Definition: What is Malonic Ester Synthesis?

Malonic ester is a diester molecule that can undergo hydrolysis to produce 1,3-dicarboxylic acid. The dicarboxylic acid, if gently heated, can undergo a decarboxylation reaction to produce carbon dioxide and an enol molecule. The enol then interconverts into a more stable carboxylic acid, like acetic acid.  This reaction is commonly known as malonic ester synthesis. This method conveniently allows the synthesis of mono- and disubstituted acetic acids, i.e., carboxylic acids bearing one or two alkyl groups on the α-carbon. The α-carbon on the malonic ester is relatively more acidic as compared to other esters. Alkylation at the alpha position can, therefore, be carried out with an alkyl halide (R-X) and relatively mild bases such as sodium hydroxide (NaOH) or sodium ethoxide (NaOEt) ^[1-7].

Examples of Malonic Ester Synthesis

The most commonly used malonic ester is diethyl malonate, also known as diethyl propanedioate. This method can also be used to synthesize amino acids ^[1-6,8].

Mechanism of Malonic Ester Synthesis

Malonic ester is an active methylene compound. The sequence of reactions is as follows ^[1-3,7]:

1. Deprotonation of the ester to form an enolate
2. Alkylation of an active methylene enolate
3. Hydrolysis of the esters to a dicarboxylic acid
4. Decarboxylation of a 1,3-dicarboxylic acid to give an enol which tautomerizes to α-alkyl carboxylic acid

Applications of Malonic Ester Synthesis

Malonic ester has been found useful in organic synthesis. For example, condensing urea with diethyl malonate produces barbituric acid. A large variety of barbiturate drugs is used for the treatment of insomnia and anxiety ^[9].