NMR Nuclear Magnetic Resonance

1
NMR Nuclear Magnetic Resonance

• Proton NMR

Index
NMR-basics
2
Anisotropy of Aromatic compounds in plane and
above
dring ? 7.27-6.95 ppm
dMe ? -0.51 ppm
dring ? 8.14-8.64 ppm
dMe ? -4.25 ppm
dOUTSIDE ? 9.28 ppm
dINSIDE ? -2.99 ppm
3
Anisotropy Aromatic
4
Electronic effects
Deshielded
7.10 ppm
6.28 ppm
6.83 ppm
5.93 ppm
6.10 ppm
7.07 ppm
6.38 ppm
7.71 ppm
6.28 ppm
5
Electronic effects conjugation with carbonyl
6
Electronic effects conjugation with carbonyl
deshielded
7
Electronic effects conjugation with heteroatom
shielded
6.06 ppm
5.48 ppm
5.81 ppm
6.22 ppm
5.78 ppm
4.82 ppm
8
Electronic effects no conjugation with heteroatom
9
Electronic effects conjugation with heteroatom
shielded
10
Electronic effects conjugation with carbonyl
m
o
p
deshielded
deshielded
11
Electronic effects conjugation with heteroatom
Shielded
shielded
o
m
p
12
Electronic effects conjugation with heteroatom
Shielded
o
m
p
shielded
13
Aromatic inductive effect and resonance effect
14
Hydrogen bond
15
Protons on Heteroatoms

• OH, NH, SH
• Exchangeable (with D2O)
• Hydrogen bonding
• On Nitrogen (14N), as the spin state of that
  nuclei is 1, there can be partial coupling that
  produce broaden lines. There can be also full
  coupling that would produce 3 lines of equal
  intensity (I1 has 3 orientations in a magnetic
  field)

16
Protons on Heteroatoms

• OH
• Aliphatic d 0.5-4.0 ppm (depend on Concentration)
• Intramolecular hydrogen bonding deshield OH and
  render it less sensitive to concentration
• Usually OH exchange rapidly (no coupling with
  neighbors
• In DMSO or Acetone, the exchange rate is slower
  gt there is coupling with neighbors
• Phenols d 7.5-4.0 ppm Intramolecular bond ?
  12-10 ppm
• Carboxylic Acids Exist as Dimers ? 13.2-10 ppm

17
H2O signal moves with temperature
H2O
18
OH in DMSO
CH3-CH2-OH
CH2 qd
OH
(CH3)2 -CH-OH
OH
CH
19
Protons on Heteroatoms

• NH 14N I1 gt 2I1 lines
• NH has different rate of exchange
• 14N can relax quickly. Depending on relaxation
  rate, heteronuclear coupling will be visible or
  produce broadened peaks.
• R-NH Aliphatic amines gt rapid exchange
• Sharp singlets no coupling to N d3-0.5 ppm
• R-NH Amides, Pyrroles, Indoles, Carbamates
• NH broad
• CHa shows coupling the NH

20
NH
21
Amide
22
Protonated Amines
23
Formamide
H14N-NMR
H-CO-NH2
H-NMR
24
NH Amide, Pyrrole Indole
d 8.5-5.0 ppm
In Amides Slow rotation can show different
isomers
In Amine Salt

• Moderate Rate of exchange gt broad peaks d
  8.5-6.0 ppm
• CHa gt show coupling to NH

Sometimes broad NHx consist of 3 broad hump
due to 14N coupling
1JNH 50 Hz
25
SH

• Slow exchange SH couple to CHa
• When shaken with D2O, SH Disapeard 1.6 1.2
  ppm Aliphatic SHd 3.6 2.8 ppm Aromatic SH

26
Chemical Shift and Coupling
27
An example C10H12O2
I 10 1 12/2 5
O-CH2-CH3
J7 Hz
Me-C
J7 Hz
J8 Hz
Me-CC
X 4 12
28
Scalar coupling Coupling through bond
2nI 1 lines
n 0 1 2 3 4 5 6
1 1 1 1 2 1 1 3 3 1 1
4 6 4 1 1 5 10 10 5
1 1 6 15 20 15 6 1
a
doublet
a
b
b
septet
29
Scalar coupling Coupling through bond
2nI 1 lines
n 0 1 2 3 4 5 6
1 1 1 1 2 1 1 3 3 1 1
4 6 4 1 1 5 10 10 5
1 1 6 15 20 15 6 1
o
m
b
p
a
o
m
p
2 x triplet
a
b
30
Scalar coupling Coupling through bond
2nI 1 lines
n 0 1 2 3 4 5 6
1 1 1 1 2 1 1 3 3 1 1
4 6 4 1 1 5 10 10 5
1 1 6 15 20 15 6 1
2 x triplet 1 quintet
c
a
b
a
c
b
31
Scalar coupling Coupling through bond C7 H14 O2
I 7 -14/2 1 1 2nI 1 lines

