Download Nuclear Magnetic Resonance spectroscopy

CHAPTER 10
Using Nuclear Magnetic Resonance
Spectroscopy to Deduce Structure
10-1 Physical and Chemical Tests
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.
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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 C7H16O:
10-2 Defining Spectroscopy
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.
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10-2 Defining Spectroscopy
Molecules undergo distinctive excitations.
Electromagnetic radiation can be described as a wave having a
wavelength (λ), a frequency (ν) and a velocity (c).
The speed of light in a vacuum is 3 x 1010 cm s-1 or 3 x 108 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 = hν
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.
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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 ~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
 basis of NMR.
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In this diagram, frequency is specified in units of wavenumbers,
defined as 1/λ, 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.
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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.
10-3 Proton Nuclear Magnetic Resonance
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: 1H.
A 1H nucleus is positively charged and its spinning motion
generates a magnetic field.
In the presence of an external magnetic field, H0, the magnetic
field of the hydrogen nucleus can be oriented either with H0
(lower energy) or against H0 (higher energy). These two states
are called  and  spin states, respectively.
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The difference in energy between the  and  states depends
directly on the external magnetic field strength, H0.
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.
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Many nuclei undergo magnetic resonance.
In general, nuclei composed of an odd number of protons (1H and its
isotopes, 14N 19F, and 31P) or an odd number of neutrons (13 C) show
magnetic behavior.
If both the proton and neutron counts are even (12C or
are non-magnetic.
16O)
the nuclei
10-4 Using NMR Spectra to Analyze Molecular
Structure
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.
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The position of an NMR signal depends on the
electronic environment of the nucleus.
In the high-resolution 1H 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, H0, in such a way as to generate a small local
magnetic field, hlocal, opposing H0.
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 H0 by its
electron cloud.
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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.
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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, (CH3)4Si.
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 (δ), a field-independent number
measured in ppm.
For (CH3)4Si, δ is defined as 0.00.
The spectrum above would be reported as:
1H
NMR (300 MHz, CDCl3) δ = 0.89, 1.80, 3.26 ppm
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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.
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Multiple substituents exert a
The deshielding influence
cumulative effect.
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 NH2 (NHR) groups.
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10-5 Tests for Chemical Equivalence
Generally, chemically equivalent Hs have the same chemical shift.
To see chemically equivalent nuclei, symmetry operations are
checked to decide on the expected NMR spectrum.
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.
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In the case of cyclohexane, the single line in the NMR spectra at
δ = 1.36 ppm at room temperature becomes two lines at a
temperature of -90o C, one at δ = 1.12 ppm for the six axial
hydrogens and one at δ = 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.