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Stereochemistry and conformations

Ref. Books:

Stereochemistry Conformation & Mechanism

- P.S. Kalsi

Organic Chemistry - L.G. Wade

Organic Chemistry - I.L. Finar Vol. 2

Stereochemistry of Carbon Compounds

- E.L. Eliel

Stereochemistry

The branch of chemistry that deals with spatial

arrangements of atoms in molecules and the

effects of these arrangements on the chemical

and physical properties of substances.

Stereochemistry refers to the 3-dimensional

properties and reactions of molecules.

Deals with:

Determination of the relative positions in

space of atoms, group of atoms

Effects of positions of atoms on the properties

Conformation: An atomic spatial arrangement

that results from rotation of carbon atoms

about single bonds within an organic molecule.

Conformation generally means structural

arrangement and may refer to:

Conformational isomerism, a form of

stereoisomerism in chemistry

Stereoisomers are isomeric molecules that

have the same molecular formula with same

connectivity, but differ in the three-dimensional

orientations of their atoms in space.

Stereoisomers

Interconverted by rotation about single bond ?

Yes

H

H

CH3

H3C

H

H

H3C

HH

CH3

HH

Conformational

No

Configurational

Optical

Yes

isomerism at a tetrahedral central ?

compounds non-superimposable

mirror image ?

No

Geometric

No

Diastereomers

H

H

H3C

Br

Cl

H3C

Cl

H

H3C

Br

H

H3C

Yes

EnantiomersCl

H3CH2C

Cl

CH2CH3HH

CH3H3C

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Conformation : interconvertible by rotations about single

bonds

Configuration : an atomic spatial arrangement that isfixed by the chemical bonding in a molecule and thatcannot be altered without breaking bonds

To change the configuration, you must always cleave and form

new covalent bonds

Different conformations, can be made identical with a rotation

of 180 about the central single bond.

Definitions

Stereoisomers – compounds with the same

connectivity, different arrangement in space

Enantiomers – stereoisomers that are non-

superimposible mirror images; only properties that

differ are direction (+ or -) of optical rotation

Diastereomers – stereoisomers that are not

mirror images; different compounds with different

physical properties

Optical activity – the ability to rotate the plane of

plane –polarized light

Polarimeter – device that measures the optical

rotation of the chiral compound

Arises from restricted rotation about a C=C

double bond.

Stereoisomerism

Stereoisomerism is the arrangement of atoms in

molecules whose connectivity remains the same but

their arrangement in space is different in each isomer.

Geometrical Isomerism

cannot be inter-converted

at lower temperatures

This process of rotation 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 CH3CH =CHCH3 exist as isolable

and stable geometrical isomers.

H

C C

H

H3C CH3

CC

cis-but-2-ene trans-but-2-ene

H3C

CH3H

H

cis-cinnamic acid trans-cinnamic acid

HH

C C

H

COOH

CC

COOH

HH5C6 H5C6

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Necessary and sufficient condition for

geometric isomerism

No two stereoisomers are possible for CH3HC=CH2,

(CH3)2C=CH2 and Cl2C=CHCl.

Compounds existing in two stereo-isomeric forms are:

Geometrical isomerism will not be possible if one of the

unsaturated carbon atoms is bonded to two identical groups.

where a b and c d

Determination of the configuration of the 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.

(b) Solubility: Cis-isomers have higher solubilities.

Maleic acid 79.0g/100mL at 293K in H2O

Fumaric acid 0.7g/100mL at 293K in H2O

(c) Dipole moment: In general, cis isomers have the

greater dipole moment.

HH

C C

H

CH3

CC

= 0.4 D = 0

CH3

HH3C H3C

ClCl H

Cl

= 0 = 1.85 D

C C

Cl

H

CC

H H

(d) Spectroscopic data :

IR: Trans 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 cis-isomer,

e.g. cis- and trans-cinnamic acids.

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E/Z notation

If there are three or four different groups attached

to the Cs of C=C double bond

E/Z notation rather than the trans/cis notation is

used to name the stereoisomers of a molecule.

