© Copyright Hans J.

Reich 2010

6. Carbon-13 Nuclear Magnetic Resonance Spectroscopy

6-CMR-1 Measuring 13C NMR Spectra

6-CMR-2 Referencing 13C NMR Spectra
6-CMR-3 Origin of Chemical Shifts
13
6-CMR-4 C Chemical Shift Effects on sp3 Carbons
6-CMR-5 Alkane 13C Shifts - Calculation using Shift increments
13
6-CMR-6 C Chemical Shift Effects on sp2 and sp Carbons
6-CMR-7 One-Bond Carbon-Proton Coupling (1JC-H)
6-CMR-8 Two- and Three-Bond Carbon-Proton Coupling (2JC-H, 3JC-H)
6-CMR-9 Long Range C-H Couplings
6-CMR-10 Assignment of Carbon-13 NMR Signals

_________________________________________

6.1 Measuring 13C NMR Spectra

13
C6 I = ½ Natural abundance: 1.1%
12
C6 I = 0 Natural abundance: 98.9%

Spectrometer Frequency:

1
H 100.0 200.0 300.0 360.0 500.0 600.0 MHz
13
C 25.14 50.28 75.4 90.5 125.7 150.8 MHz

Sensitivity

The low natural abundance of 13C has three principal consequences:

1. It is much harder to obtain 13C than 1H NMR spectra. Whereas an 1H spectrum on 1 mg of a typical
organic compound can usually be obtained in 15-30 minutes of spectrometer time, it might take several hours
to obtain a much lower quality 13C spectrum on the same sample. Thus, unless your compound does not
have useful 1H signals, you will usually measure many more 1H than 13C NMR spectra.

Inherent sensitivity: 1.59% (1H = 100). Sens. = ((C/(H)3

Actual sensitivity: 0.017% (1/5700)

2. The effects of 13C nuclei on spectra of other nuclei (e.g., 1H, 19F, 31P) are very minor. Each proton
signal is surrounded by 13C satellites separated by 1JC-H (typically 120-150 Hz), each with an intensity of 0.5%
of the central peak. The central peak arises from the 98.9% of 12C which is NMR transparent. The 13C
satellites can be readily detected for sharp peaks.

3. Coupling between carbons (JCC) is not usually observed, because two adjacent 13C nuclei occur in
only 1.1% of the carbons. There are thus 13C satellites on the carbon peaks (each about 0.5% of the intensity
of the main peak), in the same way that there are 13C satellites on proton spectra. The couplings can be
measured directly with some difficulty by accumulating many scans on a very concentrated sample, but a
better way is to use one of the multi-pulse 2D experiments (e.g., INADEQUATE) which nulls the central peaks
due to adjacent 12C atoms. Even so, large samples and long acquisition times are required.

6-CMR-1.1
Decoupling

Most 13C NMR spectra are very complex. The methyl carbon of an ethoxy group will appear as a large
quartet, with each line further split into triplets. Even in fairly simple molecules each carbon may be coupled
to a number of different protons. In complicated molecules, these multiplets overlap badly, and may be
impossible to analyze.
1
J
CH = 100-250 Hz
2,3
CH J . 2-10 Hz

To simplify 13C spectra, we usually use some form of broadband decoupling (noise decoupling) to remove
the effect of proton couplings. This also dramatically increases signal intensity, since now all carbons appear
as singlets (assuming absence of other spin 1/2 nuclei like 31P or 19F). The increase is actually greater by a
factor of 2-3 than would be predicted on the basis of simply combining the 13C multiplet intensities because
the Nuclear Overhauser Effect causes additional increases in signal intensity. More about this in Section 8.

C2 25.1 MHz 13C NMR Spectrum in CDCl3

C3

Se C4
130.96 (JSe-C = 102.8 Hz)
132.67 (JSe-C = 11.5 Hz)
129.01 (JSe-C = 2.7 Hz)
C1
126.97 (JSe-C < 2 Hz)

133 132 131 130 129 128 127 126 125

ppm

Figure 6-1.1. 13C NMR spectrum of diphenyl selenide in CDCl 3.

6-CMR-1.2
 Figure 6-1.1 shows the fully coupled and decoupled 13C NMR spectra of diphenyl selenide. Although
the large 1JC-H splittings are easy to identify, the fine structure of the individual multiplets is not first order (e.g.,
only the para carbon has an approximately centrosymmetric pattern, the others do not). This is because we
are looking at the X part of an AA'BB'CX pattern (ABC are protons, X is carbon). Since the AA' and BB’
parts are strongly coupled, we see the usual complex effects of "virtual coupling" on the X resonance (see
Section 5-15, 5-16). When noise {1H} decoupling is applied, the spectrum becomes much more intense, and
only 4 lines remain, one for each carbon.
In this compound we have a second magnetically active nucleus (77Se, natural abundance 7.5%, I =
1/2), so each of the 13C peaks has 77Se satellites, although coupling between C-4 and the selenium is too
small to detect (the satellites are under the main peak).

Attached Proton Tests

The disadvantage of obtaining fully decoupled spectra is that all information about how many protons
are coupled to each carbon is lost. Since information about the number and position of C, CH, CH2 and CH3
carbons is valuable in making structure and spectral assignments, several types of experiments to determine
13
C multiplicities have been developed (undecoupled spectra are not usually used because of extensive
signal overlap and poor signal-to-noise).

Single Frequency Off-Resonance Decoupling (SFORD).

This is the oldest method for determining attached protons, and has been largely replaced by more
efficient methods. In this technique powerful single frequency proton decoupling is applied 500-2000 Hz
upfield or downfield of the proton chemical shifts in the sample. All C-H couplings are reduced in proportion
to:
1. The distance (*) from the decoupler frequency to the proton position,
2. The power of the decoupler.
Typical experiments would reduce the normal one-bond couplings of 125-250 Hz to perhaps 12-20 Hz,
and the longer range couplings to <1 Hz. The spectrum now appears as a series of singlets, doublets, triplets
and quartet depending on whether the carbon is quaternary, or has one, two or three protons attached. Fig. 6-
2 illustrates the effect of decoupler offset on the 13C NMR spectrum of methanol.

Figure 6-1.2. Methyl carbon quartet of methanol obtained for various offsets of the decoupler frequency from
the 1H chemical shift of methanol (from Wehrli and Wirthlin).

6-CMR-1.3
Some difficulties with this technique are:
1. Sensitivity is not very good.
2. Multiplets are not always clean.
3. For complex molecules, some regions of the spectrum can become hopelessly crowded.

6-CMR-1.4
Spectral Editing

There are a number of multipulse experiments which group the signals in a 13C NMR spectrum
according to the number of attached protons.

J-Modulated Spectra. This is the most primitive form of spectral editing. By placing a suitable delay
time between the pulse and the beginning of the acquisition, spectra are obtained in which C and CH2 groups
are positive, and CH and CH3 are negative.

13
C NMR of Triterpene

O
CO2H APT
H O 4.0 msec
delay (1/2J)

APT
7.5 msec
delay (1/J)

Normal

90 80 70 60 50 40 30 20 10 0
ppm

In this experiment, after the pulse there is a short delay, during which the decoupler is turned off, and
13
the C NMR spectrum becomes modulated by the CH coupling frequency. After the delay the decoupler is
turned on, and the FID is recorded. If the delay is 1/J then the quaternary and CH2 carbons are positive, and
the CH and CH3 signals are negative. If the delay is 1/2J all peaks except quaternary are nulled. More on this
experiment in Sect 8-Tech-9.1.

