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.

Identification of Imidazolylpyrazole Ligands as Potent Urease Inhibitors: Synthesis, Antiurease Activity and In Silico Docking Studies

“…[8,9] Azoles possessed distinct structural importance due to their capability of making hydrogen bonds and other non-covalent interactions with target sites of various enzymes. These small heterocyclic moieties are incorporated in structural framework of different anti-proliferative, [10] anti-inflammatory, [11,12] anticancer, [13,14] antimicrobial, [15] anti-tubercular agents. [16,17] Many nitrogen atom containing azolic templates have recently been reported as antiurease agents as well.…”

Recent Advances in the Synthesis of Pyrazole Derivatives: A Review

“…Konwar et al [11] established an eco-friendly procedure for synthesizing pyrazole derivatives, employing lithium perchlorate as a Lewis acid catalyst. Initially, they react with acetylacetone and 2,4-dinitriphenylhydrazine as a model to determine the optimized reaction conditions.…”

Brønsted Acidic Dicationic Ionic Liquid Immobilized on Fe3O4@SiO2 Nanoparticles as an Efficient and Magnetically Separable Catalyst for the Synthesis of Bispyrazoles

“…They have a wide domain of approved biological activity such as anti‐inflammatory, antidepressants, antibacterial, antifungal, antiviral, and as pesticide . Given such intrinsic merits, various synthetic protocols have been reported for the synthesis of 4,4′‐(arylmethylene) bis (3‐methyl‐1‐phenyl‐1H‐pyrazol5‐ol) derivatives . However, the one‐pot pseudo‐five‐component reaction of phenylhydrazine (2 eq.)…”