Reaction with 1,3-oxazepines

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. 

The bis-fused 1,3-oxazepine derivative 35 can be made by treatment of amino alcohol 34 with the keto acid 33, the latter being prepared from a Grignard reaction with 3-methylglutaric anhydride. A 6 1 trans ds diastereomeric ratio was obtained with 35, which was then used in a new approach to a spiro heterocyclic system (Scheme 3) <2001SL1506>. 

The transition metal-catalyzed carbonylation reaction is an important pathway to introduce an extra carbon atom in the heterocyclic ring. Lu and Alper used this reaction with recyclable palladium-complexed dendrimers on silica to synthesize 1,4-oxazepines. Remarkably, starting from iodinated arylamine 121, as a substrate for the intramolecular carbonylation, quantitative conversion to the pentacyclic heterocycle 122, containing two oxazepine rings, was achieved (Equation 11) <2005JA14776>. 

An alternative ring construction approach to 1,4-oxazepin-7-ones (e.g. 241) utilises the Baylis-Hillman product 240, subsequent reaction with a p-aminoalcohol, and ester hydrolysis followed by DCC-mediated intramolecular coupling to afford 241. This sequence can be generalised to give a range of analogues [02S2232],... 

Dibenzothiophene bromination, 59, 254 reaction with XeF, 59, 254 Dibenzothiophenes, 4-halo-, 59, 254 Dibenzothiopyrones, see Thioxanthones Dibenz[ft/)( 1,4]oxazepines, polyfluoro-,... 

A new method of synthesis of the eyano-substituted fused 1,4-oxazepine derivative 91 has been outlined by Abramov et al. <03H(60)1611>, based on nucleophilic aromatic substitution reactions with 89 and 90. 

Formation of a cation radical of the diene may catalyze Diels-Alder reactions with certain dienophiles thus oxidation of substituted vinylindoles to the cation radical in the presence of a push-pull dienophile may form different heterocyclic compounds by the Diels-Alder reaction, for instance pyrido[l,2i7]indoles from vinylindoles and yS-enamino-esters [33]. Similarly, anodic oxidation in MeCN of certain oxazolidines in presence of vinyl ether leads to derivatives of oxazepines in a catalytic reaction in which the ring-opened radical cation of the oxazolidine adds to the vinyl ether and the radical cation of the resulting oxazepine oxidizes the oxazolidine [34]. 

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>. 

This includes cleavage of the CN bond (path a), insertion of the oxygen atom between C and Cp with expansion to an oxazepine ring (b), formation of a lactam (c), cleavage of the CC bond (path d), and insertion of the oxygen atom between the nitrogen atom and the vicinal carbon (path e, not observed with monocyclic N-oxides). Trapping reactions with evidence of the biradical or zwitterionic nature of the intermediate have been also obtained in some cases (see path/). 

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... 

Irradiation of the unsymmetrically substituted 2,3,4,6-tetraphenylpyridine 1-oxide (5) under these conditions gives 2,4,6,7-tetraphenyl-l, 3-oxazepine (7) in 30 % yield, together with 2,4,5,6-tetraphenylpyridin-3-ol (10) in 37% yield and 2,3,4,6-tetraphenylpyridine (30%).11 It has been suggested that the reaction proceeds by way of the oxaziridines 6 (which yields 7) and 8 (which yields the isomeric oxazepine 9) the latter rearranges to the pyridinol 10. 

Ethyl 2,4,7-triaryl-l,3-oxazepine-6-carboxylates 15 are formed in modest yield by the reaction of ethyl diazoacetate with 1,3-oxazinium perchlorates 14.13... 

The reaction of sodium azide with tri-, tetra- or pentaarylpyrylium salts 16 gives highly unstable 2-azido-2//-pyrans 17, which readily lose nitrogen to form 1,3-oxazepines 18 (see Houben-Weyl, Vol.E7b, p 983 ff) typical examples are listed.1415... 

Treatment of the 1,2-oxazines 52 with carbon monoxide at 1000 psi in the presence of cobalt carbonyl brings about insertion of carbon monoxide to form the 1,3-oxazepines S3 <96TL2713>. A convenient route to P-lactams fused to oxepines is made available by alkene metathesis. Thus reaction of 4-acetoxyazetidin-2-one with ally alcohol in the presence of zinc acetate, followed by iV-allylation of the nitrogen affords the derivative 54 which cyclises by RCM to form the oxazepinone 55 <96CC2231>. The same communication describes a similar synthesis of 1,3-dioxepines. 

A 1,3-oxazepine derivative (158) has been isolated in low (2-3%) or unspecified yield by treatment of the Z-ketovinylazirine 157 with diiron nonacarbonyl50 or molybdenum hexacarbonyl,51 respectively (Scheme 182) the major products of these reactions are pyrrole derivatives (see Scheme 23 in Section IV,A,1). There is no preparative value in this type of oxazepine synthesis (Scheme 182) since the transformation can be affected efficiently in a thermal reaction at 100°C.52... 

Formation of the reduced 1,3-oxazepine derivative 160 from the reaction of diiron nonacarbonyl with the tetrahydrooxazine derivative (159) involves a novel formal insertion of carbon monoxide into an N—O bond (Scheme 183).248 The synthetic applicability of this unusual reaction has not been evaluated. 

Racker et al. have developed an interesting new combinatorial method for the synthesis of [l,4]oxazepin-7-ones (eg 139, R = Ph) from aldehydes and a-amino alcohols with the Baylis-Hillman reaction being a key step . 

The reactions of 2,4,6-triphenyl-3-azapyrylium perchlorate (64) with various amino compounds were investigated in detail (Scheme 9) (81BCJ2387). Conversions into 3-phosphapyridines 65 and oxazepines 66 have been also described (74S187 87TL1093) (Scheme 9). 

One-step reduction of aldehyde and ester functions in intermediate 263a (R = Me, = H) results in a di-alcohol, which, when treated with P2O5, undergoes cyclization into oxazepine 264 (Scheme 56 (2005BMCL2515)). Similarly, this reaction sequence can start from monoester 263b (R = H, r2 = OH (2001JCS(P1)1039)). 

The unstable dibenz[c,/][l,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 Af-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). 

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). 

A range of 2,2-bis(trifluoromethyl)-l,3-oxazepin-5-ones (334) has been prepared by the reaction of oxazolidin-5-ones with 1-diethylamino-l-propyne (75TL3223). l,3-Oxazepan-2-one has been prepared by the Beckmann rearrangement of tetrahydro-2-pyranone oxime. 

Oxazepines fused to heterocyclic rings have been prepared by the reaction of ethanolamine for example with 4-chloro-3-ethoxycarbonylpyridine (71CPB2354) to give... 

As with 1,4-oxazepines the Schmidt reaction of cyclic ketones and the Beckmann rearrangement of their oximes can be applied to the synthesis of monocyclic 1,4-thiazepines, 1,4- and 1,5-benzothiazepines and their 1-oxides and 1,1-dioxides (75CJC276). 

Monocyclic 1,3-oxazepines (290) can be prepared by reaction of aliphatic diazo compounds with... 

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