Chapter 17 — Exercises
Forty-five problems on alkyne chemistry. Drawing required wherever a structure or mechanism is asked for. ∗ marks problems with full worked solutions in Appendix Answers to Selected Exercises.
Section A — Alkyne structure and acidity
17.1∗ (routine) Draw acetylene (HC≡CH) and 2-butyne. Identify the linear geometry, the σ + 2π bonds, and the sp hybridization.
17.2 (routine) Compare bond lengths and strengths of C-C, C=C, and C≡C. Why is C≡C shorter and stronger?
17.3∗ (routine) Why is the terminal alkyne C-H more acidic than alkene or alkane C-H? Use hybridization arguments.
17.4 (routine) What is the pKa of a terminal alkyne? Compare to alkane (pKa ~50) and alkene (pKa ~44).
17.5 (moderate) Predict whether each base can deprotonate 1-butyne (pKa 25): (a) NaH (pKaH 35) (b) n-BuLi (pKaH 50) (c) NaNH₂ (pKaH 38) (d) NaOH (pKaH 16)
17.6 (challenge) Why are internal alkynes (R-C≡C-R) less acidic at C than terminal alkynes? Hint: there's no C-H on the C≡C of internal alkynes.
Section B — Addition reactions
17.7∗ (routine) Predict the product: (a) 2-butyne + 1 equivalent HCl → ? (b) 2-butyne + 2 equivalents HCl → ? (c) 1-butyne + 1 HCl → ? (Specify regiochemistry.)
17.8 (routine) Predict the product: (a) 1-butyne + Br₂ (1 equiv) → ? (b) 1-butyne + Br₂ (2 equivs) → ?
17.9∗ (routine) Predict the product of the hydration: (a) 1-butyne + HgSO₄/H₂SO₄/H₂O → ? (methyl ketone) (b) 2-butyne + HgSO₄/H₂SO₄/H₂O → ? (specific ketone)
17.10 (moderate) Predict the product of hydroboration-oxidation: (a) 1-hexyne + (Sia)₂BH, then H₂O₂/NaOH → aldehyde. (b) 2-hexyne + (Sia)₂BH, then H₂O₂/NaOH → ?
17.11 (moderate) Why does hydration of a terminal alkyne give a methyl ketone but hydroboration-oxidation gives an aldehyde?
17.12 (challenge) Predict the product of: 4-octyne + HBr (excess). Show the gem-dihalide.
Section C — Reduction
17.13∗ (routine) Predict the product: (a) 2-pentyne + H₂/Pd/C (excess H₂) → ? (b) 2-pentyne + H₂/Lindlar Pd → ? (geometry) (c) 2-pentyne + Na/NH₃(l) → ? (geometry)
17.14 (routine) Why does Lindlar Pd stop at the cis-alkene rather than over-reducing to alkane?
17.15 (moderate) Sketch the mechanism of Na/NH₃ reduction of an alkyne. Identify the radical anion intermediates.
17.16 (challenge) Design a synthesis of (E)-3-hexene from 1-hexyne using selective reduction.
17.17 (challenge) Design a synthesis of (Z)-4-octenylacetate from 1-decyne using Lindlar reduction + esterification.
Section D — Alkynide nucleophiles
17.18∗ (routine) Predict the product: (a) 1-butyne + NaNH₂ → ? (b) HC≡C⁻Na⁺ + CH₃I → ? (c) HC≡C⁻Na⁺ + (CH₃)₃CCl → ? (steric problems)
17.19 (routine) Why does alkynide anion alkylation with primary alkyl halides give clean SN2, but tertiary halides give E2 elimination?
17.20 (moderate) Predict the product of: HC≡C⁻ + acetone, then aqueous workup. (Propargyl alcohol formation.)
17.21 (moderate) Use sequential alkyne synthesis to make 4-decyne from acetylene + appropriate alkyl halides.
17.22 (challenge) Design a synthesis of: (a) 5-decyne from acetylene + 2 alkyl halides; (b) 2-pentyn-4-ol from acetylene + propanal + ethyl iodide.
