Reaction of 3‐methoxy‐ or 3‐chloropyrazine 1‐oxides with refluxing phosphoryl chloride in the presence of amine led to a high regioselective formation of 3‐substituted 2‐chloropyrazines. In contrast, the use of chloroacetyl chloride instead of phosphoryl chloride enabled different regioselectivity to yield 6‐substituted 2‐chloropyrazines, particularly 3‐methoxycarbonylpyrazine 1‐oxide was almost exclusively converted into methyl 6‐chloropyrazinecarboxylate under the conditions without the amine.
This report describes a new method for the preparations of 2,3-dihydroxypyrazines 3 containing (a) , H, (b) H, CHs, (c) CH3i CHa, (d) H, C6H5, (e) CH3, CeHs and (f) CeHs, C6H5 at 5,6 positions. As starting materials, five amino ketals lb-f were prepared by two steps from phthalimido ketones 4b-f. Amino ketals la, lb, and Id (Ri = H) were readily condensed with ethyl oxamate to provide oxamoyl amino ketals 2 in good yields, although condensations of amino ketals le, le, and If, which were stericaliy crowded with methyl or phenyl groups, with ethyl oxamate required drastic conditions. The subsequent cyclizations of oxamoyl amino ketals 2a, 2b, and 2c in acetic acid proceeded in excellent yields to 2,3-dihydroxypyrazines 3a, 3b, and 3c, respectively. While a steric hindrance due to the substituents was recognized, cyclizations of 2d, 2e, and 2f (R2 = C3H5) in acetic acid in the presence of p-toluenesulfonic acid provided the corresponding 2,3-dihydroxypyrazines in 50-60% yields. The structures of these 2,3-dihydroxypyrazines were established by conversion to 2,3-dichloropyrazines 9a-f and subsequently 2,3-diaminopyrazines 10b, lOd, and lOe.
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