Lanthanide Shift Reagents in Nuclear Magnetic Resonance Spectroscopy

1. Lanthanide Shift Reagents in Nuclear Magnetic Resonance Spectroscopy
K.LOGANATHAN

2. Introduction:
As is implied in the name, nuclear
magnetic resonance is concerned with the
magnetic properties of certain atomic
nuclei. Analysis of a NMR spectrum
provides information on the number and
type of chemical entities in a molecule.
However, NMR provides much more
information than IR.

3. Why Chemical shift reagents?
Because the chemical shifts of several groups of
protons are all very similar , which shows their
proton resonances in the same area of the
spectrum and often peak overlap so extensively
that individual peaks and splitting cannot be
extracted

4. Chemical shift reagents:
Chemical shift reagents are organic complexes of
paramagnetic rare earth metals from the
lanthanide series.
Of the lanthanides, europium is probably the most
commonly used metal.
Two of its widely used complexes are Tris
(dipavalomethanato) europium and tris-(6,6,7,7,
8,8,8- heptafluoro-2,2-dimethyl-3,5-octanedionato)
europium, frequently abbreviated Eu(dpm)3 and
Eu(fod)3, respectively

5. Chemical shift reagents:
When such metal complexes are added to the
compound whose spectrum is being determined, there is
a profound shifts in the various groups of protons. The
direction of the shift (up field or downfield) depends
primarily on which metal is being used.
Complexes of europium, erbium, thulium and ytterbium
shift resonances to lower field, while complexes of
cerium, praseodymium, neodymium, samarium, terbium,
and holmium generally shift resonances to higher field.

6. Interaction of chemical shift reagents:
These lanthanide complexes interact with a relatively
basic pair of electrons ( an unshared pair ) which can
coordinate with Eu+3.
Typically, aldehydes, ketones, alcohols, thiols, ethers
and amines all interact.

7. Chemical shift reagents:
The amount of shift a given group of protons experiences
depends on
 the distance separating the metal (Eu3+)and that
group of protons and
 the concentration of shift reagent in the solution.
Hence it is necessary to include the number of mole
equivalents of shift reagents used or its molar
concentration when reporting a lanthanide shifted
spectrum

8. Chemical shift reagents:
E.g:The spectra of 1- hexanol:
In the absence of shift reagent, the spectrum shown Only
the triplet of the terminal methyl group the triplet of the
methylene group next to the hydroxyl are resolved in the
spectrum.
The protons (aside from O-H) are found together in a
broad, unresolved group.
With the shift reagent added each of the methylene groups
is clearly separated and is resolved into proper multiplet
structure.

12. β-Diketone complexes of some of the lanthanides have interesting and useful
properties as NMR shift reagents. Lewis acid complexation of the lanthanide
atom with basic sites on molecules results in substantial chemical shift effects
consistent with the presence of large shielding and deshielding cones around
the lanthanide atom. These chemical shift effects are the result of unpaired
electrons in the f shell of the lanthanide. The lanthanides are especially
effective because there is relatively little delocalization of the unpaired f
electrons onto the substrate (Fermi contact interactions), and so the principal
effect is usually the anisotropy of the metal. An optimum combination of
minimum line broadening by direct Fermi contact interaction with unpaired
spins, and maximum downfield and upfield dipolar shifts is provided by Eu and
Pr tris-β-diketone complexes. The first widely used shift reagent was
Eu(dpm)3 (tris(2,2,6,6-tetramethylhepta-3,5-dionato)europium(III))
(Hinckley, J. Amer. Chem. Soc. 1969, 91, 5160). The fluorinated
analog Eu(fod)3 (tris(7,7,-dimethyl-1,1,2,2,2,3,3-heptafluoroocta-7,7-
dimethyl-4,6-dionato)europium(III) (Rondeau, Sievers, J. Am. Chem.
Soc. 1971, 93, 1522) has better solubility and is a stronger Lewis acid

13. The choice of Europium as the main shift reagent and
Praseodymium as the alternate reagent of choice was dictated by
their properties. Eu shows shifts in the downfield direction, thus
usually accentuating the existing shift differences in 1H NMR
spectra. Pr shifts signals mostly up field, often initially making
the spectra more complicated. The shifts for some of the later
lanthanides (Dy and Tm) are much larger, but there are also
severe line-broadening effects (with the 2-proton of picoline -
200 Hz for Dy and 65 Hz for Tm, versus ca 5 Hz for Eu and Pr)

14. Observed isotropic shifts for the most shifted resonance of 1-
hexanol (H-1), 4-picoline-N-oxide (H-2) and 4-vinylpyridine (H-2),
in the presence of Ln(dpm)3 at 30 °C in CDCl3

15. The chemical shift effects of dipolar interactions are reasonably predicted by
the usual deshielding or shielding cone, as for anisotropic effects of various
functional groups.

