In addition to malonic esters, esters of acetoacetic acid (3-oxobutanoic acid) are also commonly used for these reactions and the reactions are generally referred to as the acetoacetic ester synthesis. The a-hydrogens of ethyl acetoacetate have a pK_a of about 10, and in the presence of ethoxide in ethanol, they are completely converted to the enolate anion. Again, if an alkyl halide is present, this enolate anion can undergo an S_N2 reaction to give a mono-alkyl acetoacetic ester.

Acid hydrolysis generates a b-keto carboxylic acid. These are unstable, and undergo decarboxylation in the acidic solution to give the enol, which isomerizes to give the final product, a methyl ketone. You should note that three carbons of the acetoacetic ester have been added to the carbon skeleton of the alkyl halide which was used in the first step. Thus, using the acetoacetic ester synthesis, three carbons (a CH₂, a carbonyl and a CH₃) can be appended to virtually any primary, allyl or benzyl halide.

An example of an acetoacetic ester synthesis is shown below. Reaction of 1-bromopropane with ethylacetoacetate in ethoxide/ethanol yields the alkylated product. Acidification hydrolyzes the ester and the intermediate b-keto acid decarboxylates to form the final product, 2-hexanone. The red line in the figure shows the bond which was formed in the reaction and the propyl unit and the three carbons from the acetoacetic ester can be clearly identified.

The alkylation of less acidic a-hydrogens can be accomplished using LDA to completely convert the carbonyl compound into the desired enolate anion. This is then reacted with an alkyl halide to give the alkylated product.

This reaction is useful with ketones, aldehydes, esters and nitriles, as shown below: