One-pot Multicomponent Green Chemistry Approach: Sodium Fluoride-Catalysed Highly Efficient Microwave Irradiation-Assisted Synthesis of Substituted Chromene Derivatives in Aqueous Medium

Abstract

2-Amino-4H-benzo[h]chromene-3-carbonitrile and 2-amino-5-oxo-4H,5H-pyrano[3,2-c]chromene-3-carbonitrile are two important pharmacophores with extensive applications in medicinal chemistry. The multicomponent Knoevenagel-Michael reaction is one of the most efficient strategies to construct these two scaffolds. Previous efforts have been made in converting the traditional organic solvents to eco-friendly solvents including H2O generally in the presence of complex catalysts. Here we present our work of using sodium fluoride (NaF) as the catalyst to synthesize a wide scope of the two types of substrates starting from α- or β-naphthol or 4-hydroxycoumarin. Using 12 mol% NaF under the microwave irradiation condition, the reactions were completed within 15–25 min with all the yields exceeding 85%. The reaction products were purified simply by washing with H2O and can be further purified by crystallization with MeOH. The analysis of green chemistry-related parameters suggested that the current method was highly environmentally benign, highlighting the potential of this method in the use of drug discovery and development.