Hydroxypyrazines alkylation

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 ... 

Other chlorinations have been effected with phosphorus pentachloride alone as follows piperazine-2,5-dione in carbon tetrachloride to 2,5-dichloro-3,6-dihydropyrazine (847, 849) [but at 250°/24hours to tetrachloropyrazine (850, 851)] 2[Pg.102]

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. 

Alkylation of hydroxypyrazines to give N- or 0-alkyl derivatives (and mixtures of both formed particularly from methylations with diazomethane) have been described in Section 6D. 

The antibiotic emimycin was first isolated (107) from Streptomyces No. 2021-1 and subsequent work (108) showed it to be 3-hydroxypyrazine 1-oxide which from infrared evidence (Nujol) was assigned the pyrazine structure (99, R = H) [alkyl derivatives have been assigned similar structures (978)]. It had an acidic pAi, 6.2 (108) and was a stronger acid than 2-hydroxypyrazine [acidic pA 8.23 (1082)]. Emimycin did not form acetyl derivatives under a variety of conditions acetic anhydride and pyridine, acetyl chloride and pyridine, or acetic anhydride and sulfuric acid (108). 

The alkylation of hydroxypyrazine A oxides to C- and A-alkoxypyrazine N-oxides has been described in Section 11C. 

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