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Chapter 3 NMR Coupling Red Opt
Chapter 3 NMR Coupling Red Opt
• Multiplicity identifies the number of protons (or other nuclei) that are chemical
bonded to the other nuclei
• The magnitude of the coupling constants identifies the coupling partner, and
provides information on dihedral angles, hydrogen bonds, the number of 1
intervening bonds, and the type of coupled nuclei (1H, 13C, 15N, 19F, etc.)
Coupling Constants (J)
- spin-spin coupling, scalar coupling or J-coupling
Bo
b b
ab1 ab2
Bo
a a
Mixing of Spin
Systems One and Two
bb
b b
ab ab ba ab
a a
aa
Spin System One Spin System Two
3
Coupling Constants
+J/4
bb J (Hz) J (Hz)
I S
-J/4 ab ba
S I
I S
+J/4 aa
The magnitude of the separation is called coupling constant (J) and has units of Hz
4
Coupling Constants
• Through-bond interaction that results in the splitting of a single peak into
multiple peaks of various intensities
Spacing in hertz (hz) between the peaks is a constant
Independent of magnetic field strength
• Multiple coupling interactions may exist
Increase complexity of splitting pattern
• Coupling can range from one-bond to five-bond
One, two and three bond coupling are most common
Longer range coupling usually occur through aromatic systems
• Coupling can be between heteronuclear and homonuclear spin pairs
Both nuclei need to be NMR active i.e. 12C does not cause splitting
1
H
1
H
1 1
H H
13
C three-bond
four-bond
one-bond
1
H
1
H
5
five-bond
Coupling Constants
• Splitting pattern depends on the number of equivalent atoms bonded to
the nuclei
Determines the number of possible spin-pair combinations and energy levels
Each peak intensity in the splitting pattern is determined by the number of spin
pairs of equivalent energy
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Coupling Constants
1 3 3
1 1
1 2 1 3 attached nuclei
Relative
1 3 3 1
1 J 1 Intensity
1 4 6 41 J J
1 5 10 10 5 1
1 6 15 20 15 6 1
1 7 21 35 35 21 7 1 Quartet
Pascal’s triangle
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Coupling Constants
9
Coupling Constants
• Coupling only occurs between non-equivalent nuclei
Chemical shift equivalence
Magnetic equivalence
For no coupling to occur, nuclei has to be BOTH chemical shift and magnetic
equivalent
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Coupling Constants
Rules for Chemical Shift Equivalence:
• Nuclei are interchangeable by symmetry operation
i. Rotation about symmetric axis (Cn)
ii. Inversion at a center of symmetry (i)
iii. reflection at a plane of symmetry (s)
iv. Higher orders of rotation about an axis followed by reflection in a
plane normal to this axis (Sn)
v. Symmetry element (axis, center or plane) must be symmetry
element for entire molecule
Ha
Hb Ha Ha
Ha Ha
180o
C C C
Ha Ha
Ha Hb Ha Ha Ha
Ha
11
Symmetry planes
Coupling Constants
Rules for Chemical Shift Equivalence:
• Nuclei are interchangeable by a rapid process
i. > once in about 10-3 seconds
ii. Rotation about a bond, interconversion of ring pucker, etc.
Ha
Rapid
Ha
Ha
exchange
Ha
Rapid
exchange
12
Coupling Constants
Magnetic Equivalence:
• Nuclei must first be chemical shift equivalent
• Must couple equally to each nucleus in every other set of chemically equivalent nuclei
i. need to examine geometrical relationships
ii. the bond distance and angles from each nucleus to another chemical set must be
identical
iii. Nuclei can be interchanged through a reflection plane passing through the nuclei
from the other chemical set and a perpendicular to a line joining the chemical shift
equivalent nuclei
Fa' Ha'
Hb Cl
Fa Fa'
Chemical shift
equivalent, but not C C
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http://www.chem.wisc.edu/areas/reich/chem605/index.htm
Coupling Constants
Multiple Spin Systems
multiplicity (na+1)(nb+1)
Cl H Ha
3J = 6 Hz
Hb
What is the splitting Hb C C C Ha
pattern for CH2? 3J
Ha = 7 Hz
Cl H Ha
3J = 6 Hz
Hb
Coupling to Hb splits the
CH2 resonance into a
1 doublet separated by 6 Hz
11
121
1331 Down-field resonance
14641 split into quartet
1 5 10 10 5 1
1 6 15 20 15 6 1
1 7 21 35 35 21 7 1
up-field resonance
split into quartet Coupling to Ha splits each
doublet into a quartet
15
separated by 7 Hz
Coupling Constants
What Happens to Splitting Pattern if J changes?
5.5
5.0
4.5
3J = 7 Hz 4.0
Hb 3.5
3J
3.0
Looks like a pentet!
