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STEREOCHEMISTRY

Stereochemistry Of Organic Compounds 3

3.1 CONCEPT OF ISOMERISM

• Berzelius (Greek: coined

isos

the = equal; describe the relationship between two clearly different compounds having the same elemental composition.

term

meros

Such

isomerism

= part) to pairs of compounds differ in their physical chemical properties and are called and

isomers

For example,

• Ethyl alcohol (CH

CH

OH) and • Dimethyl ether (CH

OCH

) are isomers.

Structural or Constitutional Isomerism

3.2 TYPES OF ISOMERISM

ISOMERISM Stereoisomerism Geometric Isomerism Cinfi gurational Stereoi someri sm Optical Isomerism Conformational Stereoi somerism Rotational Isomerism Amine Inve rsion Chain or Skeletal or Nuclear Isomerism Position Isomerism Functional Isomerism Metamerism Tautomerism Ring-chain Isomerism Fig 3.1 Different types of isomerism of organic compounds

1. Structural or Constitutional Isomerism

These differ from each other in the way their atoms are structures.

connected, i.e., in their It’s six types signifying the main difference in the structural features of the isomers are:

I. Chain/Skeletal/Nuclear Isomerism II.

Position Isomerism III. Functional Isomerism IV. Metamerism V.

Tautomerism VI. Ring Chain Isomerism

•

I. Chain/Skeletal/Nuclear Isomerism These have same molecular formula but different arrangement of carbon chain within the molecule.

CH 3 H 3 C—CH 2 —CH 2 —CH 3 n-Butane

(straight chain)

C 4 H 10 H 3 C—CH—CH 3 Same molecular 2-Methylpropane ( Isobutane) formula (Branched chain) CH3CH2CH2CH2CH3 n-Pentane CH3 CH3 H3C C CH 3 CH3 2, 2-Dimethylpropane (Neo-pentane) C5H12 H3C CH CH 2 CH3 Same molecular formula 2-Methylbutane (Iso-pentane)

It may be worthwhile to mention here that this type of isomerism is not confined to hydrocarbons alone.

CH3CH2CH2CH2OH n-Butyl alcohol

(Straight chain)

H3C CH CH2OH H3C Isobutyl alcohol

(Branched chain)

CH3 H3C C OH CH3 Tert-butyl alcohol

(Branched chain)

II.

Position Isomerism These have same carbon skeleton but differ in the position of attached atoms or groups or in position of multiple (double or triple) bonds .

OH CH3CH2CH2OH Propan-1-ol (The OH group at C1) CH 3 —CH—CH 3 Propan-2-ol (The OH group at C2) Cl Cl Cl o-Dichlorobenzene Cl m-Dichlorobenzene Cl Cl p-Dichlorobenzene

H3C 1 2 C 3 C 4 CH3 H H But-2-ene

(Double bond at C2)

H 1 C 2 C 3 4 CH2 CH3 H H But-1-ene

(Double bond at C1)

4 3 2

CH3CH2C

4 3

CH3 C

2 1

C CH3 But-1-yne

(Triple bond at C1)

But-2-yne

(Triple bond at C2)

•

III.

Functional Isomerism These have same molecular formula but different functional groups.

CH3CH2OH

Ethanol

CH3 O CH3

Dimethyl e ther

O O CH3 C OH

Ethanoic acid

H C OCH3

Methyl methanoate

O CH3 C CH3 Propanone (Acetone) and O CH3CH2 C H Propanal (Propionaldehyde)

CH2 CH CH CH2 But-1,3-diene (an alkene) or CH3 CH C CH2 But -1, 2-diene (an allene) CH3CH2 C CH But-1-yne (an alkyne)

CH 2 OH OCH 3

and or

Benzyl alcohol (an alcohol) Anisole

(an ether)

CH3 C C CH3 But-2-yne (an alkyne)

OH OH o-Cresol

(a phenol)

CH 3 or m-Cresol

(a phenol)

CH 3 Here it may be worthwhile to mention that o-cresol and m-cresol are position isomers also.

•

IV.

Metamerism These have different number of carbon atoms (or alkyl groups) on either side of a bifunctional group (i.e., -O- , -S-, -NH-, -CO- etc.).

Metamerism is shown by members of the same family , i.e., same functional groups.

O O CH 3 CH 2 —C—CH 2 CH 3 is a metamer of Pentan-3-one

(Diethyl ketone)

CH 3 CH 2 CH 2 —C—CH 3 Pentan-2-one

(Methyl n-propyl ketone)

or O CH3 CH 3 —C—CHCH 3 3-Methylbutan-2-one

(Isopropyl methyl ketone)

CH 3 CH 2 —O—CH 2 CH 3 Ethoxy ethane

(Diethyl ether)

is a metamer of CH 3 CH 2 CH 2 —O—CH 3 or 1-Methoxy propane

(Methyl n-propyl ether)

CH3 CH 3 CH 2 CH—O—CH 3 2-Methoxypropane

(Isopropyl methyl ether)

•

Tautomerism

Structural or constitutional isomers existing in easy and rapid equilibrium by migration of an atom or group are tautomers (

keto-enol tautomerism).

O CH 3—C—H Acetaldehyde (keto form) O CH 3—C—CH3 Acetone (keto form) OH CH2 C—H Vinyl alcohol (enol form)

(Negligible amount)

OH CH2 C—CH3 Prop-1-ene-2-ol (enol form)

(Negligible amount)

In those compounds where the enol form can be stabilized by intramolecular bonding (also called as

chelatio

hydrogen n) the amount of enol form increases.

H O O O O CH3 C CH2 C OC2H5 Keto form (93%) O O H3C C C CH Enol form (7%) H O O OC2H5 H3C C C CH2 CH3 Keto form (24%) H3C C C CH Enol form (76%) CH3

Necessary and sufficient condition for compound to exhibit keto - enol tautomerism a

•

Carbonyl compounds which contain atleast one

-hydrogen.

C CH3 Acetophenone O

C H O

a a

H3C C CH 2CH3 Butan-1-one O

CH3CH2 C H Propionaldehyde

Compounds other than carbonyl derivatives which also exhibit tautomerism Nitromethane exists in the following equilibrium.

This type of tautomerism is called

nitro-

acinitro tautomerism.

O CH3 N O Nitro form OH CH2 N Acinitro form O

•

VI.

Ring Chain Isomerism Open chain and cyclic compounds having the same molecular formula chain isomers are called ring -

CH3CH CH2 Propene and Cyclopropane CH3 C CH Propyne and Cyclopropene

Double Bond Equivalents (DBE) or Index of Hydrogen Deficiency (IHD)

•

It is of great utility in solving structural problems. It tells us about the number of double bonds or rings present in the molecule. DBE (or IHD) is calculated from the expression:



n (v



2) DBE = + 1 2

•

Here n = no. of different kinds of atoms present and v = valency of each atom.

For exmaple, • • DBE (or IHD) for molecular formula C 3 H 6 O

3 (4 - 2) + 6 (1 - 2) + 1 (2-2) = + 1 = 0 + 1 = 1 2 Thus molecules having molecular formula C 3 H 6 O will have either one double bond or one ring.

OH H 2 C==C—CH 3 O H 3 C—C—CH 3 OH H

CH 3 H

•

Now if DBE (IHD) of a molecule is 2 it means that the molecule has two double bonds or one triple bond or two rings or one double bond and one ring.

•

I.

II.

2. STEREOISOMERISM

Isomers which have the same molecular formula and same structural formula but differ in the manner their atoms or groups are arranged in the space are called stereoisomers.

It is of two types:

Configurational Isomerism Conformational Isomerism

I. Configurational Isomerism

•

The stereoisomers which cannot be interconverted unless a covalent bond is broken are called configurational isomers

These isomers can be separated under normal conditions.

•

The configurational isomerism is again of two types:

a) b) Optical Isomerism or Enantiomerism Geometrical Isomerism

• • • •

a) Optical Isomerism or Enantiomerism

The stereoisomers which are related to each other as an superimposable

optical isomers

object mirror or enantion means opposite ).

and image are

enantiomers

its non called (Greek: The optical isomers can also rotate the plane of polarised light to an equal degree but in opposite direction.

The property of rotating plane of polarised light is known as optical activity .

The optical isomers have similar physical and

chemical properties.

For example, • Molecular formula C 3 H 6 O 3 represents two enantiomeric lactic acids as shown below:

Mirror COOH COOH H OH HO H CH3 ( -) - Lactic acid

(Rotates the plane of polarized light towards left hand side i.e. anticlockwise)

CH3 ( +) - Lactic acid

(Rotates the plane of polarized light towards right hand side i.e. clockwise)

• •

b) Geometrical Isomerism

Geometric isomers are the stereoisomers which differ in their spatial geometry due to restricted rotation across a double bond.

These isomers are also called as isomers.

For example, molecular formula C 2 H 2 Cl 2 corresponds isomers as follows: to two

cis-trans

geometric

H H C C Cl Cl

cis-1,2-Dichloroethene

H Cl C C Cl H

trans-1,2-Dichloroethene

II. Conformational Isomerism

•

The stereoisomers which can be interconverted rapidly at room temperature without breaking a covalent bond are called conformational isomers or conformers.

• •

Because such isomers can be readily interconverted , they cannot be separated under normal conditions.

Two types of conformational isomers are:

a)Conformational isomers rotation about single bond resulting from b)Conformational isomers arising from amine inversion

•

a) Conformational isomers resulting from rotation about single bond

Because the single bond in a molecule rotates containing continuously, single the bonds compounds have many interconvertible conformational isomers.e.g,

'boat'

and

'chair'

forms of cyclohexane.

