By Alkylation of Hydroxypyrazines

The preparation of alkoxypyrazines by alkylation of hydroxypyrazines with several reagents is discussed in detail in Section 6D. Many such alkylations give rise to both N- and 0-alkyl derivatives. 

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- 

A series of methoxy compounds have been prepared from 2-hydroxy-3-(a-hydroxybenzyl)pyrazines and dimethyl sulfate (1045), and 2-benzyl-3,6-dihydroxy-pyrazine with diethyl sulfate and sodium ethoxide gave the 3,6-diethoxy derivative (1066). 

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Most alkoxy- or aryloxypyrazines have been made by primary synthesis (see Chapters 1 and 2), by addition of alcohols to alkynylpyrazines (see Section 3.2.4.9), by alcoholysis or phenolysis of halogenopyrazines (see Sections 4.2.3 and 4.4), by O-alkylation of tautomeric pyrazinones or extranuclear hydroxypyrazines (see Sections 5.1.2.2 and 5.2.2), or by epoxidation of alkenylpyrazines (see Section 3.2.4.1). Some of the few remaining routes (presently of minor preparative value) are illustrated briefly in the following recent examples ... 

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