Stereoisomerism including E-Z (geometric) isomerism in alkenes and optical isomerism in molecules with a chiral centre, the rotation of plane-polarised light, racemic mixtures, and the importance of stereochemistry in pharmaceuticals.

What this dot point is asking

CCEA wants you to identify and label E-Z isomers of alkenes, recognise a chiral centre and draw enantiomers, explain how optical activity relates to plane-polarised light, describe a racemic mixture, and explain why stereochemistry matters in drugs.

Stereoisomerism in context

Isomers share a molecular formula. Structural isomers differ in how the atoms are connected, but stereoisomers have the same connectivity and differ only in the arrangement of atoms in space. CCEA splits stereoisomerism into E-Z (geometric) isomerism, from restricted rotation about a double bond, and optical isomerism, from a chiral centre. A molecule can show one, both or neither.

E-Z (geometric) isomerism

The restricted rotation comes from the $\pi$ bond. A $\text{C}=\text{C}$ double bond is made of a $\sigma$ bond and a $\pi$ bond formed by the sideways overlap of $p$ orbitals. To rotate one end of the double bond relative to the other you would have to break the $\pi$ bond, which costs too much energy at room temperature, so the two ends are locked in place. In a single $\text{C}-\text{C}$ bond there is no $\pi$ bond and free rotation is possible, which is why alkanes do not show E-Z isomerism.

To assign E and Z, rank the two groups on each double-bond carbon by Cahn-Ingold-Prelog (CIP) priority: the atom of higher atomic number directly bonded to the double-bond carbon has higher priority (so $\text{Br} > \text{Cl} > \text{O} > \text{N} > \text{C} > \text{H}$). If the two higher-priority groups lie on the same side of the double bond the isomer is Z (from the German zusammen, together); on opposite sides it is E (entgegen, opposite). For but-2-ene, $\text{CH}_3\text{CH}{=}\text{CH}\text{CH}_3$, each carbon carries a $\text{CH}_3$ (higher priority) and an $\text{H}$, so the methyls on the same side give Z-but-2-ene and on opposite sides give E-but-2-ene.

But-1-ene, $\text{CH}_2{=}\text{CHCH}_2\text{CH}_3$, cannot show E-Z isomerism because the terminal $\text{CH}_2$ carbon carries two identical hydrogen atoms; swapping them produces the same molecule, so there is no distinct second isomer.

Optical isomerism

A chiral centre is often called an asymmetric carbon and marked with an asterisk. Because the four groups are all different, the molecule has no plane of symmetry, so its mirror image cannot be turned or twisted to lie on top of the original, just as a left hand cannot be superimposed on a right hand. The two forms are a pair of enantiomers. Enantiomers have identical physical properties (melting point, boiling point, density) and identical chemical reactions with non-chiral reagents; they differ only in the direction in which they rotate plane-polarised light and in their interaction with other chiral molecules, such as enzymes.

A molecule with $n$ chiral centres has up to $2^n$ stereoisomers. The angle of rotation is measured with a polarimeter.

Why stereochemistry matters

Many drugs are chiral, and the two enantiomers can behave very differently in the body because biological receptors and enzymes are themselves chiral and recognise only one shape. One enantiomer may be therapeutic while the other is inactive, less active, or harmful. The most cited case is thalidomide: one enantiomer relieved morning sickness while the other caused birth defects, and because the two interconvert in the body, separating them would not have prevented the tragedy. Modern drug development therefore favours single-enantiomer synthesis (using chiral catalysts or chiral starting materials) and rigorous chiral analysis, which is more costly than making a racemate but avoids the unwanted enantiomer.

Examples in context

A polarimeter, the instrument CCEA describes, measures how far a solution rotates plane-polarised light; a pure enantiomer of an amino acid or a sugar gives a definite angle, while the racemate reads zero. In medicine, the painkiller ibuprofen is sold as a racemate even though only one enantiomer is active, because the body interconverts them, whereas drugs where one enantiomer is toxic must be made and sold as a single enantiomer, driving the demand for stereospecific synthesis.

Amino acids, which CCEA studies in a neighbouring topic, are a clear example of chirality in biology: all the amino acids in proteins (except glycine, which has two hydrogens on the central carbon and so is not chiral) exist as a single enantiomer. The fact that life uses only one handedness is why a chiral drug can fit a receptor as snugly as a key in a lock while its mirror image cannot. E-Z isomerism also matters biologically: the conversion of an E to a Z double bond in retinal is the first step of vision, showing that a change in spatial arrangement alone can drive a chemical signal even when the connectivity is unchanged.

Try this

Q1. Define a chiral centre. [1 mark]

• Cue. A carbon atom bonded to four different groups.

Q2. State the condition needed for an alkene to show E-Z isomerism. [1 mark]

• Cue. Restricted rotation about $\text{C}=\text{C}$ and two different groups on each double-bond carbon.

Q3. Explain why a racemic mixture is optically inactive. [1 mark]

• Cue. It contains equal amounts of two enantiomers whose equal and opposite rotations cancel.