Since the advent of pulsed NMR spectroscopy, a number of advanced two- dimensional techniques have been devised. These methods afford valuable information for the solution of complex structural problems. The technical detail behind multi-dimensional NMR is beyond the scope of this book.
Two-dimensional spectra have the appearance of surfaces, generally with .two axes corresponding to chemical
shift and the third (vertical) axis corresponding to signal intensity.
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Itis usually more useful to plot two- dimensional spectra viewed directly from above (a contour plot of the surface) in order to make measurements and assignments.
Chemical shift (F2)
The most important two-dimensional NMR experiments for solving structural problems are COSY (COrrelation Spect:r;oscopY), NOESY iliuc1ear Overhauser Enhancement~pectroscopY),HSC (Heteronuclear~hift ~orrelation)and TOCSY (TOtal Correlation SpectroscopY). Most modem high-field NMR spectrometers have the capability to routinely and automatically acquire COSY, NOESY, HSC and TOCSY spectra.
Chapter 7 Miscellaneous Topics
The COSY spectrum shows which pairs of protons in a molecule are coupled to each other. The COSY spectrum is a symmetrical spectrum that has the IHNMR spectrum of the substance as both of the chemical shift axes (F1and F2) . A schematic
representation of COSY spectrum is given below.
Itis usual to plot a normal (one-dimensional) NMR spectrum along each of the axes to give reference spectra for the peaks that appear in the two-dimensional spectrum.
F2 1HNMR _
axis Spectnrn
1HNMR Spectnrn
HC Ho
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The COSY spectrum has a diagonal . set of peaks (open circles) as well as
peaks that are off the diagonal (filled circles). The off-diagonal peaks are the important signals since these occur at positions where there is coupling between a proton on the F1
axis and one on the F2axis. In the schematic spectrum on the right, the off-diagonal signals show that there is spin-spin coupling between He and Ho and also between HBand He but the proton labelled HAhas no coupling partners.
In a single COSY spectrum, all of the spin-spin coupling pathways in a molecule can be identified.
The NOESY spectrum relies on the Nuclear Overhauser Effect and shows which pairs of nuclei in a molecule are close together in space. The NOESY spectrum is very similar in appearance to a COSY spectrum. Itis a symmetrical spectrum that has the IH NMR spectrum of the substance as both of the chemical shift axes (F1and F2) .
A schematic representation ofNOESY spectrum is given below. Again, it is usual to plot a normal (one-dimensional) NMR spectrum along each of the axes to give reference spectra for the peaks that appear in the two-dimensional spectrum.
From the analysis of a NOESY spectrum, it is possible to determine the three
dimensional structure of a molecule or parts of a molecule. The NOESY spectrum is particularly useful for establishing the stereochemistry(e.g.thecis/trans
configuration of a double bond or a ring junction) of a molecule where more than one possible stereoisomer exists.
The NOESY spectrum has a diagonal set of peaks (open circles) as well as peaks which are off the diagonal (filled circles). The off- diagonal peaks occur at positions where a proton on the F1axis is close in space to a one on the F2 axis. In the schematic spectrum on the right, the off-diagonal signals show that HAmust be located near Ho and Hemust be located near He.
1HNMR Spectrun
The HSC spectrum is the heteronuclear analogue of the COSY spectrum and identifies which protons are coupled to which carbons in the molecule. The HSC spectrum has theIHNMR spectrum of the substance on one axis (F2) and the13C
spectrum (or the spectrum of some other nucleus) on the second axis (FI)' A schematic representation of an HSC spectrum is given below. Itis usual to plot a normal (one-dimensional)IH NMR spectrum along the proton dimension and a normal (one-dimensional)13C NMR spectrum along the 13C dimension to give reference spectra for the peaks that appear in the two-dimensional spectrum.
F2 1HNMR_
axis Spectrum
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The HSC spectrum does not have diagonal peaks. The peaks in an HSC spectrum occur at positions where a proton in the spectrum on the F2axis is coupled to a carbon in the spectrum on the on the F1axis.
In the schematic spectrum on the right, both HAandHeare coupled to Cz, He is coupled to Cy and Ho is coupled toCX.
He HD
F1
axis ;"
Cx Cy
r
Cz 13CNMR Spectnrn
Chapter 7 Miscellaneous Topics
In an HSC spectrum, the correlation between the protons in the1H NMR spectrum and the carbon nuclei in the l3C spectrum can be obtained. Itis usually possible to assign all of the resonances in the IH NMR spectrumi.e. establish which proton in a molecule gives rise to each signal in the spectrum, using spin-spin coupling
information. The l3C spectrum can then be assigned by correlation to the proton resonances.
The TOCSY spectrum is useful in identifying all of the protons which belong to an isolated spin system. Like the COSY and NOESY spectra, the TOCSY also has peaks along a diagonal at the frequencies of all of the resonances in the spectrum. The experiment relies on spin-spin coupling but rather than showing pairs of nuclei which are directly coupled together, the TOCSY shows a cross peak (off-diagonal peak) for every nucleus which is part of the spin system not just those that are directly coupled.
The TOCSY spectrum is symmetrical about the diagonal and has the IH NMR spectrum of the substance as both of the chemical shift axes (F1and F2). A schematic representation ofTOCSY spectrum is given below. Again, it is usual to plot a normal (one-dimensional) NMR spectrum along each of the axes to give reference spectra for the peaks that appear in the two-dimensional spectrum.
The TOCSY spectrum has a diagonal set of peaks (open circles) as well as peaks which are off the diagonal (filled circles). The off- diagonal peaks occur at positions where a proton on the F1axis is in the same spin system as one on the F2axis. In the schematic spectrum on the right, there are two
superimposed isolated 3-spin systems (HA 1, HA2 , HA3)and(HX 1, HX2•HX3 )and the cross peaks clearly indicate which resonances belong to each spin system.
F2 1HNMR --
axis Spectrum
HA1 HA2 HA3
HX1 HX2 HX3
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'H and l3CNMR spectroscopy accounts for the overwhelming proportion of all NMR observations. However, there are many other isotopes which are NMR observable and they include the common isotopes 19F, 31pand 2H. The NMR spectroscopy of these "other nuclei" has had surprisingly little impact on the solution of structural problems in organic chemistry and will not be discussed here. Itis however important to be alert for the presence of other magnetic nuclei in the molecule, because they often cause additional multiplicity in 'H andl3CNMR spectra due to spin-spin coupling.