Chemical Shift
Up to this point, we have been treating nuclei in general terms.
Simply comparing 1H, 13C, 15N etc.
If all 1H resonate at 500MHz at a field strength of 11.7T,
NMR would not be very interesting
The chemical environment for each nuclei results in a unique local
magnetic field (Bloc) for each nuclei:
Beff = Bo - Bloc --- Beff = Bo( 1 - s )
s is the magnetic shielding of the nucleus
Chemical Shift
•
Small local magnetic fields (Bloc) are generated by electrons as they circulate nuclei.
−
•
Current in a circular coil generates a magnetic field
These local magnetic fields can either oppose or augment the external magnetic field
−
Typically oppose external magnetic field
−
Nuclei “see” an effective magnetic field (Beff) smaller then the external field
−
s – magnetic shielding or screening constant
o
depends on electron density
o
depends on the structure of the compound
Beff = Bo - Bloc --- Beff = Bo( 1 - s )
Electron clouds provide
variable shielding of nuclei
from External field (B0)
Resonance frequency between
different nuclei varies based on
their local molecular environment
Chemical Shift
The chemical environment for each nuclei results in a unique local
magnetic field (Bloc) for each nuclei:
Beff = Bo - Bloc --- Beff = Bo( 1 - s )
Chemical Shift
s – reason why observe three distinct NMR peaks
instead of one based on strength of B0
HO-CH2-CH3
 = gBo(1-s)
2p
deshielding
high frequency
downfield
shielded
low frequency
upfield
Shielding – local field opposes Bo
Chemical Shift
• Magnetic shielding (s) is dimensionless and measured in parts per million (ppm)
• s is composed of three components: s = sd + sp + sn

sd – diamagnetic term depends on the density of circulating electrons
–electrons circulating within an s orbital dominates 1H chemical shifts
–depends on electronegativity of substituents
o
1H
attached to sp3 and sp carbons commonly appear at ~0-5 ppm
o
1H
attached to sp2 carbons commonly appear at ~5-10 ppm
Chemical Shift

sd – diamagnetic term depends on the density of circulating electrons
–depends on electronegativity of substituents
1H
Shifts of MenX Compounds
Higher electronegativity of substituent leads to an increase
in deshielding and a downfield shift to higher frequency
Chemical Shift
Correlation between chemical
shifts and electronegativity of
functional groups
Chemical Shift
• s is composed of three components: s = sd + sp + sn
sp – paramagnetic term depends on hindering free circulation of electrons by bonding

and the presence of other positive centers
− electron density in ground and excited p- and d-orbitals induced by magnetic field
 causes large downfield (high-frequency) shifts
 force of magnetic field is small relative to DE
– depends on:
 DE of electronic states:
DE  sp
 Orbital symmetry of HOMO and LUMO
o same symmetry after a 90o rotation
Chemical Shift
• s is composed of three components: s = sd + sp + sn
sp – paramagnetic term depends on hindering free circulation of electrons by bonding

and the presence of other positive centers
– depends on:
<1/r3>, where r is the average distance from the nucleus and the concerned orbitals
– sp is dominate for all nuclei besides 1H

sd and sp are opposite in sign
ppm range follows <1/r3>
1H
ppm range is ~ 15 ppm
13C
ppm range is ~ 210 ppm
Chemical Shift
sp – paramagnetic term depends on hindering free circulation of electrons by bonding

and the presence of other positive centers

13C
chemical shift roughly dependent on the hybridization of the carbon atom
− sp3 carbons at lowest frequency (0-70 ppm)
− sp acetylene carbons at 70 – 100 ppm
− sp carbons bonded to C and H at 100-150 ppm
− sp2 carbony;l carbons at 160 -220 ppm
− sp allene carbons at 210-220 ppm
− sp2 aromatic and double bond carbons cannot be distinguished
Chemical Shift
• s is composed of three components: s = sd + sp + sn
sn – neighbor term and accounts for magnetic anisotropy, polar effect, ring current, effect, etc.

