Oxazepines—

6 Systems containing Two Different Heteroatoms Oxazepines. - In an unusual reaction, theiV-hydroxyphthalimido-ether (170) rearranges (under basic conditions) to give the 1,2-oxazepine derivative (171) in moderate yield, together with (172)/  

Following earlier work on the conversion of azidopyrans and azido-chromenes into l,3 oxazepines and 1,3-benzoxazepines, respectively, it has now been shown that the pyrolysis of 1-azidoisochromenes (177) gives 3,1-benzoxazepines (178) in moderate yield. 

The course that is taken in reactions of 1,3-oxazolium salts (179) with stabilized carbanions is strongly dependent on the nature of the substituents on the carbanion in some cases, attack at the 2-position leads to 1,4-oxazepines, (180).  

The unsubstituted pyrrolo[l,2-a][4,l]benzoxazepine system (183) has been prepared from (182) by heating or by treatment with phosphorus pentoxide. The 6-oxo-derivative (184) was also prepared from (181), by selective reduction of the aldehyde and cyclization.  

As with the benzocondensated series, the production of 3,1-benzoxazepines via the irradiation of quinoline-N-oxides is strongly affected by the solvent, and also by the nature and position of substituents on the pyridine moiety of the quinoline (aprotic solvents and Ph, CN, OMe, or CF3 groups attached to C(2) position favor formation of 

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No monocyclic 1,2-oxazepines have been reported, but annulated derivatives are known. 

The first reported derivative of 1,2-oxazepine was dibenz[f,/][l,2]oxazepine-ll-carbonitrile (3 a). This, together with small amounts of compounds 4 and 5, is formed when acridine-9-carbonitrile 10-oxide (la) is irradiated with UV light,6,7 It is likely that the reaction proceeds by way of the oxaziridine valence tautomer 2a, which, however, was not detected.7 Photo-isomcrization of 9-chloroacridine 10-oxide (lb) yields the 11-chlorodibenzoxazepine 3b.6,7... 

Treatment of dibcnz[e,/J[1,2]oxazepine-l 1-carbonitrile or 1 l-chlorodibenz[c,/][l,2]oxazepine with triphenylphosphane in acetonitrile at room temperature yields the acridines 5 quantitatively.7... 

Cyano- and 10-chloro-acridine A-oxides yield 1,2-oxazepines on photolysis in benzene (Scheme 237). When the 10-substituent is methyl the unstable 1,2-oxazepine undergoes electrocyclization to a benzisoxazoline (320). Secondary photoproducts may be formed by direct irradiation of N- oxides or by rearrangement of the primary photoproduct. 

The Meisenheimer rearrangement of tertiary amine N- oxides has been applied to the synthesis of both monocyclic 1,2-oxazepines, e.g. (309) (65JOC3135, 65JCS1653, 82H(19)173), and those fused to benzene (80AJC833) and a variety of heterocyclic rings (80AJC1335). 

The unstable dibenz[c,/][ 1,2]oxazepines (312 R = CN, Cl) have been isolated as the major products of the UV irradiation of 9-cyano- and 9-chloro-acridine 10-oxides (310) in benzene (c/. the analogous jV-imide to 1,2-diazepine conversion on p. 598). Although none of the oxaziridine tautomer (311) was detectable by UV spectroscopy, the subsequent deoxygenation of (312) to acridine suggests the existence of a thermal equilibrium between (311) and (312) (79T1273). These dibenzo compounds (312) are the only fully unsaturated oxazepines yet isolated but the 2,3-benzoxazepin-l-one system (314) has recently been prepared by the reaction of benzonitrile oxide with the benzopyranone (313) (80JCS(Pl)846). 

There has been a modest interest in the chemistry of these systems over the past decade. In this chapter, the 1,2-oxazepines and 1,2-thiazepines are grouped together due to their sparseness in the literature. There is a general review of these systems that appeared in CHEC-II(1996) <1996CHEC-II(9)183>. The parent systems 1 and 2, respectively, are shown below however, most of the known compounds are based on their reduced derivatives. Oxidized forms of the 1,2-thiazepine system are also treated, in particular derivatives of 1,2-thiazepine 1,1-dioxide 3. 

Ring-closing metathesis methodology has been used in the synthesis of the 1,2-oxazepine derivatives 21 and 22. These derivatives were synthesized from the respective diene precursors 20 and 19, which were derived from 18 by N-acylation or N-alkylation respectively (Scheme 1) <2003SL1043>. 

In a similar metathesis process, the 1,2-oxazepines 24 were prepared from, /V-alkynyl analogues 23 (Equation 3) <2003SL2017>. A range of Diels-Alder reactions based on the dienophilic moiety in 24 have also been reported <2003SL2017> to give ring-fused 1,2-oxazepine systems. 

Ring expansion of the enantiopure 1,2-oxazines 32a and 32b involving dibromocarbene cycloaddition, followed by methanolysis of the intermediates 33a and 33b, provided a convenient route to the 1,2-oxazepines 34a and 34b in moderate yields (Scheme 2). The vinylic bromide was then used as a site for the introduction of other functionality via palladium-catalyzed C-C bond-forming reactions <2005SL2376>. 

Compared with azepine derivatives, considerable scope still exists for innovative exploration of ring-closing metathesis methodology to access multisubstituted 1,2-oxazepine and 1,3-thiazepine derivatives and benz-fused analogues. Also, the full synthetic potential of the Meisenheimer rearrangement to afford various 1,2-oxazepine derivatives with different types of functionality present is still to be realized. 

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