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

Abstract A 17 O 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 17 O 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 17 O 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 17 O 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 17 O 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 1 H 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 17 O solid‐state NMR spectra can be employed for salt/co‐crystal discrimination. A quantitative analysis of 17 O solid‐state NMR spectral parameters can provide useful information in structural studies by NMR crystallography approaches.