H H H H H H H H H H H

Cyclohexane

(Chair form)

H H H H H H H H H H H

Cyclohexane

(Boat form)

H H

•

b) Conformational isomers arising from amine inversion

Nitrogen atom of amines has a pair of non bonding electrons which allow the molecule to turn

"inside out"

rapidly at room temperature. This is called

amine inversion

Walden inversion

R2 R3 R3 R1

R2 Transition state R1 R3

• • •

•

3.3 OPTICAL ACTIVITY

Enantiomers are known to possess same physical and chemical properties but they differ in the way they interact with plane polarised light.

Substances which can rotate the plane of polarised light are said to be optically active.

•

Dextrorotatory

(Latin: dextre means right) and is indicated by (+) sign.

Laevorotatory

(Latin: laeves mean left) and is indicated by (-) sign.

Those substance which do not rotate the plane of polarised light are called inactive.

optically

TYPES OF OPTICAL ACTIVITY

new older

Dextrorotatory (+)-

-

Rotates the plane of plane-polarized light to the right.

new older

Levorotatory (-)-

-

Rotates the plane of plane-polarized light to the left.

PLANE-POLARIZED LIGHT BEAM

single ray or photon wavelength

All sine waves (rays) in the beam aligned in same plane.

END VIEW SIDE VIEW A beam is a collection of these rays.

frequency (

n n

= c

) c = speed of light polarized beam NOT PLANE-POLARIZED Sine waves are not aligned in the same plane.

unpolarized beam

Optical Activity

angle of rotation,

incident polarized light sample cell (usually quartz) a solution of the substance to be examined is placed inside the cell transmitted light (rotated)

Na lamp

The Polarimeter

plane-polarized light sample cell

observed rotation

0 0 polarizer plane is rotated analyzer chemistry nerd rotate to null

• • • • • •

Angle of rotation (

(degrees)

is the angle by which the analyser is rotated to get maximum intensity of light. It depends upon:

(i) Nature of the substance; (ii) Concentration of the solution in g/ml; (iii) Length of the polarimeter tube; (iv)

of the incident monochromatic light

(598nm).

(v) Temperature of the sample.

Specific Rotation

[a] • • •

It is defined as

rotation caused by a solution of 1.0 g of compound per the number of degrees of ml of solution taken in a polarimeter tube 1.0 dm (10 cm) long at a specific temperature and wavelength .

The specific rotation observed angle of rotation,

is calculated as below: from

a = l × c

Where sample; [

]

= specific rotation; = wave length of incident light (where sodium D-line is used

t 0 = temperature of the is replaced by D);

= observed angle of rotation; polarimeter tube in decimeters; l C = length of the = concentration of sample in g/ml of the solution.

Specific Rotation [

]

D [

a

] D t =

a

cl This equation corrects for differences in cell length and concentration.

Specific rotation calculated in this way is a physical property of an optically active substance.

a

= observed rotation c = concentration ( g/mL ) You always get the same value of [

] t D l = length of cell ( dm ) D = yellow light from sodium lamp t = temperature ( Celsius )

SPECIFIC ROTATIONS OF BIOACTIVE COMPOUNDS COMPOUND

cholesterol cocaine morphine codeine heroin epinephrine progesterone testosterone sucrose b -D-glucose a -D-glucose oxacillin

[

] D

-31.5

-16 -132 -136 -107 -5.0

+172 +109 +66.5

+18.7

+112 +201

•

Molecular Rotation [M] Molecular rotation which is preferred over specific rotation which is given by the formula:

= [a] to l 100 × M • •

Where M = molecular weight of the optically active substance.

Utility of specific/molecular rotation: Just like other physical constants such as melting point, boiling point, density, refractive index, etc., it is also a characteristic property for establishing the identity of a given optically active compound. It is an intensive property.

• • • •

3.3.1Chirality - optical activity: discovery

French chemist Louis Pasteur (1848) discovered that crystalline optically inactive sodium ammonium tartarate was a mixture of two types of crystals which were mirror images of each other.

Each type of crystals when dissolved in water was optically active . The specific rotations of the two solutions were exactly equal, but of opposite sign.

In all other properties, the two substances were identical .

As the rotation differs for the two samples in solution in which shapes of crystals disappear, Pasteur laid the foundation of stereochemisty when he proposed that like the two sets of crystals, the molecules making up the crystals were themselves mirror - images of each other and the difference in rotation was due to 'molecular dissymmetry'

PASTEUR’S DISCOVERY

Louis Pasteur 1848 Sorbonne, Paris HOOC CH CH COOH OH OH tartaric acid ( found in wine must ) Na + OOC CH CH COO OH OH 2 NH 4 + sodium ammonium tartrate Pasteur crystallized this substance on a cold day.

Crystals of Sodium Ammonium Tartrate

hemihedral faces Pasteur found two different crystals.

mirror images Biot’s results : (+) ( ) Louis Pasteur separated these and gave them to Biot to measure.

•

3.3.2 Chirality An object which cannot be superimposed on its mirror-image is said to be [Greek : Cheir chrial 'Handedness'] (ky - ral) and the property of non-superimposability is called chirality . Thus our hands are chiral.

  •

Similarly, alphabets R,F,J are chiral and A, M, O are achiral.

R R J J

Chiral objects

F F A A M M O O

(Achiral objects)

Chiral objects human hand, gloves, shoes , etc.

Achiral objects a sphere, a cube, a button, socks without thumb , etc.

Chirality or molecular dissymmetry is the necessary and sufficient condition for a molecule to be optically active.

3.3.3 Molecular Chirality and Asymmetric Carbon

•

Chirality in molecules is usually due to the presence of an different groups sp3 carbon atom with attached to it. Such a carbon atom is called a chiral carbon or a four chirality centre .

•

The presence of a chirality centre usually leads to has molecular chirality no plane of symmetry . Such a molecule and exists as a pair of enantiomers. Such a carbon atom is sometimes also referred to as asymmetric carbon atom.

•

A ball and stick model of a compound Cwxyz A derivative of methane, where w,x,y and z are all different atoms or groups and a model of its morror image.

Y X C W W C X Y

•

Z Z Mirror We may twist and turn the above two representations in any way we like so long we do not break any bond , yet we find that the two are not superimposable . Therefore, they must represent two isomers, i.e., two enantiomers.

Enantiomers

non-superimposable mirror images (also called optical isomers) X W C Z Y W Y Z C X Pasteur decided that the molecules that made the crystals, just as the crystals themselves, must be mirror images. Each crystal must contain a single type of enantiomer.

Pasteur’s hypothesis eventually led to the discovery that tetravalent carbon atoms are tetrahedral.

Van’t Hoff and LeBel (1874) C tetrahedral carbon Only tetrahedral geometry can lead to mirror image molecules: C C Square planar, square pyrimidal or trigonal pyramid will not work: C C C

ENANTIOMERS HAVE EQUAL AND OPPOSITE ROTATIONS

X W C Z Y Enantiomers W Y Z C X (+)-nn o (-)-nn o dextrorotatory levorotatory ALL OTHER PHYSICAL PROPERTIES ARE THE SAME

How to distinguish between enantiomers?

Y X W W X Y Y X C W Z Mirror W C X Y Z Z Z Fischer projection formulas represent the two enantiomers in two dimensions with the assumption that the two horizontal bonds (C-Y and C-W) project towards us out of the plane of the paper, and the two vertical bonds (C-X and C-Z) project away from us behind the paper .

The superimposability of two such flat two - dimensional structures is tested by rotating end to end without raising them (in our mind) out of the plane of the paper.

The asymmetric carbon atom is at the junction of the crossed lines.

Some examples, CHO H OH HO CHO H CH2OH CH2OH Mirror (+) and (



) - Glyce ralde hyde s H CO2H CO2H OH HO CH3 CH3 Mirror (



) and (+) - Lactic acids H

HOOC H meso from fermentation of wine H COOH Enantiomers OH OH OH OH HOOC H H COOH H HOOC H COOH (+)-tartaric acid enantiomers (-)-tartaric acid HOOC H OH OH meso H COOH HOOC H H COOH ALSO FOUND (as a minor component) [

] D = 0 more about this OH OH H HOOC H COOH enantiomers

• • • •

Inversion of configuration

An enantiomer is changed into the other (

inversion of configuration

) when two atoms or groups about the chiral interchanged.

carbon are A 90 0 rotation of the projection formula about the chiral centre or one exchange of groups inverts the configuration of the original structure.

Two such interchanges , the configuration.

give the same configuration rotation of a Fischer projection formula by 180 o as the first. In other words, in the plane of the paper does not alter These points are illustrated glyceraldehyde as an example.

by taking

H HOH2C CHO CH2OH (+) OH 90o rotation HOH2C H OH H OH (



) HOH2C CHO 90o rotation OH CHO (+) H one e xchange of groups H anothe r e xchange of groups HO CH2OH CHO (+) CHO (



)

Use of models is a very good tool to understand this type of conversion .

3.4

PROJECTION FORMULAS OF CHIRAL MOLECULES

• • • • •

Configuration of a chiral molecule is three dimensional structure and it is to depict it on a paper not very easy having only two dimensions. To overcome this problem the following four two dimensional structures known as projections have been evolved.

1. Fischer Projection 2. Newman Projection 3. Sawhorse Formula 4. Flying Wedge Formula

Fischer Projection COOH H C OH or H COOH OH Away from the ve iwe r CH2OH (I) Towards the ve iwe r CH2OH (I)

•

Characteristic features of Fischer projection: Rotation of a Fischer projection by an angle of 180 0 about the axis which is perpendicular to the plane of the paper gives identical structure. However, similar rotation by an angle of 90 0 produces non - identical structure.

