A Level Chemistry: Optical Isomerism — Revision Notes

Condensed for revision. For the full explanation, use the Optical Isomerism and Chirality study guide, then test yourself with the practice questions. For the AS basics (structural isomerism, cis/trans isomerism and identifying chiral centres), see the AS Introduction to Organic Chemistry revision notes.

Syllabus: Cambridge International AS & A Level Chemistry 9701, 2025–2027, A Level content: subtopic 29.4 Isomerism: optical.

Recap from AS: chiral centres

• A chiral centre is a carbon atom bonded to four different atoms or groups.
• A molecule with one chiral centre exists as two optical isomers, called enantiomers: mirror images that are non-superimposable.
• To draw the pair: show the chiral carbon with two bonds in the plane of the paper, one wedge (towards you) and one hashed (away from you), then draw its mirror image. Swapping any two groups on the chiral centre also gives the other enantiomer.

Molecule	Structural formula	Chiral centres	Reason
butan-2-ol	CH₃CH(OH)CH₂CH₃	1 (C2)	C2 carries H, OH, CH₃ and C₂H₅
propan-2-ol	CH₃CH(OH)CH₃	0	C2 carries two identical CH₃ groups
2-hydroxypropanoic acid (lactic acid)	CH₃CH(OH)COOH	1 (C2)	C2 carries H, OH, CH₃ and COOH
2-aminopropanoic acid (alanine)	CH₃CH(NH₂)COOH	1 (C2)	C2 carries H, NH₂, CH₃ and COOH
aminoethanoic acid (glycine)	H₂NCH₂COOH	0	the CH₂ carbon has two identical H atoms
2-bromo-3-chlorobutane	CH₃CHBrCHClCH₃	2 (C2 and C3)	C2: H, Br, CH₃, CHClCH₃; C3: H, Cl, CH₃, CHBrCH₃

A molecule can contain more than one chiral centre, as the last example shows. You need to be able to spot them; meso compounds and the term diastereoisomers are not required.

Properties of enantiomers (29.4, outcome 1)

Enantiomers have identical physical and chemical properties, apart from:

1. their ability to rotate plane-polarised light (in opposite directions), and
2. their potential biological activity.

Property	Same or different for the two enantiomers?
Melting point, boiling point, density, solubility	same
Reactions with ordinary (non-chiral) reagents	same
Direction of rotation of plane-polarised light	different (opposite)
Biological activity (for example as a drug)	can be different

Biological activity can differ because receptor sites and enzymes in the body are themselves chiral. Only one enantiomer may have the right three-dimensional shape to fit a particular receptor or active site.

Optical activity and racemic mixtures (29.4, outcomes 2 and 3)

Plane-polarised light is light whose oscillations are in one plane only.

Optically active: a substance that rotates the plane of plane-polarised light. A single enantiomer is optically active.

Effect of the two optical isomers of a single substance:

• Each enantiomer rotates the plane of polarised light by the same angle (under the same conditions) but in opposite directions.
• One enantiomer rotates the plane clockwise, the other anticlockwise.

Racemic mixture: an equimolar (50:50) mixture of the two enantiomers. It is not optically active: the rotation caused by one enantiomer is exactly cancelled by the equal and opposite rotation caused by the other, so there is no net rotation.

single enantiomer A        → rotates the plane by +θ (clockwise)
single enantiomer B        → rotates the plane by −θ (anticlockwise)
racemic mixture, 50% A : 50% B → net rotation = 0; optically inactive

Note that the individual molecules in a racemic mixture are still chiral. The mixture is inactive only because the two rotations cancel.

Chirality and the synthesis of drug molecules (29.4, outcome 4)

Why a synthesis often gives a racemic mixture

When a chiral centre is created during a reaction from non-chiral starting materials, both enantiomers usually form in equal amounts. For example, in nucleophilic addition of HCN to an unsymmetrical aldehyde or ketone, the C=O group is planar, so the CN⁻ nucleophile is equally likely to attack from either side, giving a racemic mixture.

