Pyridine, Perkin condensation with

The methylene groups of hippuric acid and malonic acid are much more reactive than that of acetic acid. They may be caused, therefore, to condense with aldehydes under much milder conditions, e.g. by the action of pyridine. The use of malonic acid forms an extension of Perkin s reaction to the aliphatic series (Doebner), e.g. 

The most important modification of the Perkin reaction was developed by Oglialoro using the sodium salt of acetic acid (e.g., phenylacetic acid, phenoxyacetic acid ) in condensation with acetic anhydride and an aldehyde (e.g., benzaldehyde, paraldehyde ). This type of reaction is referred to as the Perkin-Oglialoro reaction,Perkin-Oglialoro condensation, or Oglialoro modification. Other modifications include the use of different bases as the catalysts, (e.g., NaB(OMe)4-LiCl, CaH2, CsOAc, and CsF ), the use of microwave irradiation and cesium acetate or fluoride in combination with a small amount of pyridine as catalyst and the continuous distillation of acetic acid to enhance the conversion rate. ... 

The acid has been prepared through the Perkin reaction,1 by the condensation of furfural with malonic acid in the presence of pyridine,2 and, on a large scale, by the modified Perkin procedure of Johnson.3... 

This reaction type leading to oc,/ -unsaturated acids and esters is exemplified in the Perkin reaction (Section 6.12.3, p. 1036) and the Knoevenagel reaction (Section 5.11.6, p. 681). The Doebner reaction, which is illustrated in this section, is the condensation of an aldehyde with malonic acid in pyridine solution, often in the presence of a trace of piperidine. The reaction mechanism involves the addition of a malonate anion to the aldehydic carbonyl carbon atom followed by the elimination of water accompanied by decarboxylation. 

Decarboxylation of a-keto acids. Phenylglyoxylic acid is decarboxylated smoothly by refluxing in benzene with benzoic anhydride and pyridine. Other anhydrides can be used but benzoic anhydride is preferred because Perkin-type condensations... 

Simple aliphatic aldehydes and ketones cannot be used as the carbonyl component in the Perkin reaction. Knoevenagel5 reported the successful condensation of aldehydes and ketones with malonic acid in the presence of ammonia or amines. The most satisfactory method uses pyridine as a catalyst and is known as the Doebner modification.6 Thus, acetaldehyde 18 reacts with malonic acid (19) in the presence of a pyridine catalyst to afford the acid 20 in 60% yield. 

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