Section E — Sonogashira coupling
17.23∗ (routine) Sonogashira coupling: aryl halide + terminal alkyne + Pd + Cu + amine → aryl alkyne. Sketch the chemistry.
17.24 (routine) Why is the Sonogashira preferred over alkynide + ArX SN2? (ArX doesn't undergo SN2 well.)
17.25 (moderate) Predict the product: PhBr + HC≡C-CH₂CH₃ + Pd(PPh₃)₂Cl₂ + CuI + Et₃N → ?
17.26 (challenge) Design a synthesis of an aryl alkyne pharmaceutical intermediate using Sonogashira coupling.
Section F — Multistep synthesis
17.27∗ (routine) Design a synthesis of 2-pentanone from 1-pentyne via hydration.
17.28 (routine) Design a synthesis of pentanal from 1-pentyne via hydroboration-oxidation.
17.29 (moderate) Design a synthesis of (E)-4-octene from 1-pentyne + 1 alkyl halide + selective reduction.
17.30 (moderate) Design a synthesis of cis-3-hexene from 1-hexyne via Lindlar reduction.
17.31 (challenge) Design a synthesis of trans-4-decene from 1-pentyne + 1-pentyl bromide + Na/NH₃.
17.32 (challenge) A natural product has a (Z)-alkene at a strategic position. Plan a synthesis using alkyne + Lindlar.
Section G — Spectroscopy
17.33∗ (routine) A compound shows IR 3300 sharp + 2200 cm⁻¹ + ¹H NMR singlet at δ 1.8. Identify the compound.
17.34 (routine) A compound shows IR 2100 cm⁻¹ but no 3300 sharp peak. Identify the alkyne type (terminal vs internal).
17.35 (challenge) Distinguish 1-pentyne, 2-pentyne, and pentanal by IR + ¹H NMR.
Section H — Industrial alkynes
17.36 (routine) Industrial production of acetylene: from methane (partial oxidation) or from CaC₂ + H₂O. Sketch each.
17.37 (moderate) Vinyl chloride (CH₂=CHCl) industrial production: alkyne + HCl historically; modern: ethylene + Cl₂ then HCl elim. Why did industry switch?
17.38 (moderate) Vinyl acetate (CH₂=CH-OAc) industrial production from acetylene + acetic acid. Sketch the chemistry.
17.39 (challenge) Acrylonitrile (CH₂=CH-CN) historically from acetylene + HCN. Modern: ammoxidation of propylene + NH₃ + O₂. Why did industry switch?
Section I — Open-ended
17.40 (routine) Compare alkene chemistry (Ch 15-16) with alkyne chemistry (Ch 17). What are the similarities? Differences?
17.41 (moderate) Why is alkyne hydration (with HgSO₄) one of the few uses of mercury in modern industrial chemistry?
17.42 (challenge) Modern flow chemistry: alkyne reactions in flow reactors. Discuss advantages over batch.
17.43 (challenge) Click chemistry (Cu-catalyzed azide + alkyne cycloaddition; CuAAC) is a modern alkyne reaction (Sharpless 2022 Nobel). Sketch the chemistry.
17.44 (challenge) Strain-promoted azide-alkyne cycloaddition (SPAAC) uses cyclooctyne (a strained cyclic alkyne) without Cu. Why is the strained alkyne reactive without catalysis?
17.45 (challenge) Bioconjugation via click chemistry: how is alkyne chemistry used in modern bioconjugation (e.g., labeling proteins, sugars)?
Notes for instructors: Common stumbling blocks for Chapter 17: (1) Forgetting alkynes can react twice. (2) Mismatching Lindlar (cis) and Na/NH₃ (trans). (3) Mistaking terminal vs internal alkyne reactivity. (4) Not appreciating the SN2 limitations of alkynide alkylation (only works for 1° halides). Computational exercises: build cis-cyclooctene and try to embed it; see why cis is OK but trans is highly strained.