Newman Projection

•

In Newman projection we look at the molecule down the length of a particular carbon - carbon bond. The carbon atom away from the viewer is called 'rear' carbon and is represented by a circle . The carbon atom facing the viewer is called 'front' carbon and is represented as the centre of the above circle which is shown by dot. The remaining bonds on each carbon are shown by small straight lines at angles of 120 o as follows: i) Bonds joined to 'front' carbon intersect at the central dot.

ii) Bonds joined to 'rear' carbon are shown emanating from the circumfrance of the circle.

The concept of Newman projection for

-butane can be understood by the following drawings:

Visible H Front Carbon CH3 H H H CH3 Staggered Out of sight three groups emanating from circumfrance Rear Carbon Newman Projection H3C CH3 H H Eclipsed H H

These arise conformations due to free rotation about the carbon - carbon single bond (front and rear carbon atoms).

• •

Sawhorse projection The bond between two carbon atoms is shown by a longer diagonal line because we are looking at this bond from an oblique angle. The bonds linking other substituents to these carbons are shown projecting above or below this line.

H 3 H CH3 1 H3C 4 CH3 H3C H H H 2 H H H Staggered Eclipsed Due to free rotation along the central bond two extreme conformations are possible - the staggered and the eclipsed

• •

Flying Wedge Formula It is a three dimensional representation.

The flying wedge formulas of two enantiomeric lactic acids are shown below: COOH H H COOH H3C OH HO CH3

• •

Both these structure are mirror image of each other.

( Note: The main functional group held on the upper side in the is generally vertical plane .)

Conversion of Fischer Projection into Sawhorse Projection.

•

Fischer projection of a compound can be converted into sawhorse projection first in the eclipsed form by holding the model in horizontal plane in such a way that the groups on the vertical line point above and the last numbered chiral carbon faces the viewer. Then one of the two carbons is rotated by an angle of 180 o to get staggered form (more stable or relaxed form).

H HO Rear carbon 1 COOH 2 OH 3 4 COOH H Front carbon 4 HOOC 3 HO Eclipsed H H 1 COOH 2 OH Rotation by 180o along C2 - C3 axis HO COOH HO H Staggered Fischer Projection Sawhorse Projection H COOH

•

Conversion of Sawhorse projection into Fischer projection

First the staggered sawhorse projection is converted in eclipsed projection. It is then held in the vertical plane in such a manner that the two groups pointing upwords are away from the viewer i.e. both these groups are shown on the vertical line. Thus, for 2,3 dibromobutane.

Br CH3 H Br CH3 H Br Staggered Sawhorse Projection CH3 Rotation by 180o H CH3 Br Eclipsed Sawhorse Projection H H Br CH3 Br H Rear carbon Front carbon CH3 Fischer Projection

Conversion of Sawhorse to Newman to Fischer Projection Rear carbon H 2 N Front carbon Ph CH Br OH Staggered Sawhorse Projection 3 Cl Ph H2N Cl View through the front carbon Br OH CH 3 Staggered Newman Projection Rotate the front carbon along the central CH 3 H 2 N HO Front carbon Ph Cl B r Fischer Projection Hold in ve rtical plane ke e ping front carbon as the lowe s t HO NH 2 Br Cl H 3 C Ph Eclipsed Newman Projection

Conversion of Fischer to Newman to Sawhorse Projection Rear carbon CHO H H OH Cl Front carbon CH2OH Fischer Projection H OH Cl H Rotate front CHO CH2OH Eclipsed Newman Projection carbon by 180 o H OH CH2OH HOH 2 C Cl H Staggered Sawhorse Projection CHO H OH View through central bond Cl H CHO Staggered Newman Projection

Conversion of Fischer Projection into Flying Wedge

•

The vertical bonds in the Fischer projection are drawn in the plane of the paper using simple lines ( —) consequently horizontal bonds will project above and below the plane .

H COOH COOH When Br above the plane H Br Br When H above the plane CH3 CH3 COOH Br H3C H

•

Conversion of Flying Wedge into Fischer Projection The molecule is rotated (in the vertical plane) in such a way that the bonds shown in the plane of the paper go away from the viewer and are vertical.

H Br COOH CH3 Rotate the model in vertical plane so that C—COOH and C—CH 3 go away from the viewer H COOH Br CH3

3.5

ELEMENTS OF SYMMETRY

•

Enatiomerism depends on whether a molecule in not superimposable on its mirror image. If it is superimposable, the molecule is optically inactive otherwise is optically active. The most convenient method of inspecting superimposability is to determine whether the molecule has any following four elements of symmetry: of the 1. Plane of symmetry (s) 2. Centre of symmetry (i) 3. Simple or proper axis of symmetry (C n ) 4. Alternating or improper axis of symmetry (S n )

• •

Plane of symmetry (s)

A plane of symmetry is defined as an imaginary plane which divides a molecule in such a way that

one half is mirror image of the other half.

A molecule with atleast a plane of symmetry can be superimposed on its mirror image and is achiral.

A molecule that does not have a plane of symmetry is usually chiral; it cannot be superimposed upon its mirror image.

COOH H

•

A plan of symmetry may pass through atoms, between atoms or both.

H OH OH Plane of symme try COOH meso-Tartaric acid

•

Centre of symmetry or

inversion

(i) or (C i )

A centre of symmetry (centre of inversion) is defined as a point within the molecule such that if an atom is joined to it by a straight line which if extrapolated to an equal distance beyond it in opposite direction meets an equivalent atom

. In other words it is a point

at which all the straight lines joining identical points in the molecule cross each other.

CH3 COOH H H COOH H H Centre of symmetry 2,4-Dimethylcyclobutane 1,3-dicarboxylic acid has C i CH3

H3C CO C NH CH3 H3C C H NH cis (chiral) CO H C H CO NH NH CO trans (achiral) H C CH3

•

Simple or proper axis of symmetry (C n )

An imaginary line passing through the molecule in such a way that when the molecule is rotated about it by an angle of 360 o /n, an arrangement indistinguishable from the original is obtained

. Such an axis is called n-fold axis of symmetry . For example, cis-1,3-dimethylcyclobutane has a two fold axis of symmetry (C 2 ) i.e.

rotation indistinguishable appearance.

by 180 o gives

H CH3 H CH3 H3C H H H

C2-Axis of Symmetry

H H Rotation by 180o H3C H H H H H

Alternating or improper axis of symmetry (S n )

4 CH3 A H 3 H CH3

(a)

B H3C H 2 1 CH3 1,2,3,4-Tetramethyl cyclobutane has S 4 H

Rotation by 90o

H3C 2 H CH3 2 H H 3 CH3

(a)

H3C H 4 H 1 CH3 3 H CH3

(b)

CH3 H 1 CH3 H 4

Reflaction through mirror plane perpendicular to axis of rotation

• • •

Asymmetry v/s Dissymmetry In general the term

asymmetry is used for those optically active compounds which

have none of the four elements of symmetry.

In contrast the term dissymmetry is used for

all stereoisomeric compounds which are capable of existing as pairs of non superimposable mirror images despite the presence of some elements of symmetry.

In other words the term dissymmetry is applicable to all stereoisomers, which are related to each other as non-superimposable mirror images of each other, e.g.

2,3 dibromobutane possesses the plane of the paper.

a C 2 axis of symmetry in the molecule at right angle to

Since structures I and II are indistinguishable, the molecule has C 2 axis of symmetry. But it is non-superimposable on its mirror image so it is dissymmetric and not asymmetric and exhibits optical activity.

CH3 CH3 CH3 Br H H Br H Br H Br Br H Rotation by 180o Br H CH3

III

CH3

II All asymmetric molecules are dissymmetric dissymmetric molecules are not asymmetric.

but However, all both these types of molecules show optical activity and are chiral .

Hence, to avoid any confusion, in using these terms, asymmetry or dissymmetry - the term chirality is used.

3.6 STEREOGENIC CENTRE OR CHIRALITY CENTRE

•

In 1996, the IUPAC recommended that a tetrahedral carbon atom bearing four differnt atoms or groups may be called a chirality centre.

Several asymmetric earlier centre, terms asymmetric chiral centre, stereogenic including carbon, centre and stereocentre are still widely used.

H 1 CH3 2 C 3 4 CH2CH3 OH

2- Butanol

Chirality centre

3.7

CHARACTERISTICS OF ENANTIOMERS

• •

Necessary and sufficient condition for enantiomerism is that the molecule should be chiral or dissymmetric i.e. the molecule and its mirror image should be non superimposable, even if it may not have an assymmetric carbon or stereocentre.

In general it has been observed that compounds having one or more chirality centre show enantiomerism and therefore, optically active.

However, this statement does not hold good for all such molecules, e.g.

•

i) Compounds having chirality centre(s) but not enantiomeric

Meso-2,3-dibromobutane contains two chirality centres (marked with *) but it does not exhibit enantiomerism due to

internal compensation

and hence is optically inactive.

H CH3 * Br Br CH3 * H

Plane of Symmetry

H * Br Br * H CH3 CH3 Mirror

Meso - 2,3-dibromobutane (optically inactive)

ii) Compounds having no chirality centre but are enantiomeric

•

These molecules show chirality or dissymmetry and hence enantiomerism. Examples of such compounds are o-substitued biphenyls number of double bonds.

and allenes having even NO2 F F O2N F O2N NO2 F Mirror 2,2'-Difluoro - 6,6'-dinitrobiphenyl (No chirality centre) (Non-superimposable mirror images hence enantiomeric and optically active)

Allenes: Due to sp hybridization of central carbon which forms two

p

bonds perpendicular to each other and thus the two groups attached to terminal carbon atoms are also orthogonal. Due to this arrangement the molecule of allene is devoid of symmetry and hence is chiral.

