Amination at Ring Carbon and Nitrogen

Amination of 2,5-dimethylpyrazine proceeds very slowly with NaNH2 in xylene. Only on strong heating in solvents is an evolution of hydrogen observed, and a small quantity of 3-amino-2,5-dimethylpyrazine isolated (718) most of the 

5-dimethylpyrazine is recovered unchanged. Joiner and Spoerri (719) found that when dimethylamine was used as solvent at 165° the yield was increased to 35%. 

Direct amination of 2,5-di-s-butylpyrazine with sodamide gave 3-amino-2,5-di-s-butylpyrazine (89,171,720). 

Zoltewicz and Helmick (665) found that, whereas pyrazine reacts with potassium amide to form the anionic o complex (20), methylpyrazine undergoes deprotonation to give the delocalized carbanion (21) and the p.m.r. spectrum shows that pyrazine with phenyllithium at —45° is converted completely into a dihydro adduct analogous to (20) (720a). 

5-Trimethylpyrazinium iodide in liquid ammonia adds at the 6-position to form the 6-adduct (22) (609) nitromethide and ethanethiolate ions at — 60° add to the 6-position of 1,2,5-trimethylpyrazinium ion to give adducts (23, X = CHNO and SCH3), respectively (721). 

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