Synthesis of 1,5-Dihydroazepines

The interaction of ort/zo-phenylenediamine (o-PDA) with aliphatic cx,(3-unsatu-rated ketones, in particular, mesityl oxide, was reported for the first time as long ago as 1905 [1], Nevertheless, only in the 1950s was the reaction product convincingly proved to have the structure of dihydrobenzodiazepine [2, 3]. Meanwhile, the condensation reactions of aromatic unsaturated ketones with aromatic and heterocyclic ort/zo-diamines remained unstudied for a long time. One of the reasons for this situation was attributed to the impossibility of the formation of a dihydrobenzodiazepine cycle by the interaction between o-PDA 1 and chalcone 

The first reliable report on the synthesis of 2,-4-diphenyl-2,3-dihydro- H- 1,5-benzodiazepine 3 for the reaction of 0-PDA and chalcone was published in 1975 [5]. 

the alternative direction of the reaction of or o-hydroxychalcone 5 is not associated only with a specific influence of hydroxyl group, but most likely is due to several other reasons. Indeed, the presence of a hydroxyl group in other fragments of an unsaturated ketone does not change the reaction direction. 

Ionic liquids and room-temperature ionic liquids were also used as the media to synthesize dihydro-1,5-benzodiazepines [38, 39]. Du et al. [39] described two new acidic ionic liquids based on 1-butylpyridinium hydrogen sulfate and 1-butylisoquinolinium hydrogen sulfate as efficient catalysts to promote the formation of 1,5-benzodiazepines. The reactions were carried out in ethyl acetate at 80°C under an inert atmosphere. 

R = Ph. 4-CH3C6H4, 4-CH3OC6H4, 4-CH3OOCC6H4i 4-CIC6H4i 2-CH30-4-CI-C6H4 

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