SN1, SN2, E1, and E2 Mechanisms
Nucleophilic substitution (SN) and elimination (E) reactions are at the core of organic chemistry for halogenated compounds. Understanding when each pathway is favoured is fundamental for predicting products and designing syntheses.
Bimolecular Nucleophilic Substitution (SN2)
The SN2 mechanism is concerted (single step): the nucleophile attacks from the back of the C−X bond (opposite the leaving group), with bond formation and breaking occurring simultaneously.
- Rate law: v = k [substrate][nucleophile] — second order.
- Stereochemistry: Walden inversion — absolute configuration is inverted (R → S or S → R).
- Favoured substrates: primary and methyl halides (minimal steric hindrance). Tertiary substrates react very slowly via SN2.
- Strong nucleophiles: HO⁻, I⁻, RS⁻, CN⁻, N₃⁻.
Example: (R)-2-bromobutane + HO⁻ → (S)-butan-2-ol (inversion).
Unimolecular Nucleophilic Substitution (SN1)
The SN1 mechanism is stepwise (two stages): (1) slow ionisation of the substrate to a carbocation (rate-determining step); (2) rapid nucleophilic attack on the planar carbocation.
- Rate law: v = k [substrate] — first order (nucleophile concentration does not appear).
- Stereochemistry: partial racemisation (the planar carbocation is attacked from both faces), often with a slight enantiomeric excess (ion-pair effect).
- Favoured substrates: tertiary, benzylic, and allylic halides (stabilised carbocations).
- Polar protic solvents (EtOH, H₂O) stabilise the carbocation by solvation.
E1 and E2 Eliminations
| Criterion | E1 | E2 |
|---|---|---|
| Steps | 2 (carbocation intermediate) | 1 (concerted) |
| Rate law | v = k [substrate] | v = k [substrate][base] |
| Stereochemistry | non-specific | anti-periplanar (Zaitsev with weak base; Hofmann with bulky base) |
| Substrates | tertiary, high T | primary → tertiary with strong base |
| Base | weak or absent | strong, non-nucleophilic (t-BuO⁻, DBU) |
Zaitsev's rule predicts that the most substituted (most thermodynamically stable) alkene is the major product. Hofmann's rule applies with bulky bases (t-BuO⁻) that abstract the most accessible proton: the less substituted (kinetic) alkene is then favoured.
Competition Among the Four Pathways
Experimental conditions determine the preferred route:
- Primary halide + strong nucleophile → SN2 predominates.
- Tertiary halide + weak nucleophile, polar protic solvent → SN1.
- Tertiary halide + strong base, aprotic solvent → E2.
- Tertiary halide + weak base, high temperature → E1.
- Solvent polarity is crucial: polar aprotic solvents (DMF, DMSO, acetone) favour SN2 by poorly solvating the nucleophile (leaving it highly reactive).
Mastering these four mechanisms allows prediction of the major product for any halide reaction and selection of optimal synthetic conditions.