Unsaturated 1,3-benzodiazepines, synthesis

As with many other unsaturated seven-membered heterocyclic systems 1,2-diazepines form organometallic complexes of various types. The stable tricarbonyliron complexes of Iff-1,2-diazepines, e.g. (79), have been much studied and found useful in synthesis (81ACR348), and it has been recently shown that 317- 1,2-diazepines (5) and analogous benzodiazepines form complexes of a quite different type (105) involving the azo group only (81TL353). 

Synthesis of annelated diazepines based on unsaturated aromatic diazepines may involve the preliminary transformation of ketones into the corresponding l,3-diaryl-2,3-dibromopropane-3-ones (chalcone dibromides). The interaction between o-PDA or some of its substituted analogues with chalcone dibromides leads to the formation of aziridine derivatives [64] (see Chap. 1). However, in the case of 4-nitro-o-PDA, either azirenoquinoxalynes 53 or benzodiazepine derivatives 54 may be obtained depending on the reaction conditions [65] (Scheme 4.15). Diazepine derivatives 56 are obtained by the condensation of chalcone dibromides 51 with 5,6-diamino-1,3-dimethyluracil 55 [66], but aziridine derivatives are not isolated in this reaction. It should be noted that compounds 54 and 56 are formed owing to cyclization of the intermediate (3-enaminoketones [65, 66, 67] and are easily isolated from the reaction mixture. 

The synthesis of 1,5-benzodiazepines from o-phenylene-diamines and a,)8-unsaturated carbonyl compounds using imidazolium or pyridinium PILs is shown in Scheme 3a. 

Numerous useful organic transformations are known to be accelerated by US irradiation [51]. Compared to traditional methods, US-promoted methodologies are of more convenience and share many common features with other green chemical techniques [52]. An US-enhanced synthesis of 1,5-benzodiazepines (Scheme 12) catalyzed by p-toluenesulfonic acid (p-TSA) has been reported [53]. A variety of catalysts such as silica, Amberlyst 15, Dowef, K-10, ZnCl2, and so on were screened, but p-TSA was foxmd to be the best in terms of yield. The scope and limitation of the method was studied and it was foxmd that the reaction was unsuccessful with aryl alkyl ketones, a,(3-unsaturated ketones, and cyclic ketones. 

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