LH-2,3-Benzoxazines

A soln. of 6-chloro-4-(2-cyclohexylidene-l-methylhydrazino)-lH-2,3-benzoxazine in chloroform satd. with HCl allowed to stand 20 min. at room temp, with occasional stirring N-(6-diloro-l-phthalanylidene)-l-methylazocyclohexylamine. Y 57%. F. e. s. G. Pifferi et al., J. Heterocyclic Chem. 9, 827 (1972). 

A mixture of lH-3,4-dihydro-2,3-benzoxazine, 1.5-2 moles n-butyl bromide, and 1.5 moles finely powdered Na-carbonate stirred and heated gently so as to maintain COg-evolution until a maximum temp, of 145° is reached and gas evolution ceases N-w-butyl derivative. Y 78%. - Alkylation attempts in organic solvents in the presence of a tert. base as well as in liq. NHg with Na-amide were not successful. F. e. s. G. Pifferi, N. Di Mola, and E. Testa, Farmaco, Ed. Sci. 23, 568 (1968). 

N-(3-chloro-5-methoxycarbonylphenyl)-5-bromo-l,2,3,4-tetrahydro-quinoline-8-carboxamide was obtained from 8-bromo-6,7-dihydro-lH,3H,5H-pyrido[3,2,l-z/][3,l]benzoxazine-l,3-dione with methyl 3-amino-5-chlorobenzoate in NMP at 170 °C for 16 h (07WOP2007/028789). 

That of 7-bromo- and 7-fluoro-8-hydroxyquinolin-2(lH)-ones with epi-chlorohydrin in the presence of catalytic amount of piperidine in DMF at 85 °C gave 10-substituted 3-hydroxymethyl-2,3-dihydro-5H-pyrido [l,2,3-de][l,4]benzoxazin-5-ones (08WOP2008/120003). 

H-3,l-BENZOXAZINE-2,4(lH)-DIONE see IHN200 2H-1,3-BENZOXAZINE-2,4(3H)-DIONE, 6-CHLORO-2-THIO- see CLH800... 

In 1899, Erdmann obtained the same compound in good yield from anthranilic acid and phosgene and suggested the name isatoic anhydride. An alternative synthesis of isatoic anhydride [2//-3,l-benzoxazine-2,4(lH)-dione, subsequently abbreviated as lA] was found by Curtius and Semper from phthalic acid monoazide (5) via o-carboxyphenyl isocyanate. Similar rearrangements were discovered by Bredt and Hor [from potassium phthal-imide (6)] and by Mohr [from phthalimide (7)] leading to IA via a Hoffmann reaction. 

A solid-supported carbonate reagent was used to initiate the formation of 2H-l,4-benzoxazin-2-ones 303 from P-nitroacrylate 301 and 2-aminophenol 302 (Scheme 7.72) [154]. This hetero-Michael addition/intramolecular transesteri-fication/elimination of HN03/[l,3]-proton shift domino reaction proceeded in moderate to excellent yields. In another study, a series of various functionalized pyrrolo[l,2-r]pyrazines 305 were made synthetically available through the reaction of vinyl azides 304 and lH-2-pyrrolecarbaldehyde (Scheme 7.73). The deprotonated pyrrole initially reacts in a Michael manner with the vinyl azides, with nitrogen as... 

Cydization of N-substituted anthranilic acids using triphosgene, diphosgene, or chloroformates has been claimed in patent literature [915]. For example 2-N-cydo-propylamino-4,5-difluorobenzoic acid 1238 was converted into N-cydopropyl-6,7-difluoro-2H-l,3-benzoxazine-2,4(lH)-dione 1239 in quantitative yield. 

CeH5BrN202, N (p-Bromophenyl)sydnone, 28, 494 C8H5NO3, 2H-1,3-Benzoxazine-2,4(3H)-dione, 44B, 335 C8H5NO3, 2H-3,l-Benzoxazine-2,4(lH)-dione, 44B, 335 C8H6N2O3, 3-(p-Hydroxyphenyl)-l,2,5-oxadiazole 2-oxide, 46B, 374 C8H7BrN202, 5-Bromo-4,6-dimethylisoxazolo[3,4-b]pyridin-3(lH)-one, 45B, 397... 

C14H1eClNO, rac-cis-5-Chloro-2,3,3a,9-tetrahydro-6,8,9-trimethyl-lH-pyrrolo[2,l-b]benzoxazine, 45B, 406 Cl4H18CINO3S, 3 Chloromethylsulphonyl-p-methyl-a-morpholinostyrene (synclinal-5 and 5 ), 41B, 425... 

