Chapter 36 — Exercises

Fifty problems on oxidation and reduction reactions. Drawing required wherever a structure or mechanism is asked for. ∗ marks problems with full worked solutions in Appendix Answers to Selected Exercises.

Section A — Oxidation states

36.1∗ (routine) Assign the oxidation state of each carbon in: (a) methane (CH₄) (b) methanol (CH₃OH) (c) formaldehyde (H₂C=O) (d) formic acid (HCOOH) (e) CO₂ (f) ethanol (CH₃CH₂OH) (g) acetaldehyde (CH₃CHO) (h) acetic acid (CH₃COOH)

36.2 (routine) For 2-butanol ($CH_3CH(OH)CH_2CH_3$), assign oxidation states for each carbon. After oxidation to butan-2-one, what changes?

36.3∗ (moderate) Explain why the carbon in ethyl ether (CH₃CH₂-O-CH₂CH₃) is at the same oxidation level as the carbon in acetaldehyde. Both should be at +0.

36.4 (moderate) What is the oxidation state of the carbonyl carbon in methyl benzoate? Compare to the oxidation state of the carbonyl carbon in formaldehyde.

36.5 (challenge) What is the oxidation state of each carbon in glucose? In what state is glucose at oxidation when expressed as the sum?

Section B — Alcohol oxidations

36.6∗ (routine) Predict the product of each: (a) 1-butanol + PCC → ? (b) 1-butanol + Jones reagent → ? (c) 2-butanol + PCC → ? (d) 1-butanol + Swern → ? (e) 1-butanol + DMP → ?

36.7 (routine) Why does PCC stop at the aldehyde while Jones reagent goes all the way to the COOH?

36.8 (moderate) A student tries to oxidize 2-butanol to butanoic acid. Why is this impossible? What product can you actually make?

36.9 (moderate) Why is DMP (Dess-Martin periodinane) preferred over PCC in modern synthesis? Identify two reasons.

36.10 (challenge) Sketch the mechanism of Swern oxidation: DMSO + (COCl)₂ → activated dimethyl sulfide; alcohol + activated DMSO → oxysulfonium; base removes the α-H from oxysulfonium → aldehyde.

36.11 (challenge) Compare the chemoselectivity of: (a) PCC, (b) DMP, (c) Swern, (d) MnO₂. Which is the most selective for allylic alcohols?

Section C — Carbonyl reductions

36.12∗ (routine) Predict the product: (a) butanal + NaBH₄ → ? (b) butanal + LiAlH₄ → ? (c) butanoic acid + LiAlH₄ → ? (d) butyl butyrate + LiAlH₄ → ? (e) butyl butyrate + DIBAL-H (1 eq, -78 °C) → ?

36.13 (routine) Why does NaBH₄ not reduce esters but LiAlH₄ does?

36.14 (moderate) A student wants to reduce an aldehyde without reducing an ester nearby in the same molecule. What reagent should they use? Why?

36.15 (moderate) A student wants to reduce an ester to an aldehyde (and stop there). What reagent and conditions?

36.16 (challenge) Predict whether the reduction of a chiral ketone with NaBH₄ gives racemic product or one enantiomer. Why? What about with CBS reagent?

Section D — Hydrogenation

36.17∗ (routine) Predict the product: (a) cyclohexene + H₂/Pd/C → ? (b) phenylacetylene + H₂/Lindlar → ? (c) phenylacetylene + Na/NH₃(l) → ? (d) phenylacetylene + H₂/Pd/C (excess H₂) → ?

36.18 (routine) Why does Lindlar Pd give cis-alkene from alkyne but Pd/C with excess H₂ gives alkane?

36.19 (moderate) Why is Na/NH₃ reduction of alkynes stereospecifically anti (trans)?

36.20 (moderate) Aromatic rings (benzene) are typically not reduced by Pd/C + H₂ at room temperature. Why? What conditions are needed?

36.21 (challenge) Asymmetric hydrogenation: a chiral Rh-BINAP catalyst can reduce a prochiral alkene to give one enantiomer in high ee. Sketch the principle.

Section E — Alkene/alkyne oxidations (Ch 16-17 review)

36.22∗ (routine) Predict the product: (a) cyclohexene + OsO₄ → ? (b) cyclohexene + mCPBA → ? (c) cyclohexene + O₃ → ? (then Zn/H₂O) (d) cyclohexene + KMnO₄ (cold) → ? (e) cyclohexene + KMnO₄ (hot) → ?

36.23 (routine) Compare syn vs. anti diol formation: OsO₄ vs. mCPBA + acid hydrolysis.

36.24 (moderate) Sharpless asymmetric dihydroxylation uses OsO₄ + chiral ligand to give one enantiomer of the diol in high ee. Sketch the principle (you don't need to draw the exact ligand).

36.25 (challenge) Predict the product: a 1,3-diene (e.g., 1,3-butadiene) + O₃, then Zn/H₂O. Compare to a single alkene.

