2- Bromomethylquinoxaline

Bromo-l-methyl-2,3(177,47/)-quinoxalinedione 6-Bromo-7-methyl-2,3(177,477)-quinoxalinedione 2-Bromomethylquinoxaline 1,4-dioxide... 

The stereoisomeric cyclic dipeptides (471) and (472) were formed upon A-deprotection of the dipeptide (470) (Equation (114)). The ratio of the isomers was influenced by the nature of the solvent through stabilization of a rotamer of (470) <90JHC1661>. Compound (356) was obtained similarly by deprotection of the appropriate dipeptide with HBr/AcOH <79BSB683> The [1,4]-thiazino[4,3-a]quinoxaline (474) was prepared in good yield from 2-bromomethylquinoxaline (473) and thio-glycollic acid (Equation (115)) <90Mi 825-0l>. 

Bromomethylquinoxaline with ethyl 4,4,4-trifluoroacetoacetate gave 6-(2-ethoxycarbonyl-2-trifluoroacetylethyl)quinoxahne (93) (NaH, MeOCH2CH2-OMe, 0°C then synthon slowly then substrate), reflux, 15 h 49%). ... 

Acetoxy-2,3 (1H, 4//)-quinoxalinedione 2-Acetoxyquinoxaline 1-oxide 2-Acetyl-3-bromomethylquinoxaline 1 -oxide 2-Acetyl-6,7-difluoro-3-methylquinoxaline 2-Acetyl-6,7-difluoro-3-methylquinoxaline... 

Quinoxalines substituted in the 5- or 6-position generally follow the pattern of reactions expected for substituted benzene derivatives, although recently there have been reports of interesting and unexpected reactions with nucleophiles (see Section III, A,2 and references 85-90). 6-Methylquinoxaline is brominated in the side chain when treated with N-bromosuccinimide in carbon tetrachloride in the presence of azobisiso-butyronitrile, to form 6-bromomethylquinoxaline.182... 

Nitration of 5-methoxyquinoxaline with potassium nitrate in concentrated sulfuric acid gives the 6,8-dinitro derivative, and the 6-methoxy compound is converted to 5-nitro-6-methoxyquinoxaline with these reagents. Nitration of 6-p-toluenesulfonamidoquinoxaline in acetic acid also gives a 5-nitro derivative. 6-Methylquinoxaline is brominated in the side chain when treated with N-bromosuccinimide in the presence of azobis-isobutyronitrile, and 6-bromomethylquinoxaline is obtained. " ... 

Dimethylsulfoxide oxidation of a-bromomethylquinoxalines yields quinoxalinecarboxaldehydes, and 2,3-bis(bromomethyl)quinoxaline (2) is oxidized by this reagent to the 2,3-dicarboxaldehyde 4. This preparation yields 60% of the cyclic monohydrate 3, which is converted into the dialdehyde by vacuum sublimation. The cyclic monohydrate is also formed by treatment of 2,3-bis(hydroxymethyl)quinoxaline 1,4-dioxide... 

Methylquinoxaline has been found to participate in the Mannich reaction, as shown in Scheme 5, and in strongly acid medium reacts with bromine to give a mixture of 37% bromomethylquinoxaline and 27% dibromomethylquinoxaline. It had been shown previously that bromina-tion in acetic acid in the presence of sodium acetate gives only the tribromomethyl compound. ... 

The bis bromomethyl compound 155 reacts with primary amines to give 2-substituted 1,3-dihydro compounds such as 156. Secondary amines provide cyclic quaternary salts. Piperazine and morpholine yield the spiro quaternary derivatives 157. The mono- and di-N-oxides of the bromomethylquinoxaline 155 react with liquid methylamine to give the l,3-dihydro-2-methyl compounds in which one of the N-oxide functions has been reduced. Thus the mono-N-oxide of 155 gives the iV-methyl derivative 158. This compound is also obtained... 

Methylquinoxaline derivative 266 reacted with bromine to yield bromomethylquinoxaline 267 and then reacted with NaCN to yield cyanomethylquinoxaline 268. The latter readily coupled with aromatic diazonium salts to yield hydrazone derivative 269 that then reacted with active methylene reagents to yield the corresponding quinoxaUnylpyrida-zine 270. Quinoxaline 266 also reacted with DMFDMA to yield the enamine 271 that then coupled with a diazonium salt to yield aldehydehydrazone 272. Subsequently, 272 with active methylene compounds yielded the corresponding pyridazines 273 (2006M1901 Scheme 48). 

---