Transcript Isomerism - Rupali Handal | The Pharmacist..

ISOMERISM
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Contents
Isomers-Definitions
Geometrical isomers
Nomenclature for Geometrical isomers
Optical Isomerism
Nomenclature For Optical Isomers
Racemic Mixtures
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Isomers
Same molecular formula with different
structural formula is called Isomers &
phenomenon is called as Isomerism.

Example-(C3H8O)
H3C CH2
n propanol
CH2OH
C2H5 O
CH3
Methyl ethyl ether
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Types Of Isomers

Stereoisomer
Geometrical Isomers
Optical Isomers
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Geometrical Isomers
Introduction:
Geometrical isomers occur as a result of
restricted rotation about a carbon-carbon
bond.
Single bond between two carbons in a non
cyclic structure may rotate around each
other at room temperature because as the
carbons rotate around each other the
degree of overlap between
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the atomic orbitals is not changed and remain
at maximum overlap as rotation occurs.
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Reason:
If there is a double bond between two carbons,
these sp2 carbons have a sigma overlap or bond
between two sp2 hybrid orbitals and a Pi overlap as
a result of the p overlap.The sigma overlap would
not change its maximum overlap as a result of
rotation about the two sp2 carbons. However if the
two sp2 carbons attempt to rotate about each other
this will reduce the p-p overlap of the Pi bond. The
Pi bond prevents the carbons from rotating about
each other.
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If the similar groups are fixed on the same side
as a result of this restricted rotation, then the
isomer would be classified as “cis”.
The similar groups are fixed due to restricted
rotation by double bond on opposite side of the
double bond then this isomer is “trans”.
The cis and trans isomers are differ in their
physical and chemical properties.
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cis-trans isomers

Cis-trans isomers differ from one another in the
way the atoms/ groups are positioned in space
 Cis –same, trans –across
 They have different physical and chemical
properties
 They interact differently with enzymes/
receptor sites
 They cannot be interconverted by rotation
around C-C bonds
 Rotation is restricted by double bond or
cyclic structure
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e.g
H3C
CH3
C C
H
H
H3C
H
C C
H
CH3
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E and Z nomenclature rule

The E/Z system is based on an assignment of
priorities to the atoms or groups attached to
each carbon of the double bond
 If the higher-priority atoms or groups are on
opposite sides of the pi bond, the isomer is (E)

If the higher-priority groups are on the same
side, the isomer is (Z)
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

The atom with the higher atomic number is of
higher priority.
If two atoms are identical, the atomic numbers
of the next atoms are used to assign the
priority.
 Priority is determined at the first point of
difference along the chain if the atoms have
the same atoms directly attached.
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H
Br
H3C
H
1
2
ClH2CH 2C
Br
H3C
Cl
3
4
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



On carbon 1, the methyl substituent is of higher
priority than H
On carbon 2, the bromine substituent is of higher
priority than H
 IUPAC name is (E)-1-bromopropene
On carbon 3, the chloroethyl substituent is of
higher priority than methyl
On carbon 4, the bromine substituent is of higher
priority than chlorine
 IUPAC name is (Z)-1-bromo-1,4-dichloro-2methylbut-1-ene
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Stereoisomers
Same molecular formula - same bond connectivities different arrangement of their atoms in space
Optical Isomers
non-superimposable mirror images
(also called Enantiomers)
X
W
W
C
C
Z
Y
Y
X
Z
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Optical Activity



Stereoisomers are said to be optically
active if the rotate plane polarized light.
Each type of enantiomer rotates light the
same amount, but in different directions.
Amount and direction of rotation must be
experimentally determined using a
polarimeter.
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Plane polarized light
Light that has been passed through a
nicol prism or other polarizing medium
so that all of the vibrations are in the
same plane.
non-polarized
polarized
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Polarimeter -an instrument used to
measure optical activity.
polarizer
light source
analyzer
sample tube
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Chirality
Chiral and Achiral Molecules


Although everything has a mirror image, mirror images may
or may not be superimposable.
Some molecules are like hands. Left and right hands are
mirror images, but they are not identical, or superimposable.
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Chirality
Chiral: A molecule or object that is not
superimposable on its mirror image is said to
be chiral.
Achiral: A molecule or object that is
superimposable on its mirror image is said to
be achiral.
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Cont…

