2.8 Aliphatic Nucleophilic Substitution: SN1, SN2, SNi and Neighbouring Group Participation

2.8.1 The SN2 mechanism ★★★

• One step, bimolecular: the nucleophile's lone pair enters the C–X σ* orbital from the side opposite the leaving group while the C–X bond breaks. No intermediate; one transition state in which carbon is trigonal bipyramidal (five partial bonds, Nu and X 180° apart).SN
• Stereochemistry: the other three groups flip over like an umbrella in the wind: inversion of configuration (Walden inversion), every time. (R)-2-bromobutane + HO⁻ → (S)-butan-2-ol. The R/S label flips only if the priorities are unchanged; always decide from the drawing (2.10).SN

• Substrate: crowding at the back of the C–X carbon decides the rate. Relative S_N2 rates (RBr + I⁻, acetone): CH₃ 30 : 1° 1 : 2° 0.03 : neopentyl 10⁻⁵ : 3° ≈ 0. Tertiary and bridgehead bromides do not react by S_N2 at all; when four tertiary bromides are to be ranked, rank by how open the back of the C–Br carbon is and say that all are very slow CSE 2022 Q3(c)(ii) 10m. Allylic, benzylic and α-carbonyl halides are faster (π-overlap in the TS).SN
• Nucleophile: in protic solvents nucleophilicity rises down a group (I⁻ > Br⁻ > Cl⁻ > F⁻; RS⁻ > RO⁻): large, soft ions are less hydrogen-bonded and more polarisable. In aprotic solvents the order follows basicity (F⁻ fastest).SN

2.8.2 The SN1 mechanism ★★★

• Two (or three) steps: slow ionisation to a carbocation, then fast capture by the nucleophile (and fast proton loss if the nucleophile is water or an alcohol). The rate depends on [RX] only: first order, unimolecular IFoS 2021 Q2(b) 10m.SN
• tert-Butyl chloride in water: the free-energy profile has three maxima; the first (ionisation) is the highest. Intermediate I = (CH₃)₃C⁺, II = (CH₃)₃C–OH₂⁺. Each intermediate sits in a valley, each step has its own TS.SN

• Carbocation stability decides: 3° > 2° ≫ 1°; allyl and benzyl cations are stabilised by resonance. The slow step makes charge, so anything that stabilises the cation (alkyl groups by hyperconjugation and induction, π-conjugation, lone-pair donors) speeds S_N1. Details of carbocations: 2.3.SN
• Para-alkyl benzyl bromides: p-methyl solvolyses faster than p-tert-butyl, against the inductive order: three C–H bonds of CH₃ hyperconjugate with the ring and the benzylic cation; the C(CH₃)₃ carbon has none (Baker–Nathan order) IFoS 2023 Q1(d) 5m.SN
• Stereochemistry: the cation is planar (sp²), so a chiral substrate gives mostly racemisation, usually with a little excess of inversion: the departing anion still shields the front face (ion pair, 2.8.9).SN
• Allylic substrates give two products: 1-bromo-1-ethylcyclohex-2-ene in ethanol ionises to a delocalised tertiary allylic cation; EtOH attacks either end: 1-ethoxy-1-ethylcyclohex-2-ene and 3-ethoxy-1-ethylcyclohexene (allylic rearrangement), with dienes by E1 IFoS 2021 Q7(c)(i) 5m.SN
• (CH₃)₃CBr + C₂H₅OH, 60 °C: solvolysis, S_N1: tert-butyl ethyl ether, (CH₃)₃COC₂H₅, is the main product, with 2-methylpropene by E1 (more at higher temperature) CSE 2024 Q4(a)(ii) 5m.

2.8.3 SN1 or SN2: the four factors ★★★

• Why DMSO and DMF speed S_N2 CSE 2023 Q1(c) 10m IFoS 2022 Q1(f) 5m: a protic solvent (MeOH) hydrogen-bonds to the small anion (N₃⁻, HO⁻) and lowers its energy; that cage must be partly broken to reach the TS, so ΔG‡ is large. DMSO and DMF have no O–H or N–H; their negative oxygen solvates the cation (Na⁺) and leaves a “naked”, high-energy anion: ΔG‡ falls. CH₃I + NaN₃ runs about 10⁴ times faster in DMF than in methanol.SN
• Why protic solvents speed S_N1: the TS of the slow step is already charge-separated (R^δ+···X^δ−); hydrogen bonds to X^δ− and dipoles round R^δ+ stabilise it more than the neutral substrate (2.8.9).SN

2.8.4 SNi: SOCl₂ with and without pyridine ★★★ 10 marks twice

• Step 1 (both cases): ROH + SOCl₂ → R–O–S(O)Cl, the alkyl chlorosulfite, + HCl. The C–O bond is not touched: configuration unchanged so far.SN
• No base (ether or neat): the C–O bond ionises to an intimate ion pair R⁺ ⁻OS(O)Cl; SO₂ leaves and the Cl is delivered to the same face the oxygen left, before the ions separate: S_Ni, retention. (S)-butan-2-ol → (S)-2-chlorobutane CSE 2024 Q1(c) 10m; a 2° alcohol to a 2° chloride with retention “through an intimate ion pair” is exactly this IFoS 2021 Q4(c)(ii) 5m.SN
• With pyridine: pyridine takes the HCl as pyridinium chloride, so free Cl⁻ is in solution; it attacks the chlorosulfite from the back: S_N2, inversion. (S)-1-phenylethanol + SOCl₂/pyridine → (R)-1-chloro-1-phenylethane, with SO₂ and C₅H₅NH⁺Cl⁻ CSE 2021 Q2(c)(i) 10m.SN