Chalcogen-bonded cocrystals and salt cocrystals via automated resonant acoustic mixing with a button operative bot†

Mechanochemical approaches to the preparation of chalcogen-bonded cocrystals have not been systematically well-studied. We report here the preparation of six cocrystals and salt cocrystals of chalcogen bond (ChB) donor 3,4-dicyano-1,2,5-telluradiazole using resonant acoustic mixing (RAM). The ChB acceptors employed are tetraphenylphosphonium chloride, tetraphenylphosphonium bromide, 4-methoxypyridine N-oxide, 4-phenylpyridine N-oxide, tetrabutylammonium bromide, and tetrabutylammonium iodide. Acceptor atoms include Cl, Br, I, and O. In all six cases, RAM reproduces the known crystal forms of the ChB products as assessed by powder X-ray diffraction and FTIR spectroscopy. The role of liquid additives is also assessed. The success of RAM in generating ChB products in pure form contrasts with previous efforts to use ball milling for this purpose. We show that ball milling pure 3,4-dicyano-1,2,5-telluradiazole using standard instrumental settings results in amorphization and decomposition in five minutes or less, thereby highlighting the difficulties of using ball milling to generate ChB cocrystals. The design, construction, and implementation of a button operative bot (BOB) to help automate RAM experiments is also described herein. Overall, these results suggest that RAM offers a suitably gentle and tailorable mechanochemical approach for generating known and novel cocrystals.