Benzo oxazepine

Treatment of 2-phenyl-l,3-benzoxazepines with hydrochloric acid in acetic acid gives benzo-furans by hydrolytic opening of the oxazepine ring, followed by loss of benzamide and re-cyclization.23... 

Benzo[ 7]benzofuro[2,3-/][l,4]oxazepine 272 is the sole product obtained from chloro aldehyde 271 and o-aminophenol (Scheme 58 (2001JHC383)). 

A number of monocyclic and benzo-annelated examples of 1,2- and 1,3-thiazepines have been prepared but there has been little systematic study of these systems. The interesting photochemical interconversions of pyridine N-imides into 1,2- and 1,3-diazepines and of pyridine Af-oxides into 1,2- and 1,3-oxazepines regrettably lack parallels in thiazepine chemistry. There has been more interest in 1,4-thiazepines, as both rearrangement products and possible biogenetic precursors for penicillins and because of the pharmacological value of the benzo- and dibenzo-[l,4]thiazepines as antidepressants and coronary vasodilators. The only review (70ZC361) is excellent but not very recent. 

Actually, treating the two related ring systems in one chapter makes sense since in many cases they appear side by side in the same article or in a series of follow-up articles by the same author. There has been considerable activity concerning these two ring systems and this is certainly due to the large medicinal interest in 1,4-oxazepines and 1,4-thiazepines and their benzo derivatives. In this chapter, we have compiled the data abstracted from selected recent publications (since 1995) focusing on aspects of synthesis and reactivity as also has been the case in the previous treatments. The most important medicinal applications are mentioned at the end of the text. 

In general, 1,4-oxazepines and 1,4-thiazepine derivatives are stable compounds. Many of the (di)benzo derivatives are crystalline, while some of the more flexible monocyclic derivatives may be liquids. Conjugated (benzo)thiazepine derivatives can lose sulfur on heating, forming (fused) pyridines. This aspect of their reactivity is treated in Section 13.09.5. The completely or partially reduced derivatives of the title heterocycles and the benzo analogues may adapt different conformations, which has already been discussed in Section 13.09.2. The study of the tautomerism of lactams 9 has also been mentioned in Section 13.09.2. 

Examples of seven-membered heterocycles with significant antiviral activity include imidazo[4,5-e][l,3]diazepine-4,8-diones with anti-hepatitis C virus (HCV) activity <07BMCL2225> <07BMC4933> and benzo(indolo)fused 1,4-oxazepine derivatives as HCV RNA polymerase inhibitors that show excellent replicon potency <07BMCL3181>. Novel 2-chloro-8-[(arylthio)methyl]dipyridodiazepinone derivatives show activity against HIV-1... 

There have been no papers dealing with the reactivity of the fully unsaturated 1,2-oxazepine or 1,2-thiazepine rings or their benzo or dibenzo derivatives, apart from rearrangements of the dibenzo[c/][l,2]oxazepines (81) as outlined in Section 9.07.7.1. The Src-electron, 1,2-oxazepinium perchlorate salts (61) (see Section 9.07.7.1) are stable, consistent with the charge delocalized seven-membered ring structure proposed, and do not undergo a Diels-Alder reaction with maleic anhydride <81ZOR881>. 

In an efficient O-arylation-Smiles rearrangement-denitrocyclization reaction cascade, 2-(lH-pyrazol-5-yl)phenols reacted with 2-chloro-3-nitropyridines to afford a series of benzo[flpyrazolo[l,5-d]pyrido[3,2-l)] [l,4]oxazepines 114 regioselectively and in mosdy good yields (14T1077). 

In a similar manner,benzo[6]pyrido[3,2 [l,4]oxazepinones 115 were prepared using a ligand-free, copper-catalyzed process (14RA55640). An intramolecular 1,3-dipolar cycloaddition reaction of 6-azido-4-0-propargyl glucopyranosides generated aryl-substituted hexahydro-4H-pyrano[2,4 [l,2,3]triazolo[5,l-c][l,4]oxazepines 116 (14RA63962). 

SCHEME 3.11 Proposed mechanism for the synthesis of 4-amine-benzo[i>][l,4]oxazepines by palladium-catalyzed isocyanide reactions. 

B. Liu, Y. Li, M. Yin, W. Wu, H. Jiang, Chem. Commun. 2012, 48, 11446-11448. Palladium-catalyzed tandem reaction of o-aminophenols, bromoalkynes and isocyanides to give 4-amine-benzo[f>] [ 1,4]oxazepines. 

C1 gHi 7BrN20i, Perlolyrine hydrobromide dihydrate, 35B, 233 C16H18N2O5 0.32 H2O, 8a-Hydroxy-4-carboxy-perhydrophthal--azino[8a,2-bc]benzo[f]-2,3,4,5-tetrahydro(1,4)oxazepin-5-one hydrate, 44B, 342... 

Cl7H1UN2O2, 2-Oxo-l-phenyl-1,5-methano-1,2,4,5,6,11-hexahydro-(1,2,3)oxadiazolo[3,2-a]cinnoline, 44B, 344 Cl7H15CIN2O2, 7-Chloro-l,2-dimethyl-2,5-epoxy-5"phenyl-l,2,4,5-tet-rahydro-3H-l,4-benzodiazepin-3-one, 37B, 159 C1 H1gNOg, 7,8-Benzo-3-ethoxycarbonyl-2-methoxycarbonyl-9-methyl-9-aza-5-oxabicyclo[4.3.0]nona-(1(6),2)-dien-4-one, 46B, 275 Cl7H16CIN3O, 2-Chloro-11-(1-piperazinyl)dibenz[b,f](1,4)oxazepine, 43B, 461... 

---