Alanine Knoevenagel reaction

Amino acids may also be applied as catalysts in the Knoevenagel reaction 914,915 thus ethyl 2-cyano-4-methyl-2-pentenoate has been prepared in 87% yield from 2-butanone and ethyl cyanoacetate in the presence of /9-alanine.916 Other catalysts that have been recommended are benzylamine (additional to the salt of a secondary amine), 917 ion-exchangers,918 and alkali fluorides.919... 

Knoevenagel reactions between triethyl phosphonoacetate and salicylaldehyde or its derivatives (Scheme 11)(r1 = H or Br, = H, OMe or OEt) in the presence of piperidine acetate/ -alanine in refluxing toluene resulted in condensation followed by cyclization to give 3-coumtuinylphosphonic esters, reducible to the dihydro derivatives. 

In the formation of the first synthetic intermediate in Sequence D, the very effective Verley-Doebner modification of the fundamental Knoevenagel condensation is used. This modification uses malonic acid in place of the conventional ester to promote enoUzation. In addition, the heterocyclic amine, pyridine, functions as both the base catalyst and the solvent. A cocatalyst, P-alanine (an amino acid), is also introduced. Mechanistically, the reaction closely resembles the aldol condensation in that in both cases a carbanion is generated by abstraction, by base, of a proton alpha to a carbonyl group. The resulting carbanion is stabilized as an enolate anion (see below). 

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