Green Approach for the Synthesis of Chalcogenyl- 2,3-dihydrobenzofuran Derivatives Through Allyl-phenols/ Naphthols and Their Potential as MAO-B Inhibitors

Abstract

This work presents the design, synthesis, and MAO-B inhibitor activity of a series of chalcogenyl-2,3-dihydrobenzofurans derivatives. Using solvent- and metal-free methodology, a series of chalcogen-containing dihydrobenzofurans 7-9 was obtained with yields ranging from 40% to 99%, using an I₂ /DMSO catalytic system. All compounds were fully structurally characterized using ¹ H and ¹³ C NMR analysis, and the unprecedented compounds were additionally analyzed using high-resolution mass spectrometry (HRMS). In addition, the mechanistic proposal that iodide is the most likely species to act in the transfer of protons along the reaction path was studied through theoretical calculations. Finally, the compounds 7b-e, 8a-e, and 9a showed great promise as inhibitors against MAO-B activity.

Keywords: dihydrobenzofurans; green synthesis; monoamines oxidases; organochalcogen.