E : in opposition to trans

Z : together cis

ZE

This method, which is called the E and Z system, is based on apriority system originally developed by Cahn, Ingold and Prelog foruse with optically active substance

CC

1

2

2

1 2

1

2

1

C C

E Z

Z-But-2-ene-1,4-dioic acid

(Maleic acid)

E-But-2-ene-1,4-dioic acid

(Fumaric acid)

C C

COOH

HHOOC

HHOOC

H H

COOH

CC

2

1

2

1

1

2

2

1

C C

F

ClI

Br

1

2

1

2

2

12

1

Br

I

Cl

F

CC

Z-1-Bromo-2-chloro-

2-fluoro-1-iodoethene

E-1-Bromo-2-chloro-

2-fluoro-1-iodoethene

Z-2-Butene

2

1

2

1 H3C

H H

CH3CC C C

CH3

H

H

H3C1

2 1

2

E-2-Butene

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 .

It means the number of geometrical isomers is 2n where n is

the number of double bonds.

C

C

X

H

H

H

HY

C

CC

C

H

H

Y

C

C

H

H

X

Z,E, or cis-trans

C

C

Y

H

H

C

C

H

H

X

Z,Z, or cis-cis E,E or trans-trans

C

C

H Y

H

H

H

X

C

C

E,Z or trans-cis

Geometric isomerism of oximes

They should also exhibit geometric isomerism if groups

R1 and R2 are different.

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).

For fixing priority the lone pair of electrons on nitrogen is

taken as group of lowest priority.

or

The carbon and nitrogen atoms of oximes are sp2-

hybridized, as in alkenes.

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Nomenclature of aldoximes

The prefixes syn and anti are used in different

context for aldoximes and ketoximes

In case of aldoximes, the syn form is the one in

which both the hydrogen and the hydroxyl (-OH)

group are on the same side of the C=N, whereas in

the anti form, they are on the opposite side.

H

H5C6

C N

OH

anti-benzaldoxime

OH

NC

H5C6

H

syn-benzaldoxime

Nomenclature of ketoximes

syn-ethylmethylketoxime syn-methylethylketoxime

anti-ethylmethyketoxime or

anti-methyethylketoxime or

In case of ketoximes, the syn and anti

descriptor indicate the spatial relationship

between the first group cited in the name and

the hydroxyl group

The system of E-Z nomenclature has also been adopted

for oximes.

For fixing priority the lone pair of the electrons on

nitrogen is taken as group of lowest priority.

E-Methylphenylketoxime

CH3H5C6

C

N

OH

(2)

(2)

(1)

(1) HO

N

C

CH3H5C6(1)

(1)

(2)

(2)

E-Acetaldoxime

OH

N

C

H3C H H3C H

C

N

HO

Z-Methylphenylketoxime

Z-Acetaldoxime

Chiral Carbons

Carbons with four different groups attached

are chiral.

It’s mirror image will be a different compound

(enantiomer).

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Achiral Compounds

Take this mirror image and try to

superimpose it on the one to the left matching

all the atoms. Everything will match.

When the images can be superimposed the

compound is achiral.

Chirality - optical activity: discovery

French chemist Louis Pasteur (1848) discovered thatcrystalline optically inactive sodium ammoniumtartarate was a mixture of two types of crystalswhich were mirror images of each other.

Each type of crystals when dissolved in water wasoptically active. The specific rotations of the twosolutions 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 inwhich shapes of crystals disappear, Pasteur proposedthat like the two sets of crystals, the molecules makingup the crystals were themselves mirror - images of eachother and the difference in rotation was due to 'moleculardissymmetry'

Chirality

An object which cannot be superimposed on its mirror-

image is said to be chrial [Greek : Cheir 'Handedness']

and the property of non-superimposability is called

chirality. Thus our hands are chiral.

The presence of a chirality centre usually leads to

molecular chirality. Such a molecule has no plane of

symmetry and exists as a pair of enantiomers. Such a

carbon atom is sometimes also referred to as asymmetric

carbon atom.

Asymmetric Carbons

The most common feature that leads to chirality

in organic compounds is the presence of an

asymmetric (or chiral) carbon atom. (A carbon

atom that is bonded to four different groups)

no asymmetric C usually achiral

1 asymmetric C always chiral

> 2 asymmetric C may or may not be chiral

In general:

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C

OH

H CH3

C2H5 C

OH

HH3C

C2H5

Mirror images of each other

Non-superimposable with each other

Enantiomers

(+) or (-)butan-2-ol

Enantiomers Enantiomers: stereoisomers that are non-

superimposible mirror images

The direction of optical rotation cannot be

predicted from the structural formulae.

