Benzoxazepinone

The benzoxazepinone 2 is converted into 5-methoxy-l,4-benzoxazepine (8a) by trimethyl-oxonium tetrafluoroborate.32 An analogous reaction of 3-phenylbenzoxazepinonc 3 with tri-cthyloxonium tetrafluoroborate gives the 5-cthoxy derivative 8b. The thione 6 undergoes methylation at sulfur to yield the (methylsulfanyl)benzoxazepine 9.32... 

A solution of the benzoxazepinone 2 (4.2 g, 26 mmol) in CH2C12 (200 mL) was stirred under N2 and trimethyloxonium tetrafluoroborate (4.0 g, 27 mmol) was added. The mixture was stirred for 24 h and then neutralized with coned aq K2C03. The filtered solution was evaporated and the residue distilled in a Kugelrohr apparatus to give the product yield 4.2 g (90%) pale-yellow oil. 

The monothione 2 (vide supra) is converted into the (methylsulfanyl)benzoxazepinone 3a by sodium hydride/iodomethane an analogous reaction with ethyl bromoacetate gives the ester 3b.37... 

A more traveled route to the absolute configuration represented by cyclohexa-1,4-diene 8 involves Birch reduction-alkylation of benzoxazepinone 9.2.5 heterocycle is best prepared by the base-induced cyclization of the amide obtained from 2-fiuorobenzoyl chloride and (5)-pyrrolidine-2-metha-nol. o The molecular shape of enolate 10 is such that the hydrogen at the stereogenic center provides some shielding of the a-face of the enolate double bond. Thus, alkylation occurs primarily at the 3-face of 10 to give 11 as the major diastereomer. The diastereoselectivity for alkylation with methyl iodide is only 85 15, but with more sterically demanding alkyl halides such as ethyl iodide, allyl bromide, 4-bromobut-1-ene etc., diastereoselectivities are greater than 98 2. 

The tricyclic sesquiterpene longifolene has served as a vehicle for the illustration of new strategies for organic synthesis.25 Both enantiomers have been obtained from natural sources (-i-)-longifolene occurs in several Firms species and is commercially available while the rare (—)-longifolene has been found in certain liver mosses.2 We elected to prepare (—)-longifolene 49 from the cyclohexa-1,4-diene 45, obtained from the Birch reduction-alkylation of benzoxazepinone 9 in 96% yield with a diastereomeric excess of greater than 98% (Scheme 13).22... 

Starting from ethanolamines 72, benzoxazepinones 73 [84—86], benzodiazepi-nones 74 [47, 86] and diazepanones 75 [47] have been produced depending on the starting carboxylic components. In the last case, classical Mitsunobu conditions gave unsatisfactory yields, and the conditions developed by Hanessian (SDI and NaH) were used instead. Using a-hydroxyacids 76, both benzoxazinones 69 [55] and benzoxazepinones 77 [55] have been accessed. The same compounds can also... 

Several biologically useful medium-sized benzo-fused heterocycles have been efficiently constructed by combining the efficiency of the Ugi condensation with a post-condensation S Ar cyclization, using an internal amino or hydroxyl nucleophile, and a nitrohalobenzoic acid 63 (Fig. 16). By introducing the additional nucleophile into the amine component, benzodiazepinones 79 [72], benzodiazoci-nones 80 [72], their benzo-fused counterparts 81 [72], benzoxazepinones 82 [72] and their fused counterparts 84 [60] and finally benzoxazocinones 83 [72] have been obtained. For the first two systems, the already described UDC strategy was exploited, whereas for the oxa heterocycles, the alcoholic or phenolic hydroxyl did... 

N -(2-Hydroxymethylphenyl)pyrrole is prone to selective a-metalation with fj-BuLi-potassium ferf-butoxide. Trapping the formed anion with a variety of electrophiles and treatment of the crude products with silica gel in toluene results in pyrrolo-benzoxazepines 266 and pyrrolo-benzoxazepinone 267 (Scheme 57 (1994T2071)). 

F yridinium oxime 394 in the presence of concentrated EECl gives oxazepine 395 in 61% yield (eqnation 172) . Beckmann rearrangement of 4-chromanone oximes in the presence of polyphosphoric acid or diisobntylalnminium hydride also afforded substituted benzoxazepinone ring. 

The 1,3-oxazepine (848) is thermally labile the main products are formylpyrroles but some 3-hydroxy-2-phenylpyridine is obtained (75TL1067). The benzoxazepines of type (849) are intermediates in the photochemical breakdown of quinoline iV-oxides and can sometimes be isolated. They normally break down to give 3-hydroxyquinolines (66TL2145, 67CPB663), but compound (849) can be converted by methylamine into the diaminoquinoline (850) (67TL5237). The benzoxazepinone (851) with sodamide forms a mixture of three isoquinoline... 

Quantum-chemical (Gaussian 98W package) calculations have been used, together with spectroscopic (13C, Tl NMR) methods, to investigate the structures and stabilities of the potentially tautomeric 2-phenyl and 3-phenyl benzoxazepinones and their thiolactam analogues. Experimental and computational data indicate the predominance of (thio)lactams 9 in the gas phase and in solution over the imino tautomers 10 (Equation 1) <2004JMT(668)157>. 

Pyridazino[3,4- ]benzoxazepinones with structure of type 136 were described as multidrug-resistance-modulating agents with low toxicity <2004JME4627>. The same compounds 136 were antimycobacterial also <2000AP231>. 

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