J . Org. C h e m . 1986,51, 5023-5024
5023 Scheme I
Synthesis of 7,12-Dimethylbenz[a ]anthracene and Its 1,2,3,4-TetrahydroDerivative Ronald G. Harvey* and Cecilia Cortez B e n M a y Laboratory f o r Cancer Research, u n i v e r s i t y of Chicago, Chicago, Illinois 60637 3
Received J u l y 25, 1986
1
0
7,12-Dimethylbenz[a]anthracene(1) is a highly potent carcinogen.' It is activated by microsomal enzymes to a
PTiCI;
LiAIH,
SnCI,'
5 1
CH3
2
HCI
a2a
a 3
1
CH3
by reduction with sodium in isoamyl alcohol.6 2TiC1,.LiAlH4 was
diol epoxide metabolite that binds covalently to DNA in purchased from Aldrich. Proton NMR spectra were obtained on mammalian cells, leading ultimately to tumor i n d u c t i ~ n . ~ ~ ~ the University of Chicago 50@MHz NMR Spectrometer in CDCl, Surprisingly, 7,12-dimethyl-1,2,3,4-tetrahydrobenz[a]- with tetramethylsilane as internal standard. The integrated NMR spectra were consistent with the structural assignments and esanthracene (2), which is saturated in the ring postulated sentially identical with the spectra of authentic standard comto undergo enzymatic activation, is also highly carcinopounds. All melting points are uncorrected. genic.4 1,2,3,4-Tetrahydrobenz[a]anthracene-7,12-dione (3a). A In connection with studies to elucidate the mechanism solution of 1,2,3,4,7,12-hexahydrobenz[a]anthracene (600 mg, 2.58 of carcinogenesis of 2, we attempted to synthesize 2 from mmol) and sodium dichromate (1.20g, 4.58 mmol) in acetic acid 1,2,3,4-tetrahydrobenz[a]anthracene-7,12-dione (3a) by (60mL) was heated at reflux for 30 min. The reaction mixture utilization of methods previously reported for the prepawas cooled to room temperature and then poured into 150 mL ration of 1 from benz[a]anthracene-7,12-dione(3).5*6 of 30% sulfuric acid. The precipitate was filtered, washed with water, dried, then dissolved in benzene, and passed through a Although 1 was obtained in good yield through addition column of silica gel, eluting with benzene. The crude product of methyllithium to 3, followed by reaction of the adduct (530mg) was recrystallized from benzene-hexane to yield pure 4 with anhydrous HCl to yield 5, and reduction of the latter 3a: 420 mg (62%); mp 153-154.5 OC (lit.lo mp 152-154 "C). with SnCl,, HC1, or NaBH4, only very low yields (
