NMR Nuclear Magnetic Resonance

1
NMR Nuclear Magnetic Resonance

• Introduction

Index
2
Orientation of the magnetic moment in
absence/presence of a magnetic field
Random orientation
In presence of a magnetic field Magnetic moments
precess and Orient with or against the field
3
Precession
4
Precession and Macroscopic Magnetization
5
Energy level and resonant transitions
6
Basic Concept review
Even mass
protons Neutrons Both Even I0 (4He, 12C
) (Half-integer)
Protons Neutrons Both Odd I1, 2, .
(Integer)
Odd mass
protons odd Neutrons Even I1/2, 3/2, ...
(Half-integer)
protons even Neutrons odd I1/2, 3/2, ...
(Half-integer)
7
Energy vs Field strenght
8
Field Dependance of a spectra
9
Multinuclear NMR
MHz
10
Elements in Organic Chemistry
There are 4 important elements in Org. Chemistry
(frequency at 2.35T)

• H Best NMR element
• 1H , I ½ (sharp lines), a 99.98 , high
  frequency (n 100 MHz)
• 2H , I 1 (broad lines), a 0.02, n 15.4 MHz,
  Q0.038
• C
• 12C , I 0 (no signal in NMR)
• 13C , I ½ (sharp lines), a 1.1 , n 25.3
  MHz
• N
• 14N , I 1 (broad lines), a 99.6, n 7.2 MHz,
  Q1.0
• 15N , I ½ (sharp lines), a 0.4 , n 10.1
  MHz
• O
• 16O , I 0 (no signal in NMR)
• 17O , I 5/2 (broad lines), a 0.04, n 13.5
  MHz, Q-0.037

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Elements in Organic Chemistry

• N
• 14N , I 1 (broad lines), a 99.6, n 7.2
  MHz Q1.0
• 15N , I ½ (sharp lines), a 0.4 , n 10.1
  MHz Q0

Although N-14 has large natural abundance, the
presence of quadrupole moment and very low
frequency make it impractical for NMR
studies. The presence of quadrupole moment in
that abundant element alter the shape of nearby
protons and carbons N-15 is a better candidate
but the low abundance low frequency render its
observation extremely difficult.
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Additional Elements in Organic Chemistry

• Halogens 19F, Cl, Br, I
• 31P, S
• B, 29Si
• Na
• Co, Cd, W, Pt, Hg

13
1D NMR Pulse -gtFID Acquisition -gt Fourier
Transform
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FID
15
RF Flip Angle (Nutation Angle)
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Relaxation Time
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Relaxation Effects
T1 Spin-Lattice Relaxation reestablish
population equilibrium along Z
Convert Spin Energy to thermal energy gt spin
transition from upper to lower state
T2 Spin-Spin Relaxation Dephase nuclear dipole
in the XY plane
There are 5 mechanism for T1 Relaxation

1. Dipole-Dipole most important gt intramolecular
   interaction between nearby nuclei. Depends on
   intensity of magnetic moment and on distance
   between nuclei
2. Spin-Rotation
3. Anisotropy
4. Scalar coupling
5. Quadrupolar Relaxation (very large)

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T2 Spin-Spin Relaxation
From Classical NMR theory (Bloch Equation)
Single peak fits Lorentz Curve (Lorentzian shape)
Half width Dn1/2
In fact the experimental line width measure the
T2 influenced by inhomogeneity of the field
½
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Relaxation with unpaired electron
Neutral
Radical
Line shape become extremely broad with unpaired
electron relaxation (fast relaxation)
20
Effect of Relaxation with Quadrupolar nuclei
For nuclei having I gt ½ , there is ellipsoidal
charge distribution with 2I 1 orientations in
the magnetic field.
(below is representation of the 3 orientations
for I 1)
Fluctuating field causes transitions among
nuclear spin state gt fast relaxation
To be effective, quadrupolar relaxation require
unsymmetrical charge distribution at nucleus and
at electron cloud
e.g. (CH3)4-N gt no quadrupolar relaxation
(sharp line 14N)
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Effect of Relaxation with Quadrupolar nuclei
H-N
Relaxation rate between 14N spin states is slow
compared to JNH
Relaxation rate between 14N spin states is
moderately fast compared to JNH
Relaxation rate between 14N spin states is very
fast compared to JNH
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Me-NH
Amine
Fast chemical exchange, Fast 14N relaxation
NH
Me-NH
Amide
Slow chemical exchange moderate 14N relaxation
NH
23
Coupling to 14N broaden the lines
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Coupling with Deuterium
Most solvents used in NMR are deuterated (usually
to 99) Therefore, in proton NMR, we observe
residual protons with Deuterium coupling (when
appropriate).
HCD2OD
HCD2SOCD3
H
D
D2
2nI 1 lines
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Size of Coupling with Deuterium
When 2 protons are identical in chemical shift
but you want to measure JHH, use deuterium
substitution
1H 100 MHz 2H 15.4 MHz
In DMSO 2JHD 1.8 Hz
2JHH 12 Hz
6.514
In 13C NMR
In DMSO-d6 1JCD 21.0 Hz
6.514
1JCH 136.8 Hz
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Pulse Phase
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Free Induction Decay FID
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FID and Fourier Transform
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FID in Lab Frame vs in Rotating Frame
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Behavior of the Spins in the XY plane
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FID duration vs Line Width
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Sampling rate and Foldover
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DIGITALLIZATION
Digitallization Convert FID (Volt/Time) in
Digital form
Digitallization process is limited by

• Accuracy
• Speed

Carrier Offset or Transmitter Offset or O1 is
the frequency of the irradiating field. It is
also the Reference or Rotating Frame frequency
The Window or Spectral Width also called SW
define the range of frequencies that can be
measured
_1__2SW
The Sampling Rate gt 2 Points/Cycle Dwell Time
DW
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If Maximum Frequency to be sampled is fmax SW
We must sample at a rate no less than
2 SWsec.
Digital Resolution
The amount of memory limit the accuracy of the
signal to be recorded
For a given of memory ( Points -gt TD (time
domain)), one obtain
NP (real) and NP (Imaginary) 2 2
Digital Resolution D.R. Df (Separation
between 2 points)
D.R. 2 SW NP
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Digitallization resolution and AcQuisition time
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Example
At 200 MHz If SW2000 Hz (10 ppm) TD
16,000 points (16K)
What is the Digital Resolution
D.R. 2SW/TD 4000 / 16,000 1 / 4 0.25 Hz
What is the Acquisition Time AQ
AQ TD DW TD / (2 SW) 4 seconds
D.R. 1 / AQ 2 SW / TD
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Pulse NMR spectrometer
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Sensitivity and Receptivity
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Absolute Frequency
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Relative Chemical Shift
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Parameters in NMR

1. Chemical shift (d) ? ppm Structural information

nPEAK nREF (Hz) d (ppm)
------------------------------ ppm
Freq of the nuclei (MHz)
e.g. at 200 MHz
If R-CH(OR)2 appear at 1,000 Hz from TMS (0)
Its chemical shift is
d 1,000 Hz/200 MHz 5 ppm
d is dimensionless (independent from the applied
field) n changes with the applied field
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Parameters in NMR

1. Coupling constant (J) ? Hz Structural and
   Conformational information
2. Area of peaks Relative proportion of nuclei
3. Distance between nuclei Information is contained
   in relaxation and NOE
4. Molecular Motion Information is contained in
   relaxation, NOE and Variable Temperature

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Proton Shift
Index
H-NMR