(a) Different biological activity of the two enantiomers

• One enantiomer may be the active drug; the other may be less active, inactive, or have harmful side effects.
• Thalidomide is the standard example: one enantiomer was the intended sedative and the other was linked to birth defects. (The two enantiomers of thalidomide also interconvert in the body, so a pure enantiomer would not have removed the risk.)

(b) The need to separate a racemic mixture

Giving a drug as a single, pure enantiomer means:

• a smaller dose is needed (the inactive half is not given),
• the risk of side effects from the other enantiomer is reduced.

But separating a racemic mixture into two pure enantiomers is difficult and expensive, because the enantiomers have identical physical properties (same boiling point, same solubility), and up to half of the product may be wasted.

(c) Chiral catalysts

A chiral catalyst makes the reaction produce (mainly) a single pure optical isomer directly. Advantages:

• no need to separate a racemic mixture afterwards,
• less waste of starting materials and product, so lower cost,
• a purer drug with fewer potential side effects.

Exam traps

• A chiral centre needs four different groups. Two identical groups (two CH₃, or two H) on the carbon means it is not chiral: propan-2-ol and glycine have none.
• Enantiomers are not different in melting point, boiling point or ordinary reactions. The only differences in the syllabus are the rotation of plane-polarised light and biological activity.
• The two enantiomers rotate the plane by the same angle in opposite directions. “Different angles” is wrong.
• A racemic mixture is optically inactive because the rotations cancel, not because the molecules are not chiral.
• “Racemic” means equal amounts of the two enantiomers. A 70:30 mixture is not racemic and still rotates the plane of polarised light.
• When explaining a racemic product from HCN addition, mention the planar carbonyl group and attack from either side with equal probability.
• Look for chiral centres in every carbon of a larger molecule; there can be more than one.

Self-test

1. What is meant by a chiral centre?
2. How many chiral centres are there in butan-2-ol, CH₃CH(OH)CH₂CH₃?
3. How many chiral centres are there in propan-2-ol, CH₃CH(OH)CH₃? Explain.
4. Identify the chiral centres in 2-bromo-3-chlorobutane, CH₃CHBrCHClCH₃.
5. State the two ways in which the properties of a pair of enantiomers can differ.
6. Describe the effect of each of the two optical isomers of lactic acid on plane-polarised light.
7. Define a racemic mixture and explain why it is not optically active.
8. Explain why the reaction of HCN with propanal, CH₃CH₂CHO, gives a racemic mixture.
9. Give two reasons why a drug may be better supplied as a single enantiomer than as a racemic mixture.
10. State one advantage of using a chiral catalyst instead of separating a racemic mixture.

Answers:

1. A carbon atom bonded to four different atoms or groups.
2. One (C2, bonded to H, OH, CH₃ and C₂H₅).
3. None: C2 carries two identical CH₃ groups, so it is not bonded to four different groups.
4. Two: C2 (H, Br, CH₃, CHClCH₃) and C3 (H, Cl, CH₃, CHBrCH₃).
5. Their ability to rotate plane-polarised light (opposite directions), and their potential biological activity.
6. Each rotates the plane of plane-polarised light by the same angle, one clockwise and the other anticlockwise.
7. An equimolar (50:50) mixture of the two enantiomers. The rotations caused by the two enantiomers are equal and opposite, so they cancel and there is no net rotation.
8. The C=O group in propanal is planar, so CN⁻ is equally likely to attack the carbonyl carbon from either side. The product, CH₃CH₂CH(OH)CN, has a chiral centre, and the two enantiomers form in equal amounts.
9. Any two of: only one enantiomer may be active, so a smaller dose is needed; the other enantiomer may cause harmful side effects, which are avoided; no dose is wasted on an inactive enantiomer.
10. Any one of: produces a single pure optical isomer directly, so no separation is needed; less waste; lower cost.

These are original notes written for revision. Drug examples are given for illustration of the syllabus ideas only. Check the full syllabus wording in the official 9701 syllabus.