Optical isomerism

OPTICAL OPTICAL ISOMERISMISOMERISM

A guide for A level studentsA guide for A level students

KNOCKHARDY PUBLISHINGKNOCKHARDY PUBLISHING

TYPES OF ISOMERISMTYPES OF ISOMERISM

Occurs due to the restricted rotation of C=C double bonds... two forms - CIS and TRANS

STRUCTURAL ISOMERISM

STEREOISOMERISM

E/Z ISOMERISM

OPTICAL ISOMERISM

CHAIN ISOMERISM

Same molecular formula but different structural formulae

Occurs when molecules have a chiral centre. Get two non-superimposable mirror images.

Same molecular formula but atoms occupy different

positions in space.

POSITION ISOMERISM

FUNCTIONAL GROUP ISOMERISM

OPTICAL ISOMERISMOPTICAL ISOMERISM

Occurrence another form of stereoisomerism occurs when compounds have non-superimposable mirror images

Isomers the two different forms are known as optical isomers or enantiomers they occur when molecules have a chiral centre a chiral centre contains an asymmetric carbon atom

an asymmetric carbon has four different atoms (or groups)arranged tetrahedrally around it.


Occurrence another form of stereoisomerism occurs when compounds have non-superimposable mirror images

Isomers the two different forms are known as optical isomers or enantiomers they occur when molecules have a chiral centre a chiral centre contains an asymmetric carbon atom

an asymmetric carbon has four different atoms (or groups)arranged tetrahedrally around it.

There are four different colours arranged tetrahedrally about

the carbon atom

2-chlorobutane exhibits optical isomerism because the second carbon atom has four

different atoms/groups attached

CHIRAL CENTRES


SPOTTING CHIRAL CENTRES

Look at each carbon atom in the chain and see what is attached to it. For a chiral centreyou need an asymmetric carbon with four different atoms/groups) arranged tetrahedrally around it.

IF A CARBON HAS MORE THAN ONE OF ANY ATOM/GROUP ATTACHED, IT CAN’T BE CHIRAL

CH3CH2CH2CH2Cl C 3 H’s around it NOT chiralC 2 H’s around it NOT chiralC 2 H’s around it NOT chiralC 2 H’s around it NOT chiral

1-chlorobutane





CH3CH2CHClCH3


C 3 H’s around it NOT chiralC 2 H’s around it NOT chiralC H, CH3, Cl,C2H5 around it CHIRALC 3 H’s around it NOT chiral

1-chlorobutane

2-chlorobutane





CH3CH2CHClCH3


C 3 H’s around it NOT chiralC 2 H’s around it NOT chiralC H, CH3, Cl,C2H5 around it CHIRALC 3 H’s around it NOT chiral

(CH3)3CCl C 3 H’s around it NOT chiralC 3 CH3’s around it NOT chiral

1-chlorobutane

2-chlorobutane

2-chloro-2-methylpropanane

(CH3)2CHCH2Cl C 3 H’s around it NOT chiralC 2 CH3’s around it NOT chiralC 2 H’s around it NOT chiral1-chloro-2-methylpropanane


Spatial differences between isomers

• two forms exist which are NON-SUPERIMPOSABLE MIRROR IMAGES of each other• non-superimposable means you you can’t stack one form exactly on top of the other




Some common objects are mirror images and superimposable spoons superimposable but not mirror images books non-superimposable mirror images hands




Some common objects are mirror images and superimposable spoons superimposable but not mirror images books non-superimposable mirror images hands

NB For optical isomerism in molecules, both conditions must apply...they must be mirror images AND be non-superimposable


What is a non-superimposable mirror image?

Animation doesn’t work in old versions of Powerpoint

OPTICAL ISOMERS - OPTICAL ISOMERS - DIFFERENCEDIFFERENCE

• isomers differ in their reaction to plane-polarised light• plane polarised light vibrates in one direction only• one isomer rotates light to the right, the other to the left• rotation of light is measured using a polarimeter• rotation is measured by observing the polarised light coming out towards the observer



• If the light appears to have turned to the right turned to the left

DEXTROROTATORY LAEVOROTATORYd or + form l or - form



• If the light appears to have turned to the right turned to the left

DEXTROROTATORY LAEVOROTATORYd or + form l or - form

Racemate a 50-50 mixture of the two enantiomers (dl) or (±) is a racemic mixture. The opposite optical effects of each isomer cancel each other out

Examples Optical activity is common in biochemistry and pharmaceuticals• Most amino acids exhibit optical activity• many drugs must be made of one optical isomer to be effective

- need smaller doses (safer and cost effective) - get reduced side effects - improved pharmacological activity


The polarimeter

If the light appears to have turned to the right turned to the left DEXTROROTATORY LAEVOROTATORY

A Light source produces light vibrating in all directions

B Polarising filter only allows through light vibrating in one direction

C Plane polarised light passes through sample

D If substance is optically active it rotates the plane polarised light

E Analysing filter is turned so that light reaches a maximum

F Direction of rotation is measured coming towards the observer

A B

C DE

F


How optical isomers can be formed

Carbonyl compounds undergo nucleophilic addition. If there are two different groups attached to the C=O bond, the possibility of forming optical isomers arises.

THE NUCLEOPHILIC ADDITION OF HCN TO ETHANAL

If the nucleophilic cyanide ion attacks from above one optical isomer is formed






However, attack from below, gives the non-superimposable mirror image of the first






However, attack from below, gives the non-superimposable mirror image of the first

The reaction produces a mixture of the two optical isomers because both modes of attack are possible


Synthesis of 2-hydroxypropanoic acid (lactic acid)

LACTIC ACID can be formed from ethanal in a two stage process.

1. Nucleophilic addition of hydrogen cyanide to ethanal

2 Hydrolysis of the nitrile group

HCN H+ / H2O






HCN H+ / H2O

During the first stage, the nucleophilic CN- ion can attack from below, or above, the aldehyde.

A mixture of the two enantiomers is formed.






HCN H+ / H2O

During the first stage, the nucleophilic CN- ion can attack from below, or above, the aldehyde.

A mixture of the two enantiomers is formed.

Acid hydrolysis of the mixture provides a mixture of the two lactic acid forms.

OPTICAL ISOMERISM - OPTICAL ISOMERISM - THALIDOMIDETHALIDOMIDE

The one obvious difference between optical isomers is their response to plane polarised light. However, some naturally occurring molecules or specifically synthesised pharmaceuticals show different chemical reactivity.

The drug, THALIDOMIDE is a chiral molecule and can exist as two enantiomers. In the 1960’s it was used to treat anxiety and morning sickness in pregnant women. Tragically, many gave birth to children with deformities and missing limbs.

It turned out that only one of the enantiomers (the structure on the right) was effective and safe; its optically active counterpart was not. The major problem was that during manufacture a mixture of the isomers was produced. The drug was banned world-wide, but not after tens of thousands of babies had been affected.

OPTICAL ISOMERISM – OPTICAL ISOMERISM – Other pointsOther points

The following points are useful when discussing reactions producing optical isomers.

The formation of racemic mixtures is more likely in a laboratory reaction than in a chemical process occurring naturally in the body.

If a compound can exist in more than one form, only one of the optical isomers is usually effective.

The separation of isomers will make manufacture more expensive.

A drug made up of both isomers will require a larger dose and may cause problems if the other isomer is ‘poisonous’ like thalidomide.

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Optical isomerism