H3C C2H5 H5C2 CH3 C C C C C C H5C2 CH3 H3C C2H5 Mirror 1,3-Diethyl-1,3-dimethylallene (No chirality centre) (Non-superimposable mirror images, hence enantiomeric and optically active)

Therefore, necessary and sufficient condition for compounds to exhibit enantiomerism is that they should possesses chirality or dissymmetry rather than asymmetry.

3.7.2 Properties of Enantiomers

•

(i)They have identical physical properties but differ in the direction of the rotation of plane polarized light.

2-Methyl-1-butanols

Enantiomer Specific Rotation B.P.

Ref. Index (+) (-) +5.750

-5.750

402K 402K 1.41

1.41

It is clear that two enantiomers have the same melting points, boiling points, refractive indices, etc.

The magnitude of rotation of polarized light is also the same, but in opposite direction.

TARTARIC ACID

(-) - tartaric acid [

] D = -12.0

o mp 168 - 170 o solubility of 1 g 0.75 mL H insoluble CHCl 2 3 O 1.7 mL methanol 250 mL ether d = 1.758 g/mL (+) - tartaric acid [

] D = +12.0

o mp 168 - 170 o solubility of 1 g 0.75 mL H insoluble CHCl 2 3 O 1.7 mL methanol 250 mL ether d = 1.758 g/mL meso - tartaric acid [

] D = 0 o mp 140 o d = 1.666 g/mL solubility of 1 g 0.94 mL H 2 O insoluble CHCl 3

RACEMIC MIXTURE

an equimolar (50/50) mixture of enantiomers

[

]

= 0

o the effect of each molecule is cancelled out by its enantiomer

(ii) The enantiomers have identical properties towards optically inactive reagents.

chemical

•

As the structural environment in the two enantiomers is same and thus the optically inactive reagents such as H 2 SO 4 , HBr and CH 3 COOH encounter the same environment while approaching either enantiomer.

CH3 CH3CH2 C CH2Br H (+ and



) 2-Methylbutylbromide HBr CH3CH2 CH3 C CH2OH H (+ and



) 2-Methyl -1-butanol CH3 H 2 SO 4 C CH2 H3CH2C (+ and



) 2-Methylbutene CH3COOH CH3CH2 CH3 C CH2 H (+ and



) Esters O O C CH 3

•

(iii) The enantiomers have different properties towards optically active reagents.

chemical

If we use an optically active reagent, the reaction rates will be different. If we esterify the two enantiomers of 2-methyl-1-butanol with (-)-lactic acid, the influence exerted by the reagent will not be identical due to the different spatial disposition of the OH group in the two enantiomers in relation to the groups attached to the chirality centre of (-) lactic acid.

Therefore, the rate of esterification of (+)-2-methyl-1-butanol will be different form that of (-)-2-methyl-1-butanol.

(iv) The enantiomers have different biological properties.

(+)-Glucose plays an important role in animal metabolism and fermentation, but (-)-glucose is not metabolized by animals, and furthermore cannot be fermented by yeasts.

Penicillium glaucum

, consumes only the (+) enantiomer when fed with a mixture of equal quantities of (+)-and (-)-tartaric acids.

Hormonal activity of (-)-adrenaline is many times more than that of its enantiomer.

3.8

COMPOUNDS WITH SEVERAL CHIRALITY CENTRES

• • •

If there are exist in 2 n n chiral carbons , the compound will optically active forms , provided chiral atoms are not identically substituted .

2-Bromo-3-hydroxybutanedioic optically active forms.

acid, HOOC CH(OH)-CH(Br)-COOH, in which the two chiral carbon atoms are dissimilar, exists in 2 2 =4 The two chiral carbon atoms of tartaric acid, HOOC-CHOH-CHOH-COOH, on the other hand, are identically substituted (similar) and hence the total number of optically active isomers cannot be predicted by using 2 n formula.

Compounds with two Dissimilar Stereogenic Centres (Chirality Centres) : Diastereomers HO COOH H H COOH OH Br H H Br COOH COOH I Mirror II

(A pair of enantiomers)

HO COOH H H COOH OH H Br Br H COOH III Mirror COOH IV

(A pair of enantiomers)

•

Now the question arises as to what is the relationship between I and III or I and IV. They are optically active, but are not the mirror images. Such stereoisomers are referred to

as diastereomers.

Diastereomers are stereoisomers which have the same configuration at one chirality centre but different configuration at the

other. In other words diastereomers are stereoisomers

which are not mirror images of each other.

Properties of Diastereomers 1.

Physical properties: P roperties of tartaric acid (+) (-) ( ±)

Meso

[

]20 o D +120 -120 00 00 M. points (K) 443 443 478 413 Solubility(g/100ml) 147 Relative density 147 25 1.760 1.760 1.687

120 1.666

Therfore can be easily separated using techniques such as fractional crystallization, fractional distillation and chromatography.

Different behaviour towards plane-polarised light .

Diastereomers have similar but non-identical chemical properties. In particular they react with chiral or achiral reagents at different rates.

H Threo and Erythro Diastereomers CHO CHO CHO CHO OH HO H HO H H OH H OH HO H H OH HO H CH2OH (



)-Erythrose CH2OH (+)-Erythrose CH2OH (



)-Threose CH2OH (+)-Threose

• •

Fischer projections give the impression that the molecule exists in the eclipsed form. Actually it exists in the staggered form in which the bulky substituents are as far apart as possible.

Therefore, an erythro isomer corresponds to that diastereomer, which when viewed along the bond connecting the chiral carbons has a rotational isomer in which all similar groups are eclipsed. The threo diastereomers, on the other hand, does not have an isomer in which all similar groups are eclipsed.

H COOH OH HO

meso Compounds

COOH H H COOH OH HO COOH H HO H H OH H OH HO H • COOH

Mirror COOH

COOH

III

Mirror COOH

IV Meso- tartaric acid Pair of enantiomers

The isomers having two similar chirality centres

such as III are optically inactive due to presence of

a plane of symmetry and are termed meso compounds ( internal compensation ). Hence, meso compounds are optically inactive compounds

whose molecule is superimposable on its mirror image.

Prediction of the number of stereoisomers i.e. number

•

of optical isomers and meso-forms It depends upon the following: (i) Number of chirality centres (n) and (ii) Whether the chirality centres are similar or dissimilar.

For molecules having dissimilar chirality centres.

Number of optical isomers =

2 n

Number of meso-forms =

0 For molecules having similar chirality centres

These molecules are of two types: (a) (b) Molecules having even number of chiral carbons.

Molecules having odd number of chiral carbons.

For molecules having even number of chiral centres: No. of optical isomers=

2 (n-1)

No. of

meso

-forms =

2 (n/2-1)

For molecules having odd number of chiral centres: Number of optical isomers =

2 n-1 — 2 (n-1)/2

Number of

meso

forms =

2 (n-1)/2

Butan -1,2,3-triol

(CH 3 *CHOH-*CHOH-CH 2 OH) has two dissimilar chiral carbon atoms.Here n = 2 Now, Number of optical isomers = 2

= 4 Number of

meso

forms = 0 Total number of stereoisomers = 4 + 0 = 4 H CH3 OH HO CH3 H H CH3 OH HO CH3 H HO H CH2OH

H OH CH2OH

H OH HO CH2OH

III

H CH2OH

Tartaric acid

(HOOC — *CHOH —*CHOH — COOH) has two similar chiral carbon atoms, i.e, n =2 Number of optical isomers = 2

n-1

= 2

2-1

= 2

= 2 Number of

meso

forms = 2

n/2-1

= 2

1-1

= 2

= 1 Total number of stereoisomers = 2 + 1 = 3.

H COOH OH HO COOH H HO H COOH I Mirror H COOH II OH H H COOH OH Plane of symme try OH COOH III (Meso - form)

Trihydroxyglutaric acid

, (HOOC — *CHOH —*CHOH—*CHOH—COOH), has three chiral carbon atoms.i.e. n =3.

No. of optical isomers=2

3-1

- 2

(3-1)/2

- 2

=4-2 = 2 No. of

meso

-forms =2

(3-1)/2

= 2 Total no. of stereoisomers =2+2 = 4(or 2

3-1

=4)

1 COOH HO H H 2 3 4 H OH 5 COOH I OH H HO HO COOH COOH II OH H H H H H COOH OH OH OH H Plane of symme try HO H COOH III COOH OH H OH COOH IV

• •

3.9

PROCHIRALITY When replacement of one hydrogen atom at a time gives an enantiomer , such a hydrogen atom is called enantiotopic hydrogen . That enantiotopic hydrogen, the replacement of which gives R-configuration is called pro-R and configuration is called the pro-S other which give S The carbon atom to which the two hydrogen atoms are attached is called prochirality centre and the moelcule is called prochiral molecule .

Pro-S CH3 HS C Prochiral centre OH Ethanol HR Pro-R Replacement of HR or HS by D CH3 CH3 H OH (R-isomer) D or D OH (S-isomer) H

3.10

•

RETENTION and INVERSION of CONFIGURATION Retention or inversion depends upon:

i) The side of the molecule from which the reagent attacks the reactant.

ii) Manner of bond cleavage in the reaction i.e. whether the bond between the substituent and chirality centre is broken or not.

CH3 CH3 HO H C Cl S N 2

(Inversion)

HO C H + Cl H5C2 CH3 Walden inversion

C2H5 (Inverted configuration) CH3 -HCl H C O H + Cl Ts H C O Ts H3CH2C Optically active 2-Butanol Not broken so retention of configuration H3CH2C 2-Butyl tosylate

3.11

RACEMIC MODIFICATION or RACEMIC MIXTURE

• • • •

An not equimolar mixture of two enantiomers possess optical activity and is does called racemic mixutre or racemic modification or conglomerate.