It can only be determined experimentally.

Fischer mirror images

Easy to draw, easy to find enantiomers

Enantiomers

CH3

CH3

Cl

H

H

Cl

CH3

CH3

H

Cl

Cl

H

Properties of enantiomers

Same boiling point, melting point, and density.

Same refractive index.

Rotate the plane of polarized light in the samemagnitude, but in opposite directions.

Different interaction with other chiral molecules:

Active site of enzymes is selective for a specificenantiomer.

Taste buds and scent receptors are also chiral.Enantiomers may have different smells.

Stereochemistry

The properties of many drugs depends on

their stereochemistry:

(R)-ketamineanesthetic hallucinogen

(S)-ketamine

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Resolution of enantiomers

The process of separating enantiomers is

called resolution.

Since enantiomers have identical physical

properties, they cannot be separated by

conventional methods.

- Distillation and recrystallization fail.

Methods of resolution:

1. Mechanical separation

2. Preferential crystallization

3. Resolution through the formation of diastereomers: chemical method

4. Biochemical method

5. chromatographic method

Enantiomers, racemic

C(+)C(+) C(-)C(-)

2P(+)2P(+)

C(+)P(+)C(+)P(+) C(-)P(+)C(-)P(+)

Separate diastereomers

C(+)P(+)C(+)P(+)

C(-)P(+)C(-)P(+)

P(+)P(+)

P(+)P(+)

C(+)C(+)

C(-)C(-)

Resolution of enantiomers (chemical method)

pure

pure

Add pure

enantiomer

()Tartaric acid(racemic mixture)

+ (-)cinchonidine(resolving agent)

(+)tartaric acid (-)cinchonidine

(-)tartaric acid (-)cinchonidine+ Diastereomers

(separable)

dil. H2SO4

(+)tartaric acid(crystalize out)

dil. H2SO4

(-)tartaric acid(crystalize out)

Biochemical Method

Microorganisms or enzymes are highly stereoselective.

(+)-Glucose plays an important role in animalmetabolism and fermentation, but (-)-glucose is notmetabolized by animals, and furthermore cannot befermented by yeasts.

Penicillium glaucum, consumes only the (+)-enantiomerwhen fed with a mixture of equal quantities of (+)-and(-)-tartaric acids.

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

Limitations:

(i) These reactions are to be carried out in dilute solutions, soisolation of products becomes difficult.

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

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Chiral biological macromolecules

Proteins

Enzimes

Structural elements of membrances

Receptors

Carbohydrates

Nucleic acids

Chiral ‘building blocks’ of L-amino acids

and D-carbohydrates

Biological discrimination of enantiomers

Enantiomers can be distinguished through the use of

chiral probes. A polarimeter is one example of a chiral

probe.

Enzymes are a type of chiral probe that are found in

living systems.

In general, enantiomers do not interact identical with

other chiral molecules

Enzymes are chiral, and are capable of distinguishing

between enantiomers

Either one has no effect or has a totally different

Usually, only one enantiomers of a pair fits properly into

the active site of an enzyme

Biological significance of chirality

A schematic diagram of an enzyme surface capable of binding with

(R)-glyceraldehyde but not with (S)-glyceraldehyde.

Since most of the natural (biological) environment consists ofenantiomeric molecules (amino acids, nucleosides,carbohydrates and phospholipids are chiral molecules), thenenantiomers will display different properties. Then, in our body:

This enantiomer of glyceraldehyde fits the three

specific binding sites on the enzyme surface.

This enantiomer of glyceraldehyde

does not fit the same binding sites.

R-glyceraldehyde S-glyceraldehyde

Discrimination of enantiomers

Enzymes are

capable of

distinguishing

between

stereoisomers

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Expressed mathematically:

enantiomeric excess = % of major enantiomer - % of

minor enantiomer.

Enantiomeric excess (ee): The excess of one

enantiomer over the other in a mixture of enantiomers.

Example: A mixture composed of

86% R enantiomer

14% S enantiomer

ee of the mixture = 86% - 14% = 72%

X 100e.e =d-l

d+l

X 100=(excess of one over the other)

(entire mixture)

Optical Purity : The optical purity is a measure of

enantiomeric purity of a compound and is given in terms

of its enantiomeric excess (ee). Optical purity is

expressed as a percentage.

