NMR characterization of impurities

Abstract

The chapter discusses the nuclear magnetic resonance (NMR) characterization of impurities. The ability of NMR to provide information regarding the specific bonding structure and stereochemistry within a molecule has created broad applicability across several subjects. NMR provides a powerful analytical tool for structural elucidations. The single most important piece of non-NMR data used by the NMR spectroscopist is the total molecular mass. The nondestructive, noninvasive nature of NMR spectroscopy makes it a valuable tool for the characterization of low-level impurities and degradants. NMR can be considered close to a “universal detector” for hydrogen and carbon, as well as for other magnetically active nuclei. The general characterization strategy for NMR is presented schematically. Deuterated solvents are used in NMR for two reasons. First, deuterium provides a signal on which to lock the spectrometer frequency, thus enhancing long-term stability. Second, it dramatically reduces the protonsignal that arises from the solvent, which would otherwise overwhelm the signal of the target compound. Clean glassware is essential for characterization of low-level impurities and degradants. The high-performance liquid chromatography (HPLC) system contains various components: degasser, binary or quaternary pump, ultraviolet detector, auto or manual injector, column oven, and loop collection. The most basic NMR experiment is the one-pulse proton experiment.