Lecture notes CM

CHIROPTIC PROPERTIES IN CHIRAL MOLECULES

We know that light waves consist of oscillating electric and magnetic fields. These fields are

always at right angles to each other as well as to the direction of propagation. For simplicity we

ignore the magnetic field, which is perpendicular to the electric field. The following figure shows the

electric field of a light wave traveling along y- direction. If you imagine that you could see the light

waves coming towards you, you would see the electric field as a vertical line; ie the electric field

oscillates only in one plane. We say that the light is plane polarized.

Z

Y

X

Light coming from an ordinary lamp is not plane polarized. The electric field of the light

waves from the lamp is arranged in many planes. However if we pass the light through a piece of

Polaroid it become plane polarized.

Polaroid

Plane Polarized light wave

Some of the electric fields

of light waves from the lamp

When plane polarized radiation passes through samples of certain kinds of matter the plane of

polarization is rotated. This property is known as optical activity.

A wave of plane polarized light may be considered to be made up of two types of ‘circularly

polarized light’. In circularly polarized light the electric fields at different points along the direction

of propagation rotates continuously. That is, the field spirals around the direction of propagation. If

the rotation is towards right it is called right circularly polarized and if towards left is called left

circularly polarized. The electric field of a right circularly polarized wave may be described as a right

handed screw or helix twisting around the direction of propagation where as a left circularly polarized

wave describes a left-handed screw or helix. The arrays of arrows in the following figure show the

view of electric field when looking toward the oncoming ray.

Lecture notes CM

The plane-polarized beam may be regarded as a superposition of two oppositely rotating

circularly polarized components. It is the resultant of the two that appears as oscillation in a plane.

Right circularly polarized light

Left circularly polarized light

Source

Source

Lecture notes CM

A plane polarized light entering a sample can be regarded as the superposition of two counter

rotating circularly polarized components. According to quantum theory a ray of frequency consists

of a stream of photons, each one of which has energy E = h. Photons may also be polarized. A plane-

polarized ray of light consists of plane-polarized photons and a circularly polarized ray consists of

circularly polarized photons. Refractivity of a medium relates to the speed of light in that medium.

The lower the speed the higher the refractivity. The index of refraction is the ratio of the speed of

light in vacuum to that in the medium. When a light ray enters a transparent medium, with parallel

surfaces, normal to one of the faces the ray slows down and when it emerges from the other side it

continues in the same direction at the original speed. If on the other hand, light (for eg.

monochromatic) strikes the surface at an angle other than 900, it is refracted. This is true for

substances that are optically isotropic. These include amorphous substances and crystals belonging to

cubic system. In crystals of the other systems a ray of light is split in to two rays that usually

propagate at different velocities within the crystal. White light consists of photons of different

wavelength, vibrating along planes with different orientation in space. Monochromatic light consists

of photons of the same wavelength still vibrating along planes with different orientations. If either

white light or monochromatic light is passed through a crystal or other atomically or molecularly

ordered substance (such as a Polaroid sheet) only light whose vector (electric) is vibrating on a plane

that can pass through the layer of atoms or molecules will emerge. ie polarization occurs. Because of

their complex atomic structure these substances can; (i) let polarized light to pass through (ii) let

some light to pass through (iii) stop polarized light (iv) rotate the polarization plane with either

positive or negative helicity.

Molecular symmetry and chirality

A molecule can have only one mirror image. If the image is non-superimposable on the

original, the molecule and its mirror image form two distinct species called enantiomers. Such

molecules are called chiral. Chirality is a necessary and sufficient condition for the occurrence of

enantiomerism and is determined by the absence of rotation-reflection symmetry (Sn axis) in the

molecule. All molecules belonging to the point groups C1, Cn and Dn lack reflection symmetry and

are chiral. Three terms have almost been interchangeably used to describe molecules, which show

enantiomerism – asymmetric, dissymmetric and chiral. The term chiral is synonymous with

dissymmetry. The term asymmetric points to molecules, which are chiral and lacks all symmetry

element except the trivial C1 axis.