1/40

6-CMR-1.5
 DEPT (Distortionless Enhancement of Polarization Transfer): The DEPT technique has proven superior
to others in providing information on attached protons reliably, efficiently and with high selectivity. It is a
proton-carbon polarization transfer method, so DEPT spectra are actually more sensitive than normal
acquisitions. A set of spectra with pulse delays adjusted for B/2 (DEPT-90) and 3B/4 (DEPT-135) are taken.
The DEPT-90 spectrum shows only CH carbons, the DEPT-135 shows positive CH3 and CH, and negative
CH2 signals. It is important to understand that the appearance of positive and negative signals can be
reversed by phasing, so it is necessary to have some way of determining whether the spectrum has been
phased for CH2 positive or negative. Quaternary carbons are invisible (Fig. 6-1.3).
"Leakage" can occur in DEPT-90 spectra because 1JC-H varies as a function of environment, and the
technique assumes that all 1JC-H are identical. This can result in small peaks for CH2 and CH3 signals, which
should have zero intensity. For similar reasons the C-H of terminal acetylenes (C/C-H) will show anomalous
intensities in DEPT spectra (either nulled or very small in DEPT-90, or present in DEPT-135) because the C-
H coupling is much larger (around 250 Hz) than the normal value of 125 Hz for which the DEPT experiment is
usually parameterized.

Small amount
of "leakage"
DEPT-90 CH only

DEPT-135 CH, CH3 positive

CH2 negative

Note absence
of quaternary carbons

OH
CDCl3

Normal

120 100 80 60 40 20
ppm

Figure 6-1.3. The normal 13C NMR spectrum and a typical set of DEPT spectra of an alkyne. Note the
absence of the quaternary alkyne carbons in the DEPT spectra, and the presence of small peaks for the CH2
and CH3 signals in the DEPT-90 spectrum, which, in principle, should have only CH signals.

1/38

6-CMR-1.6
 6.2 Referencing C-13 NMR Spectra

Tetramethylsilane (TMS) is the primary reference for C-13 spectra. The relatively low sensitivity of C-13
NMR requires the addition of substantial amounts of TMS, so it is common to use solvent peaks as a
secondary reference. Below are listed chemical shifts of several common solvents used in NMR
spectroscopy. Note that isotope shifts are quite large in C-13 NMR, so separate values are reported for the
deuterated and protonated solvents (from Levy, J. Magn. Res. 1972, 6, 143; Reich unpublished work).

Compound (solvent) Protio compound (*) Per-deutero compound (*)

Cyclohexane 27.51 26.06

Acetone 30.43 29.22
Dimethyl Sulfoxide 40.48 39.56
Dichloromethane 54.02 53.61
Dioxane 67.40
Tetrahydrofuran 68.12 26.30
Ether 66.23 15.58
Chloroform 77.17 76.91
Carbon tetrachloride 95.99
Benzene 128.53 127.96
Acetic Acid (*CO) 178.27
Carbon Disulfide 192.8
Carbon Disulfide external 193.7 9/32

6-CMR-2.1
 6.3 Origin of Chemical Shifts

There are three principal effects which control NMR chemical shifts: diamagnetic, paramagnetic and
neighboring group anisotropy:
Fd Diamagnetic term - electron circulation within an s orbital causes shifts to low frequency (upfield,
shielding) of the local nucleus. This term dominates proton chemical shifts, it changes in a more or less
predictable way with electron density and hybridization so that chemists feel comfortable in rationalizing many
of the effects observed.
Fn Neighboring group anisotropy - diamagnetic circulation causes local magnetic fields, which will
have an effect on neighboring nuclei. These effects are on the order of at most a few ppm, and are constant
(same size in ppm) independent of the nucleus which is being affected. Thus, anisotropy effects are
important in proton NMR, where they are significant when compared with other effects, but are usually
insignificant for nuclei (such as 13C) that have shift ranges of hundreds of ppm.
Fp Paramagnetic term - circulation of electrons between ground and excited states of p orbitals
induced by the external magnetic field causes large high-frequency (downfield, deshielding) shifts of nearby
nuclei. Although the forces exerted on electrons by the magnetic field are small compared to the energy
differences between ground and exited states, the shifts are very large, and even minuscule amount of
paramagnetic circulation cause very large chemical shifts. All nuclei heavier than 1H (with the possible
exception of 6Li and 7Li) have Fp as the principal chemical shift effect.
The Paramagnetic Term: It is fortunate that Fp often responds in the same way to electron density
effect as does Fd, since this results in parallel 1H and 13C chemical shift features. However, a qualitative
description of the relationship between * and molecular features must consider two factors which affect Fp
and Fd quite differently and may cause very counterintuitive behavior: the 1/)E dependence, and orbital
symmetry effects.
(1) Since we are dealing with promotion of electrons from ground to excited states, the energy
separation between filled and empty orbitals (HOMO-LUMO separation) has an important effect, i.e. low-lying
unoccupied molecular orbitals of the correct symmetry (see (2) below) result in large paramagnetic (high-
frequency) shifts.

Fp % E(1/)E) where )E is the energy separation.

90°
LUMO

electronic :
HOMO
energy ΔE
levels
LUMO
HOMO
Molecular orbital symmetry
requirement for σp

(2) The orbital symmetry relationship between the orbitals determines whether circulation between any
pair of filled and empty orbitals can occur. Since the closest pair of filled and empty orbitals is the HOMO and
LUMO, we restrict our consideration to these. In order for paramagnetic electron circulation(mixing between
ground and excited states) to occur, the HOMO and LUMO orbitals must have the same symmetry after a 90°
rotation. Thus if the HOMO and LUMO are p-orbitals which are perpendicular to each other, Fp will be large.
An especially striking example is provided by the N-protonation of pyridine (Breitmeier, Spohn Tetrahedron
1973, 29, 1145). The C-3,5 and C-4 shifts move to high frequency, as expected from the increase in positive

6-CMR-3.1
charge at nitrogen. On the other hand, the C-2,6 shifts move to low frequency. The latter are close to the N-
lone pair (the HOMO in the Figure above) which has a proper symmetry relationship with the B* orbitals of the
aromatic ring, and are thus most affected by the reduction of paramagnetic electron circulation on protonation
at nitrogen. The 15N chemical shift also moves to lower frequency on protonation.

A very similar example of these chemical shift effects is provided by the comparison between methyllithium
and phenyllithium. Here the C-Li bond plays the same role as the N-lone pair in pyridine. The conversion of
CH4 to CH3Li causes a low-frequency shift, whereas the conversion of C6H5-H to C6H5-Li causes a large high-
frequency shift of the ipso carbon.

CH4 The downfield shift of C-1 in PhLi

H is the result of a favorable
-2.1 ppm HOMO-LUMO symmetry
128.5 ppm relationship and a small ΔE.
CH3 Li Li LUMO
-13.2 ppm 199.7 ppm : Li

Δδ -11.2 Δδ +71.2 HOMO

The individual vector components of the chemical shift can provide additional insights into the effect.
The three components of the 13C chemical shift tensors of the carbene below, measured by solid state NMR
techniques (Arduengo et. al J. Am. Chem. Soc. 1994, 116, 6361) are shown. The *11 component which
dominates the strong high frequency chemical shift of the carbene carbon (213.7 ppm in solution) is the one
perpendicular to the sp2 lone pair on carbon and the empty p orbital, a situation very similar to that in PhLi
above. The chemical shifts for all heavy nuclei are dominated by the paramagnetic term. The three
components of the 29Si (I = ½) chemical shift of the silylene below (R. West, G. Buffy, M. Haaf, T. Mueller, B.
Gehrhus, M. F. Lappert J. Am. Chem. Soc. 1998, 120, 1637) show a similar pattern.

δ22 = 82 t
δ22 = -2.1
Me Me Bu
t
N t
Bu N Bu
+ N
C H N Si: N
C: Si:
N C: N δ33 = -4.5
N N δ33 = 177 N
t t
Me Me t
Bu Bu Bu
δ 135.0 δC = 213.7 δ11 = 370 δSi = 114.7 δ11 = 350.7
in solution solid state (in solution)

6-CMR-3.2
 The C-13 Chemical Shift Scale. The vast majority of 13C chemical shifts fall in the range of 0-220 ppm
(Me4Si = 0.0). A rough grouping can be made according to the hybridization of the carbon atom, with sp3
carbons at lowest frequency (0-70 ppm); sp carbons of the acetylene type at 70-100 ppm, sp2 carbons
(bonded to C and H) at 100-150 ppm, sp2 carbons of carbonyl groups at 160-220 ppm, and sp carbons of the
allene type at 210-220 ppm. The chemical shift ranges given in the graph below are not the complete range,
since unusual combinations of substituents can lead to shifts outside the ranges given.