16. Evidence that the shift effects are primarily due to the magnetic anisotropy of the
metal, and not by direct contact interactions with the unpaired spins is provided by the
great similarity (in ppm) of the 1H and 13C shifts, as in the example of isoborneol below,
with Eu(dpm)3

17. Eu reagents cause mainly downfield shifts, Pr reagents
cause upfield shifts. The Eu reagents are much more
frequently used, because the shift effects enhance the
normal chemical shift differences between protons,
whereas Pr reagents initially diminish them. That is,
protons near functional groups tend to be downfield of
the others, and the Eu shift reagents continue to move
them further downfield.

19. The LCS reagents work only on molecules with Lewis basic
sites. Sequence of complexing strength varies with the nature
of the substrate, but is approximately: NH2 > OH > R2O >
R2C=O > CO2R ≈ R2S > R-CN.

20. Shift reagents are not used just to simplify spectra.
They are especially valuable for distinguishing geometric isomers,
such as cis-trans isomers of double bonds.
They have sometimes been used for conformational analysis, but
this use is constrained by the likelihood that complexation to the
lanthanide could cause changes in the conformation of the molecule.
In the examples below, the relatively small Δδ values for the beta-
hydrogens and large Δδ values of the alpha-substituents of
methacrolein and acrolein point to a predominance of the s-trans
conformation, whereas the Δδ values for acrylamide suggest an s-cis
conformation. However, these conclusions are strictly valid only for
the europium complexes, not for the free compounds.

21. Chiral Shift Reagents. One of the most useful applications of lanthanide shift reagents
is in the determination of optical purity by the use of chiral ligands on the lanthanide.
Some of the more effective reagents developed are Eu(facam)3 (tris(3-trifluoroacetyl-d-
camphorato)europium(III) and Eu(hfbc)3 (tris(3-heptafluorobutyryl-d-
camphorato)europium(III). Often sufficient separation between the R and S enantiomers
can be obtained so that the enantiomeric purity can be determined directly by NMR
integration.

22. Using Lanthanide Shift Reagents.
Here are some considerations in the practical use of LIS reagents. The
solvent must be non-complexing and dry: CCl4, CDCl3 and CD2Cl2 are
excellent.
the solution should be filtered to remove paramagnetic particles.
The usual procedure is to prepare a solution of the shift reagent in
CDCl3, filter it to remove paramagnetic impurities, and then add small
increments of this solution to the solution of the substrate, taking NMR
spectra after each addition. In this way it is possible to keep track of the
individual signals of the substrate, and determine the Δδ values for all
protons of interest.

23. Chemical Shift Reagent
These are the agents used to cause shift in the NMR spectra.
The amount of shift depends on,
 Distance between the shift reagent and proton,
 Concentration of shift reagent.
• The advantages of using shift reagents are,
 Gives spectra which are much easier to interpret,
 No chemical manipulation of sample is required,
 More easily obtained.
• Paramagnetic materials can cause chemical shift, e.g., Lanthanides.
Complexes of Europium, Erbium, Thallium and Ytterbium shift resonance
to lower field.
• Complexes of Cerium, Neodymium and Terbium shift resonance to
higher field.

24. Advantages of using chemical shift
reagents:
Gives spectra which are much easier to
interpret.
No chemical manipulation of the sample is
required with the use of shift reagents.
more easily obtained.

25. Disadvantage:
Shift reagents cause a small amount of line
broadening At high shift reagent concentrations this
problem becomes serious, but at most useful
concentrations the amount of broadening is tolerable

26. Conclusion:
Thus the chemical shift reagents and solvent
induced shifts have their application in resolving the
NMR spectra of complex structures by inducing
shifts with respect to reference compound.
Thus useful in interpretation of structures of
complex organic compounds.