SOLID-STATE INVESTIGATION OF THE TAUTOMERISM OF ACETOHEXAMIDE

Polymorphism of the anti-diabetic drug acetohexamide has been investig ated by numerous techniques. On the basis of Fourier-transform infrare d (FT-IR) data, one of the most common forms, form A, has been propose d to exist in the enol-tautomeric state, whereas form B has been propo sed to be in the keto-tautomeric state. The following article examines the solid-stale tautomerism of acetohexamide using the techniques of X-ray crystallography and C-13 solid-state nuclear magnetic resonance (NMR) spectroscopy. In the NMR spectra, resonances associated with the acetyl carbonyl and amide carbonyl groups are well resolved. By compa rison of the spectra of acetohexamide with those of the related compou nds chlorpropamide and tolbutamide, whose crystallographic structures have been determined, it is firmly established that both of the acetoh examide polymorphic forms are in the keto-form. The crystal structure of acetohexamide form A was solved and is reported herein. The structu re not only shows the keto-tautomeric state of form A, but also confir ms the NMR resonance assignments. (C) 1997 Elsevier Science B.V.