Studies on pyrazines. 14 The syntheses of 2,5-dihydroxypyrazines and their derivatives

Reaction of phenylglycinamide ( 1c ) with ethyl benzoylformate ( 2c ) in the presence of refluxing ethanolic sodium ethoxide gave 2,5-dihydroxy-3,6-diphenylpyrazine ( 3i ) in 19% yield. This synthetic method, however, was limited to the preparation of 3i . On the other hand, α-aminoamides 1 condensed with α-ketoesters 2 to give the intermediates 5 , which were also prepared by condensation of 1 with α-ketalesters 6 , followed by hydrolysis of the ketal moeity. Cyclization of 5 with refluxing methanolic sodium methoxide gave only disubstituted 2,5-dihydroxypyrazines 3 . Acetylation of 5 with refluxing acetic anhydride/acetic acid led to direct formation of 2,5-diacetoxypyrazines 9 . Similarly, compounds 5 could be converted into 2,5-dichloropyrazines 4 .