2.3- Dichloro-5-phenylpyrazine

Mcthyl-5-phenyl-2(l//)-pyrazinone (4) gave 2-chloro-3-methyl-5-phenylpyra-zine (5) (P0C13,175°C, sealed, 18 h 92% beware of pressure within the tube even when cooled ) 57 such a sealed reaction also converted 5-chloro-3-phcnyl-2( l//)-pyrazinone into 2,5-dichloro-3-phenylpyrazine (6) (185°C, 5 h 92%).1382... 

Refluxing phosphoms tribromide converted 2-bromo-3-hydroxy-5,6-diphenyl-pyrazine and 2-bromo-5-hydroxy-3,6-diphenylpyrazine to the dibromopyrazines 2,3-dichloro-5,6-dimethylpyrazine and 2,5-dichloro-3-phenylpyrazine to the dibromopyrazines (817) 5-chloro-2,3-diphenylpyrazine (and its 6-ethyl derivative) to 5-bromo-2,3-diphenylpyrazine (and its 6-ethyl derivative) (866) and 2-hydroxy-... 

The following alkoxypyrazines have been prepared from the corresponding dichloropyrazines and alkoxide ions 2,3-dimethoxy-5,6-dimethyl(and diphenyl) (797) 2,3-dibenzyloxy (sodium benzyl oxide in benzyl alcohol at reflux for 24 hours (883)] [but 23-dichloropyrazine with sodium hydride and benzyl alcohol in xylene gave l,4-dibenzyl-2,3-dioxo-l,2,3,4-tetrahydropyrazine)(988)] 2-chloro-5-methoxy (838) 2,5-diethoxy-3,6-dimethyl (872) 2methanolic sodium methoxide refluxed for 2 h) 2,5-dimethoxy-3-phenyl (817) 2-chloro-5-methoxy(and ethoxy)-3,6-diphenyl (817) 2,5-dimethoxy-3,6-dimethyl (and diisopropyl) (844) 2,5-dimethoxy-3-isopropyl-6-methyl (methanolic potassium methoxide at reflux for 6 days) (844) 2(5)-s-butyl-3-chloro-6-ethoxy-5(2)-isobutyl (93) 2-chloro-6-methoxy (838, 883) 2,6-dimethoxy (reflux for 8h) (832) 2,6-diethoxy (reflux for 14 h) (883) 2-benzyloxy-6-chloro (1 equiv. of sodium hydride and benzyl alcohol in benzene at reflux) (832) 2,6-dibenzyloxy (5 equiv. of sodium benzyloxide in benzene at reflux gave 70%) (832) and 3,5-dimethoxy-2-methyl (535). 

Hydroxy-5-nitro-3-phenylpyrazine with phosphoryl chloride at reflux gave 2-chloro-5-nitro-3-phenylpyrazine but at 170° gave 2,5-dichloro-3-phenylpyrazine (817). Phenylhydroxynitropyrazines are claimed not to react with dimethyl sulfate in alkaline solution or with sodium ethoxide and ethyl iodide in hot ethanol (817). 

Chloro-3-methyl-5-phenylpyrazine 1-oxide (44) gave 2,6-dichloro-3-methyl-5-phenylpyrazine (45) (POCl3, 80°C, 30 min 93%) analogues likewise.57... 

Preparations of halogenopyrazines utilizing primary syntheses from a-(p-toluenesulfonyloxyimino)malononitrile have been discussed in Section II.7. a-Aminophenylacetonitrile with chloral (or bromal) were claimed to give 2,3-dichloro(or dibromo)-5-phenylpyrazine (830, 893), but this has now been shown to be in error (829). 

Methoxypyrazines (31) have been prepared by diazomethane methylation of 2-hydroxy-3-isobutylpyrazine (60, 311, 367), 2-hydroxy-3-isopropylpyrazine (59, 367), 2-hydroxy-3-propyl(ethyl or hexyl)pyrazine (367), 3-hydroxy-2-isobutyl-5(and 6)methylpyrazine and 2-hydroxy-3-isobutyl-5,6-dimethylpyrazine (368), 2,3-dihydroxypyrazine (832), 2-hydroxy-5-methoxy- and 2,5-dihydroxy-3,6-diphenyl-pyrazine (832), 2-hydroxy-6-methoxy(and benzyloxy)pyrazine (832), 2,6-dihydroxy-3,5-diphenylpyrazine (873), 2,3,5-trifluoro-6-hydroxypyrazine (851), 2-chloro-6-hydroxy-3,5-diphenylpyrazine (873), 2-chloro-6-hydroxy-5-methyl-3-phenylpyrazine (873), 2-chloro-6-hydroxy-3-methyl-5-phenylpyrazine (873), 5,6-dichloro-1 -cyclohexyl-34iydroxy-2-oxo-l, 2-dihydropyrazine (853), 2-chloro-5-hydroxy-3-methoxy-6-methoxycarbonylpyrazine (881), 2-(4 -amino-3, 5 -dibromo-phenylsulfonamido)-3Tiydroxy-6-methoxypyrazine (881), 2-amino-3-hydroxy-... 

---