Crystal Forms of the Antibiotic 4-Aminosalicylic Acid: Solvates and Molecular Salts with Dioxane, Morpholine, and Piperazine

Reaction of the antibiotic 4-aminosalicylic acid with 6-membered ring compounds, such as dioxane, morpholine, and piperazine, yielded a solvate and three molecular salts. The new crystal forms were obtained using different crystallization techniques, such as grinding/kneading and solution techniques; interestingly, reaction with piperazine yields products with different stoichiometry, depending on the preparation conditions, i.e. solid-state or solution methods. All solid products were characterized by single-crystal X-ray diffraction; thermal stability was evaluated by variable temperature X-ray powder diffraction (VT-XRPD), calorimetric techniques (DSC and TGA), and hot-stage microscopy (HSM). Supramolecular interactions are discussed and compared with those in other similar crystal forms.