Alternatives to piperidine in Knoevenagel condensation of 2-cyanoacetamide with benzaldehydes

The Knoevenagel condensation (KC) is an important reaction known in organic chemistry for over a century. The catalytic version of this transformation, often with the use of piperidine as the catalyst, gained more attention in recent decades. However, piperidine is classified as a controlled substance and, therefore, its purchase, handling, and storage is highly inconvenient. To bypass the lengthy and laborious regulatory paperwork associated with the use of piperidine, we explored the Knoevenagel condensation of 2-cyanoacetamide with several benzaldehydes in the presence of selected organobases. Herein, we present a few economical and readily available, nitrogen-based homogenous organocatalysts that turned out to be viable alternatives to piperidine in the reaction of 2-cyanoacetamide with benzaldehydes to obtain (E)-2-cyano-3-phenylacrylamides for intended use in medicinal chemistry projects.