Four-Component Synthesis of pyrano[2,3-c]pyrazoles Catalyzed by Triphenylphosphine in Aqueous Medium

Abstract

Background: The pyrano[2,3-c]pyrazoles have various biological properties such as antiinflammatory, anti-cancer, antifongical, analgesics and have a potential inhibitor for human ChK1 kinase. For these reasons several synthetic methods are reported. For our part we want to propose a method which respects the environment. Method: To achieve our study we used as a model the condensation reaction of hydrazine hydrate, ethyl acetoacetate, benzaldehyde and malononitrile in the respective proportions of 1/1/1/1 and in the presence of Triphenylphosphine in various concentrations and different solvents. Results: We found that the optimal conditions for this reaction are 10 mol% of catalyst in refluxed H2O. Given these results and to show the generality of the procedure, we applied the optimized reaction conditions for the synthesis of various dihydropyrano[2,3-c]pyrazoles from a range of substituted aromatic and heteroaromatic aldehydes. We have also applied these conditions by changing hydrazine by phenylhydrazine. The desired products are obtained in good to excellent yields. Conclusion: We describe a simple, efficient and benign method for the dihydropyrano[2,3-c]pyrazoles synthesis by a four-component condensation between hydrazine (or phenylhydrazine), ethyl acetoacetate, malononitrile and a variety of aromatic and heteroaromatic aldehydes, catalyzed by Triphenylphosphine. Keywords: Aqueous medium, multicomponent reaction, pyrano[2, 3-c]pyrazoles, triphenylphosphine.