On the Use of Deuterated Organic Solvents without TMS to Report 1H/13C NMR Spectral Data of Organic Compounds: Current State of the Method, Its Pitfalls and Benefits, and Related Issues

Abstract

The quite popular, simple but imperfect method of referencing NMR spectra to residual ¹H and ¹³C signals of TMS-free deuterated organic solvents (referred to as Method A) is critically discussed for six commonly used NMR solvents with respect to their δ_H and δ_C values that exist in the literature. Taking into account the most reliable data, it was possible to recommend 'best' δ_X values for such secondary internal standards. The position of these reference points on the δ scale strongly depends on the concentration and type of analyte under study and the solvent medium used. For some solvents, chemically induced shifts (CISs) of residual ¹H lines were considered, also taking into account the formation of 1:1 molecular complexes (for CDCl₃). Typical potential errors that can occur as a result of improper application of Method A are considered in detail. An overview of all found δ_X values adopted by users of this method revealed a discrepancy of up to 1.9 ppm in δ_C reported for CDCl₃, most likely caused by the CIS mentioned above. The drawbacks of Method A are discussed in relation to the classical use of an internal standard (Method B), two 'instrumental' schemes in which Method A is often implicitly applied, that is, the default Method C using ²H lock frequencies and Method D based on Ξ values, recommended by the IUPAC but only occasionally used for ¹H/¹³C spectra, and external referencing (Method E). Analysis of current needs and opportunities for NMR spectrometers led to the conclusion that, for the most accurate application of Method A, it is necessary to (a) use dilute solutions in a single NMR solvent and (b) to report δ_X data applied for the reference ¹H/¹³C signals to the nearest 0.001/0.01 ppm to ensure the precise characterization of new synthesized or isolated organic systems, especially those with complex or unexpected structures. However, the use of TMS in Method B is strongly recommended in all such cases.

Keywords: GIAO-DFT-NMR; MestReNova; NMR spectroscopy; deuterated solvent signals; internal reference standards; residual 1H signals; tetramethylsilane; the IUPAC unified Ξ scale of chemical shifts.