On the Use of Strong Proton Donors as a Tool for Overcoming Line Broadening in NMR: A Comment.

Overcoming line broadening of labile protons and achieving high-resolution NMR spectra is crucial for the structural and conformational analysis of organic molecules. Recently, Ma et al. (Magn. Reson. Chem. 2024, 62, 198-207) demonstrated the effectiveness of 2,2,2-trifluoroacetic acid (TFA) in sharpening NMR signals for nitrogen-containing compounds which exhibit prototropic tautomerization or conformational isomerism using high molar ratio of [acids]/[solute] ~ 5 to 200. In this commentary, we provide an overview of earlier publications and highlight the extensive applications of TFA in enhancing NMR resolution across a variety of organic functional groups, with the use of very small ratios of [acids]/[solute] ~ 10 to 10. The prospects for the unequivocal structure analysis using labile protons as the starting point will be analyzed.