Pyrazole derivatives are widely studied due to their broad biological activities, such as anticancer, antioxidant, antimicrobial, antidepressant, antiviral and various other activities [1]. Meanwhile, benzimidazole derivatives, like compounds containing a pyrazole fragment, also exhibit a diverse spectrum of biological activities and are widely used in the production of pharmaceuticals, such as Omeprazole or Pimozide [2]. Combining these two bioactive fragments allows new, potentially biologically active compounds to be created, which could be applied in the developing new pharmaceuticals. Recent studies have shown, novel pyrazole-benzimidazole derivatives, has exceptional anti-proliferative activity and could significantly induce cancer cell cycle arrest and apoptosis [3]. Other identified biological activities in pyrazole-benzimidazole compounds are analgesic, antimicrobial, antioxidant and antiulcer [4].
The aim of this work is to synthesize new cyclic potential active pyrazole derivatives by applying alkylation and cyclocondensation reactions. A multi-step synthesis obtained the starting compound 3-hydroxy-1-phenyl-1H-pyrazole-4-carbaldehyde. To synthesize the carbaldehyde, a benzyl protecting group was first attached to the hydroxy group. An alkylation reaction of 1-phenyl-1H-pyrazol-3-ol was carried out using benzyl bromide as an alkylating agent and sodium hydride as a base. In the next step, 3-(benzyloxy)-1-phenyl-1H-pyrazole, an aldehyde group, was introduced into the pyrazole ring using a Vilsmeier-Hack reaction. After obtaining 3-(benzyloxy)-1-phenyl-1H-pyrazole-4-carbaldehyde, the benzyl group was removed in a reaction using trifluoroacetic acid in toluene. The intermediate pyrazole derivative was synthesized in good yield. The desired products were obtained by amination reaction and then by cyclisation reaction. The resulting functionalized cyclic pyrazole derivatives were investigated for their biological activity. Part of this work has received funding from the Research Council of Lithuania (LMTLT), agreement No. S-SV-24-167.