Reactions with HCN, H2NOH, H2NNHC6H5 , etc.) and certain reactions showing the presence of
enolic group (Reactions with Na,CH3COCl,NH3 ,PCl5 ,Br2 water and colour with neutral FeCl3 , etc.).

O OH
|| |

Acetyl acetone : CH 3 − C − CH 2COCH3 CH 3 − C = CHCOCH 3

Keto form Enol form

O OH
|| |
− C− CH 3 = C− CH 2
Keto form Enol form

OH O
Enol form Keto form

O OH

O O HO OH
Keto form Enol form

Enolisation is in order :

CH3COCH3  CH3COCH2COOC2H5  C6H5COCH2COOC2H5  CH3COCH2COCH3  CH3COCH2CHO

Acid catalysed conversion :


 O OH OH
|| | |
H −H 
CH 3 − C − CH 2 − R CH 3 − C − C H − R ⎯⎯⎯→CH 3 − C = CH − R
Keto  | (Enol)
H

Base catalysed conversion :


O O O OH
|| OH
 || | |
H 2O
CH3 − C − CH2 − R – H2O
CH3 − C − C H − R ⎯⎯→ CH3 − C = CH − R ⎯⎯⎯
→ CH3 − C = CH − R
Keto  −OH (Enol)

Triad system containing nitrogen

Examples :
O
Nitrous acid : H − O − N = O H −N
Nitrite form
OH
Nitro form

O O
Nitroethane : CH 3 − CH 2N CH 3CH = N
O OH
Nitro form Acid form

(iii) Characteristics of tautomerism

(a) Tautomerism (cationotropy) is caused by the oscillation of hydrogen atom between two
polyvalent atoms present in the molecule. The change is accompanied by the necessary
rearrangement of single and double bonds.
(b) It is a reversible intramolecular change.
(c) The tautomeric forms remain in dynamic equilibrium. Hence, their separation is a bit
difficult. Although their separation can be done by special methods, yet they form a separate series
of stable derivatives.
(d) The two tautomeric forms differ in their stability. The less stable form is called the labile
form. The relative proportion of two forms varies from compound to compound and also with
temperature, solvent etc. The change of one form into another is also catalysed by acids and bases.
(e) Tautomers are in dynamic equilibrium with each other and interconvertible (⇌).
(f) Two tautomers have different functional groups.
(g) Tautomerism has no effect on bond length.
(h) Tautomerism has no contribution in stabilising the molecule and does not lower its energy.
(i) Tautomerism may occur in planar or nonplanar molecules.
DRC :  Keto=enol tautomerism is exhibited only by such aldehydes and ketones which contain
at least one  -hydrogen. For example CH3CHO,CH3CH2CHO,CH3COCH2COCH3 .


  Tautomerism is not possible in benzaldehyde (C6H5CHO) , benzophenone (C6H5COC6H5 )
, tri methyl acetaldehyde, (CH3 )3C − CHO and chloral CCl3 − CHO as they do not carry  − H .

2.14 Geometrical or cis-trans isomerism.

The compounds which have same molecular formula but differ in properties due to different
spatial arrangement of atoms or groups in space are known as geometrical isomers and the
phenomenon is known as geometrical isomerism. The isomer in which same groups or atoms are
on the same side is known as cis form and the isomer in which same groups or atoms are on the
opposite side is called trans-isomer.
Examples :
H − C− COOH H − C− COOH H3C − C− COOH H3C − C− COOH
|| || || ||
H − C − COOH HOOC−C−H
Maleic acid (cis) H − C − COOH HOOC − C − H
Fumaric acid (trans) Citraconic acid (cis-isomer) Mesaconicacid(trnas−isomer)

H − C− Cl H − C− Cl H3C − C− H H3C − C− H
|| || || ||
H − C − Cl Cl − C − H H3C − C − H H − C − CH3
cis-1,2-Dichloroethylene trans-1,2-Dichloroethylene cis-Butene-2 trans-Butene-2

(1) Conditions for geometrical isomerism :

Compound will show geometrical iosomerism if it fulfils the following two conditions
(i) There should be frozen rotation about two adjacent atoms in the molecule.
(a) C=C frozen rotation about carbon, carbon double bond in alkenes.

(b) frozen rotation about carbon, carbon single bond in cycloalkanes.

(c) C = N – frozen rotation about carbon, nitrogen double bond in oxime and imine.
(ii) Both substituents on each carbon should be different about which rotation is frozen.
If these two conditions are fulfilled, then compound will show geometrical isomerism.
DRC :  The compounds of the following type will not show geometrical isomerism.
a − C− a x − C− a a − C− a
|| || ||
x−C−y a−C−a x−C−x

 Note the similar atoms (Groups) on one or both of the carbon atoms.
(2) Distinction between cis- and trans- isomers :
(i) By cyclization method : Generally, the cis-isomer (e.g. maleic acid) cyclises on heating to
from the corresponding anhydride while the trans-isomer does not form its anhydride at all.


 H − C − COOH Heat H − C − CO
|| ⎯⎯⎯→ || O
H − C − COOH H − C − CO
Maleic acid( cis ) Maleic anhydride

DRC : Note that the two reacting groups (-COOH) are near to each other.

H − C− COOH Heat
|| ⎯⎯⎯ → No anhydride
HOOC − C − H
Fumaric acid (trans)

 Note that the two reacting groups (-COOH) are quite apart from each other, hence
cyclisation is not possible.
(ii) By hydroxylation (Oxidation by means of KMnO4 ,OSO4 or H2O2 in presence of OsO4 ) :
Oxidation (Hydroxylation) of alkenes by means of these reagents proceeds in the cis-manner. Thus
the two geometrical isomers of an alkene leads to different products by these reagents. For
example,
H − C − COOH OH
KMnO4 H COOH
|| ⎯⎯ ⎯⎯→
H COOH
H − C − COOH OH
Maleic acid ( cis ) meso −Tartaricacid

OH OH
H − C − COOH KMnO4 H COOH HOOC H
|| ⎯⎯⎯⎯→ +
HOOC − C − H HOOC H H COOH
Fumaric acid ( trans)
OH OH
( + ) −Tartaricacid ( − ) −Tartaricacid

(iii) By studying their dipole moments : The cis-isomer of a symmetrical alkene (Alkenes in
which both the carbon atoms have similar groups) has a definite dipole moment, while the trans-
isomer has either zero dipole moment or less dipole moment than the cis-isomer. For example,
1,2-dichloroethylene and butene-2.
H − C− Cl H − C− Cl H − C− CH3 H − C− CH3
|| || || ||
H−C−Cl Cl−C−H H−C−CH3 CH3 −C−H
cis − Dichloroethylene trans − Dichloroethylene
cis− Butane−2 trans− Butane−2
( =1.9D) ( =0.0D)

In trans-isomer of the symmetrical alkenes, the effect produced in one half of the molecule
is cancelled by that in the other half of the molecule.
In case of unsymmetrical alkenes, the cis-isomer has higher dipole moment than the
corresponding trans-isomer.
For Example, H3C − C− Cl CH3 − C− Cl
|| ||
CH3 −CH2 −C−Cl Cl−C−CH2CH3
cis−2,3−Dichloropentene−2(Highdipolemoment) trans−2,3−Dichloropentene−2(Lessdipolemoment )

Similar is the case with hexene-2.