C
N
C C
O C=C
C C C
O
C C N R3C-O-
X Alkanes

220 200 180 160 140 120 100 80 60 40 20 0 -20

δ

An important point to note is that sp2 carbons of the double bond type cannot be distinguished from
those of the aromatic type. This is in contrast to the situation with proton NMR, where the distinction between
protons bonded to vinyl carbons and aromatic carbons can usually be made easily. Some specific chemical
shifts of parent members of the various functional groups are given below. The chemical shifts of more highly
substituted compounds will generally be to higher frequency.
H
C C O
CH2=N2 H
Me3COH
Me2CHOH H Me4Si
Me-Me
CH3CH2OH CH4
CH2=C=CH2 N
MeOH MeSH
HC≡CH O MeCl
Me3N MeI
HOCH=CH2 CDCl3 + MeBr
Me2O NMe4 MeLi

88.0 77.2 69.6 61.2 55.6 50.2 39.7 27.8 18.2 10.3 5.9 0.0 -2.9 -13.2 -20.0
73.9 73.2 64.6 58.2 47.6 25.223.1 6.5 2.5 -2.1

100 90 80 70 60 50 40 30 20 10 0 -10 -20

δ
Me + Me
N
O
H H
O
O H NH2
HC(OEt)3
CH2=C=CH2 OMe H2C=N-Me
H CH2=CH2
O H P≡C-Me - + Li
C≡N-Me O=C=NMe
C O
⊕ HOCH=CH2 NC-Me
H CO3H-

206.2 199.6 194.0 169.9 164.9 160 156.7 149.0 128.5 123.2 117.7 113.9 102.6
211.7 177.0 170.8 167.9 158.2 127.2 121.7

220 210 200 190 180 170 160 150 140 130 120 110 100
δ

6-CMR-3.3
6-CMR-3.4
 13
6.4 C Chemical Shift Effects on sp3 Carbons Reich Chem 605

Changes in 13C chemical shifts are usually discussed in terms of substituent perturbations ()*) on the
chemical shifts of simpler model compounds. The effects are largest for substituent changes at the carbon
itself (" effects) but sizable substituent effects are seen at the $, (, and sometimes even the * position. The
substituent effects of a number of common functional groups are summarized below. Roughly speaking, the "-
effects are strongly dependent on electronegativity of the substituent, the $-effects are all to higher frequency,
and fairly similar in size, and (-effects are all to lower frequency (except for organometallic substituents) and are
in part the result of steric interactions.

)* (H 6 X) Positive )* are to high frequency (Downfield)

" $ (
X (H-C 6 X-C) (H-CC 6 X-CC) (H-CCC 6 X-CCC)

CH3- +9.4 ("C) +9.5 ($C) -2.4

CH3CH2- +18.8 ("C+$C) +7.0 ($+() -2.1
CH2=CH- +20.4 +6.3 -2.9
HC/C- +4.5 +5.2 -3.5
HO2C- +20.8 +2.7 -2.3
N/C- +3.6 +2.0 -3.1
H2N- +29.1 +11.8 -4.5
O2N- +64.5 +3.1 -4.7
HO- +49.4 ("O) +11.2 ($O) -4.7
CH3O- +58.7 ("O+$C) +6.5 ($O+(C) -6.0
HS- +11.4 ("S) +12.1 ($S) -2.7
CH3S- +20.9 ("S+$C) +6.4 ($S+(C) -3.0
F- +70.1 +7.4 -6.7
Cl- +31.3 +10.2 -4.6
Br- +20.0 +10.4 -3.3
I- -6.1 +11.1 -0.8
(CH3)3Sn- -1.7 ("Sn+3$C) +4.1 +0.9
Li- -1.4 +6.9 +5.4

1. "-Substituent Effects

The "-effect results from the replacement of a directly bonded H by an X group (*C-H 6 *C-X). The
principal factor influencing most "-substituent effects is the electronegativity of the attached atom. Thus, for
electronegative atoms we see strong high-frequency shifts (e.g., CH3OH * 48.8), for electropositive
substituents, low-frequency shifts. For complex groups we must consider $ and ( interactions as well (e.g., X =
OCH2CH3 is "O + $C + (C). As molecules get more crowded, both the " and $ shifts become smaller (branching
effects).

Me-H -2.6
Me-F 75.2 Me-O-Me 61.2 Me|4C 31.5
Me-Cl 24.6 Me-S-Me 18.2 Me|4Si 0.0
Me-Br 10.2 Me-Se-Me 10.4 Me|4Ge -1.9
Me-I -20.2 Me-Te-Me -21.5 Me|4Sn -9.1
Me|4Pb -3.1

6-CMR-4.1
 Heavy-Atom "-Effect: The correlation with electronegativity works well for first, and to some extent,
second row atoms, but there is a "heavy atom" effect which runs counter to electronegativity. Thus iodine--
bearing carbons of all types are strongly shifted to lower frequency. Similarly for C-Te signals.
H CH3 I CH3 Te(CH3)2 CI4 CBr4 CCl4 I
Ph
-25.8
-2.1 -24.0 -21.5 -292.4 -29.4 98.6
I

"-Effect of Triple Bonds: Triple bonds (X = acetylene, nitrile) as substituents also cause unexpectedly
large low-frequency shifts (e.g., CH3-CN * 0.3, CH3C/CH at -1.9, compare with CH3CH=CH2 at 18.7). The
large diamagnetic circulation in the triple bond may be responsible for these shifts. Below is a comparison of the
chemical shifts of octane versus 1-octyne and 4-octyne.
13.6 H H 12.7 -0.7
22.7
68.7 21.4 -0.7
32.1 19.2 -12.9
84.2
29.4 -13.8
δ:
18.6
Δδ: 79.0 Δδ:
29.4 29.0 (from octane) -0.8 δ: (from octane)
79.0
32.1 28.9 -0.9
19.2 -12.9
22.7 31.8 -0.6
21.4 -0.7
13.6 22.9 -0.1 12.7 -0.7
+0.1

"-Effect of Double Bonds. Unlike the situation with proton NMR, where double bonds cause relatively
large shifts of allylic protons, the 13C shifts of carbons directly attached to double bonds are changed relatively
little. Terminal vinyl groups or trans double bonds cause small high-frequency shifts, cis-substituted ones cause
low-frequency shifts. The latter effect is a manifestation of the (-effect (see below).

13.6 -0.1 -0.4

+0.3 +0.3
22.7 +2.9
-2.3 +0.1 +0.2
+1.8
32.1 +2.7 -2.8
-0.4
29.4
Δδ:
δ: 29.4 (from octane)
-0.5 +2.8
-2.9
32.1 -0.2 -0.1 -2.8
0 +2.7
0 +0.5 -0.4 +0.2
22.7 +0.1
0 0 -0.1 +0.3
13.6 -0.4

Cycloalkenes sometimes show larger double bond substituent effects, but the size and even direction is
erratic, as can be seen from the 3,4,5,6 and 7-membered ring examples below..

-2.9 +2.3 +3.0 23.2 +7.0 -6.2 +9.0 26.5 +6.3 +15.1 +6.8
-3.2 +0.6
Δδ: Δδ: Δδ:

28.5 -0.1 -0.4

27.9 -2.4 -5.6 -1.6 +8.3
+1.0 -1.7
-4.8
Δδ: Δδ: +3.0

6-CMR-4.2
 Carbonyl substituents, on the other hand, do cause significant high-frequency shifts.
O
O O
26.5 +11.7 27.9 +14.1
+28.9
Δδ: Δδ: Δδ:
16.3 O O

+41.6

2. $-Substituent Effects

Replacement of H on an adjacent atom by an X group (*C-C-H 6 *C-C-X) is a $-substituent effect. Almost

all substituents cause substantial high-frequency $-shifts (usually ~9 ppm, smaller if crowded), and these are
not very dependent on the electronegativity of the perturbing substituent. As for the "-effect, we have to
consider simultaneous (-shifts (e.g., X = CH2-CH3 is a $C + (C interaction). The origins of $ shifts are not well
understood.

