Study insights into the different cyclization mechanisms of ethyl cyanoacetate with salicylaldehyde and efficient synthesis of coumarin-3-carboxylate ester

Abstract

The condensation of ethyl cyanoacetate and salicylaldehyde would afford either coumarin-3-carboxylate ester or 3-cyancoumarin as the final product. Herein, comparative experiments and density functional theory (DFT) calculations were investigated to pursue a deeper understanding of the critical factor in this reaction. Experimental results indicated that condensation is accomplished through a cascade process, including the Knoevenagel procedure followed by selective cyclization of the phenolic hydroxyl group to the cyano or ester carbonyl group within the intermediate. Product distribution correlates well with the acid–base properties of the catalyst and the ability of the catalyst for forming complex by hydrogen bonds. Also, an efficient and facile approach was developed for the preparation of coumarin-3-carboxylate ester as a major product from the reaction of ethyl cyanoacetate with salicylaldehyde. Low-transition-temperature mixture (LTTM) formed from L-proline and oxalic acid was proved as an inexpensive, easily available, and efficient promoter which not only affords the products in high yields but also avoids the use of hazardous solvent and tedious isolation procedures.