A pure enantiomer would have an optical purity and

enantiomeric excess of 100%.

A fully racemised compound has 0% optical purity.

If the enantiomeric excess is 90%, means 90% pure

enantiomer, remaining 10% contains equal amounts

of each enantiomer (i.e. 5% + 5%).

Enantiomeric excess of a mixture of enantiomers is

numerically equal to its optical purity.

Optical Purity

Optical Purity

Optical purity (o.p.) is sometimes called

enantiomeric excess (e.e.).

One enantiomer is present in greater amounts.

X 100o.p. = rotation of pure enantiomer

observed rotation

Problem: The specific rotation of (S)-2-iodobutane is

+15.90. Determine the % composition of a mixture of (R)-

and (S)-2-iodobutane if the specific rotation of the mixture

is -3.18.

= 20%X 100o.p. =3.18

15.90

l = ee + (100-20)/2 = 60%

d = (100-20)/2 = 40%

Enantiomeric Excess (e.e.)

Problem : When optically pure (R)-(-)-2-bromobutane is heated

with water, 2-butanol is the product. Twice as much (S)-2-

butanol forms as (R)-2-butanol. Find the e.e. and the observed

rotation of the product. [α]=13.50° for pure (S)-2-butanol.

Let consider x = amount of (R) enantiomer formed

= 33% 100=2x-x

2x+x 100e.e =

| d-l |

d+l 100=x

3x

100o.p. = rotation of pure enantiomer

observed rotation

We know, e.e. = o.p.

100observed rotaion =

33 13.50= 4.5

2x = amount of (S) enantiomer formed

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Conformational mobility of cyclohexane

Chair conformations readily interconvert, resulting

in the exchange of axial and equatorial positions by

a ring-flip

Substituted cyclohexanes

The planar diagram predicts achiral and

optically inactive.

But we know the structure is not planar.

Chirality of conformationally mobile systems

(1S,2R)

Br Br

Cis-1,2-dibromocyclohexane

Chirality of conformationally mobile systems

This is a chiral structure and would be expected to be

optically active

cis-1,2-dibromocyclohexane

Consider the chair interconversion….

Br

Br

Br

Br

Chirality of conformationally mobile systems

Br

Br

Br

Br

cis-1,2-dibromocyclohexane

The two chair forms are enantiomers but not isolatable

Two structures have the same energy. Rapid

interconversion. 50:50 mixture. Racemic mixture.

optically inactive.

Planar structure predicted correctly

SR(ax,eq) SR(eq,ax)

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No mirror planes. Predicted to

be chiral, optically active.

Each structure is chiral. Not mirror images! Not the

same! Present in different amounts. Optically active

R,R (eq.eq) R,R (ax,ax)

Trans 1,2 dibromocyclohexane

(1S,2S)

Br Br

trans-1,2-dibromocyclohexane

Br

Br

Br

Br

Mobile conformers

If equilibrium exists between two chiral

conformers, the molecule is not chiral.

Judge chirality by looking at the most

symmetrical conformer.

Cyclohexane can be considered to be planar,

on average.

Subs. Cis Trans

1,2-X2

eq,ax ax,eq

interconverting

enantiomers

eq,eq ax,ax

isolable enantiomers

two conformations each

1,2-XY

eq,ax ax,eq

isolable enantiomers

two conformations each

eq,eq ax,ax

isolable enantiomers

two conformations each

1,3-X2

eq,eq ax,ax

meso compound

two conformations

eq,ax ax,eq

isolable enantiomers

two conformations each

Nonmobile conformers

The planar conformation of the biphenyl derivative is too

sterically crowded. The compound has no rotation

around the central C—C bond and thus it is

conformationally locked.

The staggered conformations are chiral: They are

nonsuperimposable mirror images.

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The different spatial arrangements that a

molecule can adopt due to rotation about σ

bonds are called conformations and hence

conformational isomers or conformers.

The study of the energy changes that occur

during these rotations is called conformational

analysis.

Conformational AnalysisStructure of ethane

Definitions

Gauche(staggered) - A low energy

conformation where the bonds on

adjacent atoms bisect each other

(60o dihedral angle), maximizing the

separation.

Eclipsed - A high energy

conformation where the bonds on

adjacent atoms are aligned with

each other (0o dihedral angle).

