Institute of Molecules and Materials , Radboud University Nijmegen , Nijmegen , The Netherlands.
FutureChemistry Holding B.V. , Nijmegen , The Netherlands.
J Am Chem Soc. 2019 Apr 3;141(13):5369-5380. doi: 10.1021/jacs.9b00039. Epub 2019 Mar 22.
We present an in-depth study of the acetylation of benzyl alcohol in the presence of N, N-diisopropylethylamine (DIPEA) by nuclear magnetic resonance (NMR) monitoring of the reaction from 1.5 s to several minutes. We have adapted the NMR setup to be compatible to microreactor technology, scaling down the typical sample volume of commercial NMR probes (500 μL) to a microfluidic stripline setup with 150 nL detection volume. Inline spectra are obtained to monitor the kinetics and unravel the reaction mechanism of this industrially relevant reaction. The experiments are combined with conventional 2D NMR measurements to identify the reaction products. In addition, we replace DIPEA with triethylamine and pyridine to validate the reaction mechanism for different amine catalysts. In all three acetylation reactions, we find that the acetyl ammonium ion is a key intermediate. The formation of ketene is observed during the first minutes of the reaction when tertiary amines were present. The pyridine-catalyzed reaction proceeds via a different mechanism.
我们通过从 1.5 秒到几分钟的反应的核磁共振（NMR）监测，深入研究了在 N，N-二异丙基乙胺（DIPEA）存在下的苄醇的乙酰化。我们已经适应了 NMR 设备，使其与微反应器技术兼容，将商业 NMR 探头的典型样品体积（500 μL）缩小到具有 150 nL 检测体积的微流控 stripline 装置。在线谱用于监测动力学并揭示该工业相关反应的反应机理。实验与传统的 2D NMR 测量相结合，以确定反应产物。此外，我们用三乙胺和吡啶代替 DIPEA，以验证不同胺催化剂的反应机理。在所有三种乙酰化反应中，我们发现乙酰铵离子是关键中间体。当存在叔胺时，在反应的最初几分钟内观察到酮烯的形成。吡啶催化的反应通过不同的机制进行。
