Online Stereochemical Process Monitoring by Molecular Rotational Resonance Spectroscopy
Published in Organic Process Research & Development, April 2019
Authors: Justin L. Neill, Yuan Yang, Matt T. Muckle, Roger L. Reynolds, Luca Evangelisti, Reilly E. Sonstrom, Brooks H. Pate, B. Frank Gupton
Summary
Originally published in Organic Process Research & Development, this paper presents an online molecular rotational resonance (MRR) spectroscopy system for real-time monitoring of stereochemical reactions. The automated instrument continuously samples a reaction stream, vaporizes the sample, and acquires high-resolution MRR spectra to determine the relative amounts of reaction components without chromatographic separation or chemometric analysis.
The system was demonstrated using the hydrogenation of artemisinic acid, an intermediate in the semisynthesis of the antimalarial drug artemisinin. During each measurement, the instrument quantified the starting material, desired product, a diastereomeric byproduct, and an overreduction impurity. Notably, the overreduction byproduct could not be directly quantified using either HPLC or NMR methods. With a measurement cycle time of approximately 17 minutes and the ability to operate unattended for extended periods, the study highlights the potential of MRR spectroscopy for automated process monitoring and reaction control in pharmaceutical manufacturing.
Key Takeaways
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Demonstrates online stereochemical process monitoring using molecular rotational resonance (MRR) spectroscopy.
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Enables rapid quantitation of isomers and impurities without chromatographic separation.
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Automatically samples and analyzes reaction mixtures in an unattended workflow.
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Monitors the hydrogenation of artemisinic acid, a key step in artemisinin production.
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Quantifies starting material, product, diastereomer, and overreduction byproduct in a single analysis.
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Demonstrates the potential of MRR spectroscopy for real-time process monitoring and pharmaceutical manufacturing applications.