 H3C CH2CH2 − CH3 H CH 2CH 2 − CH 3
C =C C =C
H H CH 3 H
cis − Hexene − 2(more polar) trans−Hexene −2(Less polar)

DRC : Note that the −CH2CH2 − CH3 has more +I effect than the −CH3 group, hence dipole
moment of the two polar bonds do not cancel each other in the trans isomer. Thus trans-isomer is
also polar, but less than the corresponding cis-isomer.
(iv) By studying other physical properties: (a) The cis-isomer of a compound has higher
boiling point due to higher polarity, higher density and higher refractive index than the
corresponding trans-isomer (Auwers-skita rule).

CH3 − C− H CH3 − C− H H − C− Cl H − C− Cl
|| || || ||
CH3 − C−H H−C−CH3 H − C − Cl Cl − C − H
cis −2−Butene trans −2Butene cis −1,2−Dichloroethene trans −1,2−Dichloroethene
b.p 4C 1C 60C 48C
m.p −139C −106C −80C −50C

(b) The trans-isomer has higher melting point than the cis-isomer due to symmetrical
nature and more close packing of the trans-isomer.
(v) Stability : Trans-isomer is more stable than cis-isomer due to steric hindrance.
DRC :  Terminal alkenes such as propene, 1-butene and 2-methyl propene do not show
geometrical isomerism.

 Cis-trans isomers are configurational isomers but not mirror images, hence cis and
trans isomers are always diastereomers.

 Non-terminal alkenes with the same atoms or groups either on one or both the carbon
atoms of the double bond such as 2-methyl-2-butene, 2,3-dimethyl –2 – butene etc. do not show
geometrical isomerism.

(3) E and Z system of nomenclature :

‘Cis’ and ‘Trans’ designations cannot be used if four different atoms or groups are attached
to the carbon atoms of a double bond.
a d
C =C
b e

In such cases, E and Z system of nomenclature is used. This system is based on a priority
system developed by Cahn, Ingold and Prelog.

In this system, the two atoms or groups attached to each of the doubly bonded carbon are
put in order of precedence on the basis of sequence rules.

The symbol ‘E’ is assigned to an isomer in which the atoms or groups of higher precedence
are on the opposite side (E from German word Entgegen = across or opposite).


 The symbol ‘Z’ is assigned to an isomer in which the atoms or groups of higher precedence
are on the same side (Z from German word, Zusammen = together).
1 2 1 1
C =C C =C
2 1 2 2
E − isomer Z − isomer

DRC :  1 signifies higher precedence and 2 signifies lower precedence. In most of the cases
‘Z’ corresponds to cis-form and ‘E’ to trans-form. However, there are many exceptions.

The following rules are followed for deciding the precedence order of the atoms or groups;

(i) Higher priority is assigned to the atoms of higher atomic number. For example, the order
of precedence in the following atoms, H,Cl,I,Br is : I (at. no. 53)> Br (at. no. 35)>Cl (at. no. 17)>H
(at. no. 1).

(ii) If isotopes of the same element are attached, the isotope with higher mass number is given
higher order of precedence. For example, deuterium ( D)
2
1 is assigned higher priority in

comparison to hydrogen ( H) .
1
1

(iii) In the groups, the order of precedence is also decided on the basis of atomic number of fist
atom of the group. For example, in the following set, −Cl, −OH, −COOH, −NH − CH3 , −SO3H .

The order of the precedence is : − Cl  − SO3H  − OH  − NHCH3  − COOH

    
( at.no17) (at.no.16) (at.no.8) (at.no.7) (at.no. 6)

When the order of precedence of the groups cannot be settled on the first atom, the
second atom or the subsequent atoms in the groups are considered. For example, in the set
−CH2 − CH3 , −CH3 , −COOH, the order cannot be decided on the basis of first atom as it is same in
all the groups. However, in −CH2 − CH3 , the second atom is carbon, in −CH3 , the second atom is
hydrogen while in −COOH, the second atom is oxygen. Hence, the order of precedence is :
−COOH  −CH2 − CH3  −CH3
  
(at.no.8) (at.no.6) (at.no.1)

(iv) A doubly or triply bonded atom is considered equivalent to two or three such atoms. For
example,
N
|
The group C =O is equal to C− O and the group −C  N is equal to − C− N .
|
|
O N

(4) Number of geometrical isomers in polynes :


 (i) When compound has n double bonds and ends of a polyene are different, the number of
geometrical isomers = 2n

C6H5 − CH = CH − CH = CH − CH = CH − CH = CH − Cl

The given compound has four double bonds and the two ends are different (One is C6H5
and other is Cl). Therefore, number of geometrical isomers = 2n = 24 = 16 .

(ii) When the ends of polyene are same.

Case I : When number of double bonds (=n) is even then the number of geometrical isomers
= 2n−1 + 2n/2−1
Cl − CH = CH − CH = CH − CH = CH − CH = CH − Cl
n =4,even

Number of geometrical isomers = 2n−1 + 2(n/2)−1 = 23 + 21 = 8 + 2 = 10 .

Case II : When number of double bonds (=n) is odd.

Number of geometrical isomers = 2n−1 + 2(n+1)/2−1

C6H 6 − CH = CH − CH = CH − CH = CH − C6H5

Number of geometrical isomers = 22 + 22−1 = 22 + 21 = 4 + 2 = 6 .

(5) Geometrical Isomerism in nitrogen compounds
(i) Geometrical isomerism due to C = N − bond.

The important class of compounds exhibiting geometrical isomerism due to

C = N − bond are oximes, nitrones, hydrazones and semicarbazones. But the most common
compound is oxime.
Oximes : In aldoxime, when hydrogen and hydroxyl groups are on the same side, the
isomer is known as syn. (analogous to cis) and when these groups are on the opposite side, the
C6H5 − C − H C6H5 − C − H
isomer is known as anti (analogous to trans) || ||
N − OH HO − N
Syn-benzaldoxime Anti−benzaldoxime

In ketoximes the prefixes syn and anti indicate which group of ketoxime is syn or anti
to hydroxyl group. For example:
CH3 − C − C2H5
|| this compound will be named as;
N−OH

(a) Syn-ethyl methyl ketoxime  HO and C2H5 are syn or

(b) Anti-methyl ethyl ketoxime  HO and C2H3 are anti.


 C2H5 −C−CH3
Similarly consider the following structure ||
N−OH
Syn − methylethyl ketoxime
or Anti−ethyl methyl ketoxime

(ii) Geometrical isomerism due to N = N bond.

C6H5 − N C6H5 − N
|| ||
C H −N N−C6H5
6 5
Anti−azobenzene
Syn-azobenzene

(6) Geometrical isomerism show by cumulatrienes : Cumulatrienes (Trienes with three adjacent
double bonds) show only geometric isomerism. This is because their molecule is planar, as such
the terminal −CH3 groups and H- atoms lie in the same plane. Therefore, in this case their planar
structure can exist in two diastereoisomeric forms, cis- and trans- but no enantiomeric forms are
possible.
H 3C CH 3 H 3C H
C =C =C =C C =C =C =C
H H H CH 3
cis −Hexa −2,3,4 −triene trans−Hexa −2,3,4 −triene

(7) Geometrical isomerism in cycloalkanes : Disubstituted cycloalkanes show geometrical isomerism.

