Aqueous solution of biogenic carboxylic acids as sustainable catalysts and green reaction media for the high-yielding synthesis of Biginelli adducts, Hantzsch esters, and substituted pyridines

Abstract

3,4-Dihydropyrimidin-2(1H)-ones (DHPMs) and 1,4-dihydropyridines (DHPs), prepared by applying the Biginelli and Hantzsch reaction protocols, respectively, are well-documented nitrogen-containing heterocycles with intriguing pharmacological properties. The aqueous solution of biogenic carboxylic acids renewably produced from biomass via catalytic or enzymatic processes can be used as a sustainable catalyst and green reaction media for synthesizing DHPs and DHPMs. This work evaluates the efficacy of various biogenic acids in their aqueous solutions as catalysts for synthesizing DHPs and DHPMs from substituted benzaldehydes. Among the studied biogenic acids, gluconic acid aqueous solution (GAAS) proved to be the most efficient, safe, non-volatile, and recyclable catalyst. The reaction afforded excellent isolated yields (≥85%) of spectroscopically pure DHPs and DHPMs under optimized conditions and employed a straightforward work-up procedure. Aqueous ammonia was successfully employed instead of ammonium salt to improve the atom economy of DHPs. Moreover, substituted pyridines were synthesized from DHPs in a one-pot, two-step process using NaNO<inf>2</inf> as an oxidant in the GAAS medium. This journal is © The Royal Society of Chemistry, 2024