- 8 Dynamic NMR Spectroscopy
NMR spectroscopy is not only a spectroscopic method of determining the chemical structure of the unknown compounds; at the same time, it is also a powerful tool for observing the dynamic processes that may be occurring within or between molecules: bond rotation about bond axes, ring inversion, and tautomerism (intramolecular and intermolecular exchange of nuclei between functional groups). All of these dynamic processes result in changes of the chemical environment. These changes appear in NMR spectra as changes in chemical shifts and coupling constants. The most obvious way of altering the rate of these dynamic processes is to alter the temperature. With variable temperature probes as standard accessories to modem NMR spectrometers, such experiments are easily performed. With these experiments very important physical parameters can be determined, such as the rate of the dynamic processes, and the activation parameters (E^,, AH^, A5'*, and AG*) of equilibrating systems. The appearance of the NMR spectra of an equilibrating system is a function of the rate of interconversion of the molecule. To determine the existence of a dynamic process between the two molecules A and B, the NMR spectra of this system are recorded at different temperatures. Then the observed changes in the spectra are the subject of interpretation.
AF^B
By lowering the temperature, the internal dynamic processes are slowed down, and by increasing the temperature they are accelerated. Let us assume that the activation energy of an interconverting system (A ^ B) is 25 kcal/mol. Components A and B can be separately observed by NMR spectroscopy at room temperature. On raising the temperature the activation barrier is overcome, and if the rate of the interconverting becomes sufficiently rapid, compounds A and B can no longer be distinguished by NMR spectroscopy. Only one signal is then observed in the spectrum. There are some dynamic processes in which the activation barriers are much lower. For example, the activation barriers for the rotation about the C - C single bond of the substituted ethanes are between 5 and 15 kcal/mol. This kind of 'fast process' can be observed directly on cooling the system. Most spectrometers allow the NMR spectra to be measured in a range of + 200 to - 1 5 0 ° C . 213
214
8.
8.1
DYNAMIC NMR SPECTROSCOPY
BASIC THEORIES [73]
Let us assume a system (A ^ B) that is relatively fast on the NMR time scale. This process can be an electrocycHc reaction: a cycloheptatriene-norcaradiene system (56/57) or the ring inversion of cyclohexanes (131/132). Another example is keto-enol tautomerism (133/134), which involves intramolecular proton transfer from one atom to another.
56
57
131
132 ^
equatorial
axial
G O II II HsC"^ CH^ ^CH3
.
133
? ',? I II HgC^ CH ^CHg 134
In an NMR experiment, the systems shown above have two separate signals if interconversion between these systems is slow. In a fast reaction, in which we have a fast dynamic equilibrium, we describe two rate constants k and J^ for the forward and reverse reactions. Of course, the concentrations of A and B will be different (although they may be equal accidentally). The concentrations of A and B are described with the mole fractions n^ and n^.
where n^ ^nd n^ are the mole fractions of A and B, respectively. This equilibrium can be shifted to the left as well as to the right. The position of the equilibrium is determined by AG, the free energy of the process. ^
= e"^^/^^
(40)
The rate constant of the interconversion is determined by the well-known Eyring equation. )fc=^e-^^/«^ Nh
(41)
8.1 BASIC THEORIES
215
where AG^ is the free activation energy, N is the Loschmidt number, and h is the Planck constant. We have to consider two different cases: Slow exchange: As we have discussed above, if the rate of the interconversion of A and B is slow on the NMR time scale, then we will observe separate signals for A and B. The measurement of the relative intensities of the signals will directly give the mole fractions rip, and n^ and, therefore, AG. Fast exchange: If the rate of interconversion is fast, we will observe an average NMR spectrum in which the position of the signal will be determined by the mole fractions n^ and ^B • The chemical shift of the signal is given by the following equation: ^obs
=
«A^A +
(42)
WB^
Since ^A + «B = 1
we have ^obs = ^A^A + (1
- « A ) ^
With the aid of this equation, the mole fractions of the interconverting system can be determined easily provided that we know the exact chemical shifts of A and B, which can be determined by freezing the system. Figure 109 shows the temperature-dependent NMR spectra of an interconverting system. We assume that the components A and B resonate as singlets. In the range of
2>
fast exchange
Q.
E
0
slow exchange
^A
VB
Figure 109 Variable temperature ^H-NMR spectra of an equilibrating system A t=; B.
216
8. DYNAMIC NMR SPECTROSCOPY
slow exchange we can separately observe the individual compounds A and B resonating as singlets. However, by raising the temperature, the NMR spectrum will change. When the barrier of this equilibrium is overcome, and the rate of interconverting accelerates, the signals start to broaden in the intermediate temperature range, finally collapsing into a single line. The temperature at which the individual resonance lines merge into a broad resonance line is referred to as the coalescence temperature. For this coalescence temperature TQ the rate constant of this interconverting system is given by the following equation: TT
'r.-^(A.)
