Benzoxazin-2-ones, formation

Benzoxazinones pyrolysis, 3, 998 Benzoxazinones, dihydro-benzazetidine formation from, 7, 277 Benzoxazin-4-ones, dihydrosynthesis, 3, 1028... 

Reaetion of l,3-benzoxazin-4-ones (43, 44) or trithioisatoie anhydride (45) with amidrazones (46, 47) or thiosemiearbazide (48) resulted in the formation of 3-(l-amidino)- (49-51) and 3-(l-thioureido)pyrimidines (52) respeetively. Compounds 49-52 underwent thermal intramoleeular ey-elization to the eorresponding l,2,4-triazolo[l,5-c]quinazolines (53-56) [68CB2106 76MI1 80PHA582 83MI1 85H(23)2357] (Seheme 18). 

Lim et al. also investigated HMTA-phenolic reactions with somewhat larger model compounds (e.g., two- and four-ring compounds) and established that similar reaction pathways to those described previously occurred.50 For these model compounds (as opposed to one-ring model compounds), which are more representative of typical oligomeric systems, increased molecular weight favored die formation of hydroxybenzylamines but not benzoxazines. This was suggested to be a steric effect. 

Reversing the CH=N group position in 477-5,6-benzoxazin-4-one should result in the same isomerization enthalpy as from HC(NMe)OMe to MeCHNOMe. The enthalpy of formation of the latter species was calculated to be —7.1 kJmoR from the high-level quantum chemical calculations of Reference 4. The enthalpy of formation of the former species is unknown. However, if we accept the gas phase isomerization enthalpy of dimethylamides to methyl imidates (69.6 13.4 kJmoR ) in equation 52 from Reference 75,... 

Treatment of the (—)-menthone-derived 2/7-1,3-benzoxazin-4(3//)-one 202 with triflic anhydride gave the triflate 203 in quantitative yield. Palladium-catalyzed cross-coupling of 203 with 2-pyridylzinc halide resulted in formation of an approximately 3 1 mixture of the 4-(2-pyridyl)-2//-l,3-benzoxazine 204 and a 4-imino-l,3-benzodioxane derivative 205 (Scheme 36). Compound 205 was formed by the isomerization of 203, which occurred with complete retention of stereochemistry. The 4-(2-pyridyl)-l,3-benzoxazine derivative 204 was applied in enantioselective allylic alkylations of 1,3-diphenyl-2-propenyl acetate with dimethyl malonate as a chiral ligand inducing a 62% ee in the product <2005JOM(690)2027>. 

In the thermal cyclization of 3-alkoxyphenyl A -(l-aryl-2,2,2-trifluoroethylidene)carbamates 287, obtained from 3-alkoxyphenols 285 and l-aryl-l-chloro-2,2,2-trifluoroethyl isocyanates 286, 2-aryl-2-trifluoromethyl-2,3-dihydro-477-l,3-benzoxazin-4-ones 290 were formed instead of the regioisomeric l,3-benzoxazin-2-ones 288 (Scheme 53). The formation of 290 was explained by a thermal isomerization of 287 involving a skeletal 1,3-rearrangement of the electron-rich aryloxy group to the azomethine carbon, which is electron deficient due to the electron-withdrawing CF3 group <2002JFC(116)97>. 

Eormation and subsequent cyclization of a hydroxyalkyl carbamate bearing an activating O-substituent can also be achieved in a one-pot procedure. When 2-(hydroxymethyl)aniline 394 was treated with -nitrophenyl chloroformate, the formation of the /)-nitrophenylcarbamate intermediate 395 was followed by in situ ring closure to give the 3,1-benzoxazin-2-one derivative efavirenz 250 in high yield and with high purity, free from the intermediate 395 (Scheme 74) <1998JOC8536>. 

In the condensations of o-aminohenzyl alcohol 376 or anthranilic acid 401 with 4,5-dichloro-l,2,3-dithiazolium chloride (Appel s salt) 402, imino-l,2,3-dithiazoles 403 were formed. Heating of the imino alcohol 403 (X = H2) in THE in the presence of NaH afforded an 11 1 mixture of 3,1-benzoxazine 404 and 3,1-benzothiazine 405 in moderate yield. Thermal cyclization of imino acid 403 (X = 0) resulted nearly quantitatively in formation of 3,1-henzoxazin-4-one 406 (Scheme 76) <1995CC1419, 1995J(P 1)2097, 1997SL704>. 

The thermally induced cyclization of A -(benzyloxycarbonyl)phenyl ketenimines 415, obtained in a two-step, one-pot procedure from benzyl 2-azidobenzoates 414, led to 2-substituted-4/f-3,l-benzoxazin-4-ones 416 (Scheme 79). The reaction involves the formation of a new carbon-oxygen bond and migration of the benzyl group from the oxygen atom to the terminal carbon atom of the ketenimine fragment <2005S2426>. 

The products obtained in the reaction of A -cyclopropyl-4,5-difluoroanthranilic acid hydrazides 429 with triphosgene were dependent on the steric hindrance imposed by substituent R at position 3, and not the electronic effect of this group. While the unsubstituted compound 429 (R = H) gave exclusively the 4-hydrazono-3,l-benzoxazin-2-one-type product 430, the similar reactions of the chloro-, methyl-, and methoxy-substituted analogs 429 (R = Cl, Me, OMe) resulted in formation of the corresponding quinazoline-2,4-diones 431 as the sole products. For the fluoro-substituted compound 429 (R = F), a 20 80 mixture of the products 430 and 431 was obtained (Equation 46) <2005JHC669>. 

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>. 

Benzoxazin-4-ones (39) react with amines to give quinazolinones (40) (77JOC656), but this typical reaction is replaced in 1,3-benzoxazine-2-thiones (41) by the formation of imino derivatives (42) since now the oxygen ring atom is joined directly to the aryl nucleus (76MI22700). 

APCI has become a popular ionization source for applications of coupled HPLC-MS. Figure 1.33 shows an example of an application of HPLC-APCI coupling [79]. It shows the analysis obtained from extracts of maize plants. Six compounds are identified by mass spectrometry. These compounds have been identified as glucoconjugated DIMBOA (2,4-dihydroxy-7-methoxy-l,4-benzoxazin-3-one) and similar molecules that differ by the number of methoxy groups in the benzene ring and/or by the N-O methylation of the hydroxamate function. This example clearly shows the influence of the analyte on the type of observed molecular species. Indeed, the presence of an acidic group in the compound from peak 1 allows mainly the detection of deprotonated molecular ions, whereas the compound from peak 4 does not contain an acid group and thus leads only to the formation of adduct ions. 

Fatty acid w-hydroxylation is involved in the.metabolism of prostaglandins and leukotrienes, and is the first step of dicarboxylic acid formation in the cell. In this assay, lauric acid is hydroxylated to form 12-hydroxylauric acid, which is then fluorescence-labeled on the carboxyl group with 3-bromomethyl-7-methoxy-l,4-benzoxazin-2-one. 

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