– diamagnetic circulation causes local fields, which have an effect on neighboring nuclei
– on the order of a few ppm and is constant in size and independent of neighboring nuclei
– significant in 1H, but insignificant in 13C because of large chemical shift range (~220 ppm)
Chemical Shift
Magnetic shielding (s) depends on
orientation of molecule relative to Bo

magnitude of s varies with orientation
Bo
Solid NMR Spectra
Orientation effect described by the
screening tensor:
s11, s22, s33
If axially symmetric:
s11 = s22 = s||
s33 = s┴
Asymmetric environment
Axially symmetric
Chemical Shift
19F
In solution, with isotropic tumbling, the
observed shielding is an average of the
shielding tensors

narrow NMR lines in liquids
s = (s11 + s22 + s33)/3
NMR Spectra
The NMR scale (d, ppm)
Bo >> Bloc
-- MHz compared to Hz
Comparing small changes in the context of a large number is cumbersome
d=
w - wref
wref
ppm (parts per million)
Instead use a relative scale, and refer all signals (w) in the spectrum to the
signal of a particular compound (wref ).
IMPORTANT: absolute frequency is field dependent ( = g Bo / 2p)
CH 3
Tetramethyl silane (TMS) is a common reference chemical
H3C
Si
CH 3
CH 3
The NMR scale (d, ppm)
Chemical shift (d) is a relative scale so it is independent of Bo. Same
chemical shift at 100 MHz vs. 900 MHz magnet
IMPORTANT: absolute frequency is field dependent ( = g Bo / 2p)
At higher magnetic fields an NMR
spectra will exhibit the same chemical
shifts but with higher resolution because
of the higher frequency range.
NMR Spectra Terminology
TMS
CHCl3
7.27
increasing d
low field
down field
high frequency (u)
de-shielding
Paramagnetic
600 MHz
1H
0
decreasing d
high field
up field
low frequency
high shielding
diamagnetic
150 MHz
13C
ppm
92 MHz
2H
Increasing field (Bo)
Increasing frequency (u)
Increasing g
Increasing energy (E, consistent with UV/IR)
Chemical Shift
•Variation in screening is a complex combination of factors
difficult to determine dominating factor
 many factors can be simultaneously present

•Factors affecting magnetic shielding:
Change in orbital radius <1/r3>
 Oxidation state electron imbalance
– bond ionicity, p-bond order, s character, bond angles
 Substituents
– correlated with electronegativity
 Neighbor anisotropy effect
– magnetic dipole that does not average to zero from random tumbling
 Through-space electric field effects
– electric field from point charge or electric dipole with a fixed direction relative to the
rest of the molecule
 Isotope effect
– mass change effects bond vibration
 Unpaired electrons
– electron spin has a very large magnetic moment causing large effects on screening
 Solvent
Temperature

Ring Current Anisotropy (neighbor anisotropy effect)
1) external field induces a flow (current) of electrons in p system – ring
current effect
2) ring current induces a local magnetic field with shielding (decreased
chemical shift) and deshielding (increased chemical shifts)
Benzene:
1H
: 7.16 ppm
13C: 128.39 ppm
Cyclohexane:
1H : 1.38 ppm
13C: 26.43 ppm
Ring Current Anisotropy (neighbor anisotropy effect)
Decrease in chemical shifts
Increase in
chemical shifts
Ring Current Anisotropy (neighbor anisotropy effect)
Ring Current Anisotropy (neighbor anisotropy effect)
Proximity to Aromatic Rings will have
pronounced affect on NMR Chemical
shifts.
- Affect also depends on spatial
orientation  above/below plane has
different impact than edge on.
- Which atoms that are next to aromatic
rings depend on the overall structure of
the compound
Through-space Electric Field Effects
• Electric dipoles or point charges possess an electric field with a fixed direction
relative to the rest of the molecule
perturb molecular orbitals
 cause electron drift and altering electronic symmetry

