Named Reactions: Baeyer–Villiger oxidation MCQs With Answer

Introduction

Baeyer–Villiger oxidation is an essential named reaction in advanced organic chemistry, converting ketones into esters and cyclic ketones into lactones through the insertion of an oxygen atom adjacent to the carbonyl. For M.Pharm students, mastering the mechanism, reagent selection, migratory aptitude, and stereochemical outcome is crucial for drug-like molecule modification and synthesis planning. This quiz focuses on key mechanistic features (the Criegee intermediate and migration step), reagent choices (mCPBA, peracids, enzymatic BV monooxygenases), and factors controlling regio- and stereoselectivity. These MCQs will reinforce concepts relevant to medicinal chemistry, process development, and biocatalytic applications.

Q1. What is the primary chemical transformation effected by the Baeyer–Villiger oxidation?

• Conversion of ketones to esters and cyclic ketones to lactones
• Oxidation of primary alcohols to carboxylic acids
• Reduction of ketones to secondary alcohols
• Hydroxylation of aromatic rings

Correct Answer: Conversion of ketones to esters and cyclic ketones to lactones

Q2. Which reagent is most commonly used in laboratory Baeyer–Villiger oxidations for good selectivity and yields?

• meta-Chloroperoxybenzoic acid (mCPBA)
• Pyridinium chlorochromate (PCC)
• Lewis acid AlCl3
• Sodium borohydride (NaBH4)

Correct Answer: meta-Chloroperoxybenzoic acid (mCPBA)

Q3. What is the name of the characteristic tetrahedral intermediate formed when the peracid adds to the ketone in Baeyer–Villiger oxidation?

• Criegee intermediate
• Zimmerman intermediate
• Nef intermediate
• Birch intermediate

Correct Answer: Criegee intermediate

Q4. Which of the following correctly represents the general migratory aptitude (most → least) in Baeyer–Villiger reactions?

• Tertiary alkyl > secondary alkyl > aryl > primary alkyl > methyl
• Methyl > primary alkyl > aryl > secondary alkyl > tertiary alkyl
• Aryl > tertiary alkyl > secondary alkyl > primary alkyl > methyl
• Primary alkyl > methyl > secondary alkyl > tertiary alkyl > aryl

Correct Answer: Tertiary alkyl > secondary alkyl > aryl > primary alkyl > methyl

Q5. What is the expected product when cyclohexanone undergoes Baeyer–Villiger oxidation?

• ε-Caprolactone (a seven-membered lactone)
• γ-Butyrolactone (a five-membered lactone)
• Benzoic acid
• Cyclohexanol

Correct Answer: ε-Caprolactone (a seven-membered lactone)

Q6. How does an electron-donating substituent on the migrating group affect its migratory aptitude in Baeyer–Villiger oxidation?

• It increases migratory aptitude (favors migration)
• It decreases migratory aptitude (inhibits migration)
• It has no influence on migratory aptitude
• It causes complete reversal of regioselectivity

Correct Answer: It increases migratory aptitude (favors migration)

Q7. What is the stereochemical outcome at a stereogenic center that migrates during the Baeyer–Villiger rearrangement?

• Retention of configuration at the migrating center
• Complete inversion of configuration at the migrating center
• Racemization at the migrating center
• No stereochemical information is transmitted; mixture forms

Correct Answer: Retention of configuration at the migrating center

Q8. Which step is generally considered rate-determining in the Baeyer–Villiger mechanism?

• The migration (rearrangement) step of the Criegee intermediate
• Initial nucleophilic attack of the peracid on the carbonyl
• Deprotonation of the peracid
• Hydrolysis of the ester product

Correct Answer: The migration (rearrangement) step of the Criegee intermediate

Q9. Which cofactor is commonly used by Baeyer–Villiger monooxygenase enzymes (BVMOs) in biocatalytic oxidations?

• Flavin adenine dinucleotide (FAD or FMN)
• NADH alone without flavin
• Biotin
• S-adenosylmethionine (SAM)

Correct Answer: Flavin adenine dinucleotide (FAD or FMN)

Q10. When acetophenone (PhCOCH3) undergoes Baeyer–Villiger oxidation with mCPBA, which ester is predominantly formed?

