¹³C CP MAS NMR of halogenated (Cl, Br, I) pharmaceuticals at ultrahigh magnetic fields

Abstract

This work reports significantly improved spectral resolution of (13)C CP MAS NMR spectra of chlorinated, brominated and iodinated solid organic compounds when such spectra are recorded at ultrahigh magnetic field strengths. The cause of this is the residual dipolar coupling between carbon atoms and quadrupolar halogen nuclides (chlorine-35/37, bromine-79/81 or iodine-127), an effect inversely proportional to the magnetic field strength which declines in importance markedly at 21.1 T as compared to lower fields. In favorable cases, the fine structure observed can be used for spectral assignment, e.g. for Cl-substituted aromatics where the substituted carbon as well as the ortho-carbons show distinct doublets. The experimental results presented are supported by theoretical modeling and calculations. The improved spectral resolution in the studied systems and similar halogenated materials will be of particular interest and importance for polymorph identification, drug discovery and quality control in the pharmaceutical industry.

Direct Investigation of Covalently Bound Chlorine in Organic Compounds by Solid‐State 35Cl NMR Spectroscopy and Exact Spectral Line‐Shape Simulations

“…The bonding environments for these types of chlorine atoms are substantially different from the environments in those chloride-containing molecules that have been studied previously 2, 3. A partial 35 Cl NMR spectrum for hexachlorophene has been briefly mentioned in the literature 4. On the other hand, most of the interesting chlorine chemistry occurs when Cl is covalently bound to a carbon atom, where the chlorine atom often acts as a leaving group.…”

Direct Investigation of Covalently Bound Chlorine in Organic Compounds by Solid‐State 35Cl NMR Spectroscopy and Exact Spectral Line‐Shape Simulations

“…[2, 3] A partial 35 Cl NMR spectrum for hexachlorophene has been briefly mentioned in the literature. [4] On the other hand, most of the interesting chlorine chemistry occurs when Cl is covalently bound to a carbon atom, where the chlorine atom often acts as a leaving group. Chlorine atoms are also important in many organic pharmaceuticals as well as in crystal design applications where they can form halogen bonds.…”

“…All chlorine atoms bound to CH 2 carbon atoms have isotropic chemical shift (d iso ) values ranging from 150 to 200 ppm, whereas those bound to aromatic rings had d iso values on the order of 300 to 350 ppm (Table 1). Moreover, as has been explained using Townes-Dailey theory, [11] the back donation of p-electron density from the chlorine atom into the p system of the aromatic rings creates an EFG different from zero that is perpendicular to the plane of the ring and that differs from the An asterisk is used to indicate a trace NaCl or NH 4 Cl impurity, whereas a cross marks a singularity from the satellite transition of the other chlorine isotope. The sharp lines on the high-frequency ends of the spectra are caused by radio interference.…”

New Experimental Insight into the Nature of Metal−Metal Bonds in Digallium Compounds: J Coupling between Quadrupolar Nuclei

“…Both spectra show some impurity peaks which may be attributed to unreacted intermediate product (see Figure and Figure S3 in the Supporting Information). Some splittings on the order of 100 Hz observed in the 13 C CP/MAS NMR spectra may also be attributed to through‐space residual dipolar coupling (RDC) between carbon atoms and the quadrupolar 127 I nuclei ( I =5/2) . (Supporting Information, Figure S…”

“…Some splittings on the order of 100 Hz observed in the 13 CC P/MAS NMR spectra may also be attributed to throughspace residual dipolar coupling (RDC) betweenc arbon atoms and the quadrupolar 127 Inuclei (I = 5/2). [25] (Supporting Information, Figure S3). The similarity between the 1 HD UMBO/MAS NMR spectra, and between the 13 CC P/MASN MR spectra,o ft he digallium compounds 2 and 3 indicates ac omparable degree of overall crystallinity.A dditionally,adecreased presence of impurities in 2 and 3 is noted.…”