Definitions

Anti - Description given to two

substituents attached to adjacent

atoms when their bonds are at

180o with respect to each other.

Syn - Description given to two

substituents attached to adjacent

atoms when their bonds are at 0o

with respect to each other.

Syn

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Types of strain

Torsional strain- The potential

energy arises due to the repulsion

between pairs of bonds caused by

the electrostatic repulsion of the

electrons in the bonds. Groups

are eclipsed.

Steric strain- The potential

energy arises due to the

repulsion between the electron

clouds of atoms or groups.

Groups try to occupy some

common space.

Types of strain

Angle strain – The potential energy arises due to

distortion of a bond angle from it's optimum

value caused by the electrostatic repulsion of

the electrons in the bonds. e.g. cyclopropane

Rotational conformations of ethane

staggered, = 60

Sawhorse structures

Newman projections

eclipsed, = 0skew, = anything else

rotate rear

carbon 60

60o Rotation causes torsional or eclipsing strain

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Potential energy diagram of ethane

P.E

Dihedral angle

Ethane molecules have enough energy

to surmount this barrier, except at

extremely low temp. (−250 °C),

The Newman projection of propane

rotate rear

carbon 60

Propane conformations: larger barrier to rotation Butane conformations (C2-C3)

Gauche interaction in butane

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2 Different eclipsed conformations

Total : 16.0 kJ/mol

6.0 kJ/mol

6.0

kJ/m

ol

4.0

kJ/m

ol

4.0

kJ/m

ol

4.0

kJ/m

ol

4.0

kJ/m

ol

11.0 kJ/mol

Total : 19.0 kJ/mol

Strain energy can be quantified

Energy for interactions in alkane conformers

Potential energy diagram of butane

Dihedral angle between methyl groups

CyclopropaneAngle and Torsional Strain

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Newman projection of cyclopropane

All dihedral angles = 0o

Cyclobutane is not Planar Cyclopentane

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Chair conformation of cyclohexane

Viewed along the ‘seat’ bonds

Boat conformation of cyclohexane

axial up

eq. up

Axial methyl group is gauche to C3 in the ring

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Equatorial methyl group is anti to C3 in the ring

cis 1,3-dimethylcyclohexane

trans 1,3-dimethylcyclohexane

trans 1,3-dimethylcyclohexane

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cis 1-Chloro-4-t-butylcyclohexane

Cyclohexane conformationsMethods for determining conformations

A number of methods have been used to

determine configuration;

X-ray and electron diffraction, IR, Raman, UV,

NMR spectra, photoelectron spectroscopy,

Optical Rotatory Dispersion (ORD) and

Circular Dichroism (CD) measurements.

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Polarimeter

Clockwise

Dextrorotatory (+)

Counterclockwise

Levorotatory (-)

Not related to (R) and (S)

Polarimeter: Device that measures the optical

rotation of the optically active substance

Specific Rotation []D

= observed rotation

c = concentration ( g/mL )

l = length of cell ( dm )

D = yellow light from sodium lamp (5893 Å)

t = temperature ( Celsius )

Specific rotation calculated

in this way is a physical

property of an optically active substance.

You always get the same value of

It is defined as the number of degrees of rotation

caused by a solution of 1.0 g of compound per ml of

solution taken in a polarimeter tube 1.0 dm (10 cm)

long at a specific temperature and wavelength.

The specific rotation is calculated from

observed angle of rotation, as below:

Optical rotation: the rotation of linearly

polarized light by the sample

Optical Rotatory Dispersion (ORD): the

variation of optical rotation as a function of

wavelength. The spectrum of optical rotation.

Circular Dichroism (CD): the difference in

absorption of left and right circularly light.

Chiral structure can be distinguished and

characterized by polarized light

Dichroism is used to denote direction-dependent

light absorption.

Circular Dichroism (CD) The production of an

elliptically polarized wave when a linearly polarized

light wave passes through a substance that has

differences in the extinction coefficients for left- and

right-handed polarized light.

Birefringence refers to the direction-dependent

index of refraction

Circular birefringence A phenomenon in which

there is a difference between the refractive indices

of the molecules of a substance for right and left-

circularly polarized light

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Optical rotation

When a plane polarized light (PPL) is passed

through optically active compound due to it’s

circular birefringence results in unequal rate of

propagation of left and right circularly

polarized rays.

