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Experimental and theoretical studies on the effect of the oxo group in 1,4-benzodiazepines
Pablo Pertejo1, María García-Valverde, Pablo Peña
1Chemistry Department, Faculty of Science, University of Burgos, 09001-Burgos, Spain. magaval@ubu.es.
Abstract:
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).
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