SYNTHESIS OF 1-FLUOROBENZO[A]PYRENE AND 3-FLUOROBENZO[A]PYRENE

Fluoro-substituted aromatic hydrocarbons are useful probes for studyin g mechanistic details of oxygen transfer in metabolism catalyzed by cy tochrome P450. Benzo[a]pyrene (BP) is a particularly suitable substrat e for investigating this mechanism. Because 3-hydroxybenzo[a]pyrene is one of the major metabolites of BP, preparation of 3-fluorobenzo[a]py rene (3-FBP) was undertaken. Synthesis of 3-FBP was achieved,in five s teps starting from 6-chlorobenzo[a]pyrene (6-ClBP). In this synthesis 1-FBP was also produced. The overall yield was 16% for both 1-FBP and 3-FBP. After nitration of 6-ClBP at C-1 and C-3 with N2O4 and reductio n by SnCl2 to the amino group, diazotization with NaNO2 in the presenc e of NaBF4 followed. The diazonium tetrafluoroborate salts were reacte d with (CH3)2NH to produce the dimethyltriazonium tetrafluoroborate sa lts. By heating in toluene, a mixture of 1-F-6-ClBP and 3-F-6-ClBP was obtained. The two isomers were separated by normal-phase medium-press ure liquid chromatography. The chloro substituent was then selectively removed from both isomers by hydrogenolysis to yield 1-FBP and 3-FBP.