Paramagnetic Relaxation Agents for Enhancing Temporal Resolution and Sensitivity in Multinuclear FlowNMR Spectroscopy
Alejandro Bara‐Estaún, M. Harder, Catherine L. Lyall, John P. Lowe, Elizaveta A. Suturina, Ulrich Hintermair
Abstract
Abstract 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 1 H and 19 F, it significantly reduces the signal‐to‐noise ratio in 31 P and 13 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) 3 ], [Mn(acac) 3 ], [Fe(acac) 3 ] , [Cr(acac) 3 ] , [Ni(acac) 2 ] 3, [Gd(tmhd) 3 ] and [Cr(tmhd) 3 ] 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 31 P T 1 values four‐ to five‐fold at PRA concentrations as low as 10 mM without causing adverse line broadening. Whereas [Cr(acac) 3 ] 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) 3 ] 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) 3 ] in significantly improving 1 H and 31 P{ 1 H} FlowNMR data quality in a Rh‐catalysed hydroformylation reaction has been demonstrated. With the PRA added, 13 C relaxation times were reduced more than six‐fold, allowing quantitative reaction monitoring of substrate consumption and product formation by 13 C{ 1 H} FlowNMR spectroscopy at natural abundance.