2- aminopyrazine with methyl iodide

Proton magnetic resonance measurements in dimethyl sulfoxide indicate that 2-aminopyrazine and its 3-methyl derivative exist predominantly in the amino form (979, 1086), in agreement with theoretical and experimental electronic spectra (1083). Proton magnetic resonance analysis of the methylation of 2-aminopyrazine with methyl iodide in dimethyl sulfoxide at room temperature showed it to be methylated 8.8 times as fast as pyrazine to give both 3-amino-l-methyl- and 2-amino-l -methylpyrazinium iodides in the ratio 2.9 I (666). Proton magnetic resonance spectra of ionized 2-aminopyrazine in liquid ammonia have also been reported (665). 

The ultraviolet spectra in aqueous solution (821) of the methiodides isolated from the methylation of 2-amino- and 2-dimethylaminopyrazines with methyl iodide in methanol (821) differed from those obtained by protonation of 2-amino-and 2-dimethylaminopyrazine, respectively. This methiodide of 2-aminopyrazine was rapidly decomposed by aqueous alkali but did not form l-methyl-2-oxo(or imino)-l, 2-dihydropyrazine or 2-methylaminopyrazine (821). These and other observations were consistent with protonation of 2-amino(2-methylamino or 2-dimethylamino)pyrazine at N, and with the methiodides isolated involving quater-nization at N4 (821). It has been claimed from studies of ultraviolet and infrared spectra and from reactions with cyanoguanidine that in 2-aminopyrazine p-toluenesulfonate, the amino group is protonated (1189). 

The parent heterocycle and its 5- and 6-monochloro derivatives have been recently prepared from the corresponding aminopyrazines. For example, reaction of 2-amino-6-chloropyrazine with dimethylformamide dimethylacetal gave the intermediate 7, which on reaction with hydrox-ylamine gave the oxime 8. Cyclization of the oximes with polyphosphoric acid afforded the s-triazolo[l,5-a]pyrazines in 61-76% yields. Attempts to methylate 2,5,6-triphenyl-s-triazolo[l,5-aJpyrazine with methyl iodide were unsuccessful. The 2-methyl derivative of the ring system, on treatment with hydrogen peroxide in acetic acid, gave the... 

Aminopyrazine was alkylated with ethyl methyl ketone and sodium in liquid ammonia (in the absence of a catalyst) to 2-amino-6-butylpyrazine, and a similar reaction occurred with isobutyraldehyde (614) and 2-cyano-3-(A, A -dimethylamino-methyleneamino)-5-methylpyrazine was deprotonated with lithium diisopropyl-amide (from butyllithium and diisopropylamine) and alkylated with ethyl iodide followed by removal of the protecting group by acid hydrolysis to give 3-amino-2-cyano-5-propylpyrazine (1031). 

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