Ha = 7 Hz
2.5
2.0
1.5
3J = 6 Hz
Hb 3.5
3J
Ha = 3 Hz
3.0
2.5
2.0
1.5
16
Occurs because of overlap of peaks within the splitting pattern
Coupling Constants
Cl H Ha
NMR Peaks for coupled nuclei share
Hb C C C Ha the same coupling constants
Cl H Ha
CH3
CH CH2
7 Hz 7 Hz
6 Hz 6 Hz 6 Hz 6 Hz
7 Hz 7 Hz
Integral: 1 2 3
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Coupling Constants
J coupling analysis:
i. Is the pattern symmetric about the center?
ii. Assign integral intensity to each line, outer lines assigned
to 1
iii. Are the intensities symmetric about the center?
iv. Add up the assigned intensities
– Sum must be 2n, n = number of nuclei
– Ex: sum = 16, n = 4
v. Separation of outer most lines is a coupling constant
– Relative intensity determines the number of coupled
nuclei
– Ex: intensity ratio: 1:2, 2 coupled nuclei
– 1st splitting pattern is a triplet (1:2:1)
vi. Draw the first coupling pattern
vii. Account for all the peaks in the spin pattern by repeatedly
matching the 1st splitting pattern 18
viii. Smallest coupling constant has been assigned
Coupling Constants
J coupling analysis:
ix. Coupling pattern is reduced to the center lines of the 1st
splitting pattern.
x. Repeat process
– Ex: sum = 8, n = 3
– Ex: intensity ratio: 1:1, 1 coupled nuclei
– 2nd splitting pattern is a doublet (1:1)
xi. Repeat until singlet is generated
19
Coupling Constants
Hx' Cl
Ha'
[AX]2 or AA’XX’ 20
system AB system
A M X
A M X
TMS
A M X
J(MX) = 6 Hz
21
Coupling Constants (J)
Observed splitting is a result of this electron-nucleus hyperfine interaction
• Coupling is measured in hertz (Hz)
Range from 0.05 Hz to thousands of Hz
Can be positive or negative
1J
o C-H and many other one-bond coupling are positive
2J 3
o H-H in sp CH2 groups are commonly negative
3J
o H-H is always positive
reversed 22
Coupling Constants (J)
Measure the Relative Sign of Coupling Constants
• Multiple experimental approaches (different NMR pulse sequences) or
simulations
E. COSY – two-dimensional
NMR experiment
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Coupling Constants (J)
Measure the Relative Sign of Coupling Constants
• The cross-peak patterns identifies the coupling constant sign and
magnitude
24
Coupling Constants (J)
• Magnitude of the splitting is dependent on:
Number of bonds
3J 9.4 Hz
AB
4J
AC 1.1 Hz
5J
AD 0.9 Hz
3J 8 3J
HH 3J
HH 11.6 & 19.1 Hz HH 9.1 Hz
Hz
Angles between bonds
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Coupling Constants (J)
• Magnitude of the splitting is dependent on:
Cyclohexanes dihedral angles
− Fixed or average conformation
3J 9-12 Hz
aa
3J 3J
ee or ea 3-4 Hz
3J >> 3J ,3J
aa ee ea
28
Coupling Constants (J)
• Magnitude of the splitting is dependent on:
Cyclopentanes dihedral angles
− Fixed or average conformation
29
Coupling Constants (J)
30
Coupling Constants (J)
31
Coupling Constants (J)
32
Coupling Constants (J)
Magnitude of the splitting is dependent on:
Electronegativity of Substituents
33
Coupling Constants (J)
Magnitude of the splitting is dependent on:
Electronegativity of Substituents
34
Coupling Constants (J)
Magnitude of the splitting is dependent on:
Ring Size
− Coupling constants decrease as ring size gets smaller
35
Coupling Constants (J)
Magnitude of the splitting is dependent on:
Bond order
− Coupling constant decreases as bond order decreases
Heterocycles
– Heterocycles have smaller coupling constants compared to hydrocarbons
systems
36
Coupling Constants (J)
• Magnitude of the splitting is dependent on:
Proportional to gagb
1J 125 Hz
C-H
2J 48.2 Hz
F-H
1J 95 Hz
N-H
37
Coupling Constants (J)
• Magnitude of the splitting is dependent on:
Attenuated as the number of bonds increase
– Usually requires conjugated systems (aromatic, allylic, propargylic,
allenic) or favorable geometric alignment (W-coupling)
– Not usually seen over more than 4 to 5 bonds (acetylenes and allenes)
38
Coupling Constants (J)
Magnitude of the splitting is dependent on:
Geminal protons (H-C-H) fall into two major groups
– Unstrained sp3 CH2 protons: 2JH-H -12 Hz
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Coupling Constants (J)
Magnitude of the splitting is dependent on:
Geminal protons coupling constants are effected by the electronic effects of
substituents
– Based on the interaction between the filled and empty orbitals of the CH2
fragment
Note:
opposite
trend
40
Coupling Constants (J)
Magnitude of the splitting is dependent on electronic effects:
In acyclic and unstrained ring systems: 2JH-H ~ -10 to -13 Hz
