Dihydro-1,4-benzoxazines, synthesis

Perhydro derivatives of pyrido[l,2-6][l,2]oxazines are frequently applied in the total synthesis of various alkaloids to control the stereochemistry, and 4-(substituted amino)-5-fluoro-7-oxo derivatives of 3,7-dihydro-2//-pyrido[3,2,l-f7][2,l]benzoxazine- and l,2,3,7-tetrahydropyrido[3,2,l-//]cin-noline-8-carboxylic acids are considered as a subfamily of the third generation of antibacterial quinolones. 

Two types of dihydro-l,3-oxazinones are relevant to the discussed topic the e -fused hexahydro-2//-l,3-benzoxazin-4-ones and their homologs, and the d -fused hexahydro-2//-3,l-benzoxazin-4-ones and their homologs. For the synthesis of these derivatives, just two methods are known. 

Kondo, K. Seki, M. Kuroda, T. Yamanaka, T. Iwasaki, T. 2-Substituted 2,3-dihydro-4H-l,3-benzoxazin-4-ones novel auxiliaries for the stereoselective synthesis of l-/ -methylcarbape-nems. J. Org. Chem. 1997, 62, 2877—2884. 

Hayakawa I, Hiramitsu T, Tanaka Y. Synthesis and antibacterial activities of substituted 7-oxo-2,3-dihydro-7H-pyrido[l,2,3-de][l,4]benzoxazine-6-carboxylic acids. Chem. Pharm. Bull. (Tokyo), 1984, 32, 4907 1913. 

Pyrano[3,2-g]benzoxazine, dihydrosynthesis, 3, 714 Pyranobenzoxazines synthesis, 6, 190 Pyranobenzoxazoles mass spectra, 3, 615 Pyrano[2,3-a]carbazoles synthesis, 4, 235 Pyrano[2,3-h]carbazoles synthesis, 4, 235 Pyrano[3,2-a]carbazoles syntheds, 4, 235 Pyranochromones synthesis, 3, 821 Pyranochromones, dihydrosynthesis, 3, 816-817 Pyranocoumaritrs crystal data, 3, 623 mass spectra, 3, 610 Pyranodipyranones synthesis, 3, 794 Pyrano[3,2-6]indol-4-ones synthesis, 4, 302 Pyran-2-ol, dihydro-dehydratiorr, 3, 762 Pyran-2-ol, 3-methyltetrahydro-synthesis, 3, 775 Pyran-2-ol, tetrahydro-6-subs1ituted syrithesis, 3, 775 Pyran-4-ol, tetrahydro-IR spectra, 3, 594 Raman spectra, 3, 594 Pyranols, tetrahydro-bond lengths, 3, 621 synthesis, 3, 777... 

Coppola, G.M., The chemistry of 2//-3,l-benzoxazine-2,4(l//)-dione (isatoic anhydride). Part 20. Synthesis and Wittig reactions of dimethyl (4-oxo-l,4-dihydro-qurnolrn-2-yl)methanephosphonates, Synthesis. 81, 1988. 

The transition metal-catalyzed reductive carbonylation of o-substituted nitrobenzenes is a useful method for the synthesis of nitrogen heterocycles. Application of this methodology to the preparation of l,4-dihydro-2/f-3,l-benzoxazin-2-one derivatives and to the synthesis of the 3,1-benzox-azepin-2-one (42) has been reported <93JOM(451)157>. Reaction of 2-(2-nitrophenyl)ethanol (41) (100% conversion) with carbon monoxide in the presence of a palladium(Il) catalyst gave (42) in 60% yield, together with some of the macrocyclic dimer (43) ( nation (2)). It is suggested that a nitrene complex may not be involved with the palladium catalyst in view of the reaction path selectivity observed <93JOM(45i)l57>. 

Easy and efficient access routes to heterocyclic complexes are of significant interest in organic chemistry and its application in synthesis both in the laboratory and industry. During the recent years several novel routes toward such compounds in aqueous media have been described. 2-Substituted 3,4-dihydro-2H-l,4-benzoxazines have been prepared in excellent yields and short reaction times through the cyclization of hydroxysulfonamides in water under phase-transfer catalysis conditions (Scheme 3) [25]. 

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. 

A detailed study of the synthesis and conformation of stereoisomeric cis- and trans-tetramethylene- and -pentamethylene-dihydro-l,3-oxazines has been undertaken, e.g. (50). 3-Phenyl-4-hydroxy-2i/-l,4-benzoxazines, which may have some interest as antifungal agents, can be prepared as outlined in Scheme 109 4 jjjg hydroxylamines are rather unstable in air. 

A mixture of salicylaldehyde, NH4-acetate, acetic acid, and benzene refluxed 3 hrs. with azeotropic water entrainment -> tricyclo-3,4-dihydro-l,3-benzoxazine. Y 36%. F. e. s. K. Kanakarajan, V. T. Ramakrishnan, and P. Shanmugam, Synthesis 1975, 501. 

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