Right circularly

Polarized, ER

Left circularly

Polarized, EL

(Looking along the propagating

beam from the source)

Plane of polarization

Resultant electric

field, E

Lecture notes CM

Present achiral

Molecule Sn

Absent chiral, dissymmetric No Cn asymmetric

(C1, Cn and Dn) (C1)

OPTICAL ROTATORY DISPERSON (ORD)

As mentioned above, a wave of plane polarized light may be considered to be made up of two

types of circularly polarized light – the right circularly polarized wave and the left circularly

polarized wave. The electric field of a right circularly polarized wave may be considered as a right

handed screw or helix twisting around the direction of propagation and the left circularly polarized

wave describes a left-handed screw or helix. The resultant of these two represents the linearly

polarized wave. In linearly polarized light the electric field vector changes its magnitude sinusoidaly

in a plane along the direction of propagation. In circularly polarized light the magnitude of the vector

remain constant, but its direction changes continuously in a helical manner. This can be explained

using the following figures.

ELP: Electric field of linearly polarized light

ERCP: Electric field of right circularly polarized light

ELCP: Electric field of left circularly polarized light

When a linearly polarized light enters an anisotropic medium the left and right circularly

polarized waves travel with different velocities. As a result they have different refractive indices.

Now the anisotropic medium is said to be ‘circularly birefringent’. That is it has unequal refractive

indices for right and left circularly polarized light. Since the velocity of a light in a medium is given

by

, where c is the velocity of light in vacuum and n is the refractive index of the medium, the

result of circular birefringence is an unequal rate of propagation of the left and right circularly

polarized rays. For eg. If the right circularly polarized ray travels faster than the left circularly

polarized ray, the result is that the light is still linearly polarized but the plane of polarization is no

Plane of polarization

ELP

ELCP ERCP ELP

ELCP ERCP

ELCP ELCP

ELCP

ERCP ERCP

ERCP

ELP

ELP (negative)

Lecture notes CM

longer in the xz-plane, instead it will make an angle with the plane. That is the circularly

birefringent medium has rotated the plane of polarization by an angle . The situation is shown in the

following figure. If the right circularly polarized ray travels faster

is positive and the medium is dextrorotatory, whereas if the left

circularly polarized ray travels faster is negative and the medium is

levorotatory. The angle of rotation for unit path length is given by

, Where nL and nR are the indices of refraction for

the left and right circularly polarized light respectively. is the

vacuum wavelength of the light. A more convenient term specific

rotation is calculated using the following equation: [ ]

. It is

calculated for a path length of 1 dm and c is the concentration of the

sample in g/ml. The molar rotation is given by the equation;

[ ]

[ ]

. M is the molecular mass. (Since large numbers are usually obtained for molar rotation

it is a common practice to divide the result by 100).

Since refractive index is related to polarizability, the circular birefringence can be correlated

to some dissymmetry of polarizability in the molecule. The dissymmetry of polarizability may arise

in two ways or a combination of the two. The first way may be explained by taking the molecule

brochloroiodomethane, CHClBrI. Here dissymmetry of polarizability arises due to the differences in

polarizability of the groups attached to the asymmetric carbon atom. This is called atomic

asymmetry. The second way is illustrated by methylethylpropylmethane.

CH3CH2CH(CH3)CH2CH2CH3. In this case the dissymmetry of polarizability arises due to spatial

arrangement (conformation) of the groups in the molecule. This is called conformational asymmetry

and usually makes a larger contribution to molecular rotation than does atomic asymmetry.

CIRCULAR DICHROISM (CD)

Just as dissymmetric media generally have different indices of refraction for right and left

circularly polarized light their intensity of absorption (absorption coefficient) also differ. Circular

dichroism is the difference in the absorption of left circularly polarised light (L-CPL) and right

circularly polarised light (R-CPL) and occurs when a molecule contains one or more chiral

chromophores (light-absorbing groups).

Circular dichroism = ΔA(λ) = A(λ)LCPL - A(λ)RCPL, where λ is the wavelength.

Circular dichroism (CD) spectroscopy is a spectroscopic technique where the CD of molecules is

measured over a range of wavelengths. Structural, kinetic and thermodynamic information about

macromolecules can be derived from circular dichroism spectroscopy. For eg. the following figure

shows the CD spectra of the two enantiomers of camphor sulphonic acid.