• Phenyl acetate (Ph-O-CO-CH3)
• Methyl benzoate (CH3-O-CO-Ph)
• Benzoic acid
• Acetic anhydride

Correct Answer: Phenyl acetate (Ph-O-CO-CH3)

Q11. Why is mCPBA often preferred over peracetic acid for Baeyer–Villiger oxidations in sensitive syntheses?

• mCPBA is milder and gives fewer side reactions and better selectivity
• mCPBA is a stronger acid and forces complete conversion
• Peracetic acid is non-oxidizing
• mCPBA does not generate any carboxylic acid by-product

Correct Answer: mCPBA is milder and gives fewer side reactions and better selectivity

Q12. What is the general effect of Lewis acid catalysts (e.g., BF3·OEt2) on Baeyer–Villiger oxidations?

• They coordinate to the carbonyl, increasing electrophilicity and accelerating reaction
• They quench the peracid and inhibit oxidation completely
• They convert the reaction into a reduction pathway
• They change esters into ethers directly

Correct Answer: They coordinate to the carbonyl, increasing electrophilicity and accelerating reaction

Q13. For an unsymmetrical ketone, which principle best predicts regiochemical outcome in a Baeyer–Villiger oxidation?

• The group with higher migratory aptitude migrates preferentially
• The smaller group always migrates
• The less substituted group migrates preferentially
• The migration is random and cannot be predicted

Correct Answer: The group with higher migratory aptitude migrates preferentially

Q14. What is the typical stoichiometric by-product formed when an organic peracid (RCO3H) is used in a Baeyer–Villiger oxidation?

• The corresponding carboxylic acid (RCO2H)
• A ketone derived from the peracid
• An alcohol derived from the peracid
• Hydrogen gas

Correct Answer: The corresponding carboxylic acid (RCO2H)

Q15. Which ketone among the following would you expect to undergo Baeyer–Villiger oxidation most readily (fastest migration)?

• pivalophenone (tert-butyl phenyl ketone)
• acetone (dimethyl ketone)
• propiophenone (ethyl phenyl ketone)
• 1-phenyl-2-propanone (secondary alkyl phenyl ketone)

Correct Answer: pivalophenone (tert-butyl phenyl ketone)

Q16. How does an electron-withdrawing substituent on the migrating group affect the Baeyer–Villiger rearrangement?

• It decreases migratory aptitude and disfavors migration of that group
• It increases migratory aptitude and strongly favors migration
• It has no measurable effect on migration
• It causes immediate hydrolysis of the Criegee intermediate

Correct Answer: It decreases migratory aptitude and disfavors migration of that group

Q17. Which description best characterizes the Criegee intermediate in the Baeyer–Villiger mechanism?

• A tetrahedral peroxyhemiacetal-like adduct where one oxygen is bound to carbon and another to the peracid fragment
• A radical cation centered on the carbonyl carbon
• A free carbocation generated before migration
• A stable aromatic ion formed transiently

Correct Answer: A tetrahedral peroxyhemiacetal-like adduct where one oxygen is bound to carbon and another to the peracid fragment

Q18. What common side reaction should be considered when performing Baeyer–Villiger oxidation on substrates containing carbon–carbon double bonds?

• Competing epoxidation of the double bond by the peracid
• Hydrogenation of the double bond by the peracid
• Formation of Grignard reagents
• Polymerization of the double bond under neutral conditions

Correct Answer: Competing epoxidation of the double bond by the peracid

Q19. Which of the following factors does NOT favor migration of a substituent in the Baeyer–Villiger rearrangement?

• Presence of a strongly electron-withdrawing group on that substituent
• Greater tertiary substitution at the migrating center
• Ability of the migrating group to stabilize positive charge by resonance
• Electron-donating substituents on the migrating carbon

Correct Answer: Presence of a strongly electron-withdrawing group on that substituent

Q20. When 2-methylcyclobutanone undergoes Baeyer–Villiger oxidation, which lactone is most likely formed?

• A five-membered γ-lactone bearing the methyl on the carbon adjacent to the oxygen (ring-expanded product)
• A three-membered lactone with methyl substitution
• Unchanged 2-methylcyclobutanone (no reaction)
• A linear methyl ester with loss of ring structure

Correct Answer: A five-membered γ-lactone bearing the methyl on the carbon adjacent to the oxygen (ring-expanded product)

Download