5‐Triazolyluracils and Their <i>N</i>¹‐Sulfonyl Derivatives: Intriguing Reactivity Differences in the Sulfonation of Triazole <i>N</i>^1′‐Substituted and <i>N</i>^1′‐Unsubstituted Uracil Molecules

Abstract

Abstract We describe the synthesis of novel C5‐triazolyl derived N 1 ‐sulfonylpyrimidines through Cu I ‐catalyzed alkyne–azide cycloaddition followed by sulfonylation of the formed C5‐triazolyl derivatives with various sulfonyl chlorides under basic conditions. In the latter step, an intriguing difference in the reactivity of the pyrimidine N 1 was observed that depended on the nature of the substituent at a distant triazole N 1′ site. The N 1′ ‐unsubstituted compounds gave very small amounts of sulfonylation products, whereas N 1′ ‐substituted systems produced high yields of the respective N 1 ‐sulfonyl‐5‐(1,2,3‐triazol‐4‐yl)uracils. Computational analysis revealed a close correlation between the strength of the employed base catalysts and their abilities to increase the nucleophilicity of the uracil N 1 atom through subsequent deprotonation, leading to more products. Following this step, the phosphazene t Bu–P4 superbase was applied in the sulfonylation, resulting in exclusive formation of the triazole N 1′ ‐unsubstituted N 1 ‐sulfonylpyrimidines.