Isomerism: Structural and Stereoisomerism

Isomerism: Structural and Stereoisomerism

Isomers are molecules with the same molecular formula but a different arrangement of atoms. Isomerism is fundamental to organic chemistry because different isomers can have very different physical and chemical properties.

Types of Isomerism

There are two main categories:

1. Structural isomerism (constitutional isomerism) — atoms are connected in a different order

2. Stereoisomerism — atoms are connected in the same order but arranged differently in space

Structural Isomerism

There are three types of structural isomer:

Chain isomerism — the carbon skeleton is arranged differently (branched vs unbranched):

• C₄H₁₀: butane (straight chain) and methylpropane (branched)
• C₅H₁₂: pentane, 2-methylbutane, 2,2-dimethylpropane
• Branched isomers have lower boiling points because their more compact shape reduces surface area and weakens London dispersion forces

Position isomerism — the same functional group is attached at a different position on the same carbon chain:

• C₃H₇OH: propan-1-ol and propan-2-ol
• C₄H₈: but-1-ene and but-2-ene
• Position isomers have similar but not identical chemical properties (e.g. propan-1-ol is a primary alcohol, propan-2-ol is secondary)

Functional group isomerism — molecules have different functional groups:

• C₂H₆O: ethanol (alcohol, C₂H₅OH) and methoxymethane (ether, CH₃OCH₃)
• C₃H₆O: propanal (aldehyde) and propanone (ketone)
• C₃H₆O₂: propanoic acid (carboxylic acid) and methyl ethanoate (ester)
• Functional group isomers have very different chemical properties

Stereoisomerism: E/Z Isomerism (Geometric Isomerism)

E/Z isomerism occurs when there is restricted rotation around a C=C double bond AND each carbon of the double bond has two different groups attached.

The C=C double bond contains a sigma (σ) bond and a pi (π) bond. The π bond prevents rotation — the p orbitals must remain parallel to overlap.

Z (zusammen) = higher priority groups on the same side

E (entgegen) = higher priority groups on opposite sides

Priority is assigned using Cahn-Ingold-Prelog (CIP) rules: the atom with the higher atomic number gets higher priority. If the atoms directly attached are the same, move along the chain until a point of difference.

Example: But-2-ene (CH₃CH=CHCH₃)

• Z-but-2-ene: both CH₃ groups on the same side (bp 3.7 °C)
• E-but-2-ene: CH₃ groups on opposite sides (bp 0.9 °C)

Conditions for E/Z isomerism:

1. A C=C double bond (or other source of restricted rotation)

2. Each carbon of the double bond must carry two different substituents

CH₂=CHCl shows E/Z isomerism? No — one carbon has two H atoms (identical substituents).

Stereoisomerism: Optical Isomerism

Optical isomers (enantiomers) occur when a carbon atom has four different groups attached. This carbon is called a chiral centre (asymmetric carbon), marked with an asterisk (*).

The two enantiomers are non-superimposable mirror images of each other — like left and right hands.

Properties of enantiomers:

• Identical physical properties (melting point, boiling point, solubility)
• Identical chemical properties with achiral reagents
• Different interaction with plane-polarised light: one rotates the plane clockwise (+, dextrorotatory), the other rotates it anticlockwise (−, laevorotatory) by the same angle
• Different biological activity (enzymes and receptors are chiral, so they distinguish between enantiomers)

A racemic mixture (racemate) contains equal amounts of both enantiomers. It shows no net optical rotation because the rotations cancel. Many laboratory syntheses produce racemic mixtures because the attacking reagent can approach the planar intermediate from either side with equal probability.

Identifying Chiral Centres

Look for a carbon bonded to four different groups. Common examples:

• 2-bromobutane: CH₃CHBrCH₂CH₃ — the C has H, Br, CH₃, and C₂H₅ attached
• Amino acids (except glycine): the α-carbon has H, NH₂, COOH, and R (the side chain)
• Butan-2-ol: CH₃C*H(OH)CH₂CH₃

Glycine (R = H) is not chiral because two of the groups on the α-carbon are H.

Optical Activity and Plane-Polarised Light

A polarimeter measures optical rotation:

1. Light passes through a polarising filter, producing plane-polarised light

2. The light passes through a solution of the optically active substance

3. An analyser filter is rotated until maximum light transmission is achieved

4. The angle of rotation is measured

Specific rotation depends on concentration, path length, wavelength, and temperature. It is characteristic of a given enantiomer.

Chirality in Reactions

When an achiral molecule reacts to form a product with a chiral centre, a racemic mixture is usually produced:

Example: Nucleophilic addition to an aldehyde

• The planar carbonyl group can be attacked from above or below with equal probability
• This produces a 50:50 mixture of enantiomers

When one pure enantiomer reacts, the product may retain chirality, depending on whether the reaction occurs at the chiral centre itself.

SN1 vs SN2 and chirality:

• SN1 (via a planar carbocation intermediate) → racemic mixture (nucleophile attacks equally from both sides)
• SN2 (direct backside attack) → inversion of configuration (Walden inversion — the configuration at the chiral centre is flipped)

Meso Compounds (Extension)

A molecule with two or more chiral centres may be achiral overall if it possesses an internal mirror plane. Such compounds are called meso compounds — they contain chiral centres but are not optically active because one half of the molecule is the mirror image of the other.

Exam Tips

• When drawing E/Z isomers, draw the double bond horizontally and clearly show groups above and below
• For optical isomers, draw 3D representations using wedge and dashed bonds, and show the mirror image alongside
• To identify a chiral centre, check for a C with four different groups — trace along each branch far enough to confirm they are genuinely different
• State that a racemic mixture has no overall optical activity because equal and opposite rotations cancel