4,1-Benzoxazepine-2,5 diones

Chloroacctamido)bcnzoic acids cyclize in aqueous alkali to give 4,1-benzoxazepine-2,5(l//,3//)-diones 2 as stable colorless solids.36... 

An analogous reaction of 6-chloro-2-(chloroacetamido)benzoic acid in aqueous dimethylform-amide for two hours at 90"C gives 6-chloro-4,l-benzoxazepine-2,5(l//,3/f)-dione (2b). 

The dione 1 is converted into 2,6-dichloro-4,l-benzoxazepin-5(3i/)-one (2) by the action of phosphoryl chloride in jV.lV-dimethylaniline. The crude product on treatment with 3-isocyano-methyl-5-isopropyl-l,2,4-oxadiazole gives the imidazobenzoxazepinone 3.36... 

Via (N—C—C—C—O—C—C) intermediates (type c). Salicylamide (351 R = H) can be converted to 1,4-benzoxazepine derivatives, e.g. its reaction with 2-chloropheny-lacetic acid gives (351 R = CH(Ph)C02H) which on treatment with acetyl chloride cyclizes to the 3,5-dione (352). Similarly reaction of (351 R = H) with phenacyl bromide gives (351 R = CH2COPh) which undergoes acid-catalyzed cyclization to give (353). 

There has been little systematic study of the chemistry of 1,4-oxazepines. Vigorous acid hydrolysis cleaves the amide linkage in (369 R1=Ph, R2 = H) and recyclization gives 2-o-hydroxyphenyl-5-phenyloxazoline and l,2,3,4-tetrahydro-l,8-dihydroxy-3-phenyl-isoquinoline. The l,4-benzoxazepin-5-one (353) can be alkylated at N but on treatment with triethyloxonium fluoroborate it is converted to 5-ethoxy-3-phenyl-l,4-benzoxazepine — one of the very few examples of a fully unsaturated 1,4-oxazepine ring. This product is isomerized to l-ethoxy-4-hydroxy-3-phenylisoquinoline when boiled in methanol. The 4,l-benzoxazepine-2,5-diones (348) are converted to quinazolines by reaction with ammonia. The dihydro-l,4-oxazepin-5-one (343) can be acetylated at nitrogen and bromi-nated at the 6-position. 

In a tandem isomerization/Prins strategy utilizing cooperative catalysis between an iridium(III) catalyst and a Bronsted acid, indole 182 underwent an isomerization/protonation sequence via a Prins-type oxocarbenium intermediate, with subsequent C—C bond formation to give oxepane-fused indole 183 (13AGE12910). Various anthranilic acids were coupled with chiral a-haloacids to afford N-acylated anthranilic acid intermediates which underwent cyclization to (3R)-3-alkyl-4,l-benzoxazepin-2,5-diones... 

Bartsch, H. and Erker, T. (1989) Synthese und Reaktivitat des l,5-Benzoxazepin-2,4 (3H,5H)-dions. Annalen Der Chemie-Justus... 

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