Structural Determination of a Novel Polymorph of Sulfathiazole?Oxalic Acid Complex in Powder Form by Solid-State NMR Spectroscopy on the Basis of Crystallographic Structure of Another Polymorph

摘要

Two polymorphic forms of a sulfathiazole (STZ):oxalic acid (OXA) 1:1 complex were successfully prepared by different cogrinding methods and characterized by multiple analytical techniques. Rod-milled and ball-milled ground mixtures had different powder X-ray diffraction patterns, showing polymorph formation of the STZ-OXA complex (complex A and complex B). The heat of fusion from differential scanning calorimetry curves and terahertz timedomain spectra helped differentiating the polymorphs. According to infrared spectra, ~(13)C NMR chemical shifts, and the relative intensities of ~(15)N NMR peaks, both polymorphs were salts where the proton of a ?COOH group in OXA was transferred to a ?NH_2 group in STZ. High-resolution 1H NMR and ~1H?~(13)C heteronuclear correlation NMR spectra indicated that complex B in powder form had a cocrystal type structure compared to complex A having a clathrate-type structure. Complex B structure suggested by solid-state NMR coincided well with the experimentally determined one, which was formed from three layers of thiazole rings, benzene rings, and OXAs, by using single-crystal X-ray diffraction (SC-XRD) measurement. Advanced solid-state NMR spectroscopy measurements was useful to elucidate the structure of a polymorph, for which SC-XRD data are not available, by referring to the SC-XRD data of another polymorph.