11B Double Quantum - Single Quantum Correlation Spectroscopy

The 2D ¹³C INADEQUATE method provides double quantum - single quantum (DQ/SQ) correlations and enables one to determine the carbon - carbon skeleton of small organic molecules.  The method is quite insensitive for ¹³C since the natural abundance of ¹³C is only 1.1% and the chance of having two adjacent ¹³C nuclei is only 1 in 8264.  For spins other than ¹³C, for which the natural abundance is high, one expects the sensitivity of DQ/SQ correlation spectroscopy to be much higher.  ¹¹B has a natural abundance of 80.42% and the chance of having two adjacent ¹¹B nuclei in compounds with boron-boron bonds is 1 in 1.55.  ¹¹B NMR spectra are often sufficiently broad due to efficient quadrupolar relaxation such that homonuclear ¹¹B - ¹¹B J coupling is unresolved however the T₂'s are long enough to allow the collection of  2D ¹¹ B COSY and 2D DQ/SQ data.  The figure below shows the 2D ¹¹B DQ/SQ correlation spectrum of ortho-carborane.  The ¹¹B bonding connectivity can be determined easily from the spectrum.

2D 13C INADEQUATE

The 2D ¹³C INADEQUATE (Incredibe Natural Abundance DoublE QUAmtum Transfer Experiment) is undoubtedly one of the most definitive, yet under-used NMR techniques able to assign chemical structures of small organic molecules.  It gives a connectivity map for all carbon atoms in the molecule.  The reason that it is so under-used is that it relies on one bond ¹³C - ¹³C coupling therefore, adjacent carbon atoms must both be of the ¹³C isotope.  Since ¹³C is only 1.1% naturally abundant, the chance of having two adjacent ¹³C atoms is approximately 1 in 8300, reducing the sensitivity of the measurement drastically.  As a result, 2D INADEQUATE spectra can only be run on very concentrated samples.  The sensitivity afforded by high magnetic field strengths and cryogenically cooled probes has certainly made these measurements more accessible than they have been in the past and they may be within reach when sample quantity and solubility are not a problem.  The 2D ¹³C INADEQUATE spectrum of ~450 mg of limonene in benzene-d6 was acquired on a Bruker TCI H/C/N cryoprobe at 600 MHz and is shown in the figure below.

The spectrum was acquired with the gradient version of the INADEQUATE pulse sequence using a shaped refocusing pulse (Bruker pulse program inadgpqfsp).  It was acquired in 11.8 hours with 64 scans for each of 128 increments using a 5 second recycle delay. The proton decoupled ¹³C spectrum is in the horizontal F2 domain.  The spectrum is interpreted by locating the vertical cross peaks for each ¹³C resonance.  Each cross peak has a partner peak along the horizontal axis.  The partner peak lies on the same vertical axis as the carbon atom bonded to the initial carbon.  This is shown in the figure for C1 which is bonded to C2, C3 and C4.  The entire carbon skeleton of the molecule can be traced unambiguously in this manner to provide a complete assignment.  The same sample was run under the same conditions in 45 minutes with only 4 scans.  A comparison of the signal-to-noise ratio for both data sets is shown in the figure below.

It is clear that usable 2D INADEQUATE data can be acquired in less than an hour for extremely concentrated samples at high field with a cryoprobe.