Green synthesis of Hantzsch dihydropyridines from biorenewable furans derived from lignocellulosic biomass

Abstract

Hantzsch dihydropyridines constitute a class of N-heterocycles with significant pharmacological and technological applications. Due to their importance, the development of new sustainable synthetic methodologies for producing dihydropyridines is of great interest. This work presents the synthesis of dihydropyridines via the Hantzsch multicomponent reaction. Furanic aldehydes derived from lignocellulosic biomass are used as substrates, and p-sulfonic acid calix[4]arene (CX4SO3H) is employed as an organocatalyst, under microwave irradiation (MWI). The furanic compounds are reacted with ethyl acetoacetate and ammonium acetate in the presence of 1.0 mol% of CX4SO3H for 10 min at 80 °C under MWI. Twenty one dihydropyridines are synthesized in yields ranging from 43% to 96%. Two dihydropyridines are obtained as crystals suitable for X-ray diffraction analysis, and their crystallographic data are provided. Moreover, the catalytic system can be reused for seven reaction cycles without significant yield loss. The developed methodology offers numerous advantages. It enables the production of dihydropyridines from renewable substrates via a multicomponent reaction in a single step, with a short reaction time. The process uses a reusable organocatalyst and eliminates the need for solvents or metal catalysts.