• (ppm) Int mult J (Hz) COMMENT
• 0.9 3H triplet 7 CH3-gt(CH2)
• 1.1 3H triplet 7 CH3-gt(CH2)
• 1.35 2H sixtet 7 CH2 (CH3, CH2)
• 1.55 2H quintet 7 CH2 (CH2, CH2)
• 2.3 2H quartet 7 C- CH2 (CH3)
• 4.1 2H triplet 7 CH2 -O (CH2)

n 0 1 2 3 4 5 6
1 1 1 1 2 1 1 3 3 1 1
4 6 4 1 1 5 10 10 5
1 1 6 15 20 15 6 1
2 x triplet
3H
Triplet
3H
O
2H
Quartet
2H
Quintet
Sixtet
2H
2H
32
Scalar coupling Coupling through bond
2nI 1 lines
n 0 1 2 3 4 5 6
1 1 1 1 2 1 1 3 3 1 1
4 6 4 1 1 5 10 10 5
1 1 6 15 20 15 6 1
2 x triplet 6 1
Triplet 4
Quartet 5
Quintet 3
Sixtet 2
33
Common first order spin system 2nI 1 lines
34
Common first order spin system 2nI 1 lines
Jab
Jab
qd
Jab
td
35
Geminal Coupling
36
Vicinal Coupling
3J gt Perch
3J gt tool 1
3J gt Mestrec tool
37
Using Vicinal Coupling to establish isomer
Ha
Jab
Jad
Jac
38
Long Range Coupling
39
Long Range coupling
4JH1-H3 1.07 Hz 5JH1-H4 1.21 Hz 5JH1-H5
0.95 Hz 5JH4-H7 0.67 Hz
4JH-H 9 Hz
5JH-H 3 Hz
4JH-H 1-2 Hz
4JH-H 3 Hz
4JH-H 1.1 Hz
5JH-H 3 Hz
40
Spin System in Pople notation
Structural Unit
Spin system
Partial spectrum
-CH2-CH3
A3X2
-CH-CH3
A3X
CH2-CH2-CH3
A3M2X2
Each chemical shift is represented by a letter
(far way letter for very large shift difference
compare with the size of the coupling)
41
Second Order spectraAB instead of AX
Dn
Dn / J
J
J
5.0
1 2 3 4
As the difference in shift become smaller-
compare with the size of the coupling the outer
peaks become smaller in intensity
4.0
3.0
nA and nB center of gravity of doublet Chemical
shift
2.0
1.0
SpinWorks gt load AB
0.5
42
AB-Spectra
43
AMX
C6 H4 O5 N2 I 6 - 4/2 2/2 1 I 6
Phenyl 4 I NO2 1 I
44
A2X and A2B
SpinWorks gt load A2B
45
AMX
46
AMX
Substituants 2 OMe ( 3.9 ppm) CHO ( 9.8 ppm)
J Meta Para
J Ortho Meta
J Ortho Para
47
meta bromo nitro benzene
Calculated shifts dHA8.44 dHB7.82
dHC7.31 dHD8.19
HA
HB
HC
HD
48
AFMX
C5 H4 N Br I 5 4/2 1/2 1/2 1 I 4
(aromatic ring)
d
J
49
Assignment of 1H NMR of cartilagineal
Me
CHO
50
dd
Jcis10.5
H-5 dd 3J4,5 8.5 4J3,5 1.0
H-3 ddd 3J3,415.5 4J3,5 1.0 4J4,92.0
CHO-9 J 2.0 Hz
H-1(s)
Jtrans17 Hz
3J3,415.5 3J4,5 8.5
H-4 dd
51
Complicated proton spectra CH3-CH2-S-PF2
Almost quintet
3JPH
3JHH
3JHH
t
t
4JFH
52
Identifying 31P couplings
31P
dd
53
Identifying 31P couplings another example
NMR From Spectra to Structures An Experimental
approachSecond edition (2007) Springler-Verlag Te
rence N. Mitchellm Burkhard Costisella
Ph, 2H
CH3
1H
CH2
1H
54
NMR From Spectra to Structures An Experimental
approachSecond edition (2007) Springler-VerlagTe
rence N. Mitchellm Burkhard Costisella
P31 NMR
55
Identifying 31P couplings another example
NMR From Spectra to Structures An Experimental
approachSecond edition (2007) Springler-VerlagTe
rence N. Mitchellm Burkhard Costisella
H-nmr P31 decoupled
1H
CH2
56
To identify a compound PF215NHSiH3
Use as many techniques as possible
Proton nmr spectra is difficult to analyze with
so many Js But with 19F, 15N and 31P spectra
its easier (get heteronuclear J)
57
To identify a compound PF215NHSiH3
Use as many techniques as possible
Using decoupler easier analysis
Another example HX
58
Changing the solvent
Changing solvent can be used to improve
dispersion of chemical shifts
C6D6
CDCl3
59
Changing the solvent
Me
CH2
CH2
C6D6
CH-OH
CH2
CH2 ABX
CDCl3
CH-OH
60
Decoupling
Me
CH2
CH2 ABX
CDCl3
CH-OH
CH2 AB
61
Spin-Spin Decoupling
dq
dq
dd
62
Homo decoupling