CH3
H OH OH
H
H CH3
H OH HO
H
H
Cis-1,2-dimethylcyclopropane Cis-1,2-cyclohexanediol Trnas-1,2-cyclopentanediol

DRC :  Certain compounds show geometrical as well optical isomerism. Such type of
isomerism is know as geometrical enantiomerism.

2.15 Optical isomerism.

(1) Compounds having similar physical and chemical properties but they have the ability to rotate the
plane of polarised light either to the right (Clockwise) or to the left (Anticlockwise) are termed as
optically active or optical isomer and the properly is called optical activity or optical isomerism.

The optical activity was first observed in organic substances like quartz, rock-crystals and
crystals of potassium chlorate (KClO3 ) , potassium bromate (KBrO3 ) and sodium periodate
(NaIO4 ) .

Biot (In 1815) suggested that optical activity of an organic compound was a molecular
phenomenon, i.e., it was due to constitution of an organic compound rather than its crystalline
nature.


 The light whose vibrations occur only in one plane is termed plane polarised or simply polarised light. The
device that brings polarisation in light is called a polariser (Nicol prism, made of calcite, CaCO 3 ) . The
apparatus which measures the extent of rotation of polarised light is called polarimeter.

Nicol Or ga n ic
p r is m com p ou n or
d

Ligh t Or d in a r y Rot a t ed Rot a t ed Eye

Pola r is ed
s ou r ce ligh t r igh t t o r igh t t o left

(2) Measurement of optical activity : The measurement of optical activity is done in terms of
specific rotation which is defined as the rotation produced by a solution of length of 10
centimetres (One decimetre) and unit concentration (1 g/mL) for the given wavelength of
the light at the given temperature.

t C obs
Specific rotation,   wavelength =
lC
Where  obc is the rotation observed, l is the length of the solution in decimeters and C is the
number of grams in 1mL of solution. The specific rotation of the sucrose at 20°C using sodium light
20C
(D-line, =5893Å) is + 66.5°C and is denoted as:   D = +66.5C(C = 0.02g / mL water) + sign
indicates the rotation in clockwise direction.
(3) On the basis of the study of optical activity, the various organic compounds were divided into
four types :
(i) The optical isomer which rotates the plane of the polarised light to the rigth (Clockwise)
is known as dextrorotatory isomer (Latin: dextero = right) or d-form or indicated by +ve sign.
(ii) The optical isomer which rotates the plane of the polarised light to the left (Anticlockwise)
is known as laevorotatory isomer (Latin; laevo = left) or l-form or indicated by –ve sign.
(iii) The optical powers of the above two isomers are equal in magnitude but opposite in sign.
An equimolar mixture of the two forms, therefore, will be optically inactive due to external
compensation. This mixture is termed racemic mixture or dl-form or () mixture.
(iv) Optical isomer with a plane of symmetry is called meso form. It is optically inactive due to
internal compensation, i.e., the rotation caused by upper half part of molecule is neutralised by
lower half part of molecule.
(4) Chirality
(i) Definition : A molecule (or an object) is said to be chiral or dissymmetric, if it is does not
possess any element of symmetry and not superimposable on its mirror image and this property
of the molecule to show non-superimposability is called chirality.


 On the other hand, a molecule (or an object) which is superimposable on its mirror
image is called achiral (non-dissymmetric or symmetric).
To understand the term chiral and achiral let us consider the alphabet letters ‘P’ and
‘A’ whereas ‘P’ is chiral, ‘A’ is achiral as shown in fig.
Mirror Mirror

Non-superimposable Superimposable
(Chiral or dissymmetric) (Achiral or non-dissymmetric)

(ii) Elements of symmetry : There are three elements of symmetry,

(a) Plane of symmetry : It may be defined as a plane which divides a molecule in two equal
parts that are related to each other as an object and mirror image. e.g.,

COOH
|
H − C − OH
| Plane of symmetry
H − C − OH
|
COOH

(b) Centre of symmetry : It may be defined as a point in the molecule through which if
a line is drawn in one direction and extended to equal distance in opposite direction, it meets
another similar group or atom, eg.

Cen t r e of s ym m et r y
CH 3 CH 3 CH 3 H
| NH − CO | | NH − CO |
C C and C • C
| CO − NH | | CO − NH |
H H H CH 3
cis −Dimethyl diketo piperazine Trans−Dimethyl diketo piperazine

Since trans form contains a centre of symmetry, it is optically inactive.

(c) Alternating axis of symmetry : A molecule is said to possess an alternating axis of

symmetry if an oriention indistinguishable from the original is obtained when molecule is rotated
Q degree around an axis passing through the molecule and the rotated molecule is reflected in a
mirror that is perpendicular to the axis of rotation in step (I).


 Reflection perpendicular to
Cl H axis rotation
H F Cl H
H F 180o rotation
Cl H H F
F H
around axis H Cl F H
H Cl
F H H Cl

(iii) Symmetric, Asymmetric and Dissymmetric molecules

(a) Symmetric molecules : If any symmetry is present in the molecule then molecule will
be symmetric molecule.
(b) Dissymmetric molecules : Molecule will be a dissymmetric molecule if it has no plane
of symmetry, no centre of symmetry and no alternating axis of symmetry.
(c) Asymmetric molecules : If all types of symmetry are absent.
COOH
| CHO
 |
H — C — OH
| H — C — OH
H — C — OH |
| CH3
No plane of symmetry
C6H5 
Noplaneof symmetry Dissymmetric molecule
 
Dissymmetric molecule Asymmetricmolecule

Asymmetricmolecule

(iv) Chiral or asymmetric carbon atom : A carbon bonded to four different groups is called
a chiral carbon or a chirality centre. The chirality centre is indicated by asterisk. e.g.,
a CH3
| |
d —* C — b HO — C* — H
| |
c COOH
Lacticacid

DRC :  Carbons that can be chirality centres are sp3 -hybridised carbons; sp2 and sp -
hybridised carbons cannot be chiral carbons because they cannot have four group attached to
them.
 Isotopes of an atom behave as different group in stereoisomerism.


 D H1
| |
H —C* — T Cl35 — C* — Cl37
| |
Br H2
Lacticacid

 Carbon of the following groups will not be a chiral carbon

O
||
−CH3 , − CH2OH, − CHX2 , − CHO, − C − Z

 Maleic acid (HOOC − CH = CH − COOH) show geometrical isomerism while malic acid
(HOOC − CH2 − CHOH − COOH) show optical isomerism.

(5) Calculation of number of optical isomers

(i) If molecule is not divisible into two identical halves and molecule has n asymmetric
carbon atoms then

Number of optically active forms = 2n = a

Number of enantiomeric pair = a /2

Number of racemic mixture = a /2

Number of meso form = 0

  
Examples : C6H5 − CHOH − CHOH − CHOH − CH3

This molecule cannot be divided into two identical halves and it has three asymmetric
carbons. Hence number of optical active isomers = a = 2n = 23 = 8 .

