aldol reactions

Meaning: An aldol reaction is a nucleophilic addition that forms a new carbon–carbon bond. Base removes an acidic α hydrogen from an aldehyde or ketone, giving a resonance-stabilized enolate. The enolate's α carbon attacks the electrophilic carbonyl carbon of a second molecule. Protonation of the resulting alkoxide gives a β-hydroxy aldehyde or ketone (the name combines aldehyde and alcohol). With heat, the product can lose water to give an α,β-unsaturated carbonyl. This is called aldol condensation, and conjugation with the C=O helps drive it. The addition step is reversible; the reverse is a retro-aldol reaction.

On the MCAT: You may be given two carbonyl compounds and asked for the product. Find the α carbon of the nucleophile, bond it to the carbonyl carbon of the electrophile, and turn that carbonyl carbon into a carbon bearing OH. A compound with no α hydrogens, such as formaldehyde or benzaldehyde, can act only as the electrophile. In biochemistry, aldolase cleaves fructose 1,6-bisphosphate in glycolysis by a retro-aldol mechanism.

Common confusion: Students join the two carbonyl carbons, or two α carbons. The nucleophile is the α carbon of the enolate and the electrophile is the carbonyl carbon. Also, aldol addition keeps all atoms and gives a β-hydroxy product; only condensation loses H₂O.