Oxazepine 1,3-, 2-phenyl

Another photochemical ring enlargement leading to a 1,3-oxazepine is the formation of 2-phenyl-l,3-oxazepine (13) by irradiation of 4-phenyl-2-oxa-3-azabicyclo[3.2.0]hepta-3,6-diene (11).12 It is proposed that the process involves the azirine 12 as an intermediate. 

Dimethyl-5-phenyl-l,4-oxazepine isomerizes to 6,7-dimethyl-4-phenyl-l,3-oxazepine in boiling benzene.30 The process involves successive valence isomerization, a walk rearrangement and a second valence isomerization. 

Oxazepines are readily decomposed by heat and light and by acids and bases.8 Some of these reactions proceed by hydrolytic opening of the oxazepine ring, as in the formation of 1-benzoylpyrrole (1) from 2-phenyl-l,3-oxazepine and cold dilute hydrochloric acid,12 while others involve valence-tautomeric oxazanorcaradienes, as in the thermal conversion of 2-phenyl-l,3-oxazcpine into 2-phenylpyridin-3-ol (2).12... 

At 75 C, 2-phenyl-l,3-oxazepine undergoes a [27r + 47t] cycloaddition to 2,5-dimethyl-3,4-diphenylcyclopentadienone to give 3, which at 120 C is transformed into the isomer 4 by a Cope rearrangement.16... 

Both 1,3- and 3,1-benzoxazepines are known. The parent compounds are unstable oils, which decompose on attempted chromatography 17 cyano or phenyl substituents on the oxazepine ring stabilize the systems. 

Treatment of 2-phenyl-l,3-benzoxazepines with hydrochloric acid in acetic acid gives benzo-furans by hydrolytic opening of the oxazepine ring, followed by loss of benzamide and re-cyclization.23... 

For the isomerization of 2,7-dimethyl-5-phenyl-l,4-oxazepine to 6,7-dimethyl-4-phenyl-1,3-oxazepine, see Section 4.1.1.2.1.1. 

Heating 5-phenyl-l,4-oxazepine in benzene gives 6-phenylpyridin-3-ol.30... 

Heating phenacyl 2-aminobenzoate with phosphoryl chloride yields 2-phenyl-4,1-benz-oxazepin-5(17/)-one (1. R = H). The method has been applied to the synthesis of a number of analogs.423... 

Dibenz[(j,/][1,4]oxazepines 2 are readily obtained by the cyclodehydration of 2-(acylamino)-phenyl phenyl ethers 1 in polyphosphoric acid.38... 

Finally, formation of seven-membered rings by vinylaziridines possessing carbonyl or thiocarbonyl groups are shown in Scheme 2.46. Thermolysis of 182 in toluene at reflux yielded 4,7-dihydro-l,3-oxazepine 183 [71]. Similarly, treatment of N-unsubstituted vinylaziridine 184 with phenyl isothiocyanate in ether at 0 °C gave seven-membered ring 185, via a l-thiocarboxanilide-2-vinylaziridine intermediate [72]. 

The diastereoselectivity and the stereochemical outcome of the addition of 2,3,4,6-tetrahydro-3, 4-dimethyl-2-phenyl-1,4-oxazepine-5,7-dione, derived from ephedrine and methyl hydrogen malonate, to 1 -nitrocyclohexene was found to be dependent on the nature of the base and the solvent. The highest diastereoselectivity was obtained when potassium /tr/-butoxide in the presence of dicyclohcxyl-18-crown-6 was employed. In the absence of crown ether the diastereoselection was poor and the sense of the stereochemical outcome was reversed26. 

VL,3S,6R)-2,3,4,6-tetrahydro-3,4-dimethyl-6-(2-nitrocyclohexy[)-2-phenyl-1,4-oxazepine-5,7-dione ... 

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. 

Hi) Preparation from other heterocyclic systems 2-Vinylaziridine (392) reacted with phenyl isothiocyanate or 4-chlorothiobenzoylthiogly-collate to give (394), presumably via the intermediate (393) (cf. the analogous preparation of 1,3-oxazepines, p. 627) (71JOC3076). 

