Carbonyl Chemistry

Reactivity of the C=O Group

The carbonyl carbon is electrophilic because oxygen withdraws electron density; nucleophiles attack the carbon and the pi bond breaks to an alkoxide. Aldehydes are more reactive than ketones (less steric hindrance, less electron donation). Aldehydes and ketones undergo nucleophilic addition, while carboxylic acid derivatives undergo nucleophilic acyl substitution because they carry a leaving group.

Key Reactions

Alcohols add to give hemiacetals then acetals (the basis of sugar ring formation); amines give imines; hydride reagents reduce. NaBH$_4$ is mild (aldehydes and ketones only), LiAlH$_4$ is strong (also esters and acids). Alpha-hydrogens are acidic, enabling enolate formation and the aldol condensation, which joins two carbonyl compounds into a beta-hydroxy carbonyl and, after dehydration, an enone.

Carboxylic Acid Derivatives

Reactivity follows leaving-group ability: $\text{acyl chloride} > \text{anhydride} > \text{ester} \approx \text{carboxylic acid} > \text{amide}$ More reactive derivatives convert into less reactive ones. Esters hydrolyze by acid catalysis or by base (saponification); thioesters like acetyl-CoA are biology's activated acyl carriers.

Key Takeaways

• Addition for aldehydes/ketones; acyl substitution when a leaving group exists.
• Memorize the derivative reactivity ladder — interconversions only run downhill.
• NaBH$_4$ vs. LiAlH$_4$ selectivity is a recurring discrete question.
• Aldol and enolate chemistry hinge on acidic alpha-hydrogens.