• Screening by electric fields (se):
se = -AEz – BE2
where:
A and B are constants (A>>B)
Ez – electric field along bond to the atom
E – maximum electric field at the atom
Electric field of
point charge
Through-space Electric Field Effects
• -AEz term

increase in screening if the field causes an electron to drift from the bond to the atom
• -BE2 term

always deshielding

only important in proton screening in solvation complexes of highly charged ions (large E)
• se is distance dependent
• Intramolecular effect

averages to zero as molecule tumbles
Through-space Electric Field Effects
Polarity of C-Cl bonds effect 1H shielding
effect diminishes with
distance from C-Cl bonds
Isotope Effects
• Change in mass effects bond vibration and electron density

greatest for larger fractional change in mass (2D/1H)

screening is generally greatest near the heavier isotope
– not always true

effect of multiple isotope substitution is additive

magnitude of effect is dependent on overall screening
Isotope effect has many experimental applications
– aid in assigning NMR resonance
– follow mechanisms of reactions
– monitor exchangeable nuclei
– determine chemical composition
Effects of Unpaired Electrons
• Electrons have very large magnetic moments (ESR – electron spin resonance)
transition metal ion complexes can induce several hundred ppm changes in 1H chemical shifts
– typical 1H chemical shift range is 20 ppm, where majority of chemicals shifts are in the
0-10 ppm range
– either through-space interaction (pseudo-contact) of electron
– or electron delocalized throughout molecule (contact)
 induces large line-broadening (LB)
– LB ~ g2/r6
– may need to use a low g nucleus to observe NMR signal
– broadening falls off rapidly with distance
• use to monitor metal binding sites  resonances that bind metal disappear in
presence of transition metal

Isoshielding diagram for nucleus in
xy plane for a d1 transition metal
ion with octahedral symmetry
J. Mag. Res. (1979) 33:627
Effects of Unpaired Electrons
• Electrons have very large magnetic moments (ESR – electron spin resonance)

transition metal ion complexes can induce several hundred ppm changes in 1H chemical shifts

induces large line-broadening (LB)
1H
spatially close to Co
are broadened
Note the large 1H
chemical shift range
Effects of Unpaired Electrons
• Shift Reagents

lanthanides and actinides give relatively sharp 1H NMR spectra
– Pr, Eu, Dy, Yb
– form high coordinated complexes with organic compounds
– organic compound needs to contain oxygen or nitrogen donor site

large 1H and 13C chemical shifts for organic compound
– depends on distance from lanthanide
– may need to use a low g nucleus to observe NMR signal

Used to resolve overlapped chemical shifts

Used to determine geometry of compound (LB ~ 1/r6)

Used to determine chirality
– Requires chiral shift reagents
– different isomers generate different shifts
Similar Shielding and
Deshielding cones
Effects of Unpaired Electrons
• Shift Reagents

chemical shifts changes are distance dependent, not as dramatic as unpaired electrons

line-broadening is distance dependent (LB ~ 1/r6), not as dramatic as unpaired electrons
Two overlapping peaks are
resolved by shift reagent
Effects of Temperature
• Chemical shifts are temperature dependent

temperature changes during an experiment leads to broaden lines  decreased resolution.

RF pulses, particularly decoupling and spin-lock pulses can heat the sample
– using “dummy” scans before collecting the spectra allows for the sample to reach
thermal equilibrium.
PNAS, Vol. 102, No. 4, 2005
Effects of Temperature
• Chemical shifts are temperature dependent
monitoring chemical shift changes as a function of temperature is a valuable tool that is
frequently used.

– changes in structure, kinetics, dynamics, reaction rates, etc.
Chemical shift changes as a function of
temperature that follows the doublestrand to single strand DNA transition
Biochemistry, Vol. 38, No. 49, 1999
Chemical shift changes as a function of temperature
for aromatic residues in trp repressor indicate
structural changes
Biochemistry, Vol. 34, No. 40, 1995
Effects of Solvent
• Solvent needs to be deuterated (minimize solvent peaks in spectra)

