Main topic Organic Subtopic Optical isomerism Paper 2

Main topic: Organic Sub-topic: Optical isomerism Paper 2 and 3

Optical isomerism LO: What is optical isomerism How can you distinguish between optical isomers 2

Starter • Name and draw an example for each type of isomerism you have learnt so far. • Group them into: – Structural isomerism – Stereoisomerism 3

Same molecular formula but different arrangement of their atoms. Same molecular formula, but atoms joined up in different orders CHAIN ISOMERISM POSITIONAL ISOMERISM FUNCTIONAL GROUP ISOMERISM Same structural formula, but bonds are arranged differently in space. GEOMETRIC ISOMERISM (E/Z) OPTICAL ISOMERISM Rotation prevented by double bond. Nonsuperimposable mirror images.

Use the molymods to. . • Create 2 isomers of the same product when ethanal reacts with CN • Can you explain your results?

Synthesis of optically active compounds -: CN Equal chance of attack from above or below flat carbonyl group gives racemic mixture R C O R’ -: CN 6

• All molecules have a mirror image – but for most molecules it is the same molecule. 7

• For some molecules the mirror image is a different molecule (the mirror image is non-superimposable). 8

• Left and right hands are an example of non-superimposable mirror images. 9

What’s different? Carbon has 4 different groups attached 10

• This usually happens when a molecule contains a C atom with four different groups attached (chiral / asymmetric C). C • Such molecules are said to be chiral or optically active 11

• The optical isomers are called enantiomers • These are distinguished by +/-, D/L or R/S. (+ clockwise, - anticlockwise) • A 50/50 mixture of the two enantiomers is called a racemic mixture or a racemate (“rassemate”) 12

TASK 1. Some of the following molecules are optically active. 2. For each one, decide whether it is optically active or not. You can use the molymods to help you. 3. If it is draw out the structure and identify the chiral carbon with an * a) propan-2 -ol e) butanone b) 2 -chlorobutane f) 2 -methylbutanoic acid c) 1 -chlorobutane g) butan-2 -ol d) 3 -methylhexane h) 1 -chloro-3 -methylpentane 13

propan-2 -ol NOT OPTICALLY ACTIVE Click here to go back to the optical isomerism task 14

2 -chlorobutane OPTICALLY ACTIVE Click here to go back to the optical isomerism task 15

1 -chlorobutane NOT OPTICALLY ACTIVE Click here to go back to the optical isomerism task 16

3 -methylhexane OPTICALLY ACTIVE Click here to go back to the optical isomerism task 17

butanone NOT OPTICALLY ACTIVE Click here to go back to the optical isomerism task 18

propan-2 -ol NOT OPTICALLY ACTIVE Click here to go back to the optical isomerism task 19

2 -methylbutanoic acid OPTICALLY ACTIVE Click here to go back to the optical isomerism task 20

butan-2 -ol OPTICALLY ACTIVE Click here to go back to the optical isomerism task 21

1 -chloro-3 -methylpentane OPTICALLY ACTIVE Click here to go back to the optical isomerism task 22

• Molecules that are optical isomers are called enantiomers. • Enantiomers have identical and physical properties, except: • Their effect on plane polarised light; • Their reaction with other chiral molecules 23

Light is a form of electromagnetic radiation 24

• The wave vibrations are perpendicular to the direction of travel of the wave. 25

• Optical isomers rotate the plane of plane polarised light. Notice a racemic mixture of enantiomers has no effect on the rotation of plane polarised light – why? 26

• How would you describe the test to distinguish between enantiomers? Rotate plane polarised light in opposite directions Key phrase 27

POLARIMETERS can be used to analyse the effect optical isomers have on plane polarised light: Heriot Watt University has a web page with an interactive tutorial and self-test questions about this topic: http: //scholar. hw. ac. uk/site/chemistry/activity 5. asp? outline 28

• 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. 29

• 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 rotate polarised light to the left). 30

• Many drugs are optically active, with one only enantiomer only having the beneficial effect, the other is inactive. • 3 solutions to this problem: – Separate the 2 isomers Difficult & expensive – Sell the mixture as the drug Wasteful as half inactive Nurofen – Design an alternative way of synthesising making only the required isomer Expensive and time-consuming Naproxen 31

What’s the story here? In the case of some drugs, the other enantiomer can even be harmful. The photographs are both from ‘Molecule of the Month’ at Bristol University: http: //www. chm. bris. ac. uk/motm/thalidomide/start. html 32

• In the 1960’s 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. The photographs are both from ‘Molecule of the Month’ at Bristol University: http: //www. chm. bris. ac. uk/motm/thalidomide/start. html 33

R thalidomide (effective drug) S thalidomide (dangerous drug) • Never tested on pregnant animals • Drug supplied as racemic mixture – isomers never tested separately • The body racemises each enantiomer, so even pure R is dangerous as it converts to S in the body. 34

• 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). 35

S carvone (caraway seed) Caraway Seed has a warm, pungent, slightly bitter flavour with aniseed overtones. R carvone (spearmint) 36

S limonene (lemons) R limonene (oranges) 37

The specification is clear (in three places) that your understanding of the formation of reacemic mixtures is limited to cases where there is a 50%: 50% chance of either enantiomer due to the equal possibility of attack from either side of a planar e. g. carbonyl group , C=O. Here’s what is says… (3 separate entries) So you could skip the next slide… which is about how non-racemates form

Synthesis of optically active compounds -: CN Equal chance of attack from above or below flat carbonyl group gives racemic mixture R C O R’ -: CN 39

Exam question plenary (c) State the type of isomerism shown by 2 hydroxypropanoic (lactic) acid, CH 3 CH(OH)COOH, and point out the structural feature of the molecule which causes the existence of two isomers. With the aid of diagrams, show the structural relationship between the two isomers and state how these isomers can be distinguished. Type of isomerism . . . . . . Structural feature . . . . . . Isomer 1 Isomer 2 Method of distinguishing . . . . . . (5) 40

Answer (c) Type of isomerism: optical (1) Structural feature: atom with 4 different substituents or asymmetric or chiral (1) Isomer 1 Isomer 2 Method of distinguishing: opposite rotation of plane polarised light (1) (5) 41