Solvent benzoxazines

Poly(phenylquinoxaline—arnide—imides) are thermally stable up to 430°C and are soluble in polar organic solvents (17). Transparent films of these materials exhibit electrical insulating properties. Quinoxaline—imide copolymer films prepared by polycondensation of 6,6 -meth5lene bis(2-methyl-3,l-benzoxazine-4-one) and 3,3, 4,4 -benzophenone tetracarboxyUc dianhydride and 4,4 -oxydianiline exhibit good chemical etching properties (18). The polymers are soluble, but stable only up to 200—300°C. 

A careful and NMR study of 1,5-benzoxazine and 1,5-benzo-diazepine shows that these compounds exist in the amino-thione forms 55 and 56, respectively. Compound 55 displays a solvent-dependent amino/imino tautomerism (92MRC673).Tricyclic compounds 57, analogous to the bicyclics discussed above have been described they exist in the tautomeric form shown below (87BSB399,92BSB995,96BSB345). 

Condensation of [3- or "y-amino alcohols with aldehydes or ketones RR CO gives the product 27. In solution the position of the equilibrium varies with R and R, and with the solvent (73). When the carbonyl reactant is a substituted benzaldehyde, the solid is found (IR, KBr) to comprise molecules of the open-chain structure 27a, whereas aliphatic aldehydes and ketones give crystals of dihydro- 1,3-benzoxazines, 27b. An interesting case is that of the condensation product of o-hydroxybenzylamine with cyclopentanone, for which McDonagh and Smith (73) suggest that ring and chain tautomers coexist in the solid. 

Cyclocarbonylation of o-iodophenols 503 with isocyanates or carbodiimides and carbon monoxide in the presence of a catalytic amount of a palladium catalyst (tris(dibenzylideneacetone)dipalladium(O) Pd2(DBA)3) and l,4-bis(di-phenylphosphino)butane (dppb) resulted in formation of l,3-benzoxazine-2,4-diones 504 or 2-imino-l,3-benzoxazin-4-ones 505 (Scheme 94). The product yields were dependent on the nature of the substrate, the catalyst, the solvent, the base, and the phosphine ligand. The reactions of o-iodophenols with unsymmetrical carbodiimides bearing an alkyl and an aryl substituent afforded 2-alkylimino-3-aryl-l,3-benzoxazin-4-ones 505 in a completely regioselective manner <1999JOC9194>. On the palladium-catalyzed cyclocarbonylation of o-iodoanilines with acyl chlorides and carbon monoxide, 2-substituted-4f/-3,l-benzoxazin-4-ones were obtained <19990L1619>. 

As part of an extensive study of the 1,3-dipolar cycloadditions of cyclic nitrones, Ali et al. (392-397) found that the reaction of the 1,4-oxazine 349 with various dipolarophiles afforded the expected isoxazolidinyloxazine adducts (Scheme 1.78) (398). In line with earlier results (399,400), oxidation of styrene-derived adduct 350 with m-CPBA facilitated N—O cleavage and further oxidation as above to afford a mixture of three compounds, an inseparable mixture of ketonitrone 351 and bicyclic hydroxylamine 352, along with aldonitrone 353 with a solvent-dependent ratio (401). These workers have prepared the analogous nitrones based on the 1,3-oxazine ring by oxidative cleavage of isoxazolidines to afford the hydroxylamine followed by a second oxidation with benzoquinone or Hg(ll) oxide (402-404). These dipoles, along with a more recently reported pyrazine nitrone (405), were aU used in successful cycloaddition reactions with alkenes. Elsewhere, the synthesis and cycloaddition reactions of related pyrazine-3-one nitrone 354 (406,407) or a benzoxazine-3-one dipolarophile 355 (408) have been reported. These workers have also reported the use of isoxazoles with an exocychc alkene in the preparation of spiro[isoxazolidine-5,4 -isoxazolines] (409). 

A solution of 6-chloro-3,4-dihydro-4-methyl-3-oxo-2H-l,4-benzoxazine-8-carboxylic acid in tetrahydrofuran and dimethylformamide is cooled to below 0°C and triethylamine is added under stirring thereto. Further, ethyl chlorocarbonate is added and the mixture is stirred at room temperature. To the resultant mixture is added 3-amino-8-azabicyclo[3.2.1]octane and the mixture stirred. After completion of the reaction, aqueous sodium hydrogen carbonate and ethyl acetate are added. The organic layer is separated, washed with water and dried over magnesium sulfate. The solvent is distilled off to give 6-chloro-3,4-dihydro-4-methyl-N-(8-azabicyclo[3.2.1]oct-3-yl)-3-oxo-2H-l,4-benzoxazine-8-carboxamide. 

A solution of 2-(2-amino-5-chlorophenyl)-4-cyclopropyl-l,l,l-trifluoro-3-butyn-2-ol (15.00 g, 0.0518 mol) and 41.98 g (0.259 mol) of 1,1 -carbonyldiimidazole in 250 mL of dry THF was stirred under argon at 55°C for 24 hours. The solvent was removed on a rotary evaporator and the residue was partitioned between 500 mL of ethyl acetate and 400 mL of water. The layers were separated and the aqueous phase was extracted once more with ethyl acetate. The combined ethyl acetate extracts were washed with 2 times 200 mL of 2% aqueous HCI, saturated aqueous NaHC03, and brine. Drying over MgS04, filtration, and removal of the solvent in vacuo provided 16.42 g of the title compound as a solid. Recrystallization from ethyl acetate/hexane afforded 12.97 g of analytically pure ()-6-chloro-4-cyclopropylethynyl-4-trifluoromethyl-l,4-dihydro-2H-3,l-benzoxazin-2-one as a white crystals. Melting point 178°-180°C. 

To 2.0 ml of Amberlite XAD 7 was added 2.0 ml of a 0.05 M phosphoric acid buffer (pH 7.0) having dissolved therein 20 mg of lipoprotein lipase, and the system was allowed to stand at room temperature for 18 hours to thereby adsorb the enzyme onto the resin. The resin was filtered. A solution of 250 mg of 3,5-dinitrobenzoyl derivative of ()-3-acetoxymethyl-7,8-difluoro-2,3-dihydro-4H-[l,4]benzoxazine as a substrate in 25 ml of a mixed solvent of benzene and n-hexane (4 1 by volume) was added to the resin, followed by... 

See Table X, Footnote (b). b Solvents DMSO-d (benzoxazines), benzene (benzothiazine), or CDC13. 

The reagent ratio 1 2 leads to a disubstituted product, which reacts with aminoethanol in an alkaline solvent to give 5,8-bis(vinylthio)-6,7-difluoro-2,3-dihydro-l,4-benzoxazine 164 along with other products (92ZOR1463) (Scheme 154). The formation of compound 165 is possibly explained by a Smiles type rearrangement. 

When 2-methyl-3,l-benzoxazin-4-one (103) is reacted with pyrrolidine in diethyl ether, the zwit-terion (104) is formed, together with some of the diamide (105) (Scheme 25). However, in boiling propanol, or when the reagents are heated without solvent, only the diamide is produced. This suggests that the zwitterion is formed first and then rearranges to the diamide on heating <85ZC103>. 

A concise preparation of pharmaceutically useful benzoxazin-2-ones in a few steps from salicylaldehydes and 2-hydroxyacetophenone, on montmorillonite KIO clay and alumina-supported copper sulfate, under solvent-free MW irradiation conditions, has been reported [189]. This high-yielding, expeditious, and eco-friendly... 

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