Pyrazine alkoxycarbonylation

Derivatives of 1,2-, 1,4-, 2,3-, and 2,5-dihydropyrazine are known, but the structures of these compounds are not easy to establish because of the tendency of dihydropyrazines to isomerize, dimerize, and oxidize. Dihydro structures are stabilized by groups such as alkoxycarbonyl and phenyl 1,4-dihydro-2,3,5,6-tetraethoxycarbonyl-pyrazine and 2,3-dihydro-5,6-diphenylpyrazine are relatively stable compounds. 

The preparation of guanidinocarbonylpyrazine A -oxides by ring opening reactions has been described in Section VI11.3A(2), and from alkoxycarbonyl-pyrazine V-oxides in Section 9B.6-Chloro-2-methyl-4//-pyrazino[2,3-[Pg.307]

In comparison to the ease of alkoxycarbonylation of halopyrazines, the aminocarbonylation was dramatically influenced by both the phosphorus ligands and carbon monoxide pressure. Pyrazinecarboxamide was prepared via aminocarbonylation using diethylamine as solvent. For example, 2-chloropyrazine was converted into 2-(diethylaminocarbonyl) pyrazine (173) in 85% yield along with 8% of the nucleophilic substitution product 174. Intriguingly, when butylamine was used, the corresponding S Ar product similar to 174 was the major product (72% yield), whereas the amide was isolated as a minor product (28%). 

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