L,3-Diazepin-2-ones

Wentrup s paper [98JCS(P2)2247] contains one of the very few contributions to the tautomerism of functionalized 1,3-diazepines. l,3-Dihydro-l,3-diazepin-2-ones (49a) exist as such and not as hydroxy tautomers 49b ( H and NMR in DMSO solution and IR in the solid state). 

Because of the importance of l,3-diazepin-2-ones as human immunodeficiency virus 1 (HIV-1) protease inhibitors, considerable computational effort has been devoted to the analysis of the structure <1998JA4570> and binding properties <2004JME6673, 2004BMC5819, 1999JME249> of these compounds. 

Chloromethylpyrimidines, e.g., 398, with bases (X) undergo ring expansion to l,3-diazepin-2-ones 399 (Scheme 186) <1977CJC895>. 

An interesting new approach to l,3-diazepin-2-ones 61 via a palladium-catalysed highly regioselective, cyclisation of 2-vinylpyrrolidines 59 with aryl isocyanates 60 has been developed by Zhou and Alper <03JOC3439>. This reaction has considerable potential for further applications in heterocyclic synthesis. 

Schreiner, E. P. Pruckner, A., Syrc-Selective Michael Addition of Amines to Bis-Enones Synthesis of 1,3,4,7-Tetrasubstituted (4R, 5S, 6S, 7R)-Hexahydro-5,6-dihydroxy-2H-l,3-diazepin-2-ones J. Org. Chem. 1997, 62,5380. 

Variously substituted tetrazolo[l,5-a]pyridines (19) and 2-azidopyridines (20) are photolysed to 2-alkoxy-lH-l,3-diazepines (21), 2-dialkylaraino-5H-1,3-diazepines (22), 2,3-dihydro-lH-l,3-diazepin-2-ones (23), and 2,4-diazabi-cyclo[3.2.0]-hepten-3-ones (24) the relative stabilities of the 2-alkoxy- and... 

It has also been observed that bromomagnesium complexes of hexahydro-l,3-diazepin-2-one, prepared using Grignard reagents, undergo the fixation of carbon dioxide. The resulting carbamate complexes transfer the fixed carbon dioxide to active methylene compounds such as acetophenone... 

Hexahydro-l,3-diazepin-2-thione may be conveniently converted into the iV,iV -dialkyl-hexa-hydro-l,3-diazepin-2-one by treatment with alkyl halides in the presence of aqueous sodium hydroxide and a catalytic amount of benzyltriethylammonium chloride <82S464> and its reaction with (2-bromo-1 -phenylethylidene)malononitrile affords 7-amino-8-cyano-9-phenyl-2,3,4,5-tetrahydro-pyrido[ 1,2-a][l, 3]diazepine <90JOC4740>. 

Even strain-free 2-vinylpyrrolidine can be cleaved by Pd to generate the ir-allylpalladium intermediate, and the l,3-diazepin-2-one 248a was obtained by the reaction with phenyl isocyanate as shown by 248. The use of Pd2(dba)3 and DPPP is important. When Pd(OAc)2 and PPha were used, conjugated diene was obtained by elimination [91]. 

Scheme 6 Iodine(III)-mediated synthesis of dibenzodihydro-l,3-diazepin-2-ones...

Similarly, vinylpyrrolidines react with aryl isocyanates to give l,3-diazepin-2-ones. For example, from 375 and p-chlorophenyl isocyanate (R = 4-ClPh) an 82 % yield of the cycloadduct 376 is obtained... 

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