The Knoevenagel Reactions of Aldehydes with Carboxy Compounds. I. Reactions ofp-Nitrobenzaldehyde with Active Methine Compounds

The Knoevenagel reactions of p-nitrobenzaldehyde (1) with β-keto acids, methylmalonic (2a) and α-methylacetoacetic acids (2b) were carried out in the presence of a tertiary amine such as pyridine. We have isolated the corresponding β-hydroxy intermediate (3a) by the reaction of 2a which positively suggested the reaction proceeded by the Hann and Lapworth mechanism. A kinetic study using 1H NMR revealed the existence of the reversibility between the starting materials and the β-hydroxy intermediate and that the rate determining step was decarboxylattion. But, when using the secondary amine, both the β-hydroxy acid and the corresponding condensation product were obtained via this reaction. These findings led to the conclusion that the reaction proceeded according to the two competing mechanisms, i.e., the Hann and Lapworth and Knoevenagel mechanisms. It was further clarified that either the decarboxylation step or the formation of the bis(dialkylamino) derivative was the rate determining step. The stereosel...