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.

32223 CHCHCHCHCH epenn tan

323 CHCHCHCH

3

|

CH

epeniso tan

CH3 3CHC

3CH

3CH

epenneo tan

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.

iodidepropyln

ICHCHCH

223

iodidepropyliso

CHCHICH

33

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.

deopanaldehy

CHOHC

Pr52

Acetone

COCHCH 33

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.

etherDiethyl

HOCHC 5252

etheropylnMethyl

CHCHCHOCH

Pr3223

etherpropylisoMethyl

CHCHOCH

333

52HC

C

52HC

ketoneDiethyl

3CH

223 CHCHCH

OC

ketonepropylnMethyl

CHCH

OC

CH

23

3

ketoneisopropylMethyl

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.

kaneIsonitroaleNitroalkan

OO

NCHRNCHR

OHO

2

acidanicIsohydrocyacidcHydrocyani

CNHNCH |

(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

2CHOCHO COOHCH 2

OHCO

OH

OCHO

(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.

BrCH

BrCH

||

HCBr

BrCH

||

053..

2,1

pm

cisenedibromoeth 065

2,1

transenedibromoeth

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 Cis-trans 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.

3

3

||

CHCH

CHCH

CHCCH

CHCH

3

3

||K673

Butenecis 2 Butenetrans 2

• (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.

heneDichloroet2,1cis trans

060..pb 048..pb080.. pm

050.. pm

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-Z-configuration.

• 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).

ClBr

C

C

HCH3

BrCl

C

C

HCH3

Z EenechloropropBromo 11

ClBr

HCH

3

ClH

C

C

BrCH3

HCl

C

C

BrCH3

Z EenechloropropBromo 12

HCl

CHBr

3

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-1-chloropropene.

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

SOURCE

LIGHT

SAMPLE

TORYDEXTROROTA

CONTAINING

TUBE 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.

AchiralChiral

• 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.

AxisFoldFour AxisFoldTwo

AxisFoldThree AxisFoldFive

COOH

OHCH

OHCH

COOH

|

|

|

|

Symmetry

Plane

)

(

symmetryofplaneato

dueinactiveOptically

acidTartaricmeso

Symmetry

ofCentre

HOOC

COOHH

H

)

(

4,1

symmetryofcentrea

ofpresencethetodueinactiveOptically

acidicdicarboxyleCyclohexanTrans

’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.

COOHCOOH

HH

OH HO

3CH 3CH

• 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.

)( tetrahedraorformulaeePerspectiv

formulaeojectionFischer Pr

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 )

COOHCOOH

HH

OH HO

3CH 3CH

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.

56

|

|

|

HC

BrH

BrH

COOH

56

|

|

|

HC

HBr

HBr

COOH

56

|

|

|

HC

BrH

HBr

COOH

56

|

|

|

HC

HBr

BrH

COOH

sEnantiomer

sEnantiomer

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

OHCHO

OHCH

COOH

|

|

|

COOH

OHCH

HCHO

COOH

|

|

|

COOH

OHCH

OHCH

COOH

|

|

|

|

Two dissimilar Chiral Carbons – 2,3-dibromopentane:

• 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.

COOH

OHCH

CH

|

|2

OHCHO

OHC

CH

||

|3

acidLacticd

ytemporaril

disappears

Chirality

formEnolic

COOH

OHCH

CH

|

|3

COOH

OHCHO

CH

|

|3

acidLacticd acidLacticl

form

Racemic

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

HOH

OHCH 2

CHO

HOH

OHCH 2

I

hydeglyceralde II

hydeglyceralde

OHCH

OHCH

CHO

2

|

|

OHCH

OHCH

COOH

2

|

|

hydeglyceraldeD acidGlycericD

O

OHCH

OHCH

CHO

2

|

|

BrCH

OHCH

COOH

2

|

|

2

|

|

CH

OHCH

CHO

hydeglyceraldeD

3PBrii

oxidationi reduction

acidLacticD

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.

ClI

CH

Br

|

ICl

CH

Br

|

(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

OHandCHHCHCH 323 ,,

OH

CHCCHCH

H

|

|

323

( c ) . A doubly or triply bonded atom ‘x’ is considered as equivalent to two or three “x’s.

But –X > =x . Examples,

OHCH

OHCH

OCH

2

|

|

OC

H

OC

H

|

|

toequivalentis

O

OC

H

|

|

OHCHOHH 2,,

toequivalent toequivalent

CHCHC

C

|

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.

3

|

CHHO

CH

COOH

OHCH

CH

COOH

2

|

R S

acidLactic