Water is 55 M  most samples are mM to mM
Effects of Solvent
• Chemical shifts are solvent dependent

usually less than 1 ppm for 1H

arises from an interaction between the solvent and the compound
– polarity of the solvent
– molecular shape of the solvent
– aromaticity of the solvent
– consider the common solvents:
(a) water, (b) DMSO, (c) acetone, (d) benzene, (e) chloroform

change in solvent may remove peak overlap (like shift reagents)
Some Examples of SolventSolute Interactions
Effects of Solvent
• Chemical shifts are solvent dependent

solvent chemical shifts (dS) depend on: dS = dB + dA + dE + dH + dW
– bulk susceptibility (dB)
– anisotropy (ring current) (dA)
– reaction field (solvent dielectric constant e) (dE)
– hydrogen bonding (dH)
– van der Waal interaction (dW)
Effects of Solvent
Chemical shift changes going
from CDCl3 to C6D6. Overlap
of resonances change between
the two solvents.
C6D6
CDCl3
Effects of Solvent
• Hydrogen bonding effects on chemical shifts of OH, NH, and SH

Chemical shifts of OH and NH vary over a wide range
– very strongly affected by hydrogen bonds
– large downfield shifts of H-bonded groups compared to free OH or NH groups
– OH and NH signals move downfield in H-bonding solvents like DMSO or acetone
– more acidic OH and NH protons move further downfield because of higher Hbond propensity
o
carboxylic amides and sulfonamides NH protons are shifted well downfield of
related amines
o
OH groups of phenols and carboxylic acids are downfield of alcohols.
NH and OH protons can be recognized from their characteristic chemical shifts or
broadened appearance

− labile protons are also identified by watching peaks disappear with the
addition of D2O
In non hydrogen-bonding solvents (CCl4, CDCl3, C6D5), OH signal generally
appears at δ 1-2


In a pure liquid, OH signal generally appears at d 5
Effects of Solvent
• Hydrogen bonding effects on chemical shifts of OH, NH, and SH

Chemical shifts of OH and NH vary over a wide range
Downfield shift of OH
as non-hydrogen bonding
solvent decreases
Effects of Solvent
• Hydrogen bonding effects on chemical shifts of OH, NH, and SH

Chemical shifts of phenols are further downfield of OH
– δ 5-7 in CDCl3
– δ 9-11 in DMSO

β-Dicarbonyl Compounds - dramatic shifts for strongly intramolecularly H-bonded
enol forms of β-dicarbonyl compounds, o-ketophenols and related structures.
Effects of Solvent
• Hydrogen bonding effects on chemical shifts of OH, NH, and SH

Carboxylic Acids - strongly hydrogen bonded in non-polar solvents,
– OH protons in carboxylic acids are downfield shifted
Amine and Amide N-H Protons

Coupling and peak broadening depends on exchange rate, solvent, and H-bonding

− NH2 protons of primary alkyl amines typically appear as a somewhat broadened
signal at δ 1-2 in CDCl3
− NH signals of ammonium salts are strongly downfield shifted, typically appearing
at δ 4-7 in CDCl3 and δ 8-9 in DMSO
− NH protons of anilines are typically at δ 3.5-4.5 in CDCl3, moving downfield by 12 ppm in DMSO
− Amide NH signals typically appear around δ 7
Effects of Solvent
• Hydrogen bonding effects on chemical shifts of OH, NH, and SH

Thiol S-H Protons.- strongly hydrogen bonded in non-polar solvents,
– S-H protons of alkyl thiols typically appear between δ 1.2 and 2.0 in CDCl3
– only weakly hydrogen bonds, no strong solvent affect
Aryl thiol S-H signals are further downfield, typically δ 3.5-4.5

− result of ring-current effects, and the greater electron withdrawing effect of aryl vs
alkyl groups.
Effects of pH
• Chemical shifts may be pH dependent

changes protonation state of molecule
– effects electron distribution
– point charge electric field effect
– may alter molecular geometry or structure
– may create tautomers
– may change chemical reactivity stability
Effects of pH
• Chemical shifts may be pH dependent
monitoring chemical shift changes as a function of pH is a valuable tool that is frequently used.

