Pyrazine Chichibabin amination

There is but one example of nonfused pyrazine Chichibabin amination in the literature, reported by Van der Plas in 1982. In KNH2-NH3/ KMn04 at room temperature, the reaction gives 2-aminopyrazine (33) in a 65% yield. 

The Chichibabin amination of phenylpyrazine with N-labeled potassium amide/liquid ammonia gave two products, 3-amino- and 5-amino-2-phenylpyrazine in both products the label is only present in the amino group, and no label was found to be incorporated into the pyrazine ring (82MI1). This result proves that in the aminodehydrogenation of phenylpyrazine, no Sn(ANRORC) mechanism is involved. This result is confirmed by the fact that amination of phenylpyrazine in the presence of the radical scavenger azobenzene, a compound that has been found to prevent the Sn(ANRORC) mechanism in the Chichibabin amination of 4-phenylpyrimidine, still yields both aminopyrazines. 

Pyrazine is more reactive than pyridine towards nucleophiles. Although the Chichibabin amination is unsatisfactory, substitution of the halogen in 2-halopyrazine occurs readily by ammonia, amines, amide, cyanide, alkoxide and thiolate. 

In 1972, Zoltewicz and Helmick reported the first evidence of anionic o-adducts in the Chichibabin amination reaction. The parent diazines a-adduct complex (pyrimidine, pyridazine and pyrazine) in KNH2-NH3/KMn04 (at low temperature 0 to 0 °C) are shown below. Despite the fact that the parent pyrimidine has three possible amination spots, 18 is the adduct formed and similarly for pyridazine and pyrazine, adducts 19 and 20 are formed under the aforementioned conditions. The regio-chemical outcome changes when these rings are substituted. 

The only reported substitution of unsubstituted pyrazines with nucleophilic reagents involves amination via the Chichibabin reaction (84MI4). 

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