STREOCHEMISTRY
By
K.V. Murali Krishna
Lecturer in Chemisry
Silver Jubilee Govt. College (A)
KURNOOL - 518002
ISOMERISM
• The phenomenon of existence of various
compounds with identical molecular formulae.
• The individual organic compounds are called
‘Isomers’.
CLASSIFICATION
• Structural Isomerism
• Stereoisomerism.
STRUCTURAL ISOMERISM
• This type of Isomerism is observed in Organic
compounds with identical molecular formulae,
but differing in their structural formulae.
•
•
•
•
•
TYPES
a. Chain Isomerism
b. Position Isomerism
c. Functional Isomerism
d. Metamerism
e. Tautomerism
•
•
•
•
•
•
A. CHAIN ISOMERISM
The type of Isomerism arises due to difference
in the Carbon chain structure in organic
compounds with identical molecular formulae.
The chain Isomers of a compound are
designated as
n- ( normal)
iso- (one side chain or with a tertiary Carbon)
neo- ( two side chains or with a quaternary
Carbon)
Ex: The Chain isomers of Pentane.
H3C  CH 2  CH 2  CH 2  CH3
n  pen tan e
H3C  CH 2  CH  CH3
|
CH 3
iso  pen tan e
CH3
H 3C
C
CH3
CH3
neo  pen tan e
B. POSITION ISOMERISM
This type of isomerism arises due to difference in
the position of a substituent or a double or a
triple bond in organic compounds with identical
molecular formulae.
Ex; Position isomers of Idopropane and Butene.
CH 3  CH 2  CH 2 I
n  propyl iodide
CH 3  CHI  CH 3
iso  propyl iodide
FUNCTIONAL ISOMERISM
This type of Isomerism arises due to
difference in the nature of functional group
In Organic compounds with
identical molecular formulae.
Ex; Functional Isomers of molecular formula
C3H6O.
C2 H 5CHO
Pr opanaldehy
de
CH 3COCH 3
Acetone
D. METAMERISM
• This type of isomerism arises due to difference
in the nature of Alkyl groups present on either
side of a functional group in Organic
compounds with identical molecular formulae.
• The isomers of this type are called ‘Metamers’.
• Ex;(a). The Metamers of molecular formula
C4H10O.
• (b). The Metamers of molecular formula
C5H10O.
C2 H 5OC2 H 5
Diethyl ether
CH 3O  CH 2  CH 2CH 3
Methyl n  Pr opyl ether
CH 3O  CH CH 3 3
Methyl iso  propyl ether
CH 3
C2 H 5
C O
C
CH 3  CH 2  CH 2
C2 H 5
Methyl n  propyl ketone
Diethyl ketone
CH 3
CH 3 2 CH
C O
Methyl isopropyl ketone
E. TAUTOMERISM
• This type of Isomerism arises due to the
wandering of a labile Hydrogen atom between
two polyvalent atoms within the molecule.
• The isomers of this type are called ‘Tautomers’.
• Ex, (i) Nitroalkane and Isonitroalkane
• (ii). Cyanic acid and Isocyanic acid.
O
R  CH 2  N
O
Nitroalkane
OH
R  CH  N
O
Isonitroalkane
|

H C  N
Hydrocyanic acid
H N C
Isohydrocyanic acid
(iii). KETO-ENOL TAUTOMERISM
• The Acetoaceticester exhibits the properties of
both Ketones and Unsaturated hydroxyl
compound.
• This dual behaviour can be explained by
assuming that it exists in two isomeric forms
namely,
• Keto form and
• Enol form.
STREOISOMERISM: (SPACE ISOMERISM)
• This type of isomerism is exhibited by two or more
compounds
• with the identical molecular and structural formulae,
but with different spatial arrangements of atoms or
groups.
• The Isomers of this type are called ’Stereomers’. The
CLASSIFICATION
• Conformational Isomerism
• Configurational isomerism.
•
CONFORMATIONAL ISOMERISM
In this type of Isomerism, the various structures
are non super imposable and are easily inter
convertible by rotation about a single bond.
•
The isomers of this type are called Conformational
diastereomers or rotational isomers or
Conformations. Ex, Alkanes
•
An Alkane molecule can have three different
Conformations namely,
Staggered
Eclipsed
Skew or Gauche.
