Formation of the enolate nucleophile
The aldol condensation begins with deprotonation of an alpha hydrogen on a ketone or aldehyde by a base (often hydroxide or an amine). This removes a proton from the carbon next to the carbonyl, creating an enolate ion that has negative charge and can move between the carbon and oxygen atoms. The enolate is stabilized by resonance; the negative charge lives on both the carbon and the oxygen. This carbanion character makes the alpha carbon nucleophilic and ready to attack.
Nucleophilic addition and dehydration
The enolate attacks the electrophilic carbonyl carbon of another ketone or aldehyde molecule, forming a C-C bond and creating an alkoxide intermediate. Protonation of the alkoxide gives the aldol product, a beta-hydroxy ketone or aldehyde. If the reaction is heated or the conditions are acidic, the aldol typically loses water (dehydrates) to form an alpha-beta unsaturated carbonyl. This condensation product is often the observed result and is more stable than the aldol itself.
Scope and synthetic utility
The aldol is a carbon-carbon bond formation that builds larger molecules from smaller carbonyl compounds. If both reactants have alpha hydrogens, the reaction can be complicated by multiple possible enolates and products. Controlling selectivity requires using a ketone (or aldehyde) that cannot form an enolate as the electrophile, or using an enolate equivalent like an enamine or silyl enol ether. The aldol and its dehydrated product appear in countless natural products and syntheses, making it a fundamental reaction in organic chemistry and pharmaceutical manufacturing.