Chapter 21 — Exercises
Forty-five problems on electrophilic aromatic substitution. Drawing required wherever a structure or mechanism is asked for. ∗ marks problems with full worked solutions in Appendix Answers to Selected Exercises.
Section A — Mechanism
21.1∗ (routine) Draw the full mechanism for: benzene + Br₂/FeBr₃ → bromobenzene + HBr.
21.2 (routine) What is the rate-limiting step of EAS? Why?
21.3∗ (moderate) Sketch the arenium ion intermediate of EAS. Show the three resonance structures with positive charge at different ring carbons.
21.4 (moderate) Why is the arenium ion called a "σ-complex"? Connect to the sp³ ring C.
21.5 (challenge) Compare the EAS mechanism with alkene electrophilic addition (Ch 15). Why does benzene give substitution while propene gives addition?
Section B — Halogenation
21.6∗ (routine) Predict the product of: (a) benzene + Cl₂ + FeCl₃ → ? (b) benzene + Br₂ + FeBr₃ → ? (c) benzene + I₂ alone → ? (does it react?)
21.7 (routine) Why is a Lewis acid catalyst (FeBr₃) needed for halogenation of benzene?
21.8 (moderate) Sketch the mechanism of generating the electrophile from Br₂ + FeBr₃.
21.9 (challenge) Why is direct fluorination of benzene difficult? Suggest alternative routes to fluorobenzene.
Section C — Nitration
21.10∗ (routine) Predict the product of: benzene + HNO₃ + H₂SO₄ → ?
21.11 (routine) Sketch the mechanism: HNO₃ + H₂SO₄ → NO₂⁺. Then the EAS step.
21.12 (moderate) Industrial production of nitrobenzene: ~1 million tons/year. Sketch the process and the major use (precursor to aniline → many dyes/drugs).
21.13 (challenge) Why is nitrobenzene unreactive toward further EAS without much harsher conditions? Connect to deactivation (Ch 22).
Section D — Sulfonation
21.14∗ (routine) Predict the product of: benzene + SO₃ in conc. H₂SO₄ → ?
21.15 (routine) Why is sulfonation reversible (unlike nitration)?
21.16 (moderate) Use sulfonation as a directing/blocking group: install a sulfonate to direct further EAS, then remove. Sketch a synthesis.
21.17 (challenge) Linear alkylbenzene sulfonate (LAS): industrial detergent. Outline the synthesis from benzene + linear alkene + sulfonation.
Section E — Friedel-Crafts alkylation
21.18∗ (routine) Predict the product: (a) benzene + 2-chloropropane + AlCl₃ → ? (b) benzene + 1-chloropropane + AlCl₃ → ? (note the rearrangement)
21.19 (routine) Why does 1-chloropropane + AlCl₃ + benzene give isopropylbenzene (not n-propylbenzene)? Carbocation rearrangement.
21.20 (moderate) Why does FC alkylation give polyalkylation problems? Connect to alkyl group activation of the ring (Ch 22).
21.21 (moderate) A student wants to make linear butylbenzene. Why doesn't FC alkylation with 1-bromobutane work cleanly? Suggest an alternative.
21.22 (challenge) FC alkylation doesn't work on nitrobenzene. Why? What workaround would you use to install an alkyl group on a nitro-substituted ring?
Section F — Friedel-Crafts acylation
21.23∗ (routine) Predict the product: (a) benzene + acetyl chloride + AlCl₃ → ? (acetophenone) (b) benzene + benzoyl chloride + AlCl₃ → ?
21.24 (routine) Sketch the mechanism: RCOCl + AlCl₃ → R-C≡O⁺ (acylium ion). Then EAS.
21.25 (routine) Why doesn't FC acylation give polyacylation? Connect to acyl group deactivation.
21.26 (moderate) Why doesn't acylium ion rearrange (unlike alkyl carbocation)? Connect to resonance stabilization.
21.27 (moderate) Design a synthesis of butylbenzene from benzene using FC acylation + reduction.
21.28 (challenge) Compare two reductions of ArCOR to ArCH₂R: Clemmensen (Zn(Hg) + HCl) vs Wolff-Kishner (NH₂NH₂ + KOH). When would you use each?
Section G — Multistep synthesis
21.29∗ (routine) Design a synthesis of ethylbenzene from benzene using FC acylation + reduction.
21.30 (routine) Design a synthesis of: 4-bromonitrobenzene from benzene. Step order matters!
21.31 (moderate) Design a synthesis of 2-aminobenzoic acid (anthranilic acid) from benzene.
21.32 (moderate) Design a synthesis of 2,4,6-trinitrotoluene (TNT) from toluene. Use sequential nitration.
21.33 (challenge) Design a synthesis of phenacetin (an old analgesic) from benzene.
21.34 (challenge) Design a synthesis of 4-bromobenzoic acid from toluene.
Section H — Industrial EAS
21.35∗ (routine) Cumene production: benzene + propylene + acid catalyst → cumene. Outline. Why is this industrially important?
21.36 (moderate) Industrial nitration of benzene: outline the process, scale, products.
21.37 (challenge) Modern industrial EAS uses heterogeneous solid acid catalysts (zeolites) instead of liquid AlCl₃. Why?
Section I — Other EAS
21.38 (routine) Vilsmeier-Haack formylation: ArH + DMF + POCl₃ → ArCHO. Sketch the chemistry.
21.39 (moderate) Reimer-Tiemann formylation of phenols: ArOH + CHCl₃ + NaOH → o-OH-ArCHO. Sketch the chemistry; identify the dichlorocarbene intermediate.
21.40 (challenge) Kolbe-Schmitt reaction: ArO⁻ + CO₂ → o-OH-ArCOOH. The basis of salicylic acid synthesis (precursor to aspirin). Sketch.
Section J — Spectroscopy and analytics
21.41∗ (routine) A starting benzene + EAS gives a product with new IR peaks at 1500-1600 cm⁻¹ (aromatic C=C) + 700-900 cm⁻¹ (out-of-plane bends). What does the substitution pattern tell us?
21.42 (routine) A monosubstituted benzene's ¹H NMR shows aromatic H peaks at δ 7-8 (5 H total). After EAS, the product has 4 H total. Identify the substitution pattern by additional analysis.
21.43 (challenge) Distinguish o-, m-, and p-bromochlorobenzene by ¹H NMR coupling patterns.
Section K — Open-ended
21.44 (challenge) Compare EAS (Ch 21) with alkene electrophilic addition (Ch 15). What's the same? Different?
21.45 (challenge) Modern EAS-like chemistry: Pd-catalyzed C-H activation (Ch 37) achieves aromatic substitution without harsh conditions. Compare with classical EAS.
Notes for instructors: Common stumbling blocks for Chapter 21: (1) Forgetting Lewis acid catalyst for halogenation. (2) Confusing FC alkylation rearrangement. (3) Not appreciating FC acylation's clean stop-after-one. (4) Order of operations in multistep syntheses. Computational exercises: visualize the arenium ion's positive charge delocalization in 2D.