•
•
•
• Eclipsed Conformation:• The three groups or Hydrogen atoms attached to the
front Carbon will be exactly in front of those attached
to the rear Carbon atom.
• Staggered Conformation:• All the six groups or Hydrogen atoms attached to the
two Carbon atoms are clearly seen from the front side
of the molecule.
• Skew Conformation:• This is an intermediate conformation to that of
Eclipsed and Staggerted Conformations.
CONFORMATIONS – MODELS
(a). BALL AND STICK MODEL:
• This model is quite helpful to visualize the relative
positions of different atoms of rotational
Conformations.
• But this model only gives a two dimensional picture
. Ex, Conformations of Ethane
(b). SAWHORSE MODEL
• This model is quite easy to draw.
• It gives a three dimensional picture.
• The molecule is viewed slightly from above and from
the right.
• The lower left hand Carbon is always taken to be
towards the front.
• The Sawhorse drawings for Staggered and Eclipsed
Conformations of Ethane are given below.
Staggered
eclipsed
( c). NEWMAN PROJECTION FORMULAE
• The front Carbon atom is represented by a
point.
• The three bonds linking groups or atoms with
this Carbon atom are indicated by three lines
radiating from this point.
• The rear Carbon atom is represented by a
circle.
• Its three bonds are shown by three lines
radiating from the edge of the circle.
Staggered
eclipsed
II. CONFIGURATIONAL ISOMERISM
• In this type of Stereo isomerism the two structures are
non super imposable and non inter convertible by
rotation around the single bond.
Types
• (i). ENANTIOMERS: These are the mirror images of
each other and they are also called Optical or
Inversional Isomers. Ex, Enantiomers of Lactic acid.
OH
OH
HO  OC
HO  OC  CH 2
CH 2COOH
CO  OH
(ii). DIASTREOMERS
•
The Configurational Optical isomers which are not
mirror images of each other are known as
‘Diastereomers’.
• Ex, Diastereomers of Beta-dibromocinnamic acid.
(iii). GEOMETRICAL ISOMERS
• The isomers of this type differ in the
arrangement of atoms or groups around two
doubly bonded Carbon atoms.
• These isomers are also called ‘Cis-trans
Isomers’.
• Ex, Cis-teans isomers of dibromoethene.
H  C  Br
||
H  C  Br
1,2  dibromoethene  cis
m. p.  53 
0
H  C  Br
||
Br  C  H
1,2  dibrom oethene  trans
  65 
0
GEOMETRICAL ISOMERISM
• This type of Isomerism arises due to difference in the
arrangement of atoms or groups around two doubly
bonded Carbon atoms in Organic compounds with
identical molecular and structural formulae.
• The Isomers of this type are called Geometrical or Cistrans isomers. In a Cis-isomer similar atoms or groups
lie on the same side of the molecule and in a trans
isomer similar atoms or groups lie on either side of the
molecule.
• Ex, (i). Cis-trans isomers of 2-butene.
H  C  CH 3
||
H  C  CH 3
cis  2  Butene
673 K
H  C  CH 3
||
H 3C  C  CH
trans 2  Butene
• (ii). 1,2-dichloroethene
• The Geometrical Isomerism cannot exist in
Alkene molecule if either Carbon carries two
identical groups.
• Thus Propylene, 1-butene and Isobutylene do
not exhibit Geometrical isomerism.
cis 
1,2  Dichloroethene
b.p.600
m. p.  800
trans 
b.p.480
m. p.  500
E-Z-CONFIGURATION
• The Geometrical isomers of a molecule of molecular
formula abC=Ccd cannot be shown in the form of cis
and trans isomers, but can be assigned E-Zconfiguration.
• A priority is assigned between a and b groups of first
carbon atom and
• also between c and d groups of the second carbon
atom in accordance with Cahn-Ingold-Prelog
sequence rules.
• The isomer with higher priority groups of both the
carbon atoms lying on the same side of the molecule
is assigned ‘Z’-configuration ( Zusammen in German
meaning on the same side)
• The other isomer with higher priority groups of both
the carbon atoms lying on either side of the molecule
is assaigned ‘E’- configuration ( Entegegen in German
meaning opposite).
