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5-Triazolyluracils and Their N1-Sulfonyl Derivatives: Intriguing Reactivity Differences in the Sulfonation of Triazole N1'-Substituted and N1'-Unsubstituted Uracil Molecules

We describe the synthesis of novel C5-triazolyl derived N1-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 N1 was observed that depended on the nature of the substituent at a distant triazole N1' site. The N1'-unsubstituted compounds gave very small amounts of sulfonylation products, whereas N1'-substituted systems produced high yields of the respective N1-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 N1 atom through subsequent deprotonation, leading to more products. Following this step, the phosphazene tBu–P4 superbase was applied in the sulfonylation, resulting in exclusive formation of the triazole N1'-unsubstituted N1- sulfonylpyrimidines.

Nucleobases ; Sulfonylation ; Substituent effects ; Regioselectivity ; Density functional calculations

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