Nucleophilic substitution

The carbon of a C–X bond is slightly positive, so a nucleophile (an electron-rich species such as OH⁻, CN⁻ or NH₃) can attack it and push the halide out. This is nucleophilic substitution, and it happens in two ways.

SN2 (substitution, nucleophilic, two species in the slow step):

• It happens in one step. The nucleophile attacks from the back, exactly opposite the leaving halogen, while the halogen leaves.
• Rate = k[RX][Nu]: it depends on both.
• Because the attack is from behind, the molecule turns inside out, like an umbrella in the wind: inversion of configuration.
• The backside must be open, so crowding slows it: CH₃X > 1° > 2° > 3°.

SN1 (substitution, nucleophilic, one species in the slow step):

• It happens in two steps. First the halide leaves on its own, giving a carbocation; then the nucleophile attacks it.
• Rate = k[RX]: only the haloalkane matters.
• The flat carbocation can be attacked from either face, so a chiral starting material gives a mixture of both mirror-image products: racemisation.
• It needs a stable carbocation, so the order is the reverse: 3° > 2° > 1°. Allylic and benzylic halides also react fast, because their carbocations are stabilised by resonance.

The leaving group. The weaker the C–X bond and the more stable the X⁻, the faster either reaction goes: R–I > R–Br > R–Cl > R–F.

Ambident nucleophiles can attack through either of two atoms. Cyanide: KCN (ionic) attacks through carbon, giving alkyl cyanides (R–CN); AgCN (mostly covalent) attacks through nitrogen, giving isocyanides (R–NC). Nitrite: KNO₂ gives alkyl nitrites (R–ONO), while AgNO₂ gives nitroalkanes (R–NO₂).

A word on chirality. A carbon with four different groups is chiral: the molecule and its mirror image cannot be placed on top of each other, like left and right hands. The two forms, enantiomers, rotate plane-polarised light by the same amount in opposite directions (dextro, +, and laevo, –). An equal mixture of both, a racemic mixture, has no effect on the light.