3. (-Substituent Effects

A gamma effect is defined as the replacement of an H by X on the second atom (*C-C-C-H 6 *C-C-C-X).
The (-effect is seen for virtually all X-substituents, provided the (-carbon has an attached hydrogen. There is a
strong proximity component (syn (-effect, (-gauche effect) , which results in a dependence on stereochemistry.
Syn (-effects are to low-frequency ()* is negative). The effect is largely independent of the nature of the
intervening groups. For X = CH3, the effect is upfield by ~6 ppm if X and *C are close in space (gauche or
eclipsed). For acyclic systems, the (C-effect is approximately -2 ppm, reflecting the fraction of the gauche
conformation. The (-effect is extensively used for stereochemical assignments. If a (-atom is close to a carbon
in one isomer, and remote in another, then that carbon will be upfield in the first isomer, as illustrated below (for
a theoretical analysis see: Kleinpeter, E.; Seidl, P. R. J. Phys. Org. Chem. 2005, 18, 272).
The effect is valuable for distinguishing E and Z isomers of alkenes, especially trisubstituted ones, where
other techniques (such as 3JHH) are not available. A CH3 (or other carbon group) which is cis to a substituent
will be to lower frequency (upfield) of the isomer in which the carbon substituent is cis to a hydrogen The effects
are very similar across C=N double bonds.
C C
This carbon shift will be to lower frequency (upfield)
The γ-effect:
X can be C, O, N, halogen, S, etc
X H H X

OH
OCH3 OCH3
137.5 132.2

17.6 12.1 12.5 8.8

25.6 17.7 17.6 12.9

H H OH
75.8 82.1 NHTs OH N
82.5 80.3 N N
110.1 109.4
31.9 25.7
141.3 140.3
18.6 25.3 17.1 21.5 14.7
15.9

6-CMR-4.3
 Stereochemical relationships in a variety of cyclic compounds can be deduced from the presence or
absence of (-gauche interactions.
H O-
28.0 22.1 26.3 30.9 27.0
21.1
N N+
S S
29.3 S S
35.5

12.5 14.4 39.0 37.5 15.6 CH3 17.3 CH3

48.8
31.1 30.7 H
H CH3 CH3 -7.0
25.1 Si Si Si
Si -4.4
23.2 CH3
25.5 135.5 25.9 132.4 21.8 137.8 H
CH3 -7.3 H
-2.3

58.4 56.0 54.9 Cl Cl

O 12.9 O
N N N N N N
17.6 18.2
22.5

O O O 26.2 23.8
S S S
S 22.0
S 18.7
32.1 28.8 20.4 29.4 26.2
O
OH
S 13.7
S
Some substituents also cause anti (-effects, i.e. when X and the (-carbon are antiperiplanar. Alkyl
substituents show very small antiperiplanar (-shifts, but for X = O, N, or F significant effects are seen. Anti (-
effects are almost always smaller than gauche (-effects and they can be either to lower or higher frequency
depending an a variety of structural factors. For example, if the perturbing substituent is at a quaternary center
in a cyclohexane (as in 1-methyl-1X-cyclohexanes) then the anti (-effects are to high frequency (downfield),
whereas they are to lower frequency (upfield) when the substituent at C-1 is H (Schneider, Hoppen J. Org.
Chem. 1978, 43, 3866).
48.7 48.0 47.3 47.2

H CH3 F OH
27.4 26.9 36.0 33.5 91.5 36.0 70.9
32.6
27.9 27.7 25.3 25.6
H H H H

49.2
47.8 48.1
H H
H
33.0 27.0 31.8 87.3 33.4 68.7
21.4
CH3 21.5 20.9
OH
F

6-CMR-4.4
 Determination of Acyclic Syn-Anti Stereochemistry. The (-interactions present in axial substituents provide
the basis for configurational assignment of syn and anti 1,3-diols using the methyl group chemical shifts of their
acetonide derivatives. In the syn isomers of the acetonides the 6-membered ring has a well-defined chair
conformation, with both R-substituents equatorial. This places one of the acetonide methyl groups axial, the
other equatorial, leading to a ca 10 ppm shift difference between the two methyls. The anti acetonides have a
twist boat conformation, which places the two methyls in a very similar environment, and hence there is a very
small chemical shift differences between them (Rychnovsky Tetrahedron Lett. 1990, 31, 945).
SPh
H δ ~20 TBSO
H O O O O
R1 O δ ~30
syn O
R2 30.13, 19.68
30.02, 19.85
H
H SnBu3
1
R2 R O POMO OH
anti R1 O δ ~25
O O O O O
O R2
H
H
24.48, 24.44 24.50, 24.26

In addition to providing configurational information for systems with well-defined gauche/anti or cis/trans
relationships as in the systems above, the generalized upfield shifts of all four of the atoms involved in gauche
interactions can also be the basis for stereochemical assignments of diastereomeric pairs in acyclic systems.
Thus syn and anti 1,3-diols show a well defined upfield shift for C-O carbons in the anti compared to the syn
isomer. The rationale for this behavior is that intramolecularly H-bonded conformations place a substituent in a
pseudo-axial orientation in the anti isomers, hence upfield shifts, whereas all substituents can be equatorial in
the syn isomer. Similar shift effects are found in boronic acid esters, where this conformational effect is more
rigorously enforced. The effect is easily quantitated by summing the * values of the two C-O carbons - the one
with lower E will be the anti isomer (Hoffmann Tetrahedron Lett. 1985, 26, 1643; Chem. Ber. 1985, 218, 3980;
for applications see: Pelter Tetrahedron 1993, 49, 3007).
Ph
H
OH OH B
H O O
Ph H
syn 47.0 23.6
O
H 45.0 23.0
Ph 67.8 O
74.1
Me Ph 73.3 68.1
Σ (C1 + C3) = 141.9 Σ (C1 + C3) = 141.4

γ-gauche interaction Ph

H B
OH OH Me H O O
anti H O H 40.4
46.7 23.3 Ph O 22.4
Me O
Ph 70.9 64.7 O H H Ph 70.5 64.3
H Ph
Σ (C1 + C3) = 135.6 H Σ (C1 + C3) = 134.8

The stereochemistry of aldol adducts ($ -hydroxy ketones and esters) can also be determined from 13C
chemical shifts by application of similar arguments (Heathcock, Pirrung, Sohn J. Org. Chem. 1979, 44, 4294).
The stereochemistry of 1,2-diols can also be determined from analysis of 13C shifts using related arguments.

