Joyce Leo A, Schultz Danielle M, Sherer Edward C, Neill Justin L, Sonstrom Reilly E, Pate Brooks H
Department of Process Research & Development , Merck & Co., Inc. , Rahway , NJ 07065 , USA . Email:
Department of Computational and Structural Chemistry , Merck & Co., Inc. , Rahway , NJ 07065 , USA.
Chem Sci. 2020 Jun 8;11(24):6332-6338. doi: 10.1039/d0sc01853h. eCollection 2020 Jun 28.
Direct analyses of crude reaction mixtures have been carried out using molecular rotational resonance (MRR) spectroscopy. Two examples are presented, a demonstration application in photocatalytic CH-arylation as well as generation of an intermediate in a natural product synthesis. In both cases, the reaction can proceed at more than one site, leading to a mixture of regioisomers that can be challenging to distinguish. MRR structural parameters were calculated for the low lying conformers for the desired compounds, and then compared to the experimental spectra of the crude mixtures to confirm the presence of these species. Next, quantitation was performed by comparing experimentally measured line intensities with simulations based on computed values for the magnitude and direction of the molecular dipole moment of each species. This identification and quantification was performed without sample purification and without isolated standards of the compounds of interest. The values obtained for MRR quantitation were in good agreement with the chromatographic values. Finally, previously unknown impurities were discovered within the photocatalytic CH-arylation work. This paper demonstrates the utility of MRR as a reaction characterization tool to simplify analytical workflows.
已使用分子旋转共振（MRR）光谱对粗反应混合物进行了直接分析。本文给出了两个示例，一个是光催化CH-芳基化的示范应用，另一个是天然产物合成中一种中间体的生成。在这两种情况下，反应都可以在多个位点进行，从而产生区域异构体混合物，难以区分。计算了所需化合物低能构象体的MRR结构参数，然后将其与粗混合物的实验光谱进行比较，以确认这些物种的存在。接下来，通过将实验测量的谱线强度与基于每个物种分子偶极矩大小和方向的计算值进行模拟比较来进行定量。这种鉴定和定量是在无需样品纯化且无需目标化合物分离标准品的情况下进行的。MRR定量获得的值与色谱值吻合良好。最后，在光催化CH-芳基化工作中发现了以前未知的杂质。本文证明了MRR作为一种反应表征工具在简化分析工作流程方面的实用性。
