Comparison of Amino Acid-Catalyzed Reaction Options for the Knoevenagel Condensation

Abstract

The Knoevenagel condensation reaction is a classic condensation reaction that is frequently utilized in the production of fluorescent probes important to biological and disease research. Piperidine is the most common catalyst, although a few reports have used amino acids, particularly glycine. Amino acid catalysts are less toxic than piperidine, can efficiently catalyze condensations without need for isolation separation, or purification, and will not interfere with photophysical or biological studies. The amino acid-catalyzed option has been examined more closely, with a focus on glycine, histidine, arginine, or prolinate. Reaction rates and product yields have been compared across several reactions. The presence of histidine resulted in faster reaction rates across several reactions as compared with the presence of glycine, while prolinate best catalyzed reactions using less acidic active methylene compounds.