Structural similarity and similarity in thermal properties of the polymorphs: melting and crystallization from the melt of tolbutamide and chlorpropamide

The polymorphism of tolbutamide and chlorpropamide under melting/crystallization was investigated with using DSC and in situ X-ray powder diffraction. The asymmetry in thermal transformations was revealed for both substances. Under heating, all tolbutamide/chlorpropamide polymorphs transform into high-temperature I-H/epsilon polymorph, which melts at 128 degrees C. The crystal structures of the high-temperature polymorphs, I-H and epsilon, are very similar to each other in the unit cell parameters and in the arrangement of z-shaped infinite hydrogen-bonded ribbons. Under cooling, other polymorph crystallizes from the melt, V for tolbutamide and beta for chlorpropamide, thus making easy the obtaining of these metastable polymorphs. The polymorphs of tolbutamide and chlorpropamide crystallized from their melts turned out to be also very similar to each other in their structures (space group, unit cell parameters, arrangement of pi-shaped infinite hydrogen-bonded ribbons). Solid-solid transformation V II in tolbutamide was detected both in samples stored under room conditions and those melted in capillaries, thus providing new easy way for II tolbutamide crystallization. In generalizing our results, one can expect that if evident similarity is found among the polymorphs of similar molecules in their crystal structure, the similarity in their thermal properties can be also found, and vice versa.