EFFICIENT SYNTHESIS OF N-PHENYLBENZAMIDES VIA AMIDATION OF VINYL ESTERS OF AROMATIC CARBOXYLIC ACIDS WITH ANILINE
Аннотация
In this work, the amidation reaction of various substituted vinyl esters of aromatic carboxylic acids with aniline was carried out in toluene solution. The effect of substituents on the aromatic ring on the product yield was investigated, and a reaction mechanism was proposed. The following amides of aromatic carboxylic acids were synthesized from the reaction of aniline with the vinyl esters of 4-bromobenzoic acid, 4- chlorobenzoic acid, 4-tert-butylbenzoic acid, 4-nitrobenzoic acid, and benzoic acid: 4-bromo-Nphenylbenzamide (75%), 4-chloro-N-phenylbenzamide (70%), 4-tert-butyl-N-phenylbenzamide (60%), 4- nitro-N-phenylbenzamide (80%), and N-phenylbenzamide (65%). The structures of the synthesized amides were confirmed by ¹H and ¹³C NMR spectral analysis. An in silico molecular docking approach was used to evaluate the interaction potential of the synthesized amides with two biological target proteins: the main protease of SARS-CoV-2 (PDB ID: 6LU7) and sphingosine-1-phosphate receptor 3 (S1PR3, PDB ID: 7C4S). Docking calculations were performed using AutoDock Vina 1.2, and the resulting ligand–protein complexes were visualized and analyzed using PyMOL and Discovery Studio software. Binding energy results were used to assess ligand affinity toward both targets. The results showed that 4-tert-butyl-N-phenylbenzamide exhibited the highest affinity for 7C4S, with a binding energy of –10.5 kcal/mol. It also demonstrated strong binding to 6LU7, with a binding energy of –6.7 kcal/mol. Molecular interaction analysis indicated that these compounds occupy key active sites through hydrogen bonding and hydrophobic interactions. Based on these findings, 4- tert-butyl-N-phenylbenzamide may serve as a promising dual-target inhibitor for proteins associated with disease. Further research involving in vitro validation and molecular dynamics simulations is recommended.