Loss of optical activity rotation is due to cancellation of (external compensation).

Prefixes such as ( it is racemic.

dl ) or ( ± ) or ( RS ) are used before the name of the compound to specify that The optical rotation as well as other physical properties of the racemic mixture such as melting point, boiling point, solubility in a given solvent etc., are also different from those of enantiomers.

RACEMIC MIXTURE

an equimolar (50/50) mixture of enantiomers

[

]

= 0

o the effect of each molecule is cancelled out by its enantiomer

Methods of Racemisation

1.Racemisation involving a carbanion as an intermediate 2.Racemisation involving a carbocation as an intermediate (SN1 mechanism) 3.Racemisation involving Walden Inversion (SN2 mechanism) 4.Racemisation involving rotation about carbon - carbon single bond

1. Racemisation involving a carbanion as an intermediate

When an optically active aldehyde or ketone having a hydrogen atom on the

-carbon, which is chiral, is treated with an acid or a base, it produces recimate.

HO OH O H C C O H3C (-)-Lactate ion OH O H3C C C O H (+)-Lactate ion H2O -OH HO H3C C O C O HO H3C C O C O

Resonance stabilized planar carbanion

HO H

2. Racemisation involving a carbocation (SN1 mechanism)

•

Carbocations are planar and hence achiral.

Recombination of an anion can take place from either side of the carbocation with equal ease thereby leading to racemisation.

H Ph C Cl + SbCl 5 (Liq. SO 2 ) H3C (+) -

- Chloroethylbenzene Cl a b Ph C H CH3 Planar carbocation a (front side attack) b (back side attack) H Ph C H3C (+) 50% Cl Cl Ph C H CH3 (-) 50% Racemic mixture

3. Racemisation involving Walden Inversion (SN2 mechanism)

•

Any one enantiomer of 2-iodobutane can undergo Walden inversion when treated with sodium iodide to

•

give 1:1 mixture of the two enantiomers (racemate).

Enantiomers having the halogen at chirality centre can undergo racemization by S N 2 mechanism. For instance, a solution of (+) or (-) -2- iodobutane on treatment with NaI in acetone produces ( ±)-2 iodobutane.

I H CH3 C H5C2 (One enantiomer) I

Walden

inversion CH3 I C H C2H5 (Other enantiomer) I

4. Racemisation involving rotation about C - C single bond

•

Optical activity of biphenyls arises due to restricted rotation . It is, therefore, reasonable to believe that if the rings of such biphenyl derivatives become planar their optical activity should be lost. In agreement with this it has been found that a number of optically active compounds can be racemised under suitable conditions, e.g., heating which overcomes energy barrier between two enantiomers.

the COOH NO2



NO2 COOH NO2 COOH 6, 6'-Dinitrodiphenic acid (Racemic mixture) COOH NO2

Methods of Resolution Usual methods of separation such as fractional distillation, fractional crystallization or adsorption techniques cannot be used the separation of enantiomers. Therefore, some special procedures are needed for resolution of racemic mixtures. Some of the more important methods are: for 1 Mechanical Separation 2 Preferential Crystallization 3 Biochemical Method 4 Resolution through the formation of diastereomers: The Chemical Method 5 Chromatographic Method

•

1 Mechanical Separation Pasteur (1948) proved that the compound called acids.

These “racemic acid” crystals had is actually an equimolecular mixture of (+) and (-) tartaric He found that when racemic sodium ammonium tartarate was crystallized below 300K, two types of crystals, were obtained.

distinguishable hemihedral faces and were non superimposable . He separated them with tweezers and magnifying glass.

Limitations:

(i) This method consuming.

is painstaking and time (ii) It is of limited use being applicable to those compounds only which can crystallize as two well defined types of crystals.

2 Preferential Crystallization

• • •

Preferential crystallization is closely related to mechanical separation of crystals.

A supersaturated solution of the racemic mixture is inoculated with a crystal of one of the enantiomers or an isomorphous crystal of another chiral compound.

For example, when the saturated solution of ( ±) sodium ammonium tartarate is seeded with the crystal of one of the pure enantiomer or a crystal of ( –) asparagine, ( –) sodium ammonium tartarate crystalises out first.

This method is also called as

entrainment

the seed crystal is called

entrainer

and

3 Biochemical Method

• • •

Microorganisms or enzymes are highly stereoselective.

Fermentation of ( ±) tartaric acid in presence of yeast or a mold, e.g., Pencillium glaucum. The (+) tartaric acid is completely consumed leaving behind ( –) tartaric acid.

( ±) Amino acids can be separated using of D-amino acid.

hog kidney acylase

until half of acetyl groups are hydrolysed away, only acetyl derivative of L-amino acid is hydrolysed leaving behind acetyl derivative Limitations: (i) These reactions are to be carried out in dilute solutions, so isolation of products becomes difficult.

(ii)There is loss of one enantiomer which is consumed by the microorganism. Hence only half of the compound is isolated (partially destructive method).

Basic Principle

The Chemical Method Step 1.

A racemic mixture ( ±)-A reacts with an optically pure reagent (+) or ( –)-B to give a mixture of two products which are diastereomers .

The reagent (+) or ( –)-B is called the resolving agent.

( ±) - A + (+)-B



(+)A(+)B + (-)A(+)B Step 2.

The mixture of diastereomers obtained above can be separated using the methods of fractional distillation, fractional crystallization, etc.

Step 3.

The decomposed enantiomer pure each and the diastereomers into the original reagent, which are then separated.

are corresponding optically then active

(±) - Tartaric acid + (



)-Cinchonidine (Racemic modification) (Resolving agent) (+) - Tartaric acid - ( + (



) - Tartaric acid - (



) - cinchonidine



) - cinchonidine Diastereomers (separable) Separated by crystallization (+) - Tartaric acid - (



) - cinchonidine (+) - Tartaric acid (crystallizes out) (



) - Tartaric acid - (



) - cinchonidine Dil. H2SO4 (



) - Tartaric acid (crystallizes out)

Similarly resolution of a ( ±) base with an optically active acid.

(+) - base + (+) - acid (



) - base Racemic modification (



HO ) - (+) - salt (



) - base Diastereomers

(separable)

Advantages of chemical method The chemical method of resolution is and has the advantage that widely used both the enantiomers are obtained.

This method will be successful if the following conditions are fulfilled:

(i) (ii) (iii) The resolving agent should be optically pure.

The substrate resolving agent (racemic should mixture) have functional groups for reaction to occur.

and the suitable The resolving agent should be cheap and be capable of regeneration and recycling.

(iv) (v) The resolving agent should be such which produces easily crystallizable diastereomeric products.

The resolving agent should be easily separable from pure enantiomers.

• • •

5 Chromatographic Method The rates of movement by elution with suitable solvent .

of the two enantiomers through the column should be different (due to difference in the extent of adsorption ). They should thus be separable This method has an advantage over chemical separation as the enantiomers need not be converted into diastereomers.

The techniques used include paper, column, thin layer, gas and liquid chromatography.

• • •

Optical Purity For an enantiomerically pure sample (i.e.

only one enantiomer) the value of specific rotation [

] is the highest. Any contamination by the other enantiomer lowers the value of specific rotation proportionately.

The positive sign of the observed specific rotation means that the mixture has some excess of (+) enantiomer. This enantiomer excess enantiomeric excess (ee).

is over known (-) as The amount of each enantiomer present in the mixture can be calculated in two steps from the observed specific rotation.

Step-I:

The

optical purity

of the sample is determined using the following formula: Observed specific rotation, [ a ]

obs

Optical purity (OP) = ---------------------------------------------- Sp. rotation of pure enantiomer [ a ]

max Step-II:

Now suppose a sample of 2-bromobutane has observed specific rotation of +9.20. We know that for the pure sample [ a ]

max

is + 23.10.

+9.20

Optical purity = ---------- = 0.4 or 40% +23.10

It means that 40% of the mixture is excess of (+) isomer and 100-40=60% is racemic mixture.

Total amount of enantiomer (+) in the mixture will be 40 + 60/2 = 40 + 30 = 70% and enantiomer (-) is therefore 30%.

3.12 ABSOLUTE AND RELATIVE CONFIGURATIONS

•

Absolute configuration

denotes the actual arrangement of atoms or groups of atoms in the space of a particular stereoisomer of a compound. Absolute configuration can be ascertained by x-ray studies of the crystals of pure compound.

•

Relative configuration

denotes the arrangement of atoms or groups of atoms in the space of a particular stereoisomer relative to the atoms or groups of atoms of another compound chosen as arbitrary standard for comparison.

Configuration of (+)-glyceraldehyde

•

The configuration (A) was arbitrarily assigned to designate the configuration of (+)-glyceraldehyde. Taking this as standard, the relative configuration of ( –) lactic acid was assigned as shown below: CHO COOH H OH [O] Bromine water H OH P/Br 2 CH2OH CH2OH

(A)

(+)-Glyceraldehyde (Arbitrarily assigned that OH group is on right hand and H on left hand side) (



)-Glyceric acid H COOH OH Redn.

H CH2Br 1-Bromo-2 hydroxypropanoic acid (



COOH CH3 OH )-Lactic acid

What is cofiguration of any enantiomer?

Two commonly used conventions are: 1.

D-L System 2.

R-S System • • •

1. D-L System: This is one of the oldest and the most commonly used system for assigning configuration to a given enantiomer. It is based upon the comparison of the projection formula of one enantiomer to which the name is to be assigned, with that of a standard substance arbitrarily chosen for comparison .

The following two conventions are used for this purpose.

