A new approach to the synthesis of benzofuro[3,2-b]quinolines, benzothieno[3,2-b]quinolines and indolo[3,2-b]quinolines

Treatment of 2-hydroxy-, 2-mercapto-, and 2-ethoxycarbonylamino-benzonitril es 12 with 2-fluoro- or 2-nitrophenacylbromides 13 under alkaline condition s provided the corresponding benzofuran, benzothiophene, and indole interme diates 10, respectivelly. Nucleophilic cyclization of these compounds led t o the corresponding tetracyclic quinolinones 7a, 7b, and 3. Denitrocyclizat ion reaction of compounds 10 (R = NO2) was found especially useful. Compoun ds 7a, 7b, and 3 were converted to their chloro derivatives 14a-c, which we re reduced with hydrogen and a catalyst to the corresponding compounds 8a, 8b, and 2. The presented pathway represents a new method of preparation of quindoline 2 and its O and S analogs 8. Chloro derivatives 14 are reactive enough to provide the corresponding methoxy derivatives 15 and dimethylamin o derivatives 16. Methylation of compounds 7a and 7b with iodomethane provi ding mixtures of major N-methyl derivatives 17 and minor O-methyl derivativ es 15 were also studied.