3-Oxobutanoate esters, acidity acylation

In 1887, Claisen and Lowman reported that the condensation of 2 mol of an ester, such as ethyl acetate, in the presence of base gave the p-keto ester, ethyl acetoacetate (ethyl 3-oxobutanoate equation 1). The intramolecular equivalent was recognized by Dieckmann in 1894. He found that heating an adipic acid ester with sodium and a trace of alcohol led to cyclization, with the formation of a cyclopentanone (equation 2). The reaction was, at an early stage, extended to the acylation of ketones. Claisen himself reported the base-catalyzed reaction of acetophenone and ethyl benzoate to give dibenzoylmethane in 1887. This reaction, too, has an intramolecular parallel. The acylation of ketones with esters and other acid derivatives is sometimes called a Claisen condensation, although this usage is criticized by some writers and avoided by others. A widely used example of ketone acylation is the synthesis of a-formyl (hydroxymethylene) ketones (equation 3). Intramolecular variants of this reaction include the classical synthesis of dimedone (Scheme 1). 

MCI-186, has been developed as a medical drug for brain ischemia. The preparation of pyrazol-3-ones 57a-m was achieved by refluxing /i-keto esters 56a-m and hydrazines 2a-m in ethanol or acetic acid. /i-Keto esters 56d,e,j,l,m, which are not commercially available, were synthesized from acyl chlorides 52a,b, nitrile 53 or ethyl esters 55a,b with the appropriate reagents (Scheme 13). Ethyl 2-acetyl-3-methylbut-3-enoate 56k was prepared in 43% yield from ethyl 3-oxobutanoate 56a by first forming ethyl 3-oxobutanoate sodium salt and then treating the salt with isobutyl iodide in THF at 80 °C. 

Under the catalysis of ligases of the acid-thiol type, 2-oxoacids are transformed into acyl-CoA esters or by the action of decarboxylases (carboxylyases) into aldehydes having one carbon atom less than the original amino acid. For example, decarboxylation of pyruvic acid yields acetaldehyde and decarboxylation of 2-oxobutanoic acid gives propanal. The same aldehydes also form by Strecker... 

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