Advanced NMR Topics
Second Order Effects in NMR
• Splitting does not follow N+1; cannot be
solved graphically
– Different intensities
– Additional peaks
– Cannot directly measure coupling constants
Causes of Second Order Spectra
• Strong Coupling
• Virtual Coupling
• Magnetic nonequivalence
Strong Coupling
• Compare coupling constant (J) to
difference in shift (Dn)
• If Dn < 5J, then second order
• Simplified by higher field
instrument
• 60MHz: Dn=0.3ppm(60Hz/ppm)
= 18Hz; J= 18 Hz
• 360MHz:Dn=0.3ppm(360Hz/ppm)
= 108Hz; J= 18 Hz
Pople Coupling Nomenclature
• Spin system named by how close protons are in
shift: A, M, X
• AX2 system: one proton coupled to two protons
with distant chemical shift (first order)
• AB2 system: one proton coupled to two protons
with similar shift (second order)
• AMX3: one proton coupled to one proton
coupled to three protons, all distant chemical
shift (first order)
First and Second order systems
• http://www.chem.wisc.edu/areas/reich/nmr/05hmr-07-pople.htm
• http://www.chem.wisc.edu/areas/reich/chem605
/index.htm
Virtual Coupling
Magnetic Equivalence
• Chemical
equivalence
• Magnetic
equivalence
• AA’BB’ system:
disubstituted
benzene
• Deceptively
simple spectra
Modern C-13 NMR Spectroscopy
C-13 Sensitivity
• Only 1% natural abundance
• Split by protons
• 13C/1H J = 125 Hz for sp3 carbon
• Solution to problem: Broadband Decoupling
– No splitting observed
– Increases signal
DEPT NMR
• Distorsionless Enhancement by Polarization
Transfer
• Transfer signal from protons to carbon
2D NMR
• 2 basic experiments – COSY and HETCOR
• COSY
– H-H Correlation spectroscopy
– 1H spectra on x and y axes
• HETCOR
– Heteronuclear correlation spectroscopy
– 13C on one axis, 1H on the other (same sample)
• There are many more 2D experiments – these
are two of the most common
Reading a COSY
spectrum
• X-axis = 1H
spectrum
• Y-axis = 1H
spectrum
• Diagonal =
reference points
(mirror plane:
C=D)
• Off-diagonal
peaks = coupled
protons
Isopentyl acetate
A = 1-2 coupling
B=
C=
How to read a
HETCOR spectrum
• X-axis = 13C
spectrum
• Y-axis = 1H
spectrum
• No diagonal (no
mirror plane)
• Peaks indicate a
13C and the 1H’s
directly
attached to it.
Isopentyl acetate
In the C-13
spectrum, which
carbon signal is
furthest upfield?
From induction, we
might think that it
is carbon 1, but…
5 6
1
• Very useful for
– Finding
overlapping
proton signals
– Identifying
diasteriotopic
carbon and
protons atoms
3
3
4
2
Interpret all NMR spectra for 6-chlorohexanol
(don’t need to calculate coupling constants):
1
2
4
3
6
5
7
Note: These NMR spectra were obtained in a solvent in which
acidic protons are visible, and coupling to these protons is
observed.
1H
NMR 600 MHz
1
2
4
3
13C
6
5
7
NMR 150.9 MHz
DEPT-90
DEPT-135
normal
COSY 600 MHz
1
2
4
3
6
5
7
HETCOR 600 MHz
1
2
4
3
6
5
7
Ribavirin
• Anti-viral
• Used to treat hepatitis C
• Guanosine analog—
inhibitor or viral RNA
synthesis
Riboflavin DEPT
DEPT 135
O
N
H
HO
H
N
O
H
160
X : parts per Million : 13C
160.0
150.0
140.0
140
140.0
H
N
H
HO
150.0
H
H
H
160.0
N
H
130.0
130.0
OH
120.0
120
120.0
110.0
ppm
110.0
100.0
90.0
100.0
90.0
100
80.0
70.0
80.0
70.0
80
60.0
60
60.0
10.0
g
f
e
d
i
h
k
j
l
6.0 5.9 5.8 5.7 5.6 5.5 5.4 5.3 5.2 5.1 5.0 4.9 4.8 4.7 4.6 4.5 4.4 4.3 4.2 4.1 4.0 3.9 3.8 3.7 3.6 3.5 3.4 3.3 3.2 0
Y : parts per Million : 1H
(Millions)
Ribavirin COSY
l
k
j
i
h
g
f
e
d
6.0
5.9
5.8
5.7
5.6
X : parts per Million : 1H
5.5
5.4
5.3
5.2
5.1
5.0
4.9
4.8
4.7
4.6
4.5
4.4
4.3
4.2
4.1
4.0
3.9
3.8
3.7
3.6
3.5
3.4
3.3
0
(Millions)
10.0
20.0 40.0
A B
C
D
G
E F
H
0
(Thousands)
Ribavirin HETCOR
4.0
l k
j
i
h
5.0
g
6.0
f
e
d
7.0
g
8.0
b
a
9.0
Y : parts per Million : 1H
c
160.0
150.0
X : parts per Million : 13C
140.0
130.0
120.0
110.0
100.0
90.0
80.0
70.0
60.0
50.0
0
2.0
(Millions)
4.0
6.0
8.0