Nucleophilic substitution and SN2

Haloalkane reactions fall into three groups: nucleophilic substitution, elimination, and reaction with metals.

An electron-rich nucleophile attacks the δ+ carbon of the C–X bond and the halogen departs as a halide ion, the leaving group. The haloalkane is the substrate.

Products with common nucleophiles: OH⁻ (NaOH/KOH) or H₂O gives an alcohol; R′O⁻ an ether; I⁻ an alkyl iodide; NH₃ a primary amine, R′NH₂ a secondary and R′R″NH a tertiary amine; KCN a nitrile; AgCN an isonitrile; KNO₂ an alkyl nitrite; AgNO₂ a nitroalkane; R′COOAg an ester; LiAlH₄ (H⁻) a hydrocarbon; R′⁻M⁺ an alkane RR′.

Cyanide and nitrite are ambident nucleophiles, each with two donor sites. Cyanide can bond through C (alkyl cyanide) or N (isocyanide); nitrite through O (alkyl nitrite) or N (nitroalkane).

KCN is mostly ionic, so free CN⁻ attacks mainly through carbon, since a C–C bond is more stable than C–N: the product is the alkyl cyanide. AgCN is mostly covalent, leaving nitrogen to donate: the main product is the isocyanide.

SN2 (substitution nucleophilic bimolecular): CH₃Cl + OH⁻ → CH₃OH + Cl⁻ follows second order kinetics; the rate depends on both [CH₃Cl] and [OH⁻]. Hughes and Ingold proposed the mechanism in 1937.

It is one step with no intermediate. OH⁻ attacks from the side opposite the leaving group; as the C–O bond forms, the C–Cl bond weakens. In the transition state carbon is partly bonded to five groups and its three H atoms lie in one plane. This transition state cannot be isolated.

The three substituents flip over like an umbrella blown inside out, so the product has an inverted configuration (inversion of configuration).

Because the nucleophile must reach the back of the carbon, bulky groups on or near it slow SN2 sharply. Methyl halides react fastest (only three small H atoms) and tertiary halides slowest: CH₃X > 1° > 2° > 3°.