   
CH 2OH − C HOH − C HOH − − C HOH − C HOH − CHO
n =4

Number of optically active forms = a = 24 = 16

 
CH 3 − C HOH − − C HCl − CH 3
n =2

Number of optically active forms = 22 = 4

(ii) If molecule is divisible into two identical halves, then the number of configurational
isomers depends on the number of asymmetric carbon atoms.


Case I : When compound has even number of carbon atoms, i.e., n = 2,4,8,10,12,..... :

(i) Number of optically by active forms = a = 2n−1

(ii) Number of enantiomeric pairs = a /2

(iii) Number of racemic mixture = a /2

(iv) Number of meso forms = m = 2(n/2)−1

(v) Total number of configurational isomers = a + m
Example :

 
COOH − C HOH − − C HOH − COOH
(I) (II)

Two idenitcal halves (I) and (II) having n = 2 .

Thus number of optical isomers = a = 22−1 = 2

Number of meso form = m = 2(n/2)−1 = 2(2/2)−1 = 20 = 1

Total number of configurational isomers = 2 + 1 = 3

   
C6 H 5 − C HCl − C HCl − − C HCl − C HCl − C6 H 5
n = 4, even

a = 24−1 = 23 = 8

m = 2(n/2)−1 = 21 = 2
Total number of configurational isomers = 8 + 2 = 10
Case II : When compound has odd number of carbon atoms, i.e., n = 3,5,7,9,11,...... :

(i) Number of optically active forms = a = 2n−1 − 2(n−1)/2

(ii) Number of enantiomeric pairs = a /2

(iii) Number of racemic mixutre = a /2

(iv) Number of meso forms = m = 2(n−1)/2

(v) Total number of configurational isomers = a + m
Example :

  
CH 2OH − C HOH − C HOH − C HOH − CH 2OH
(I) (II)

Compound has two identical halves and has three asymmetric carbons.


 Thus, a = 2n−1 − 2(n−1)/2 = 22 − 21 = 4 − 2 = 2

m = 2(n−1)/2 = 21 = 2
Hence total number of configurational isomers = 2 + 2 = 4
    
COOH − CHCl − CHOH− CHBr − CHOH − CHCl − COOH
(I) (II)
n =5

(6) Optical activity of compounds containing one asymmetric carbon

 
Examples : CH3 − CHOH− COOH ; CH3 − CHOH− CHO

 
CH2OH − CHOH− CHO ; C6H5 − CHCl− CH3

Any molecule having one asymmetric carbon atom exists in two configurational isomers
which are nonsuperimposible mirror images.
COOH COOH
| |
H — C — OH HO — C — H
| |
CH3 CH3
(I) (II)

(I) and (II) have the same molecular formula, the same structure but different
configurations, hence (I) and (II) are known as configurational isomers. (I) and (II) are
nonsuperimposable mirror images, hence (I) and (II) are optical isomers. Configurational isomers
which are nonsuperimposable mirror images are known as enantiomers. Thus (I) and (II) are
enantiomers. Pair of (I) and (II) is known as enantiomeric pair.
(i) Properties of Enantiomers : All chemical and physical properties of enantiomers are
same except two physical properties.
(a) Mode of rotation : One enantiomer rotates light to the right and the other by an equal
magnitude to the left direction. For example

Enantiomer [
] bp d

(+) 2-methyl-1-butanol + 5.78 128.9 1.41

(–2) -methyl-1-butanol – 5.78 128.9 1.41

(b) Rate of chemical reaction with an optically active compound : Both the
enantiomers of 2-methyl-1-butanol are converted to 2-methyl butene when treated with conc.
H2SO4 . The rate of the reactions is the same.


 CH2OH
|
conc.H SO
CH3 —C— H ⎯⎯⎯⎯⎯
2 4
→ CH3 − CH2 − C = CH2 K1
|  |
C2H5 CH3
(+)

CH2OH
|
conc.H SO
H — C— CH3 ⎯⎯⎯⎯⎯
2 4
→ CH3 − CH2 − C = CH2 K2
|  |
C2H5 CH3
(−)

When both these compounds are treated with lactic acid, the rate of the reaction is
different.
(+) –2–methyl-1-butanol
K3 (–) lactic acid

Ester
(–) –2-methyl-1-butanol
K4 (–) lactic acid

Ester
K3  K 4

Thus rate of reactions of enantiomers with optically active compound is different.

(ii) Racemic Mixture : An equimolar mixture of two enantiomers is called a racemic mixture
(or racemate,  form, (dl) form or racemic modification). Such a mixture is optically inactive
because the two enantiomers rotate the plane polarised light equally in opposite directions and
cancel each other’s rotation. This phenomenon is called external compensation.
 Racemic mixture can be separated into (+) and (–) forms. The separation is known as
resolution.
 The conversion of (+) or (–) form of the compound into a racemic mixture is called
racemisation. It can becaused by heat, light or by chemical reagents.

 Racemic mixture is designated as being (  ) or (dl).

(iii) Enantiomeric Excess : A sample of an optically active substance that consists of a single
enantiomer is said to be enantiomerically pure or to have an enantiomeric excess of 100%. An
enantiomeric pure sample of (+)-2-butanol shows a specific rotation of 13.52º. On the other hand,


 a sample of (+)-2-butanol that contains less than an equimolar amount of (–)-2-butanol will show
a specific rotation that is less than +13.52o but greater than 0o .
Such a sample is said to have an enantiomeric excess less than 100%. The enantiomeric
excess (ee) is defined as follows :
% Enantiomeric excess = (moles of one enantiomer – moles of other enantiomer)
100
Total number of moles of both enantiomers
The enantiomeric excess can be calcualted from optical rotation :
Observed specific rotation
% Enantiomeric excess =  100
Specific rotation of pure enantiomer

Enantiomeric excess is also known as optical purity.

(7) Optical activity of compounds containing two asymmetric carbon
Case I : When molecule is not divisible into two identical halves.

The number of optical isomers possible in this case is four (a = 22 = 4) . Further there
will be two pairs of enantiomers and two racemic modifications. In practice also it is found to be
so. For example dibromocinnamic acid exists in the following four optically active forms.

COOH COOH COOH COOH

| | | |
H — C— Br Br — C— H H — C— Br Br — C— H
| | | |

H — C— Br Br — C— H Br — C— H H — C— Br
| | | |

C6H5 C6H5 C6H5 C6H5

(I) (II) (III) (IV)
First pair of enantiomers Second pair of enantiomers

Thus there are two pairs (I), (II) and (III), (IV) of enantiomers. Further, more
equimolar mixutre of (I) and (II) will give one racemic mixture. Similarly, equimolar mixture of
(III) and (IV) will give other racemic mixutre.
Now let us examine the relationship between the structures (I) and (III), (I) and (IV),
(II) and (III) and (II) and (IV). These are configurational isomers but these are not mirror images.
Configurational isomers which are not mirror images are known as diastereomers.
Thus (I) and (III) are diastereomers
(I) and (IV) are diastereomers
(II) and (III) are diastereomers
(II) and (IV) are diastereomers


 Properties of Diastereomes : Diastereomers have different physical properties, e.g.,
melting and boiling points, refractive indices, solubilities in different solvents, crystalline
structures and specific rotations. Because of differences in solubility they often can be separated
from each other by fraction crystallisation; because of slight differences in molecular shape and
polarity, they often can be separated by chromatography.
Diastereomers have different chemical properties toward both chiral and achiral
reagents. Neither any two diastereomers nor their transition states are mirror images of each
other and so will not neccessarily have the same energies. However, since the diastereomers have
the same functional groups, their chemical properties are not too dissimilar.
Case II : When molecule is divisible into two identical halves.