This unequal rate of propagation of both left

and right circularly polarized light deviates the

PPL from it’s original direction and it is called

as optical rotation

Optical rotation caused by compound changed

with wavelength of light was first noted by Biot

in 1817.

Light and Polarization

Light can be represented as a transverse electromagnetic

wave made up of mutually perpendicular, fluctuating

electric and magnetic fields. The left side of the following

diagram shows the electric field in the xy plane, the

magnetic field in the xz plane and the propagation of the

wave in the x direction. The right half shows a line tracing

out the electric field vector as it propagates. Traditionally,

only the electric field vector is dealt with because the

magnetic field component is essentially the same.

Polarized Light

Consider two light waves, one polarized in the YZ plane and the

other in the XY plane. If the waves reach their maximum and minimum points at the same

time (they are in phase), their vector sum leads to one wave,

linearly polarized at 45 degrees.

Similarly, if the two waves are 180 degrees out of phase, the resultant

is linearly polarized at 45 degrees in the opposite sense.

If the two waves are 90 degrees out of phase (one is at an

extremum and the other is at zero), the resulting wave is circularly

polarized.

In effect, the resultant electric field vector from the sum of the

components rotates around the origin as the wave propagates.

The following diagram shows the sum of the electric field vectors for

two such waves.

The most general case is when the phase difference is at an

arbitrary angle (not necessarily 90 or 180 degrees.) This is called

elliptical polarization because the electric field vector traces out anellipse (instead of a line or circle as before.)

These concepts can be rather abstract the first time they are

presented. The following simulation allows the user to change thephase shift to an arbitrary value to observe the resultant polarization

state.

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The basics of polarisation

To really understand circular dichroism, one must first

understand the basics of polarisation.

Linearly polarised light is light whose oscillations are

confined to a single plane.

All polarised light states can be described as a sum of two

linearly polarised states at right angles to each other, usually

referenced to the viewer as vertically and horizontally

polarised light. This is shown in the animations below.

Vertically Polarised Light Horizontally Polarised Light

If we take horizontally and vertically polarised light

waves of equal amplitude that are in phase with each

other, the resultant light wave (blue) is linearly polarised

at 45 degrees, as shown in the animation below:

45 Degree Polarised Light

If the two polarization states are out of phase, the resultant

wave ceases to be linearly polarized. For example, if one of

the polarized states is out of phase with the other by a

quarter-wave, the resultant will be a helix and is known as

circularly polarized light (CPL).

The helices can be either right-handed (R-CPL) or left-

handed (L-CPL) and are non-superimposable mirror images.

The optical element that converts between linearly polarized

light and circularly polarized light is termed a quarter-wave

plate. A quarter-wave plate is birefringent, i.e. the refractive

indices seen by horizontally and vertically polarised light are

different.

A suitably oriented plate will convert linearly polarized light

into circularly polarized light by slowing one of the linear

components of the beam with respect to the other so that

they are one quarter-wave out of phase. This will produce a

beam of either left- or right-CPL.

Left Circularly Polarised (LCP) Light

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Right Circularly Polarised (RCP) Light

The difference in absorbance of left-hand and right-

hand circularly polarised light is the basis of circular

dichroism. A molecule that absorbs LCP and RCP

differently is optically active, or chiral.

When a ray of monochromatic polarized light

strikes a solution, several phenomenon’s occurs

like:

1. Reflection on the surface

2. Refraction

3. Rotation of plane polarization

4. Absorption

Enantiomers are optically active compounds.

Optically active molecules have different

refractive indices, and different extinction

coefficients for L and R circularly polarized

light.

Optical Rotatory dispersion (ORD)

ORD is defined as the rate of change of

specific rotation or rotatory power with change

in wavelength.

Light is an electromagnetic radiation and

consist of vibrating electric and magnetic

vector perpendicular to each other.

ORD curves in recent years are made use in

structural determination by comparing the

curve obtain from compound believed to have

related structures particularly applied to

carbonyl compounds.

E.g.. ORD curves have been used to locate

the position of carbonyl groups in steroid

molecules.

Rotatory dispersion curves (i.e. plot of optical

rotation against wavelength.) can be classified

into two main types.

1. Plain curves

2. Cotton effect curves.

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According to Fresnel, a plane polarized light may

be considered as the combination of two circularly

polarized light of which one is right circularly

polarized light (RCPL) & other is left circularly

polarized light (LCPL) which are in equal &

opposite in nature.

