Monitoring chemical reactions by low-field benchtop NMR at 45 MHz: pros and cons

• Published in: Magnetic resonance in chemistry 2016-06, Vol.54 (6), p.437-443
• Main Authors: Silva Elipe, Maria Victoria, Milburn, Robert R.
• Format: Article
• Language: English
• Subjects: 1D 1H NMR; 45 MHz; Fischer esterification; low-field NMR; NMR; reaction monitoring; Suzuki coupling; tubeless NMR; two-phase reaction
• ISSN: 0749-1581; 1097-458X
• DOI: 10.1002/mrc.4189

Monitoring chemical reactions is the key to controlling chemical processes where NMR can provide support. High‐field NMR gives detailed structural information on chemical compounds and reactions; however, it is expensive and complex to operate. Conversely, low‐field NMR instruments are simple and relatively inexpensive alternatives. While low‐field NMR does not provide the detailed information as the high‐field instruments as a result of their smaller chemical shift dispersion and the complex secondary coupling, it remains of practical value as a process analytical technology (PAT) tool and is complimentary to other established methods, such as ReactIR and Raman spectroscopy. We have tested a picoSpin‐45 (currently under ThermoFisher Scientific) benchtop NMR instrument to monitor three types of reactions by 1D 1H NMR: a Fischer esterification, a Suzuki cross‐coupling, and the formation of an oxime. The Fischer esterification is a relatively simple reaction run at high concentration and served as proof of concept. The Suzuki coupling is an example of a more complex, commonly used reaction involving overlapping signals. Finally, the oxime formation involved a reaction in two phases that cannot be monitored by other PAT tools. Here, we discuss the pros and cons of monitoring these reactions at a low‐field of 45 MHz by 1D 1H NMR. Copyright © 2015 John Wiley & Sons, Ltd. Chemical reactions were followed by low‐field NMR. A 45 MHz benchtop NMR instrument was tested to monitor three types of reactions by 1D 1H NMR: a Fischer esterification, a Suzuki cross‐coupling, and the formation of an oxime. Only protonated solvents were used with no observation of lineshape degradation by magnetic drift. Aliquots were injected over time into the NMR flow cell at the temperature of the magnet. A low signal‐to‐noise ratio of 10 : 1 for the solvent/analyte signals is reasonable.