Abstract
The general synthetic method of pyrazines1 has been established. The method for synthesizing symmetrically substituted pyrazine derivatives, however, has not been well-studied.2 Especially for synthesis of the title pyrazines, it is only described in a few words by Adkins3 and co-workers that ethyl 2-aminoacetoacetate employed in process to preparing of the threonine synthesis is spontaneously autoxidized to give 2,5-dimethyl-3,6-dicarbetoxy pyrazine as a byproduct. On the basis of this finding of Adkins, we have established a convenient method for the synthesis of 2,5-di-methylpyrazine-3,6-dicarboxylic acid derivatives (D1–5) using the corresponding acetoacetic acid derivatives (A1–4) as the starting materials (Scheme).