Chapter 36 — Quiz

Twenty-five questions on oxidation and reduction reactions. ∗ marks questions answered in the answer key.

Multiple choice

1.∗ PCC oxidizes a primary alcohol to: (a) aldehyde (stops there; mild) (b) carboxylic acid (full oxidation) (c) alkene (d) alkane

2.∗ Jones reagent (CrO₃/H₂SO₄) oxidizes a primary alcohol to: (a) aldehyde (b) carboxylic acid (full oxidation) (c) alkene (d) ester

3.∗ NaBH₄ reduces: (a) aldehydes and ketones (selective; doesn't touch esters/amides/COOH) (b) everything (c) only esters (d) only nitriles

4.∗ LiAlH₄ reduces: (a) only aldehydes (b) aldehydes, ketones, esters, amides, COOH, nitriles, epoxides (universal) (c) only ketones (d) only acids

5.∗ Catalytic hydrogenation (H₂/Pd/C) reduces: (a) alkenes, alkynes, nitro groups (b) aldehydes and ketones primarily (c) esters (d) all amides

6.∗ DIBAL-H (1 equiv, -78 °C): (a) reduces ester to a primary alcohol (b) reduces ester to an aldehyde (stops short; partial reduction) (c) reduces ester to a ketone (d) doesn't reduce esters

7.∗ Swern oxidation uses: (a) DMSO + oxalyl chloride + base; mild and chromium-free (b) Cr-based reagent (c) only base (d) only iodine

8.∗ Dess-Martin periodinane (DMP) is: (a) modern, mild, hypervalent iodine oxidation; replaces PCC (b) aggressive Cr oxidation (c) reducing agent (d) for double bonds only

9.∗ Sodium in liquid ammonia reduces an alkyne to: (a) cis-alkene (b) trans-alkene (anti addition; dissolving metal reduction) (c) alkane (d) aldehyde

10.∗ Lindlar Pd + H₂ reduces an alkyne to: (a) cis-alkene (stops short of alkane; cis addition) (b) trans-alkene (c) alkane (d) carboxylic acid

11.∗ The oxidation state of carbon in formaldehyde (H₂C=O) is: (a) -4 (b) -2 (c) 0 (d) +2

12.∗ A ketone (R₂C=O) has the same carbon oxidation state as: (a) an aldehyde (b) an alcohol (c) an alkane (d) carbon dioxide

13.∗ The CBS reagent is used for: (a) asymmetric reduction of ketones to chiral alcohols (b) hydrogenation (c) ester hydrolysis (d) decarboxylation

14.∗ OsO₄ converts an alkene to a: (a) syn-1,2-diol (cis) (b) anti-1,2-diol (trans) (c) two carbonyls (d) epoxide

15.∗ mCPBA + alkene + acid hydrolysis gives: (a) syn-diol (b) anti-diol (trans, from epoxide opening) (c) carbonyl cleavage (d) alkane

16.∗ Sharpless asymmetric dihydroxylation: (a) enantioselective version of OsO₄ oxidation; uses chiral cinchona ligand (b) asymmetric reduction (c) achiral (d) only on alkynes

17.∗ NAD⁺ in biology functions as: (a) a hydride acceptor (becoming NADH); coupled to enzyme dehydrogenations (b) a phosphate group (c) an electron pair acceptor only (d) a coenzyme for amino acid metabolism only

18.∗ Cytochrome P450 enzymes catalyze: (a) oxidation reactions: $C-H + O_2 + NADPH \to C-OH + H_2O + NADP^+$ (b) reductions only (c) hydrolysis (d) phosphorylation

19.∗ Why does grapefruit juice interact with many drugs? (a) it inhibits CYP3A4, slowing drug metabolism and elevating blood levels (b) it activates CYP3A4 (c) it directly binds drugs (d) it changes blood pH

20.∗ A drug-drug interaction via CYP3A4 inhibition can: (a) elevate blood levels of one drug to potentially toxic levels (b) reduce drug efficacy (c) cause unexpected metabolites (d) all of the above

Short answer

21. Calculate the oxidation state of each carbon in: methanol, formaldehyde, formic acid. Show the method.

22. Compare PCC, Jones, and DMP for oxidizing a primary alcohol. When would you use each?

23. A substrate has both an aldehyde and an ester. Predict the products of: (a) NaBH₄ at room T, (b) LiAlH₄ at 0 °C.

24. Design a synthesis of trans-2-butenedicarboxylic acid (fumaric acid) from acetylene + CO₂ + Na/NH₃. Show all steps.

25. Sketch the mechanism of NAD⁺-dependent alcohol dehydrogenase: ethanol + NAD⁺ → acetaldehyde + NADH + H⁺. Identify the hydride transfer.

