Two families of regioisomeric 1,4-benzodiazepines, 4-benzyl-3H-benzo[e][1,4]diazepin-5-ones and 4-benzoyl-4,5-dihydro-3H-benzo[e][1,4]diazepines, have been synthesized through a similar Ugi/reduction cyclization sequence. Their conformation and stability depend on the position of the tautomeric imine/enamine equilibrium present in the diazepine nucleus, which in turn depends on the relative position of the carbonyl group adjacent to the nitrogen at the 4-position in the benzodiazepine system. Moreover, the electrophilic center on the imine tautomer is essential for the antitumor activity of some benzodiazepines as a DNA binding position. The mechanism of tautomerization in the presence or absence of the oxo group has been studied computationally using DFT methods (B3LYP/6-31G** level).Ministerio
de Economía y Competitividad, Spain (project CTQ2012-
31611), from Ministerio de Ciencia e Innovación, Spain and
Fondo de Desarrollo Regional (project MAT2011-22781), as
well as from Junta de Castilla y León, Consejería de Educación
y Cultura y Fondo Social Europeo (project ref. BU246A12-1 and
BU327A11-2)
