19 F-NMR spectroscopy

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Fluorine nuclear magnetic resonance spectroscopy ( 19 F-NMR spectroscopy from English : nuclear magnetic resonance ) is a spectroscopic method for the characterization of fluorinated compounds. Their characteristic properties lie in their sensitivity and their great significance with regard to chemical shifts . It is used in organic , inorganic and pharmaceutical chemistry .

General information on 19 F-NMR spectroscopy

Fluorine is one of the pure elements and has only one natural isotope ( 19 F), which is characterized by the nuclear spin I = 1/2 and its high gyromagnetic ratio .

The 19 F-NMR scale covers a range of over 1300 ppm chemical shift. The local reference substance (0 ppm) is pure CFCl 3 or, more precisely, the isotopologous signal C 19 F ( 35 Cl 2 ) ( 37 Cl).

The large range of the 19 F-NMR scale does not have to be exhausted, because chemical shifts of organic molecules can already be found in smaller areas, such as for reagents at +50 - +10 ppm, for -57 - -59 ppm, for at −58 - −64 ppm and for at −90 - −170 ppm.

Due to its excellent sensitivity, the smallest changes have a strong effect on the chemical shift in fluorine NMR. The chemical shift is of particular importance in 19 F-NMR spectroscopy, as it contains more information about the chemical environment than in 1 H-NMR spectroscopy , in which coupling patterns represent the greatest source of information.

The 19 F nucleus is also suitable for 2D NMR spectroscopic methods such as HSQC , HMBC and NOESY .

Chemical shifts

Chemical shifts vary widely in the literature, even for simple compounds like fluorobenzene or trifluorotoluene . This can mainly be explained by ambiguities in the definitions regarding the reference compound CFCl 3 and the use of various, erroneous referencing methods .

The solvent has the greatest influence on 19 F-NMR chemical shifts with typical deviations of Δδ = ± 2 ppm or more.

Referencing methods

In 19 F-NMR spectroscopy, so-called internal referencing is often used, a reference substance with a known chemical shift being added to the analysis solution.

Typical reference compounds are CFCl 3 , C 6 H 5 F , PhCF 3 , C 6 F 6 and CF 3 CO 2 H , which are corrected for their correct shift relative to pure CFCl 3 after the measurement according to the solvent used. Using a referencing table, spectra are correctly adjusted:

Extract from the referencing table for 19 F-NMR spectroscopy
CFCl 3 C 6 H 5 F PhCF 3 C 6 F 6 CF 3 CO 2 H
solvent [ppm] [ppm] [ppm] [ppm] [ppm]
CDCl 3 0.65 −112.96 −62.61 −161.64 -75.39
CD 2 Cl 2 0.02 −113.78 −62.93 −162.61 −75.76
C 6 D 6 −0.19 −113.11 −62.74 −163.16 −75.87
Acetone- d 6 −1.09 −114.72 −63.22 −164.67 −76.87

Individual evidence

  1. ↑ Klaus Müller, Christoph Faeh, François Diederich: Fluorine in Pharmaceuticals: Looking Beyond Intuition . In: Science . tape 317 , no. 5846 , September 28, 2007, ISSN  0036-8075 , p. 1881–1886 , doi : 10.1126 / science.1131943 , PMID 17901324 ( sciencemag.org [accessed June 11, 2018]).
  2. ↑ a b c d e Mason, Joan: Multinuclear NMR . Springer US, Boston, MA 1987, ISBN 978-1-4613-1783-8 ( springer.com ).
  3. ^ A b Everett, Jeremy R., Harris, Robin K. (Robin Kingsley), Lindon, John C., Wilson, Ian D.,: NMR in pharmaceutical sciences . Chichester, West Sussex, UK 2015, ISBN 978-1-118-66024-9 ( wiley.com ).
  4. ↑ a b c 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 11, 2018]).
  5. ↑ a b c d e f g Carl Philipp Rosenau, Benson J. Jelier, Alvar D. Gossert, Antonio Togni: Fluorine NMR spectroscopy recalibrated . In: Angewandte Chemie . May 16, 2018, ISSN  0044-8249 , doi : 10.1002 / anie.201802620 ( wiley.com [accessed June 11, 2018]).
  6. ↑ a b c d e f g 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, ISSN  1433-7851 , doi : 10.1002 / anie.201802620 ( wiley.com [accessed June 11, 2018]).