Number of optical isomers = a = 22−1 = 2

Number of meso forms = m = 20 = 1

Total number of configurational isomers = 3
For example, tartaric acid exists in the following three forms :
COOH
COOH COOH |
| | H — C — OH
H — C — OH HO — C — H |
| | H — C — OH
HO — C — H H — C — OH |
| | COOH
(III)No non - super imposible mirror
COOH COOH image because it has a plane of
(I) (II) symmetry

(I) and (II) are enantiomers

(I) and (III) diastereomers
(II) and (III) are diastereomers
(III) is optically inactive due to symmetry of the molecule. It is known as meso form.
(8) Optical activity in compounds containing no assymmetric carbon :
Although the largest number of known optically active compounds are optically active due
to the presence of chiral carbon atom, some compounds are also known which do not possess any
chiral carbon atom, but on the whole their molecules are chiral (such molecules were earlierly
called dissymmetric); hence they are optically active. Various types of compounds belonging to
this group are allenes, alkylidene cycloalkanes, spiro compounds (spirans) and properly
substituted biphenyls.
(i) Allenes : Allenes are the organic compounds of the following general formulae.
C =C =C


 Allenes exhibit optical isomerism provided the two groups attached to each terminal
carbon atom are different, i.e.,

a a a x
C =C =C or C=C=C
b b b y

For example, 2 3-pentadiene shows enantiomerism (optical isomerism)

H H H H
C =C =C C =C =C
H3C CH 3 H3C CH 3

Non-superimposable mirror images of 2, 3-pentadiene

(ii) Alkylidene cycloalkanes and spiro compounds : When one or both of the double bonds
in allenes are replaced by one and two rings, the resulting systems are respectively known as
alkylidene cycloalkanes are spirans.
H3C H a CH 2 CH 2 a
=C C C C
H COOH b CH 2 CH 2 b
1-Methylcyclohexylidene-4- acetic
acid (Alkylidene cycloalkane) Spirans

(iii) Biphenyls : Suitably substituted diphenyl compounds are also devoid of individual chiral
carbon atom, but the molecules are chiral due to restricted rotation around the single bond
between the two benzene nuclei and hence they must exist in two non-superimposable mirror
images of each other. Such types of stereoisomerism which is due to restricted rotation about
single bond, is known as atropisomerism and the stereoisomers are known and atropisomers.
Examples
COOH O2N F HOOC

NO2 HOOC COOH F

The above discussion leads to the conclusion that the essential condition for optical
isomerism is the molecular disymmetry or molecular chirality and not the mere presence of a
chiral centre. However, it may be noted that the molecules having only one chiral centre are
always chiral and exhibit optical isomerism.
(9) Fischer projection formulae :

The arrangement of the atoms or groups in space that characterizes a stereoisomer is called its
configuration.


 Emil Fischer (1891) provided an easy method to represent the three dimensional
formulae of various organic molecules on paper. Fischer projection is, thus, a planar
representation of the three dimesional structure.
By convention, the following points are followed in writing the Fischer formula.
(i) The carbon chain of the compound is arranged vertically, with the most oxidised carbon at the
top.
(ii) The asymmetric carbon atom is in the paper plane and is represented at the interaction of
crossed lines.
Asymmetric
Carbon atom

(iii) Vertical lines are used to represent bonds going away from the observer, i.e., groups
attached to the vertical lines are understood to be present behind the plane of the paper.

(iv) Horizontal lines represent bonds coming towards the observer, i.e., groups attached to the
horizontal lines are understood to be present above the plane of the paper.

Some Fischer projections are given below :

COOH CH3

COOH HO H Br H

HO H H OH H Br

CH 3 COOH CH3
Fischer projection of one of Fischer projection of one of the Fischer projection of one of the
the enantiomers of Lactic acid enantiomers of Tartaric acid enantiomers of 2,3 - dibromobutane

(10) Name of optical isomers : Following three nomenclatures are used for optically active
compounds,

(i) D,L. System of nomenclature : This nomenclature is mainly used in sugar chemistry or
optically active polyhydroxy carbonyl compounds. This nomenclature was given by Emil Fischer
to designate the configurations of various sugars relative to the enantiomeric (+) and (–) glucose
as reference.


 All sugars whose Fischer projection formula shows the OH group on the chiral carbon
atom adjacent to the terminal CH2OH group on the right hand side belong to the D -series.
Similarly if OH is on the left hand side, then the sugars belong to the L -series.

| |
H — C — OH HO — C — H
| |
CH2OH CH2OH
D−series L −series

Examples :

CHO CHO
| |
H — C— OH HO — C— H
| |

CH2OH CH2OH
D(d)glyceraldehyde L(l)glyceraldehyde
or or
D( + )glyceraldehyde L( − )glyceraldehyde

 It must be noted that there is no relation between the sign of rotation (+, – or d, l) and the
configuration (D and L) of an enantiomer.

 Any compound that can be prepared from, or converted into D(+) glyceraldehyde will
belong to D-series and similarly any compound that can be prepared from, or converted into L(–)
glyceraldehyde will belong to the L-series.

 This nomenclature is also used in  -amino acids.

(ii) Erythro and Threo System of Nomenclature : This nomenclature is used only in those
compounds which have
(a) Only two chiral carbons and

(b) The following structure, R − Cab − Cbc − R

i.e., out of six substituents on two asymmetric carbons, at least two should be same.

When two like groups (in the given example, group is b ) in Fischer projection
formula are drawn on the same side of the vertical line, the isomer is called erythro form; if these
are placed on the opposite sides, the isomer is said to be threo form.


