Themalonic ester synthesis is achemical reaction wherediethyl malonate or anotherester ofmalonic acid isalkylated at the carbonalpha (directly adjacent) to bothcarbonyl groups, and then converted to a substitutedacetic acid.^[2]

A 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.^[3]

The carbons alpha tocarbonyl groups can be deprotonated by a strong base. The carbanion formed can undergonucleophilic substitution on the alkyl halide, to give the alkylated compound. On heating, the di-ester undergoesthermal decarboxylation, yielding an acetic acid substituted by the appropriate R group.^[1] Thus, the malonic ester can be thought of being equivalent to the⁻CH₂COOHsynthon.

The esters chosen are usually the same as the base used, i.e. ethyl esters withsodium ethoxide. This is to prevent scrambling bytransesterification.

The ester may be dialkylated ifdeprotonation and alkylation are repeated before the addition of aqueous acid.^{[citation needed]}

Intramolecular malonic ester synthesis occurs when reacted with adihalide.^[4][5] This reaction is also called thePerkin alicyclic synthesis (see:alicyclic compound) after investigatorWilliam Henry Perkin, Jr.^[6]

In the production of medicines, malonic ester is used for the synthesis ofbarbiturates, as well as sedatives and anticonvulsants.

Used in organic synthesis.

• Knoevenagel condensation
• Acetoacetic ester synthesis

• Malonate esters
• Substitution reactions
• Carbon-carbon bond forming reactions

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