SN1 and SN2 Reaction Mechanisms

Nucleophilic substitution replaces a leaving group on a carbon with a nucleophile. Two distinct mechanisms compete:

SN2 (bimolecular): One concerted step — the nucleophile attacks from exactly 180° behind the leaving group (backside attack) while the leaving group simultaneously departs. This causes Walden inversion of configuration (like an umbrella flipping inside out). The rate depends on both reactants: $\text{rate} = k[\text{substrate}][\text{Nu}]$.

SN1 (unimolecular): Two steps — (1) the leaving group departs to form a planar carbocation intermediate (rate-determining step); (2) the nucleophile attacks from either face, giving racemisation. The rate depends only on the substrate: $\text{rate} = k[\text{substrate}]$.

The deciding factors: substrate degree (1°/2°/3°), nucleophile strength, and solvent polarity.

Energy profile for SN2 (one transition state, no intermediate):

$\Delta G^\ddagger_{\text{SN2}} \uparrow \text{ as steric bulk increases} \Rightarrow \text{methyl} > 1° > 2° \gg 3°$

Carbocation stability order (governs SN1 rate):

$3° > 2° > 1° \gg \text{methyl}$

(Hyperconjugation and inductive donation from alkyl groups stabilise the positive charge.)

Substrate: 2-bromo-2-methylpropane (tertiary). Conditions: aqueous ethanol (polar protic), NaOH (moderate nucleophile).

• Mechanism: SN1 — the tertiary carbocation $(CH_3)_3C^+$ forms readily; polar protic solvent stabilises it by hydrogen bonding to $Br^-$.
• Stereochemistry: racemisation (if the carbon was a chiral centre, equal amounts of $R$ and $S$ product form).
• Rate: $k[(CH_3)_3CBr]$ — independent of $[\text{NaOH}]$.

Contrast: bromomethane $CH_3Br$ + $NaCN$ in acetone (polar aprotic) → SN2, complete inversion, rate $= k[CH_3Br][CN^-]$.

Pharmaceutical chemists use SN2 reactions to build drug molecules with precise stereochemistry — the wrong enantiomer may be inactive or toxic (e.g., thalidomide). SN1 conditions are exploited in protecting-group chemistry where clean inversion is not required. Understanding solvent effects guides green chemistry: replacing polar protic solvents (water, ethanol) with aprotic ones (DMSO, DMF) can switch selectivity entirely.

1. Predict the mechanism (SN1 or SN2) and stereochemical outcome for the reaction of $(R)$-2-bromobutane with $NaI$ in acetone. Justify your answer.

2. Why does a tertiary alkyl halide undergo SN1 rather than SN2, even with a strong nucleophile?