The two enantiomers can be clearly distinguished from the spectra. Circular dichroism spectra are

generally suitable for advanced spectral analysis.

E

ER

EL

x

z

y

220 290 320 nm

CD

(1S)-(+)- camphor-10- sulphonic acid

220 290 320 nm

CD

(1R)-( )- camphor-10- sulphonic acid

Lecture notes CM

ORD Spectra

Circular Dichroism (CD) is difficult to measure and it is more convenient to measure a

combination of circular dichroism and circular birefringence known as the Cotton effect. It may be

studied by observing the change of optical rotation with wavelength, called ‘optical rotatory

dispersion’ (ORD). there are three types of rotator dispersion curves: (a) Plain curves (b) Single

Cotton effect curves (c) multiple Cotton effect curves.

(a) Plain curves: These show no maximum or minimum and are smooth curves. They may be

positive or negative according as the rotation become more positive or negative as the wave

length changes from longer to shorter values. Plain curves are also referred to as normal

curves.

(b) Single Cotton effect curves: These are anomalous dispersion curves which show a maximum

and a minimum which occur in the region of maximum absorption. The curves are said to be

positive or negative according as the peak or trough occurs in the longer wave length. The

above figure shows both positive and negative cotton curves. The vertical distance between

the peak and trough is called the amplitude and the horizontal distance is the breadth of the

cotton curve. The point at which curves crosses the zero axis of rotation corresponds very

closely to UV absorption region.

(c) Multiple Cotton effect curves: Multiple cotton effect curves show two or more peaks and

corresponding number of troughs. Such curves are generally obtained in the case of

complicated molecules.

Applications of CD and ORD curves

CD and ORD curves are extremely useful for providing structural and configurational

information. Two procedures are generally adopted: (i) a comparison method in which the dispersion

curve of a compound of unknown configuration is compared with those of reference compounds of

similar structure with known absolute configuration (ii) a semi-quantitative approach based on

comparison of experimental parameters such as sign of Cotton effect, its amplitude and position with

those estimated from certain empirical or semi-empirical rules.

Use of plain curves: optical rotation of chiral compounds are generally represented for wavelength of

589 nm (sodium D-line) which is quite far from UV region where electronic transition of most

organic compounds takes palace. As a result the values of specific rotations at this wavelength are not

usually high. In some cases the rotation at D-line of sodium is so small that it cannot be detected;

however, it is usually greater in the UV region. Some compounds on the other hand may remain

optically inactive throughout the accessible region and thus may constitute a racemic mixture.

Plane curves may be of importance in making configurational assignments in cases where the

rotator dispersion curve crosses the zero axis of rotation. iodophenoxy)propionic acid is an

example.

300 nm 700 nm

(+)

( )

[ ]

300 nm 700 nm

(+)

( )

[ ]

peak

trough

Positive cotton curve

Negative cotton curve

Single Cotton effect curves Plain curves

Lecture notes CM

The ortho isomer shows levorotation at longer wavelengths, crosses the zero rotation axis and

become dextrorotatory at shorter wavelengths. But all the three have the same absolute configuration

R. below about 400 nm all three isomers of same configuration have same sign of rotation. Thus we

can distinguish between the ortho and other isomers.

Curves with Cotton effect: Curves which exhibit cotton effects are much more useful and give

information on structure, configuration and conformation of the molecules. Studies on the ORD

curves of steroid and terpenoid skeleton showed that the sign, magnitude and overall shape of the

Cottton effect curve can be closely correlated with the immediate structural and stereochemical

environment of the carbonyl group and are little affected by the structural changes away from this

group.

The keto group absorbs in the UV region around 280 – 290 nm and this absorption generally

leads to a Cotton effect. Thus the position or configuration of a carbonyl group in a compound can be

found by comparing its cotton curve with those of suitable analogs.

OCTANT RULE

The octant rule is an empirical rule which permits one to deduce the sign of the Cotton effect for a

considerable number of compounds from their structure, configuration, and conformation. This is

generally used in the case of ketosteroids. The compound to be studied is considered to be oriented in

a three dimensional coordinate system as shown below.

