Alkylmalonic esters

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... 

The synthesis of a-alkylglutaric acids (e.g. 2-propylglutaric acid, Expt 5.136), is conveniently achieved by allowing an alkylmalonic ester to react with the a, / -unsaturated nitrile, acrylonitrile, in thfe Michael manner and then subjecting the product to vigorous acidic hydrolysis. 

Sasson and Webster119 reported some examples of monoprotic carbon acids, for example alkylmalonic esters and phenylacetylene, that are directly halogenated in high yield by polyhalo alkanes under mild conditions when catalyzed by tetrabutylammonium fluoride (TBAF) (equation 76). They do not discuss the halogenation mechanism other than to say that the reaction is apparently taking place via nucleophilic attack on the tetra-halomethane (equation 77). It is reasonable to believe that it is the carbanion of the sub-... 

Hydrolysis of the alkylated diethyl malonate (a diethyl alkylmalonic ester) gives a malonic acid derivative. 

The alkylmalonic ester has a second acidic proton that can be removed by a base. Removing this proton and alkylating the enolate with another alkyl halide gives a dialkylated malonic ester. Hydrolysis and decarboxylation lead to a disubstituted derivative of acetic acid. 

The Claisen condensation of diethyl oxalate with esters of fatty acids (cf. method 211) produces a-ethoxalyl esters which are thermally de-carbonylated to alkylmalonic esters. The over-all yields range from 78% to 91% for the conversion of fatry esters up to ethyl stearate. Phenyl-malonic ester is made in 85% yield. Powdered glass is sometimes used... 

Hydrolysis of alkylmalonic esters leads to alkylmalonic acids and is invariably carried out with aqueous or alcoholic potassium hydroxide. 

Reaction of this salt with an alkyl halide yields a substituted malonic ester, an ethyl alkylmalonate, often called an alkylmalonic ester ... 

The alkylmalonic ester still contains one ionizable hydrogen, and on treatment with sodium ethoxide it, too, can be converted into its salt this salt can react with an alkyl halide—which may be iKe same as, or different from, the first alkyl halide— to yield a dialkylmalonic ester ... 

Attempts have also been made to replace the sulfuric acid in nitrating acid by other mineral acids. Kispersky and Klager had good success in applying a mixture of anhydrous nitric acid and polyphosphoric acid to the nitration of alkylmalonic esters.113 A mixture of hydrofluoric acid and nitric acid has also been shown114 to have a powerful nitrating action and to convert, e.g., benzene into nitrobenzene in 83% yield at about 0°. 

Alkylmalonic esters are especially suitable starting materials for the preparation of -(hydroxyimino) esters. Shivers and Hauser261 obtained high yields in such cases by means of ethyl nitrite and an equimolar amount of sodium ethoxide. Barry and Hartung recommend carrying out the nitrosation in ethereal solution with sodium nitrite and hydrogen chloride.262... 

Feroci M, Orsini M, Palombi L, Sotgiu G, Colapietro M, Ineci A (2004) Diastereoselective electrochemical carboxylation of chiral a-bromocarboxylic acid derivatives an easy access to unsymmetrical alkylmalonic ester derivatives. J Org Chem 69 487-494... 

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