6-CMR-4.5
4. *-Substituent Effects

Remote substituents effects across single bonds are small (* 0.2 ppm, , < 0.1 ppm) unless groups are
jammed into each other, (e.g., cis 1,3-diaxial) in which case downfield shifts of several ppm are seen (for a
theoretical analysis see: Kleinpeter, E.; Seidl, P. R. J. Phys. Org. Chem. 2005, 18, 272).
(Δδ 0.8 ppm) (Δδ = 2.5)
12.6
(Δδ 0.6 ppm) 13.4
12.3 δ OH 15.1
12.9 (Δδ = 3.2) 15.5

HO

29.5 32.2
ε
O 22.6 O 22.6 27.2 δ

α γ
20.6 β
31.8 31.8
28.7

A downfield ε-shift
Unavoidable δ-effect

5. 3-Membered Rings

Cyclopropanes, cyclopropenes, epoxides, aziridines and other 3-membered rings tend to show
pronounced upfield shifts. Cyclobutanes and four-membered heterocycles do not show similar effects.
Ring Size Effects
16.1 133.1 H
115.1 18.7 O N S
59.2 18.2
38.2

2.3
H
O N S
-2.9 108.7 40.8 28.7 18.1

23.3 30.2 H
O N S
137.2 72.8 45.3 29.7 27.5
23.1 19.3

23.3 H
32.8 O N S
26.5 68.6 31.7
47.1

130.8 26.7 31.2

25.7
25.4 H
27.0 23.0 127.4 O 69.5 N 47.5 S 29.9

27.7 27.3
27.8
24.9 25.2 26.6

6. Neighboring Group Anisotropy Effects

These effects, which play such an important role in 1H NMR spectroscopy, are usually overshadowed by
other effects in heavier nuclei. This is because anisotropy effects are the same size (in ppm) for all nuclei. A
very striking 2 ppm shift in a proton NMR spectrum will be an (almost) insignificant 2 ppm shift for a carbon at
the same position in the molecule (e.g.; it is often trivial to distinguish vinyl from aromatic protons from their
chemical shift alone, this distinction cannot be made in the 13C spectrum).

6-CMR-4.6
6.5 Alkane 13C Chemical Shift Calculations

Analysis of the 13C chemical shift of acyclic alkanes led to the first accurate method for the prediction of
chemical shifts. Grant-Chaney Calculations (J. Am. Chem. Soc. 1964, 86, 2984, plus later improvements) are
based on the observation that, in addition to ", $, (, and * effects, there are predictable branching effects, such
that the " and $, effects, which are nearly constant for linear molecules, become progressively smaller when
there are nearby tertiary and quaternary carbons. This is illustrated in the graphic below.
β β β
5.9 CH3 9.7 15.6 CH3 8.7 24.3 CH3 7.2 31.5 CH3
α α α α
-2.1 CH4 8.0 5.9 CH3 10.2 16.1 CH2 9.1 25.2 CHCH3 2.7 27.9 C(CH3)2

15.6 CH3 24.3 CH3 31.5 CH3

β' β' γ
13.2 CH3 8.8 22.0 CH3 6.9 28.9 CH3 -1.7 27.2 CH3
α α α β'
15.6 CH3 9.4 24.3 CH2 4.9 29.9 CHCH3 0.5 30.4 C(CH3)2 1.5 32.9 C(CH3)2
β β β α
16.1 CH2 8.9 25.2 CH2 6.8 31.8 CH2 4.9 36.7 CH2 1.4 38.1 CHCH3
γ γ γ β
15.6 CH3 -2.4 13.2 CH3 -1.7 11.5 CH3 -2.8 8.7 CH3 7.2 15.9 CH3

CH3
α 27.8 α
6.0 1.4 CH3
β β
9.0 5.4
γ 0.0 -6.4 γ
δ -0.2 0.0 δ

The Grant-Chaney system uses a constant set of "-, parameters, but then applies branching corrections
which depend on the number of adjacent branched carbons. The method is quite flexible, and provides a basis
for accurately predicting chemical shifts of most alkanes, and can be extended to include other classes of
molecules, using model systems close in structure to the molecule of interest.

*C = -2.1 + EniAi + branching corrections (in * from TMS)

Ai Branching Corrections (1°(3°) = a CH3 carbon (1°) with a CHR2 carbon (3°) attached to it).

" +9.1 1°(1°) 0 2°(1°) 0 3°(1°) 0 4°(1°) -1.5

$ +9.4 1°(2°) 0 2°(2°) 0 3°(2°) -3.7 4°(2°) -8.4
( -2.5 1°(3°) -1.1 2°(3°) -2.5 3°(3°) -9.5 4°(3°) -15.0
* +0.3 1°(4°) -3.4 2°(4°) -7.5 3°(4°) -15.0 4°(4°) -25.0
, +0.1

Observed Calculated by Grant-Chaney Error

8.5 CH3 -2.1 + α + β + 3γ + 1°(2°) = -2.1 + 9.1 + 9.4 - 7.5 + 0 = 8.9 +0.4
36.5 CH2 -2.1 + 2α + 3β + 2°(1°) + 2°(4°) = -2.1 + 18.2 + 28.2 + 0 - 7.5 = 36.8 +0.3
30.3 C -2.1 + 4α + β + 4°(2°) + 3[4°(1°)] = -2.1 + 36.4 + 9.4 - 8.4 - 4.5 = 30.8 +0.5
28.7 CH3 CH3 -2.1 + α + 3β + γ + 1°(4°) = -2.1 + 9.1 + 28.2 - 2.5 - 3.4 = 29.3 +0.6
CH3

In this system, a primary carbon will have one branching correction, a secondary two, a tertiary three, and a
quaternary carbon will have four branching corrections (although some may be zero).

6-CMR-5.1
 A less extensively parameterized but much more general scheme for the estimation of chemical shifts of
alkanes substituted by a variety of functional groups is given below. Instead of branching parameters, this
system uses two types of " and $ parameters - those for the substituent at the end of the chain (n) and those in
which the substituent is in the middle of it (iso). The smaller values of the iso versus the n " and $ parameters
correspond to the branching corrections of the Grant-Chaney system. These parameters are not able to assist
in estimation of shifts for quaternary carbons, and carbons attached to quaternary carbons. One would expect
this much simpler system to produce poorer results, and that is what is observed. It is permissible to mix Grant-
Chaney and the n-iso systems in the same calculation, as long as the same effect is not counted twice
R R

γ α γ α γ
β β β
n iso
α β γ α β γ
R n iso n iso R n iso n iso
CH3 + 9 + 6 +10 +8 -2 NH2 +29 +24 +11 +10 -5
NH3+ +26 +24 + 8 + 6 -5
CO2- +21 +16 + 3 +2 -2
NHR +37 +31 + 8 + 6 -4
COOH +25 +20 + 5 +3 -2
NR2 +42 + 6 -3
COOR +20 +17 + 3 +2 -2
NO2 +63 +57 + 4 + 4 -5
COCl +33 +28 +2 -2
COR +30 +24 + 1 +1 -2 SH +11 +11 +12 +11 -4
CHO +31 0 -2 SR +20 + 7 -3
C≡N + 4 + 1 + 3 +3 -3 S(O)Me +42 - 1 -3

CH=CH21 +21 - + 7 - -2 F +68 +63 +9 +6 -4

C≡CH2 + 5 - + 6 - -3 Cl +31 +32 +11 +10 -4
Phenyl +23 +17 + 9 +7 -2 Br +20 +18 +11 +10 -3
I - 6 + 4 +11 +12 -1
OH +48 +41 +10 +8 -5
OR +58 +51 + 8 +5 -4 SnMe3 - 2 - + 4 - -
OCOR +51 +45 + 6 +5 -3 Li3 - 2 - 9 + 7 + 6 + 6
1
1-Octene. 21-Octyne. 3n-, s-BuLi
To use this system, the chemical shifts of an appropriate model system are corrected for the presence of
substituents by using the parameters in the table. For example, to estimate the C-2 chemical shift of 1-phenyl-
2-methylpropane we use the C-2 shift of isobutane (23.3) and add the $-Ph-n increment (+9), giving 32.3
(observed 30.1). Similarly, C-1 would use C-1 of isobutane (24.6) and "-Ph-n increment (+23) giving 47.6 (obs
45.3). In this case the shifts are estimated with reasonable accuracy.
Model Calculated Ph Observed Error
CH3 24.6 + α-Ph-n (+23) = 47.6 CH2 45.3 2.3

CH3 CH 23.3 + β-Ph-n (+9) = 32.3 CH3 CH 30.1 2.3

CH3 CH3

However, attempts to use this method to calculate the C-2 shift of methyl 2-bromopropionate are a little less
successful. Using methyl propionate as a model, C-2 is in error by 5 ppm, whereas using bromoethane as
model the error is 4 ppm.
Model Calculated Observed Error
CO2CH3 CO2CH3
CH2 27.3 + α-Br-iso(+18) = 45.3 Br CH 39.8 5

CH3 9.0 + β-Br-iso(+10) = 19 CH3 21.2 2

CO2CH3
Br CH2 27.5 + α-COOR-iso(+17) = 44 Br CH 39.8 4

CH3 19.1 + β-COOR-iso(+2) = 21 CH3 21.2 0.2

6-CMR-5.2
 Substituent Effects Across Heteroatoms. The Grant-Chaney $ and ( substituent parameters seem to
work remarkably well even across heteroatoms like N (in amines) and O (in ethers).

