EFFICIENT SYNTHESIS OF 1-(BROMOMETHYL)-3,5-DIMETHOXYBENZENE: X-RAY STRUCTURE, HIRSHFELD SURFACE ANALYSIS, DFTs, AND MOLECULAR MODELLING INVESTIGATIONS AS TYROSINASE INHIBITOR

Abstract

The synthesis of 1-(bromomethyl)-3,5-dimethoxybenzene, a crucial intermediate in the formation of various natural products, was carried out through a straightforward three-step procedure starting from 3,5-dihydroxybenzoic acid. The structure of the synthesized derivative was fully characterized using a combination of spectroscopic techniques and single crystal X-ray diffraction. The crystalline sample was found to possess monoclinic symmetry with dimensions a = 8.4054(10) Å, b = 4.4245(6) Å, c = 25.016(3) Å, volume V = 928.9(2) Å3 and Z = 4.0. In order to assess the inhibitory potential of the synthesized crystal, a comprehensive in-silico investigation was conducted which involved molecular docking, density function theory (DFT) analysis, and molecular dynamics (MD) simulation studies. The docking analysis was utilized to determine the binding orientation of the compound with respect to the target proteins, while DFT analysis was utilized to evaluate the molecule’s reactivity profile. The MD simulation approach was used to evaluate the structural rearrangements and chemical interactions that occurred during the simulation period. The results of these studies suggest that the synthesized crystal could potentially serve as a dual inhibitor of RNR and tyrosinase and could be a suitable candidate for the synthesis of noval anti-cancer agent for the treatment of associated malignancies.

Keywords

• benzyl bromide
• synthesis
• crystal structure
• molecular docking
• MD simulation.