Nuclear Overhauser Effect (NOE)
Dr. V. Vijayakumar, Centre for
Organic and Medicinal Chemistry
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Nuclear Overhauser Effect (NOE)
• Nuclear Overhauser effect is a phenomenon in which the signal of a 1H
is effect if the another 1H close in space is irradiated
• This effect arises due to dipolar interactions between the two spins close
in space (through-space effect)
• This method can be used to determine the proximity between two spins
Dr. V. Vijayakumar, Centre for
Organic and Medicinal Chemistry
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Nuclear Overhauser Effect (NOE)
1H-13C pair
Dr. V. Vijayakumar, Centre for
Organic and Medicinal Chemistry
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Difference NOE method
• This method is used to determine the proximity of different 1H in a molecule
• This is carried out by irradiating a chosen 1H peak in the 1D spectrum and
monitoring the intensity of other peaks in the spectrum
• Any other peak which is effected is concluded to be in proximity to the 1H signal
that is being irradiated.
• The extent of NOE enhancement is dependent on the distance
Dr. V. Vijayakumar, Centre for
Organic and Medicinal Chemistry
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Difference NOE method
Dr. V. Vijayakumar, Centre for Organic and Medicinal Chemistry
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Difference NOE method
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Dr. V. Vijayakumar, Centre for Organic and Medicinal Chemistry
Dr. V. Vijayakumar, Centre for Organic and Medicinal Chemistry
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Dr. V. Vijayakumar, Centre for
Organic and Medicinal Chemistry
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Dr. V. Vijayakumar, Centre for
Organic and Medicinal Chemistry
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Dr. V. Vijayakumar, Centre for
Organic and Medicinal Chemistry
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Hydroxyl Proton Exchange and the Influence of Hydrogen Bonding
• The Two compounds in the lower row are alcohols. The OH proton signal is seen
at 2.37 δ in 2-methyl-3-butyne-2-ol, and at 3.87 δ in 4-hydroxy-4-methyl-2pentanone.
•
• A six-membered ring intramolecular hydrogen bond in the latter compound is in
part responsible for its low field shift, and will be shown by clicking on the
hydroxyl proton.
• We can take advantage of rapid OH exchange with the deuterium of heavy water
to assign hydroxyl proton resonance signals . As shown in the following
equation, this removes the hydroxyl proton from the sample and its resonance
signal in the nmr spectrum disappears.
• R-O-H + D2O R-O-D + D-O-H
Experimentally, one simply adds a drop of heavy water to a chloroform-d
solution of the compound and runs the spectrum again. The result of this
exchange is displayed below.
Dr. V. Vijayakumar, Centre for
Organic and Medicinal Chemistry
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Hydrogen bonding shifts the resonance signal of a proton
to lower field (higher frequency).
The chemical shift of the hydroxyl hydrogen of an alcohol varies with
concentration. Very dilute solutions of 2-methyl-2-propanol, (CH3)3COH, in
carbon tetrachloride solution display a hydroxyl resonance signal having a
relatively high-field chemical shift (< 1.0 δ ). In concentrated solution this
signal shifts to a lower field, usually near 2.5 δ.
The more acidic hydroxyl group of phenol generates a lower-field resonance
signal, which shows a similar concentration dependence to that of alcohols.
OH resonance signals for different percent concentrations of phenol in
chloroform-d are shown in the following diagram (C-H signals are not shown).
Dr. V. Vijayakumar, Centre for Organic and Medicinal Chemistry
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Because of their favored hydrogen-bonded dimeric
association, the hydroxyl proton of carboxylic acids
displays a resonance signal significantly down-field of
other functions. For a typical acid it appears from 10.0 to
13.0 δ and is often broader than other signals. The spectra
shown below for chloroacetic acid (left) and 3,5-dimethyl
benzoic acid (right) are examples.
Dr. V. Vijayakumar, Centre for
Organic and Medicinal Chemistry
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• Intramolecular hydrogen bonds through six-membered ring,
generally display a very low-field proton resonance.
• The 4-hydroxypent-3-ene-2-one (the enol tautomer of 2,4pentanedione) not only illustrates this characteristic, but also
provides an instructive example of the sensitivity of the nmr
experiment to dynamic change.
• In the nmr spectrum of the pure liquid, sharp signals from both the
keto and enol tautomers are seen, their mole ratio being 4 : 21 (keto
tautomer signals are colored purple).
• Chemical shift assignments for these signals are shown in the
shaded box above the spectrum. The chemical shift of the hydrogenbonded hydroxyl proton is δ 14.5 exceptionally downfield.
• It can be concluded the rate at which these tautomers interconvert is
slow compared with the inherent time scale of nmr spectroscopy.
Dr. V. Vijayakumar, Centre for
Organic and Medicinal Chemistry
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Dr. V. Vijayakumar, Centre for
Organic and Medicinal Chemistry
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Lanthanide Shift Reagents
• 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.
Dr. V. Vijayakumar, Centre for
Organic and Medicinal Chemistry
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• 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-βdiketone 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-4,6dionato)europium(III) (Rondeau, Sievers, J. Am. Chem. Soc. 1971, 93,
1522) has better solubility and is a stronger Lewis acid.
•
• 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.
Dr. V. Vijayakumar, Centre for
Organic and Medicinal Chemistry
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• 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 (Gansow JACS 1971, 93, 4295):
•
Dr. V. Vijayakumar, Centre for Organic and Medicinal Chemistry
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• 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.
Dr. V. Vijayakumar, Centre for
Organic and Medicinal Chemistry
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Dr. V. Vijayakumar, Centre for
Organic and Medicinal Chemistry
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Dr. V. Vijayakumar, Centre for Organic and Medicinal Chemistry
Dr. V. Vijayakumar, Centre for
Organic and Medicinal Chemistry
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Dr. V. Vijayakumar, Centre for
Organic and Medicinal Chemistry
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Removal of complex spectra
Name multiplets such that the biggest coupling constant determines the "first name" of the multiplet and
the smallest coupling constant determines the "last name." In this system of nomenclature, a doublet of
triplets (dt) is six-line pattern with one large coupling and two equal small couplings. It may be thought of
as a "pair of triplets." Conversely, a triplet of doublets (td) is a six-line pattern with two equal large
couplings and one small coupling. It may be thought of as a "trio of doublets in 1:2:1 ratio"
Dr. V. Vijayakumar, Centre for Organic and Medicinal Chemistry
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The Probe
Probe
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a
H
H
C C
c
Hb
Complex Splitting
• Signals may be split by adjacent protons,
different from each other, with different
coupling constants.
• Example: Ha of styrene which is split by an
adjacent H trans to it (J = 17 Hz) and an
adjacent H cis to it (J = 11 Hz).
=>
Chapter 13
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a
H
H
C
C
c
Splitting Tree
Hb
=>
Chapter 13
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Spectrum for Styrene
=>
Chapter 13
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