Chemical Shift Effects Across Heteroatoms

β γ
CH3 49.3 10.7 CH3 60.0 -2.1 CH3 57.9
O O O
α
H CH3 60.0 8.0 CH2 68.0
CH3 15.0

β
H CH3 36.7 7.8 CH3 45.6
N H N H N CH3
β β
CH2 42.7 9.7 CH2 52.4 7.8 CH2 60.1
γ γ
CH2 34.6 -4.1 CH2 30.5 -2.2 CH2 28.3 Djerassi
δ δ JACS-73-3711
CH2 27.1 0.4 CH2 27.6 0.0 CH2 27.6
CH2 32.3 CH2 32.4 CH2 32.3
CH2 23.2 CH2 23.2 CH2 23.2
CH3 14.2 CH3 14.2 CH3 14.3

6-CMR-5.3
 13
C Chemical Shift Calculations

1. For acyclic alkanes the Grant-Chaney Parameters are the most effective. They can be used either to
calculate shifts completely (from methane), or by a difference method (perturbation).
From methane:
δcalc = -2.1 + 2α + 3β + 3γ + 5 δ + 2°(2°) + 2°(3°) = 35.8
36.7
δobs = 36.7, error = 0.9 ppm
28.3

H From methane:
δcalc = -2.1 + 3α + 1β + 1γ + 1δ + 2ε + 3°(1°) + 3°(1°) + 3°(2°) = 28.9
H H
δobs = 28.3, error = 0.6 ppm
HO
Perturbation

23.3 28.3

δcalc = 23.3 + 1β + 1γ + 1δ + 2ε - 3°(1°) + 3°(2°) = 27.0

δobs = 28.3, error = 1.3 ppm

2. For more complicated systems, use model compounds as close as possible to the actual structures, and
then apply corrections for any structural differences using Grant-Chaney and other parameters (including
branching corrections). If needed, a chemical shift parameter can be calculated by comparing two model
compounds.

Estimate the marked carbon:

Perturbation:
Perturbation: 31.3
OH Base: 31.3
Model: βOH-iso 8.0
CO2H γCH2 -2.5
36.8 δCH2 0.3
36.8
HO δcalc 37.1
OH
δ effect, but OH
δobs = 36.8, error = 0.3 ppm
can ignore

If a parameter is missing,
Perturbation: 36.2
such as the βvinyl-iso needed here, Base: 36.2
try to estimate it: Model: βvinyl-iso 6.2
OH γCH2 -2.5
δCH2 0.3
16.3 32.7 36.8 2°(3°)OH -2.0
16.1 22.3
δcalc 38.2
βvinyl-iso = 22.3 - 16.1 = 6.2 OH
δobs = 36.8, error = 1.4 ppm
αvinyl-iso = 32.7 - 16.3 = 16.4

6-CMR-5.4
 13
6.6 C Chemical Shift Effects on sp2 and sp Carbons

The carbons of double and triple bonds also show the ", $ and ( effects which have been well
established for saturated carbons. In addition, these carbons show large charge density effects resulting from
partial positive and negative charges in the B-system.
There are also heavy atom effects, seen mostly for carbons bonded to iodine.
Heavy Atom Effect - α-Effect of Iodine on sp2 Carbons

H 128.5 114.1
H H H
123.2 71.6
139.2

I
I
130.7 11.2
I I I
85.9 (7.7) 94.4 I
153.3 0.6
(Δδ -37.4) (Δδ -34.1)

1. Conjugation with B-Acceptors and B-Donors

Chemical shifts in B-polarized double and triple bonds follow charge densities in a reasonable way as
qualitatively predicted by drawing resonance structures. Thus the $-carbon of ",$-unsaturated carbonyl
compounds is downfield, whereas those of enol ethers and enamines is strongly upfield. The normal ", $, (
effects discussed in Section 6.4 are seen here also.

O
N OSiMe3 O-Li+
127.4 142.5 149.8 158.6
129.3
δ: 102.8 91.7
127.4 150.7 93.0

O +7.9
-25.1 -8.3 +6.7
Δδ: EtO MeO
+35.5 -2.1 +4.9 -2.7

Δδ from 1,3-butadiene

O
CH3 OCH3 OH O Li+ N(CH3)2 NO2
+8.9 +31.4 +26.9 +40.5 +22.6 +9.1 +20.0
-0.1 -14.4 -12.7 -7.6 -15.6 0.1 -4.8
Δδ:
+0.7 +1.0 +1.4 +1.7 +1.0 0.0 +0.9

-3.3 -7.7 -7.3 -14.2 -11.5 +4.2 +5.8

Δδ from benzene (128.5)

Alkynes with first-row element substituents are also polarized in the same sense. However with second
and third row elements more complicated chemical shifts effects come into play.
O
OEt SEt SiEt3

+12.8 +12.0 +8.7 +13.7

Δδ: +6.0 +15.0 +0.9
-6.3 -5.8 -3.4 -51.2 +9.7 +4.9 +22.9

H H H H H H H
Δδ from acetylene (71.6)

6-CMR-6.1
2. Strongly Charged Systems

Carbanions, carbonium ions. Must be very careful here. If charge is localized (F-charge, sp3 systems),
effects are quite variable, and frequently the opposite of those in B-systems (e.g., C-1 of PhLi is at * 171.9,
CH3Li * -13.2).
On the other hand, if charge is part of a B system, chemical shifts follow charge density rather well (160
ppm/e). The various monocyclic aromatic anions and cations show a remarkably consistent set of chemical
shifts, which can be accurately predicted from the excess charge density at each carbon using the formula
shown (Prog. Phys. Org. Chem 1976, 12, 229).

++ +
+

δ Observed: 207.2 175.0 155 128.5 108.5 102

Charge (ρ): + 1/2 + 1/3 + 1/7 0 1/9 1/5
Calc δ: 208.5 181.3 150.9 128.5 110.9 96.5
(δ = 128.5+160ρ)

6-CMR-6.2
3. Carbonyl Groups

Carbonyl groups appear in two regions: ketones and aldehydes from 190-220 ppm, esters, acids amides
and related carbonyl functions between 150 and 175 ppm. The ketone region is quite distinctive, the only
reasonably common function that appears around 200 ppm is the central carbon of allenes. There are more
interferences in the acyl-X region, with occasional double bond and aromatic sp2 carbons, as well as C=N
carbons appearing in the same range. Unfortunately, the various carboxylic acid derivatives do not have
distinct chemical shifts ranges, so that acids, esters, acid chlorides, amides, anhydrides are not readily
distinguished in the 13C NMR spectrum (this can often be done by examining the carbonyl stretch in the IR
spectrum). Even carbonates, ureas, and carbamates are not well separated from the carboxylic acid
derivatives.
O O O=C=O
C=O 124.2
166.1
181.3
O
O O
Se=C=Se S=C=S
180.4 170.5
209.9 O 192.8
NaO Cl
198.6
O O O
209.7
169.6 162.6
O H
Me2N Me2N H
O O C O
194.0
200.4 H 170.7
O H MeO
219.6 209.1 O O S O O O
188.1 178.1 165.7 156.5
204.1
Me2N H HO Me2N NMe2 MeO OMe

220 210 200 190 180 170 160 150

There are several chemical shift effects of carbonyl groups which are large and consistent enough to be
useful for structure assignment.
Conjugation Effects. Conjugation to a double bond or aromatic ring causes upfield shifts (smaller *
value) of 6-10 ppm for all types of carbonyl compounds. The effect is smaller for nitriles, but in the same
direction.
O O
O O O 120.8
219.6 209.7

206.3 201.4 173.3

NC
H MeO

O O
O O O
117.2 209.8 199.0
197.5 193.3 166.0
NC
H MeO

O O O
195.6 199.0 205.5 As the carbonyl is rotated
out of conjugation, the
chemical shift moves
downfield.

