Diazepines rings

The 1,2-diazepine ring system is related, thermally and photoehemieally, to two pyrazole [4.5] bicyclie systems (511) and (512). A large number of publieations by Moore, Sharp, Snieekus and Streith deal with these isomerizations (72CC827, 80CC444). 

In a similar vein, acylation of ami noketone 67 with chloroacetyl chloride affords the corresponding chloroamide 68. Reaction of that intermediate with ammonia serves to form the diazepine ring, possibly via the glycinamide. The product bentazepam (69) is described as a tranquilizer. ... 

Finally, three ring-enlargement reactions should be referenced in this section. Gerecke et al. reported <1994H(39)693> that treatment of the 5-chloromethyl-substituted triazolo[4,3-c]quinazoline compound 141 with sodium hydroxide results in the formation of a seven-membered diazepine ring 142 in good yield. 

Hydrolytic cleavage of a seven-membered ring occurs in the metabolism of chlordiazepoxide (5.82, Fig. 5.22,a) and other benzodiazepines (see also Sect. 11.9). The lactam ring opened metabolite 5.83 was detected in humans and dogs and is believed to be generated by hydrolysis of the intermediate lactam [181][182], However, the diazepine ring can be split by other mech-... 

Fusion of an additional aromatic ring onto the diazepine ring... 

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

BZDs -contain nitrogen atoms at positions 1 and 4 in the diazepine ring. This grouping accounts for most therapeutically important agents (e.g.. 

The central pyridazine ring of the condensed indole derivative in 4.31. was built up by the electrophilic attack of the pyridylpalladium intermediate on the indole ring.38 By blocking the 2-position of indole through substitution the ring closure was directed into the peri-position forming a diazepine ring.39... 

Crystal structures of 1,2- or 2,3-benzodiazepines are relatively rare. Three interesting examples are illustrated. The geometry of diazepine ring of 12 is unaffected by a wide range of substituents at C-4. Two planes (N(2)-N(3)-C(5a)-C(9a) and N(3)-C(4)-C(5)-C(5a)) adequately described all sets of isomers <1995AXC1621>. Benzodiazepine 13, an... 

After the failure of the direct synthesis of the completely unsaturated heterocycle 34, an attempt was made to synthesize the partially saturated cyclopenta[t]-l, 2-diazcpine, which then could be dehydrogenated to the 5,6-diazaazulene 34. However, this approach by starting with a 1,2-diazepine ring 36 (made successfully by following published method) and its [3+2] palladium-catalyzed cycloaddition with allyl chlorosilane 35 to the bicyclic diazepine 37 failed (Scheme 8). 

From reviewing the literature for the synthesis of 1,2-diazepines, just from the volume of the work it is apparent that the most preferred route to make 1,2-diazepines, starting from fragments, has been the type bg approach by using a 1,5-dielectrophile with hydrazine (a 1,2-nucleophile). In the case of ring transformation approach to 1,2-diazepines, the conversion of a pyrylium or a thiapyrylium salt to 1,2-diazepines has been the preferred route. In the end, the preferred method would depend on the nature of substituents and the unsaturation required on the 1,2-diazepine ring. 

With the exception of ring-contraction reactions that are discussed below, new insights into the reactivity of fully unsaturated diazepine ring systems that add to the current level of understanding have been limited. 

The application of transition metal catalysis provided new opportunities to introduce diverse functionality to the diazepine ring system. Iron-catalyzed cross-coupling of Grignard reagents with the imidoyl chloride 40 provided a convenient and efficient method for substituting the heterocyclic ring (Scheme 9) <20060L1771>. 

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>. 

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