Optical Activity

Lesson
The Physical Properties of Diastereomers
How do enantiomers differ from each other ?

Enantiomers share many of the same

properties—they have the same boiling
points, the same melting points, and the
same solubilities.

However, enantiomers differently

interact with plane polarized light
 Plane polarized light

Normal light consists of electromagnetic waves that oscillate in all directions

in contrast, plane polarized light has one single plane of vibrations

 Chiral compounds can rotate plane polarized light
In 1815, physicist Jean-Baptiste Biot discovered that certain naturally occurring organic substances such as camphor and
oil of turpentine are able to rotate the plane of polarization.

A compound that rotates the plane of polarization is said to be optically active

• chiral compounds are optically active.

• achiral compounds are optically inactive.
 Polarimeter
• The degree of optical rotation caused by an optically active substance can be measured by
using a polarimeter

Observed rotation [a] depends on

1. concentration(c) of the test solution
2. Path length (length of the sample tube)
3. Temperature
4. Wavelength of the light
 Specific rotation

Observed rotation (degrees) of a solution having the compound concentration of 1.0 g/ml
in a sample tube 1.0 dm long at specified temperature and the wave length 589 nm is
used
𝑇 𝛼
[ 𝛼] =𝜆
𝑙 ×𝑐

Where =specific rotation

= observed rotation
= length of the sample tube
= concentration of the sample
If an optically active compound rotates the plane of polarization clockwise, it is called
dextrorotatory, indicated by (+) or D or d

If an optically active compound rotates the plane of polarization anticlockwise, it is

called levorotatory, indicated by (-) or L or l

Do not confuse D and L with R and S.

 Exercise
The observed rotation of 2.0 g of a compound in 50 mL of solution in a polarimeter tube 50 cm long is +13.4°. What is
the specific rotation of the compound?

𝑇 𝛼
[ 𝛼] =𝜆
𝑙 ×𝑐
 Racemic mixture Racemus = bunch of grapes

A solution in which both enantiomers of a compound are present in equal amounts

is called a racemic mixture (racemate)
Racemic mixtures do not rotate the plane of polarized light.
 Optical Purity and Enantiomeric Excess

an enantiomerically pure compound contains only one enantiomer

e.g. specific rotation of (S)-(+) -2-bromobutane is + 23.1 o

• if the specific rotation of a given sample of 2-bromobutane is + 23.1 o ???????

This means the given sample contains only (S) isomer and the sample is optically pure

• if the specific rotation of a given sample of 2-bromobutane is < +23.1 o ???????

This means the given sample contains both (S) and (R) isomers , but S isomer is in excess
For example, if a sample of 2-bromobutane has an observed specific rotation of + 9.2 o . What is the optical purity of the
sample

Enantiomeric Excess
 Resolution (Separation) of enantiomers

Enantiomers have identical chemical and physical properties (identical boiling points and solubilities)

Therefore, they cannot be separated by usual separation techniques such as distillation , crystallization etc
 Chiral drugs
• Approximately one-third of the drugs we are using today are either naturally occurring substances or their chemical
modifications.

• most of the drugs derived from natural sources are chiral and are almost always obtained as a single enantiomer

• However until recently many synthetic drugs were prepared, sold and administered as racemic mixtures because
separation of racemates into individual enantiomers is a costly process

• In a racemic mixture, both enantiomers are not equally active , or sometimes one enantiomer may cause severe
side effects

(S)-(+)-ketamine is four times more potent

an anesthetic than (R)-(-) –ketamine
(R)-(-) –ketamine shows more disturbing
side effects
 Thalidomide disaster 1953
• Sedative and antinausea drug, administered as
a racemic mixture (in 1950’s)

• (R)-thalidomide showed stronger sedative

properties than S isomer

• Pregnant women used to take thalidomide to

overcome disturbance due to morning sickness

• Later recognized that the levorotatory isomer

was highly teratogenic (unfortunately it took 3
years to realize the true effect)
Thousands of infants were born with severe birth
defects. They ranged from brain damage to
deformed limbs.

Thalidomide recently has been approved by FDA, with

restrictions, to treat leprosy as well as melanomas
 Prochirality

If a carbon is bonded to two hydrogens and to two different groups, the two hydrogens are called enantiotopic hydrogens

The C atom which bears two enantiotopic Hydrogens is called prochiral C

If we replace one enantiotopic Hydrogen with deuterium atom , then the molecule becomes chiral

D
3
Ha

replace Ha with D
HO CH3
HO CH3 1 2

Hb
Hb
S configuration

HO
1

D CH3
3 2

Ha

R configuration
 Prochirality

OH
O
Alcohol dehydrogenase
Ha Hb
H3C Hb
CH3
Acetaldehyde

Ethanol

when the oxidation of ethanol to acetaldehyde is catalyzed by the enzyme alcohol

dehydrogenase, only one of the enantiotopic hydrogens is removed

Enzyme will identify only one enantiotopic hydrogen

diastereotopic hydrogens.