(i) Hydroxy Acid or Amino Acid Convention (ii) Sugar Convention

• • •

(i) Hydroxy Acid or Amino Acid Convention According to this convention the prefix D-and L- refer to the configuration of hydroxy or

a

-amino acids (i.e.

a

the lowest numbered chirality centre

) in the Fischer projection formula.

If the

a

-OH or

a

-NH 2 group is on the right hand side (of the viewer), the prefix D-is used.

Whereas if these groups are on the left hand side the prefix L-is used.

H COOH X On the right hand side of the viewer On the left hand side of the viewer X COOH H

D-Hydroxy acid ( X = OH) D-Amino acid (X = NH2) Examples

H COOH OH HO COOH H CH3

D-(



)-Lactic acid

CH3

L-(+)-Lactic acid L-Hydroxy acid ( X = OH) L-Amino acid (X = NH2)

H COOH OH HO COOH H HO H H OH COOH

D-(+)-Tartaric acid

COOH

L-(



)-Tartaric acid

COOH COOH H NH2 H2N CH3

D-(



)-Alanine

H CH3

L(+)-Alanine

(ii) Sugar Convention

•

Emil Fischer configurations arbitrarily to (+) assigned and D and L ( –)-glyceraldehydes, respectively. He assigned D-configuration (OH on the right) to (+)-glyceraldehyde and L-configuration (OH on the left) to ( –)-glyceraldehyde.

CHO H OH CH2OH D-(+)-Glyceraldehyde CHO HO H CH2OH L-(



)-Glyceraldehyde

•

The relative configurations of a large number of compounds were determined by correlating them with D(+) or L( –)-glyceraldehyde, e.g., relative configuration of ( –)-lactic acid was designated as D-(–) -lactic acid as it had the same configuration as D (+) glyceraldehyde.

For compounds containing several chiral carbon atoms

the configuration

numbered chiral carbon

the highest

centre is related to glyceraldehyde and the configuration at other carbon atoms are determined relative to the first.

In the case of glucose, this carbon atom is C 5 which is next to the CH2OH group. Since naturally occuring glucose was assumed to have the OH group of this carbon projecting at right hand side, it belongs to the D series of compounds and hence designated D-glucose.

In case of the compounds having the OH group on the highest numbered chiral carbon on left side, notation L-is used.

Limitations of Sugar Convention 1. The configuration of only the highest numbered chirality centre is assigned and that of the other centres are not shown (hidden in their names).

2. The same molecule can have both D- and L configurations. This is a very serious drawback.

CHO COOH COOH H HO H H OH H [O] OH OH H HO H H OH H OH OH Rotation by180 o HO HO H HO H H OH H CH2OH D-(+) - Glucose COOH D-Sachharic acid COOH L- form of same D-Sachharic acid

The same molecule of sachharic acid have both D- and L configurations.

Cases of (+) - Tartaric Acid and (-) - Threonine

•

Both these compounds be assigned as D- or L-depending compound upon is whether the glyceraldehyde reference (highest numbered chiral carbon) or hydroxy or amino acid (lowest numbered chiral carbon).

D (Amino acid or hydroxy acid convention) H HO COOH OH H L (Amino acid convention) H2N H COOH H OH L

(Sugar convention) COOH COOH D -(Sugar convention) It may be concluded that this system is of limited use as it is confined only to: 1. Sugars 2. Hydroxy acids 3. Amino acids.

•

R-S System To overcome the problem of D-L system, R.S.

Cahn (England), Sir (England), and V. Prelog Christopher Ingold (Zürich) evolved a new and unambiguous system for assigning absolute configuration to chiral molecules.

This system is named as CIP ( C ahn, I ngold, P relog) system after their names. It is called as R-S system as the prefixes R -and S -are used to designate the configuration at a particular chirality centre. A racemic mixture is named as (RS). This system is based on certain rules called as also as CIP rules

sequence rules and

Steps for R-S nomenclature of a chirality centre Step I: Assign a sequence of priority by using greek numerals 1,2,3 and 4 where number 1 is assigned to atom or group of highest priority and 4 is assigned to the group of lowest priority.

Step II: lowest ranked group (priority 4) points away from you.

View the molecule in such a way that the Step III: Move your eye from the group of priority number 1 to group of priority number 3 via the group of priority number 2.

Step IV: the If during this movement your eye travels in clockwise direction , the molecule under examination is designated as R (Latin : rectus meaning right) and if it moves in the anticlockwise direction it is designated as parenthesis.

S (Latin : sinister meaning left). The letters R and S are written in

For example, (-)-butan-2-ol H3C H C OH CH3H2C (-) 2-Butanol CH3 OH CH2CH3

The priorities of the substituents as determined by CIP rules are -OH is

, CH 3 CH 2 - is

CH 3 - is

and H is the highest priority and H has the lowest priority.

i.e. -OH has

(Third Highest) 3 H3C 1 OH (Highest) 2 CH2CH3 (Second Highest) Our eye moves in clockwise direction, so the absolute configuration of ( –) 2-butanol is R.

Priority sequence order of various groups

Lowest

: Non-bonding electrons (At. No. = 0) -H, -D, -CH 2 OH, -CH 3 , -CH 2 CH=CH 2 , -CH(CH 3 ) 2 , -CH=CH 2 , -C(CH 3 ) 3 -CHO, -CH 2 CH 3 , -CH 2 -C -COR,



CH, -CH -C -CONH



2 2 , (CH 2 ) n CH, -C CH 6 H 3 -CH 2 -C 6 H 5 , 5 -COOH, , , -COOR, -NH 2 , -NHCH 3 , -N(CH 3 ) 2 , -NO, -NO 2 , -OH, -OCH 3 , -OC 6 H 5 , -OCOR, -F, -SH, -SR, -SOR, -Cl, -Br, -I

Highest.

Some examples: 2 COOH 2 COOH H HO 1 3 CH3 3 H3C H 1 OH

Sequence Rules

•

Sequence Rule I

attached different, number to the is the given

: If four atoms/groups

chirality atom with the centre highest highest are all atomic priority .

However if two isotopes of the same element are attached to the chirality centre, the atom with higher mass number is given higher priority.

2 Br H 4 4 F 3 Cl 2 H3C 1 Br D 3 I1

• •

Sequene Rule 2 If on basis of the sequence rule 1 the priorities of two groups cannot be decided, it can be

determined by a similar comparison of the next atoms, in both groups

. If by doing so the priority cannot be decided, one goes to ‘next’ atom and continues moving outwards commencing with the chiral atom till one reaches the first point of difference .

(

Note

The decision about priority should be made at the very first point of difference, and should not be effected from the consideration of substituents further along the chain.)

•

Sequence Rule 3

In case the group attached to the chiral carbon contains a double bond or a triple bond , both atoms joined by multiple bonds are considered to be duplicated (in case of a double bond) and triplicated (in case of a triple bond).

C X

C X is considered to be equal to

X C X C

—C  X is considered to be equal to

C X X C

is consisered equal to

HC C C C CH

Very Good Mnemonic : Very good or Vertical good rule

•

Fix up priorities of the groups and move your eye from 1



3 ignoring 4. Now, if (i) Group of lowest priority (4) is on the vertical line (whether on top or bottom), and the sequence 1



3 is in clockwise direction the configuration is R and if it is in counter clockwise direction the configuration is S.

(ii) Group of lowest priority (4) is on the horizontal line assign the configuration which is opposite to what you see i.e.; if the movement of the eye from 1



3 is in clockwise direction, assign S-configuration and if it moves in anticlockwise direction assign R- configuration.

Lowest priority 4 on vertical line

H 4 1 Br 2 Cl F 3

R-configuration

2 Cl F 3 H 4 1 Br

R-configuration

3 H3C 2 COOH 1 OH 4 H

S-configuration

Lowest priority 4 on horizontal line

2 CHO 3 CH3 4 H 1 OH 4 H 1 OH 3 CH2OH 2 CH2CH3

R-configuration S-configuration

R-S Nomenclature of Compounds having more than one Chiral Carbon CHO HO HO H H CH2OH L-Erythrose (2S, 3S) CHO HO H H OH CH2OH D-Threose (2S, 3R) CHO H HO OH H CH2OH L-Threose (2R, 3S)

• • • • •

3.13 GEOMETRICAL ISOMERISM Geometric or

cis-trans

or E-Z isomers.

This type of isomerism arises if there is free rotation about the double bond.

no Due to different arrangement of atoms or groups in the space, geometric isomerism is designated as stereoisomerism.

The geometric isomers belong category of configurational isomers they cannot be interconverted breaking two covalent bonds.

to the because without Further, geometric isomers are examples of diastereomers because they are not mirror images of each other.

Geometric isomerism is not confined only to the compounds having carbon-carbon double bonds. In fact the following compounds exhibit this type of isomerism: i) ii) Compounds having a double bond, i. e., olefins (C=C), compounds (N=N).

imines (C=N) and azo Cyclic compounds.

iii) Compounds exhibiting geometric isomerism due to restricted rotation about carbon carbon single bond.

Cause of Geometric Isomerism :

Hindered Rotation

•

Carbon atoms involved in double bond formation and all the atoms attached to these doubly bonded carbon atoms must lie in the same plane because

bond can be formed only by parrallel overlap of the two p-orbitals. There will be decrease in the overlap of p-orbitals if an attempt is made to destroy this coplanarity. In other words, neither of the doubly bonded carbon atom can be rotated about the double bond without destroying the

-orbital.

Rotation by 90o Overlap of

-orbitals not possible as they are perpendicular to each other. Rotation about a C = C bond.

This process of rotation which is really a transfer of electrons from the

-molecular orbital to the p atomic orbital is associated with high energy (271.7 kJ mol -1 ). Thus at ordinary temperatures, rotation about a double bond is prevented and hence compounds such as CH 3 CH =CHCH as isolable and stable geometrical isomers.

