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ISOMERISMISOMERISM

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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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IsomersSame molecular formula with different structural formula is called Isomers & phenomenon is called as Isomerism.

Example-(C3H8O)

H3C CH2 CH2OH

n propanol

C2H5 O CH3

Methyl ethyl ether

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Types Of Isomers

Stereoisomer Geometrical Isomers Optical Isomers

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

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HC C

H3C CH3

H HC C

H3C H

CH3

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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Br

H

H

H3C

1 2

Br

Cl

ClH2CH2C

H3C

3 4

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-2-

methylbut-1-ene

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StereoisomerStereoisomerss

Optical Isomers

Same molecular formula - same bond connectivities - different arrangement of their atoms in space

non-superimposable mirror images

W

CX

ZY

W

CXY

Z

(also called Enantiomers)

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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.

light source sample tube

polarizer analyzer

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ChiralityChiralityChiral 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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Chiral:Chiral: A molecule or object that is not A molecule or object that is not superimposable on its mirror image is said to superimposable on its mirror image is said to be chiral.be chiral.

Achiral:Achiral: A molecule or object that is A molecule or object that is superimposable on its mirror image is said to superimposable on its mirror image is said to be achiral.be achiral.

ChiralityChirality

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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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C

C

HOCH3

H

OHO

C

C

OHCH3H

O OH

OHOH

O

OHHO

O

EnantiomersEnantiomers The enantiomers of lactic acid drawn in two different representations

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EnantiomersEnantiomers 3-Chlorocyclohexene

Cl Cl

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A nitrogen chiral center

NCH2CH3H3C

NCH3CH3CH2

A pair of enantiomers

++

EnantiomersEnantiomers

Diastereomers

cc

C H 3

C H 3

C lH

H O H

cc

C H 3

C H 3

C l H

H O H

M irro r p lane

cc

C H 3

C H 3

C l H

H O H

cc

C H 3

C H 3

C lH

H O H

Not mirror images.Not mirror images.Not mirror images.Not mirror images. Not mirror images.Not mirror images.

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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)

1.1.D & L NomenclatureD & L Nomenclature

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2. R,S Nomenclature2. 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

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

(53)(35)(17)(16)(8)(7)(6)(1)

Increasing priority-H -CH3 -NH2 -OH -SH -Cl -Br -I

Increasing priority

(8)(7)(6)(1)-CH2-OH-CH2-NH2-CH2-CH3-CH2-H

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R,SR,S NomenclatureNomenclature3. Atoms participating in a double or triple bond

are considered to be bonded to an equivalent number of similar atoms by single bonds.

-CH=CH2

O-CH

C CH

O

HC

CO

C-CH-CH2

C

C C HC

C

C

C

is treated as

is treated as

is treated as

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Naming Chiral CentersNaming Chiral Centers1. 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 RR ; if they are read counterclockwise, the configuration is SS..

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2 3

S1

ClH

(S)-2-Chlorobutane

Naming Chiral CentersNaming Chiral Centers

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Naming Chiral CentersNaming Chiral Centers (R)-3-Chlorocyclohexene

(R)-Mevalonic acid

Cl

H 2

3

R

1

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HO OH

OHO CH3 23

1

R

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Racemic mixtureRacemic 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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H2CCH2

C

NHO O

HN

O

O

H2CCH2

C

NH OO

HN

O

O

S-thalidomide (effective drug) R-thalidomide (dangerous drug)

Racemic mixture of Racemic mixture of Thalidomide

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Racemic mixtureEqual amounts of (+) and (-) enantiomers - rotation is 0

H3CC

OHH

COOH

CH3C

HOH

COOH

DD []21 = -2.6°= +2.6°21[]

Net rotation is zero.

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References References Stereochemistry of carbon compounds by Ernest L Eliel Stereochemistry of Organic Compounds, Principles and Applications,by D. NasipuriStereochemistry Conformation and Mechanism by P.S. KalsiOrganic Chemistry, Sixth Edition, by Robert Thornton Morrison, Robert Neilson Boyd www. google.com

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