Trimesic acid as a building block for ternary and quaternary Salts and salt cocrystals

In the field of cocrystals, the synthon-based design of two-component crystals is well established and the interest is now shifting toward higher order cocrystals as the next challenge. Carboxylic acids form a robust synthon with pyridyl coformers and interact with 2-aminopyrimidines through a pair of strong, charge-assisted hydrogen bonds. In this work we describe the formation of higher order salts and salt cocrystals of trimesic acid using 2,4- diaminopyrimidine (pyrimethamine, trimethoprim) and pyridyl (4,4′-bipyridine, 1,2-di(4-pyridyl)ethylene, 1,3-di(4-pyridyl)propane, 4-phenylpyridine) coformers. We report the single crystal structures of five binary, eight ternary and three quaternary systems with the compositions AB, A2B, A3B, A2BC, A3BC, A2BC1.5, ABC1.5, A1 2A2 B, ABC1 C,2 A2BC1 C2 0.5, and A1 A2 BC where A is a 2,4- diaminopyrimidine cation, B is the mono-, di- or trianion of trimesic acid and C is a pyridine. We also show that the ternary and quaternary salts and salt cocrystals can be prepared in bulk quantities by liquid-assisted grinding