Mechanism comparison
| Feature | SN2 | SN1 | E2 | E1 |
|---|---|---|---|---|
| Rate law | k[RX][Nu] | k[RX] | k[RX][Base] | k[RX] |
| Steps | One, concerted | Two, carbocation | One, concerted | Two, carbocation |
| Best substrate | Methyl > 1° > 2° (3° no) | 3° > 2° (benzylic, allylic) | 3° > 2° > 1° | 3° > 2° |
| Nucleophile / base | Strong nucleophile | Weak (often the solvent) | Strong base | Weak base, heat |
| Solvent | Polar aprotic (DMSO, DMF, acetone, CH₃CN) | Polar protic (H₂O, ROH) | Varies | Polar protic |
| Stereochemistry | Inversion (backside attack) | Racemization (mostly) | Anti-periplanar H and LG | Mixture |
| Rearrangement | No | Yes (hydride/methyl shifts) | No | Yes |
Decision guide
- Methyl or 1° + strong nucleophile → SN2. 1° + bulky strong base (t-BuOK) → E2.
- 2° + strong base (HO⁻, RO⁻) → mostly E2. 2° + good nucleophile that is a weak base (I⁻, Br⁻, CN⁻, N₃⁻, RS⁻) in aprotic solvent → SN2.
- 2° or 3° + weak nucleophile in protic solvent → SN1/E1 (heat favors E1).
- 3° + strong base → E2. 3° never does SN2.
- Zaitsev: E1/E2 give the more substituted alkene. Bulky bases (t-BuOK, LDA) give the less substituted (Hofmann) alkene.
Leaving groups and nucleophiles
- Good leaving groups are weak bases: I⁻ > Br⁻ > Cl⁻ ≫ F⁻; tosylate (OTs), mesylate (OMs), triflate are excellent. OH⁻ is poor unless protonated (–OH₂⁺) or converted to OTs.
- In polar protic solvents nucleophilicity rises DOWN a group (I⁻ > Br⁻ > Cl⁻ > F⁻) because small ions are tightly solvated.
- In polar aprotic solvents nucleophilicity follows basicity (F⁻ > Cl⁻ > Br⁻ > I⁻).
- Neopentyl halides are 1° but react very slowly by SN2 (β-branching blocks the back side).
- Carbocation stability: 3° > 2° > 1° > methyl; allylic and benzylic cations are resonance-stabilized.
⚠️ Common traps
- Predicting SN2 at a tertiary carbon.
- Forgetting carbocation rearrangements in SN1/E1.
- Calling every strong base a good SN2 nucleophile (bulky bases eliminate).
- Ignoring the anti-periplanar requirement in cyclohexane E2 (H and leaving group must both be axial).
Mini-quiz
- (R)-2-Bromobutane reacts with NaCN in DMSO. What is the stereochemical outcome?
- tert-Butyl bromide is warmed in aqueous ethanol with no added base. Which pathways operate?
- 2-Bromo-2-methylbutane is treated with potassium tert-butoxide. What is the major product?
- Which is the best leaving group?
- Which rate law fits an SN2 reaction?
Answer key: 1 B · 2 C · 3 B · 4 A · 5 C