Synthesis of 1- and 3-Fluorobenzo[a]pyrene

Patrick P J Mulder, N. V S RamaKrishna, Paolo Cremonesi, Eleanor G Rogan, Ercole Cavalieri

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Fluoro-substituted aromatic hydrocarbons are useful probes for studying mechanistic details of oxygen transfer in metabolism catalyzed by cytochrome P450. Benzo[a]pyrene (BP) is a particularly suitable substrate for investigating this mechanism. Because 3-hydroxybenzo[a]-pyrene is one of the major metabolites of BP, preparation of 3-fluorobenzo[a]pyrene (3-FBP) was undertaken. Synthesis of 3-FBP was achieved in five steps starting from 6-chlorobenzo-[a]pyrene (6-C1BP). In this synthesis 1-FBP was also produced. The overall yield was 16% for both 1-FBP and 3-FBP. After nitration of 6-C1BP at C-1 and C-3 with N2O4 and reduction by SnCl2 to the amino group, diazotization with NaNO2 in the presence of NaBF4 followed. The diazonium tetrafluoroborate salts were reacted with (CH3)2NH to produce the dimethyltriazonium tetrafluoroborate salts. By heating in toluene, a mixture of 1-F-6-C1BP and 3-F-6-C1BP was obtained. The two isomers were separated by normal-phase medium-pressure liquid chromatography. The chloro substituent was then selectively removed from both isomers by hydrogenolysis to yield 1-FBP and 3-FBP.

Original languageEnglish (US)
Pages (from-to)657-661
Number of pages5
JournalChemical Research in Toxicology
Volume6
Issue number5
DOIs
StatePublished - Jan 1 1993

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Isomers
Salts
Nitration
Aromatic Hydrocarbons
Hydrogenolysis
Benzo(a)pyrene
Liquid chromatography
Toluene
Metabolites
Metabolism
Liquid Chromatography
Heating
Cytochrome P-450 Enzyme System
Oxygen
Pressure
3-fluorobenzo(a)pyrene
1-fluorobenzo(a)pyrene
Substrates
3-hydroxybenzo(a)pyrene
pyrene

ASJC Scopus subject areas

  • Toxicology

Cite this

Synthesis of 1- and 3-Fluorobenzo[a]pyrene. / Mulder, Patrick P J; RamaKrishna, N. V S; Cremonesi, Paolo; Rogan, Eleanor G; Cavalieri, Ercole.

In: Chemical Research in Toxicology, Vol. 6, No. 5, 01.01.1993, p. 657-661.

Research output: Contribution to journalArticle

Mulder, Patrick P J ; RamaKrishna, N. V S ; Cremonesi, Paolo ; Rogan, Eleanor G ; Cavalieri, Ercole. / Synthesis of 1- and 3-Fluorobenzo[a]pyrene. In: Chemical Research in Toxicology. 1993 ; Vol. 6, No. 5. pp. 657-661.
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