TT (^A -
(43)
^ )
Here Ai' is the difference in hertz between the two signals in the absence of exchange. This equation shows that the rate constant at the coalescence temperature depends only on the chemical shift difference ^v. Since this difference varies with the strength of
84 °C
65 °C
HaC^
/CH3
O'
'CH3
Coalesence Temperature •
^
61 °C
4-
57 °C
4-
38 °C
^W 1 4
1
Oppm
Figure 110 60 MHz ^H-NMR spectra of dimethyl acetamide, recorded at different temperatures. (Reprinted with permission of John Wiley & Sons, Inc. from R.J. Abraham and P. Loftus, Proton and Carbon-13 NMR Spectroscopy: An Integrated Approach, 1978.)
8.2 EXERCISES 61-101
217
the magnetic field, it is expected that the coalescence temperature for a given system will vary with the strength of the magnetic field. By replacing k in the Eyring equation (eq. 41) we obtain the following equation:
^ ( , - , , =
^ e - ' -
(44,
and
^(f = RTc\n J^^"^
^
(45)
Measurement of TQ and the resonance frequencies in hertz can then provide the free activation energy AG*:
AG* = 19 X 10~^Tc(9.91 + log Tc - logiv^ " ^ ) )
(46)
The temperature-dependent ^H-NMR spectra of dimethylformamide 135 are given in Figure 110. The C-N bond between the carbonyl group and the nitrogen atom has a significant double bond character. Rotation of the dimethylamino group is restricted at room temperature. The protons of the two methyl groups are in different chemical environments and therefore resonate at different frequencies. When the temperature is raised, the high energy barrier of rotation is overcome, and then two methyl groups exchange position (cis and trans to carbonyl group) so fast that they cannot be distinguished by NMR spectroscopy. At first, the signals broaden and finally, at temperatures above 85 °C, coalesce to a single line. It is interesting to observe that the acetyl methyl resonance remains sharp during the line broadening of the amide methyl resonances. At the coalescence temperature, the rate constant of this dynamic process can easily be determined by using Eq. (43).
8.2
EXERCISES 61-101
Determine the structure of the compounds whose NMR spectra and molecular formulae are given below. All the spectra (61-101) given in this section are reprinted with permission of Aldrich Chemical Co., Inc. from C.J. Pouchert and J. Behnke, The Aldrich Library oflSC and IH FT-NMR Spectra, 1992.
218
8. DYNAMIC NMR SPECTROSCOPY 61.
1 200
10
10
1<0
120
100
(0
40
«
20
0
1!
C7H17NO
1 1
\
"—
• .4 J ^
1
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_«
-•eL-rr-r-:--10
•
1
lao
lao
J '
'1 "
:::i„ •—K\ 4
3
ioo
so
ao
70.76 68.93 39.78 33.68 31.85 19.39 13.94
'\\\\\
A-
1
13CNMR
mM
1
v^
a»
0
62. [200
140
',^
120
U Li,
i 1
40
^
i 1
i
! • . A
1
C7H12O
k:,,,,,,
»'
1
,
L
. ^ ,
|k,
a
i
4
1
120
100
BO
flO
T
nfnqS .uVi L i
1
40
pt
194.62 150.50 133.70 29.95 27.52 22.39 13.82
=4 1^
113C NMR
.. }
63. T
'
'^W
IfO
140
i
0
C7H14O2
1
1
'
IfIj n i
1
,, 1 , , 1
10
•
,_^
. _ « - « — • ^
1 ''''
—4
1
p3CNMR
,,, 1 i
1111 f "'""i—
jJULWl
176.64 60.02 41.13 26.85 16.63 14.30 11.60
8.2
EXERCISES 61-101
219
64. 200
1 !S
!^iSj
1i
ISfi
ifi
1CS
ii
B
1
11.
