Isoxazole 3-bromo-5-methyl

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]. 

Intramolecular nucleophilic substitution of electrogenerated phenoxonium ions has been investigated . In connection with naturally occurring bromo compounds, methyl 3,5-dibromo-4-hydroxyphenyl pyruvate oxime (98) was subjected to anodic oxidation (-1-1.3 V Vi. SCE 2.1 Fmol ) in MeOH to afford spiro-isoxazole 99 in almost quantitative yield . Methyl 3-bromo-4-hydroxyphenyl pyruvate oxime (100) was also electrolyzed under similar conditions to give three compounds 101, 102 and 103 in 34, 14 and 17% yields, respectively. The latter two products are formed by C—O and C—C radical couplings, respectively, as shown in Scheme 19 °. 

The replacement of an halogen atom by amines in 3-chloro(bromo)isoxazoles 155 does not occur on heating however it can be induced by microwave irradiation (04TL3189). The halogen atom may be easily replaced in 2-methyl-3-chloroiso-xazolium salts 156 (84CPB530) (Scheme 69). 

---