Benzox azines

The methine chain is obtained by reacting ethyl o-formate (method A ) or ethylisoformanilide (method B) with a bis quaternary salt of bis-(2-thiazolyllbutane. Concerning dyes with fused thiazolo rings pyrrolo[2. lb]thiazoIe. thiazolo[2.3a]indole. thiazolo[2.3c]1.4-benzox-azine. the a carbon directly linked to the carbon 2 of the thiazoJe ring is also responsible for the classical syntheses giving trimethine or penta-methine dyes. 

The analogous reaction with 1,1,3-trimethyl-2-(trimethylsilyloxy)cyclohexene employing titani-um(IV) as the Lewis acid also proceeded in the same stereochemical sense and gave 1,2-benzox-azin-2-ium 2-oxide 6 as the only diastereomeric product in 75% yield16. 

S)-[(7,8-difluoro-2,3-dihydro-3-methyl-4 -l,4-benzox-azin-4>yl)methylene]propanedioic acid diethyl ester... 

However, it was claimed that the thermal cyclization of (7,8-difluoro-3-fluoromethyl-2,3-dihydro-1,4-benzoxazin-4-yl)methylenemalonate (560) in diphenyl ether at 250°C for 30 min gave pyridoH J-c/el-M-benzox-azine-6-carboxylate (561) in 71% yield [86JAP(K)204188]. 

Studies on the stereostructures of cis- and /ra r-perhydro-l,3- and 3,1-benzoxazines 86-89 revealed that/ra r-fused derivatives 87 and 89 attain a biased chair-chair conformation, while their -counterparts 86 and 88 can be characterized by conformational equilibria of the O-in/N-in (a) and O-out/N-out (b) isomers, which, for 3,1-benzox-azines 88, are strongly influenced by the bulkiness of the substituent R attached to the nitrogen <1996CHEC-11(6)301, 1998AHC(69)349>. 

From a structural analysis of as- and /ra r-2-imino-l,3- and -3,1-perhydrobenzoxazines 92 and 93, it was concluded that all these /ra r-fused compounds exist in biased chair-chair conformations 92, as expected, whereas the m-fused 1,3-benzoxazines 93 (X = O, Y = NMe) attain exclusively the O-in conformations 93a. For the m-fused 3,1-benzox-azines 93 (X = NMe, Y = O), predominance of the N-out form 93b was found, owing to the favorable axial orientation of the A -methyl substituent <2003MRC435>. 

When o(l-piperidyl)benzyl alcohol was stirred in methylene chloride in the presence of an excess of active MnC>2, a 9 1 mixture of 1,2,3,4,4a,6-hexahydropyrido[l,2-a][3,l]benzoxazine and o-(l-piperidyl)benzaldehyde was obtained (83TL2213). l,2,3,4,4a,6-Hexahydropyrido[l,2-a][3,l]benzox-azin-6-ones were prepared from o-(2-piperidyl)benzoic acids either with Mn02 in chloroform [68JCS(C)1722], or with the Hg(OAc)2-EDTA reagent (81AP524 82AP119). 

Thermal isomerization of l-trifluoroacetyl-2-(l-piperidyl)benzenes or their hydrates by heating in 1-butanol for 20-90 h gave diastereomeric mixtures of 6-trifluoromethyl-l,2,3,4,4a,6-hexahydropyrido[l,2-a][3,l]benzox-azines (83TL3923 89RTC147). Cyclization did not occur under acidic conditions (88TL4599). 

Simazine and atrazine have little effect on com, sorghum, sugarcane, and some other grasses, apparently because of the ability of the plant to metabolize the parent molecule. Com and wheat gave a cyclic hydrox-amate, namely, the 2-D-glucoside of 2,4-dihydroxy-7-methoxy-l, 4-benzox-azin-3-one (11), m.p. 168-70°, aglycon m.p. 156-7 (dec.), believed to... 

The first representative 57 of pyrido[2,l-/]-3,l-benzoxazine ring system was synthesized by the ring-closing methathesis of perhydro-3,l-benzox-azine 113 in the presence of the second generation of Grubb s catalyst (06TL3815). 

Enantiomers of 3-[(4-aminopiperidin-l-yl)methyl]-5-oxo-2,3-dihy-dro-5H-pyrido[l,2,3-cfe][l,4]benzoxazine-10-carbonitril and 10-meth-oxy-3-( 4-[(3-oxo-3,4-dihydro-2H-pyrido[3,2-fr][l,4]oxazin-6-yl)methyla-mino]piperid-l-yl methyl)-2,3-dihydro-5H-pyrido[l,2,3-de][l,4]benzox-azin-5-one were separated by chiral HPLC (08WOP2008/120003). 

