Stereochemistry of substitution

Plane polarised light is made by passing ordinary light through a Nicol prism. Optically active compounds rotate its plane; a polarimeter measures the angle. Clockwise rotation is dextrorotatory, d or (+); anticlockwise is laevorotatory, l or (−). Such (+) and (−) forms are optical isomers.

Pasteur (1848) found crystals that were mirror images, whose solutions rotated light by equal amounts in opposite directions. In 1874 van't Hoff and Le Bel independently proposed that carbon's four bonds point to the corners of a tetrahedron.

A carbon holding four different groups is an asymmetric carbon (stereocentre); its molecule and mirror image cannot be superimposed. Such objects are chiral and optically active; objects superimposable on their mirror image are achiral and optically inactive.

Propan-2-ol has no asymmetric carbon and is achiral; butan-2-ol has one and is chiral. Other chiral examples: 2-chlorobutane, 2,3-dihydroxypropanal, bromochloroiodomethane (BrClCHI) and 2-bromopropanoic acid.

Enantiomers are non-superimposable mirror-image stereoisomers. They share melting point, boiling point and refractive index, and differ only in the direction they rotate plane polarised light.

An equal mixture of two enantiomers has zero rotation: a racemic mixture, written dl or (±), e.g. (±)-butan-2-ol. Turning one enantiomer into a racemic mixture is racemisation. The sign of rotation does not tell the actual (absolute) configuration.

Retention: if no bond to the stereocentre breaks, the arrangement around it is kept. Heating (−)-2-methylbutan-1-ol with concentrated HCl keeps the configuration, yet the chloride has the opposite sign of rotation, because a different compound can rotate light differently.

When a bond to the asymmetric carbon itself breaks, three outcomes are possible: retention (same arrangement), inversion (mirror arrangement) or racemisation (a 50:50 mixture, optically inactive).

SN2 gives inversion, because the nucleophile enters opposite the halogen: (−)-2-bromooctane with NaOH gives (+)-octan-2-ol, the –OH on the side away from where Br was.

SN1 gives racemisation: the sp² carbocation is planar and achiral, so the nucleophile adds from either face, giving both configurations. Hydrolysis of optically active 2-bromobutane gives (±)-butan-2-ol.