Antitumour polycyclic acridines. Part 5.¹ Synthesis of 7H-pyrido[4,3,2-kl ]acridines with exploitable functionality in the pyridine ring

Abstract

Two series of new 9-(1,2,3-triazol-1-yl)acridines 8 and 11 have been synthesised by base catalysed cyclisation reaction of 9-azidoacridine 5 with either 1,3-dicarbonyl compounds or activated acetonitriles. Ring formation occurred in a regiospecific manner indicating a stepwise ionic reaction sequence. The combination of activating base and solvent, as well as the solubility of the products, are crucial for achieving acceptable yields. Several of the 9-(1,2,3-triazol-1-yl)acridines have been converted to fluorescent 7H-pyrido[4,3,2-kl ]acridines 14 by Graebe–Ullmann nitrogen-expulsion degradations employing boiling diphenyl ether as the thermolytic medium. In one case, the thermolysis of 9-[4-methoxycarbonyl-5-(4-chlorobutyl)-1,2,3-triazol-1-yl]acridine 16, the chlorobutyl side-chain participated in an additional intramolecular cyclisation step leading to the pentacyclic quinolizino[2,3,4-kl ]acridine 18.

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