1,4-Diazepine ring

FIGURE 27.1. A Benzodiazepine core structure, benzene ring B 1,4 diazepine ring. and R2 often form a 5-aryl substituent. 

Reaction of the dilithio anion of 1-vinylbenzotriazole 90 with 2equiv of an aryl isocyanate led to a fused 1,4-diazepine ring formation via an intramolecular Michael addition of the intermediate aryl amide to the vinyl moiety, a type c ring closure that proceeded in good overall yield (Scheme 44) <2003JOC5713>. 

Archetypal benzodiazepines contain a 5-aryl substituent ring and a 1,4-diazepine ring, so the term benzodiazepine drug has come to refer to 5-aryl-1.4-benzodiazepine. Various modifications of the ring system have yielded compounds with similar activity. These include 1,5-benzodiazepines (e.g. clobazam) and replacement of the fused benzene ring with heteroaromatic systems such as thieno (e.g. brotizolam). 

From a detailed analysis of the NMR spectra (proton and C) of some 5-methyl-7-alkyl-l//-2,3,5,6-tetrahydro-l,4-diazepines (28), it was concluded that these compounds adopt a chair conformation with the 7-alkyl substituents (R = Me, Pr , Bu ) in an equatorial position. The introduction of a methyl group at C-3, when the C-7 substituent is Bu, gave two separable isomers one of which was considered to have a chair conformation (29) and the other a boat or twist-boat conformation (30) <84PJC72i>. The conformation of the saturated 1,4-diazepine ring is sensitive to the nature and position of substituents in the ring. Proton NMR and molecular mechanics calculations for some N,N -dialkylamino-l,4-diazepine-2,3-diones (31) and their monothio and dithio analogues point to a twist-boat conformation with C-2 symmetry (32) <81JCS(P2)1344>. 

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