Monitoring Hydrogenation Reactions using Benchtop 2D NMR with Extraordinary Sensitivity and Spectral Resolution

Abstract

Low‐field benchtop nuclear magnetic resonance (BT‐NMR) spectrometers with Halbach magnets are being increasingly used in science and industry as cost‐efficient tools for the monitoring of chemical reactions, including hydrogenation. However, their use of low‐field magnets limits both resolution and sensitivity. In this paper, we show that it is possible to alleviate these two problems through the combination of parahydrogen‐induced polarization (PHIP) and fast correlation spectroscopy with time‐resolved non‐uniform sampling (TR‐NUS). PHIP can enhance NMR signals so that substrates are easily detectable on BT‐NMR spectrometers. The interleaved acquisition of one‐ and two‐dimensional spectra with TR‐NUS provides unique insight into the consecutive moments of hydrogenation reactions, with a spectral resolution unachievable in a standard approach. We illustrate the potential of the technique with two examples: the hydrogenation of ethylphenyl propiolate and the hydrogenation of a mixture of two substrates – ethylphenyl propiolate and ethyl 2‐butynoate.

Low‐field benchtop NMR spectroscopy: status and prospects in natural product analysis†

“…Research is on‐going to increase the sensitivity 10000‐fold or more through hyperpolarisation. This would accomplish a 13 C spectrum in one scan, 70–74 or enable metabolite analysis in sec 75 . SABRE (signal amplification by reversible exchange) is such a promising technique but it is not universal for all analytes, requires additional chemicals and logistically it is rather complicated 70–72 .…”

Enhancing Compression Level for More Efficient Compressed Sensing and Other Lessons from NMR Spectroscopy

“…Usually, such mixtures require at least 2D NMR experiment to resolve important peaks in a spectrum, which makes monitoring troublesome using conventional sampling. One may also apply NUS/CS NMR spectroscopy to track different chemical reactions when a good temporal resolution and the benefits provided by 2D NMR experiments are required [85,86].…”

A comparison of non‐uniform sampling and model‐based analysis of NMR spectra for reaction monitoring

“…[15,16] However, the reduced sampling permitted by NUS methods also enables the study of dynamic processes, and in recent decades, NUS methods have been increasingly used in reaction monitoring applications. [17][18][19][20][21][22] Nevertheless, it is a key challenge to ensure that the NUS spectra are inherently quantitative. Specifically, qNMR spectra require long relaxation delays (typically 5 × T 1 , or about 30 s for 1 H NMR) before each excitation to ensure that the magnetisation has returned to the equilibrium.…”

“…If homonuclear pulse sequences are used, the problem of quantification becomes less important as the 2D peak integrals are inherently quantitative and lead to the same quantification results as standard 1D NMR experiments. [ 21 ] However, homonuclear sequences are not applicable to complex reaction mixtures, where many overlapping peaks make it difficult to assign all species.…”