Synthetic Access to Bis(pyrazolyl)methanes using cost‐efficient Triethylammonium Hydrogen Sulfate Ionic Liquid: Evaluation of Antioxidant Activity via in silico and in vitro Studies

Abstract

AbstractA highly efficient, facile and greener approach has been developed for the synthesis of bis(pyrazolyl)methanes. The method involves a reaction of 3‐methyl‐1‐phenyl‐2‐pyrazoline‐5‐one and substituted aromatic/heterocyclic aldehydes at ambient reaction conditions using ionic‐liquid, triethylammonium hydrogen sulfate to yield desired bis(pyrazolyl)methanes in excellent yields (85–96 %). The significant aspect of this protocol is the use of ionic liquid as a replacement of toxic and expensive metal catalysts thereby reducing the production of harmful chemical wastes and avoiding the use of toxic and volatile reagents in the synthesis. The catalyst was easily separated and reused up‐to five runs without significant decrease in its catalytic activity. Molecular docking studies were conducted on Cytochrome P450 3 A4, methylenetetrahydrofolate reductase, and tumor protein to predict their utility as potential anti‐oxidant, and anti‐cancer compounds. The outcome indicates that these synthesized compounds have the scaffold that binds well in the hydrophobic‐pocket of the respective enzyme and the polar groups present in their scaffold form hydrogen‐bonding too. Furthermore, we infer from the docking calculations that, all were docked in the binding domain of 4D75, eleven were docked in the active site of 6FCX and nine compounds were docked within the binding site of 3S7S. Furthermore, the in‐vitro antioxidant activity of synthesized compounds was explored against DPPH and ABTS, and most of the compounds were found to have high to excellent radical scavenging activity.