– pKa, equilibrium, kinetics, reactivity, etc
pKa measurement of macrocyclic nitrogen
(2)
(1)
(3)
Inorg. Chem. 2001, 40, 4310-4318
Chemical Shift Trends
CHARACTERISTIC PROTON CHEMICAL SHIFTS
Common Chemical Shift Ranges
Type of Proton
Structure
Chemical Shift, ppm
Cyclopropane
C3H6
0.2
Primary
R-CH3
0.9
Secondary
R2-CH2
1.3
Tertiary
R3-C-H
1.5
Vinylic
C=C-H
4.6-5.9
Acetylenic
triple bond,CC-H
2-3
Aromatic
Ar-H
6-8.5
Benzylic
Ar-C-H
2.2-3
Allylic
C=C-CH3
1.7
Fluorides
H-C-F
4-4.5
Chlorides
H-C-Cl
3-4
Bromides
H-C-Br
2.5-4
Iodides
H-C-I
2-4
Alcohols
H-C-OH
3.4-4
Ethers
H-C-OR
3.3-4
Esters
RCOO-C-H
3.7-4.1
Esters
H-C-COOR
2-2.2
Acids
H-C-COOH
2-2.6
Carbonyl Compounds
H-C-C=O
2-2.7
Aldehydic
R-(H-)C=O
9-10
Hydroxylic
R-C-OH
1-5.5
Phenolic
Ar-OH
4-12
Enolic
C=C-OH
15-17
Carboxylic
RCOOH
10.5-12
Amino
RNH2
1-5
Chemical Shift Trends
Acids
Aldehydes
Alcohols, protons a
to ketones
Aromatics
Amides
Olefins
Aliphatic
ppm
15
C=O in
ketones
10
7
5
Aromatics,
conjugated alkenes
Olefins
2
0
TMS
Aliphatic CH3,
CH2, CH
ppm
210
150
C=O of Acids,
aldehydes, esters
100
80
50
0
TMS
Carbons adjacent to
alcohols, ketones
Carbon chemical shifts have similar trends, but over a larger sweep-width range (0-220 ppm)
Common 13C Chemical Shift Ranges
Chemical Shift Trends
• Electronegativity
Proton shifts move downfield when electronegative substituents are attached to the
same or an adjacent carbon

– chemical shifts of protons attached to sp2 hybridized carbons also reflect charges
within the p system
– even without formal charges, resonance interactions can lead to substantial
chemical shift changes due to p polarization
Chemical Shift Trends
• Lone Pair Interactions
when lone pairs on nitrogen or oxygen are anti to a C-H bond, the proton is shifted
upfield (ns* interaction)

– strong conformational dependence of chemicals shifts of protons adjacent to
heteroatoms
– also present in 13C chemical shifts
Chemical Shift Trends
• Steric Compression
when molecular features causes a proton to be close to other protons or to various
functional groups, the proton will be deshielded (higher chemical shift)

– hard to distinguish from magnetic anisotropy interactions
– especially large in highly compressed compounds
Chemical Shift Trends
• Magnetic Anisotropy

local circulation of electrons leads to both shielding and deshielding effects
Chemical Shift Trends
• Magnetic Anisotropy

Aromatic Effect
– effect depends on if the protons are above or below the plane of the aromatic ring
Chemical Shift Trends
• Magnetic Anisotropy
The effect is opposite if the cyclic conjugated system is planar and antiaromatic (i.e., 4n
p electrons)

– effect of phenyl group is highly dependent on conformation
Chemical Shift Trends
• Magnetic Anisotropy

Double Bonds (similar to aromatic rings)
– shielding region above and below the plane of the double bond is controversial
Chemical Shift Trends
• Magnetic Anisotropy

Double Bonds (similar to aromatic rings)
– shielding region above and below the plane of the double bond is controversial
Chemical Shift Trends
• Magnetic Anisotropy

Carbonyl groups- strongly deshielding in the plane of the carbonyl group
Chemical Shift Trends
• Magnetic Anisotropy