Tandem mass spectrometry has been used to demonstrate that M+ as well as MH+ of substituted A-(ort/zo-cyclopropylphenyl)benzamides isomerizes before the fragmentation, with formation of 3-aryl-1-ethyl-lH-benzoxazines and 5-ethyl-2-oxodi-benzoazepines (Scheme 5.14). The methyl group in /V-[ortho-( 1 -methylcvclopropyl )-phenyl]benzamides quenches the latter process, leaving the formation of benzoxazines as the only cyclization reaction. A subsequent chemical experiment in solution confirmed the mass spectral predictions [24]. A similar study confirmed the analogy of cyclization of substituted A-(ort/zo-cyclopropylphenyl)-A -aryl ureas and N- ortho-cyclopropylphenyl)-A -aiyl thioureas in the ion source of mass a spectrometer and in solution [25]. 

Mesoionic pyrido[2,l- >][1,3]oxazines (54) afforded 4-oxo-4//-pyrido[l,2-a]pyrimidin-l-iumolates (55) and 4//-quinolizin-4-one (56) with phenyl iso(thio)cyanates [78LA1655 79CB1585 82ZN(B)222] and dimethyl acetylenedicarboxylate (79CB1585), respectively. Reaction of 2-cyano-3-methyl-lH,6//-pyridol[l,2-a][3,l]benzoxazine-l,6-dione with ammonium acetate and hydroxylamine, hydrazines, primary aliphatic or aromatic amines, and (thio)ureas gave 5-unsubstituted and 5-substituted 2-cyano-3-methyl-l//,6H-pyrido[l,2-a]quinazoline-l,6-diones (93CCC1953). 

Catalytic hydrogenation of 9-(3-substituted prop-l-enyl, -2-enyl)-7-oxo-1 H,3/T,7H-pyrido[3,2, l -//[ [3,l]benzoxazine-6-carboxylic acids (07WOP2007/ 054296) and 9-(3-substituted prop-1 -ynyl)-7-oxo-lH,3H,7H-pyrido[3,2, -ij] [3,l]benzoxazine-6-carboxylates (06WOP2006/050940, 06WOP2006/... 

An acetoxy moiety, present in a side chain in the position 9 on 7-oxo-lH,3H,7H-pyrido[3,2,l-zy][3,l]benzoxazine skeleton, was hydrolyzed under basic condition to yield a hydroxy derivative (07WOP2007/ 054296). Phtalimido, and benzyloxycarbonylamino (07JP2007131577) and ferf-butoxycarbonylamino groups (06WOP2006/050940, 06WOP2006/ 050943), present in a side chain on pyrido[3,2,l-zy][3,l]benzoxazin-7-one and pyrido[3,2,l-zy]quinazolin-4-one skeletons, were converted to an... 

Reaction of 8-hydroxymethyl-4-oxo-l,4-dihydroquinoline-3-carboxy-lates 132 with C1CH2I, 1,1-diethoxyethane (06WOP2006/050940, 06WOP206/050943) and 2,2-dimethoxypropane (06WOP2006/050940, 06WOP206 /050943, 07WOP2007/054296) yielded 7-oxo-lH,3H,7H-pyr-ido[3,2,l-zy][3,l]benzoxazine-6-carboxylates 133. 

The carboxylic acid 95, obtained from the methyl ester by alkaline hydrolysis, was converted by an Arndt-Eistert sequence to the higher homolog 96 (84JA3240). The ethyl esters of 7-oxo-lH,3//,7//-pyrido[3,2,l-y][3,l]benzoxazine-6-carboxylates were hydrolyzed under basic conditions (90EUP373531). The carboxylic acid derivative was obtained by alkaline hydrolysis of methyl trans-4a,8-H-l-oxo-l,3,4,4a,7,8-hexahydropyrido[l,2-... 

Aus 2,4-Dioxo-l,2-dihydro-4H-3,l-benzoxazin wird beim Verschmelzen mit 3(5)-Hydroxy-5(3)-methyl-lH-pyrazol das Benzo-analoge des Pyrazolo[l,5-a]pyrimidins gebildet2180. 

Lithium borohydride reduces the carbonyl group at position 4 in anhydride 1, and 4H-3,l-benzoxazin-2(lH)-one is formed with a yield of 73% [132],... 

Bao and coworkers [28] have reported efficient synthesis of 2H-l,4-benzoxazin-3-(4H)-ones and quinoxalin-2-(lH)-ones via domino SjjAr/copper-catalyzed coupling of ohalophenols or N-(2-halophenyl)methylsulfonamides with 2-haloamides. Dai and coworkers [29] have also developed a general base mediated synthesis of 2-alkyl-3,4-dihydro-3-oxo-2H-l,4-benzoxazine by domino Sjj condensation of 2-aminophenols with 2-bromoalkanoates under controlled microwave heating. 

Sodium hydroxide/carbon dioxide N-Subst. 2H-3,l-benzoxazine-2,4(lH)-diones... 

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