Dihydrobenz acridines

Tumorigenicity of tetrahydroepoxides. As yet, only Ch H -epoxide has been directly demonstrated to be tumorigenic (18). However, indirect evidence has been found in the high tumorigenicity of 3,4-dihydro BA, 9,10-dihydro BeP and 3,4-dihydrobenz[c]acridine (19-21), each of which is a likely metabolic precursor of a bay-region H -epoxide. In the case of 9,10-dihydro BeP, cis- and trans-9,10-dihydroxy -9,10,11,12-tetrahydro BeP were identified as products of metabolism of 9,10-dihydro BeP (22), and are the expected products of hydration of the epoxide. Diols are also formed from 7,8-dihydro BaP upon metabolism with prostaglandin endoperoxide synthase (23) or with rat liver homogenates (24). 

Tetralone gives with 194,343 or with l,3-di-m-tolyl-2-thiourea,344 dihydrobenz[a]acridines (199, R = H, Me) this ketone, on reaction with l,3-di-2-naphthyl-2-thiourea, gives a dihydrodibenz[a,j]acridine.343... 

Tetralone gives with 194, or with l,3-di-m-tolyl-2-thiourea, dihydrobenz[a]acridines (199, R = H, Me) this ketone, on reaction with l,3-di-2-naphth3d-2-thiourea, gives a dihydrodibenz[a,j]acridine. A ketone contained in a five-membered ring was also employed in these reactions when a-indanone was fused with 194 to give the indeno[3,2-fo]quinoline 200 and with 1,3-di-2-naphthyl-2-thiourea to give the indeno[3,2-6]-l-azaphenanthrene 201. 

Pyrolysis of the Mannich base (109) derived from 2-naphthol leads to generation of a quinone methide which when trapped with an aromatic amine leads to benz[a]acridines (0. Bilgic and D.W. Young, J. chem. Soc. Perkin I, 1980, 1233). Thus, aniline yields the parent compound together with 7,12-dihydrobenz[a]acridine. Formation of the dihydro compound appears to be variable for whereas /7-metlylaniline and o-anisidine yield only... 

The H-nmr spectra of the 7,12-dihydrobenz[a]acridines show the 12-methylene group as a singlet between 6 4 and 6 5, whereas it is strongly deshielded in the fully aromatic compounds and appears near to 6 9.5. 

An alternative approach to the tetracyclic systan forms the heterocyclic ring by nucleophilic addition of an amine to a carbonyl group. Application of the Friedlander quinoline synthesis to various methoxy-1-tetralones yields the methoxy-5,6-dihydrobenz-[c]acridines, which are dehydrogenated to the aromatic compound by distillation from palladium-charcoal (M. Croisy-Delcey et al. J. med. Chem., 1983, 26, 303). 

When treated with lithiun diisopropylamide, 1-tetralone oxime is dimetallated. Upon reaction with 2-aminobenzophenones, the dilithiooxime gives a 7-aryl-5,6-dihydrobenz[c]acridine (D.J. Park, T. D. Fulmer and C. F. Beam, J. heterocyclic Chem., 1981, 649). 

Vilsmeier fom lation of 6-methoxy-l-tetralone yields the 1-chloronaphthalene-2-aldehyde which on treatment with aniline and subsequent thermolysis affords the 5,6-dihydrobenz[c]acridine. The presence of electron... 

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