Green one-pot solvent-free synthesis of pyrano[2,3-c]-pyrazoles Catalyzed by cerium oxide nanoparticles under microwave irradiation

Green chemistry is an increasingly important aspect of chemical research devoted to minimizing the use and generation of hazardous substances, organic solvents, and toxic catalysts on the environment. Pyrano[2,3-c]pyrazoles are an important class of heterocyclic compounds that play an essential role as biologically active compounds and represent an interesting template in medicinal chemistry. Many types of bioactive molecules with broad medicinal and agrochemical applications contain both pyran and pyrazole rings such as pyrano[2,3-c]pyrazoles. The pyrano[2,3-c]pyrazole heterocyclic scaffold is an important substructure showing anticancer, anti-inflammatory, anti-microbial, hypoglycaemic, analgesic, and Chk1 kinase inhibitory properties; it is also used in biodegradable agrochemicals. Multicomponent reactions (MCRs) are the most efficient one-pot route to achieving structural diversity. MCRs provide a rapid and powerful method for synthesizing versatile heterocycles. They are also useful for drug discovery, from the initial recognition of a lead structure to the production of large libraries of analogs. The use of MCRs in green synthesis has been reviewed recently [1-4]. In this work, a facile one-pot, multicomponent protocol for the synthesis of pyrano[2,3-c]-pyrazoles derivatives in the presence of cerium oxide nanoparticles as a highly effective heterogeneous base catalyst in solvent free conditions is reported. This transformation proceeds via a four component reaction of ethyl acetoacetate, hydrazine hydrate, malononitrile and various aldehydes. This synthetic method has several advantages, including good yield, simple work-up, harmless by-products, and simple purification.