15.33 : Alkylation of β-Ketoester Enolates: Acetoacetic Ester Synthesis

In acetoacetic ester synthesis, β-keto esters containing acidic α protons are converted to substituted acetones in the presence of a base via an alkylated ester intermediate.

The reaction begins with an alkoxide base abstracting the α proton of the substrate to generate a nucleophilic enolate ion.

The carbanion then attacks the electrophilic carbon of the alkyl halide in an S_N2 reaction to give an alkylated ester with a new C–C bond.

Subsequent hydrolysis, followed by acidification produces a β-keto acid, which, upon heating, undergoes a concerted process and expels CO₂ to produce an enol that tautomerizes to the stable keto form of the substituted acetone.

Since in the reaction, only one proton is removed, the resulting acetone is monosubstituted.

If, however, the monoalkylated intermediate undergoes a second alkylation process, the resulting acetone will be disubstituted.