Isoxazole 5- methyl-4-nitro-3-

Nitrones or aci-nitro esters react with alkenes to give in some cases A/-substituted isoxazolidines and in others 2-isoxazolines. When the intermediate isoxazolidines were observed, a number of procedures transformed them into the 2-isoxazolines. Acrylonitrile and phenyl rzcf-nitrone esters produced an A/-methoxyisoxazolidine. Treatment with acid generated a 2-isoxazole while treatment with base generated an oxazine (Scheme 118) (68ZOR236). When an ethoxycarbonyl nitrone ester was reacted with alkenes, no intermediate isoxazolidine was observed, only A -isoxazolines. Other aci-mtro methyl esters used are shown in Scheme 118 and these generate IV-methoxyisoxazolidines or A -isoxazolines which can be further transformed (72MI41605). 

Abbreviations N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA), L(+)-2 amino-3-phosphonopropionic acid (L-AP3), 6-cyano-7-nitroqninoxaline (CNQ5Q, 2,3-dihydroxy-6-nitro-7-sulfamyl-benzo-f-quinoxaline (NBQX), 3-(2-carboxypiperazin-4-yl)-propyl-l-phosphonic acid (CPP), 7 Chlorokynnreic... 

This method gives a somewhat tower yield than method 1. Dissolve 14.1 g l-nitro-3-butanone in 30 ml glacial acetic acid and heat to 35° add slowly with stirring to a solution of 5.3 g bromine in 10 ml glacial acetic acid. Evaporate in vacuum, dissolve residue in ether and wash with water, NaHC03 and water. Dry and evaporate in vacuum the ether (can distill 84/2) to get 6 g 1 -nitro-4-Br-3-butanone (1). Add 4.4 g (I) to 25 ml 48% HBr and reflux three hours. Add 50 ml water and steam distill. Neutralize the distillate with K carbonate and extract with ether. Dry and evaporate the extract (can distill 128/20) to get 5.6 g 2-Br-5-Br-methyl-isoxazole... 

The electron impact mass spectra of 3-methyl-4-nitro-5-styryl-isoxazoles exhibit, on the contrary, only negligible loss of OH"80. This has been interpreted in terms of an isoxazole-to-azirine rearrangement80. The latter fragments directly to an abundant cinnamoyl ion as well as rearranges to oxazole and an epoxide through an intramolecular oxidation of the ethylenic bond by the nitro group80 see Scheme 10. 

The idea of employing the reaction of a nitroarene or nitroheterocycle with a mtinchnone to synthesize a fused pyrrole ring system has been developed by two groups. Nesi et al. (109) found that mtinchnone 38 reacts with 3-methyl-4-nitroisoxazole (196) and 4-nitro-3-phenylisoxazole (197) to give the corresponding 5//-pyrrolo[3,4-tf]isoxazoles 198 and 199, respectively, in good yield. Presumably loss of carbon dioxide in a retro-Diels-Alder reaction follows loss of nitrous acid. 

Eulite (Eulyt, in Ger) or 5-Methyt-4-nitro-3 (l,1.dinitroethyl) i oxazole, Beil name 4-Nitro-5-methyl-3 [a,0-diniuoathyli-isoxazoI. Called by Quilico et al y-Metbyl-a-isoxazole-1 -d ini tTO 2-dinitToe thane,... 

Later work has shown that 3-methyl-5-phenylisoxazole is nitrated as the conjugate acid in mixed acid to give the 4-nitrophenyl product exclusively, whereas in nitric acid acetic anhydride, poor yields of 4-nitro-5-(4-nitro-phenyl)isoxazole are obtained as the only product. 

The introduction of electron-donating substituents into the isoxazole ring facilitates the nitration process. Thus, the nitration of 3,5-dialkylisoxazoles [168-171] or bis(3-methylisoxazolyl-5) [172] gave the corresponding 4-nitro derivatives Under the same conditions, however, 3-methyl-5-(2-methoxy-2-phenylethyl)isoxazole was only nitrated in the phenyl ring [173], Conversely, even at room temperature the nitration of 3-methyl-5-dichloromethyl- and 3-dichloromethyl-5-methylisox-azole gives the corresponding 4-nitro derivatives [174], The nitration of 3-bromo-5-methylisoxazole is similar [175]. 

The product from the reaction of citraconic acid (or its anhydride) with nitric acid was initially assigned the structure of 3-methyl-5-(l,l,2-trinitroethyl)isoxazole [588], However, it was subsequently established that this compound was 5-methyl-4-nitro-3-(l,l-dinitroethyl)isoxazole [589], As mentioned earlier, the antibiotic azomycin (2-nitroimidazole) and some of its derivatives can be obtained by microbiological synthesis [331, 450, 590, 591],... 

Dipolar addition to unsaturated compounds affords routes to unique and interesting structures. The 1,3-dipolar cycloaddition of the 0-methyl ether of dinitromethane to methyl acylate produced N-methoxy-3-nitro-5-carbomethoxy-isoxazolidine in 65% yield. Similar results were obtained with other olefins. Acetonitrile N-oxide adds to enynes to form isoxazolines and isoxazoles. ... 

Isoxazoles are weakly basic. Isoxazole has a pATa of -2.97 at 25 °C, and the values for its 3-methyl, 5-methyl and 3,5-dimethyl derivatives are -1.62, -2.01 and -1.61, respectively a 4-nitro group reduces the pATa of 3,5-dimethylisoxazole to -6.43. For 4-substituted 3,5-diphenylisoxazoles the pATa values showed a good correlation with the Hammett am constants for the substituents (79AHC(25)147) (see also Section 4.16.2.4.4, Tables 3 and 4). 

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