Chemical shift

As a chemical shift ( English chemical shift ) is referred to in the NMR spectroscopy the relative distance of the center of a resonance line of the sample (frequency ) of the one arbitrarily chosen standard (frequency ) to which the chemical shift is assigned to the 0th The chemical shift, which is independent of the magnetic field strength of the spectrometer used, is specified in ppm and is calculated according to: ${\displaystyle \delta }$ ${\displaystyle \nu _{\mathrm {Probe} }}$ ${\displaystyle \nu _{\mathrm {ref} }}$

${\displaystyle \delta ={\frac {\nu _{\mathrm {Probe} }-\nu _{\mathrm {ref} }}{\nu _{\mathrm {ref} }}}}$

The cause of the chemical shift is the magnetic susceptibility of the electrons that surround the respective atomic nucleus . This leads to a partial shielding of the external magnetic field by the electrons. If the atom is part of a molecule , the electron density and thus the shielding effect is influenced by the neighboring atoms. On the whole, the more electronegative the neighboring atoms, the weaker the shielding effect . The chemical shift can therefore be used to identify individual substituents or functional groups in an NMR spectrum . The chemical shift of a group can be estimated using the Shoolery rule . Exact values ​​always depend on the solvent used, especially in polar solvents or concentrated solutions / substance, there are sometimes strong deviations.

The resonance lines of TMS ( tetramethylsilane = (CH ₃ ) ₄ Si) are normally used as the standard for ¹ H and ¹³ C NMR spectroscopy in organic solvents . Since the silicon atom in TMS has an electropositive character, i.e. the TMS reference lines show an above-average shielding effect, the spectra of most molecules are positive , but negative values ​​are also possible. In aqueous solutions in which TMS is insoluble, the water-soluble derivatives DSS (sodium salt of 2,2-dimethyl-2-silapentane-5-sulfonic acid) or TSP ( sodium salt of 3- (trimethylsilyl) propionic acid ) are used instead. ${\displaystyle \delta }$

In the older literature, the τ (tau) scale was sometimes still used, in which the reference signal from TMS is 10 ppm. This scale is no longer in use today. A conversion to the δ scale is easily possible: δ = 10 ppm - τ.

Because of the electron density distribution along chemical bonds, CS shows strong spatial anisotropy in molecules. However, this only appears in measurements on solids, since it is averaged out in solution by the rapid Brownian molecular movement on the NMR time scale. Spectra of insoluble compounds e.g. B. can be won with the help of Magic Angle Spinning .

In ¹ H and ¹³ C NMR spectroscopy, the standard TMS is often no longer added to the sample itself, but the evaluation is carried out relative to the known shift in the solvent signal (residual protons) compared to TMS (see internal referencing).

Referencing methods

In practice, several methods can be used to correctly reference chemical shifts during or after an NMR experiment . These can be divided into indirect and direct referencing methods. Indirect referencing uses a different channel than the one of interest for correct adjustment of the ppm scale. Modern NMR spectrometers routinely adjust the scale of other nuclei by indirect referencing with the aid of the solvent signal, more precisely with its deuterium signal. Both indirect and direct referencing can be carried out using various methods defined by IUPAC :

1. Internal referencing , whereby the reference substance is added directly to the system to be analyzed. Example: Chloroform- d with 1% TMS, whereby the ¹ H-TMS signal is set to 0 ppm by definition. As mentioned above, internal referencing is common practice in ¹ H and ¹³ C-NMR spectroscopy , since the signals of the solvent used are adjusted to the correct shift using calibrated referencing tables. A possible problem with internal referencing arises if the solvent itself is not used as a reference substance. In this case, the sample is contaminated with a reference substance, which can affect the chemical shifts.
2. External referencing , whereby the sample and the reference substance are in two separate coaxial cylindrical vessels. With this method, the reference signal is also present in the spectrum to be analyzed, although the reference compound and the analyte are in different vessels. This contamination-free type of referencing is mainly used in biomolecular (aqueous) systems. If the reference substance and the analyte are dissolved in different media, mathematical correction calculations must be carried out afterwards in order to correct the different magnetic susceptibility of the media. This considerably reduces the suitability for everyday use of this procedure.
3. Substitution method: the sample and the reference substance are prepared in different NMR tubes and their NMR spectra are measured separately (successively). Similar to external referencing, this method enables contamination-free referencing. If field / frequeny lock is used by means of the ² H signal of the deuterated solvent and the solvent of the sample and the reference are the same, this method is uncomplicated. If, on the other hand, different solvents are used for the sample and reference substance, correction calculations must be carried out with regard to different magnetic susceptibility . If non-deuterated solvents are used and field / frequency locking is therefore not possible, shimming the magnet between the analyte and reference sample must be strictly avoided, as this changes the magnetic field (and thus influences the chemical shift).

