A new finding in the old Knoevenagel condensation reaction

Abstract

Reaction of benzaldehyde (5a) with defined quantities of ethyl cyanoacetate (6) in presence of piperidine was studied. In a neat condition, hexasubstituted cyclohexeneamine (7a) with three ester substituents was formed along with ethyl acrylate (9a); occasionally the triesters (7) were transformed to diesters (8). (7) and (8) had uniquely defined stereochemistry. Many substituted aromatic aldehydes and pyridine-3 and 4-aldehydes exhibited this reaction. Cyclohexenes were also formed in solutions. Mass spectral evidence showed the presence of small percentage of isomeric tri and diesters. Mechanistic and other aspects are discussed. Richly substituted cyclohexene amine esters are attractive substrates for medicinal chemistry.

Keywords

• Knoevenagel
• Ethyl cyanoacetate
• Cyclohexene
• Neat reaction