15.34 : β-ジエステルエノラートのアルキル化: マロン酸エステルの合成

In malonic ester synthesis, β-diesters bearing acidic α protons in the presence of a base and an alkyl halide generate substituted acetic acids via alkylated malonic ester intermediates.

Initially, the base removes the α proton of the diester to generate a nucleophilic enolate ion that is highly stabilized by three resonance structures.

Alkylating the anionic carbon through an S_N2 mechanism produces an alkyl malonic ester intermediate. This undergoes hydrolysis followed by acidification to give the β-diacid.

The β-diacid, at high temperatures, undergoes a concerted process that expels CO₂ to produce an enol. This rapidly tautomerizes to the stable keto form of the substituted acetic acid.

As the reaction comprises the elimination of a single proton, the resulting acid is monosubstituted.

If, however, the monoalkylated intermediate is subjected to the second alkylation process, a disubstituted acid will result.