Questions: Nucleophilic Addition to Aldehydes and Ketones

Question 1

Cyclohexanone reacts with diethylamine (a secondary amine, Et₂NH) under acid catalysis with removal of water. What is the primary organic product?

• A. An imine (C=N–Et)
• B. An enamine (C=C–N)
• C. A hemiacetal
• D. A cyanohydrin

Answer: (B)

Secondary amines (R₂NH) cannot form imines because they have no N–H bond left after the initial addition — they cannot lose a proton to form a C=N double bond. Instead, the reaction proceeds by eliminating the adjacent C–H (an α-hydrogen) to give a C=C–N enamine. Primary amines (R–NH₂) retain an N–H and so can form imines.

Question 2

Aldehydes undergo nucleophilic addition more readily than ketones under equivalent conditions.

• T. True
• F. False

Answer: True

Two factors favor aldehydes. First, ketones bear two alkyl groups on the carbonyl carbon, which creates more steric hindrance that slows nucleophilic attack. Second, alkyl groups are electron-donating, which slightly reduces the electrophilicity of the carbonyl carbon in ketones. Both effects make aldehydes more reactive toward nucleophiles than ketones.

Question 3

Why does acetal formation from an aldehyde and an alcohol require acid catalysis, and why is base catalysis ineffective for this reaction?

Model answer: Acid protonates the carbonyl oxygen, activating it toward nucleophilic attack, and later protonates the hemiacetal hydroxyl to make it a good leaving group. Base would deprotonate the alcohol to give an alkoxide, but alkoxides are poor nucleophiles toward neutral carbonyls and base cannot activate the hydroxyl leaving group — the critical protonation steps simply don't occur under basic conditions.

The mechanism proceeds through protonation of C=O, nucleophilic addition of ROH, protonation of the resulting alkoxide, loss of water to form an oxocarbenium ion, and final addition of a second ROH. Every protonation step requires acid. Base-catalyzed addition of alkoxide to the carbonyl can occur but produces a hemiacetal alkoxide that cannot be further converted to acetal without acid.