Methods utilising diethyl malonate

The retrosynthetic summary emphasises that diethyl malonate may be regarded as an acetic acid equivalent, and may be used when a disconnection gives rise to the synthonseCH2-C02H or 20CH,CO2H. The use of diethyl malonate in the preparation of carboxylic acids is illustrated in the sections below. 

When treated with one equivalent of sodium ethoxide, diethyl malonate is converted into the mono-sodio derivative, as a result of removal by base of one of the oc-methylene protons to yield a mesomeric anion (12). This nucleophilic anion undergoes an SN2 reaction with an alkyl halide to give a C-substituted malonic ester. A second, different, alkyl group can be similarly introduced on to the a-carbon atom, or alternatively two identical alkyl groups may be introduced in a one-step operation by using appropriate proportions of reactants. 

Alkaline hydrolysis of an alkylmalonic ester followed by careful acidification at 0°C gives the alkylmalonic acid (e.g. Expt 5.133). The alkylmalonic acids 

Typically the addition of the mesomeric anion (12) to the a, /1-unsaturated ester, diethyl fumarate, proceeds in a 1,4-manner (the Michael reaction or Michael addition). 

The resulting tetraethyl ester on hydrolysis and decarboxylation yields propane-1, 2,3-tricarboxylic acid.155 In this example the malonate anion is generated by using one molar proportion of sodium ethoxide this is Michael s original method. However, these conditions sometimes lead to competing side reactions and the formation of abnormal reaction products. Better yields of the required product are often obtained with small amounts of sodium ethoxide (the so-called catalytic method) or in the presence of a secondary amine (e.g. diethyl-amine, see below). 

---