NMR From Spectra to Structures An Experimental
approachSecond edition (2007) Springler-Verlag Te
rence N. Mitchellm Burkhard Costisella
JPH
JHH
63
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64
Decoupling H-1 glucose derivative
H-2
H-1
65
Several Decoupling
66
NOE
nOe
67
NOE applying gB2 to the A of an AX spin system
X2
A2
A
A1
X1
Immediately after irradiation, there is NO change
in the intensity of X Turning on the Decoupler do
not change population of the X transition
68
NOE relaxation with double quantum pathway W2
probability (positive NOE)
delay
T1 Dec. continue
W2
After W2 relaxation, there is a net increase in
the intensity of X (50)
Relaxation takes time to establish a new
equilibrium T1 process
69
NOE Relaxation with zero quantum pathway W0
probability (negative NOE)
delay
T1 Dec. continue
W0
W0
After W0 relaxation, there is a net decrease in
the intensity of X (50) ? negative NOE
Relaxation takes time to establish a new
equilibrium T1 process
70
NOE summary of relaxation pathways
W1 probability of single quantum relaxation do
not create nOe
W2
W0
A new population ditribution is generated by
relaxation through dipole-dipole relaxation
double quantum and zero quantum pathway ?W2 and W0
If W2 is efficient (small molecule fast motion
? large frequency )
Level ? increase ? level ? increase also with
decoupler continuing
W2 pathway yield positive nOe
If W0 is efficient (large molecule slow motion
?small freq. Diff.)
Level ? increase ? level ? increase also with
decoupler continuing
W0 pathway yield negative nOe
71
NOE difference nOe-d
NOE is a kinetic effect need delay T1 ? It
take time to develop ? It takes time to decay
control
nOe
difference
72
NOE
Me cis gt 19
Me trans gt -2
Ha gt 45
73
Choosing a structure by nOe
OH
OMe
H3
H6
H5
74
NOEd
NMR From Spectra to Structures An Experimental
approachSecond edition (2007) Springler-Verlag Te
rence N. Mitchellm Burkhard Costisella
75
NOEd example
76
(No Transcript)
77
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78
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79
Organometallic compounds Proton - NMR
Increasing the 1 s orbital density increases the
shielding
Shift to low field when the metal is heavier
(SnH4 - ? 3.9 ppm)
80
Proton NMR Chemical shift

• Further contribution to shielding / deshielding
  is the anisotropic magnetic susceptibility from
  neighboring groups (e.g. Alkenes, Aromatic rings
  -gt deshielding in the plane of the bound)
• In transition metal complexes there are often
  low-lying excited electronic states. When
  magnetic field is applied, it has the effect of
  mixing these to some extent with the ground
  state.
• Therefore the paramagnetic term is important for
  those nuclei themselves gt large high frequency
  shifts (low field). The protons bound to these
  will be shielded (? gt 0 to -40 ppm) (these
  resonances are good diagnostic. )
• For transition metal hydride this range should be
  extended to 70 ppm!
• If paramagnetic species are to be included, the
  range can go to 1000 ppm!!

81
Exchange DNMR Dynamic NMR
NMR is a convenient way to study rate of
reactions provided that the lifetime of
participating species are comparable to NMR time
scale (10-5 s)
At low temperature, hydrogens form an A2B2X spin
system At higher temperature germanium hop from
one C to the next
Index
NMR-basics
NMR-Symmetry