CHAPTER 10

Using Nuclear Magnetic Resonance

Spectroscopy to Deduce Structure
Physical and Chemical Tests 10-1
Purification:
Chromatography
Distillation
Recrystallization
Comparison to known compounds:
Melting point
Boiling point
many other properties
When the properties of an unknown purified substance match
those in the literature for a known compound, the identity and
structure of the substance are still not known with certainty.
Many new substances are newly synthesized for the first time and
their properties are not in the literature.
Elemental analysis reveals the gross composition of the sample.
Chemical tests identify the functional groups present.
For larger molecules, knowledge of the composition and functional
groups present in a substance are not enough to determine the
chemical structure of the substance. For instance, the alcohol
C
7
H
16
O:
Defining Spectroscopy 10-2
Spectroscopy is a technique for analyzing the structure of
molecules, usually based on how they absorb electromagnetic
radiation. Four types are most often used in organic chemistry:
Nuclear Magnetic Resonance spectroscopy (NMR)
Infrared spectroscopy (IR)
Ultraviolet spectroscopy (UV)
Mass spectroscopy (MS)
NMR spectroscopy of C and H provides the most detailed
information regarding the atomic connectivity of a molecule.
Defining Spectroscopy 10-2
Molecules undergo distinctive excitations.
Electromagnetic radiation can be described as a wave having a
wavelength (), a frequency () and a velocity (c).
The speed of light in a vacuum is 3 x 10
10
cm s
-1
or 3 x 10
8
m s
-1
.
The units of wavelength must match those used for the speed of
light.
The units of frequency are cycles s
-1
(or just s
-1
) or Hertz (Hz).
Molecules absorb energy in discrete packets called quanta. A
quanta of electromagnetic radiation is referred to as a photon.
The energy of a photon is determined by the frequency of the
incident radiation:
E = h
When a photon of energy is absorbed by a molecule, it causes
electronic excitation or mechanical motion to occur.
The electronic excitations and motions of a particular molecule
are also quantized so only certain frequencies of radiation are
able to be absorbed.
An analysis of the frequencies of electromagnetic radiation
absorbed by a molecule provides information about the
arrangement of the atoms in the molecule.
The lowest energy state of a molecule is called the ground state.
Absorption of electromagnetic radiation causes the molecule to
move to an excited state.
The difference in energy between the excited state and the
ground state must be exactly equal to the energy of the photon
absorbed.
Absorption of X-rays results in the promotion of electrons from
inner atomic shells to outer ones (electronic transitions). This
requires X-ray energies greater than 300 kcal mol
-1
.
UV and visible absorption excites valence shell electrons, typically
from a filled bonding to an unfilled antibonding orbital. This
involves energies between 40 and 300 kcal mol
-1
.
IR absorption causes bond vibration excitation: 2 to 10 kcal mol
-1
.
Microwave radiation excites bond rotations: ~10
-4
kcal mol
-1
.
Radiowaves, in the presence of a magnetic field, produces
alignment of nuclear magnetism: ~10
-6
kcal mol
-1
. This is the
basis of NMR.
In this diagram, frequency is specified in units of wavenumbers,
defined as 1/, which is the number of waves per centimeter.
Wavenumbers are used to specify energy in infrared spectroscopy.
A spectrometer records the absorption of radiation.

Continuous Wave Spectrometry (CW)
Radiation of a specific wavelength (UV, IR, NMR, etc.) is
generated and passes through a sample.
The frequency of the radiation is continuously changed and
the intensity of the transmitted beam is detected and
recorded.
Frequencies that are absorbed by the sample appear as peaks
deviating from a baseline value.

