Oxidative Bromination in a Liquid−Liquid Two-Phase System to Synthesize Organic Intermediates: 2-Bromophenol, 2,6-Dibromophenol, and 2-Bromo-4-methylphenol

An alternative manufacturing process-scheme was developed to synthesize 2-bromophenol and 2,6-dibromophenol involving oxidative bromination of a substrate protected in the para position in a two-phase system followed by deprotection involving decarboxylation. Thus, selective oxidative bromination of 4-hydroxybenzoic acid in ethylenedichloride with HBr−H2O2, and subsequent decarboxylation in quinoline gave 90−95% yield to the mono- or dibromophenol depending upon the mol ratio of HBr:H2O2 employed in the oxidative bromination. Similarly, 4-methylphenol under identical reaction conditions gave 99.6% selectivity to 2-bromo-4-methylphenol at 89% conversion ratio of 4-methylphenol.