Diethyl malonate, alkylation carboxylic acids from

Section 21 7 The malonic ester synthesis is related to the acetoacetic ester synthesis Alkyl halides (RX) are converted to carboxylic acids of the type RCH2COOH by reaction with the enolate ion derived from diethyl mal onate followed by saponification and decarboxylation... 

If the first two steps of the reaction sequence are repeated prior to hydrolysis and decarboxylation, then a carboxylic acid having two new alkyl groups on the a carbon can be synthesized. This is illustrated in the synthesis of 2-benzylbutanoic acid [CH3CH2CH(CH2CgH5)COOH] from diethyl malonate ... 

The second method for preparing amino acids is based on the malonic ester synthesis. Recall from Section 23.9 that this synthesis converts diethyl malonate to a carboxylic acid with a new alkyl group on its a carbon atom. 

A combination of two of the reactions discussed in this chapter—alkylation of an a-carbon and decarboxylation of a j8-dicarboxylic acid—can be used to prepare carboxylic acids of any desired chain length. The procedure is called the malonic ester synthesis because the starting material for the synthesis is the diethyl ester of malonic acid. The first two carbons of the carboxylic acid come from malonic ester, and the rest of the carboxylic acid comes from the alkyl halide used in the second step of the reaction. 

Microwaves Alkylation of ethylphenyl sulfonyl acetate, diethyl malonate, anions derived from active methylene Dihalocyclopropanation of substituted olefins under LLPTC and SLPTC conditions Ethoxylation of o,p-nitrochlorobenzene Reactions of carboxylic acids with halides Wang and Jiang (1992), Wang et al. (1995) Villemin and Labiad (1992) Yuan et al. (1992a) Yuan et al. (1992b)... 

When this reaction is carried out on the parent diethyl malonate, acetic acid results, and the process is of no practical synthetic utility. As with the synthesis of ketones starting from P-keto esters, this process is far more usefiil when combined with the alkylation reaction. One or two alkylations of malonic ester give substituted diesters that can be hydrolyzed and decarboxylated to give carboxylic acids (Fig. 19.62). Substituted acetic acids are potential sources of esters, acid halides, and any other compound that can be made from a carboxylic acid. 

Alkyl halides are converted to carboxylic acids by reaction with the enolate derived from diethyl malonate, followed by saponification and decarboxylation. 

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