Fourier Transform Spectroscopy (FT)
A much faster technique.
A pulse of electromagnetic radiation covering the entire
spectrum under scrutiny (NMR, UV, IR) is used to obtain the
whole spectrum instantly.
The pulse may be applied multiple times and the results
accumulated and averaged, which provides for very high
sensitivity.
The signal measured is actually the decay, with time, of the
absorption event. This signal is then mathematically
transformed using a Fourier transform, producing the more
familiar frequency versus absorption plot.
Proton Nuclear Magnetic Resonance 10-3
Nuclear spins can be excited by the absorption of
radio waves.
Many nuclei can be thought of as spinning on their axes, either
clockwise or counterclockwise.
One such nucleus is the hydrogen nucleus:
1
H.
A
1
H nucleus is positively charged and its spinning motion
generates a magnetic field.
In the presence of an external magnetic field, H
0
, the magnetic
field of the hydrogen nucleus can be oriented either with H
0
(lower
energy) or against H
0
(higher energy). These two states are
called and spin states, respectively.
The difference in energy between the and states depends
directly on the external magnetic field strength, H
0
.
21,150 G 90 MHz
42,300 G 180 MHz
70,500 G 300 MHz
The actual energy difference is small. At 300 MHz, the energy
difference for a proton is about 3 x 10
-5
kcal mol
-1
.
Because the energy difference is so small and the equilibrium
between the two states is so fast, the numbers of nuclei in the
two states are nearly equal, however, a slight excess will be in the
state because of the external magnetic field.
When electromagnetic radiation having the same energy as
energy difference strikes the nucleus, the electromagnetic
radiation is absorbed and the slight excess of nuclei in the state
is reduced.
Many nuclei undergo magnetic resonance.
In general, nuclei composed of an odd number of protons (
1
H and its
isotopes,
14
N
19
F, and
31
P) or an odd number of neutrons (
13
C) show
magnetic behavior.
If both the proton and neutron counts are even (
12
C or
16
O) the nuclei
are non-magnetic.
In a hypothetical scan of CH
2
ClF in a 70,500-G magnet, the
following spectrum would be observed:
High-resolution NMR spectroscopy can differentiate
nuclei of the same element.
In the NMR spectrum of ClCH
2
OCH
3
at 70,500-G from 0 to 300
MHz, one peak would be observed for each element present.
Using high-resolution NMR spectroscopy, the region around each
of these peaks can be expanded and additional spectral details
can be observed.
Using NMR Spectra to Analyze Molecular
Structure
10-4
The position of an NMR absorption of a nucleus is called its
chemical shift.
Chemical shifts depend upon the electron density around a
nucleus and are thus controlled by the structural environment of
the nucleus.
The NMR chemical shifts provide important clues for determining
the molecular structure of a chemical compound.
The position of an NMR signal depends on the
electronic environment of the nucleus.
In the high-resolution
1
H NMR spectrum of
chloro(methoxy)methane above, two separate resonance
absorptions of hydrogen are observed.
These absorptions reflect the differing electronic environments of
the two types of hydrogen nuclei present.
Electrons in the bonds connecting the hydrogen atoms to the
molecule affect the NMR absorptions.
Bound hydrogens are connected to a molecule by orbitals whose
electron density varies:
Bond polarity
Hybridization of the attached atom
Presence of electron withdrawing/donating groups
The electrons in these orbitals are affected by the external
magnetic field, H
0
, in such a way as to generate a small local
magnetic field, h
local
, opposing H
0
.
The total magnetic field seen
by the hydrogen nucleus is
the sum of these two fields
and is thus reduced. The
hydrogen nucleus is said to
be shielded from H
0
by its
electron cloud.
The degree of shielding of a nucleus depends upon its
surrounding electron density.
Adding electrons increases shielding.
Removing electrons causes deshielding.
Shielding causes a displacement of an NMR peak to the right in
the spectrum (shifted upfield).
Deshielding causes a displacement to the left (shifted downfield).
Chemically equivalent hydrogens in a molecule all have identical
electronic environments and therefore show NMR peaks at the
same position.
In the NMR spectrum of 2,2-dimethyl-a-propanol, there are three
different peaks due to absorptions by:
Nine equivalent methyl hydrogens on the butyl group (most
shielded);
One hydrogen on the OH;
Two equivalent methylene hydrogens.
The chemical shift describes the position of an NMR
peak.
Rather than reporting the exact frequency of each resonance in
an NMR spectrum, we measure frequencies relative to an internal
standard, tetramethylsilane, (CH
3
)
4
Si.
To remove the effect of differing applied magnetic fields using
different spectrophotomers, the frequencies relative to
tetramethylsilane are divided by the frequency of the
spectrometer.
This yields the chemical shift (), a field-independent number
measured in ppm.
For (CH
3
)
4
Si, is defined as 0.00.
The spectrum above would be reported as:
1
H NMR (300 MHz, CDCl
3
) = 0.89, 1.80, 3.26 ppm

