aldol addition

Meaning: A base removes an acidic α-hydrogen from an aldehyde or ketone, giving a resonance-stabilized enolate, because the negative charge is delocalized onto oxygen. The nucleophilic α-carbon attacks the carbonyl carbon of a second molecule, and protonation of the resulting alkoxide gives a β-hydroxy aldehyde or ketone. Example: 2 CH₃CHO → CH₃CH(OH)CH₂CHO in dilute base. The name combines aldehyde and alcohol.

On the MCAT: Expect to predict the product from a carbonyl compound and base, to identify which carbons join, or to recognize a β-hydroxy carbonyl. Heating, or acid, often drives loss of water to give a conjugated α,β-unsaturated carbonyl; this is aldol condensation. Intramolecular versions can form five- or six-membered rings. The reverse, retro-aldol, appears in biochemistry: aldolase cleaves fructose 1,6-bisphosphate in glycolysis.

Common confusion: Students join the wrong carbons. The nucleophile is the α-carbon and the electrophile is the carbonyl carbon, so the new C–C bond runs from the α-carbon of one molecule to the carbonyl carbon of the other. A carbonyl compound with no α-hydrogens, such as benzaldehyde or formaldehyde, cannot form an enolate and can act only as the electrophile. Also, addition keeps the OH group; condensation loses it as water.