APPLICATION OF 2-DIMENSIONAL C-13 SOLID-STATE NMR TO THE STUDY OF CONFORMATIONAL POLYMORPHISM

Two-dimensional C-13 solid-state nuclear magnetic resonance (2D SSNMR) spectroscopy was applied to the study of three conformational polymor phs of 5-methyl-2- [(2-nitrophenyl)amino]-3-thiophenecarbonitrile. The separation of sidebands by order experiment (de Lacroix, S. F.; Titma n, J. J.; Hagemeyer; A.; Spiess, H. W. J. Magn. Reson. 1992, 97, 435-4 43) allowed the separation of isotropic and anisotropic chemical shift information over two dimensions, making it possible to distinguish in dividual carbon atoms and analyze the full chemical shift anisotropy p atterns using magic angle spinning (MAS) at moderate spinning speeds. The C-3 carbon of the thiophene ring, alpha 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 the oretically predicted isotropic and anisotropic chemical shifts for thi s carbon site. The results summarized in this paper demonstrate the ut ility in using 2D SSNMR methods for studying polymorphism in crystalli ne compounds with moderate molecular weights.