Studies On The Synthesis Of Benzodiazepine Derivatives

In recent years, Benzodiazepine derivatives have become widely applied in medicinal research areas. Pharmacological research show that: a lot of compounds have a potential effect of anti-depression,anti-convulsions, relief of pain and so on. Generally speaking, there are two methods widely used in literatures: the cyclization of the substituted benzene derivatives, and rearrangement of the proper cyclic precursors.α-oxo ketene dithioacetals are a kind of versatile intermediates in organic synthesis. It can construct many compounds with special structures. In recent years, our research group has devoted to the synthetic applications ofα-oxo ketene dithioacetals. Based on the research ofα-oxo ketene dithioacetals, in this theme, we describe a new, easy and straightforward synthesis of multi-substituted benzodiazepine derivatives.Substratesα-oxo ketene dithioacetals were treated with aromatic aldehyde andα-alkenoyl ketene-(S,S)-acetals were obtained in good yields. From the view of structure,α-alkenoyl ketene-(S,S)-acetals contain two enone fragments, so they should have the potential to be attacked two times by binucleophilic species,α-alkenoyl ketene-(S,S)-acetals and diethyl malonate were carried out with K2CO3 in DMF, formation of cyclic vinylogous thiol esters involves two steps: an intermolecular Michael reaction and an intramolecular reaction. Finally, multi-substituted benzodiazepine derivatives were obtained via amide exchange.In this theme, 8 new products were synthesized and characterized via MS, 1HNMR, 13CNMR.