Salt/Co-Crystal Discrimination Made Easy by 17O Solid-State NMR

A ¹⁷O solid-state NMR method for salt/co-crystal discrimination in binary compounds of carboxylic acids is presented. The method incorporates a quick and relatively inexpensive labelling protocol for mechanochemical ¹⁷O enrichment of the carboxyl oxygen positions, as previously described by Metro et al. Angew. Chem. 2017, 56, 6803, followed by a visual interpretation of the recorded ¹⁷O solid-state magic-angle spinning (MAS) NMR spectra in terms of the nature of the enriched oxygen sites in the prepared binary compound. Care must be taken where variable-temperature changes in the ¹⁷O MAS spectra are observed. Nevertheless, we observe that, at low temperatures, the averaging effect of chemical exchange of the carboxyl/carboxylate moieties can be avoided and two well separated ¹⁷O lines are obtained for a carboxylic acid, whereas the almost equivalent carboxylate oxygen sites give rise to a single NMR signal. The method is illustrated in two cases, one in which salts can be identified also from their ¹H solid-state NMR spectra by the absence of high ppm resonances due to hydrogen bonding, and another one, the more general case of organic crystals with multiple hydrogen bonding, where only ¹⁷O solid-state NMR spectra can be employed for salt/co-crystal discrimination. A quantitative analysis of ¹⁷O solid-state NMR spectral parameters can provide useful information in structural studies by NMR crystallography approaches.