1H J-Resolved Spectroscopy to Evaluate 1H-1H and 1H-19F Coupling Constants

2D ¹H J-RESolved spectroscopy (JRES) is able to separate the ¹H chemical shift and J coupling interactions in the F2 and F1 domains of the 2D data, respectively. The F2 projection represents the pure-shift ¹H decoupled ¹H NMR spectrum while the individual F1 slices at each chemical shift reveal the ¹H - ¹H J coupling for each resonance.  When this technique is applied to a spin system with both homonuclear ¹H-¹H coupling and heteronuclear coupling, it has the ability to provide both the homonuclear and heteronuclear coupling constants.  This is demonstrated in the figure below for 2,3-difluoro pyridine which has both ¹H-¹H and ¹H-¹⁹F coupling.

The top trace in the figure is the ¹H NMR spectrum showing the complex resonances due to both the homonuclear and heteronuclear coupling.  The 2D JRES spectrum is highlighted in grey.  The ¹H-¹H coupling is shown in the F1 slices which were summed to produce the blue, red and green vertical traces in the figure for ¹H resonances A, C and B, respectively.  These traces are identical to the resonances in the separately collected ¹H spectrum with ¹⁹F decoupling shown in the bottom trace of the figure.  The F2 projection of the JRES spectrum is shown in the trace directly on top of the 2D spectrum, colour coded in yellow.  The F2 projection represents the ¹H decoupled ¹H spectrum showing only the ¹H- ¹⁹F coupling.  It can be compared to the separately collected PSYCHE pure-shift ¹H spectrum, colour coded in orange which is very nearly identical.  Clearly this very simple, often overlooked, technique can provide a great deal of both homonuclear and heteronuclear coupling information. 

The limitations of 19F GARP Decoupling

In a previous post, it was shown that distorted line shapes are obtained for resonances in broadband decoupled NMR spectra when the resonances of the decoupled nuclide are outside of the effective decoupling bandwidth.  This can be a particularly difficult problem when observing ¹H NMR spectra with ¹⁹F decoupling.  ¹⁹F has a large chemicals shift range so, if there are multiple widely spaced ¹⁹F resonances, it will be difficult or impossible to decouple all ¹⁹F sites at once, particularly at higher magnetic field strengths.  If one is not aware of this problem, data misinterpretation may be an issue as distorted line shapes will  lead incorrect splittings used to measure coupling constants.  The figure below illustrates this problem.  The top three panels of the figure show the 300 MHz ¹H[¹⁹F] NMR spectra for the three ¹H resonances of 1,2-difluoropyridine as a function of the ¹⁹F decoupler offset.  The GARP decoupling scheme was used with 90° pulses of 80 µsec.  The decoupler offsets, depicted in the bottom panel of the figure, were varied in 5 ppm increments.

Of the 11 decoupler offsets used, only offset 6 (at -116 ppm) effectively decoupled both ¹⁹F sites.  Varying the decoupler offset by only ± 5 ppm leads to distorted line shapes, which are particularly pronounced for the H₃ resonance.  These distorted line shapes could easily lead to data misinterpretation and erroneous coupling constants.  In this case, the ¹⁹F decoupling bandwidth is 55 ppm.  Since the chemical shift difference between the two  ¹⁹F resonances is 52 ppm, one is able to obtain a fully ¹⁹F decoupled ¹H spectrum with the careful choice of the decoupler offset frequency however, there will be cases where the decoupling bandwidth would not be sufficient to decouple all ¹⁹F resonances in some molecules.  How then can one generally evaluate all of the coupling constants in fluorine containing molecules?  The ¹⁹F-¹⁹F couplings can be evaluated in a ¹⁹F[¹H] spectrum (not shown).  Specific ¹H-¹⁹F coupling constants can be determined by measuring a ¹H PSYCHE spectrum or be collecting ¹H spectra with selective ¹⁹F continuous wave (CW) decoupling  for each of the¹⁹F resonances.  The latter is shown in the figure below.  The bottom panel shows a standard ¹H spectrum.  The middle two panels show the ¹H spectra for each of the ¹⁹F sites decoupled separately using CW decoupling.  The top panel shows the fully ¹⁹F decoupled spectrum.

Using these data, all of the coupling constants can be evaluated and are shown in the figure below.

In conclusion, one must be careful in interpreting ¹H[¹⁹F] spectra and understand the limits of the ¹⁹F decoupling scheme used.

PSYCHE to Evaluate 1H-19F Coupling Constants

Even small molecules can yield very complex ¹H NMR spectra as the result of spin - spin coupling.  This is particularly true for small molecules that contain fluorine.  It can sometimes be challenging to determine which splittings are due to ¹H-¹H coupling and which are due to ¹H-¹⁹F coupling.  One can collect a ¹H spectrum with ¹⁹F decoupling to give a spectrum with only ¹H-¹H coupling present.  Even with this data, it may be difficult to evaluate the ¹H-¹⁹F coupling constants by comparing the ¹H[¹⁹F] spectrum to the ¹H spectrum due to the complexity of the multiplets.  The ¹H-¹⁹F coupling constants can however be read directly from a ¹H PSYCHE spectrum.  The PSYCHE spectrum provides a ¹H decoupled ¹H spectrum, leaving only the ¹H-¹⁹F coupling behind.  The bottom trace of the figure below shows the 300 MHz ¹H NMR spectrum of 2,3-difluoro pyridine.  The spectrum is quite complex, making it difficult to assign ¹H-¹H and ¹H-¹⁹F couplings.  The middle trace shows the ¹H[¹⁹F] spectrum which allows the evaluation of all of the ¹H-¹H coupling constants (³J_H5-H4 = 4.8 Hz, ⁴J_H5-H3 = 1.6 Hz and ³J_H4-H3 = 8.0 Hz.  The top trace shows the ¹H PSYCHE spectrum which allows one to evaluate all of the ¹H-¹⁹F coupling constants.  For this compound, ⁴J_H3-F1 = ³J_H3-F2 = 9.8 Hz, ⁴J_H4-F2 = 3.2 Hz and ⁴J_H5-F1 = 1.8 Hz.

1H with 19F Decoupling

The proton NMR spectra of compounds containing fluorine often show ¹H - ¹⁹F J coupling. This can of course provide useful information but is also sometimes seen as an unwanted complication. In such cases, it can be removed by ¹⁹F decoupling. An example of this is shown in the figure below. Depending on the NMR equipment used, observing ¹H [¹⁹F] spectra may be more difficult than for example observing protons with ³¹P, ¹³C, ¹¹B or even ²⁷Al decoupling. The difficulty arises because the frequencies of ¹H and ¹⁹F are very close to one another. A probe must be either doubly tuned on the high frequency channel to both ¹⁹F and ¹H or the broadband channel must be able to be tuned as high as ¹⁹F. In either case, additional filters are usually required.