Synthesis of trans-3,4-Dihydroxy-3,4-dihydrobenz- and -acridines, Possible Proximate Carcinogenic Metabolites of Polycyclic Azaarenes

Article abstract of DOI:10.1021/jo00327a011

The vicinal trans-3,4-dihydro 3,4-diols of benz- and -acridine have been synthesized via modified Birch reduction of the parent heterocycles.Thus the pyridine moiety and the angular benzene ring could be reduced selectively.Controlled reoxidation re-formed the stable acridine part, leaving the angular ring partially hydrogenated.Isomerization of the isolated double bond led to 1,2-dihydrobenzacridines as key intermediates of the synthesis.Prevost reaction, bromination, dehydrobromination, and hydrolysis of the 3,4-dihydrodioldiacetates in the angular ring didnot interfere with the basic acridine moiety.This strategy has been applied to both series, i.e., benz- and -acridine.In some reaction steps the product ratio and total yield were strongly influenced by the position of nitrogen, indicating intrinsic differences in the chemical reactivity of the two systems.The new title compounds which have not been prepared previously are presumably the proximate carcinogenic metabolites of benzacridines.The benzacridines were chosen as model compounds of polycylcic azaarenes (PAA) which impose an increasing environmental risk with the industrial processing of synthetic fuel from shale and oil.