Θ = 0° Θ = 28° Θ = 50°

6-CMR-6.3
 Hydrogen Bonding Effects. Intramolecular hydrogen bonding causes substantial downfield (larger *
value) shifts.

O H O H O H O H
191.0 187.5 H 197.2 190.2

O O
Me

OMe
O O O HO
O
206.3 211.2
OH 206.5
F 209.2

Most carbon signals are quite insensitive to solvent effects. Carbonyl groups are an exception – they move
downfield in protic solvents, an effect also attributed to hydrogen bonding.

6-CMR-6.4
 Olefinic Carbon Shifts

(Roberts et al., J. Org. Chem. 1971, 36, 2757; F. W. Wehrli and T. Wirthlin, "Interpretation of
C-13 NMR Spectra", Wiley, 1974, p. 41). Note that "' is beta to the carbon being calculated, $' is gamma.

C(-C$-C"-C=C-C"'-C$'-C(' *c(olefin) = 123.3 + EAi + corrections

8

Ai Corrections.

" 10.6 ","' (trans) 0

$ 7.2 ","' (cis) -1.1
( -1.5 "," -4.8
"' -7.9 "',"' +2.5
$' -1.8 $,$ +2.3
(' +1.5

Obs Calculated

112.9 CH2 123.3 + "' +2$' + (' = 113.3

5
144.9 CH3 CH 123 + " + 2$ + ( = 146.8
\/
CH
*
CH2
*
CH3

There are quite characteristic differences between the two olefinic carbons as a function of substitution:

e.g. for n $ 3

H2C=CH(CH2)nH CH3HC=CH(CH2)nH CH3CH2HC=CH(CH2)nH

115.1 139.6 125.7 131.7 132.8 129.9

)* = 24.5 )* = 6.0 )* = -2.9

6-CMR-6.5
 6.7 One-Bond Carbon-Proton Coupling (1JCH)

The size of 1JCH is correlated closely with the hybridization of the C-H bonding orbital - the values are
roughly proportional to the % s-character. This arises because the principal coupling mechanism is the Fermi
contact term, which involves transmission of coupling information between the nuclei via the s-electrons (only
s-electrons have finite electron density at the nucleus).

%s 1
%s
1
JCH = 500 JCH = 570 18.4
100 100

The above formulas can be used to estimate hybridization for simple hydrocarbons, but the method works
less well for systems having electronegative substituents. For these the coupling constants go up consistent
with increased s-character in the C-H bond (see CHF3) but the molecular structures do not show the large
distortions from tetrahedral geometry that would be expected from simple application of these formulas.

sp3 (25% s) sp2 (33% s) sp (50% s)

(predict 125 Hz)) (predict 167 Hz) (predict 250 Hz)

H-CH3 125.0 Hz H2C=CH2 156.2 H-C≡C-H 249

H-CH2CH3 124.9 H2C=C=CH2 168.2 H-C≡C-Ph 248
H-CH(CH3)2 119.4 159 H-C≡C-F 275
H-C(CH3)3 114.2 H-C≡N 269
H +
H-CH2NH2 133.0 CH3 H-C≡N-H 320
+ H 168
CH3

Electronegative substituents cause increases in 1JCH, electropositive substituents a decrease.

H-CH3 125.0 Hz
H-CH2Cl 150.0 H-CH2F 149.1 H-CH2OMe 140.0 H-CH2SiMe3 118 H-CH2MgBr 107.7
H-CHCl2 178.0 H-CHF2 184.5 H-CH(OMe)2 161.8 H-CH(SiMe3)2 107 H-CH2Li 98
H-CCl3 209.0 H-CF3 239.1 H-C(OMe)3 186.0 H-C(SiMe3)3 100.4

162.2
H H H F H H F HO O
O NH O O O
H H H H H H H H H
156.2 159.2 200.2 172.0 175.0 267.0 222.0 194.8

Strained rings show unusually large C-H couplings, consistent with the idea that carbons in such rings
have high s-character in the C-H bonds and high p-character in the endocyclic C-C bonds.

H H H
S O N

127 131 136 161 167 170.5 175.5 171

H H

H H H H H
H
H
180 153.8 212 156.2 228.2 168.6

6-CMR-7.1
 Hybridization effects in 1JC-H in Carbanions

Organometallic compounds of electropositive metals generally show the effects of significant

rehydridization to accomodate the negative charge on carbon. For localized lithium and magnesium reagents
there is a tendency for the "lone pair" orbital to maximize s-character, resulting in enhanced p-character for
the C-H bonding orbitals. This can be seen in the sequence of methyl derivatives, where the 1JC-H becomes
progressively smaller as the substituent becomes more electropositive. Similarly for the vinyl series.
H-CH3 125.0 Hz H Li
H H
H-CH2SiMe 3 118
156.2 93.0
H-CH2MgBr 107.7 H H H H
JA-93-10871
H-CH2Li 98
(dimer, THF, -90 °C)
For lithium reagents where B or F delozalization is possible, the opposite effect can be seen, in that the
coupling becomes larger as the C-M bond becomes more polarized, or is broken entirely. This is assigned to
increased planarization of the carbanion center (towards sp2 hybridization) to maximize B overlap. Both
effects can be seen for benzyllithium - in benzene solution the benzyl carbon is strongly coordinated to lithium
(in an aggregate) and J is smaller than in toluene, whereas in THF, and even more so for benzylpotassium
the J becomes larger as the carbanion becomes less strongly coordinated by the metal cation. The chemical
shift behavior can also be interpreted in these terms (Waack, McKeever, Doran Chem. Commun. 1969, 117;
Bauer J. Am. Chem. Soc. 1994, 116, 528)
1
JC-H δ
Ph-CH3 126 20.8

Ph-CH2Li (benzene) 116 18.3

(THF) 132 29.8

Ph-CH2K (PMDTA complex, THF) 151 52.6

The effect ion pair separation for lithium reagents which are delocalized is generally to increase the iJC-H as
a result of planarization of the carbanion center (Reich, H. J.;Dykstra, R. R. J. Am. Chem. Soc. 1993, 115,
7041)

H Li - Li+(HMPA)4
PhSe
:

PhSe PhSe H
Ph Ph Ph
H H
1
JCH = 144 Hz 147 Hz 174 Hz
H
Li Li+(HMPA)4
PhS -
PhS PhS
:

Ph3Si H
H Ph3Si Ph3Si
H
1
JCH = 135 Hz 131 Hz 151 Hz

Ph Ph Li+
Ph -
S S S
:

Si Si H
H Li Si
Ph 135 114 154
H Ph Ph
H
1
JCH = 135 Hz 114 Hz 154 Hz

6-CMR-7.2
 Stereoelectronic Effects on 1JC-H

There are well-defined stereoelectronic effects on the C-H couplings of axial and equatorial protons in
cyclohexanes (Perlin effects). These are most pronounced for situations where strong electronic interactions
of n 6 F* type or F 6 B* type cause perturbations of the C-H bond length and bond strength either by electron
donation into the C-H F* orbital or electron withdrawal from the F orbital. In cyclohexane itself the axial C-H
coupling is slightly smaller than the equatorial ()J = 4.0 Hz), attributable to a stronger donation by the axial
H-C F bond, compared to the equatorial C-C bond. In 1,3-dioxane the difference is much larger ()J = 10.1
Hz), reflecting the larger donation by the p lone pair on each oxygen.
H 154.1
H 122.4 H 157.4 H
O H S H
H O H S 144.9
O 167.5
O
126.4 +

JACS-77-6750 (-104 °C) Bock, ACS, 1973, 27, 2676 Bailey TL 1988, 29, 5621

It is interesting that dithiane shows an inverse effect, attributed to a relatively weak n 6 F*CH interaction,
and a stronger FCS 6 F*CH interaction. There are other indications that n 6 F*CH interaction in dithianes is
weak. For example, the conformational equilibrium of H vs D (measured by the Saunders' isotope
perturbation method) indicates no preference for 4,4-dimethyl-1,3-dithiane, but a significant preference for
C-H to be axial for the 1,3 dioxane and diazane (Anet Chem. Comm. 1987, 595).
H D H D

S D S H O D O H
S S O O

ΔG* = 0 cal/mole ΔG* = 49 cal/mole

6-CMR-7.3
 6.8 Two and Three Bond Carbon-Proton Couplings

Couplings between carbon and protons across two and three bonds are generally small, and can be both
positive and negative. They show many of the trends found for H-H couplings, including the effects of B and
F donors and acceptors for 2J, and the Karplus relationship for 3J.

