The mechanism of formation of o-bromophenol from bromobenzene

Terrence Monks, Serrine Lau, L. R. Pohl, J. R. Gillette

Research output: Contribution to journalArticle

15 Citations (Scopus)

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 - 1984
Externally publishedYes

Fingerprint

Epoxy Compounds
Benzene
Liver Microsomes
Liver
Rats
Oxygen
Hydroxylation
Methylcholanthrene
Deuterium
Metabolites
2-bromophenol
bromobenzene
Isotopes
Carbon
Atoms
4-bromophenol

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

The mechanism of formation of o-bromophenol from bromobenzene. / Monks, Terrence; Lau, Serrine; Pohl, L. R.; Gillette, J. R.

In: Drug Metabolism and Disposition, Vol. 12, No. 2, 1984, p. 193-198.

Research output: Contribution to journalArticle

@article{ae42e1bbdeca4035ad53b551512afdb5,
title = "The mechanism of formation of o-bromophenol from bromobenzene",
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.",
author = "Terrence Monks and Serrine Lau and Pohl, {L. R.} and Gillette, {J. R.}",
year = "1984",
language = "English (US)",
volume = "12",
pages = "193--198",
journal = "Drug Metabolism and Disposition",
issn = "0090-9556",
publisher = "American Society for Pharmacology and Experimental Therapeutics",
number = "2",

}

TY - JOUR

T1 - The mechanism of formation of o-bromophenol from bromobenzene

AU - Monks, Terrence

AU - Lau, Serrine

AU - Pohl, L. R.

AU - Gillette, J. R.

PY - 1984

Y1 - 1984

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0021245945&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0021245945&partnerID=8YFLogxK

M3 - Article

C2 - 6144485

AN - SCOPUS:0021245945

VL - 12

SP - 193

EP - 198

JO - Drug Metabolism and Disposition

JF - Drug Metabolism and Disposition

SN - 0090-9556

IS - 2

ER -