Trimesic Acid as a Building Block for Ternary and\nQuaternary Salts and Salt Cocrystals

In the field of cocrystals,\nthe synthon-based design of two-component\ncrystals is well established and the interest is now shifting toward\nhigher order cocrystals as the next challenge. Carboxylic acids form\na robust synthon with pyridyl coformers and interact with 2-aminopyrimidines\nthrough a pair of strong, charge-assisted hydrogen bonds. In this\nwork we describe the formation of higher order salts and salt cocrystals\nof trimesic acid using 2,4-diaminopyrimidine (pyrimethamine, trimethoprim)\nand pyridyl (4,4′-bipyridine, 1,2-di(4-pyridyl)ethylene, 1,3-di(4-pyridyl)propane,\n4-phenylpyridine) coformers. We report the single crystal structures\nof five binary, eight ternary and three quaternary systems with the\ncompositions AB, A<sub>2</sub>B, A<sub>3</sub>B, A<sub>2</sub>BC,\nA<sub>3</sub>BC, A<sub>2</sub>BC<sub>1.5</sub>, ABC<sub>1.5</sub>,\nA<sup>1</sup><sub>2</sub>A<sup>2</sup>B, ABC<sup>1</sup>C,<sup>2</sup> A<sub>2</sub>BC<sup>1</sup>C<sup>2</sup><sub>0.5</sub>, and A<sup>1</sup>A<sup>2</sup>BC where A is a 2,4-diaminopyrimidine cation,\nB is the mono-, di- or trianion of trimesic acid and C is a pyridine.\nWe also show that the ternary and quaternary salts and salt cocrystals\ncan be prepared in bulk quantities by liquid-assisted grinding.