Imidazole as an organocatalyst for the rapid synthesis of 1H-pyrazolo[1,2-b]phthalazine-5,10-diones in aqueous medium

Abstract

A facile one-pot multicomponent reaction employing aromatic aldehydes, malononitrile, and phthalhydrazide in H₂O and EtOH (1:1) mixture at 80ºC has been innovated for the synthesis of 1H-pyrazolo[1,2-b]phthalazine-5,10-diones. This approach stands out for its simplicity, ease of execution, and high efficiency. The reaction employs 20 mol% of imidazole as an organocatalyst, enhancing its practicality and applicability. A total of 14 compounds were synthesized within 0.5 to 4 h under a greener reaction medium, with the yields of products ranging from 85–94%. The key components of this protocol are the use of H₂O:EtOH (1:1) mixture as green solvent, recyclable reaction medium, imidazole as an organocatalyst, mild reaction conditions, easy isolation of products, good to excellent yields, and no column chromatographic purification. Using the microbial dilution method, all the synthesized compounds underwent evaluation for their antibacterial activity against a spectrum of strains, including E. coli, S. aureus, P. aeruginosa, B. subtilis, as well as antifungal activity against A. flavus and A. niger. The synthesized derivatives exhibited diverse inhibitory effects on the growth of both bacterial and fungal strains, showcasing their potential utility across various microbial targets.

Graphical abstract

A simple one-pot multicomponent reaction using substituted aromatic aldehydes, malononitrile, and phthalhydrazide in 10 ml of H₂O and EtOH (1:1) mixture at 80ºC for the synthesis of 1H-pyrazolo[1,2-b]phthalazine-5,10-dione derivatives has been developed. This methodology involves the use of greener solvents and imidazole as an organocatalyst which leads to good to excellent yields of the products with less reaction time.