 R CH3 CH3
| | |
a —C— b H — C — Cl H — C — Cl
| | |
c—C— b H — C — Br Br — C — H
| | |
R  C6H5 C6H5
Erythroform Erythro form Threo form

(c) R,S Nomenclature (Absolute configuration)

The order of arrangement of four groups around a chiral carbon (stereocentre) atom
is called the absolute configuration around that atom. System which indicates the absolute
configuration was given by three chemists R.S. Cahn, C.K. Ingold and V. Prelog. This system is
known as (R) and (S) system or the Cahn-Ingold Prelog system. The letter (R) comes from the
latin rectus (means right) while (S) comes from the latin sinister (means left). Any chiral carbon
atom has either an (R) configuration or an (S) configuration. Therefore, one enantiomer is (R) and
other is (S). A racemic mixture may be designated (R) (S), meaning a mixture of the two. (R) (S)
nomenclature is assigned as follows :
Step I : By a set of sequence rules given below the atoms or groups connected to the chiral
carbon are assigned a priority sequence.
Sequence Rules for Order of Priority
Rule 1 : If all four atoms directly attached to the chiral carbon are different, priority
depends on their atomic number. The atom having highest atomic number gets the highest
priority, i.e., (1). The atom with the lowest atomic number is given the lowest priority, i.e., (4), the
group with next higher atomic number is given the next higher priority (3) and so on. Thus,
Cl 3
| |
F —C — I  4 —C —1
| |
Br 2
F Cl Br I
⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯→
Increasing atomic number

1 2 3 4
Increasing priority


 COOH 4
| |
H 2N — C — Br  3 —C —1
| |
OH 2
C N O Br
⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯ ⎯→
Increasing priority

Rule 2 : If two or more than two isotopes of the same element is present, the isotope of
higher mass receives the higher priority.
1 2 3
1 H 1H 1H
Increasing priority

3 2 1

Rule 3 : If two or more of the atoms directly bonded to the chiral carbon are identical, the atomic
number of the next atoms are used for priority assignment. If these atoms also have identical
atoms attached to them, priority is determined at the first point of difference along the chain. The
atom that has attached to it an atom of higher priority has the higher priority.
I 2HandBr
| 
I − H2C − H2 C − C− CH2 − Br
 |
2HandC CH2 −CH2 −CH3

2HandC

In this example the atoms connected directly to the chiral carbon are iodine and three
carbons. Iodine has the highest priority. Connected, to the three carbons are 2H and Br, 2H and C
and 2H and C. Bromine has the highest atomic number amongst C,H and Br and thus CH2Br has
highest priority among these three groups (i.e., priority no. 2).The remaining two carbons are still
identical (C and 2H) connected to the second carbons of these groups are 2H and I and 2H and aC.
Iodine has highest priority amongst these atoms, so that −CH2 − CH2 − I is next in the priority list
and CH2 − CH2 − CH3 has the last priority.
I
| 1
I − CH 2 − CH 2 − C − CH 2 − Br  3 2
|
CH 2 −CH 2 −CH 3 4

Rule 4 : If a double or a triple bond is linked to chiral centre the involved atoms are
duplicated or triplicated respectively.
O N O O
| | || |
− C = O  − C− O ; −C  N  − C− N ; − C− OH  − C− OH
| | | |
N O

By this rule, we obtained the following priority sequence :


 − CH = CR 2 , − CN , CH 2 OH , CHO, CO, COOH

Increasing priority

Step 2 : The molecule is then visualised so that the group of lowest priority (4) is directed away
from the observes (At this position the lowest priority is at the bottom of the plane). The remaining
three groups are in a plane facing the observer. If the eye travels clockwise as we look from the
group of highest priority to the groups of second and and third priority (i.e., 1 → 2 → 3 with respect
to 4) the configuration is designated R. If arrangement of groups is in anticlocwise direction, the
configuration designated S.
For example:
2 2
| |
1 −C − 3 3 −C − 1
| |
4 4
Clockwise arrangement of Anticlockwise arrangement of
1 , 2 and 3 R 1 , 2 and 3 S

Let us apply the whole sequence to bromochlorofluoro methane.

F 3
| |
Br − C − H  1 −C − 2
| |
Cl 4

This Fischer projection the least priority number is not at the bottom of the plane.
In such cases the Fischer projection formula of the compound is converted into another
equivalent projection formula in such a manner that atom or group having the lowest priority is
placed vertically downward. This may be down by two interchanges between four priority
numbers. The first interchange involves the two priority numbers, one is the least priority number
and other is the priority number which is present at the bottom of the plane. In the above case first
interchanges will takes place between 2 and 4.
3 3
| First interchange |
1 −C − 4 1 −C − 2
| Between 2 and 3 |
2 4
(A) (B)

First interchange of two groups at the chiral centre inverts the configuration and this gives
enantiomer of the original compound. Thus (A) and (B) are enantiomer. The second interchange
involves the remaining two groups.


 3 1
| Second interchange |
1 −C − 2 3 −C − 2
| between remaining |
4 groups, i.e., 1 and 4 4
(B) (A)
Arrangement of 2 , 2and 3are
clockwise, hence configuration is R

Example :
H O
CHO C 2 2 1
| O | | First interchange | Second interchange
H − C − OH  H − C − OH  4 −C − 1 3 −C − 1 3 2
| | | Between 3 and 4 | Between 1 and 2
CH2OH CH2OH 3 4 4

Clockwise
R-configuration

CHO 2 1
| | (i) First interchange between 3 and 4
HO − C − H  1 −C − 4 2 3
| |
CH2OH 3 (ii) Sec. interchange between 1and 2 4
Anticlockwise

S-configuration

Glyceraldehyde (For example) has one asymmetric carbon, hence it has two configurational isomers
(I) and (II).

CHO CHO
| |
H − C− OH HO − C− H
| |
CH2OH CH2OH
(R)glyceral dehyde (S)glyceral dehyde
(I) (II)

One can draw a number other configurations for glyceraldehyde but each of them will be
a repetition of either (I) or (II). In this connection it is important to note that if two projection
formulae of differ by an odd number of interchagnes (1, 3, 5, 7, …..) of positions of groups on the
chiral carbon, they are different, but if the two differ by an even number of interchanges (2, 4, 6,
…..) they are identical.

For example :
CHO CHO OH
| | |
H,CH2OH Second interchange
H − C− OH ⎯⎯⎯⎯
→ CH2OH − C− H ⎯⎯⎯⎯⎯⎯⎯
→ CH2OH − C− CHO
| First interchange | between OH,CHO |
CH2OH H H
(I) (II) (III)


 CH2OH CH2OH
| |
Third intrerchange Fourth interchange
⎯⎯⎯⎯⎯⎯⎯ → HO − C− CHO ⎯⎯⎯⎯⎯⎯⎯ → HO − C− H
CH2OH,OH | H,CHO |
H CHO
(IV) (V)

Thus (I), (III) and (V) are identical. Similarly (II) and (IV) are identical.

(11) Resolution of racemic modifications :

The separation of racemic mixture into its enantiomers is known as resolution. The following
methods are used for resolution.

(i) Resolution by mechanical separation : Since (+) and (–) forms have opposite crystalline
shapes, this property can be used in the separation of the two forms from a racemic mixture.

(ii) Biochemical separation : When a living organism is added to or developed to a racemic

mixture, they eat up one of the enantiomers preferentially leaving the other behind. Thus, resolution
of forms can be done using this specific property of living organisms. For example, Penicillium
glaucum can be used to remove (d)-ammonium tartrate from the racemic mixture to leave back
only the (l)-ammonium tartrate after a suitable time interval.

