L-Cysteine Catalyzed Environmentally Benign One-pot Multicomponent Approach Towards the Synthesis of Dihydropyrano[2,3-c]pyrazole Derivatives

Abstract

Background: The pyrano[2,3-c]pyrazole derivatives are important building blocks of many biologically active compounds owing to their diverse biological potential for example, anti-inflammatory, anticancer, anti-microbial and anti-oxidant properties. Objective: Keeping in mind the wide range of applications of pyrano[2,3-c]pyrazoles, herein we intended to develop a novel synthetic methodology for dihydropyranopyrazoles. We were also interested in determining the influence of amino acids and dipeptides as a catalyst on the synthesis of pyrano[2,3-c]pyrazole derivatives. Methods: To achieve our objectives, we used a one-pot multi-component reaction of ethyl 3-oxobutanoate, propanedinitrile, hydrazine monohydrate and several substituted benzaldehydes by using different catalysts and solvents to synthesize our desired products in the presence of various catalysts. Results and Discussion: We found that optimal conditions for the preparation of pyrano[2,3-c]pyrazoles were L-cysteine (0.5 mol) in the presence of water:ethanol (9:1) at 90 °C. Various 1,4-dihydropyrano[2,3- c]pyrazoles were afforded by using several substituted benzaldehydes in 66-97% yields. Conclusion: We described a green and environmentally benign method to synthesize pyrano[2,3-c]pyrazoles in a one-pot four component reaction of ethyl 3-oxobutanoate, propanedinitrile, hydrazine monohydrate and different substituted benzaldehyde in the presence of L-cysteine in aqueous ethanol (9:1) at 90 oC. Excellent yields of the products, simple work-up, easily available starting materials, use of green solvents, naturally occurring catalyst, non-toxicity, non-chromatographic purification and environmentally benign reaction conditions are some main advantages of this protocol.