3-Chloro-5-hydroxy-2-methylpyrazine

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]

Cyanopyrazine 1-oxide and 3-cyanopyrazine 1-oxide each with alkaline 3% hydrogen peroxide at 55° gave 2-carbamoylpyrazine 1-oxide and 3-carbamoyl-pyrazine 1-oxide, respectively (838). 3-Amino-2-cyanopyrazine 1-oxide refluxed with trifluoroacetic anhydride in triHuoroacetic acid for 5 hours gave 3-amino-2-carbamoylpyrazine 1-oxide (538), and 2-amino-3-cyano-5-methylpyrazine 1-oxide with sulfuric acid (d. 1.8) at 100° gave 2-amino-3-carbamoyl-5-methylpyrazine 1-oxide (1255). 2-Amino-6-chloro-3-cyano-5-methylpyrazine 1-oxide with 0.5N sodium hydroxide at room temperature for 48 hours formed a mixture of 2-amino-3-cyano-6-hydroxy-5-methylpyrazine 1-oxide (56%) and 2-amino-3-carbamoyl-6-chloro-5-methylpyrazine 1-oxide (22%)(533). 3-7V-Acetylcarbamoylpyrazine 1-oxide was hydrolyzed by hot 10% sodium hydroxide to 3-carboxypyrazine 1-oxide (1057). 

Chloro-5-hydroxy-3,6-dimethylpyrazine with phosphoryl chloride gave a low yield of 2,5-dichloro-3,6-dimethylpyrazine (312) 3-chloro-5-hydroxy-2-methyl-pyrazine gave 3,5-dichloro-2-methylpyrazine (535) and 2-chloro-5-hydroxy-3,6-diisobutylpyrazine with phosphoryl chloride at 150° for 5 hours gave 2,5-dichloro-3,6-diisobutylpyrazine (101). 

Some chlorinations have been reported with thionyl chloride. 23-Dicyano-5,6-dihydroxypyrazine refluxed with thionyl chloride in pyridine was reported to give 23-dichloro-5,6-dicyanopyrazine (862) and 2-hydroxy-3-nitro-5,6-diphenyl-pyrazine with thionyl chloride gave 2-chloro-3-hydroxy-5,6-diphenylpyrazine (817, 841) but with thionyl chloride and pyridine it gave the betaine of 2-hydroxy-5,6-diphenyl-3-pyridiniopyrazine chloride (5) (863), which was hydrolyzed in acid to 2,3-dihydroxy-5,6-diphenylpyrazine (863). No product could be isolated from 2-methylpyrazine when refluxed with thionyl chloride (864). 1,4-Dimethylpiperazine-... 

Chloro-3-hydroxy-5(and 6)-methylpyrazine with ammonium hydroxide, copper, and cupric chloride at 125° for 15 hours gave 2-amino-3-hydroxy-5(and 6)-methylpyrazine (373, 835), but 2-chloro-5-hydroxy-3,6-dimethylpyrazine was recovered unchanged after treatment with alcoholic ammonia under drastic conditions (312) and 2-chloro-3-hydroxy-5,6-diphenylpyrazine with pyridine and its hydrochloride at reflux gave the betaine (33) from 2-hydroxy-5,6-diphenyl-3-pyridiniopyrazine chloride (863). Replacement of the chloro substituent occurred... 

Klein et al. (978) first attempted the alkaline hydrolysis of 3-chloropyrazine 1 -oxide to 3-hydroxypyrazine 1 -oxide, and although spectroscopic evidence indicated the formation of the hydroxy compound, good quality homogeneous material could not be isolated. Later work by Berkowitz and Bardos (1034) has shown that 3-chloropyrazine 1-oxide was hydrolyzed by refluxing with two equivalents of aqueous sodium hydroxide, and treatment of the product with trimethylsilyl chloride and triethylamine gave 3-(trimethylsilyl)oxypyrazine 1-oxide. 3,6-Di-s-butyl-2-hydroxypyrazine 1-oxide has been prepared from the chloro analogue (no details given) (982). Hydrolysis of 2-amino-6-chloro-3-cyano-5-methylpyrazine... 

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-... 

Typical preparations have been described for 2-(r-hydroxyiminomethyl)pyrazine (138) 2-(4 -dimethylamino-T-hydroxyiminobutyl)pyrazine (1186) 2-(2 -hydroxy-iminopentyl)-6-methylpyrazine (645) 2-(2 -hydroxyimino-3, 3 -dimethylbutyl)-6-methylpyrazine (645) 2-[r-hydroxyimino-2-(pyridin-2"-yl) (hyl]pyrazine (642) 2-[2 -hydroxyimino-2 -(pyridin-2"-yl, pyrazin-2"-yl, or pyrimidin-4 -yl)ethyl]pyrazine (642) 2-[l, 2 -bishydroxyimino-2 -(pyridin-2"-yl)ethyl]pyrazine (642) 2-12 -(2",4"-dinitrophenylhydrazono)-3 -methylbutyl]-6-methylpyrazine (645) 2-[ 1-(substituted hydrazono)ethyl]pyrazine (1196) 2-[l -phenyl-1 -(substituted hydrazono)methyl]-pyrazine (1196) 2-(r-thiosemicarbazonoethyl)pyrazine (138) 2-(2 -chloro-l -thiosemicarbazonoethyOpyrazine (138) and 2,5-dimethyl-3,6-bis(r-semicarbazono-ethyl)pyrazine (1196). 

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