Green chemistry approaches to the Knoevenagel condensation: comparison of ethanol, water and solvent free (dry grind) approaches

We report a comparative study of the Knoevenagel condensation with a variety of substituted benzaldehydes (17 examples) and cyanoamides (3 examples), using three different methodologies: (a) traditional ethanol reflux; (b) water reflux; and (c) solvent free conditions. Almost without exception these reactions proceeded faster, more cleanly and in higher yields when the reactions were conducted in a solvent-free fashion. Additionally, our solvent free approach allowed the use of nitrobonzaldehydes, which failed to yield the desired products under traditional and water based approaches. (C) 2002 Elsevier Science Ltd. All rights reserved.