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.