A circularly polarized light (CPL) is one whose

plane of polarization rotates continuously & in the

same sense around the axis of the polarization of

the wave & it may be described as right handed

screw or helix twisting around the direction of

propagation, where LCPL wave describe the left

handed screw.

Rotation of plane polarized light

(Fresnel’s explanation) -: The figure below represents how the electric vector of

RCPL (ER) & that of LCPL (EL) combined to give a

plane polarized wave (E)

E

El ER

RCPL + LCPL = PPL

Plane of polarization

The two circularly polarized light vibrate in

opposite direction with the same angular

velocity if refractive index is same

Zero resultant

The two circularly polarized light vibrate in

opposite direction with same angular velocity if

refractive index is same.

Variation of E as a resultant of two rotating vector EL and ER

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Specific rotation (Rotatory power):

It is the rotation produced by a solution in 10 cm

length tube having 1 gm of substance in 100 ml.

denoted by [ α ]

The specific rotation depends on following

factors:-

Nature of substance.

Length of the column.

Conc. of the sol.

Temp of the sol.

Nature of the solvent.

Wavelength of the light used.

The angle of rotation per unit path length is,

α = (nL – nR ) π / λ

Where,

λ = wavelength of incident light

n = refractive index

If RCPL travels faster α is positive & the

medium is dextrorotatory,

If LCPL travels faster then α is negative & the

medium is levorotatory.

The combination of circular dichroism and

circular birefringence is known as cotton

effect. Which may be studied by observing the

change of optical rotation with the wavelength

so called ORD.

It was discovered by a French physicist A.

COTTON.

The curves obtained by plotting optical rotation

v/s wavelength down to about 220nm using

photoelectric spectropolarimeters, known as

ORD curves or Cotton effects.

Cotton effect The absolute magnitude of the optical rotation

at first varies rapidly with , crosses zero at

absorption maxima and then again varies

rapidly with but in opposite direction, this is

known as Cotton effect and the curves

describing such effect is called Cotton effect

curves.

They are of two types:

1. Plain curves

2. Anomalous curves

(a) Single cotton effect curves

(b) Multiple cotton effect curves

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Plain curves (Normal smooth curves or single curves)

Cotton effect is not seen for compounds which absorbs

in far UV well below 220nm, because it occurs only

near absorption maximum.

The curves obtained do not contain any peak or

inflections and that the curve do not cross the zero

rotation line and devoid of maxima and minima within

the measurable range.

These curves on the other hand shows a

number of extreme peaks and troughs

depending on the number of absorbing groups

and therefore known as Anomalous dispersion

of optical rotation.

This type of curves is obtained for the

compounds which contain an asymmetric

carbon atom and also contain chromophore,

which absorb near the UV region.

Anomalous curves

These are anomalous dispersion curves which

shows maximum and minimum both of them

occurring in the region of maximum

absorption.

If in approaching the region of cotton effect

from the long wavelength, one passes first

through maximum (peak) and then a minimum

(trough), the cotton effect is said to be

positive.

Single cotton effect curves

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In this type of ORD curves two or more peaks

and troughs are obtained.

E.g. Ketosteroids, camphor etc.

Multiple cotton effect curves Circular dichroism (CD)

Chiral substances show differential absorption

of circularly polarized light which is called

Circular dichroism.

Measurement of how an optical active

compound absorbs right and left circularly

polarized light (ER and EL)

For CD the resultant transmitted light is not

plane polarized but elliptically polarized.

Circular dichroism

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Applications of CD

Determination of secondary structure of proteins that cannot be

crystallized

Investigation of the effect of e.g. drug binding on protein

secondary structure

Dynamic processes, e.g. protein folding

Studies of the effects of environment on protein structure

Secondary structure and super-secondary structure of

membrane proteins

Study of ligand-induced conformational changes

Carbohydrate conformation

Investigations of protein-protein and protein-nucleic acid

interactions

Folding recognition

Difference between ORD & CD

Graphs are obtained by

specific rotation vs

wavelength

Circularly polarized light Plane polarized light

Dispersive phenomena

Plane polarized is used

and is not converted to

elliptical light

Circular polarized is

used and is converted

to elliptical

Absorptive phenomena

Graphs are obtained

molar ellipicity vs

wavelength