Nguyen Huong Giang Thi, Nguyen Vinh Ngoc, Kamounah Fadhil S, Hansen Poul Erik
Institute of Drug Quality Control, Ho Chi Minh City, Vietnam.
Department of Chemistry, University of Copenhagen, Copenhagen, Denmark.
Magn Reson Chem. 2018 Nov;56(11):1094-1100. doi: 10.1002/mrc.4760. Epub 2018 Jul 2.
In a conventional Mannich reaction using piperidine, hydroxypiperidines, morpholine, and N-methylpiperazine with usnic acid, a deacetylation was observed resulting in a substitution at C-2, a loss of an acetyl group, and a Mannich base with a stabilized enol. The enol has a hydrogen bond to the nitrogen of the secondary amine. The structure was investigated by nuclear magnetic resonance and deuterium isotope effects on C chemical shifts as well as with density functional theory calculations to study the changed hydrogen bond pattern. It was found that the hydrogen bond involving the OH-9 group in chloroform forms a strong hydrogen bond than in usnic acid itself and that this hydrogen bond becomes even stronger in the more polar solvent, dimethylsulfoxide. Tautomerism was observed in the Mannich base as demonstrated by deuterium isotope effects on chemical shifts. The position of the tautomeric equilibrium depends on the solvent, and the position of the equilibrium governs the strength of the OH-9…O═C hydrogen bond.
在使用哌啶、羟基哌啶、吗啉和N - 甲基哌嗪与松萝酸进行的传统曼尼希反应中，观察到了脱乙酰化现象，导致在C - 2处发生取代、乙酰基的丢失以及形成了具有稳定烯醇的曼尼希碱。该烯醇与仲胺的氮形成氢键。通过核磁共振、氘同位素对碳化学位移的影响以及密度泛函理论计算来研究该结构，以探究氢键模式的变化。研究发现，在氯仿中涉及OH - 9基团的氢键比松萝酸本身形成的氢键更强，并且在极性更强的溶剂二甲亚砜中，这种氢键会变得更强。如氘同位素对化学位移的影响所示，在曼尼希碱中观察到了互变异构现象。互变异构平衡的位置取决于溶剂，并且平衡的位置决定了OH - 9…O═C氢键的强度。
