The mechanism of formation of o-bromophenol from bromobenzene

T. J. Monks, S. S. Lau, L. R. Pohl, J. R. Gillette

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Both o-bromophenol and p-bromophenol are formed from bromobenzene in rat liver microsomes. It has been established that p-bromophenol is formed via bromobenzene-3,4-oxide, but o-bromophenol could conceivably arise via either the 2,3-epoxide or the 1,2-epoxide or by direct insertion of oxygen. As described in the present article, we have isolated and identified bromobenzene 2,3-dihydrodiol as a microsomal metabolite of bromobenzene. Identification of the dihydrodiol therefore indicates the formation of its obligatory precursor, bromobenzene-2,3-oxide. Moreover, using bromo(2,4,6-2H3)benzene, we have clarified the mechanism of formation of o-bromophenol from bromobenzene. The rate of formation of o-bromophenol from bromobenzene and bromo(2,4,6-2H3)benzene in liver microsomes from 3-methylcholanthrene-treated rats was 0.72 ± 0.02 and 0.74 ± 0.06 nmol/mg/min (K(H)/K(D) = 0.99), respectively. The lack of a significant isotope effect indicates that the hydroxylation of bromobenzene to o-bromophenol is not by a direct insertion mechanism. Furthermore, the mass spectrum of o-bromophenol isolated from a microsomal incubation with bromo(2,4,6-2H3)benzene indicated that 70% of the product retained all three deuterium atoms. These results are consistent with the view that o-bromophenol is formed from the 2,3-epoxide intermediate but do not preclude formation by the addition of oxygen to the 2-position carbons followed by an NIH shift and rearrangement before an epoxide is formed.

Original languageEnglish (US)
Pages (from-to)193-198
Number of pages6
JournalDrug Metabolism and Disposition
Volume12
Issue number2
StatePublished - Jan 1 1984

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

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