Functional groups cause characteristic chemical
shifts.
Each type of hydrogen
in a molecule has a
chemical shift which
depends upon its
chemical environment.
The absorptions of alkane hydrogens occur at relatively high field.
Hydrogens close to an electron withdrawing group (halogen or oxygen)
are shifted to relatively lower field (deshielding).
The more electronegative the atom, the more the deshielded methyl
hydrogens are relative to methane.
Multiple substituents exert a cumulative effect.
The deshielding influence of electron withdrawing groups diminishes
rapidly with distance.
Hydroxy, mercapto, and amino hydrogens absorb over a range of
frequencies.
The absorption peak of the proton attached to the heteroatom may be
relatively broad.
This variability of chemical shift is due to hydrogen bonding and depends
upon:
Temperature;
Concentration;
Presence of H-bonding species such as water (moisture).
When line broadening is observed, it usually indicates the presence of
OH, SH, or NH
2
(NHR) groups.
Tests for Chemical Equivalence 10-5
In general, chemically equivalent protons have the same chemical
shift.
To identify chemically equivalent nuclei, we often have to resort to
symmetry operations to decide on the expected NMR spectrum for
a compound.
Tests for Chemical Equivalence 10-5
Molecular symmetry helps establish chemical
equivalence.
Rotational symmetry
results in equivalent
protons when the
group of protons is
rapidly rotating, as
in a methyl group.
Conformational interconversion may result in
equivalence on the NMR time scale.
In the case of the rapid rotation of the methyl group in
chloroethane, or the rapid conformation flip in cyclohexane, the
observed chemical shifts are the averages of the values that
would be observed without the rapid rotation or flip.
In the case of cyclohexane, the single line in the NMR spectra at
= 1.36 ppm at room temperature becomes two lines at a
temperature of -90
o
C, one at = 1.12 ppm for the six axial
hydrogens and one at = 1.60 for the six equatorial hydrogens.
At this temperature, the conformational flip of the benzene is
slower than the NMR time scale.
In general, the lifetime of a molecule in an equilibrium must be on
the order of one second to allow its resolution by NMR.
Integration 10-6
Integration reveals the number of hydrogens
responsible for an NMR peak.
The area under an NMR peak is proportional to the number of
equivalent nuclei contributing to the peak.
By comparing peak areas, it is possible to quantitatively estimate
the relative numbers of contributing protons.
The areas are obtained by the controlling computer and plotted
on top of the regular spectrum by choosing integration mode.

Chemical shifts and peak integration can be used to
determine structure.
Consider the monochlorination of 1-chloropropane:
NMR spectroscopy distinguishes all three isomers:
1,1-Dichloropropane: Three NMR signals in the ratio of 3:2:1.
= 5.93 ppm (CH), 2.34 pm (CH2), and 1.01 (CH
3
).
1,2-Dichloropropane: Three NMR signals in the ratio of 3:2:1.
= 4.17 ppm (CH), 3.68 ppm (CH
2
), and 1.70 ppm (CH
3
).
1,3-Dichloropropane: Two NMR signals in the ratio of 2:1.
= 3.71 ppm (CH
2
Cl) and 2.25 ppm (CH
2
).

Spin-Spin Coupling: The Effect of Non-
Equivalent Neighboring Hydrogens
10-7
When non-equivalent hydrogen atoms are not separated by at
least one carbon or oxygen atom, an additional phenomenon
called spin-spin splitting or spin-spin coupling occurs.
Instead of single peaks (singlets), more complex patterns occur
called multiplets (doublets, triplets or quartets).
The number and kind of hydrogen atoms directly adjacent to the
absorbing nuclei can be deduced from the multiplicity of the peak.
One neighbor splits the signal of a resonating
nucleus into a doublet.
Consider two protons, H
a
and H
b
. The population of each of these
protons is very close to 50% and 50% in the external
magnetic field, H
0
.
This means that in 50% of the molecules, H
a
protons will have H
b

