The use of exchangeable nuclei to observe enantiomers through deuterium NMR in chiral liquid crystalline solvents

Abstract

It is demonstrated that (2)H NMR in chiral liquid crystalline solvents can be used to measure enantiomeric excesses using exchangeable deuterons in alcohols. This is performed in a trivial way at low temperature (260-270 K) where a slow exchange regime was reached. Among the various alcohols used to explore the possibilities of this technique, an unusually large isotopic effect on molecular orientation between two isotopomers has been observed.

Enantiodifferentiation of promethazine using (S)-(−)-BINOL as the NMR chiral solvating agent: determination of the enantiomeric purity and performance comparison with traditional chiral HPLC

“…The four different tactics that are mainly employed during NMR measurements include utilization of chiral derivatization agents (CDA), 25 lanthanide shift reagents (LSR), 26 chiral solvating agents (CSA), 27 and chiral ordering agents (COAs). 28 Although several chromatographic approaches for the chiral analysis of promethazine have been already reported, 29 no information on the application of NMR as a chiral technique for this drug can be found in the literature. This is likely due to its low affinity with chiral lanthanide compounds, and the lack of functional groups capable of reacting with Mosher-like reagents.…”

Determination of the Enantiomeric Purity of the Antiasthmatic Drug Montelukast by Means of 1H NMR Spectroscopy

“…In other words, we needed to implement an NMR technique for a responsive monitoring of the “in‐process” samples coming from the synthetic laboratories and pilot plant batches. Thus, among the current arsenal of NMR chiral reagents capable of discriminating between enantiomers in solution (chiral solvating agents (CSAs), chiral derivatizing agents (CDAs), and chiral ordering agents (COAs)), we chose the use of CSAs mainly in view of their availability and ease of sample preparation, since they act through the formation of diastereomeric complexes in solution, with no need for chemical derivatizations or tedious sample conditioning. On the other hand, the use of well‐known chiral derivatization products like Mosher acid chloride or analogs would not be feasible in the case of montelukast, since the only nucleophile group of the molecule is a tertiary alcohol, which shows low reactivity towards electrophiles.…”

Multinuclear NMR in polypeptide liquid crystals: Three fertile decades of methodological developments and analytical challenges

“…Thus satisfactory enantio-separations are obtained at 260 K with PBLG system (see Fig. 31, where the spectrum of racemic [O-2 H]-1phenylethanol is presented at different temperatures) [238].…”

“…Provided this precaution is taken, 2 H-{ 1 H} NMR spectra obtained in this manner are very similar to those where the H/D exchange is made prior to the anisotropic NMR sample preparation, but additionally to the HOD signals, the quadrupolar doublet of MeOD is also visible when the latter is used. [238].…”