Malonic ester synthesis

The malonic ester synthesis is a chemical reaction where diethyl malonate or another ester of malonic acid is alkylated at the carbon alpha (directly adjacent) to both carbonyl groups, and then converted to a substituted acetic acid.^[1] The major drawback of malonic ester synthesis is that the alkylation stage can also produce dialkylated structures. This makes separation of products difficult and yields lower.^[2]

Mechanism[]

The carbons alpha to carbonyl groups can be deprotonated by a strong base. The carbanion formed can undergo nucleophilic substitution on the alkyl halide, to give the alkylated compound. On heating, the di-ester undergoes thermal decarboxylation, yielding an acetic acid substituted by the appropriate R group.^[3] Thus, the malonic ester can be thought of being equivalent to the ⁻CH₂COOH synthon.

The esters chosen are usually the same as the base used, i.e. ethyl esters with sodium ethoxide. This is to prevent scrambling by transesterification.

Variations[]

Dialkylation[]

The ester may be dialkylated if deprotonation and alkylation are repeated before the addition of aqueous acid.

Cycloalkylcarboxylic acid synthesis[]

Intramolecular malonic ester synthesis occurs when reacted with a dihalide.^[4][5] This reaction is also called the Perkin alicyclic synthesis (see: alicyclic compound) after investigator William Henry Perkin, Jr.^[6]

See also[]

• Knoevenagel condensation
• Acetoacetic ester synthesis

References[]