Modern NMR spectrometers use the absolute scale ( IUPAC recommendations from 2001 and 2008), which defines the ¹ H-TMS signal as 0 ppm in the proton NMR spectrum and expresses the frequencies of all other nuclei as a percentage of the TMS resonance frequency:

${\displaystyle \Xi [\%]=100(\nu _{X}^{obs}/\nu _{TMS}^{obs})}$

The above-mentioned use of the deuterium (lock) channel, i.e. the ² H solvent signal in combination with the Ξ value of the absolute scale, is a form of internal referencing. This is particularly useful in heteronuclear NMR spectroscopy , since the local reference substances are not always available or easily measurable (e.g. liquid NH ₃ as 0 ppm for ¹⁵ N NMR spectroscopy ).

Criticism of lock-based internal referencing

Lock-based internal referencing, however, also harbors dangers, as it is based on a spectrometer-internal solvent table that contains the ² H shifts of all solvents. These ² H-shifts can be inaccurately determined and error-prone - this corresponds to a solvent- specific systematic error which is transferred to the heteronuclear scale. The Ξ values ​​of the individual nuclei made available by IUPAC can also be error-prone and represent a further potential source of error. A recently published study showed that lock-based internal referencing by means of ¹⁹ F-Ξ value for ¹⁹ F-NMR spectroscopy leads to larger errors in chemical shift. These can easily be avoided by internal referencing using calibrated reference connections.

literature

Robin K. Harris, Edwin D. Becker, Sonia M. Cabral De Menezes, Robin Goodfellow, Pierre Granger: NMR Nomenclature. Nuclear Spin Properties and Conventions for Chemical Shifts . In: Pure and Applied Chemistry . tape 73 , 2001, pp. 1795-1818 , doi : 10.1351 / pac200173111795 .

Web links

Directory of databases and reference works of chemical shifts

Individual evidence

1. ↑ Joseph B. Lambert, Scott Gronert, Herbert F. Shurvell, David A. Lightner: Spectroscopy - structure clarification in organic chemistry . 2nd Edition. Pearson Germany, Munich 2012, ISBN 978-3-86894-146-3 , pp. 75-131 .
2. ↑ ^{a b c d e f g h i j} Robin K. Harris, Edwin D. Becker, Cabral de Menezes, Sonia M, Robin Goodfellow: NMR nomenclature. Nuclear spin properties and conventions for chemical shifts (IUPAC Recommendations 2001) . In: Pure and Applied Chemistry . tape 73 , no. 11 , 2001, ISSN  0033-4545 , p. 1795–1818 , doi : 10.1351 / pac200173111795 ( iupac.org [accessed June 15, 2018]).
3. ^ Hugo E. Gottlieb, Vadim Kotlyar, Abraham Nudelman: NMR Chemical Shifts of Common Laboratory Solvents as Trace Impurities . In: The Journal of Organic Chemistry . tape 62 , no. October 21 , 1997, p. 7512-7515 , doi : 10.1021 / jo971176v .
4. ↑ Gregory R. Fulmer, Alexander JM Miller, Nathaniel H. Sherden, Hugo E. Gottlieb, Abraham Nudelman: NMR Chemical Shifts of Trace Impurities: Common Laboratory Solvents, Organics, and Gases in Deuterated Solvents Relevant to the Organometallic Chemist . In: Organometallics . tape 29 , no. 9 , May 10, 2010, p. 2176-2179 , doi : 10.1021 / om100106e .
5. ↑ Holzgrabe, U. (Ulrike), Wawer, I. (Iwona), Diehl, B. (Bernd): NMR spectroscopy in pharmaceutical analysis . Elsevier, Oxford 2008, ISBN 978-0-444-53173-5 ( elsevier.com ).
6. ↑ ^{a b c d} Robin K. Harris, Edwin D. Becker, Cabral de Menezes, Sonia M, Pierre Granger: Further conventions for NMR shielding and chemical shifts (IUPAC Recommendations 2008) . In: Pure and Applied Chemistry . tape 80 , no. 1 , 2008, ISSN  0033-4545 , p. 59-84 , doi : 10.1351 / pac200880010059 ( iupac.org [accessed June 15, 2018]).
7. ↑ ^{a b c d e} Carl Philipp Rosenau, Benson J. Jelier, Alvar D. Gossert, Antonio Togni: Fluorine NMR spectroscopy recalibrated . In: Angewandte Chemie . May 16, 2018, doi : 10.1002 / anie.201802620 .
8. ^ ^{A b c d e} Carl Philipp Rosenau, Benson J. Jelier, Alvar D. Gossert, Antonio Togni: Exposing the Origins of Irreproducibility in Fluorine NMR Spectroscopy . In: Angewandte Chemie International Edition . May 16, 2018, doi : 10.1002 / anie.201802620 .