Pyrazolines containing aryl substituents with some functional groups can be used in the synthesis of new heterocycles. For example, the reaction of 5-(2-hydrohyphenyl)pyrazolines 111 with noncyclic 112 or cyclic carbonyl compounds under acidic conditions yields dihydropyrazolo[l,5-c]-l,3-benzox-azines 114 and 115, respectively [167, 168, 169] (Scheme 2.30). 

Hartenstein, H. and Sicker, D. 1994. (2R)-2-D-D-Glucopyranosyloxy-4-hydroxy-2H-1,4-benzox-azin-3(4H)-one from Secale cereale. Phytochemistry 35, 827-828... 

Optically active pipecolic acid and its derivatives can be prepared via 4-phenylpyrido[2,l-c][l,4]oxazin-l-one derivatives. Representatives of the third generation of quinoline-3-carboxylic acid antibacterial agents ofloxacin (19), its levorotatory enantiomer, levofloxacin (20), and rufloxacin (21) have gained wide acceptance for the treatment of bacterial infections of the respiratory and urinary tracts, skin, and soft tissues, as well as sexually transmitted diseases, and pazufloxacin (22) is under development. Other 10-aryl-9-fluoro-7-oxo-2,3-dihydro-7//-pyrido[l,2,3-de]-l,4-benzox-azine-6-carboxylic acids and 7//-pyrido[l,2,3-de]-l,4-benzothiazine-6-carboxylic acids exhibit mammalian topoisomerase II inhibitory activity. 

Reaction of 8-amino-2,5,6,7-tetrahydro-3//-pyrido[l,2,3-de]-l, 4-benzox-azin-3-one with tetrahydrophthalic anhydride gave 100 (91EUP406993). The hydroxy group of 9-[2,2,2-trifluoro-l-hydroxy-l-(trifluoromethyl)-ethyl]-2,3-dihydro-5//-pyrido-[l, 2,3-de]-l,4-benzoxazin-5-ones was acy-lated (79GEP2854727). Treatment of 9-fluoro-10-phenyl-3-methyl-7-oxo-2,3-dihydro-7//-pyrido-[l,2,3-de]-l,4-benzoxazine-6-carboxylate with CISO3H afforded the 10-(p-chlorosulphonylphenyl) derivative, which was converted to the 10-(p-aminosulphonylphenyl) derivative with NH3 (86EUP184384). 

Other syntheses of this type are exemplified by the conversion of 126 to 127 by treatment with sodium sulfide (Scheme 79) <2004T4361, CHEC-III(11.16.6.1.2)711 >, the synthesis of the tricyclic [l,2,4]triazolo[l,5-z][l,3]benzox-azine 129 by reaction of the triazolylphenol 128 with bis-trichloromethyl carbonate (Scheme 80) <1995JME2196, CHEC-III(11.16.6.1)710>, and the preparation of indolo[2,l-z]benzo[l,2,4]triazine derivatives 131 by diazotization of 2-amino- 1-aryltetrahydroindoles 130 followed by an intramolecular coupling of the diazonium group with the aryl moiety (Scheme 81) <2003H2519, CHEC-III(11.14.8.4)638>. 

Fluoro-10-(cyclic amino)-7-oxo-l//,3//,7//-pyrido[3,2,l-y][3,l]benzox-azine-6-carboxylic acids exhibit antibacterial activities (90EUP373531). Xhe dopaminergic (D2) and serotonergic (5HXia) activities of 6-(di- -propy-lamino)-6,7-dihydro-l//,3//,5//-pyrido[3,2,l-ry][3,l]benzoxazin-3-one were measured (92JMC1076 93MI4). 

Upon thermolysis, 3-aroyl-l,2-dihydro-4ff-pyrrolo[2,l-f][l,4]benzox-azine-l,2,4-triones 156a-f in inert aprotic solvents at 168—190 °C led to generation of 4-aroyl-3-aroyloxy-2-(2-oxo-2H-l,4-benzoxazin-3-yl)-lH,5H-pyrido-[2,l-c][l,4]-benzoxazine-l,5-diones 318a—f (Scheme 100)... 

In another case rotor-synchronized H DQ MAS spectra were used to elucidate the supramolecular structures adopted by two different aUcyl-substituted benzox-azine dimers [(V,(V-bis(3,5-dimethyl-2-hydroxybenzyl) R amine], where R = methyl or ethyl. ... 

Atkinson J, Morand P, Amason JT, Niemeyer HM, Bravo HR (1991) Analogs of the cyclic hydro xamic acid 2,4-dihydroxy-7-methoxy-2H-1,4-benzox-azin-3-one (DIMBOA) decomposition to benzox-... 

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