CH 3
H
CH 3
H
C
C
C
C
Br
Cl
Cl
Z
Br
CH 3
Br
CH 3
E
1  Bromo 1  chloropropene
CH 3  H
Br  Cl
Br
C
C
C
C
H
Cl
Cl
Z
H
E
2  Bromo 1  chloropropene
Br  CH 3
Cl  H
CAHN-INGOLD-PRELOG SEQUENCE RULES:
• 1. The group with higher molecular complexity should
be given higher priority.
• 2. In the case of individual atoms, the atom with higher
atomic number should be given higher priority.
• 3. If the first atoms of the groups are identical then the
atomic numbers of the second atoms should be
considered for assigning the priority of the groups.
• Ex: Z and E-configurations of 1-bromo-1chloropropene.
OPTICAL ISOMERISM
• The phenomenon in which compounds with similar
chemical and physical properties differ only in their
behavior towards plane polarized light optical activity)
is known as ‘Optical Isomerism’.
• The isomers of this type are called Optical isomers.
• The type of light, whose vibrations occur in only in a
single plane, is known as ‘Plane polarized light’.
• The plane polarized light can be obtained by passing
the ordinary light through a Nicol prism.
• The optically active substances can rotate the plane
polarized light either towards right or towards left by a
certain angle.
• The Optical active substances which rotate the plane
polarized light towards right are called Dextrorotatory
(d or +) and
• those which rotate the plane polarized light towards
left are called ‘Laevorotatory’ (l or -).
• The Optical activity of a substance is measured by
using a Polarimeter.
POLARIZER
LIGHT
SOURCE
TUBE
CONTAINING
DEXTROROTATORY
SAMPLE
ANALYZER
• The Polarimeter consists of two Nicol prisms, which
are called Polarizer and Analyzer.
• The Nicol prism is made by joining two prisms by
means of a special adhesive known as ‘Canada
balsam’.
• A space is provided in between the two Nicol prisms
for inserting a tube containing the sample liquid or
solution, whose Optical activity is to be determined.
•
•
•
•
•
SPECIFIC ROTATION
This is defined as the observed rotation, when the
polarized light is passed through one decimeter (10
cms) of the solution with a concentration of one gram
per milliliter.
The + or – signs denoted along with angle of rotation
indicates the direction of rotation. The (-) sign denotes
the rotation towards left, while (+) sign denotes the
rotation towards right.
Specific rotation [ α]dt = αobs / l .C
Where αobs = Experimental rotation
l = length of the solution in decimeters
• C = grams of substance per milliliter of solution
• The magnitude of rotation depends upon the following
factors:
• (a). Nature of the substance.
• (b). concentration of the solution.
• (c). Length of the sample tube.
• (d). Nature of solvent.
• (e). the temperature of the solution.
• (f). the wavelength of the light used. Generally the light
used is Sodium D-line of wavelength 589 Millimicrons.
CHIRAL CARBON OR CHIRAL CENTER
• A Carbon atom which is linked to four different mono
valent atoms or groups is known as ‘Chiral Carbon’ or
‘asymmetric Carbon’ or a ‘Chiral Center’ (Cheir in
Greek means hand, which has no symmetry).
• The Chiral Carbon is responsible for the Optical
activity of substances.
• A molecule with a Chiral Carbon is called a chiral or
asymmetric or dissymmetric molecule.
• But meso-tartaric acid with two Chiral Carbons is
‘Achiral’ (Symmetric).,
ELEMENTS OF SYMMETRY - CHIRALITY
Features of the Chiral molecule,
• A molecule with one Chiral center is always Chiral.
• A molecule with more than one Chiral centers may be
Chiral or achiral.
• A Chiral molecule should not have the following three
Elements of symmetry,
• Plane of symmetry
• Center of symmetry
• Axis of Symmetry
• The Plane of symmetry is a plane that divides the
molecule in ti two equal halves.
• A chiral molecule has no Plane of Symmetry.
• A hand is a chiral object and the ball is an Achiral
object.
Achiral
Chira
• Center of symmetry is a point from which if lines are
drawn on any group, on both sides to an equal
distance, it divides the molecule in to two equal
halves.
• Axis of symmetry – Two types.
• Simple axis of symmetry (Cn): Symmetry operation
means, an operation which produces an orientation
identical with that of the original.
• A molecule when rotated through an angle of 360 0, if
presents identical appearance by ‘n’ times then the
axis is called n-fold axis .
