2- Substituted benzoxazin-4-ones, formation

An efficient method for the synthesis of 2-substituted benzoxazin-4-ones was performed by the condensation of anthranilic acid (436) with various orthoesters by classical heating for 1 2h to give 75 91% yields. But under MWI in an open vessel, a rapid formation of benzoxazin-4-ones 439 in high yields (76-94%) took place within 1-5 min (Scheme 86). The reaction may proceed through the imidic ester intermediate 437, which upon nucleophilic attack by the carboxyl oxygen produced the cycKzed intermediate 438 that then eliminated a molecule of alcohol to give 439 (97JCR(S)286). 

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>. 

When acid chlorides were used instead of cumulenes in the reaction with o-iodoanilines 3 and carbon monoxide (20atm), 2-substituted-4H-3,l-benzoxazin-4-ones 8 were obtained in good to excellent yields, also in the absence of a phosphine ligand [23]. The reaction is believed to proceed via in situ amide formation from o-iodoaniline and acid chloride, followed by oxidative addition to Pd(0), CO insertion, and intramolecular cyclization (Scheme 13.3). 

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