Chapter 23 — Quiz
Twenty-five questions on nucleophilic aromatic substitution, benzyne, and side-chain reactions. Answers and brief explanations follow.
1. SNAr requires the substrate to have: (a) an electron-donating group para to the leaving group (b) an electron-withdrawing group ortho or para to the leaving group (c) a benzyne intermediate (d) only an aryl halide; nothing else
2. The Meisenheimer complex is: (a) the intermediate in SNAr (negatively charged, sp³ ring C) (b) a diradical (c) the product of EAS (d) the same as the arenium ion of EAS
3. Reactivity order of leaving groups in SNAr: (a) I > Br > Cl > F (b) F > Cl > Br > I (c) all the same (d) only I works
4. Why is fluorobenzene more reactive than iodobenzene in SNAr? (a) F is more electronegative; activates the ring more for nucleophilic attack (b) The C-F bond is shorter, making the C more accessible (c) Both (a) and (b) (d) F is a better leaving group than I
5. The benzyne intermediate has: (a) a normal triple bond (b) a strained, in-plane π bond perpendicular to the aromatic π (c) a sp³ ring carbon (d) a positive charge
6. Benzyne is formed by: (a) elimination of H and X (where X = leaving group) (b) addition of H and Nu (c) electron transfer from Pd (d) protonation of an aryl Grignard
7. Benzyne mechanism gives a mixture of products because: (a) the nucleophile can add to either carbon of the strained π bond (b) the benzyne is achiral (c) statistical distribution of regiochemistry (d) all of the above
8. The benzyl radical (PhCH₂•) is more stable than a typical alkyl radical because: (a) of resonance delocalization into the aromatic ring (b) of hyperconjugation (c) of inductive effects from the ring (d) it has an extra C-H bond
9. Benzylic C-H bond strength is approximately: (a) 105 kcal/mol (like CH₄) (b) 95 kcal/mol (like 2° alkyl) (c) 88 kcal/mol (resonance-stabilized; like allyl) (d) 60 kcal/mol (very weak)
10. Toluene + Br₂ + Lewis acid (FeBr₃) gives: (a) bromobenzene (ring substitution; EAS) (b) benzyl bromide (side chain; radical) (c) the same product as Br₂ + light (d) no reaction
11. Toluene + Br₂ + light gives: (a) bromobenzene (ring substitution) (b) benzyl bromide (side chain; radical) (c) the same product as Br₂ + FeBr₃ (d) no reaction
12. NBS is used because: (a) it provides a low, steady concentration of Br₂ (b) it is selective for benzylic and allylic positions (c) it avoids over-bromination (d) all of the above
13. KMnO₄ + n-propylbenzene (PhCH₂CH₂CH₃) at high temperature gives: (a) propylbenzene oxide (b) benzoic acid + 2 carbons (CO₂ or formate) (c) PhCH₂CH₂CHO (d) PhCH(OH)CH₂CH₃
14. Why does KMnO₄ oxidize ethylbenzene → benzoic acid (not 1-phenylethanol)? (a) The oxidation goes all the way; the alkyl chain is degraded to -COOH (b) Hot KMnO₄ is strong enough to break C-C bonds (c) Both (a) and (b) (d) Only the benzylic H is involved
15. tert-Butylbenzene + KMnO₄ + heat gives: (a) benzoic acid (b) tert-butyl alcohol (c) tert-butyl + benzene (d) no reaction (no benzylic H!)