3 exist H H C C H3C Cis-But-2-ene CH3 H3C H C C H CH3 Trans-But-2-ene H H C C H5C6 COOH Cis-Cinnamic acid H COOH C C H5C6 H Trans-Cinnamic acid

• • •

Necessary and Sufficient Condition for Geometric Isomerism

Geometrical isomerism will not be possible if one of the unsaturated carbon atoms is bonded to two identical groups.

No two stereoisomers are possible for CH 3 HC=CH 2 , (CH 3 ) 2 C=CH 2 and Cl 2 C=CHCl.

Examples of compounds existing in two stereo isomeric forms are:

H H C C H5C6 COOH

Cis-Cinnamic acid

H COOH C C H5C6 H

Trans-Cinnamic acid

H H C C H3C H2C CH3

Cis-Pent-2-ene

H CH3 C C H3C H2C H

Trans-Pent-2-ene

Determination of the Configuration of the

I.

Geometric Isomers

Physical methods

(a) Melting points and boiling points

: Trans isomer has a higher m. p. due to symmetrical packing.

Cis isomer has a higher b. p. due to higher dipole moment which cause stronger attractive forces.

H H C C H 3 C b.p. 277K CH 3 H H HOOC C C m.p. 403K COOH H C C H 3 C b.p. 274K CH 3 H HOOC H C C H COOH m.p. 575K

(b) Solubility

: Cis-isomers have higher solubilities.

Maleic acid 79.0g/100ml at 293K Fumaric acid 0.7g/100ml at 293K

(c) Dipole moment

: In general, cis isomers have the greater dipole moment.

H H C C H 3 C



= 0.4 D CH 3 H H Cl C C



= 1.85 D Cl H H 3 C C



= 0 C CH 3 H H Cl Cl C



= 0 C H

• •

(d) Spectroscopic data :

IR:

rans

isomer is readily identified by the appearance of a characteristic band near 970 960 cm

-1

. No such band is observed in the spectrum of the

cis

isomer.

NMR:

The protons in the two isomers have different coupling constants e.g.

trans

– vinyl protons have a larger value of the coupling constant than the cinnamic acids.

cis

-isomer , e.g.

cis

- and trans H H H CO2H C C C C C6H5 CO2H C6H5 H

cis-Cinnamic acid (J

= 12Hz) trans-Cinnamic acid (J

= 16Hz)

•

II Chemical Methods

a) Methods compounds: of formation

Oxidation of

from cyclic

benzene or quinone gives maleic acid (m. p. 403K).

From the structure of benzene or quinone, it becomes clear that the two carboxyl groups must be on the same side (cis).

O H CO2H

[O]

or H CO2H m.p. 403 K O Therefore, maleic acid i.e. the isomer having m.

p. 403K, must be cis and the other isomer fumaric acid (m. p. 575K) must be trans.

b) Method of formation of cyclic compounds

•

Cis isomer will undergo ring closure much more readily than the trans isomer.

H CO2H C C H CO2H Maleic acid 423K

-H2O

H CO C O C H CO Maleic anhydride Hydrolysis H CO2H C H CO2H C 573K

-H2O

C HO2C H Fumaric acid C H CO2H Maleic acid

It is, therefore, reasonable to conclude that maleic acid is the cis isomer and fumaric acid is the trans –isomer. The latter forms the anhydride via the formation of maleic acid at high temperature which involves rupture of

bond and rotation of the acid groups followed by reformation of the

-bond and loss of water.

H C CO2H



H C CO2H

Rotation

H C CO2H C C C HO2C H Fumaric acid HO2C H Diradical H CO2H Diradical H CO C O C H CO Maleic anhydride

-H2O

H CO2H C C H CO2H Maleic acid

•

(ii) Ortho-aminocinnamic acids: The Ba-salt of an isomer of ortho-aminocinnamic acid on treatment with CO 2 at room temperature gives carbostyril. This shows that the carboxyl group and the substituted phenyl group must be cis in this isomer. On the other hand, the Ba-salt of the other isomer of ortho aminocinnamic acid does not give carbostyril under the same condition and, therefore, it must have the trans configuration.

H H C NH2 C CO2 Ba/2 CO2

Cis

N H Carbostyril O × H C

Trans

NH2 C CO2 Ba/2 H

•

c) Method of chemical correlation

Suppose configuration of a geometric isomer, say A is known. Let A be converted under mild conditions to a geometric isomer A', of another compound.

Since under mild conditions interconversion of the geometric isomers will not take place, therfore, the configuration of A' will be the same as that of A.

H H H H C C CO2 Ba/2 1. HNO 2 2. H3PO2 C C CO2H A NH2 Cis isomer of ortho-aminocinnamic acid salt H C C CO2 Ba/2 H 1. HNO 2 2. H3PO2 NH2 Trans isomer of ortho-aminocinnamic acid salt

Cis, m.p. 341K

Allocinnamic acid H C CO2H C H

Trans, m.p. 406K

Cinnamic acid A’

d) Method of stereoselective addition reactions

(i) Hydroxylation of double bond is

cis

H COOH C aq. KMnO4 H C or Os O4 H stereospecifically COOH OH OH H COOH Maleic acid COOH meso-Tartaric acid COOH COOH H HOOC C C COOH aq. KMnO4 or Os O4 H HO H H OH + H HO OH H Fumaric acid COOH (+) - Tartaric acid (50%) COOH (



) - Tartaric acid (50%) Racemic mixture

ii) Addition of bromine to double bond:

•

In contrast to hydroxylation, addition of bromine to alkenes is stereospecifically

trans .

Therefore, addition of bromine to trans-isomer will give rise to meso and to cis-isomer gives racemic mixture.

CH3 CH3 H3C H C Br2 / CCl4 H Br Br H + C Br H H Br H3C H Cis-But-2-ene CH3 CH3 Racemic mixture CH3 H3C C H C H CH 3 Trans-But-2-ene Br2 / CCl4 H H Br Br CH3 Meso -2,3-Dibromobutane

•

E and Z System of Nomenclature Consider a molecule in which the two carbon atoms of a double bond are attached with four different halogens.

Br F

•

C C I Cl When we say that Br and CI are trans to each other we can also say with equal degree of confidence that I and CI are cis to each other.

It is thus difficult to name such a substance either the cis or the trans isomer. To eliminate this confusion, a more general and easy system for designating configuration about a double bond has adopted. This method, which is called the been

E and Z system

, is based on a priority system originally developed by Cahn, Ingold and Prelog for use with optically active substance

2 Br 1 I 2 C 1 2 1 C C C 1 2 E Z C F 2 2 Br C C C Cl 1 1 I 1 2 Cl 1 F 2 Z-1-Bromo-2-chloro 2-fluoro-1-iodoethene 1 H3C 2 CH3 1 C C H Z-2-Butene H 2 E-1-Bromo-2-chloro 2-fluoro-1-iodoethene 1 H3C H 2 C C 2 H E-2-Butene CH3 1 1 HOOC COOH 1 C C 2 H H 2 Z-But-2-ene-1,4-dioic acid

(Maleic acid)

2 H COOH 1 C C 1 HOOC H 2 E-But-2-ene-1,4-dioic acid

(Fumaric acid)

Number of Geometrical isomer of compounds containing two or more Double Bonds with Non equivalent terminii

•

Dienes in which the two termini are different (i.e.

XHC=CH –CH=CHY), has four geometrical isomers .

H X H X H X H X C C C C H C C H H C C H C H Y Z,E, or cis-trans C Y H Z,Z, or cis-cis H C H C C H C H C H Y E,Z or trans-cis C Y H E,E or trans-trans

It means the number of geometrical isomers is 2

where n is the number of double bonds.

• •

Geometric Isomerism of Oximes The carbon and nitrogen atoms of oximes are sp2 hybridized, as in alkenes.

Thus, all groups in oximes lie in the same plane and hence they should also exhibit geometric isomerism if groups R and R 1 are different. Accordingly Beckmann (1889) observed that benzaldoxime existed in two isomeric forms and Hantzsh and Werner (1890) suggested that these oximes exist as the following two geometric isomers (I and II).

H5C6 H H5C6 C C N N OH HO

I II

H5C6 C H H5C6 C N N OH HO

I II

Nomenclature of Oximes

• •

The prefixes different ketoximes.

syn

context H

Aldoximes

C and for N

anti

are used in aldoximes and OH H5C6 I syn-Benzaldoxime H C N H5C6 OH II anti-Benzaldoxime

•

Ketoximes

H3C C N H5C2 anti-Ethylmethylketoxime H3C C N H5C2 OH syn-Ethylmethylketoxime

As in the nomenclature confusion .

To case is of

cis-trans

ambiguous and isomerism, often this creates avoid this, the system of E-Z nomenclature has been adopted.

For fixing priority the lone pair of electrons on nitrogen is taken as group of lowest priority. Some examples are given below (1) H5C6 CH3 (2) (1) H5C6 CH3 (2) C C N N (2) OH (1) (1) HO (2) E-Methylphenylketoxime Z-Methylphenylketoxime H3C C N H H3C C N H OH HO E-Acetaldoxime Z-Acetaldoxime

•

Determination of Configuration of Oximes

a) Aldoximes: The acetyl derivative of one isomer regenerated the original oxime whereas that of the other isomer eliminated acetic

mechanism to form aryl cyanide.

acid by

E2 Ar H C Ac2O N OH E or syn - Oxime Ar H C Ac2O N HO Z or anti -Oxime Ar H C N OAc Aq. Na 2CO3

(Hydrolysis)

Ar C H N OH Original oxime Ar H C N Aq. Na 2CO3

Elimination

Ar | C N + Acetic acid AcO Aryl cyanide

•

b) Ketoximes

The configuration of the geometric isomers of the unsymmetrical ketoximes are determined by Beckmann rearrangement which consists in treating ketoxime with acidic reagents such as PCI 5 , H 3 PO 4 , P 2 O 5 , etc.

when the oxime isomerizes to substituted amide by migration of the group (R 1 a or R 2 ) which is anti to the hydroxyl group.

