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 SN2 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.
15.33:
Alkylation of β-Ketoester Enolates: Acetoacetic Ester Synthesis
Acetoacetic ester synthesis is a method to obtain ketones from alkyl halides and β-keto esters. The reaction occurs in the presence of an alkoxide base that abstracts the acidic proton of the β-keto esters. The step results in an enolate ion which is doubly stabilized. The enolate then reacts with an alkyl halide via the SN2 process to produce an alkylated ester intermediate with a new C–C bond. The hydrolysis of the intermediate, followed by acidification, results in an alkylated β-keto acid. Under high-temperature conditions, the β-keto acid undergoes decarboxylation to form a ketone. However, if the alkylation is repeated before hydrolysis and decarboxylation steps, a disubstituted ketone is obtained.