Synthesis and X-ray crystal structures of polyfunctionalized 4H-chromene derivatives via tricomponent reaction with Knoevenagel adducts as intermediates in aqueous medium

Abstract

Chromenes and their derivatives are an important class of compounds known for their biological properties. In this study, synthetic methodologies were described to obtain 4H-chromene derivatives. Two routes were investigated, the first being a bicomponent reaction using Knoevenagel adducts as reagents and the second using one-pot tricomponent reactions, both under microwave irradiation, using H2O as solvent and triethylamine as catalyst. Twenty 4H-chromene derivatives were synthesized with 50–95% yields from aromatic aldehydes, 5,5-dimethyl-1,3-cyclohexadione and malononitrile or methyl cyanoacetate, being further characterized by Fourier Transform Infrared and Nuclear Magnetic Resonance. We also report three crystal structures from the synthesized chromene derivatives, by single-crystal X-ray diffraction, showing the main supramolecular features of each structure – a poorly unexplored approach involving this class of compounds so far.