Tautomeric preference in polymorphs and pseudopolymorphs of succinylsulfathiazole: fast evaporation screening and thermal studies

摘要

Succinylsulfathiazole (SST) is known to exist in seven different crystalline forms, namely two unsolvated polymorphic forms (SST-I, SST-II), a monohydrate (SST/H2O), dihydrate (SST/2H(2)O) and solvates of butanol (SST/But), pentanol (SST/Pnt) and dioxane (SST/Diox). Most of these forms have been characterised only by IR and PXRD, while the single crystal structures have been determined for SST/But, SST/Pnt, SST/H2O and SST/Diox solvates. Previous studies also noted a lack of reproducibility in preparation of these different forms. Here, we employed a fast evaporation (FE) crystallization method and identified two new solvates from acetone (SST/AcMe) and tetrahydrofuran (SST/THF), as well as determined the single crystal structures for SST-I, SST-II, SST/AcMe and SST/THF. This revealed that SST exclusively adopts the imidine tautomeric form in all its solid form structures, but never the amidine form. The succinyl group of SST shows a conformational flexibility and adopts either anti-or syn-geometry to facilitate hydrogen bonding in the different structures. The study also allowed us to rationalize the hydrogen bonding preferences of various functional groups in all the forms. Notably the neat grinding and liquid assisted grinding methods resulted in only SST/H2O from various solvents, while the FE method produced polymorphs or pseudopolymorphs from different solvents.