Quantitative reaction monitoring using parahydrogen-enhanced benchtop NMR spectroscopy

Abstract

The parahydrogen-induced polarisation (PHIP) NMR signal enhancement technique is used to study H₂ addition to Vaska's complex (trans-[IrCl(CO)(PPh₃)₂]) with both standard high-field (9.4 T) NMR and benchtop (1 T) NMR detection. Accurate and repeatable rate constants of (0.84 ± 0.03) dm³ mol⁻¹ s⁻¹ and (0.89 ± 0.03) dm³ mol⁻¹ s⁻¹ were obtained for this model system using standard high-field and benchtop NMR, respectively. The high-field NMR approach is shown to be susceptible to systematic errors associated with interference from non-hyperpolarised signals, which can be overcome through a multiple-quantum filtered acquisition scheme. This challenge is avoided when using benchtop NMR detection because the non-hyperpolarised signals are much weaker due to the lower magnetic field, enabling the use of a simpler and more efficient single RF pulse detection scheme. Method validation against several experimental parameters (NMR relaxation, %pH₂ enrichment and temperature) demonstrates the robustness of the benchtop NMR approach but also highlights the need for sample temperature control throughout reaction monitoring. A simple temperature equilibration protocol, coupled with use of an insulated sample holder while manipulating the sample outside the spectrometer, is found to provide sufficient temperature stabilisation to ensure that accurate and repeatable rate constants are obtained. Finally, the benchtop NMR reaction monitoring protocol is applied to the analysis of a complex mixture, where multiple reaction products form simultaneously. H₂ addition to a mixture of three Vaska's complex derivatives was monitored, revealing the presence of competitive reaction pathways within the mixture.