An Unexplored Lewis Acidic Catalytic System for Synthesis of Pyrazole and its Biaryls Derivatives with Antimicrobial Activities through Cycloaddition-Iodination-Suzuki Reaction

Abstract

Here an environmentally friendly process has been developed for the synthesis of pyrazole and its derivatives through cycloaddition-iodination-Suzuki type reaction by the use of lithium perchlorate as a Lewis acid catalyst. The synthetic pathway involves the synthesis of pyrazoles with various electron donating and electron withdrawing functional groups containing hydrazines and 1,3-diketones (70-95% yields); then one step formation of 4-iodo-pyrazoles (59% yield) followed by modification via palladium catalyzed Suzuki-Miyaura cross coupling reaction to obtain the desired biaryls substituted pyrazoles under mild reaction conditions with high efficiency and product purity (53-70% yields). The biological activity was evaluated through in vitro analysis towards the antimicrobial activities against the growth of Staphylococcus Aureus (for Gram positive) and Pseudomonas Aeruginosa (for Gram negative) with minimum inhibitory concentration (MIC) values ranging from 225 to 850 μg/ml. Molecular docking studies of the compounds into the active site of thymidylate kinase receptor of Pseudomonas Aeruginosa PAO1 revealed notable information on the probable binding interaction.