16. Birch reduction of benzene gives: (a) cyclohexane (full reduction) (b) 1,3-cyclohexadiene (conjugated diene) (c) 1,4-cyclohexadiene (kinetic product) (d) phenol
17. Birch reduction conditions: (a) Na or Li in liquid NH₃ + ROH (proton source) (b) H₂ + Pt (c) NaBH₄ (d) Wolff-Kishner reagents
18. When the aromatic substrate has an electron-withdrawing group like -COOH, Birch reduction gives: (a) addition of H at C2 and C4 (acceptor stays on sp²) (b) addition of H at C1 and C4 (acceptor stays on sp³ — opposite of donor case) (c) full reduction (d) phenol
19. Aryl Grignard (Ar-MgX) is made from: (a) Ar-H + Mg (b) Ar-X + Mg in dry ether (c) Ar-X + Pd (d) Ar-X + Li only
20. Aryl Grignard + CO₂ gives: (a) Ar-COO⁻ (then -COOH on workup) (b) Ar-CHO (c) Ar-OH (d) Ar-H
21. Sanger's reagent (2,4-dinitrofluorobenzene) reacts with: (a) the N-terminal amine of a protein, displacing F⁻ (b) all amines indiscriminately (c) all carboxylic acids (d) cysteine SH groups only
22. Why is fluorine the right leaving group for Sanger's reagent? (a) F is highly electronegative — activates the ring for SNAr by making C electrophilic (b) F is small — fits well in the Meisenheimer geometry (c) Both (a) and (b) (d) F is the cheapest of the halogens
23. Imatinib (Gleevec, leukemia drug) is synthesized by SNAr of a chloropyrimidine with an aniline. Pyrimidine is more SNAr-reactive than benzene because: (a) the two ring nitrogens act like built-in EWGs (b) the ring is more electron-deficient (c) The Meisenheimer complex has resonance structures with charge on the ring N (d) all of the above
24. SRN1 (radical aromatic substitution) requires: (a) light or a metal reductant + nucleophile (b) a Lewis acid catalyst (c) acidic conditions (d) basic conditions only
25. The aromatic substitution toolkit consists of: (a) EAS only (electrophilic) (b) SNAr only (nucleophilic, EWG-activated) (c) EAS + SNAr + benzyne + Pd cross-coupling (d) just radical substitution
Answer Key
| # | Answer | Explanation |
|---|---|---|
| 1 | b | EWG ortho/para stabilizes Meisenheimer; activates SNAr |
| 2 | a | Meisenheimer = SNAr intermediate; sp³ C; − charge |
| 3 | b | F > Cl > Br > I (because attack is rate-determining) |
| 4 | c | F's electronegativity + small size both help |
| 5 | b | In-plane π perpendicular to aromatic π; strained |
| 6 | a | Base deprotonates ortho-H; carbanion expels X⁻ |
| 7 | a | Either C of the strained π can be attacked |
| 8 | a | Resonance stabilization into the ring |
| 9 | c | ~88 kcal/mol; like allylic |
| 10 | a | Lewis acid → EAS, ring substitution |
| 11 | b | Light → radical chain; benzylic selectivity |
| 12 | d | NBS is the classic mild radical brominator |
| 13 | b | KMnO₄ degrades chain → benzoic acid |
| 14 | c | Hot KMnO₄ is strong; oxidizes & cleaves C-C |
| 15 | d | No benzylic H = no oxidation |
| 16 | c | 1,4-cyclohexadiene (kinetic product) |
| 17 | a | Standard Birch conditions |
| 18 | b | EWG: H at 1,4 — acceptor on sp³ |
| 19 | b | Standard Grignard formation; ArBr or ArI preferred |
| 20 | a | Carboxylation → carboxylic acid |
| 21 | a | Sanger SNAr on N-terminal amine |
| 22 | c | Both — electronics + geometry |
| 23 | d | All three reasons; pyrimidine activates SNAr |
| 24 | a | SRN1 = light or reductant + Nu |
| 25 | c | Full toolkit |
Concept connections
- EAS vs SNAr: opposite reactivity. Activator on ring → EAS. EWG on ring → SNAr.
- Reactivity reversal: F > I in SNAr (vs I > F in SN1/SN2). Diagnostic of the addition-elimination mechanism.
- Benzylic vs ring halogenation: light → benzylic; Lewis acid → ring. Same Br₂, different products.
- Side-chain oxidation: KMnO₄ converts any alkyl-with-benzylic-H to -COOH. Major industrial route to terephthalic acid.
- Birch: complement to full hydrogenation. 1,4-diene product is a versatile synthon for natural product synthesis.