H H +11.5 H +8
H
JH-H C CH3 H H
O -13 H +9.1
+2.3 H H +19.0 H
+41 H

CH3 CH3 H +7.6 CH3 4.9

JC-H CH3 H
O C CH3
-4.5 H 3.4
+26.7 H +5.0 H H +12.7 H

H 1
JC-H = 126.4
1
JC-H = 122.4 Cyclohexane-d11 at -104 °C
H
2 Sergeyev
4
2
JC-H = -3.94 JC-H = -3.69
JC-H = -0.31 4
JC-H = -0.50 J. Am. Chem. Soc.
3
JC-H = 2.12
3
JC-H = 8.12 1977, 99, 6750

A very useful effect is the reliable difference in cis and trans C-H couplings across double bonds, which
allows assignment of stereochemistry to trisubstituted olefins where H-H couplings are not available. In
applying this technique, it is important to recognize that any given carbon may be coupled to a number of
other protons. Thus some means of recognizing the coupling to the proton of interest must be available,
either from the size of J or multiplicity of the coupling pattern, or from NMR techniques such as 2D
heteronuclear correlation or decoupling experiments.
C
C H
H
3 3
Jtrans = 7-15 Hz Jcis = 5-9 Hz

To determine stereochemistry this way it is desirable to have both isomers, because the cis and trans
coupling ranges do overlap.
O 13.2
7.7
Ph Ph Ph CH3 8.5 CO2H
10.2

H OEt H Ph H CO2H H 6.9

8.3 7.4
O O 6.4

8.7 10.2
Br CO2H 7.0
N N Ph

H CO2H H Br
6.9 H Ph H
5.7 5.9

10.8 9.5
8.3
O2C O2C CO2 O2C Br
O2C CO2

H CO2 H Br H CO2
H
7.3 4.3
6.7

6-CMR-8.1
 6.9 Long Range C-H Couplings

Longer range couplings also show many of the trends found for H-H couplings, including the exceptionally
large 5-bond couplings in 1,3-cyclohexadienes.
2
JCH = -11.0 Hz
cis trans
H CO2H
5
JHH 9.19 7.57
5
JCH 5.75 4.65

JACS-1977-321
H H
2
JHH = -22.0

6-CMR-8.1
 6.10 Assignment of Carbon-13 NMR Signals

The complete assignment of all of the 13C signals of a complex molecule can be a very difficult and time-
consuming process, but one that is necessary for the detailed use of 13C spectra for stereochemical
determinations and conformational analysis, or isotopic labeling studies in biosynthesis or physical organic
chemistry. The techniques that are used are the following:

1. Chemical Shifts. The principal method of roughly grouping 13C signals is by their chemical shift.
Hybridization (sp3, sp2, sp) and electronegative groups (" effect of O, N, F, Cl, Br) cause large 13C chemical
shift effects which can be used to classify groups of resonances. Within groups there are smaller effects
which are useful: resonance interactions within B systems cause predictable upfield and downfield chemical
shift effects. Heavy atoms (e.g., iodine, tellurium) cause upfield shifts, as does the accumulation of adjacent
sterically crowded carbon atoms (branching effects). For detailed assignments involving stereochemical
considerations the (-effect is important.
Even applying chemical shift arguments in a sophisticated way does not provide a way of assigning closely
spaced resonances. In most cases a complete assignment requires a group of compounds with very similar
structures. Within a series of model compounds substituent effects and stereochemical effects can provide
very powerful tools for assignments of even very closely spaced resonances. This is because the direction
and magnitude of a change in chemical shift ()*) resulting from a small structural change is much easier to
predict than the absolute magnitude of the shift (*).

2. Attached Proton Tests (APT). There are a variety of techniques for distinguishing carbons signals on
the basis of the number of attached protons (CH3, CH2, CH, C).
The simplest methods is to measure the 13C NMR spectrum without decoupling (coupled spectrum). This
has the disadvantage that overlapping multiplets are observed for all but the very simplest molecules. Since
a given carbon may be coupled to a number of protons two or three bonds removed, in addition to the one-
bond coupling of interest, these multiplets can be very complicated.
More efficient are various APT tests, in particular the DEPT pulse sequences, which can be run so that
only C-H carbons are visible (DEPT-90), or that all carbons with an even number of hydrogens attached give
positive signals, and all with odd give negative signals (DEPT 135). Quaternary carbons give no signal.
Such techniques depend on the size of 1JCH, and can give ambiguous results when these are unusually large
or small (such as for acetylenic carbons).

3. Proton-Carbon Correlation. For most molecules, the proton signals are easier to assign than the
carbon signals. H-H coupling information is usually easily obtained, and supplements chemical shift
arguments. Some techniques such as homonuclear decoupling and 2D-COSY experiments, which are not
available for carbon because of its low natural abundance, can be easily used. Thus techniques for making
correlations between proton signals and carbon signals, using JC-H, are valuable for assigning 13C NMR
spectra. These experiments include various 2D heteronuclear correlation experiments (HETCOR, HMBC,
HMQC, see Section 8) and can use either 1-bond or longer range (2-bond, 3-bond) CH couplings for the
correlation.

4. Isotopic Labeling. Replacement of an atom attached to carbon by a lighter or heavier isotope results
in small chemical shift changes of the attached carbon, as well as of other nearby carbons. If the isotopic
labeling is done with high specificity, then assignment of several nearby carbons may be possible.
Replacement of H by D in some positions can be easily carried out, for example by base-catalyzed H/D
exchange of protons " to carbonyl groups. There are two effects: the C-D signal will be split into a 1:1:1
triplet by coupling with the spin 1 deuterium nucleus (JCD . JCH/6, typical coupling constant is 20 Hz), and the
carbon signal will be isotopically shifted (the center peak of multiplet will be upfield from that of the C-H signal,
typically by 0.5 ppm, see Section 7). If there are no protons attached to the C-D carbon, then the signal will
also be much weaker because of longer relaxation times (loss of C-H dipole-dipole relaxation), some line

6-CMR-10.1
broadening (due to relatively short deuterium T1), and loss of NOE intensity enhancement. Carbons two and
even three bonds removed from the C-D carbon may also show small chemical shifts and intensity losses
(due to broadening by 2JCCD and 3JCCCD, typical couplings of 1-2 Hz), thus distinguishing them from more
remote carbons, which will be unaffected.

5. Shift Reagents. Lanthanide shift reagents (Eu or Pr $-diketone complexes, see Section 8) will cause
diagnostic chemical shift changes of carbons near polar functional groups complexed to the Lewis acidic
lanthanide atom.

6. T1 Effects. There are predictable effects on T1 relaxation times which can occasionally be used to
make assignments of carbon signals. Carbon signals may be distinguishable either by their relative distance
from nearby protons, by the variable effects of anisotropic motion on carbons on or off a principal axis of
rotation of the molecule, or by differences in the degrees of segmental motion. See Section 8, Dipole-Dipole
relaxation.
38-02

6-CMR-10.2