13C NMR
s
L
. _
C9H-14O4
IT
l\
1 1 i . 1i^ I r
_ ^
1
171.69 61.03 22.35 15.26 14.18
65. 1 200
180
100
140
IS•0
80
100
60
40
20
0
Ml 1
i 1
13C NMR C7H14O2
k.. ~
174.47 70.41 27.77 27.64 19.09 9.21
1
1
r
lao
140
>
10
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1
i
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LL 1
t
1
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66. [MO
'00
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100
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0
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1
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1
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T
e
jl ,,, M
•
•
•
"
•
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1
f
'
L 4
r*
3
1\
;
13CNMR C9H-14O4 165.34 163.89 144.54 129.80 61.14 15.47 14.13
220
8. DYNAMIC NMR SPECTROSCOPY
67. r?S
180
1<0
140
1
120
ao
100
u
60
I
40
20
13CNMR j
0
1)
1J
C7H12O3 166.37 130.71 128.41 64.42 62.03 29.03 25.10
r*
11
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-
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-
1
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1
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1
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201.67 171.25 168.32 61.77 60.95 54.62 32.36 29.93 14.11 14.02
/
f
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<>
69. »2
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92
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13C N M R C5H802Br2
M
167.36 62.51 41.21 29.72 13.89
8.2
EXERCISES 61-101
221
70. 1 200
180
160
140
120
100
tO
ao
M
20
0
13c NMR 1
_ 1
C4H6O2 1 • • • 1
h i : rr\ii hir
ii i n 1 n!tei n 1 10
1
1
180
160
168.20 68.03 44.30 20.60
hn ilU i;
4
2
1
40
20
1
71. [MO
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120
'
100
8(
'
1
\ 1
60
jiSCNMR "
0
[., II.
C6H12O3
^^-^
109.38 76.28 65.83 63.05 26.72 25.30
., _ ^ /
10
1
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A
, .,HJt~*
1
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3
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gs
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112
1M
40
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2
1 ,
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,,, /,
_^r' r - ^
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uL=j
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13c NMR C11H17N
H
144.02
132.86
Tl
129.03 115.11 35.04
,1 /j
31.49 22.58
14.06
I
Jkd
1
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222
8.
DYNAMIC NMR SPECTROSCOPY
74. fw
'
180
1^
140
120
i
1
\
\i
100
ao
aO
20
40
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0
1
1
!
JL
C12H8
•
139.53 129.23 128.15 127.99 127.54 127.08 124.02
r 1 1 I 10*
i
S:
A^^i^
...,,.t., 7
i''''''' '
1
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4
75. [200
180
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140
120
100
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mf
, ,
4f
20
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if /
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1
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1 lo"^'""^' '
1
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1
7
4
1 jli 1 2
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J C9H8CI2 134.50 128.75 128.19 127.48 60.70 35.39 25.62
8.2
EXERCISES 61-101
223
76, [200
11 0
14p
11 0
120
100
80
BO
40
20
13CNMR
(
C6H4BrCI 1
n '
133.18 132.71 130.13 120.22
\\
1 ,Q
,wl/ ^l,
t
7
1
1
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1
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un
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100
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4^
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1
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] i1
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1 10
i
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1
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78. |200
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40
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134.69 133.99 130.63 128.60 128.06 122.73
/| 1J
n1
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1
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(t
7
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t
I
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1
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224
8. DYNAMIC NMR SPECTROSCOPY
79. Izoo
too
110
140
t21
100
1 1 >
1 1
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an
m
i.
40
»
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0
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—
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r
141.70 131.17 130.09 119.18 35.02 33.43 22.23 13.89
rA
,: ./I I
ii
::'; 1 1 , 1 10
' ' '"
8
1
i
4
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--
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1B
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1
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J
Irf
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139.60 135.42 130.56 129.92 129.05 124.79 122.67 115.27
1 1
1H
13C NMR
Hdbi-rJL^
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81. iao
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lae
i 10
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100
10
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40
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0
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135.32 132.48 131.61 129.90 129.11 128.90 128.56 126.76 125.03 122.88 39.82 19.56
8.2
225
EXERCISES 61-101 82. [200
180
160
140
120
100
80
J
60
40
20
0
13C N M R
J ^1
C9H10O2 158.38
,
129.43 121.13 114.54 68.61 50.10 44.64
A
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)
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7
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100
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1
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1
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.
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1
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40
M3CNMR C9H10O2
1
137.80 129.10 128.26 126.35 103.65 65.22
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84. 10
1
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20
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il 1
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147.31
1
145.27 145.02 117.76 107.57 106.32 100.66 34.59 31.57
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/
1 01
lil 9
8
7
6
S
^3CNMR
4
3
\
^ w -
2
0
226
8.
DYNAMIC NMR SPECTROSCOPY
85. n
i(
19
140
120
M
too
M
40
20
1
L_ ,1.-1
_^__
0
_
1 13C NMR
I -J CsHsCINOa
J_ 1
151.37 138.30 133.72 131.56 126.73 124.37 43.85 14.45
"' / /.i
10
1
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1
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1
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j
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40
4
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"
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L
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N.