Chiral Centre : A carbon that is bonded to
four different groups of atoms.
CH3
*
CH
CH2
CH3
Cl
2-chlorobutane
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Enantiomers
The enantiomers of lactic acid drawn in two different representations
O
OH
HO
O
C
C
C
C
H
CH3
OH
HO
O
O
OH
OH
H
CH3
HO
OH
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Enantiomers

3-Chlorocyclohexene
Cl
Cl
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Enantiomers

A nitrogen chiral center
+
+
N
H3 C
N
CH2 CH3
CH3 CH2 CH3
A pair of enantiomers
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Diastereomers
Mirror plane
CH3
H
CH3
Cl
c
c
c
c
OH
H
H
HO
CH3
Not mirror images.
H
Cl
CH3
Not mirror images.
Not mirror images.
CH3
Cl
CH 3
H
H
Cl
c
c
c
c
OH
H
CH3
H
HO
CH3
Nomenclature
1. D & L Nomenclature
Dextrorotatory – when the plane of polarized light is
rotated in a clockwise direction when viewed
through a polarimeter.
(+) or (d)
Levorotatory – when the plane of polarized light is
rotated in a counter-clockwise direction when
viewed through a polarimeter.
(-) or (l)
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2. R,S Nomenclature

Priority rules
1. Each atom bonded to the chiral center is assigned a
priority based on atomic number; the higher the atomic
number, the higher the priority
(1)
(6)
(7)
(8)
(16)
(17)
(35)
(53)
-H
-CH3
-N H2
- OH
- SH
- Cl
- Br
-I
Increas ing priority
2. If priority cannot be assigned per the atoms bonded to the
chiral center, look to the next set of atoms; priority is
assigned at the first point of difference
(1)
- CH 2 -H
(6)
- CH 2 -CH 3
(7)
- CH 2 -NH2
(8)
- CH 2 -OH
Increasing priority
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R,S Nomenclature
3. Atoms participating in a double or triple bond
are considered to be bonded to an equivalent
number of similar atoms by single bonds.
C
-CH=CH2
is treated as
O
-CH
is treated as
C
-CH-CH2
O C
C
O
H
C CH
is treated as
C C
C C H
C C
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Naming Chiral Centers
1. Locate the chiral center, identify its four
substituents, and assign priority from 1
(highest) to 4 (lowest) to each substituent.
2. Orient the molecule so that the group of
lowest priority (4) is directed away from you.
3. Read the three groups projecting toward
you in order from highest (1) to lowest
priority (3).
4. If the groups are read clockwise, the
configuration is R ; if they are read
counterclockwise, the configuration is S.
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Naming Chiral Centers
(S)-2-Chlorobutane
1
H Cl
S
2
3
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Naming Chiral Centers

(R)-3-Chlorocyclohexene
3
1
Cl
2
H

R
(R)-Mevalonic acid
1
1 4
HO CH3 O
HO
3
2
R
3
2
OH
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Racemic mixture

an equimolar mixture of two enantiomers
because a racemic mixture contains equal
numbers of dextrorotatory and levorotatory
molecules, its specific rotation is zero.

i.e. it is optically inactive.
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O
NH
O
O
O
H2C
NH
O
C
C
N
CH2
N
S-thalidomide (effective drug)
H2C
CH2
H
O
O
H
O
R-thalidomide (dangerous drug)
Racemic mixture of Thalidomide
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Racemic mixture
Equal amounts of (+) and (-) enantiomers - rotation is 0
COOH
C H
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[]D = +2.6° H3 C OH
COOH
H C
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CH3 [] = -2.6°
D
HO
Net rotation is zero.
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References
Stereochemistry of carbon compounds
by Ernest L Eliel
Stereochemistry of Organic Compounds, Principles
and Applications,
by D. Nasipuri
Stereochemistry Conformation and Mechanism
by P.S. Kalsi
Organic Chemistry, Sixth Edition,
by Robert Thornton Morrison, Robert Neilson Boyd
 www. google.com
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