Funk Petr, Motyka Kamil, Soural Miroslav, Malon Michal, Koshino Hiroyuki, Kusz Joachim, Hlavac Jan
Department of Organic Chemistry, Institute of Molecular and Translational Medicine, Faculty of Science, Palacky University, Olomouc, Czech Republic.
Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacký University, Olomouc, Czech Republic.
PLoS One. 2017 May 30;12(5):e0175364. doi: 10.1371/journal.pone.0175364. eCollection 2017.
2-Aminoquinolin-4(1H)-one was reacted with various primary/secondary amines and paraformaldehyde under Mannich reaction conditions. In the case of secondary amines, the reaction in N,N-dimethylformamide yielded expected Mannich products accompanied with 3,3'-methylenebis(2-aminoquinolin-4(1H)-one). Except these main products, the pyrimido[4,5-b]quinolin-5-one derivative was also identified as co-product. The reaction with primary amines led to the formation of pyrimido[4,5-b]quinolin-5-ones. The Mannich reaction products were thermally unstable and afforded a mixture of bis-(2-aminoquinolin-4(1H)-one) and tris-(2-aminoquinolin-4(1H)-one) derivative, probably via reactive methylene species. This retro-Mannich reaction was tested in reaction with indole and thiophenole as nucleophilles, and appropriate conjugates were formed. The mechanism of above discussed reactions in which 2-aminoquinolinone displays the nucleophilicity on C3 carbon as well as N2 nitrogen is discussed.
2-氨基喹啉-4(1H)-酮在曼尼希反应条件下与各种伯胺/仲胺和多聚甲醛反应。对于仲胺，在N,N-二甲基甲酰胺中的反应产生预期的曼尼希产物，并伴有3,3'-亚甲基双(2-氨基喹啉-4(1H)-酮)。除了这些主要产物外，嘧啶并[4,5-b]喹啉-5-酮衍生物也被鉴定为副产物。与伯胺的反应导致嘧啶并[4,5-b]喹啉-5-酮的形成。曼尼希反应产物热不稳定，可能通过活性亚甲基物种生成双-(2-氨基喹啉-4(1H)-酮)和三-(2-氨基喹啉-4(1H)-酮)衍生物的混合物。该逆曼尼希反应在与吲哚和苯硫酚作为亲核试剂的反应中进行了测试，并形成了适当的共轭物。讨论了上述反应的机理，其中2-氨基喹啉酮在C3碳以及N2氮上表现出亲核性。
