Department of Chemistry, University of Bath Claverton Down, Bath, BA2 7AY, United Kingdom.
Dynamic Reaction Monitoring Facility, University of Bath, Claverton Down, Bath, BA2 7AY, United Kingdom.
Chemistry. 2023 Jul 6;29(38):e202300215. doi: 10.1002/chem.202300215. Epub 2023 May 17.
Sensitivity in FlowNMR spectroscopy for reaction monitoring often suffers from low levels of pre-magnetisation due to limited residence times of the sample in the magnetic field. While this in-flow effect is tolerable for high sensitivity nuclei such as H and F, it significantly reduces the signal-to-noise ratio in P and C spectra, making FlowNMR impractical for low sensititvity nuclei at low concentrations. Paramagnetic relaxation agents (PRAs), which enhance polarisation and spin-lattice relaxation, could eliminate the adverse in-flow effect and improve the signal-to-noise ratio. Herein, [Co(acac) ], [Mn(acac) ], [Fe(acac) ] [Cr(acac) ] [Ni(acac) ] [Gd(tmhd) ] and [Cr(tmhd) ] are investigated for their effectiveness in improving signal intensity per unit time in FlowNMR applications under the additional constraint of chemical inertness towards catalytically active transition metal complexes. High-spin Cr(III) acetylacetonates emerged as the most effective compounds, successfully reducing P T values four- to five-fold at PRA concentrations as low as 10 mM without causing adverse line broadening. Whereas [Cr(acac) ] showed signs of chemical reactivity with a mixture of triphenylphosphine, triphenylphosphine oxide and triphenylphosphate over the course of several hours at 80° C, the bulkier [Cr(tmhd) ] was stable and equally effective as a PRA under these conditions. Compatibility with a range of representative transition metal complexes often used in homogeneous catalysis has been investigated, and application of [Cr(tmhd) ] in significantly improving H and P{ H} FlowNMR data quality in a Rh-catalysed hydroformylation reaction has been demonstrated. With the PRA added, C relaxation times were reduced more than six-fold, allowing quantitative reaction monitoring of substrate consumption and product formation by C{ H} FlowNMR spectroscopy at natural abundance.
在流进 NMR 光谱学中，由于样品在磁场中的停留时间有限，反应监测的灵敏度通常会受到预磁化水平低的影响。虽然这种流动效应对于高灵敏度核，如 H 和 F 是可以容忍的，但它会显著降低 P 和 C 谱中的信噪比，使得 FlowNMR 对于低浓度的低灵敏度核是不切实际的。顺磁弛豫增强剂 (PRA) 可以增强极化和自旋晶格弛豫，从而消除不利的流动效应并提高信噪比。在此，研究了 [Co(acac) ]、[Mn(acac) ]、[Fe(acac) ]、[Cr(acac) ]、[Ni(acac) ]、[Gd(tmhd) ]和 [Cr(tmhd) ]在 FlowNMR 应用中提高单位时间信号强度的有效性，同时还额外考虑了对催化活性过渡金属配合物的化学惰性。高自旋 Cr(III) 乙酰丙酮盐化合物表现出最有效的化合物，在低至 10mM 的 PRA 浓度下，成功地将 P T 值降低了四到五倍，而不会引起不利的谱线展宽。虽然 [Cr(acac) ]在 80°C 下与三苯基膦、三苯基氧化膦和三磷酸酯的混合物在数小时内表现出化学反应性的迹象，但在这些条件下，更大体积的 [Cr(tmhd) ]是稳定的，并且作为 PRA 同样有效。还研究了与许多在均相催化中常用的代表性过渡金属配合物的兼容性，并证明了 [Cr(tmhd) ]在 Rh 催化的加氢甲酰化反应中显著提高 H 和 P{ H} FlowNMR 数据质量中的应用。添加 PRA 后，C 弛豫时间减少了六倍以上，允许通过 C{ H} FlowNMR 光谱以自然丰度定量监测底物消耗和产物形成。
