2-Benzyloxy-6-hydroxypyrazine

Khydroxypyrazine (which was converted into its jV -dimethyl derivative by treatment with dimethyl sulfate and alkali) gave, on reaction with an excess of ethereal diazomethane a mixture of its N,N-, 0,N-, and 0,0-dimethyl derivatives (58-60) (832). 2-Hydroxy-5-methoxy- and 2,5-dihydroxy-3,6-diphenylpyrazine with ethereal diazomethane gave predominantly 2,5-dimethoxy-3,6-diphenyl-pyrazine and only minor amounts of A -methylated products (832). Methylation of 2-hydroxy-6-methoxypyrazine with ethereal diazomethane produced a mixture of 0- and A -methyl derivatives in which the 0-methyl derivative predominated but the corresponding reaction of 2-benzyloxy-6-hydroxypyrazine gave almost exclusively the 0-methyl derivative (832) [the results of these methylations were correlated with the carbonyl stretching frequency (1103) in the parent lactam (832)]. 

Other hydrolyses with sodium hydroxide have been described as follows. 2-Benzyloxy-6-chloropyrazine in ethanol with 3.5N sodium hydroxide at reflux for 4.5 hours gave 2-chloro-6-hydroxypyrazine (832), 2-chloro-6-metho)Qrpyrazine with aqueous ethanolic sodium hydroxide gave 2-chloro-6-hydroxypyrazine (43%) possibly containing a small amount of 2-hydroxy-6-methoxypyrazine) (883), and 2,6-dimethoxypyrazine with aqueous ethanolic sodium hydroxide at reflux for 24 hours formed 2-hydroxy-6-methoxypyrazine (832). 

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-... 

Alkoxypyrazine A -oxides may be hydrolyzed with acid to hydroxypyrazine A -oxides. Some examples are the hydrolysis of 3-ethoxy-2,5-dimethylpyrazine 1-oxide at reflux with 3 A hydrochloric acid to give 3-hydroxy-2,5-dimethylpyrazine 1-oxide (872) 2,5-diethoxy-3,6-dimethylpyrazine 1,4-dioxide with 2N hydrochloric acid at 70° gave 2-ethoxy-5-hydroxy-3,6-dimethylpyrazine 1,4-dioxide and 2,5-dibenzyloxy-3,6-dimethylpyrazine 1,4-dioxide similarly treated but at room temperature gave the 2-benzyloxy analogue (842), but with lOAf hydrochloric acid at room temperature it gave 2,5-dihydroxy-3,6-dimethylpyrazine 1,4-dioxide (842). 

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