Synthesis of C4-substituted coumarins via Pechmann condensation catalyzed by sulfamic acid. Insights into the reaction mechanism by HRMS analysis

Abstract

A series of functionalized C4-substituted coumarins were synthesized by exploring the reaction of activated and non-activated phenols and β-ketoesters under solvent-free conditions in the presence of sulfamic acid as a Br∅nsted acid catalyst. Fifteen examples were prepared with moderate to excellent yields (50% to 90%) using 10 mol % of the catalyst. Furthermore, it was possible from the proposed methodology to scale up the synthesis of coumarins to obtain up to 11 g of product. This work also provides a preliminary insight into the reaction mechanism using high-resolution mass spectrometry analysis. The key cinnamic acid derivative intermediate was detected, implying that under the evaluated conditions, the mechanistic pathway starts with an aromatic electrophilic substitution followed by dehydration reaction and intramolecular transesterification.