One of the most useful reactions involving enolates is their alkylation, using an alkyl halide as electrophile. These reactions are best performed using compounds with acidic a-hydrogens, typically those adjacent to two carbonyls or nitrile groups. Esters of malonic acid (propanedioic acid) are commonly used for these reactions and the reactions are generally referred to as the malonic ester synthesis. The a-hydrogens of diethyl malonate have a pK_a of about 10, and in the presence of ethoxide in ethanol, they are completely converted to the enolate anion.

If an alkyl halide is present, the enolate anion can undergo an S_N2 reaction to give a mono-alkylmalonic ester.

Acid hydrolysis of the diester generates the diacid, which is a b-carbonyl carboxylic acid. These are unstable, and undergo decarboxylation in the acidic solution to give the acid-enol, which isomerizes to give the final product, a simple carboxylic acid. You should note, however, that two carbons of the malonic ester have been added to the carbon skeleton of the alkyl halide which was used in the first step. Thus, using the malonic ester synthesis, two carbons (a CH₂ and a COOH) can be appended to virtually any primary or secondary alkyl halide.

An example of a malonic ester synthesis is shown below. Reaction of benzyl bromide with diethylmalonate in ethoxide/ethanol yields the alkylated product. Acidification hydrolyzes the esters and the intermediate diacid decarboxylates to form the final product, 3-phenylpropanoic acid. The red line in the figure shows the bond which was formed in the reaction and the benzyl unit and the -CH₂COOH (from the malonic ester) can be clearly identified.

Identifying the alkyl halide necessary for a malonic ester synthesis simply requires you to remember that the carboxyl group and the a-carbon will come from the malonic ester, and the remainder of the molecule must come from the alkyl halide. For example, 3-methyl-3-phenylpropanoic acid can be prepared using (1-bromoethyl)benzene, as shown below:

2-Methylpropanoic acid can be prepared by alkylating diethylmalonate twice with bromomethane,

and 4,4-diphenylbutanoic acid can be prepared by alkylation with (2-bromo-1-phenylethyl)benzene.