• Ex, Two, three, four and six fold axes are observed in
crystals.
Four Fold Axis
Two Fold Axis
Three Fold Axis
Five Fold Axis
H
COOH
|
 C  OH
HOOC
Centre of
Sym m etry H
Plane
Sym m etry
|

|
H  C 
OH
|
COOH
m eso Tartaric acid
(Optically inactive due
to a plane of sym m etry)
H
COOH
Trans  Cyclohexane  1,4  dicarboxylic acid
(Optically inactive due to the presence of
a centre of sym m etry)
’Alternating axis of symmetry’
• The rotation of the molecule by 360/n 0 about an axis
and then its reflection through a plane perpendicular
to the axis of rotation produces an orientation identical
with the original.
• This is ‘Improper rotation’ and such an axis is called
’Alternating axis of symmetry’ (Sn) ( S = Spiegelung,
Spiegel = mirror)
• Ex, 1,2,3,4 - tetramethylcyclobutane
a
b
c
•
•
•
•
•
•
ENANTIOMERS
The non super imposable pairs of a compound
and its mirror image. ( Enantio- Gk = opposite,
morph = form).
Ex, The enantiomers of Lactic acid
Characteristics
Physical properties are identical.
Differ in their action on plane polarized light.
Laevo (l or - ), Dextro ( d or +)
Possess identical Chemical properties except
when they are reacting with optically active
reagents.
COOH
COOH
OH
H
CH 3
H
HO
CH 3
• Ex, The dextro Tartaric acid gets consumed by the
mould penicillium glaucum, but not the laevo tartaric
acid.
• The racemic form is an equi molecular mixture of the
dextro and laevo forms of a compound.
• It is inactive due to internal compensation of rotation.
• Enantiomers are represented either as Tetrahedral
models or as Fischer projection formulae.
( Perspective formulaeor tetrahedra)
Fischer Projection formulae
Single chiral Carbon – Lactic acid
• The central carbon atom in lactic acid is linked
to four different groups namely,
• Hydrogen, Hydroxyl, methyl and Carboxylic
acid.
• Three Isomers of Lactic acid are
• d or (+) – Lactic acid ( + 2.24o )
• l or (-) – Lactic acid ( - 2.24o )
• dl – Lactic acid –Optically inactive due to
external compensation of rotation.( 0.00 )
COOH
COOH
OH
H
CH 3
H
HO
CH 3
NUMBER OF ENANTIOMERS
• 2n will be the number of isomers for a molecule with
‘n’ number of Chiral Carbons.
• These can be shown as 2n-1 pairs of enantiomers and
same number of racemic modifications.
• Ex, dibromocinnamic acid with two Chiral centers
exists in four Optically active forms.
• Enantiomers: I and II , III and IV = 2 Pairs
• Racemic modification: Equi mloecular mixtures of I
and II, III and IV.
COOH
COOH
|
|
H     Br
Br     H
|
H     Br
|
Br     H
|
|
C6 H 5
C6 H 5
Enantiomer s
COOH
COOH
|
|
Br     H
H     Br
|
H     Br
|
Br     H
|
|
C6 H 5
C6 H 5
Enantiomer s
Two Similar Chiral Carbons – Tartaric acid
• Tartaric acid with two similar Chiral Carbons
exists in the forms given below,
• d or (+) – Tartaric acid ( + 12o )
• l or (-) – Lactic acid ( - 12o )
• Meso – Tartaric acid, optically inactive due to
internal compensation of rotation.
• dl – Lactic acid –Optically inactive due to
internal compensation of rotation.( 0.00 )
COOH
|
H  C  OH
|
HO  C  OH
|
COOH
COOH
|
HO  C  H
|
H  C  OH
|
COOH
COOH
|
H  C  OH
|

|
H  C  OH
|
COOH
Two dissimilar Chiral Carbons – 2,3dibromopentane:
• It exists in four optically active forms.
• Enantiomers/ Racemic modifications: I and III,
III and IV.
• Diastereoisomers: I and III, I and IV, II and III, II
and IV
RACEMIZATION
• The process of converting an optically active dextro or
laevo compound in to Racemic modification by means
of heat, light and Chemical reagents.
• Racemization involves the formation of an unstable
‘enolic’ intermediate which is responsible for the loss
of chirality.
• Lactic acid
• Malic acid
• Tartaric acid.
CH 2
|
H  C  OH
|
COOH
d  Lactic acid
CH 3
CH 3
CH 3
|
C  OH
||
HO  C  OH
|
H  C  OH
|
COOH
Enolic form
d  Lactic acid
 Chirality 


 disappears 
 tem porarily 



|
HO  C  OH
|
COOH

l  Lactic acid
Racem ic
form
RESOLUTION
• The process of separation of the Racemic modification
in to two pure enentiomers.
METHODS
• Mechanical separation:- By Pasteur. The individual
isomers of Sodium ammonium tartarate can be picked
by forceps while observing under a magnifying lens.
• Bio-chemical separation:- The bacteria, yeast, moulds
and fungi when grown in a dilute solution of Racemic
modification selectively digest one isomer and do not
affect the other isomer.Penicillin glaucum digests
dextro Ammonium tartarate.
• Diastereoisomers formation:- An optically active acid
or base is used to convert Racemic modification in to
diastereo isomers ( salts).
• These salts are separated by fractional crystallization.
• Then they are hydrolysed by acids or bases to obtain
original active compounds.
• Dacid + Lacid + 2Dbase  ( Dacid – Dbase) + ( Lacid – Dbase)
Racemic acid
Active base
Diastereo isomers
• Selective adsorption:• The optically active substances get selectively
adsorbed by certain optically active acids such as
Camphor sulfonic acids, Methoxy acetic acid, Tartaric
acid, Malic acid and so on .
• The active constituents of Racemic Camphor can be
separated by selective adsorption over dextro lactose
adsorbent.
Specification of configuration
D – L – Notation
• Glyceraldehyde is taken as the reference.
• D – Glyceraldehyde - -OH on right hand side and –H
on the left hand side.
• The compounds which can be produced from D –
Glyceraldehyde or which can be converted in to D –
Glyceraldehyde are assigned D – configuration.
• The compounds which can be produced from L –
Glyceraldehyde or which can be converted in to L –
Glyceraldehyde are assigned L – configuration.
CHO
CHO
OH
H
H
HO
CH 2OH
CH 2OH
   glyceraldehyde
  glyceraldehyde
I
II
CHO
COOH
|
H  C  OH
|
O 

H  C  OH
|
|
CH 2OH
CH 2OH
D  glyceraldehyde
D  Glyceric acid
CHO
COOH
|
|
CHO
i oxidation
 H  C  OH reduction


H  C  OH 
ii  PBr3
|
|
CH 2OH
D  glyceraldehyde
CH 2 Br
|
H  C  OH
|
CH 2
D  Lactic acid
R & S Notation ( Rectus and Sinister System)
Cahn – Ingold – Prelog system: Assigning the configuration
to O. Isomers;
1, The four different groups attached to the chiral carbon are
assigned priority in accordance with the sequence rules.
a.
If four different atoms are linked to a Chiral Carbon, The
atom with maximum atomic number gets highest priority.
Ex, I > Br > Cl > H.
Br
Br
|
|
H C
I
H C
Cl
Cl
I
(b). If the first atoms of two or more groups are same
then the atomic number of the next atom is considered
for assigning the order of priority.
Ex, 2 - butanol
CH3CH 2 , H ,  CH3 and  OH
H
CH 3  CH 2
|
 C  CH 3
|
OH
( c ) . A doubly or triply bonded atom ‘x’ is
considered as equivalent to two or three “x’s.
But –X > =x . Examples,
H C  O
|
H  C  OH
|
CH 2OH
H
|
H , OH , CH 2OH
 C O
H
H
|
|
C  O
is equivalentto
 C O
|
O
equivalentto
equivalentto
|
C
HC C CH
II. Assigning the configuration:
• The optical isomer in which the different groups are
arranged clockwise in the decreasing order of priority
is assigned ‘R’ ( rectus = right) configuration.
• The optical isomer in which the different groups are
arranged anti clockwise in the decreasing order of
priority is assigned ‘S’ ( sinister = left ) configuration.
• The group of least priority is supposed to be away
from the rest of the molecule.
COOH
COOH
|
H C
HO
|
H C
CH 3
H 2C
OH
S
R
Lactic acid