Nitro groups- small effect similar to carbonyl group
Upfield shift because
methyl group turns the
nitro group out of the plane
Halogens – protons near lone-paired atoms like halogens show downfield shifts, but
close approach can cause geometry and orbital distortions and affect chemical shifts

Chemical Shift Trends
• Magnetic Anisotropy
Acetylenes – strong diamagnetic affect of electron circulation around the triple bond psystem reverses the shielding relative to double bonds and aromatic rings


Nitriles – cyano group has the same anisotropy as the alkynyl group
Chemical Shift Trends
• Magnetic Anisotropy
Single Bonds – because of many single bonds, it is difficult to define, but some special
cases

•
Axial and equatorial cyclohexane shifts
o
o
o
Axial protons are generally upfield of equatorial protons, but a number of
exceptions
Equatorial in the deshielding (+d) cone of C-C anisotropy, an axial in
shielding (-d)
C-H bond is a strong s-donor than a C-C bond, which leads to increased
electron density in the axial protons (-d).
Chemical Shift Trends
• Magnetic Anisotropy
Single Bonds – because of many single bonds, it is difficult to define, but some special
cases

•
Assignment of syn and anti Aldol adducts
o
o
o
dsyn > danti
Favored conformation of the hydrogen-bonded anti-isomer, the carbinol
proton is in a pseudo-axial orientation
Similar anisotropy effects as an axial cyclohexane
Hsyn
Hanti
Chemical Shift Trends
• Magnetic Anisotropy
Single Bonds – because of many single bonds, it is difficult to define, but some special
cases

•
Cis-substitution effect in Rigid Rings
o
Eclipsed or nearly-eclipsed cis-vicinal substituents cause upfield shifts to
trans proton
Chemical Shift Trends
• Magnetic Anisotropy
Single Bonds – because of many single bonds, it is difficult to define, but some special
cases

•
Stereochemical Relations in Cyclopentanes
o
o
protons with cis-vicinal substituents are generally shifted to lower δ values
(upfield) than those with cis hydrogens
chemical shift is a function of the number of cis-alkyl substituents on the ring
Chemical Shift Trends
• Magnetic Anisotropy
cyclopropanes– similar to benzene, shielding above the ring and deshielding in the
plane of the ring

Chemical Shift Trends (Carbon)
• sp3 carbons
Changes in 13C chemical shifts are usually discussed in terms of substituent
perturbations (Δδ) on the chemical shifts of simpler model compounds

−

carbon chemical shift changes resulting from substituents at a, b, g,
and d positions
13C
effects are largest for substituent changes at the carbon itself (α effects)
−
α-effects are strongly dependent on electronegativity of the substituent
−
b-effects are almost all to higher frequency and similar in size
− g-effects are all to lower frequency (except for organometallic) and are in
part a result of steric interactions
− d-effects are not common and weak
Chemical Shift Trends (Carbon)
• sp3 carbons

Common substituents effects on 13C chemical shifts
Dd (HX) Positive Dd are 13C
chemical shift changes to high
frequency (downfield)
Chemical Shift Trends (Carbon)
• sp3 carbons (a-effects)

a electronegative substituents cause a strong high frequency shift

a electropositive substituents cause a low frequency shift
− For complex groups, need to consider b and g interactions
− As molecules get more crowded, both a and b shifts become smaller –
branching effects
Heavy atom a effect

− Heavy atom effect runs counter to electronegativity effect
o
Electronegativity trends only holds for first row and some second row elements
o
I and Te substituted carbons are strongly shifted to lower frequency
Chemical Shift Trends (Carbon)
• sp3 carbons (a-effects)

Double bond effect
−
13C
shifts of carbons directly attached to double bonds are changed very
little compared to saturated alkane
− Differs significantly from the impact on 1H chemical shifts
− Cyclohexanes show large double bond substituents effect
o
Size and direction is erratic
Chemical Shift Trends (Carbon)
• sp3 carbons (a-effects)

Triple bond effect
− Cause unexpectedly large low-frequency shifts
− Large diamagnetic circulation in triple bond may be partly responsible
Carbonyl substituents

