Chapter 12 — Exercises
Fifty problems on $E2$ and $E1$ mechanisms.
Section A — Drawing E2 mechanisms
12.1∗ Draw the $E2$ mechanism for 2-bromobutane + sodium ethoxide. Show all three arrows, the transition state, and the product.
12.2 Draw the mechanism for 1-bromopropane + sodium ethoxide. What is the product? Why is this primary substrate doing E2 here (vs. SN2)?
12.3 Draw the mechanism for 2-bromopentane + sodium t-butoxide. Predict major and minor products.
12.4 Show the anti-periplanar geometry required for E2 on (R)-2-bromobutane. Draw the Newman projection along C2-C3 and identify which H is anti-periplanar.
12.5 (moderate) Draw the mechanism of E2 on 1-bromo-2-methylcyclopentane. Note the geometric requirement for the cis vs trans isomers.
Section B — Anti-periplanar geometry
12.6∗ Draw the two chair conformations of (1R,2S)-1-bromo-2-methylcyclohexane. In which chair can E2 happen? Explain why.
12.7 For (1R,2R)-1-bromo-2-methylcyclohexane, the bromine and methyl are on opposite faces. Draw the chair where Br is axial. Is the C2-H anti-periplanar to the C1-Br? Predict the product.
12.8 Why does cis-1-bromo-4-t-butylcyclohexane undergo E2 ~600× faster than trans-1-bromo-4-t-butylcyclohexane? (The t-butyl is locked equatorial in both isomers.)
12.9 (moderate) A bicyclic substrate has the leaving group at a bridgehead position. Why doesn't it undergo E2? What about SN2?
12.10 (moderate) In cyclopropane, the H and X are forced cis (eclipsed). Why is E2 difficult on cyclopropyl halides?
Section C — Zaitsev vs Hofmann
12.11∗ Predict the major product of 2-bromobutane + NaOEt. Assign Zaitsev or Hofmann.
12.12 Predict the major product of 2-bromobutane + KO-tBu. Different from 12.11?
12.13 For 2-bromopentane + small base, list all possible E2 products. Which is Zaitsev?
12.14 (moderate) A reaction gives 60% Zaitsev and 40% Hofmann product. Propose a base that might give this ratio.
12.15 (challenge) Why is the more-substituted alkene more stable? Use bond energies and hyperconjugation in your explanation.
Section D — E1 mechanism
12.16∗ Draw the $E1$ mechanism for 3-bromo-3-methylpentane. Show both steps and the carbocation intermediate.
12.17 What is the product of $E1$ on 2-bromo-2-methylpentane in methanol at 80 °C?
12.18 (moderate) Show how a carbocation rearrangement could change the product distribution in $E1$.
12.19 (moderate) Compare the products of (a) (CH₃)₃CBr in methanol at 80°C and (b) (CH₃)₃CBr + NaOEt in DMSO at 25°C. Mechanism in each case?
12.20 (challenge) A tertiary alkyl chloride is dissolved in 80% aq EtOH at 70 °C. The product is 30% alkene + 70% alcohol. Mechanism of each? What experimental change would shift toward more alkene?
Section E — E1 vs E2 distinguishing
12.21∗ Substrate-base-solvent combinations. Predict mechanism (SN1, SN2, E1, E2): (a) 2-bromobutane + NaOH in DMSO, 25°C (b) 2-bromobutane + NaOH in water, 70°C (c) (CH₃)₃CBr + KO-tBu in t-BuOH, moderate T (d) (CH₃)₃CBr in 50% aq EtOH at 70°C (e) 1-bromobutane + KO-tBu, 80°C (f) 1-bromobutane + NaCN in DMF at 25°C
12.22 (moderate) A reaction shows first-order kinetics, gives a Zaitsev alkene as major product, and the rate is unchanged when the base concentration is doubled. Mechanism?
12.23 (challenge) A reaction shows second-order kinetics and gives Hofmann alkene. What does this combination tell you about the base?
Section F — Acid-catalyzed dehydration
12.24 Draw the mechanism for acid-catalyzed dehydration of 2-methyl-2-butanol with H₂SO₄. Which alkene is the major product?
12.25 Why is acid-catalyzed dehydration usually E1 rather than E2?
12.26 (moderate) Predict the products of dehydration of 2-pentanol with hot H₂SO₄. Discuss possible carbocation rearrangement.
Section G — Hofmann elimination
12.27∗ Outline the Hofmann elimination of butyltrimethylammonium hydroxide. What's the product?
12.28 Why does Hofmann elimination give the less-substituted alkene? (Hint: the leaving group is bulky.)
12.29 (challenge) A natural alkaloid contains a tertiary amine. Outline how Hofmann elimination could be used as part of structure determination (heat after methylation; identify alkene; deduce amine position).
Section H — Cope elimination
12.30 What is the geometric requirement for Cope elimination (different from E2)?
12.31 (moderate) Compare Cope elimination to standard E2 in terms of TS structure and stereochemistry of products.
Section I — Industrial / biological eliminations
12.32 (moderate) Industrial dehydration: ethanol → ethylene over Al₂O₃ at 300-400°C. Mechanism? Why is this commercially useful?
12.33 (challenge) Fumarase (a citric-acid-cycle enzyme) reversibly converts malate ↔ fumarate. Is this E1, E2, or something different (E1cb)?
12.34 (challenge) Β-oxidation of fatty acids includes a dehydration step (β-hydroxyacyl-CoA → α,β-unsaturated acyl-CoA). What's the mechanism?
Section J — Synthesis applications
12.35 Design a synthesis of 2-methyl-2-butene starting from 2-methyl-2-butanol. Use E1.
12.36 Design a synthesis of 1-butene starting from 1-butanol. Use E2 (with what base?).
12.37 (moderate) Why are eliminations commonly the most efficient way to install a C=C double bond?
12.38 (challenge) A medicinal chemistry route requires installing a specific cis-alkene. Could E1 or E2 give it cleanly? Why might the chemist choose alkyne reduction (Lindlar, Ch 17) instead?
Section K — Distinguishing all four mechanisms
12.39 A 2° halide reacts with NaOH in 80% aq EtOH at 70°C. The rate is partly first-order in [OH⁻] and partly zero-order. The products are mixed: alcohol, ether, and alkene. What's happening?
12.40 (challenge) Design a single experiment (one substrate, one set of conditions) that gives information about all four possible mechanisms (SN1, SN2, E1, E2).
Section L — Conceptual & cumulative
12.41-12.50 Cumulative exercises combining $E2$, $E1$, $S_N1$, $S_N2$ for various substrates. (Various substrate-base-solvent combinations to predict.)
Preview of Chapter 13
Chapter 13 unifies $S_N2$, $S_N1$, $E2$, $E1$ into a single decision tree. The exercise set will be primarily about applying that tree to predict products.