OPTICAL ISOMERISM A guide for A level students

1. OPTICAL ISOMERISM A guide for A level students KNOCKHARDY PUBLISHING

2. TYPES OF ISOMERISM CHAIN ISOMERISM STRUCTURAL ISOMERISM POSITION ISOMERISM Same molecular formula but different structural formulae FUNCTIONAL GROUP ISOMERISM E/Z ISOMERISM Occurs due to the restricted rotation of C=C double bonds... two forms - CIS and TRANS STEREOISOMERISM Same molecular formula but atoms occupy different positions in space. OPTICAL ISOMERISM Occurs when molecules have a chiral centre. Get two non-superimposable mirror images.

3. OPTICAL ISOMERISM Occurrenceanother 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.

4. OPTICAL ISOMERISM Occurrenceanother 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. CHIRAL CENTRES 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

5. OPTICAL ISOMERISM SPOTTING CHIRAL CENTRES Look at each carbon atom in the chain and see what is attached to it. For a chiral centre you 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 C 3 H’s around it NOT chiral C 2 H’s around it NOT chiral C 2 H’s around it NOT chiral C 2 H’s around it NOT chiral CH3CH2CH2CH2Cl  1-chlorobutane

6. OPTICAL ISOMERISM SPOTTING CHIRAL CENTRES Look at each carbon atom in the chain and see what is attached to it. For a chiral centre you 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 C 3 H’s around it NOT chiral C 2 H’s around it NOT chiral C 2 H’s around it NOT chiral C 2 H’s around it NOT chiral CH3CH2CH2CH2Cl  1-chlorobutane CH3CH2CHClCH3 C 3 H’s around it NOT chiral C 2 H’s around it NOT chiral C H, CH3, Cl,C2H5 around it CHIRAL C 3 H’s around it NOT chiral  2-chlorobutane

7. OPTICAL ISOMERISM SPOTTING CHIRAL CENTRES Look at each carbon atom in the chain and see what is attached to it. For a chiral centre you 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 C 3 H’s around it NOT chiral C 2 H’s around it NOT chiral C 2 H’s around it NOT chiral C 2 H’s around it NOT chiral CH3CH2CH2CH2Cl  1-chlorobutane CH3CH2CHClCH3 C 3 H’s around it NOT chiral C 2 H’s around it NOT chiral C H, CH3, Cl,C2H5 around it CHIRAL C 3 H’s around it NOT chiral  2-chlorobutane (CH3)2CHCH2Cl C 3 H’s around it NOT chiral C 2 CH3’s around it NOT chiral C 2 H’s around it NOT chiral  1-chloro-2-methylpropanane (CH3)3CCl C 3 H’s around it NOT chiral C 3 CH3’s around it NOT chiral  2-chloro-2-methylpropanane

8. OPTICAL ISOMERISM 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

9. OPTICAL ISOMERISM 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 aremirror images and superimposable spoons • superimposable but not mirror images books • non-superimposable mirror images hands

10. OPTICAL ISOMERISM 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 aremirror 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

11. OPTICAL ISOMERISM What is a non-superimposable mirror image? Animation doesn’t work in old versions of Powerpoint

12. OPTICAL ISOMERS - DIFFERENCE • 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

13. OPTICAL ISOMERS - DIFFERENCE • 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 haveturned to the rightturned to the left • DEXTROROTATORY LAEVOROTATORY • d or + form l or - form

14. OPTICAL ISOMERS - DIFFERENCE • 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 haveturned to the right turned to the left • DEXTROROTATORY LAEVOROTATORY • d or + form l or - form • Racematea 50-50 mixture of the two enantiomers (dl) or (±) is a racemic mixture. • The opposite optical effects of each isomer cancel each other out • ExamplesOptical 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

15. A B D C E F OPTICAL ISOMERISM The polarimeter 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 If the light appears to have turned to the rightturned to the left DEXTROROTATORYLAEVOROTATORY

16. OPTICAL ISOMERISM 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

17. OPTICAL ISOMERISM 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

18. OPTICAL ISOMERISM 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 The reactionproduces a mixture of the two optical isomers because both modes of attack are possible

19. OPTICAL ISOMERISM 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 H+ / H2O HCN

20. OPTICAL ISOMERISM 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 H+ / H2O HCN During the first stage, the nucleophilic CN- ion can attack from below, or above, the aldehyde. A mixture of the two enantiomers is formed.

21. OPTICAL ISOMERISM 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 H+ / H2O HCN 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.

22. OPTICAL ISOMERISM - THALIDOMIDE 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.

23. OPTICAL ISOMERISM – Other 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.