− Cause significant high-frequency shifts
Chemical Shift Trends (Carbon)
• sp3 carbons (b-effects)

Cause substantial high-frequency shifts
− Usually 9-10 ppm
− Smaller if the b or a carbon is tertiary or quaternary

not correlated with electronegativity
− Need to consider g-effects

not well understood
Chemical Shift Trends (Carbon)
• sp3 carbons (g-effects)

Dependency on stereochemistry
− Syn g-effects are to low frequency (Dd is negative)
− Independent on nature of intervening groups
− Shift of ~ -6 ppm for carbon (gauche or eclipsed)
− Shift of -2 ppm for acyclic systems (reflecting fraction of gauche
conformation)
Chemical Shift Trends (Carbon)
• sp3 carbons (g-effects)

Dependency on stereochemistry
− Cis related substituents in cyclopentanes and 5-membered heterocycles
cause upfield shifts (Dd is negative)
Chemical Shift Trends (Carbon)
• sp3 carbons (g-effects)

Dependency on stereochemistry
− Some substituents cause anti g-effects
o Substituent and g-carbon are antiperiplanar
o Significant effects for O, N, F, very little for alkyl
o Always smaller than gauche g-effect, to low or higher frequency
Chemical Shift Trends (Carbon)
• sp3 carbons (g-effects)

Routinely used to determine syn-anti stereochemistry (gauche/anti or cis/trans)
−
based on large chemical shift differences
Chemical Shift Trends (Carbon)
• sp3 carbons (d-effects)

remote substituents effects across single bonds is small
−
~ < 0.2 ppm, unless groups are jammed into each other
Chemical Shift Trends (Carbon)
• sp3 carbons (3-Membered Rings)

3-membered rings show pronounced upfield shifts
−
4-membered rings do not show a similar effect
Chemical Shift Trends (Carbon)
• sp2 and sp carbons

also show the same a, b and g effects
−
show upfield g-effects and downfield b-effects similar in magnitude for sp3
carbons
− There is also the same heavy atom a-effects
Chemical Shift Trends (Carbon)
• sp2 and sp carbons

conjugation with p-Acceptors and p-Donors
−
Vinyl and alkynyl carbons show large charge density effects resulting
from partial positive and negative charges in the p-system
− Chemical shifts in p-polarized double and triple bonds follow charge
densities in a reasonable way as qualitatively predicted by drawing
resonance structures
Chemical Shift Trends (Carbon)
• sp2 and sp carbons

conjugation with p-Acceptors and p-Donors
−
Alkynes with first-row element substituents are also polarized in the
same sense
−
second and third row elements more complicated chemical shifts effects
come into play
Chemical Shift Trends (Carbon)
• sp2 and sp carbons

Strongly Charged Systems
−
If charge is localized (s-charge, sp3 system) effects are variable and
opposite of p-system
−
If charge is part of p-system, chemical shift follow charge density (160
ppm/e)
Chemical Shift Trends (Carbon)
• sp2 and sp carbons

Carbonyl groups
−
ketones and aldehydes from 190-220 ppm
o Very distinct chemical shifts (only overlaps with allenes)
−
esters, acids, amides and related carbonyls from 150-175 ppm
o acids, esters, acid chlorides, amides, anhydrides are not readily
distinguished
o carbonates, ureas, and carbamates are not well separated from the
carboxylic acid derivatives
Chemical Shift Trends (Carbon)
• sp2 and sp carbons

Carbonyl groups
−
Conjugation effects
o Conjugation to double bond or aromatic ring causes upfield shift of
6-10 ppm for all types of carbonyls
o Effect is smaller for nitrile carbons
Chemical Shift Trends (Carbon)
• sp2 and sp carbons

Carbonyl groups
−
Hydrogen Bonding Effects
o Intramolecular hydrogen bonding causes substantial downfield (larger d
values) shifts
•
Carbonyl groups move downfield in protic solvents due to H-bonds
o Most carbon signals are incentive to solvent effects
Chemical Shift Trends (Carbon)
• sp3 , sp2 and sp carbons (anisotropy effects)

