2.4- Benzoxazepine systems

One-pot reactions involving successive nucleophilic attack by oxygen and nitrogen on a 1,1-bis-carbon electrophile are used in the synthesis of 2,4-benzoxazepine systems (325) and (326) (72JHC1209,... 

Fully unsaturated 1,3-benzoxazepine system (319) can be obtained by intramolecular aza-Wittig reaction (90S455) of the esters (318) induced by triethyl phosphite (90S455,92CC81). 

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. ... 

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. 

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). 

The reactions of anthranilic acids and esters (65CB983, 75BSF(2)283) with halohydrins give the 4,l-benzoxazepin-5-one system (357). o-Methylaminobenzamide reacts with ethylene oxide to give (358) which can be cleaved to (359) by treatment with aqueous ammonia (66JOC4268). 

The 2,3-benzoxazepin-l-one system (436) is prepared by the reaction of benzonitrile oxide with the benzopyranone (435) (80JCS(P1)846). The tetrahydro-3,2-benzothiazepine 3,3-dioxide (438) was prepared from (437) by intramolecular sulfonamidomethylation (76CC470). 

Benz-fused analogues are also covered in this chapter. The possible benz-fused parent systems are 2,1-benzothiaze-pine 4, 1,2-benzoxazepine 5, 3,2-benzoxazepine 6, 2,3-benzoxazepine 7, 2,1-benzothiazepine 8, 1,2-benzothiazepine 9, 3,2-benzothiazepine 10, and 2,3-benzothiazepine 11 derivatives of some of these systems are included. A major reference series has reviewed seven-membered heteroarenes with two or more heteroatoms <1997HOU(E9d)299>, while the syntheses of benzoxazepines, including 2,3-, 3,2-, and 2,1-skeletons, have also been reviewed <1997MI1>. 

Other polycyclic systems containing an azidoazomethine moiety which exist in the cyclic form include tetrazoloadamantanes,391 dihydro-benzoxazepine tetrazole derivatives,392 and steroid tetrazoles.393-398 The... 

Tricyclic systems as compounds of potential pharmacological interest prepared by conventional cyclisation procedures include thienoanellated [l,4]benzoxazepines <94JHC1053>, pyrido[l,4] and [l,5]benzoxazepines and thiazepines <94JMCS19>, and IH- and 2H-pyrazolo[3,4-c][2,l]benzothiazepines <94JHC93>. A number of... 

An alternative ring expansion process involving the benzopyranone (77) and the 1,3-dipole benzonitrile oxide, generated in situ from A-a-chlorobenzylidenehydroxylamine, affords access in low yield (8.4%) to the functionalized 2,3-benzoxazepin-l-one system (78) (m.p. 155-156°C). An analogous reaction is demonstrated by A-benzylideneaniline A-oxide to give (79) (m.p. 266-267°C) in 16% yield (Scheme 9) <80JCS(Pi)846>. 

Selected spectroscopic data have also been reported for the 1,3-benzoxazepine derivative (14) <90HCA739>. In this case, the signal at 6 7.57 in the H NMR spectrum was assigned to H-5 in the parent system, 1,3-benzoxazepine, H-5 and H-4 appeared as doublets (/=8 Hz) at S 6.57 and S 6.25, respectively <79TL376l>. 

Extensive spectroscopic data on substituted 1,3-benzoxazepines have been reported by Desbene and Cherton <84T3567>, while H NMR and infrared absorption data on the parent isomeric system. 

Ring opening is characteristic of the reactions of the fully conjugated systems. For example, on reaction of the dibenz[d/][l,3]oxazepine (25) with methylamine, the phenolic imine (27) was obtained in near quantitative yield, most probably via the intermediate adduct (26) (Scheme 2) <78CPB2508>. Ring opening of 1,3-benzoxazepine and 3,1-benzoxazepine was also observed on treatment with piperidine, and with 7V-methylaniline in the latter case <79TL376I>. 

NHC (IMS HCl) as the ligand or even under ligand-free conditions. Copper salts were applied in these transformations as well. In 2003, a nickel-catalyzed system was also developed. With Ni(0) generated in situ as the catalyst and 2,2 -hipyridine or N,A/ -his(2,6-diisopropylphenyl)dihy-droimidazol-2-ylidene (SIPr) as the ligand, the intramolecular coupling of aiyl chlorides with amines was achieved with NaOfBu as the base. Indoles, quinolines, benzazepines, benzoxazines, and benzoxazepines were produced in good yields from the corresponding substrates. 

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