On the Question of the Application Potential and the Molecular Mechanism of the Formation of 1,3-Diaryl-5-Nitropyrazoles from Trichloromethylated Diarylnitropyrazolines.

The molecular mechanism of the formation of 1,3-diaryl-5-nitropyrazoles via a CHCl3-elimination reaction was investigated using ωB97xD/6-31+G(d,p) (PCM) calculations. It was found that, regardless of the polarity of the reaction environment or the nature of the substituents on the phenyl rings of the starting molecules, the elimination process proceeds through a single-step mechanism characterized by an extremely asynchronous transition state. The ELF (Electron Localization Function) analysis of selected critical structures confirms the proposed mechanism and reveals a pronounced reorganization of electrons within the heterocyclic ring. The in silico analysis based on ADME (Activity, Distribution, Metabolism, and Excretion) and PASS (Prediction of Activity Spectra for Substances) predictions indicates that the title 1,3-diaryl-5-nitropyrazoles exhibit promising biological potential, showing inhibitory activity against both oxidoreductases and proteases. The most consistent targets include hyponitrite reductase, (R)-6-hydroxynicotine oxidase, acrocylindropepsin, saccharopepsin, and chymosin. Thus, the presented CHCl3-elimination provides an efficient and versatile route to functionalized pyrazoles, and, together with their promising bioactivity, confirms the utility of this approach for their synthesis.