Copper-Catalyzed Tandem Reactions of 2‑Amine-[1,3,5]triazines with Nitriles

Copper-catalyzed intermolecular annulation of 2-amine-[1,3,5]­triazines and aryl nitriles for the synthesis of [1,2,4]­triazolo­[1,5-a]­[1,3,5]­triazines via N–C bond formation and oxidative N–N coupling [oxidative 3 + 2 cyclization] is presented. A wide range of aryl nitriles, including electron-rich benzonitriles, electron-poor benzonitriles, 2-cyanothiophene, and 4-cyanopyridine, were all functionalized with 2-amine-[1,3,5]­triazines. Furthermore, amidation of 2-amine-[1,3,5]­triazines via Cu-catalyzed C–CN bond cleavage of phenylacetonitriles is also demonstrated. The reaction occurred in moderate to satisfactory yields and tolerated alkyl- or aryl-substituted 2-amine-[1,3,5]­triazines. Aniline, aminopyridine, and aminopyrimidine also afforded the desired products.

本研究报道了铜催化2-氨基-[1,3,5]三嗪（2-amine-[1,3,5]triazines）与芳基腈（aryl nitriles）的分子间环化反应，该反应通过N-C键形成与氧化N-N偶联（氧化3+2环化）路径合成[1,2,4]三唑并[1,5-a][1,3,5]三嗪（[1,2,4]triazolo[1,5-a][1,3,5]triazines）。多种芳基腈底物均可与2-氨基-[1,3,5]三嗪发生官能化转化，涵盖富电子苯甲腈、缺电子苯甲腈、2-氰基噻吩以及4-氰基吡啶等。此外，本研究还证实该催化体系可通过铜催化苯乙腈的C-CN键断裂，实现2-氨基-[1,3,5]三嗪的酰胺化反应。该反应可获得中等至良好的收率，且兼容烷基或芳基取代的2-氨基-[1,3,5]三嗪底物。苯胺、氨基吡啶以及氨基嘧啶同样可顺利得到目标产物。