These effects are present for ALL nuclei with the same relative magnitude
While a 2 ppm shift for 1H is large and dominates all other effects, it is
inconsequential for 13C

Instead, all of the other effects we have discussed are more important to
understanding 13C chemical shifts than anisotropy effects

Predicting Chemical Shift Assignments
Numerous Experimental NMR Data has been compiled and general trends identified
• See:
 “Tables of Spectral Data for Structure Determination of
Organic Compounds” Pretsch, Clerc, Seibl and Simon
 “Spectrometric Identification of Organic Compounds”
Silverstein, Bassler and Morrill
• Spectral Databases:
 Aldrich/ACD Library of FT NMR Spectra
 Sadtler/Spectroscopy (UV/Vis, IR, MS, GC and NMR)
 http://www.chem.wisc.edu/areas/reich/chem605/index.htm
Ongoing effort to predict chemical shifts from first principals (quantum
mechanical description of factors contributing to chemical shifts)
See: Cynthia J. Jameson, “Understanding NMR Chemical Shifts”, Annu. Rev. Phys. Chem. 1996. 47:135–69
Predicting Chemical Shift Assignments
Empirical Observations
Predicting Chemical
Shift Assignments
Empirical Observations
Example:
Base value:
-O-C:
-COOH:
-phenyl:
-Cl:
1.50
1.35
0.87
1.28
0.31
Estimated: 5.31 ppm
Predicting Chemical
Shift Assignments
Predicting Chemical
Shift Assignments
Example:
Base value:
Zgem Me:
Zcis Br:
Ztrans Ph:
5.25
0.45
0.45
-0.07
Estimated: 6.08 ppm
Observed: 6.23 ppm
Predicting Chemical
Shift Assignments
Predicting Chemical
Shift Assignments
Predicting Chemical
Shift Assignments
Predicting Chemical
Shift Assignments
Predicting Chemical
Shift Assignments
Predicting Chemical Shift Assignments
Empirical Chemical Shift Trends (Databases) Have Been Incorporated Into A
Variety of Software Applications
Example: ChemDraw
• Program that allows you to generate a 2D sketch of any compound
• can also predict 1H and

13C
chemical shifts
matches sub-fragments of structure to structures in database
Fulvene
Protocol of the H-1 NMR Prediction:
5.22
H
H5.22
Node
Shift
Base + Inc.
H
6.44
H
6.44
H
6.44
H
6.44
H
5.22
H
5.22
5.25
1.24
-0.05
5.25
-0.05
1.24
5.25
1.24
-0.05
5.25
-0.05
1.24
5.25
-0.03
5.25
-0.03
6.44
H
H6.44
H
6.44
H
6.44
Estimation Quality: blue = good, magenta = medium, red = rough
6
5
4
PPM
3
Comment (ppm rel. to TMS)
1-ethylene
1 -C=C gem
1 -C=C trans
1-ethylene
1 -C=C trans
1 -C=C gem
1-ethylene
1 -C=C gem
1 -C=C trans
1-ethylene
1 -C=C trans
1 -C=C gem
1-ethylene
2 -C=C c + t
1-ethylene
2 -C=C c + t
2
1
0
Predicting Chemical Shift Assignments
How Does the Predicted Results Compare to Experimental Data?
Parameter
D(A)
D(B)
D(C)
Experimental (ppm)
6.22
6.53
5.85
Predicted (ppm)
6.44
6.44
5.22
Typical accuracy
A number of factors can affect prediction:
Similarity of structures in reference database
 Solvent
 Temperature
 structure/conformation
 additive nature of parts towards the whole

Predicting Chemical Shift Assignments
Experimental NMR Data has also been used to Develop Web-Based Tools to
Predict NMR Spectra
Example: nmrdb.org NMR Predictor (http://www.nmrdb.org/new_predictor)
• Program that allows you to generate a 2D sketch of any compound
• Predicts 1H chemical shifts
Demo of ChemDraw