A facile catalyst-free one-pot three component synthesis of pharmacologically important indole-centered 4H-chromenes in a deep eutectic solvent (DES)*

Popularity of the multicomponent reactions (MCRs) lies in the versatility as well as simplicity of their synthetic procedures which unlock the access to a variety of valuable bioactive products as well as fine chemicals by means the manifold prospects of the reagent combinations. In this paper, we report a simple, green, and highly efficient protocol to assemble diverse indole-based 4H-chromenes in good yields using a low melting mixture of choline chloride and urea. Herewith, we have employed inexpensive and easily accessible indole derivatives, salicylaldehyde, 2-hydroxy-1-naphthaldehyde, malononitrile, and ethyl cyanoacetate to prepare a variety of indolecentered 4H-chromenes. Importantly, the reaction medium was recycled/reused without any noticeable decrease in both yield as well as the catalytic activity. More importantly, the deep eutectic medium play a dual role, solvent as well as catalyst, and hence avoid the usage of volatile organic solvent and corrosive catalyst, as well. Moreover, we have also revealed the preliminary photophysical (absorption and emission) properties of thus prepared molecules. Since this particular method involve both green reaction medium as well as straightforward catalyst-free multicomponent procedure, it may open up new possibilities to synthesize a wide variety of hybrid indole and chromene based heterocycles of therapeutic uses under green and mild conditions in many years to come.

Automated summary

The popularity of multicomponent reactions (MCRs) lies in their versatility and simplicity, which allows for the synthesis of a variety of valuable bioactive products and fine chemicals. In this paper, a simple and efficient protocol for assembling diverse indole-based 4H-chromenes using a low melting mixture of choline chloride and urea is reported. This method makes use of inexpensive and easily accessible starting materials and the reaction medium can be recycled without loss of yield or catalytic activity. Additionally, the reaction medium serves as both a solvent and catalyst, eliminating the need for volatile organic solvents and corrosive catalysts. Preliminary photophysical properties of the synthesized molecules are also investigated. This method, combining a green reaction medium and catalyst-free multicomponent procedure, offers new possibilities for the synthesis of a wide range of indole and chromene based heterocycles under mild conditions.