Selective N-alkylation of amines using nitriles under hydrogenation conditions: facile synthesis of secondary and tertiary amines
Selective N-alkylation of amines using nitriles under hydrogenation conditions: facile synthesis of secondary and tertiary amines
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DOI：
10.1039/c1ob06303k
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发表时间：
2012-01-01
影响因子：
3.2
通讯作者：
Sajiki, Hironao
中科院分区：
文献类型：
--
作者：
Ikawa, Takashi;Fujita, Yuki;Sajiki, Hironao
腈类化合物是一种高效的烷基化试剂，在催化加氢条件下可用于胺的选择性N-烷基化反应。对于芳族伯胺，相应的仲胺选择性地得到Pd/C催化加氢条件下。虽然使用贫电子芳族胺或大体积腈显示出对还原烷基化的较低反应性，但NH 40 Ac的加入增强了反应性，以良好至优异的产率得到仲芳族胺。在相同的反应条件下，芳香族硝基化合物可以代替芳香族伯胺，通过硝基的一锅加氢和胺的还原烷基化的多米诺反应直接转化为仲胺。虽然在Pd/C催化条件下脂肪胺有效地转化为相应的叔胺，但Rh/C是用于脂肪伯胺的N-单烷基化而不过度烷基化为叔胺的高效催化剂。此外，Rh/C催化的脂肪族伯胺的N-单烷基化和另外的Pd/C催化的脂肪族仲胺的烷基化的组合可以选择性地制备具有三个不同烷基的脂肪族叔胺。根据机理研究，似乎可以合理地得出结论，在反应的第一步中，腈在胺的亲核攻击之前被还原为醛亚胺。
Nitriles were found to be highly effective alkylating reagents for the selective N-alkylation of amines under catalytic hydrogenation conditions. For the aromatic primary amines, the corresponding secondary amines were selectively obtained under Pd/C-catalyzed hydrogenation conditions. Although the use of electron poor aromatic amines or bulky nitriles showed a lower reactivity toward the reductive alkylation, the addition of NH4OAc enhanced the reactivity to give secondary aromatic amines in good to excellent yields. Under the same reaction conditions, aromatic nitro compounds instead of the aromatic primary amines could be directly transformed into secondary amines via a domino reaction involving the one-pot hydrogenation of the nitro group and the reductive alkylation of the amines. While aliphatic amines were effectively converted to the corresponding tertiary amines under Pd/C-catalyzed conditions, Rh/C was a highly effective catalyst for the N-monoalkylation of aliphatic primary amines without over-alkylation to the tertiary amines. Furthermore, the combination of the Rh/C-catalyzed N-monoalkylation of the aliphatic primary amines and additional Pd/C-catalyzed alkylation of the resulting secondary aliphatic amines could selectively prepare aliphatic tertiary amines possessing three different alkyl groups. According to the mechanistic studies, it seems reasonable to conclude that nitriles were reduced to aldimines before the nucleophilic attack of the amine during the first step of the reaction.