Monitoring the On‐line Titration of Enantiomeric Omeprazole Employing Continuous‐flow Capillary Microcoil ¹H NMR Spectroscopy

Abstract

The titration of the (S)-enantiomer of omeprazole with the (R)-enantiomer in chloroform-d(1) is monitored by continuous-flow capillary microcoil (1)H NMR spectroscopy employing a microcoil with a detection volume of 1.5 µl. The observed changes of the (1)H NMR chemical shifts indicate the formation of a heterochiral (R,S) dimer of omeprazole via its sulfinyl group and the NH group of the benzimidazole ring.

Miniaturization of NMR Systems: Desktop Spectrometers, Microcoil Spectroscopy, and “NMR on a Chip” for Chemistry, Biochemistry, and Industry

“…A similar example of continuous flow NMR application toward reaction monitoring was reported by Albert and co-workers . The capillary probe with detection volume of 1.5 μL demonstrated excellent line shape characteristics that allowed one to discriminate between two diastereomers being formed in the reaction.…”

The Phenomenon of Self-Induced Diastereomeric Anisochrony and Its Implications in NMR Spectroscopy

“…Hentschel et al employed a continuous-flow capillary microcoil for the 1 H NMR monitoring of the enantiomeric titration of omeprazole (66, Figure 8) and highlighted the SIDA behavior of the drug in chloroform-d solution [56].…”

Convenient and accurate insight into solution-phase equilibria from FlowNMR titrations

“…With the recent commercial availability of versatile, small-scale FlowNMR hardware solutions that are compatible with standard high-field spectrometers, the use of FlowNMR spectroscopy for titrations is becoming relevant again, especially when also considering the advances in NMR methodology over the past 30 years. 21 Here we demonstrate the application of a simple FlowNMR setup for accurate and precise titrations of Brønsted acid/base systems in aqueous and organic media (including mixtures and examples of solvent participation), associations of Lewis acid/base pairs (including air-and moisture-sensitive frustrated Lewis pairs), hydrogen bonding interactions, and dynamic metal-ligand binding using 1 H, 11 B, 13 C, 19 F and 31 P FlowNMR methods. The use of mid-acquisition variable temperature and diffusion analysis is demonstrated, and aspects of technique hyphenation and process automation are discussed.…”