When CH2 is substituted with a p-acceptor, like carbonyl or cyano coupling
becomes more negative: 2JH-H ~ -16 to -25 Hz
− Reliable and can help with structure assignments
41
Coupling Constants (J)
Magnitude of the splitting is dependent on electronic effects:
In unsaturated carbons: 2JH-H ~ 2.5 Hz
Electronegative substituents (F,O) behave as p-acceptors with a negative
effect with 2JH-H close to zero
Electropositive substituents (Si, Li) behave as p-donors with a negative
effect with 2JH-H
42
Coupling Constants (J)
Magnitude of the splitting is dependent on electronic effects:
Summary of effects, s and p acceptors have opposite effects on coupling, as
do s and p donors
43
Coupling Constants (J)
44
Coupling Constants (J)
45
Coupling Constants (J)
46
Coupling Constants
Weak coupling or first-order approximation
• Up to now, we have assumed the frequency difference (chemical shift) between the
coupled nuclei is large
i. Dn >> J
• Second order effects come into play when this assumption is no longer valid
i. Dn < 5J
• Second order effects lead to very complex splitting patterns that are difficult, if not
impossible to interpret manually and leads to incorrect chemical shifts and coupling
constants
• Interpreting NMR spectra with second-order effects usually requires software
47
Coupling Constants (J)
AB spin system
48
Coupling Constants (J)
Second-Order Effects (Strong Coupling)
perturbs peak intensity and position
AB spin system
49
Coupling Constants (J)
Second-Order Effects (Strong Coupling)
becomes easier to interpret at higher magnetic field strengths
50
Coupling Constants (J)
May be misinterpreted
as a quartet
54
Coupling Constants (J)
Second-Order Effects (AB)
– analysis of second-order splitting patterns
remember: resonance positions are also perturbed
separation between outer lines and inner lines (a-b, c-d) yields coupling constant
JAB = (na-nb) = (nc-nd)
true chemical shift is not the doublet centers
ncenter = ½(nb+nc)
DnAB = √ (na-nd) (nb-nc)
nA = ncenter + ½ DnAB
nB = ncenter - ½ DnAB
dA dB
55
Coupling Constants (J)
56
AB2 spin system
Coupling Constants (J)
57
Coupling Constants (J)
Second-Order Effects (AB2)
– four A lines n1 – n4 and four B lines n5 – n8 and the very weak combination line n9
– calculation of nA, nB, and JAB is simple:
59
Coupling Constants (J)
Second-Order Effects (ABX)
– most complex spin-system that can still be manually analyzed
– ABX has a common appearance
AB – unsymmetrical 8-line pattern that integrates to 2 protons
AB – 4 doublets with the same separation JAB with strong leaning
X – symmetric 6-line pattern that integrates to 1 proton
X – 5th and 6th lines are small and not often seen, apparent doublet of doublet
JAB and nX are directly measurable from spectrum
nX - center of peaks
AB X
JAX, JBX, nA and nB need to be calculated 60
Coupling Constants (J)
Second-Order Effects (ABX)
– Many ABX patterns are sufficiently close to AMX (nAB >> JAB)
first-order solution has an excellent chance of being correct
Center doublets
and get AB pattern
62
Coupling Constants (J)
Second-Order Effects (ABX)
– Correct choice of ab quartet
63
Coupling Constants (J)
Second-Order Effects (ABX)
– Solve the two ab quartets
Treat as normal AB patterns and obtain four chemical shifts (na+,nb+,na-,nb-)
Don’t know which half is a and which is b - two possible solutions
64
Coupling Constants (J)
Second-Order Effects (ABX)
– Solution 1 and Solution 2 – depends on the relative sign of JAX and JBX
Solution 1: JAX and JBX same sign
Solution 2: JAX and JBX different sign
65
Coupling Constants (J)
Second-Order Effects (ABX)
– Which solution is the correct one?
– Several criteria can be used:
1. Magnitude of the couplings – one solution may give dubious (very large or very
small) couplings
2. Signs of coupling constants – the signs can sometimes be predicted and rule
out a solution
all vicinal 3J couplings are positive,
geminal 2J couplings at sp3 carbons are usually negative
CHXCHAHB – JAX and JBX have the same sign
CHACHBHX – JAX and JBX have different signs
3. Analysis of the X-part – the intensities of the lines in the X-part are always
different – most reliable way to identify the correct solution
Solution 1 Solution 2
JAX and JBX same sign JAX and JBX different sign
67
Coupling Constants (J)
Second-Order Effects (ABX)
– AB pattern from ABX spin
system as a function of
changing nAB
68
JAX and JBX same sign JAX and JBX different sign
Coupling Constants (J)
Second-Order Effects (ABX)
– AB pattern from ABX spin
system as a function of
the relative sign and
Magnitude of JAX and JBX
69