Ring expansion has also been observed in the transformation of certain 1-cyano- and 1-phenylisoquinoline 2-oxides to the corresponding benz[/]-l,3-oxazepines,163 of phenyl-substituted quinoxaline 1-oxides to the substituted benz[d]-l,3,6-oxadiazepines,161 164 and of 4-phenylquinazoline 3-oxide (190) to 2-phenylbenz[/]-l,3,5-oxadiazepine (191).165... 

After [2n+2n] cycloaddition reaction of imine 271 and benzyne 272, the formed benzazetidine 273 underwent ring opening into its valence tautomer 274. Moisture attacked the tautomer 274 to give oxazepine 275. This method yielded 60-68% of the bicyclic 1,4-oxazepine 275. One extra mole of benzyne led to the formation of N-phenylated 276 (Scheme 48) <2003T6067>. 

Buchardt, O., Lohse, C., Duffield, A.M. and Djerassi, C. (1967) The photolysis of 1-phenyl and 1-cyano substituted isoquinoline N-oxides to benz[f]-l,3-oxazepines. Tetrahedron Letters, 8 (29), 2741-2745. 

Monocyclic 1,3-oxazepines 419 can be prepared by reaction of aliphatic diazo compounds with 1,3-oxazinium perchlorates 418 (Scheme 194) <1974S187>. Tetra- and penta-phenyl-1,3-oxazepines 421 (R = H or Ph) have been obtained by the reaction of azide ion with pyrylium salts 420 (Scheme 195) <1978H(11)331>. 

The preparation of 3,1-benzoxazepines by photochemical isomerization of quinoline A-oxides constitutes a rather general entry into this class of seven-membered heterocycles. Since the structure of the photoisomer of 2-phenylquinoline A-oxide was first recognized as 2-pheny 1-3,1-benzoxazepine by Buchardt et al.,3 the scope of this method for oxidative ring expansion of six-membered heterocyclic A-oxides to 1,3-oxazepines has been extensively explored.4 For example, irradiation of 2-cyano-, 2-phenyl-, and 2-methoxyquinoline A-oxides affords the corresponding 2-substituted 3,1-benzoxazepines in 70-90% yield.5 However, isolation of the moisture-sensitive parent compound was only recently accomplished in the submitters laboratories.6... 

Related 1,3-oxazepines have been obtained from irradiation of many other heterocyclic A-oxides including pyridine A-oxides, isoquinoline A-oxides, quinoxaline A-oxides, quinazoline A-oxides, phenanthridine A-oxides, benzophenazine A-oxides, and acridine A-oxides.4 However, the reported yields are variable and have generally been higher for phenyl and other aryl-substituted derivatives. 

In the reaction of 4-ethoxycarbonyl-5-phenyl-2,3-dihydrofuran-2,3-diones 427 with di-isopropylcarbodimimide, insertion into the furan ring occurs to give the oxazepin-6,7-dione derivative 428 in 68 % yield. ... 

Oxazepin 2-Methyl-3(bzw. 7)-phenyl-2,3,6,7-tetrahydro- E16a, 313 (Amin-oxid-Umlager.) 4H-l,3-Oxazin... 

Similar attack of methanol on the presumed oxaziridine intermediate in the photolysis of C,N-diphenylnitrone led to the formation of 2- and 4-methoxyazoben-zenes."" The reaction converting dibenz[b,f] [l,4]oxazepine 60 to 2-(2-hydroxy-phenyl)benzoxazole 62 seems better explained by a nucleophilic substitution on protonated 61 than by the electrophilic process suggested by the authors. ... 

The Michael addition of (2/ ,3S)-3,4-dimethyl-5,7-dioxo-2-phenylperhydro-1,4-oxazepine (236) to l-phenyl-2-buten-l-one (237) and 2-cyclopenten-l-one (238) in tetrahydrofuran at 0°C gave a mixture of diastereomeric... 

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