The Well-Characterized Synthetic Molecule:  A Role for Quantitative ¹H NMR

Abstract

Experimental evidence is reported to illustrate the role of quantitative 1H NMR in the analytical characterization of new synthetic molecules. This evidence includes comparison with results obtained for reference materials and for extensively characterized substances, precision data on a statistically significant set of different molecules, elemental analysis data. These data prove that 1H NMR estimates quantitative purity with a precision of about 1% and with a comparable or better accuracy. Moreover, many of the limitations that generally afflict other methods (variability of response factors, incomplete accounting for inorganic or volatiles) do not apply to the quantitative 1H NMR method, whose only requirement is the presence of at least one integrable signal in the spectrum. Because of the widespread usage of 1H NMR in modern synthetic chemistry, it is suggested that spectra are routinely run under quantitative conditions, with a corresponding reduction of other quantitative characterization tools (elemental analysis, HPLC, loss on drying and residue on ignition determination) and speed-up of the whole analytical process. For a budget-conscious laboratory either connected to a discovery environment or in the field of process chemistry, this could be a considerable economic advantage, without a compromise on quality.