Perhydro-1,4-diazepine

Pyrazinecarboxylic acid gave l-benzyl-4-methyl-6-[C-(pyrazin-2-yl)for-mamido]perhydro-1,4-diazepine (41) (1 -benzyl-4-methylperhydro-1,4-di-... 

Nefl997b Nefzi, A., Ostresh, J.M. and Houghten, R.A., Solid Phase Synthesis of 1,3,4,7-Tetrasubstituted Perhydro-1,4-diazepine-2,5-diones. Tetrahedron Lett., 38 (1997) 4943-4946. 

Taddei and coworkers [49] also reported an MW-promoted solid-phase synthesis of 3,6-disubstituted perhydro-diazepin-2,5-dione 70 (Scheme 10) involving a Mitsunobu cyclization of a hydroxamic acid derivative anchored to PS-DVB 2-chlorotrityl resin (69). The prepared compound was proved to be useful as constrained peptidomimetics. 

In a correction to previous work, the cyclization of 4-ureidobutyric acids with thionyl chloride has been shown (by NMR spectroscopy) to result in pyrrolidinone carboxamide derivatives and not aryl perhydro-l,3-diazepine-2,4-diones <00JHC111>. Optimization of the geometry of l-(o-nitrophenyl)-2-phenyl-l//-4,5,6,7-tetrahydro-l,3-diazepine has been undertaken using computer-based molecular modelling, and correlations made with theoretical and experimental UV spectra . 

Amblard and co-workers42 from Montpellier University optimized the synthesis of a 3,7-disubstituted perhydro-l,4-diazepine-2,5-dione 64 on polystyrene Crowns (Scheme 18). Seven-membered heterocyclic... 

Starting from TV-o-Fmoc-aspartic acid a-f-butylester, a wide range of 1,3,4,7-tetrasubstituted perhydro-l,4-diazepine-2,5-diones 3 were synthesized (Fig. 2).28 After deprotection of the aspartic acid amino function and reductive alkylation, a second amino acid was coupled and a second reductive alkylation was carried out. Following fBu cleavage, the thermodynamically favorable coupling of the resulting secondary amine to the side chain of aspartic acid was readily accomplished. 

NMR studies have been used to investigate the conformational preferences of a number of fused 1,3-diazepine systems. The preferred conformation of Ar,AT -dimethyl-2,3,4,6-tetrahydro-2,4(l//)-diazepine is reported to be the chair-axial-equitorial conformer (4) <85TL13> whereas the perhydro-system (5) is predominantly the rranj-fused conformer <90MRC426>. An extensive NMR study of a number of hexahydropyrimidines Ar,AT -bridged by methylene groups has been undertaken in support... 

The diimine prepared from 1,3-diaminopropane and benzaldehyde was reduced electrochemically using a lead cathode in an acidic medium to perhydro-frawj -2,3-diphenyl-l,4-diazepine (141) in 79 /i yield (Equation (8)) <9UOC3063>. This reaction complements the cyclopropane diimine cyclization to cis products discussed below. 

However, this compound has served as a neonicotinoid lead structure. Thirteen years later Nihon Tokushu Nohyaku (a subsidiary of Bayer AG in Japan) achieved, with the synthesis of nitromethylene and nitroguanidine derivatives of imidazoli-dines, perhydro-pyrimidines, and diazepines of type 7 (Table 29.2.3.2), an important breakthrough in this chemistry [9, 10]. 

Krchnak, V. and Weichsel, A. S. (1997) Polymer supported synthesis of diverse perhydro-l,4-diazepine-2, 5-diones. Tetrahedron Lett. 38,7299-7302. 

Diazepines are available from the reaction of aminoazirine with maloni-mides (Scheme 79)/° The products may be reduced to the perhydro-derivative or rearranged in acid to an imidazole derivative. A useful account of the photochemistry of cyclic imides has appeared and describes the synthesis of a wide range of heterocyclic compounds. 

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