Cocrystals "Divorce and Marriage": When a Binary System Meets an Active Multifunctional Synthon in a Ball Mill. Issue 58 (11th September 2020)

• Record Type: Journal Article
• Authors: Dudek, Marta K.; Śniechowska, Justyna; Wróblewska, Aneta; Kaźmierski, Sławomir; Potrzebowski, Marek J.
• Is Part Of: Chemistry. Volume 26:Issue 58(2020)
• Page Start: 13264
• Page End: 13273
• Publication Date: 2020-09-11
• Subjects: barbituric acid -- cocrystals -- hydroxydimethylimidazole oxide -- mechanochemistry -- solid-state NMR spectroscopy -- thiobarbituric acid; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.202002238
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: A well‐defined and stable "AB" binary system in the presence of "C" a crystalline synthon ground in a ball mill undergoes selective transformation in the solid state according to the equation AB+C→AC+B. When the amount of C is increased two times then the equation AB+2C→AC+BC is valid. The other variants are more complex. The pathway BC+A is allowed and leads to the AC and B products. The pathway AC+B is not preferred, and no transformation is observed. These non‐obvious correlations were observed for cocrystal of barbituric acid (BA):thiobarbituric acid (TBA) recently reported by Shemchuk et al. ( Chem. Commun . 2016, 52, 11815–11818) in the presence of 1‐hydroxy‐4, 5‐dimethyl‐imidazole 3‐oxide (HIMO). This synthon shows high affinity for the BA0.5 TBA0.5 cocrystal as well for its individual components, BA and TBA. Single‐quantum, double‐quantum (SQ‐DQ) 2D 1 H very fast MAS NMR with a spinning rate of 60 kHz was employed as a basic and most diagnostic tool for the study of cocrystals transformations. Analysis of the experimental data was supported by theoretical calculations, including computation of the stabilization energy, E stab, defined as the energy difference between the energy of a co‐crystal and the sum of the energies of particular components in the respective stoichiometric ratios. Two mechanisms of synthon replacement have been proposed. Pathway 1 assumes a concerted mechanism of substitution. In this approach, synthon attack is synchronized in time with the departure of one of the components of the binary system. Pathway 2 implies a non‐concerted process, with an intermediate stage in which three separate components are present. Evidence suggesting a preference for Pathway 2 is shown. Abstract : In concert… or not : Monitoring the processes that occur while grinding a stable cocrystal of barbituric acid:thiobarbituric acid with an imidazol‐ N ‐oxide derivative in a ball mill reveals surprising synthon preferences and indicates the mechanism of synthon substitution.