Design, Synthesis, and Antioxidant Studies of Newer 4′-(3-Substituted Phenyl-6,6-dimethyl-4-oxo-2,3,5,7-tetrahydrobenzofuran-2-yl)-[1,1′-biphenyl]-2-carbonitriles: Adaptability of Sartans Drug Reactant

Abstract

A one-pot reaction of dimedone, 4′-(bromomethyl)-[1,1′-biphenyl] was used to produce a variety of tetrahydrobenzofuran-4(2H)-one derivatives 4a–4j in acetonitrile using pyridine and triethylamine as an economic catalyst under mild reaction conditions. The designed approach involves the formation of three bonds: two C–C bonds and one C–O bond. A greater yield and exceptional purity were achieved for all of the compounds. Several techniques were employed to study the benzofurans that were synthesized from sartan series benzyl bromide fragments. These techniques included FTIR, ¹H, ¹³C NMR, and MS. The antioxidant capabilities of the synthetic chemicals were evaluated through screening. Substituents in benzaldehyde fragments as dimethoxy (4f), trimethoxy (4g), and nitro (4h) groups exhibited increased efficacy in a controlled laboratory setting utilizing the 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) free radical assay, with IC₅₀ values of 14, 16, and 15 µM, respectively. In contrast to the standard (ascorbic acid, IC₅₀ =14.06 µM), compounds containing halogen substituents were discovered to be somewhat effective in the free radical scavenging experiment. They identified a strong correlation between their binding modalities and the antioxidant characteristics in their molecular docking experiment with the myeloperoxidase (PDB: 3MNG) enzyme, which showed high binding affinities (docking score = –19.2 kcal/mol for 4f).