3- Chloro-5-hydroxy-2-phenylpyrazine

Chloro-3-methylpyrazine (101,535) and 2-chloro-5-phenylpyrazine (363, 365a, 377, 824, 825) have been prepared from the corresponding hydroxy compound and phosphoryl chloride, 2-chloro-6-methylpyrazine from 2-hydroxy-6-methylpyrazine and phosphoryl chloride with one drop of dimethylformamide (681), and 2-benzyl(or s-butyl, isobutyl, or isopropyl)-3phosphoryl chloride with a trace of concentrated sulfuric acid (80). 2-Chloro-6-methyl-3-propyl- (826), 3[Pg.99]

Many chloropyrazines have been prepared from hydroxypyrazines by reaction with mixed phosphorus pentachloride-phosphoryl chloride as follows 2-hydroxy-pyrazine to 2-chloropyrazine (818), 2-hydroxy-3-phenylpyrazine to 2-chloro-3-phenylpyrazine (535), 2-hydroxy-6-methyl- and 5-hydroxy-23-[Pg.102]

Dichloropyrazines have also been prepared from the corresponding hydroxy compounds as follows 2,3-dihydroxypyrazine with phosphoryl chloride containing pyridine (481, 757) [see Schneller and May (828) re the use of phenylphosphonic dichloride at 150-170°] 2,3-dihydroxypyrazine and its methyl, dimethyl, phenyl, diphenyl, and 5-methy 1-6-phenyl derivatives with phosphoryl chloride (483, 829) [N.B. error in work of Minovici and Bente (830)] 2-chloro-5-hydroxypyrazine with phosphoryl chloride (831) 2-chloro-6-hydroxypyrazine with phosphoryl chloride at reflux for 6hours (832) and 2,5-dihydroxy-3-phenylpyrazine and3,5-dihydroxy-2-phenylpyrazine with phosphoryl chloride at 180-200° (829). 

Hydroxy-3-methoxy-5-phenylpyrazine refluxed with phosphoryl chloride formed 2-chloro-3-methoxy-5-phenylpyrazine (365a). 

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-... 

Amino-5-bromo-3-carbamoylpyrazine heated with trifluoroacetamide and sodium ethoxide (or butoxide) gave 6-ethoxy(or butoxy)-4-hydroxy-2-trifluoro-methylpteridine (49) (987) and 2-chloro-3-pyridiniopyrazine chloride with methoxide ion gave 2,3-dimethoxypyrazine (765). 2-Amino-3-bromo-5-phenyl-pyrazine with sodium methoxide in methanol at 134° for 8 hours formed 2-amino-3-methoxy-5-phenylpyrazine (365a) and 3-bromo-2-hydroxy-5-phenylpyrazine similarly treated gave 2-hydroxy-3-methoxy-5-phenylpyrazine (365a). 

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-... 

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). 

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