(iii) Separation by conversions into diasteremoers : Enantiomers have identical physical

properties while diastereomers have different physical properties. This fact is utilised in
separation of enantiomers from racemic mixture. The racemic mixtrue to be resolved is allowed
to react with an optically active compound. This leads to the formation of two diastereomers.
These have different physical properties, so both diastereomers can be separated by physical
methods. Each of the enantiomers may then be regenerated and isolated from the diastereomers.
Resolution of enantiomers through the use of diastereomers is given below:


 Pair of diastereomers. Top of the molecules are
mirror images but bottom s are not.
B B
| |
1:1enantiomers A − C− D D − C− A
B B | |
| |
Chemical
A − C− D + D − C− A ⎯⎯⎯⎯ → W + W
| | reaction
| |
X X U − C− W U − C− W
(R) (S) | |
O V V
| (R ,R) (R ,S)
U − C− W
|
V
(R)
Single optically active enantiomer

B
|
Chemiocal
R,R ⎯⎯⎯⎯→ A − C − D
reconversion |
X
(R)
Physical
⎯⎯⎯⎯ →
separation
B
|
Chemical
R,S ⎯⎯⎯⎯
→D − C− A
reconversion |
X
(S)
Separated enantiomers

DRC :  Group X reacts with group O to give new group W.

(12) Asymmetric synthesis and Walden inversion

(i) Asymmetric synthesis : The synthesis of an optically active compound (asymmetric)

from a symmetrical molecule (having no asymmetric carbon) without resolution to form (+) or (-
) isomer directly is termed asymmetric synthesis. For example the reduction of pyruvic acid
O
||
(CH3 − C − COOH) in presence of nickel catalyst gives () lactic acid (racemic mixture). On the other

hand, pyruvic acid is reduced to (–) lactic acid only by yeast.


 CH3 CH3
| |
2H
⎯→H − C − OH + H − C − H
⎯⎯
'Ni ' | |
COOH COOH
CH3 ( + ) Lactic acid ( − ) Lactic acid
|  
Reduction mixture
C =O ⎯⎯ ⎯⎯ ⎯→
|
COOH CH3
(Pyruvic acid)
(2 - Keto propanoic acid) |
2H
⎯⎯⎯→ HO − C − H
Yeast |
COOH
( − ) Lactic acid

(ii) Walden inversion : The conversion of (+) form into (-) form and vice-versa is called
Walden inversion. When an atom or group directly linked to an asymmetric carbon atom is
replaced (inverse); the configuration of the new compound may be opposite to that of the original,
i.e.,

CH3 CH3 COOH COOH COOH

| | | | |
PCl AgOH PCl AgOH
H − C− OH → Cl − C− H
⎯⎯5⎯ ⎯⎯⎯ → HO − C− H → H − C− Cl
⎯⎯5⎯ ⎯⎯⎯ → H − C− OH
| | | | |
CH2COOH CH2COOH CH2COOH CH2COOH CH2COOH
( + ) Malic acid ( − ) Chloro succinic acid ( − )Malic acid ( + ) Chloro succinic acid ( + ) Malic acid

2.16 Conformational isomerism .

(1) Definition : The different arrangement of atoms in a molecule which can be obtained due to
rotation about carbon-carbon single bond are called conformational isomers (conformers) or
rotational isomers (rotamers). This type of isomerism is found in alkanes and cycloalkanes and
their substituted derivatives.

It may be noted that rotation around a C − C sigma bond is not completely free. It is in fact
hindered by an energy barrier of 1 to 20 kJ mol-1 in different bonds. There is a possibility of weak
repulsive interactions between the bonds or electron pairs of the bonds on adjacent carbon atoms.
Such type of repulsive interaction is known as torsional strain.

(2) Difference between conformation and configuration : The term conformation should not be
confused with the configuration which relates to those spatial arrangements of the atoms of a
molecule that can be changed only by the breaking and making of bonds whereas the spatial
arrangements in conformation are changed simply by rotation about a single bond.

(3) Representalion of conformations : Represent conformations we can draw three dimensional

pictures. However, chemists represent conformations in two simple ways. These are : (i) Saw
horse representation and (ii) Newman projection


 (i) Saw horse representation : In this projection, the molecule is viewed along the axis of
the model from an oblique angle. The central carbon-carbon bond ( C − C ) is draw as a straight line
slightly tilted to right for the sake of H
clarity. The front carbon is shown as the Back carbon
lower left hand carbon and the rear C
carbon is shown as the upper right hand H H H Back
H H
carbon. The three bonds around each H H
C Front Front carbon
carbon atom (C − H in ethane or C − C in H H
higher alkanes) are shown by three H H
Saw horse representation Newman projection
lines.
(ii) Newman projection : This is a simple method to represent the conformations. In this
method, he molecule is viewed from the front along the carbon-carbon bond axis. The two carbon
atoms forming the -bond are represented by two circles; one behind the other so that only the
front carbon is seen. The front carbon atom is shown by a point whereas the carbon further from
the eye is represented by the circle. Therefore, the C − H bonds of the front carbon are depicted
from the centre of the circle while C − H bonds of the back carbon are drawn from the
circumference of the circle at an angle of 120° to each other.

(4) Conformation in alkanes

(i) Conformations of ethane : When one of the H H H H

carbon atom is kept fixed and other is rotated C C
about C − C bond an infinite numbers of isomers 60°
H H H H
possible. Out of all the conformations for ethane,
C C
only two extreme conformations are important
H H H H
and these are: Staggered Eclipsed
conformation conformation
(a) Staggered conformation

(b) Eclipsed conformation


(a) Staggered conformation : In this H
H
arrangement, the hydrogens of he two carbon H H
H H
Eclipsed
atoms are staggered with respect to one another.
(less stable)
As a result, they are at maximum distance apart
and have minimum repulsion between them.
12.5 kJ
(b) Eclipsed conformation : In this

Energy
H H
conformation, the hydrogens of one carbon atom H H Staggered H H
are directly behind those of the other. H H ( t bl ) H H
H H
Consequently, the repulsion in these atoms is
The variation of energy versus
rotation about C–C bond
maximum. The saw horse projections of these
conformations are represented in fig.

Saw horse representation of staggered and eclipsed conformations of ethane

60°
H H
H H 60° 60° H
H H
H H H H
H
60° Eclipsed
Staggered conformation
conformation
Newman projections for staggered and eclipsed conformations of ethane

The Newman projections for staggered and eclipsed conformations of ethane are
shown in figure. It is clear that when the staggered conformation is rotated through angle of 60°,
it changes to eclipsed conformation and similarly, when eclipsed conformation is rotated through
the same angle, it gives back the staggered conformation.

Relative stabilities of the conformations of ethane : The two conformations of ethane

differ in their relative stabilities. The staggered conformation has minimum repulsions between
the H-atoms attached tetrahedrally to the two carbon atoms. On the other hand, the eclipsed
conformation has maximum force of repulsion between H-atoms. Therefore, the staggered
conformation is more stable than the eclipsed conformation. The difference in the energy contents
of the staggered and eclipsed conformations is 12.5 kJ mol-1. This small barrier to rotation is also
called torsional barrier of the single bond. However, this energy difference is not large enough
to prevent rotation. Even at ordinary temperatures, the molecules have thermal of kinetic energy
to overcome this energy barrier. Therefore, the two conformations of ethane go on changing from


 one form to another and consequently, it is not possible to isolate the different conformations of
ethane.

The variation of energy versus rotation about the C − C bond has been shown in figure.

(ii) Conformations of propane : The next higher member in alkane series, propane
(CH3 − CH2 − CH3 ) has also two extreme conformations, staggered conformation and eclipsed
conformation. In figure only Newman projections are shown for simplicity. However, the energy
barrier in propane is 14 kJ mol-1, which is slightly higher than that in ethane.

