An Examination of Factors Influencing Small Proton Chemical Shift Differences in Nitrogen-Substituted Monodeuterated Methyl Groups

Lynda Brown,Daniel O’Leary,Stuart Elliott,O Ogba

doi:10.3390/sym13091610

Lynda Brown, Daniel O’Leary + Show 2 more

Open Access

https://doi.org/10.3390/sym13091610

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Abstract

Monodeuterated methyl groups have previously been demonstrated to provide access to long-lived nuclear spin states. This is possible when the CH2D rotamers have sufficiently different populations and the local environment is chiral, which foments a non-negligible isotropic chemical shift difference between the two CH2D protons. In this article, the focus is on the N-CH2D group of N-CH2D-2-methylpiperidine and other suitable CH2D-piperidine derivatives. We used a combined experimental and computational approach to investigate how rotameric symmetry breaking leads to a 1H CH2D chemical shift difference that can subsequently be tuned by a variety of factors such as temperature, acidity and 2-substituted molecular groups.

Highlights

Symmetry 2021, 13, 1610. https://The decay of conventional magnetization in the majority of traditional solution-state nuclear magnetic resonance (NMR) experiments is limited by the longitudinal relaxation time constant T1
The proton chemical shift differences are averaged over all populated CH2 D rotamers, which results in a small CH2 D chemical shift difference ∆ν12 observable in the 1 H NMR spectrum, see Section 3
In the cases of N-CH2 D-2-methylpiperidine and N-CH2 D3-methylpiperidine, the lone pair of the adjacent nitrogen atom causes a significant perturbation to the conformational equilibria, as discussed above, and as a result; there is a clear non-uniformity in the CH2 D rotamer populations, i.e., rotameric symmetry breaking

Summary

Introduction

The decay of conventional magnetization in the majority of traditional solution-state nuclear magnetic resonance (NMR) experiments is limited by the longitudinal relaxation time constant T1. Synthesized a 13 C2 -labelled derivative of naphthalene with a small chemical shift difference between the 13 C nuclear sites by introducing tailored molecular groups on either side of the two naphthalene rings [20]. This molecule supports an LLS with a lifetime which exceeds 1 h in room-temperature solution [21]; (ii) Isotopic substitution. We employ a blend of experimental and computational methods to assess the symmetry-breaking requirements to forge an appreciable chemical shift difference between the CH2 D protons in the monodeuterated methyl group of N-CH2 D-2methylpiperidine, which allows access to the CH2 D LLS. We further tailor the magnitude of the CH2 D proton chemical shift difference by several environmental influences such as temperature, acidity and nearby molecular groups

Symmetry Breaking

Illustrative Examples

The Role of Nitrogen

Environmental Influences

CH2 D LLS

Conclusions

Methods and Modest