Department of Chemistry, Faculty of Science, University of Zagreb, Horvatovac 102A, 10000 Zagreb, Croatia.
Int J Mol Sci. 2022 Oct 15;23(20):12331. doi: 10.3390/ijms232012331.
In the present study, four -substituted oximes of quinuclidin-3-one were synthesized using appropriate -substituted hydroxylamine hydrochlorides. In order to perform these reactions in a solvent, a mixture of () and () products was yielded. Using mechanochemical and microwave synthesis, we then obtained pure () oximes. In almost all cases, the conversion to oxime ethers was completed. Reactions were monitored by ATR spectroscopy and the ratios of () and () oxime ethers were deduced from H NMR data. Several reactions were very rapid (1 min) with 100% conversion and stereospecificity. To investigate the reaction mechanisms, full conformational analyses of the reaction intermediates were performed and the lowest energy conformers were determined. These conformers differed in spatial arrangement around the nitrogen atom of the amino group and were in the correct orientation for reactions to occur. Calculated standard Gibbs energies of the formation were in agreement with the experimentally obtained ratios of ( and () isomers. This work shows alternatives to the classical synthesis of -substituted oxime ether precursors and highlights the fast reaction rate and stereoselectivity of microwave synthesis as well as the "green" aspects of mechanochemistry.
在本研究中，使用适当取代的羟胺盐酸盐合成了四种取代的奎宁啶-3-酮肟。为了在溶剂中进行这些反应，得到了（）和（）产物的混合物。然后，我们通过机械化学和微波合成获得了纯（）肟。在几乎所有情况下，肟醚的转化率都完成了。通过 ATR 光谱监测反应，从 H NMR 数据推导出（）和（）肟醚的比例。一些反应非常迅速（1 分钟），转化率和立体选择性达到 100%。为了研究反应机制，对反应中间体进行了全构象分析，并确定了最低能量构象。这些构象在氨基氮原子周围的空间排列方式不同，并且处于发生反应的正确取向。计算得到的形成标准吉布斯自由能与实验获得的（和（）异构体的比例一致。这项工作展示了取代的肟醚前体的经典合成的替代方法，并强调了微波合成的快速反应速率和立体选择性以及机械化学的“绿色”方面。
