HMBC vs. H2BC

NMR spectroscopy is an indispensable tool for assigning the structure of organic compounds.  One very useful method in the NMR toolbox is the Heteronuclear Multiple Bond Correlation (HMBC) experiment.  HMBC data are ¹H detected and provide a 2D correlation map between ¹H and ¹³C similar to HMQC or HSQC except that the correlations are between protons and carbons separated by two, three and sometimes even four bonds.  This long range information is very helpful in elucidating chemical structures, especially those with non-protonated carbons.  The problem, however with HMBC data is that the correlations depend only on the magnitude of the long-range ¹H-¹³C coupling constants.  Two- or three- bond coupling constants are very similar in magnitude to one another and therefore it is not possible to distinguish between two- and three- bond correlations.  Also, since many long range ¹H-¹³C coupling constants (including two-bond coupling constants) are near zero, some correlations may be absent.  These problems may make structure elucidation frustrating or impossible.  The Heteronuclear 2 Bond Correlation (H2BC) experiment¹ provides an HMBC-like correlation map with (almost) exclusively two-bond ¹H-¹³C correlations.  Unlike the correlations in the HMBC measurement, which rely exclusively on long range ¹H-¹³C coupling constants, the ¹H-¹³C correlations in the H2BC experiment rely on three-bond ³J_H-H coupling between the protons on adjacent carbons.  It is a combined HMQC-COSY experiment.  The size of the H2BC correlations depends on the magnitude of the ³J_H-H coupling constant.  Three-bond ¹H-¹³C correlations are possible only if four-bond ⁴J_H-H coupling is significant.  One disadvantage to the H2BC experiment is that all correlations between protons and non-protonated carbons are necessarily absent because of the absence of H-H coupling.  In general, two-bond ¹H-¹³C correlations that are weak or absent in HMBC spectra are strong in H2BC spectra and three-bond ¹H-¹³C correlations which are strong in HMBC spectra are absent or very weak in H2BC spectra.  The techniques are very complimentary.  The figure below illustrates  the complimentary nature of the two methods for styrene.

The HMBC spectrum in the left panel was scaled up until some of the HMQC artifacts (color coded in blue) were visible.  The data show only one 2-bond ¹H-¹³C correlation (color coded in pink). The three-bond ¹H-¹³C correlations are color coded in yellow.  In comparison, the H2BC spectrum in the right panel shows exclusively two-bond ¹H-¹³C correlations with the exception of those involving the C1 non-protonated carbon.

1. Nyberg, Duus, Sorensen.  J. Am. Chem. Soc. 127, 6154 (2005).