1
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1
197.04 163.44 146.88 129.53 126.25 112.98 112.52 55.37 38.87 30.14 23.36
f
-/ 10
>
r
ii
8
i
1
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I
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4
3
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a0
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1
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11
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r
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1
1
s
T
166.60 150.92 131.56 119.73 113.69 62.84 51.23 47.82 12.14
8.2
227
EXERCISES 61-101
88. r»pp
~0
1»
18
t20
BO
too
00
fi
Li
:>L Ll_ 1 10
S
a
1 90
1»
r
6
S
4
1»
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80
>
20
1 1ii 1
J
-uJI
40
3
13CNMR
j
CioHioBrCIO 197.74 135.35 131.88 129.45 128.30 44.52 35.21 26.59
/
-^
n
2
1
0
89.
rs
»
1 10
L
8p
4p
a
h
II
1 1
0
C13H18O2
V
1
1 10
9
~JI
1
»
1
173.45 143.19 128.40 127.23 126.58 69.08 38.99 36.19 18.42 18.05 13.61
/
/ H 4
I
k
1
3
2
81D
*D
13CNMR
f[ ) i. Jt A
0
90. XK)
It10
1n
140
1»
1C10
8(3
JJ
21»
0
C14H12O2
1
1
165.25 148.66 135.40 133.40 130.07 129.92 129.64 128.45 121.30 20.87
/ / .... J
1 '0
t
L/ n ^—^
1M
B
13C NMR
6
S
4
i
t
1
3
1
228
8. DYNAMIC NMR SPECTROSCOPY
91, w
Sp
vn
u
p
S1
!J
!S2
t
4g
22
J
13C NMR C10H9NO5
1 1
164.31 150.62 134.97 130.84 123.54 66.44 49.18 44.65
w k
—/I
L JL1
1
1 >
LA
J
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=iss=
92. f?oo
r»
1 50
1410
ta1
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m.
0
20
40
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>
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1
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y
71.87 71.22 70.42 59.03 30.13
A
'/ /
K„l 11 10
93.
5
B
7
6
5
4
13c NMR
3
2
i
5
8.2
229
EXERCISES 61-101
94. |200
11 0
1 0
1 0
120
It P
,
to
60
40
20
Ji
CeHgO
^
1
1
J
157.78 140.62 110.02 103.77 21.34 12.18
ii
J
Jr /
Jr n MO
a
-
13CNMR i
I
T
N
6
i
4
3
t20
1»
80
90
A
.A 1
0
20
)
2
95. 200
i(HJ
t{n
140
410
J
1 ..L
CsHioOa
J
151.32 142.83 110.24 109.52 70.54 64.98 50.67 44.22
r
/"• • •
r' •
..,,,,, ._.^-.—— o"
^
96. ru0
•
1»
1«10
_____
L_ L
T
120
1 (0
1i
j1
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a
X JL
S
J I. Ixk 4
3
2
100
80
60
40
1 1 11,[
1
i\
0
«
2
)
/._ .. HJc
174.13 136.12 126.84 122.08 120.80 118.10 113.31 111.23 34.54 20.26
0«»« 23ppm.
u "
9
L-J.if i.„
a
7
e
5~
!
4
1
luL
3~"
13C NMR C11H11NO2
,
^ .^-^
•
1
13c NMR
^. 2
1 ~
0
8.
230
DYNAMIC NMR SPECTROSCOPY
97. no
180
160
140
120
80
100
— U LUI
a_J.
60
40
20
M3CNMR
S
C10H9ON
J
1
150.06 147.94 144.08 129.95 128.96 128.18 126.15 123.70 121.74 18.52
:MJ1
— ^ < IJ o
1^
1ULiL 1
7
6
140
1»
4
3
2
1
0
98. 0
1. 1
MO
80
J
1 .
80
40
»
L
J
13CNMR
g
C11H10O3 162.17 161.06 155.85 143.36 128.70 112.84 112.38 101.32. 64.16 14.55
::::;;:;;/ •
\\j\ i .-•" "
h
——
i
i
U»
1 90
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i
Li:;LiJ
ILU
;
3
1
1
)
e0
40
20
0
99. 200
1»
1 40
L. ^
1 1 11
1»
80
L
JL
13c NMR CiiHeOa 160.01 155.52 151.35 147.75 144.84 124.40 120.51 115.21 113.94 106.59 99.17
'•
/
1 1 01
«
«
7
•
5
4
3
2
1
0 ^
i
8.2
231
EXERCISES 61-101 100.
1 200 _ _
0~i
1 5
10
laO
1
100
80
«0
M-/:;:
113C N M F T ] C12H8O4
: : : i r ! :::
;;:;;;[,;;
MIMMjk : M M J ~
0
^^ilW i i i i i-r*: :
\\\\\m
-
20
JL
1 1 11 m ^
1J
40
. . ^ --^ : 5 - -
J
niMiM mnln
5
5
J
5
:-;«::;:
2
;
5
'
159.93 157.60 151.94 149.26 145.67 139.27 112.14 112.14 112.08 105.52 105.41 92.92 60.08
101, 1 200
1iK)
1BO
U 10
1 !0
,.^iJ
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