Synthesis and Characterization of New Bases Derived from Nitrophenylpyrazoles, Coordination to Palladium and Antifungal Activity and Catalytic Activity in Mizoroki–Heck Reactions

Abstract

In this study, we report the synthesis of eight Schiff bases (3–10) type N-heterocycle (N-het) using conventional refluxing conditions as well as different eco-friendly techniques such as grinding, thermal fusion, microwave irradiation (MWI) and ultrasound, all of them in the presence of a catalytic amount of acetic acid. These procedures had the additional advantage of being environmentally friendly and high-yield, making these protocols an alternative for Schiff-base syntheses. The obtained Schiff bases were coordinated to palladium, generating new complexes of type [Pd2Cl4(N-het)2]. Complexes [Pd2Cl4(5)2] and [Pd2Cl4(9)2] showed high activity and selectivity for a model Mizoroki– Heck C-C coupling reaction of styrene with iodobenzene and bromobenzaldehydes. All compounds and complexes were evaluated for antifungal activity against clinically important fungi such as Candida albicans and Cryptococcus neoformans. Although the Schiff bases (3–10) showed low antifungal activity against both fungi, some of their palladium complexes such as [Pd2Cl4(3)2], [Pd2Cl4(5)2], [Pd2Cl4(8)2] and [Pd2Cl4(10)2] showed comparatively higher antifungal effects mainly against C. neoformans. The product of the Mizoroki–Heck-type C-C coupling reactions, 4-styrylbenzaldehyde, was isolated and purified to be later used in the synthesis of four new nitrophenylpyrazole derivatives of styrylimine, which also displayed antifungal activity, especially against C. neoformans.