protons in the state and in 50% of the molecules, H
a
protons
will have H
b
protons in the state.
The total field seen by 50% of the H
a
protons will therefore be
slightly greater than H
0
and slightly less than H
0
for the other 50
% of the H
a
protons.
What would have been a singlet NMR peak is now split into a
doublet of peaks, symmetrically displaced from the original peak.
The chemical shift of the H
a
nucleus is reported as the center of
the doublet.
The amount of mutual splitting is equal. The distance between the
individual peaks making up the doublet is called the coupling
constant (J). Here J is 7 Hz.
Coupling constants are independent of the field strength of the
NMR spectrometer being used.
Spin-spin splitting is usually observed only between hydrogen
atoms bound to the same carbon (geminal coupling) or to
adjacent carbons (vicinal coupling).
Hydrogen nuclei separated by more than two carbon atoms
(1,3 coupling) is usually negligible.
Finally, equivalent nuclei do not
exhibit mutual spin-spin splitting.
Ethane exhibits only a single line at
= 0.85 ppm.
Splitting is observed only between
nuclei with different chemical shifts.
Local-field contributions from more than one
hydrogen are additive.
Consider the triplet above. It corresponds to the methyl protons
being split by the methylene protons.
The methylene proton spins will statistically orient in the
external magnetic field as , , and . Each methyl
proton will see an increased field 25% of the time (), no
change 50% of the time ( and ), and a decreased field 25%
of the time ().
The integrated intensity of the triplet will be 6 since there are a
total of 6 equivalent methyl protons.
In the case of the methylene protons, the methyl proton spins will
statistically distribute as , , , , , , , and
.
This will result in a 1:3:3:1 quartet of peaks.
The integrated intensity of the quartet will be 4, corresponding to
the 4 equivalent methylene protons.
In many cases, spin-spin splitting is given by the
N+1 rule.
A simple set of rules:
Equivalent nuclei located adjacent to one neighboring
hydrogen resonate as a doublet.
Equivalent nuclei located adjacent to two hydrogens of a
second set of equivalent nuclei resonate as a triplet.
Equivalent nuclei located adjacent to a set of three equivalent
hydrogens resonate as a quartet.
This table illustrates the N+1 rule: Nuclei having N adjacent
equivalent neighbors split into N+1 peaks. The heights of the N+1
peaks follow Pascals triangle.
It is important to note that non-equivalent nuclei split each other.
A split in one requires a split in the other. In addition, the
coupling constants will be the same for each type of nuclei.
Two additional examples:
Spin-Spin Splitting: Some Complications 10-8
Complex multiplets sometimes occur when there is a relatively
small difference in between two absorptions.
The N+1 rule may not apply in a direct way if several neighboring
hydrogens having fairly different coupling constants are coupled
to the resonating nucleus.
The hydroxy proton may appear as a single, even if coupled to
vicinal hydrogens.
Close-lying peak patterns may give rise to non-
first-order spectra.
The intensity patterns in many NMR spectra do not follow the
idealized pattern of Pascals triangle but instead are skewed
towards each other.
The intensities of the lines facing each other is slightly larger than
expected.
Perfectly symmetrical splittings are observed only when the
resonant frequency difference of the two groups of protons is
much larger than the coupling constant between them.
When >> J, the spectra is said to be first-order.
Non-first-order spectra assume more complex shapes and can
only be analyzed with the help of computers.
Since the resonant frequency difference increases with higher
field strengths (J remains the same), a complicated spectrum can
be made first order by measuring it at higher field strengths.
Coupling to non-equivalent neighbors may modify
the simple N+1 rule.
The spectrum of 1,1,2-trichloropropane illustrates the effects of
two sets of non-equivalent neighbors.
The H
a
proton is split by the H
b
proton into a doublet as expected.
This doublet is at low field due to the effect of two adjacent
chlorine atoms.
The methyl protons are also split by the H
b
proton into a doublet
as expected. This doublet is at high field.
The H
b
proton is split by both H
a
and the methyl protons. In this
case eight lines are observed because H
a
and the methyl protons
have different coupling constants to H
b
.
The methyl group splits the
H
b
resonance into a quartet
(1,3,3,1). Each line of the
quartet is then split into a
doublet by the H
a
proton
(1,1,3,3,3,3,1,1).
In the case of 1-bromopropane, the hydrogens on C2 are also
coupled to two non-equivalent sets of neighbors. A theoretical
analysis of this resonance would predict as many as 12 lines (a
quartet of triplets).
Because the coupling constants are very similar, however, many
of the lines overlap, thus simplifying the pattern.
Fast proton exchange decouples hydroxy
hydrogens.
In the spectra of 2,2-
dimethyl-a-propanol, the OH
absorption appears as a
single peak and is not split by
the CH
2
protons. In addition,
the CH
2
protons are not split
by the OH.
The OH proton is weakly
acidic and is both between
alcohol molecules and traces
of water on the NMR time
scale at room temperature.
This type of decoupling is called fast proton exchange. It may be
slowed or removed by removal of traces of water or acid or by
cooling.
Rapid magnetic exchange self-decouples chlorine,
bromine, and iodine nuclei.
Fluorine is the only halogen that exhibits spin-spin coupling to
1
H
in a proton NMR spectra.
Chlorine, bromine, and iodine exhibit a fast internal magnetic
equilibration on the NMR time scale which precludes an adjacent
proton from recognizing them as having different alignments in
the external field.
This is termed self-decoupling, in contrast to exchange-
decoupling, as exhibited by the hydroxy protons.
Carbon-13 Nuclear Magnetic Resonance 10-9
The NMR spectroscopy of
13
C is of greater potential utility than
that of
1
H NMR.
The
13
C spectra of an organic compound is much simpler than the
1
H spectra because spin-spin coupling between adjacent carbon
atoms and between carbon and hydrogen atoms can be avoided.
Carbon NMR utilizes an isotope in low natural
abundance:
13
C.
Carbon occurs as a mixture of two principle isotopes,
12
C
(98.89%) and
13
C (1.11%). Of these, only
13
C is active in NMR.
Because of the low abundance of
13
C and its weaker magnetic
resonance (1/6000 as strong as
1
H), FT NMR is usually used for
13
C spectroscopy because multiple pulsing and signal averaging
allows the accumulation of strong signals than would otherwise be
possible.
Carbon-carbon coupling is absent in
13
C spectra due to the very
low probability of two
13
C nuclei being adjacent to each other in a
single molecule (.0111 x .0111 ~ .0001).
13
C-
1
H coupling is present, however, the chemical shift range of
13
C is much greater than the splittings due to
1
H, which precludes
the overlapping of adjacent multiplets.
The
13
C chemical shifts are reported relative to an internal
standard, usually (CH
3
)
4
Si.

