2-Amino-3-cyano-6-hydroxy-5-methylpyrazine 1-oxide

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). 

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... 

Amino-2prepared from 2-amino-3-cyanopyrazine 1-oxide by reflux with acetic acid-acetic anhydride followed by ready deacetylation by refluxing in methanol (538), and in a similar manner 3-amino-2-ethoxycarbonyl-5-hydroxypyrazine has been prepared from 2-amino-3-ethoxycarbonylpyrazine 1 -oxide through 3-acetamido-2-ethoxycarbonyl-5 ydroxy-pyrazine (538), and 2-amino-3-carbamoyl-6-hydroxy-5-methylpyrazine from 2-amino-3-cyano-5-methylpyrazine 1-oxide (538). The preparation of 24 ydroxy-6-methoxycarbonylpyrazine (10) has been claimed from 3-methoxycarbonylpyrazine 1-oxide with acetic anhydride followed by hydrolysis (1057) [cf. Nov Cek et al. (839), who claim it to be the 5-isomer, and Foks (744)]. 

Amino-3-cyano-5-methylpyrazine 1,4-dioxide (91) refluxed for several minutes with acetic anhydride formed 3-acetamido-2-cyano-5-hydroxy-6-methylpyrazine 1-oxide (92) (24%) (532) and 2-acetoxymethyl-5-methylpyrazine 1,4-dioxide refluxed with acetic anhydride afforded a mixture of2,5-di(acetoxymethyl)pyrazine 1-oxide, with some 2,5-diacetoxymethylpyrazine and a monoxide of 2-acetoxy-methyl-5-methylpyrazine (625). 2-Formylpyrazine hydrate 1,4-dioxide with aqueous sodium hydroxide or bicarbonate at < 37° in an unusual reaction gave 3-carboxy-pyrazine 1-oxide mixed with 5 [Pg.188]

The preparation of extranuclear alkoxypyrazines from extranuclear halogeneo-pyrazines has been described in Section V.6A (654, 672,679,685, 687,688,694, 756, 872, 1027). 2-Amino-3-cyano-5-methoxymethylpyrazine 1-oxide with phosphorus trichloride in tetrahydrofuran afforded 2-amino-3-cyano-5-methoxy-methylpyrazine (529) and 3-(bromoacetamido)-l-ethoxy4-oxopentane (44) with alcoholic ammonia gave 5-hydroxy-3-(2 -ethoxyethyl)-2-methylpyrazine (45) (248). 

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