Single-crystal to single-crystal conformational polymorphic transformation in tolbutamide at 313 K. Relation to other polymorphic transformations in tolbutamide and chlorpropamide

Three polymorphs of tolbutamide (I-L, II, and III) were studied using single-crystal X-ray diffraction, from 100 K to room temperature (forms II and III) and to 350 K (form I), and differential scanning calorimetry. The reversible transformation, I-L double left right arrow I-H, was found to be of the single-crystal to single-crystal type and the structure of the high-temperature form (I-H) was solved and refined. The structure of I-H differs from that of I-L only in the conformation of the molecule, with molecular arrangements being practically unchanged (isostructural conformational transformation). The transition takes place at 313 K with no sign of hysteresis. The volume change, Delta V/V, across the reversible transformation I-L double left right arrow I-H was calculated and compared to those for the other conformational transformations. Two types of conformational polymorphic transformations (irreversible reconstructive and reversible isostructural) in tolbutamide and chlorpropamide were compared.