The
13
C NMR spectra of bromoethane above exhibits
13
C splitting
by the methyl and methylene protons.
The
13
C peak due to C1 is first split by its own two hydrogens to
produce a triplet. Each of the triplet peaks is then split into a
quartet by the adjacent protons on the C2 carbon.
The
13
C peak due to C2 is first split by its own three hydrogens to
produce a quartet. Each of the quartet peaks is then split into a
triplet by the adjacent protons on the C1 carbon.
Hydrogen decoupling give single lines.
13
C-
1
H coupling can be completely removed by a technique called
broad-band hydrogen (or proton) decoupling.
In this technique, a strong broad radio frequency signal covering
the entire resonant frequency range for hydrogen is
simultaneously applied at the same time as the
13
C signal.
The broad-band hydrogen signal causes rapid - flips of the
hydrogen nuclei, effectively averaging their local magnetic field
contributions.

Using this technique simplifies the
spectra of bromoethane to two single
lines.
Proton decoupling is particularly powerful when analyzing
complex molecules because every magnetically distinct carbon
gives only a single peak.
The decoupled
13
C spectra of methylcyclohexane shows only five
peaks, revealing the twofold symmetry in the structure.

A limitation of FT
13
C NMR spectroscopy is that, due to difficulties
in integration, peak intensities (areas) no longer correspond to
the numbers of nuclei present.

