Design, Synthesis and X‐ray Crystal Structure of Iodinated Benzoboroxole Derivatives by Consecutive Metal–Iodine Exchange of 3,4,5‐Triiodoanisole

Abstract

A series of iodinated benzoboroxoles was designed and synthesized by using a successive metal–iodine exchange reaction of 3,4,5‐triiodoanisole. The reactivity and regioselectivity of the metal‐iodine exchange are remarkably controlled and provide the iodinated products in good yields. The synthesized iodobenzoboroxoles were screened for in vitro antimicrobial activity against two Gram‐positive strains of bacteria, Micrococcus luteus (ATCC 9341) and Bacillus cereus (ATCC 11778), and two Gram‐negative strains, Escherichia coli (ATCC 25922) and Serratia marcescens (ATCC 27117), by using a well‐diffusion assay and dilution methods. The in vitro antimicrobial evaluation indicated that 4‐iodo‐6‐methoxybenzo[c][1,2]oxaborol‐1(3H)‐ol (compound 24) possesses the most‐potent antibacterial activity against Gram‐positive strains with a minimum inhibitory concentration (MIC) of 0.016 and 0.013 mg/mL for Micrococcus luteus and Bacillus cereus, respectively. This report discloses a two‐step protocol for the synthesis of hitherto unknown 4‐iodobenzoboroxole and 7‐iodobenzoboroxole derivatives that is efficient, general in scope and scalable.