Answer key

  1. a — PCC stops at aldehyde.
  2. b — Jones goes to COOH.
  3. a — NaBH₄ reduces aldehydes/ketones only.
  4. b — LiAlH₄ is universal.
  5. a — Pd/C + H₂ reduces alkenes, alkynes, nitros.
  6. b — DIBAL stops at aldehyde.
  7. a — Swern is DMSO + oxalyl chloride.
  8. a — DMP is modern oxidation.
  9. b — Na/NH₃ → trans-alkene.
  10. a — Lindlar → cis-alkene.
  11. c — Formaldehyde C is at oxidation state 0.
  12. a — Ketone and aldehyde are both at oxidation level 0.
  13. a — CBS reduces ketones asymmetrically.
  14. a — OsO₄ → syn-diol.
  15. b — mCPBA + acid → anti-diol.
  16. a — Sharpless AD enantioselective.
  17. a — NAD⁺ accepts hydride.
  18. a — CYP enzymes oxidize C-H bonds.
  19. a — Grapefruit inhibits CYP3A4.
  20. d — All correct.

21. Methanol ($CH_3OH$): C bonds = 3 H + 1 O = -3 + 1 = -2. Formaldehyde ($H_2C=O$): C bonds = 2 H + 2 O (the C=O is two bonds) = -2 + 2 = 0. Formic acid ($HCOOH$): C bonds = 1 H + 3 O (1 to OH, 2 to =O) = -1 + 3 = +2. The progression -2 → 0 → +2 is two oxidations: methanol → formaldehyde → formic acid.

22. PCC: stops at aldehyde; uses toxic Cr(VI). Standard for many syntheses but environmental concerns. Use when the substrate is mild and selectivity for aldehyde is critical. Jones: goes all the way to COOH. Good for primary alcohol → COOH. Aggressive; uses Cr(VI). DMP: modern, mild, non-toxic; gives clean aldehyde. Higher cost than PCC. Standard in modern synthesis where chromium-free conditions are preferred. Choice depends on: target product, substrate sensitivity, environmental constraints, scale.

23. (a) NaBH₄ reduces aldehydes only (not esters); the substrate's ester is untouched. Product: a hydroxyaldehyde where the aldehyde is reduced to alcohol. (b) LiAlH₄ reduces both aldehyde AND ester. Product: a primary alcohol from the aldehyde + a primary alcohol from the ester. Both groups are reduced; you get a diol or alcohol product. The key difference: NaBH₄ is selective for aldehydes/ketones; LiAlH₄ reduces almost everything.

24. Step 1: acetylene (HC≡CH) + 2 NaNH₂ → disodium acetylide. Then + 2 CO₂ → trans-fumarate (after protonation). Wait, this is actually tricky. Let me re-do: acetylene + Na/NH₃ at low T does add Na to give vinyl sodium, but the standard synthesis of fumaric acid is from maleic acid (cis-2-butenedioic acid) or directly from butenedioic acid synthesis. Better synthesis: HC≡CH + 2 CO₂ (via 2-step process: deprotonation by NaNH₂ to give acetylide, then addition to CO₂ to give the carboxylic acid; repeat for the other end after deprotonation). Then reduce alkyne to trans-alkene with Na/NH₃. Final product: HOOC-CH=CH-COOH (fumaric acid, trans).

25. Mechanism: 1. Ethanol's α-C-H bond breaks; the H is transferred as H⁻ (hydride) to the C4 position of NAD⁺'s nicotinamide ring. 2. Simultaneously, the ethanol's O-H bond is deprotonated (proton goes to the enzyme's active site Zn²⁺ or to a buffer). 3. NAD⁺ + H⁻ → NADH (the C4 of nicotinamide now has 4 substituents: H + bonds to C3 and C5 of the ring + the old H₃C part is unchanged). NADH is a 1,4-dihydropyridine. 4. The substrate is now acetaldehyde (the carbonyl is restored). The whole reaction: ethanol's α-C-H is "removed" with both bond electrons going to NAD's C4. The carbonyl is reformed. This is essentially the mechanism of NaBH₄ in reverse (NaBH₄ donates H⁻ to a carbonyl; here, the carbonyl is generated by H⁻ removal). Same mechanism, different direction.