Antitumour polycyclic acridines. Part 3.1 A two-step conversion of 9-azidoacridine to 7H-pyrido[4,3,2-kl ]acridines by Graebe–Ullmann thermolysis of substituted 9-(1,2,3-triazol-1-yl)acridines

Abstract

9-Azidoacridine 5 reacted with a series of alkynes to form mixtures of regioisomeric 9-(4- and 5-substituted-1,2,3-triazol-1-yl)acridines 6, except for the reaction with trimethylsilylacetylene which gave a single regioisomer. Structural assignments have been confirmed by 1H NMR and NOE experiments and the X-ray structure of 9-(4-butyl-1,2,3-triazol-1-yl)acridine 6a corroborates the positioning of the butyl group and shows that the plane of the triazole ring intersects that of the acridine moiety by 65.97(5)° in the crystal structure. Graebe–Ullmann fragmentation of the triazolylacridines was monitored by differential scanning calorimetry and preparative thermolytic conversion to 2- or 3-substituted 7H-pyrido[4,3,2-kl]acridines 8 was performed in hot diphenyl ether. Whereas 9-[4-(3-chloropropyl)-1,2,3-triazol-1-yl]acridine 11 cyclised to 3-(3-chloropropyl)-7H-pyrido[4,3,2-kl]acridine 13, the isomeric triazole 12 afforded the pentacyclic salt 1H,8H-2,3-dihydroindolizino[7,6,5-kl]acridinium chloride 15.