Section F — Dissolving metal reductions

36.26∗ (routine) Predict the product of each: (a) benzene + Na/NH₃(l) + EtOH → ? (b) toluene + Na/NH₃(l) + EtOH → ? (regiochemistry) (c) anisole (methoxybenzene) + Na/NH₃(l) + EtOH → ? (regiochemistry) (d) 4-aminobenzene → product after reduction (use Zn/HCl or H₂/Pd)

36.27 (moderate) What is the Birch reduction? Identify the chemistry: single-electron reduction by Na to form a radical anion, then protonation by EtOH.

36.28 (challenge) Why does the Birch reduction of substituted benzenes give the 1,4-cyclohexadiene with the substituent in a specific position? Discuss for both donor and withdrawing substituents.

Section G — Selectivity

36.29∗ (routine) A substrate has both an aldehyde and an ester. Predict the products of: (a) NaBH₄, (b) LiAlH₄.

36.30 (routine) A substrate has both a ketone and a nitro group. Predict the products of: (a) H₂/Pd/C, (b) NaBH₄.

36.31 (moderate) A substrate has both an alkene and an aldehyde. Predict the products of: (a) NaBH₄, (b) H₂/Pd/C, (c) NaBH₄ + H₂/Pd/C.

36.32 (challenge) Design a synthesis that selectively reduces a specific functional group while sparing others. Use a flowchart (or decision tree) to describe the reagent choice.

Section H — Biology

36.33∗ (routine) Sketch the chemistry of NAD⁺ + alcohol → NADH + ketone. Identify the hydride transfer.

36.34 (routine) The mitochondrial electron transport chain shuttles electrons from NADH and FADH₂ to O₂. What happens at each complex (I-IV)? What is the net product (water)?

36.35 (moderate) Cytochrome P450 enzymes oxidize many drugs. What is the chemistry: $RCH_3 + O_2 + NADPH \to RCH_2OH + H_2O + NADP^+$. Identify the oxygen activation step.

36.36 (moderate) A drug is metabolized by CYP3A4 to its inactive form. Why does this matter clinically? Connect to drug-drug interactions.

36.37 (challenge) Glucose oxidation in the body: glucose + O₂ + NAD⁺ → CO₂ + H₂O + NADH (eventually). Trace the pathway: glycolysis (glucose → 2 pyruvate, generating NADH), pyruvate dehydrogenase (pyruvate → acetyl-CoA + NADH + CO₂), citric acid cycle (acetyl-CoA → 2 CO₂ + 3 NADH + FADH₂ + ATP). What is the final electron acceptor?

Section I — Mechanism drawing

36.38∗ (moderate) Draw the mechanism for: cyclohexanol + PCC → cyclohexanone + CrO(OH).

36.39 (moderate) Draw the mechanism for the Swern oxidation of cyclohexanol to cyclohexanone.

36.40 (challenge) Draw the mechanism for the catalytic hydrogenation of cyclohexene to cyclohexane on a Pd surface. Identify the four key steps: alkene adsorption, H₂ adsorption, H transfer, and product desorption.

36.41 (challenge) Draw the mechanism for the OsO₄ + alkene → osmate ester → diol cycle. Identify the [3+2] cycloaddition.

Section J — Multistep synthesis

36.42∗ (routine) Design a synthesis of 4-chlorobenzaldehyde from 4-chlorotoluene using a side-chain oxidation.

36.43 (moderate) Design a synthesis of cyclohexanecarboxylic acid from cyclohexene using: alkene oxidation + alcohol oxidation.

36.44 (moderate) Design a synthesis of 1,2-cyclohexanediol (cis) from cyclohexene using OsO₄.

36.45 (challenge) Design a synthesis of 4-aminobenzoic acid from toluene: nitration, oxidation of methyl to COOH, then reduction of NO₂ to NH₂. Show the order of steps.

36.46 (challenge) Design a synthesis of 2-butanol with a specific (R)-configuration: use asymmetric reduction of butan-2-one with CBS reagent.

Section K — Spectroscopy

36.47∗ (routine) A reaction starts with a compound showing IR at 3300 (broad) + 2950. After oxidation, the IR shows 1715 + 2820/2720 (aldehyde C-H). What was the reaction?

36.48 (routine) A reaction starts with IR at 1715 (carbonyl). After reduction, the IR shows 3300 (broad) + 2950. ¹H NMR shows new -CH(OH)- multiplet at δ 3.5. What was the reaction?

36.49 (challenge) Three compounds with formula C₅H₁₀O. (a) IR 3300 broad, ¹H NMR -CH(OH)- multiplet. (b) IR 1715, ¹H NMR -CO-CH₃ singlet. (c) IR 1720 + 2820/2720 (aldehyde doublet). Identify each by IR and ¹H NMR. What's the relationship in oxidation state?

36.50 (challenge) Combine reduction + oxidation: take an aldehyde, reduce to an alcohol with NaBH₄, then re-oxidize with PCC. What changes? What stays the same? Sketch the cycle.

Notes for instructors: Common stumbling blocks for Chapter 36: (1) Confusing PCC (stops at aldehyde) with Jones (goes to COOH). (2) Forgetting that NaBH₄ can't reduce esters. (3) Mismatching catalysts (Lindlar vs Pd/C vs Na/NH₃) for alkyne reductions. (4) Failing to assign correct oxidation states. Computational exercises: predict which carbon in a complex molecule will be most reactive toward CYP-mediated oxidation using an electronic-property descriptor.