CH3 CH3
H H H
H H
H H H H
H
Staggered Eclipsed
propane propane
Newman projection of propane

In the eclipsed conformation of the propane, there are two ethane type H − H interactions
and an additional interaction between C − H bond and C − C bond (of methyl group). The variation
of energy versus rotation about C − C bond as shown in fig.

(iii) Conformations of butane : As the alkane

CH CH CH
molecule becomes larger, the conformation situation H H H CH H
H3 H
becomes more complex. In butane H H H H H H
ew H
(CH3 − CH2 − CH2 − CH3 ) , for example, the rotation
I II III
about the single bond between two inner atoms ( C2 E li d Sk
CH ew CH
and C3 ) is considered. In this case, all the staggered as CH S Sk H
well as eclipsed conformations will not have same H H II k H H
H H I H CH
stability and energy because of different types of Energy Anti II
interaction between C − C (Of methyl) and C − H
I
bonds. Different conformations of butane
The lowest energy conformation will be the one, in which the two methyl groups are as
far apart as possible i.e., 180° away form each other.


 This conformation will be maximum staggered and is called anti conformation (marked
I). Other conformations can be obtained by rotating one of the C2 or C3 carbon atoms through an
angle of 60° as shown ahead.
60°
As is clear from the above Newman 109.5° deviation
projection the Gauche or Skew conformations (III
and V) are also staggered. However, in these
conformations, the methyl groups are so close that
d eclipse
they repel each other. This repulsion causes gauche

109.5°
conformations, to have about 3.8 kJ mol-1 more ed
energy than anti conformation. This conformations Fully VI
II and VI are eclipsed conformations. These are Eclips
unstable because of repulsions. These are 16 kJ mol-
1 less stable than anti conformation. Conformation IV IV

is also eclipsed and it is least stable having energy 19 Eclipsed

kJ mol-1 more than anti conformation. This is because
of repulsion between methyl-methyl groups which are very closed together. It is called fully
eclipsed conformation.

The order of stability of these conformations is, Anti > Skew or Gauche > Eclipsed > Fully
eclipsed.

The energy differences between various conformations is shown in figure.

(5) Conformations in cycloalkanes

(i) Stability of cycloalkanes : Compounds with three and four membered rings are not as
stable as compounds with five or six membered rings.

The German chemist Baeyer was the first to suggest that the instability of these small rings
compounds was due to angle strain. This theory is known as Baeyer-strain theory.

Baeyer strain theory was based upon the assumption that when an open chain
organic compound having the normal bond angle 109.5° is convert into a cyclic compound, a
definite distortion of this normal angle takes place leading to the development of a strain in the
molecule.

Baeyer assumed that cyclic rings are planar. Assuming that the rings are planar, the
amount of strain in various cycloalkanes can be expressed in terms of angle of deviation (d).
1 2(n − 2)  1
d = 109.5 −  90 or d = [109.5 − ]
2 n  2

where n = number of carbon-carbon bonds in cycloalkane ring;  = inner bond angle in the cycloalkane
ring.


 1 1
Angle strain  d  ; Stability   innerangle( )
inner angle d

Now let us take the case of three to eight membered cyclic compounds.
 
  

Cyclopropan Cyclobutane Cyclopentane Cyclohexane Cycloheptane Cycloactane
e  = 90°  = 108°  = 120°  = 128.6°  = 135°
 = 60° d = 9.4° d = 0.44° d = –5.16° d = –9.33° d = –12.46°
The positive and negative values of (d) indicate whether the inner angle is less than or
more than the normal tetrahedral value.
Beayer thus predicted that a five membered ring compound would be the most stable.
He predicted that six membered ring compounds would be less stable and as cyclic compound
became larger than five membered ring they would become less and less stable.
Contrary to what Baeyer predicted, however cyclohexane is more stable than
cyclopentane. Furthermore, cyclic compounds do not become less and less stable as the number
of sides increase. Thus Baeyer strain theory is applicable only to cyclopropane, cyclobutane and
cyclopantane.
deviatio
The mistake that Baeyer made was to assume that
all cyclic compounds are planar. In real only cyclopropane
is planar and other cycloalkanes are not planar. Cyclic
° n
compounds twist and bend in order to achieve structure
that minimises the three different kinds of strain that can 24.44
destabilise a cyclic compound. 24.44°

(a) Angle strain is the strain that results when the

bond angle is different from desired tetrahedral bond angle of 109.5°.
(b) Torsional strain is caused by repulsion of the bonding electrons of one substituent with
bonding electrons of a nearby substituent.
(c) Steric strain is caused by atoms or groups of atoms approaching each other too closely.
(ii) Conformation of cyclohexane : Despite Baeyer’s prediction that five-membered cyclic
compounds would be the most stable, the six membered cyclic compound is the most stable. Six
membered cyclic compound are most stable because they can exist in a conformation that is
almost completely free of strain. This conformation is called the chair conformation. In a chair
conformation of cyclohexane all bond angles are 111° which is very close to the 109.5° and all the
adjacent carbon-hydrogen bonds are staggered.


 a a
c
c c H H
a a H CH2 H
c
c c H CH2 H
a a H H

Chair conformation of cyclohexane Newmann projection of the

chair conformation

 Each carbon in chair conformation has an axial bond and an equatorial bond.

 Axial bonds are perpendicular to the plane of the ring equatorial bonds are in the plane of
the ring.

 If axial bond on carbon-1 is above the plane of the ring then axial bond on carbon-2 will be below
the plane of the ring. Thus

C − 1,C − 3 and C − 5 axial bonds are above

C − 2,C − 4 and C − 6 axial bonds are below

a a
1 6
5
a a
2 3 4
a a

 Thus C − 1 axial and C − 2 axial are trans to each other. Similarly C − 1 and C − 5 axials are
cis to each other.

 If axial bond on carbon-1 will be above the plane then equatorial bond on this carbon will be below
the plane.

Above
Belo

Above
Belo

(a) Thus C − 1 equatorial and C − 2 equatorial bonds are trans.

(b) C − 1 axial and C − 2 equatorial will be cis.


 As a result of rotation abut carbon-carbon single bonds cyclohexane rapidly interconverts
between two stable chair conformations. This interconversion is know as ring –flip. When the two
chair forms interconvert, axial bonds become equatorial and equatorial bonds become axial.

Flippin

 Cyclohexane can also exist in a boat conformation. Like the chair conformation, the boat
conformation is free of angle strain. However, the boat conformation is less stable than the chair
conformation by 11 kcal/mole. Boat conformation is less stable because some of the carbon-
hydrogen bonds in boat conformation are eclipsed.
Flagpole
hydrogen CH2
HH HH
CH2
H H
HH HH
Boat conformation Newmann projection of boat
of cyclohexane conformation

The boat conformations is further destabilised by the close proximity of the flagpole
hydrogens. These hydrogens are 1.8 Å apart but the vander Waal’s radii is 2.4 Å. The flagpole
hydrogens are also known as trans nuclear hydrogens.
Note :  The selective stabilities of the four conformations of cyclohexane decrease in the order:
Chair > twist boat > boat > half chair.


 () () () () ()

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