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Synthesis of the Novel Benzo[b]pyrrolo[2,3-e]azepinone and Benzo[b]pyrrolo[3,2-e]azepinone Ring Systems

Athanasios Kimbaris and George Varvounis*

Department of Chemistry, University of Ioannina, 45110, Ioannina, Greece

Recently we reported the synthesis of the novel 9,10-dihydro-10-oxo(or thioxo)-12H-pyrrolo[2,1-e][1,3,6]benzotriazocine ring system by reaction of 1-(2-aminophenyl)-2-amino-methylpyrrole with triphosgene and thiophosgene, respectively1. Here we report, among others, the application of this chemistry for the synthesis of benzo[b]pyrrolo[2,3-e]azepinone 7 and benzo-[b]pyrrolo[3,2-e]azepinones 8 and 12 from 1-tosylpyrrole2 by a three step procedure.
Using essentially the method of Kakushima et al.3, Friedel-Crafts acylation of 1-tosylpyrrole with o-nitrobenzoyl chloride and stannic chloride as catalyst gave a mixture of compounds 1 and 2 in 56% and 11% yield whereas with aluminium trichloride as catalyst the yield of compounds 1 and 2 was 13% and 52%, respectively. Catalytic hydrogenation of nitro compounds 1 and 2 gave the corresponding amino derivatives 3 and 4 in 96 and 93% yield. The latter were reduced with sodium borohydride to the respective methylene compounds 5 (88%) and 6 (84%). Reaction of compounds 5 and 6 with triphosgene in tetrahydrofuran containing triethylamine gave, via intramolecular coupling, the novel tricycles 7 and 8 in modest yield. By contrast treatment of compounds 5 and 6 with thiophosgene under a variety of reaction conditions gave in each case a dark intractable oil which on TLC showed to consist of several polar spots. Compounds 3 and 4 were deprotected to the corresponding methanones 9 and 10 by heating with a solution of 10% sodium hydroxide in methanol. Isothiocyanate 11 was obtained in 93% yield by treating 9 with thiophosgene at 0oC. Attempts to cyclise this compound by heating in PPA or toluene containing p-toluenesulfonic acid, failed. On the other hand, when compound 10 was reacted with thiophosgene at 0oC 10-thioxo-1,4,9,10-tetrahydrobenzo[b]pyrrolo[3,2-e]azepine-4-one 12 was isolated in 55% yield.


  1. Korakas, D.; Kimbaris, A.; Varvounis, G. Tetrahedron, 1996, 52, 10751-10760
  2. Anderson, H.J.; Loader, C.E.; Xu, R.E.; Le, N.; Gogan, N.J.; McDonald, R.; Edwards, L.J. Can. J. Chem. 1985, 63, 896.
  3. Kakushima, M.; Hamel, P.; Frenette, R.; Rokach, J. J. Org. Chem. 1983, 48, 3214-3219.