Application of Two-Dimensional ¹³C Solid-State NMR to the Study of Conformational Polymorphism

Abstract

Two-dimensional 13C solid-state nuclear magnetic resonance (2D SSNMR) spectroscopy was applied to the study of three conformational polymorphs of 5-methyl-2-[(2-nitrophenyl)amino]-3-thiophenecarbonitrile. The separation of sidebands by order experiment (de Lacroix, S. F.; Titman, J. J.; Hagemeyer; A.; Spiess, H. W. J. Magn. Reson. 1992, 97, 435−443) allowed the separation of isotropic and anisotropic chemical shift information over two dimensions, making it possible to distinguish individual carbon atoms and analyze the full chemical shift anisotropy patterns using magic angle spinning (MAS) at moderate spinning speeds. The C-3 carbon of the thiophene ring, α to the nitrile carbon, was chosen to probe the differences in chemical environment between forms. The three forms exhibited a large variation in both measured and theoretically predicted isotropic and anisotropic chemical shifts for this carbon site. The results summarized in this paper demonstrate the utility in using 2D SSNMR methods for studying polymorphism in crystalline compounds with moderate molecular weights.