Paramagnetic Relaxation Agents for Enhancing Temporal Resolution and Sensitivity in Multinuclear FlowNMR Spectroscopy

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 ¹H and ¹⁹F, it significantly reduces the signal-to-noise ratio in ³¹P and ¹³C 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 ³¹P 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 ¹H and ³¹P{ ¹H} FlowNMR data quality in a Rh-catalysed hydroformylation reaction has been demonstrated. With the PRA added, ¹³C relaxation times were reduced more than six-fold, allowing quantitative reaction monitoring of substrate consumption and product formation by ¹³C{ ¹H} FlowNMR spectroscopy at natural abundance.