Ecofriendly Approach for the Large‐Scale Synthesis of 4‐Unsubstituted Coumarin‐3‐carboxylic Acids from o‐Hydroxy‐araldehydes with Meldrum's Acid in the Water‐SDS Micellar System

Abstract

This paper introduces a base and catalyst‐free “on water” protocol for the “Green” access to a series of privileged, potential biologically active important synthetic targets coumarin‐3‐carboxylic acids of diverse structures bearing electron withdrawing/donating groups, hydrophobic long chain alkyl groups in aromatic ring. The target compounds were synthesized by reacting substituted o‐hydroxy‐aryldehydes with Meldrum's acid in the water ‐ SDS micellar system. Water‐SDS is a proven, yet powerful surfactant system to provide hydrophobic cavities in water as a reactor for the organic reactants. It is believed that the condensation occurs inside the hydrophobic cavity which helps the completion of the reaction. Multi‐gram scale reaction was also performed to demonstrate the scalability and practical applicability of the developed methodology. Moreover, the reusability of the post‐reaction waste shows that the waste can be reused in consecutive cycles without compromising the yield. The structure of one of the synthesized compounds was further confirmed by single‐crystal XRD studies. This developed protocol promises advantages like energy efficiency, operational simplicity, easy workup, chromatography‐free purification, recyclability of post‐reaction waste, scalable method and provides excellent yields of the targeted coumarin ‐3‐carboxylic acids.

Synthesis and in vitro antimicrobial activity evaluation of coumarin-3-carboxylic acids obtained via cascade reaction using chitosan as a recyclable catalyst

“…This methodology provided results superior to those achieved by various methods related in the literature as sustainable and eco-friendly using homogeneous catalysts and water as solvent. 13,17,29,30 However, when using monosubstituted salicylaldehyde derivatives containing bulky groups (entry 8, Table 4) or disubstituted (entry 9, Table 4), the reactions proceeded slowly. In this case, their reaction showed low yields, likely due to the low solubility of these substrates in water.…”

“…15 Several other conditions for the synthesis of coumarin-3-carboxylic acids can also be found in the literature. [16][17][18] However, to the best of our knowledge, the application of natural polymers has not still been reported.…”