THE MECHANISM OF FORMATION OF ORTHO-BROMOPHENOL FROM BROMOBENZENE

  • 1 January 1984
    • journal article
    • research article
    • Vol. 12  (2) , 193-198
Abstract
Both o-bromophenol and p-bromophenol are formed from bromobenzene [a toxic agent] in rat liver microsomes. 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. Bromobenzene 2,3-dihydrodiol was isolated and identified as a microsomal metabolite of bromobenzene. Identification of the dihydrodiol indicates the formation of its obligatory precursor, bromobenzene-2,3-oxide. Using bromo(2,4,6-2H3)benzene, the mechanism of formation of o-bromophenol from bromobenzene was clarified. The rate of formation of o-bromophenol from bromobenzene and bromo(2,4,6-2H3)benzene in liver microsomes form 3-methylcholanthrene-treated rats was 0.72 .+-. 0.02 and 0.74 .+-. 0.06 nmol/mg per min (kH/kD = 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. 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 3 deuterium atoms. o-Bromophenol is evidently 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.