R1 R2 C N OH R2 CO NHR1 R2COOH + R 1NH2 Determination of structure of amine formed in the above sequence of reactions plays a key role in deciding which group has migrated during Beckmann rearrangement.

•

Geometric Isomerism in Alicyclic Compounds Cyclic compounds derivatives of such as the cyclopropane, disubstituted cyclobutane, cyclopentane and cyclohexane can also show cis- trans isomerism, because the basic condition for such isomerism- that there should be sufficient hindrance to rotation about a linkage between atoms- is also satisfied in these systems. Atoms joined in a ring are not free to rotate around the sigma bond.

Away from us CH3 Above the plane Vertical line Towards us Below the plane CH3 1,2-Dimethylcyclohexane

Sometimes, a broken wedge is used to indicate a group below the plane of the ring, and a solid line represent a group above the plane.

Above the plane CH3 CH3 Below the plane

• • •

3.14 Conformational isomerism A carbon – carbon

-bond is formed by an end-on overlapping of sp3-orbitals of the two carbon atoms.

This bond is cylindrically symmetrical about the axis and has the highest electron density along the bond axis.

Almost an infinite number of spatial arrangements of atoms about the cabon-cabon single bond exist. All those arrangements which result from free rotation about a single bond are called conformations or conformers rotamers .

or rotational isomers or simply bond axis

A cylindrically symmetric MO of a single bond obtained by sp3-sp3 overlap of two carbon atoms.

Conformations of Ethane

• •

Pitzer (1936) postulated that there exists a potential energy barrier which causes restriction in rotation.

The extra energy of eclipsed conformation is called torsional strain .

The term torsional strain is used for the repulsion felt by bonding electrons on one substituent when it passes close to the bonding electrons of another substituent.

H H H H H H H H H

Eclipsed conformation H H H

Staggered conformation

Eclipsed Staggered

15 I 10 I I I Eclipsed conformation 5 II II II Staggered conformation 0 60 120 180 240 300 360 Torsion angle (degrees)

I at 0o, 120o and 240o II at 60o, 180o and 300o

Fig. 3.7 Rotational or torsional energy in ethane

CH3 CH3 Conformations of n-Butane CH3



H CH3 CH3 H H H H I Fully Eclipsed (



= 0o) H H CH3 H H H H II Gauche (



= 0o) CH3 H H H H3C III H Partially Eclipsed (



= 120o) CH3 H3C H H H CH3 IV Anti or Trans (



= 180o) H3C H H

Partially Eclipsed (



= 240o) H H H H VI Gauche (



= 300o) Due to congestion in space a repulsive force acts between the methyl groups which is called van der Waals strain or steric hindrance . In butane, gauche conformation is less stable than anti-conformation due to vander Waals strains i.e. n-butane gauche (or skew) intraction.

25 20 I 15 10 5 III V I II 4.0

16 IV VI I = Fully Eclipsed III and V = Partially Eclipsed II and VI = Gauche IV = Anti-conformation 0 60 120 180 240 300 360 Torsion angle (degrees) Fig. 3.8 Rotational or torsional energy in n-butane At room temperature, almost all molecules exist in staggered conformation and amongst staggered conformations 78% exist in anti and 22% in gauche conformations.

•

Conformation of 1,2-Dibromoethane On the basis of torsional strain and vander Waals steric hindrance, staggered (anti) conformation of 1,2 dibromoethane is the most stable followed by gauche.

Br Br Br H H Br Br H Br H

• •

H H H Fully Eclipsed H H H Br H Partially Eclipsed H H H H Br Gauche Anti H Dipole moment of anti-conformation is zero while gauche conformation has some finite dipole moment since the two C —Br dipoles are at an angle of 60 0 to each other.

Actual dipole moment of 1,2-dibromoethane is 1.0D, therefore, the molecule cannot exist entirely in the anti form. Hence

Anti Gauche

•

Conformations of 1,2-Glycols : Ethylene Glycol In case of ethylene glycol due to intramolecular H bonding the gauche form becomes more stable than anti-conformation bonding because there will be no such H possible in anti-conformation.

The formation of such H-bond stabilizes the molecule by approximately 20-30 kJ mol-1.

H OH OH OH H H O O H H OH H H H H H Fully Eclipsed H H HO H Partially Eclipsed H H H H OH Gauche Anti H

•

Similarly due to intramolecular H- bonding ethylene chlorohydrin, (CH 2 Cl — CH 2 OH), exists in gauche conformation which is more stable than anti-form.

•

Alicyclic System: Cyclohexane Cyclohexane can have two conformations free from Baeyer or angle strain , called the

chair

form (I) and the

boat

form (II), respectively. I II H a H a H e e H e H e H H a a H H a H a H e H e Chair conformations of cyclohexane with axial and equatorial bonds

H 4 H (fp) H 3 H H 5 H (fp) H 1 H H 2 H H 6 H Boat 4 H H 5 3 H 1 6 2 H Ha Hb Boat Twist Boat Twist chair 4 H H H 1 3 6 5 Hb Twist boat 2 Ha H

41.9

30.6

22.6

b d c a Fig. 3.10 Potential energy of cyclohexane, a, chair; b, twist chair; c twist boat; d, boat.

•

Cyclohexane Derivatives In methylcyclohexane , the axial conformer will have two more n-butane skew interactions (7.54 kJ mol -1 ) whereas in the equatorial conformer no additional interaction or torsional strain is introduced since the two new n-butane segments in it are both fully staggered (anti).

2 H H 4 3 H 6 H 1 5 6 H 1 CH3 H H 5 3 CH3 H The two new skew (gauche) interactions in the axial conformer are best demonstrated by drawing the Newman projection formula for the n-butane segment, CH 3 , C 1 , C 2 , C 3 and CH 3 , C 1 , C 6 , C 5 .

Newman projection for the equatorial conformer, as shown below, clearly shows the absence of any additional skew interaction.

H H H 6 CH3 1 5 H H 3 H H We reach the same conclusion if we consider that in the axial conformer the two axial hydrogens on C 3 and C 5 closer to the axial than to the equatorial methyl group.

are H 4 3 H H 2 5 Axial methyl 6 CH3 1 H H H Equatorial methyl CH3

•

Cis 1,3-dimethylcyclohexane The interactions between the axial atoms or groups at 1- and 3- or 5-positions are called 1,3-diaxial

interactions

and in the case of 1,3 dimethylcyclohexane, the 1,3-diaxial interaction has been assigned the value of 22.6kJmol

-1 . Thus cis 1,3 dimethylcyclohexane exists at room temperatures almost wholly in the diequatorial conformation.

CH3 CH3 H H H CH3 H H3C cis 1,3-Dimethylcyclohexane

(diaxial conformer; much less stable)

cis 1,3-Dimethylcyclohexane

(diequatorial conformer; much more stable)

tert-Butylcyclohexane exists 100 per cent in the equatorial conformation (A), the ring being frozen due to the prevention of the flip to a conformation (B) in which the non-bonded 1,3-diaxial interactions between the axially bound tert-butyl group and the two axial hydrogens at the 3-and 5 positions will be forbiddingly large.

H H H CH3 CH3 CH3 H H H A B H3C CH3 CH3

It is clear from the above considerations that the axial bonds experience non-bonded interactions with other axial bonds at 3-and 5-positions whereas the equatorial bonds are free from such steric interactions , i.e.

experience more axially bound groups will steric crowding than the equatorially bound groups.

This explains why in most of the cases the equatorially bound groups in cyclohexane derivatives are more reactive than the axially bound ones.

E.g. equatorially bound hydroxyl groups are more easily esterified than the axial ones. Similarly, the equatorial acetoxy group undergoes hydrolysis faster than the axial group.

3.15

•

Difference between conformation and configuration Conformations is used for various spatial isomers which can be easily inter-converted .

•

Configurations is used for various spatial isomers which can be interconverted only by breaking and making of covalent bonds .

•

The can energy be difference interconverted between conformers is very small due to which they by molecular collisions even at room temperature.

two

•

Conformational separated. But conformational isomers can be separated easily.

isomers cannot be

Dipole moment of meso form is much lower (



=1.27 D) than optically active form (



= 2.75D) of stilbene dichloride. Why?

meso

-form

C6H5 Cl C6H5 I

(+ or -) form

C6H5 Cl H through 120 o Cl C6H5 Rotate H H H Cl Rotate Cl through 120 o H Cl H IV C6H5 H II C6H5 C6H5 V C6H5 H Rotate through 120 o H5C6 Cl Cl Cl Rotate through 120 o H5C6 H C6H5 Cl III C6H5 Cl VI H H H Cl

How many asymmetric carbon atoms are created during the complete reduction of benzil (PhCOCOPh) with LiAIH 4 ? Also write the number of possible stereoisomers of the product.

Ans.

O O Ph C C Benzil Ph OH OH LiAIH 4 Ph

1 C C

2 Ph H H 1,2-Diphenylethane-1,2-diol As 1,2-diphenylethane-1,2-diol has two similar asymmetric carbons (cf. tartaric acid) it exists as three steroisomers.

Ph Ph Ph H HO OH H HO H H OH H H OH OH I Ph Enantiomers Ph II Ph III meso-form