4.7- Dihydro-1,3-oxazepin-2 -ones

Monocyclic 1,3-oxazepines (325) with aryl substituents at the 2-, 4- and 7-positions can be prepared in moderate yield (20-40%) by the reaction of aliphatic diazo compounds with 1,3-oxazinium perchlorates (324) (74S187). Tetra- and penta-phenyl-l,3-oxazepines (328 R = H or Ph) have been obtained via the reaction of azide with pyrylium salts (326) (78H(l 1)331). This principle had earlier been applied to the preparation of 1,3-benzoxazepines (74CR(C)(278)1389> and more recently to 3,1-benzoxazepines (81JHC847). The preparation of 2-phenyl-1,3-oxazepine.(331) by the UV irradiation of (329) is mechanistically interesting in that it apparently involves an intermediate (330) of the same type as (327) (73TL1835), but the method has only been used in this one case. One of the few examples of a dihydro-1,3-oxazepine (333) has been prepared by the thermolysis of the aziridine (332) (68JOC4547). 

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. 

A one-atom cobalt carbonyl-mediated ring expansion of the 3,6-dihydro-2//-1,2-oxazincs 56 provided access to the 4,7-dihydro-l,3-oxazepin-2(3//)-ones 57 in modest yields (Equation 11) <1996TL2713> however, these conditions were quite severe with carbon monoxide at 1000 psi being required for the cobalt carbonyl used. 

The lactam derivative dibenz[h/]l 4-oxazepin-ll-(lOH)-one is a primary metabolic product of metabolism and a direct precursor of the urinary hydroxylated metabolites. In rats, the lactam, a dihydro-CR metabolite, an amino alcohol of CR, and an arene oxide are metabolites in CR degradation. In the rat, the major mechanism for elimination is sulfate conjugation and biliary excretion to a limited extent. Phase I metabolism by microsomal mixed fimction oxidases involves reduction of CR to the amino alcohol, oxidation to form the lactam ring, and hydroxylation to form the hydroxylactams. Phase II conjugation reactions sulfate the hydroxylactam intermediates for renal elimination. Amino alcohol intermediates are conjugated with glucuro-nide for biliary secretion. 

An interesting ring contraction to form dihydro-1,2,4-triazine (151) was reported by Halladin and Hassner240 by the reaction of l,4-oxazepin-7-ones (150) with hydrazine [Eq. (68)]. 

Richard, S. Prie, G. Guignard, A. Thibonnet, J. Parrain, J.L. Duchene, A. Abarbri, M. A new synthesis of optically active 3-substituted (3S)-3,4-dihydro-5-(perfluoroalkyl)-2H-[l,4]oxazepin-7-ones. Helv. Chim. Acta 2003, 56(3), 726-732. 

Table 2 Yields and melting points of the 4,7-dihydro-1,3-oxazepin-2(3//)-ones.

Typical examples of oxazoline monomers to be polymerized via CROP mode are shown in Scheme 3. Not only five-mem-bered monomers of ROZO and 5-oxazolones (4,5-dihydro-l,3-oxazol-5-one, ROZLO) but also six-membered analogs (5,6-dihydro-4H-l,3-oxazines, ROZI) and seven-membered ones (4,5,6,7-tetrahydro-4H-l,3-oxazepine, ROXP) have been polymerized. 2-Iminotetrahydrofurans (ITHFs) are known as an exo-cydic imino ether derivative of ROZO. CROP of ITHF was reported in 1963, which was preceded by the studies on the CROP of OZOs. Preparations of these monomers have been well known and documented. ... 

---