1,2,4-TRIAZOLO AND 1,2,5-TRIAZINO[4,3-D][1,4]BENZODIAZEPINONE RING-SYSTEMS - SYNTHESIS AND BARRIER TO RING INVERSION

Reaction of the chloroimide 5, 7-dichloro-1-methylbenzodiazepin-2-one with acylhydrazines produced annelated 3-substituted triazoles, and reaction with ethyl carbazate gave the analogous triazolone, which in turn could be alkylated on the 2 position via its thallous salt. Condensation of the chloroimide with 4-morpholineglyoxylic acid hydrazide gave the corresponding annelated triazinedione, which could also be alkylated via its thallous salt. The lactam moiety of the seven-membered ring proved labile to aminolysis by several cyclic secondary amines, yielding ring-opened amides. Temperature-dependent NMR studies revealed that the seven-membered rings of the triazolo derivatives were significantly less conformationally rigid (ΔF* = 13.0-14.2 kcal/mol) than diazepam (ΔF* = 18.1 kcal/mol), while the triazinedione derivatives were more rigid (ΔF* = 19.9-20.7 kcal/mol). The solid state conformations (X-ray) of both annelated systems were distinctly nonplanar. Consistent with its higher ΔF*, the triazinedione exhibited a greater degree of puckering than the triazolone. © 1979, American Chemical Society. All rights reserved.