Carbon, like hydrogen, has chemical shifts which depend upon its
chemical environment.
Electron withdrawing groups cause deshielding. The chemical
shifts go up in order: primary < secondary < tertiary carbon.
The numbers of non-equivalent carbons in the isomers of C
7
H
14

are clearly demonstrated by the numbers of
13
C peaks in their
NMR spectra.
Advances in FT NMR are greatly aiding structure
elucidation: DEPT
13
C and 2D-NMR.
Using sophisticated time-dependent pulse sequences (two-
dimensional NMR), it is now possible to establish coupling (e.g.
bonding) between close-lying hydrogens (homonuclear
correlation) or connected carbon and hydrogen atoms
(heteronuclear correlation).
This, in effect, determines the molecular connectivity of a
molecule by measuring the magnetic effect of neighboring atoms
on one another along a carbon chain.

On such pulse sequence is the distortionless enhanced
polarization transfer (DEPT)
13
C NMR spectrum.
DEPT gives information specifying which type of carbon gives rise
to a specific signal in the normal
13
C spectrum: CH
3
, CH
2
, CH, or
C
quaternary
.
A DEPT experiment consists of three spectra:
Normal broad-band decoupled spectra;
DEPT-90 pulse sequence spectra, which reveals signals only of
carbons bound to one hydrogen;
DEPT-135 pulse sequence spectra which produces normal CH
3

and CH signals, but negative absorptions for CH
2
and no peaks
for quaternary carbons.
Limonene DEPT spectra:
Spectrum A: All 10 lines 6 alkyl C at high field, 4 alkenyl C at
low field
Spectrum B: CH carbons
Spectrum C: CH carbons, positive signal CH
3
carbons, negative
signal CH
2
carbons
Spectrum A lines Spectrum C lines: quaternary carbon

We can apply
13
C NMR spectroscopy to the problem
of the monochlorination of 1-chloropropane.
Both 1,1- and 1,2-dichloropropane should exhibit three carbon
signals each. The groups of three signals would be spaced
differently due to the different arrangement of chlorine
substituents.
1,3-dichloropropane should exhibit only two carbon signals.
The two deshielded chlorine bearing
carbons assignments in 1,2-
dichloropropane can be made using DEPT
data.
The signal at 49.5 ppm appears inverted in
a DEPT-135 spectrum (CH
2
).
The signal at 55.8 ppm is the only
absorption in a DEPT-90 spectrum
Important Concepts 10
1. NMR Most important spectroscopic tool for
elucidating organic structures.
2. Spectroscopy Based on lower energy forms of
molecules being converted into higher energy forms by
the absorption of electromagnetic radiation.
3. NMR Based on alignment of the nuclei of certain
nuclei (i.e..
1
H and
13
C) with () and against () a
strong magnetic field.
to transition affected by radio-frequency radiation leading
to resonance and characteristic absorption spectra.
High magnetic fields lead to higher resonant frequencies.
4. High Resolution NMR Allows differentiation of
1
H and
13
C nuclei in different environments.
Spectral positions are measured as the chemical
shift, , in ppm from an internal standard (TMS).
Important Concepts 10
5. Chemical Shifts Highly dependent on presence
(shielding) or absence (deshielding) of electron
density.
Electron donor substituents shield.
Electron withdrawing substituents deshield.
Hydrogen bonding or proton exchange result in broad peaks.
6. Chemical Equivalency Equivalent hydrogens
or carbons have the same chemical shift.
7. Integration of peak area indicates number
of contributing hydrogens.
8. Spin-Spin Splitting
Pattern determined by number of hydrogen
neighbors (N+1 Rule).
Equivalent hydrogens show no mutual splitting.
Important Concepts 10
9. Non-First-Order Spectra Complicated patterns
created when chemical-shift difference between
coupled hydrogens is comparable to their coupling
constant.
10. Non-Equivalent Neighboring Hydrogens
(N + 1) rule is applied sequentially.
11. Carbon NMR Utilizes low abundance
13
C nuclei.
C-C coupling is not observed. C-H coupling can be
removed by proton decoupling.
12. DEPT
13
C NMR Allows peak assignment to CH
3
,
CH
2
, CH, and quaternary carbons respectively.