The midpoint of the C = O bond is taken as the origin of the system. The space around the C = O

group is divided into eight sectors (octants) with the help of three orthogonal planes a, B, and C

defined by xz, xy and yz respectively. The vertical plane A bisects the cyclohexane chair and passes

through C1, C2 and O. The horizontal plane B contains the C = O moity and the two attached carbon

atoms C2 and C6. The C = O double bond is made the x- axis with origin at the midpoint of the bond.

The projection contains four back octants. The sign of each octant is obtained from the sign of the

(+)

( )

(0)

400 nm

ortho

para

meta iodophenoxy)

propionic acid

x

y

-y z

z

y

1

2

3

4

5

6

1

6

2

5

4

3

Lecture notes CM

product of the coordinates of any given atom. For example atom 3 has coordinates, x, y and +z.

The product is +xyz. On the other hand for atom 5 the coordinates are x, +y, +z. The product is

xyz. Since it is unusual for substituents to lie in front of the oxygen atom, front octants are generally

unoccupied.

The octant rule states that atoms lying in the back upper left and back lower right octants

make positive contribution to cotton effect, atoms in the back lower left and back upper right octants

make negative contribution to cotton effect, and atoms lying in any of the three planes make no

contribution. Since the contribution from hydrogen atoms are insignificant they are ignored.

Contribution of the substituents lying in different sectors towards the sign of the Cotton effect are

considered according to the following rules:

1. Substuents lying in the coordinate planes contribute negligibly and are usually ignored.

2. Substituents lying in the (+) sectors make positive contribution and substituents lying in the

() sectors make negative contribution to the Cotton effect. This is generally true for

substituents which are more polarisable than hydrogen atom. On the other hand fluorine atom

which is less polarizable than hydrogen does not conform to octant rule.

3. The axial substituents on C2 and C6 contribute strongly to Cotton effect while equatorial

substituents on C2 and C6 do not contribute much as they lie in plane B.

Axial Haloketone Rule

When a halogen atom is introduced into the α-position of a cyclohexanone, and if the

orientation is equatorial, there will be no change in the sign of the ORD curve. But if it is in the axial

position the sign of the ORD curve changes. The Cotton effect of axial α-halocyclohexanone may be

predicted by viewing along the O = C axis in a model so placed that the carbonyl group occupies the

head of the chair (or boat) close to the observer. If the halogen is now on the left of the line of view

the compound will exhibit a negative cotton effect and if it is on the right a positive Cotton effect will

be observed. Fluoroketones do not follow axial haloketone rule.

16

5

4

3

2

Positive cotton effect

1 2

3 4 5

6

a

e

a a

a

e

e e

Plane B

Plane A

+

+

Plane B

Plane A

Upper Left

(+) Upper Right

()

Lower Left

() Lower right

(+)

1 2

3

4 5

6

+

+

X

2

Lecture notes CM

16

5

43

2

X

Negative cotton effect

Applications

Conformation of (+) 3- methy cyclohexanone: Since cyclohexanone does not contain a chiral centre

let us consider 3-methyl cyclohexanone, which has a chiral centre at C3. Two possible orientations

are equatorial and axial methyl. To apply octant rule the two forms are drawn with carbonyl bond

horizontal.

12

34

5

6

R-(+)

Positive cotton curve. Negative Cotton curve

According to octant rule the equatorial conformaer has a positive Cotton effect, as the Me group fall

in the positive sector. On the other hand the axial conformer display negative Cotton effect as the Me

group fall in the negative sector. Thus the sign of the ORD curve will be expected to be positive if

methyl group is equatorial and negative if axial. The observed sign is positive and so the orientation

is equatorial. Thus if we know the sign of the ORD curve we can elucidate the conformation.

However, since the equatorial conformation is the preferred one, on this basis we can predict sign of

ORD curve.

Reference:

1. Stereochemistry – D. Nasipuri, P 486 – 89

2. Stereochemistry of Organic compounds – E. L. Eliel, P. 399 – 433

3. http://en.wikipedia.org.wiki/

4. http://www.photophysics.com/chiroscan

5. http://www.nsmbuffalo.edu/~jocher

16

5

4

3

2

Methyl equatorialMethyl axial

1

6

5

4

3

2

+

+

X

2

+

+

2

Me 3 4 5

6 +

+

2

Me

3 4 5

6

Lecture notes CM