Viscosity-enhanced spectroscopY combined with dynamic NMR for atropisomers analysis of synthetic (−)-cannabidiol derivatives

Mixture analysis by NMR is a topic that is nearly as old as NMR itself and for which only a few solutions have been proposed, such as LC-NMR hyphenation, diffusion-ordered spectroscopy (DOSY), assisted or not by matrix effect, multiquantum spectroscopy combined (or not) with broadband homonuclear decoupling, sparse sampling, ultrafast data acquisition, multiplet selective excitation, or tensor decomposition methods.

The recent use of viscous solvents has provided an exciting approach called ViscY (Viscosity-enhanced spectroscopY) for studying mixtures by lowering the molecular tumbling rate in solution [1], [2], [3], [4]. As a result, the molecules display a negative nOe regime, and their resonances can be sorted according to their ability to exchange magnetisation through intramolecular spin diffusion. The 2D 1H-1H NOESY spectrum of a mixture reveals correlations between all 1H resonances of each analyte when recorded in spin diffusion conditions, thus giving access to individual 1H NMR spectra of the mixture components.

Dynamic NMR is suitable to characterise atropisomerism, associated principally with single bonds that join a pair of hindered planar groups. The kinetic/activation parameters of the chemical exchange process resulting from barrier to rotation are accessible [5]. To date, conformational control about C(sp2)-C(sp3) single bonds remains unexplored because restricted rotation around such bonds is extremely rare.

We have first combined the spin diffusion phenomenon with dynamic NMR to reach the same time, the structure elucidation, and the determination of kinetic/activation parameters of the restriction rotation about Aryl-C(sp3) bond of synthesised (−)-cannabidiol derivatives (see [Fig. 1]), using the viscous binary solvent DMSO-d6/water.

Fig. 1 Structure of (−)-Cannabidiol and their synthetic derivatives.

 

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• References

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Publication History

Article published online:
12 December 2022