Coupling proton-carbon, long-range

H. Kessler, W. Bermel, and C. Griesinger, Recognition of NMR proton spin systems of cyclosporin A via heteronuclear proton-carbon long range couplings, J. Am. Chem. Soc., 107, 1083 (1985). 

Figure 5.3 GHMBC spectrum of a colored impurity formed during the synthesis of Tipranavir. The long-range delay in the experiment was optimized for 10 Hz the data were acquired in 12.5 h. Chemical shift labels show the chemical shift of the carbon to which a given proton is long-range coupled. As can be seen by simple inspection, there was considerable degradation of the sample during the course of the data acquisition as there are peaks in the contour plot corresponding to responses that were not observed in the proton spectrum taken at the outset of data acquisition, which is plotted above the contour plot.

C-5 of the ribofuranose residue can easily be assigned. Another rule is found for the anomeric carbons C-l of the ribofuranose residue which always absorb at lowest field [696]. C-4 can be assigned by noting the phosphorus-carbon long-range coupling in the proton broadband-decoupled 13C NMR spectra of nucleotides [750] as demonstrated in Fig. 5.9. 

Correlations between long-range coupled protonated carbons are denoted by double-headed soHd black arrows. Diagonally symmetric signals with positive phase are observed. 

Two-dimensional carbon-proton shift correlation via long-range CH coupling... 

Two-dimensional C//correlations such as C//COSY or HC HMQC and HSQC provide the Jqh connectivities, and thereby apply only to those C atoms which are linked to H and not to non-protonated C atoms. Modifications of these techniques, also applicable to quaternary C atoms, are those which are adjusted to the smaller Jqh and Jqh couplings (2-25 Hz, Tables 2.8 and 2.9) Experiments that probe these couplings include the CH COLOC (correlation via long range couplings) with carbon-13 detection (Fig. 2.16) and HC HMBC (heteronuclear multiple bond coherence) with the much more sensitive proton detection (Fig. 2.17)... 

CH COLOC Correlation via long-range CH coupling, detects CH connectivities through two or three (more in a few cases) bonds in the CH COSY format, permits localisation of carbon nuclei two or three bonds apart from an individual proton... 

Long-range coupling between protons more than two carbon atoms apart is sometimes observed when v bonds intervene. An example is found in l-methoxy-l-buten-3-yne. Not only does the acetylenic proton, Ha, couple with the vinylic proton H, it also couples with the vinylic proton Hc, four carbon atoms away. The data are ... 

The HMBC spectrum of podophyllotoxin is shown. The cross-peaks in the HMBC spectrum represent long-range heteronuclear H/ C interactions within the same substructure or between different substructures. Interpretation should start with a readily assignable carbon (or proton), and then you identify the proton/s (or carbon/s) with which it has coupling interactions. Then proceed from these protons, and look for the carbon two, three, or, occasionally, four bonds away. One-bond heteronuclear interactions may also appear in HMBC spectrum. 

Cross-peaks A and B represent interactions of the C-4 proton (H ) resonating at 8 2.20 with the C-3 and C-5 carbons (8 72.2 and 43.7, respectively). Cross-peak C corresponds to the coupling between the C-4 proton (8 2.70) (H ) with the C-2 iminic carbon (8 160.4). Crosspeaks D, E, and F represent long-range correlations between the C-5a... 

The selective heteronuclear /-resolved experiment (Bax, 1984) is used to determine heteronuclear long-range coupling constants via a selecdve n pulse that causes splitting of all carbon signals coupled to that proton. 

A P,C correlation experiment also requires that we use a predefined coupling constant value to determine the mixing time. A brief look at the proton decoupled carbon-13 spectrum (Fig.14) shows that is very large (around 200 Hz), while the long-range JPC values are much smaller (around 5-10 Hz). 

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