Synthesis of substituted 10,11-dihydro-5H-dibenz[b,f]azepines; Key synthons in syntheses of pharmaceutically active compounds

Substituted 10,11-dihydro-5H-dibenz[b,f]azepines are key synthons in the sy ntheses of a number of pharmaceutically active compounds such as imipramine , chlorimipramine, and desimipramine analogues. A facile synthesis of subst ituted 10,11-dihydro-5H-dibenz[b,f]azepines is described, starting out from commercially available 2-bromotoluenes or 2-nitrotoluenes. Initial alpha-b romination with N-bromosuccinimide and subsequent reaction with triethylpho sphite afforded the corresponding benzyl phosphonic ester derivatives. Afte r reaction with benzaldehyde derivatives, the expected Horner-Emmons reacti on products were obtained. Hydrogenation gave the amino derivatives which w ere transformed into the corresponding formamides. Under Goldberg condition s [1], the final ring closing step was performed to give the substituted 10 ,11-dihydro-5H-dibenz[b,f]azepines in 46-75% yield.