OPTICAL ISOMERISM

All molecules have a mirror image but for most molecules it is the same molecule.

H C H H F H F

H C H

fluoromethane

 For some molecules the mirror image is a different molecule (the mirror image is non-superimposable).
OH C H COOH CH3 HOOC H3C OH C H

(-) lactic acid in sour milk

(+) lactic acid in muscles

 Left and right hands are an example of non-superimposable mirror images.

 This usually happens when a molecule contains a C atom with four different groups attached (chiral / asymmetric C). Such molecules are said to be chiral or optically active.
a C b c d d c a C b

 The optical isomers are called enantiomers. These are distinguished by +/-, D/L or more correctly R/S. A 50/50 mixture of the two enantiomers is called a racemic mixture or a racemate.

TASK Which of the following molecules are optically active?

1) 2) 3) 4) propan-2-ol 2-chlorobutane 1-chlorobutane 3-methylhexane 5) 6) 7) 8) butanone 2-methylbutanoic acid butan-2-ol 1-chloro-3-methylpentane

propan-2-ol

CH3

CH OH

CH3

NOT OPTICALLY ACTIVE

2-chlorobutane

CH3

CH Cl

CH2

CH3

CH2CH3 C H CH3 Cl H3C Cl

CH2CH3 C H

OPTICALLY ACTIVE

1-chlorobutane

CH2 Cl

CH2

CH2

CH3

NOT OPTICALLY ACTIVE

3-methylhexane

CH3 CH2 CH CH2 CH2 CH3 CH3

CH2CH2CH3 C H CH3 CH2CH3 CH3 CH3CH2

CH2CH2CH3 C H

OPTICALLY ACTIVE

butanone

O CH3 C CH2 CH3

NOT OPTICALLY ACTIVE

propan-2-ol

CH3

CH OH

CH3

NOT OPTICALLY ACTIVE

2-methylbutanoic acid
CH3 CH2

CH3 O CH C OH

CH2CH3 C CH3 H COOH

H HOOC

CH2CH3 C CH3

OPTICALLY ACTIVE

butan-2-ol
CH3 CH2

OH CH CH3

CH2CH3 C CH3 H OH
H HO

CH2CH3 C CH3

OPTICALLY ACTIVE

1-chloro-3-methylpentane
CH3 CH2

CH3 CH CH2

Cl CH2

CH2CH3 C CH3 H CH2CH2Cl

H CH2ClCH2

CH2CH3 C CH3

OPTICALLY ACTIVE

 Molecules that are optical isomers are called enantiomers. Enantiomers have identical chemical and physical properties, except:
Their effect on plane polarised light Their reaction with other chiral molecules

 Light is a form of electromagnetic radiation.

 The wave vibrations are perpendicular to the direction of travel of the wave.

normal light (wav es v ibrate in all directions)

plane-polarised light (v ibrates in only one direction)

plane-polarised light af ter clockwise rotation

 Optical isomers rotate the plane of plane polarised light.

(-)-enantiomer (anticlockwise rotation)

(+)-enantiomer (clockwise rotation)

()-racemate (no ov erall ef f ect)

http://scholar.hw.ac.uk/site/chemistry/activity5.asp?outline

 Chiral molecules often react differently with other chiral molecules. This is like the idea that a right hand does not fit a left handed glove the molecule must be the correct shape to fit the molecule it is reacting with. Many natural molecules are chiral and most natural reactions are affected by optical isomerism.

 For example, most amino acids (and so proteins) are chiral, along with many other molecules.

In nature, only one optical isomer occurs (e.g. all natural amino acids are rotate polarised light to the left).

 Many drugs are optically active, with one enantiomer only having the beneficial effect. In the case of some drugs, the other enantiomer can even be harmful, e.g. thalidomide.

 In the 1960s thalidomide was given to pregnant women to reduce the effects of morning sickness.
This led to many disabilities in babies and early deaths in many cases.

NH

O O

O O C

NH

H2C CH2

C N H O

H2C CH2

N H O

S thalidomide (effective drug)

R thalidomide (dangerous drug)

The body racemises each enantiomer, so even pure S is dangerous as it converts to R in the body.

 Thalidomide was banned worldwide when the effects were discovered.

However, it is starting to be used again to treat leprosy and HIV. Its use is restricted though and patients have to have a pregnancy test first (women!) and use two forms of contraception (if sexually active).

CH3 O

CH3 O

C H3C

CH2

H2C

C CH3

S carvone (caraway seed)

R carvone (spearmint)

Caraway Seed has a warm, pungent, slightly bitter flavour with aniseed overtones.

CH3

CH3

CH2

C CH3

H H3C

CH2

S limonene (lemons)

R limonene (oranges)