Nuclear Magnetic Resonance Spectroscopy

1
Nuclear Magnetic ResonanceSpectroscopy

• Introductory Theory and Interpretation

2
Physical Principles
Some (but not all) nuclei, such as 1H, 13C, 19F,
31P have nuclear spin. A spinning charge
creates a magnetic moment, so these nuclei can be
thought of as tiny magnets. If we place these
nuclei in a magnetic field, they can line up with
or against the field by spinning clockwise or
counter clockwise.
3
Alignment with the magnetic field (called a) is
lower energy than against the magnetic field
(called b). How much lower it is depends on the
strength of the magnetic field
Note that for nuclei that dont have spin, such
as 12C, there is no difference in energy between
alignments in a magnetic field since they are not
magnets. As such, we cant do NMR spectroscopy
on 12C.
4
NMR Basic Experimental Principles
Imagine placing a molecule, for example, CH4, in
a magnetic field. We can probe the energy
difference of the ?- and ?- state of the protons
by irradiating them with EM radiation of just the
right energy. In a magnet of 7.05 Tesla, it
takes EM radiation of about 300 MHz (radio
waves). So, if we bombard the molecule with 300
MHz radio waves, the protons will absorb that
energy and we can measure that absorbance. In a
magnet of 11.75 Tesla, it takes EM radiation of
about 500 MHz (stronger magnet means greater
energy difference between the ?- and ?- state of
the protons)
5
But theres a problem. If two researchers want
to compare their data using magnets of different
strengths, they have to adjust for that
difference. Thats a pain, so, data is instead
reported using the chemical shift scale as
described on the next slide.
6
The Chemical Shift (Also Called ?) Scale
Heres how it works. We decide on a sample well
use to standardize our instruments. We take an
NMR of that standard and measure its absorbance
frequency. We then measure the frequency of our
sample and subtract its frequency from that of
the standard. We then then divide by the
frequency of the standard. This gives a number
called the chemical shift, also called d, which
does not depend on the magnetic field strength.
Why not? Lets look at two examples.
Imagine that we have a magnet where our standard
absorbs at 300,000,000 Hz (300 megahertz), and
our sample absorbs at 300,000,300 Hz. The
difference is 300 Hz, so we take 300/300,000,000
1/1,000,000 and call that 1 part per million
(or 1 PPM). Now lets examine the same sample in
a stronger magnetic field where the reference
comes at 500,000,000 Hz, or 500 megahertz. The
frequency of our sample will increase
proportionally, and will come at 500,000,500 Hz.
The difference is now 500 Hz, but we divide by
500,000,000 (500/500,000,000 1/1,000,000, 1
PPM).
7
(No Transcript)
8
The Chemical Shift of Different Protons
NMR would not be very valuable if all protons
absorbed at the same frequency. Youd see a
signal that indicates the presence of hydrogens
in your sample, but any fool knows theres
hydrogen in organic molecules. What makes it
useful is that different protons usually appear
at different chemical shifts (d?. So, we can
distinguish one kind of proton from another. Why
do different protons appear at different d?
There are several reasons, one of which is
shielding. The electrons in a bond shield the
nuclei from the magnetic field. So, if there is
more electron density around a proton, it sees a
slightly lower magnetic field, less electron
density means it sees a higher magnetic field
9
How do the electrons shield the magnetic field?
By moving. A moving charge creates a magnetic
field, and the field created by the moving
electrons opposes the magnetic field of our NMR
machine. Its not a huge effect, but its enough
to enable us to distinguish between different
protons in our sample.
Learning how an NMR machine works is
straightforward. What is less straightforward is
learning how to use the data we get from an NMR
machine (the spectrum of ethyl acetate is shown
below). Thats because each NMR spectrum is a
puzzle, and theres no single fact that you
simply have to memorize to solve these spectra.
10
Interpreting Spectra
You have to consider lots of pieces of data and
come up with a structure that fits all the data.
What kinds of data do we get from NMR spectra?
For 1H NMR, there are three kinds each of which
we will consider each of these separately

• Chemical shift data - tells us what kinds of
  protons we have.
• Integrals - tells us the ratio of each kind of
  proton in our sample.
• 1H - 1H coupling - tells us about protons that
  are near other protons.

11
Chemical Shift Data
Different kinds of protons typically come at
different chemical shifts. Shown below is a
chart of where some common kinds of protons
appear in the d scale. The reference,
tetramethylsilane (TMS) appears at 0 ppm, There
is a page in your lab handout with more precise
values for this chart.Note that these are typical
values and that there are lots of exceptions!
12
(No Transcript)
13
Integration--the number of protons
Integrals tell us the ratio of each kind of
proton. They are lines, the heights of which are
proportional to the intensity of the signal.
Consider ethyl acetate. There are three kinds of
protons in this molecule, the CH3 next to the
carbonyl, the CH2 next to the O and the CH3 next
to the CH2. The ratio of the signals arising
from each of these kinds of protons should be 3
to 2 to 3, respectively. So, if we look at the
height of the integrals they should be 3 to 2 to
3. With this information, we can know which is
the CH2 signal (its the smallest one), but to
distinguish the other two, we have to be able to
predict their chemical shifts. The chart on the
previous page allows us to make that assignment
(the CH3 next to the CO should appear at 2
PPM, while the other CH3 should be at 1 PPM).
14
1H - 1H Coupling
Youll notice in the spectra that weve seen that
the signals dont appear as single lines,
sometimes they appear as multiple lines. This is
due to 1H - 1H coupling (also called spin-spin
splitting or J-coupling). Heres how it works
Imagine we have a molecule which contains a
proton (lets call it HA) attached to a carbon,
and that this carbon is attached to another
carbon which also contains a proton (lets call
it HB). It turns out that HA feels the presence
of HB. Recall that these protons are tiny little
magnets, that can be oriented either with or
against the magnetic field of the NMR machine.
When the field created by HB reinforces the
magnetic field of the NMR machine (B0 ) HA feels
a slightly stronger field, but when the field
created by HB opposes B0, HA feels a slightly
weaker field. So, we see two signals for HA
depending on the alignment of HB. The same is
true for HB, it can feel either a slightly
stronger or weaker field due to HAs presence.
So, rather than see a single line for each of
these protons, we see two lines for each.
15
(No Transcript)
16
More 1H - 1H Coupling
What happens when there is more than one proton
splitting a neighboring proton? We get more
lines. Consider the molecule below where we have
two protons on one carbon and one proton on
another.
17
Why are There Three Lines for HB?
HB feels the splitting of both HA and HA.
So, lets imagine starting with HB as a single
line, then lets turn on the coupling from HA
and HA one at a time
Because the two lines in the middle overlap, that
line is twice as big as the lines on the outside.
More neighboring protons leads to more lines as
shown on the next slide.
18
Splitting Patterns with Multiple Neighboring
Protons
If a proton has n neighboring protons that are
equivalent, that proton will be split into n1
lines. So, if we have four equivalent neighbors,
we will have five lines, six equivalent
neighbors well, you can do the math. The lines
will not be of equal intensity, rather their
intensity will be given by Pascals triangle as
shown below.
We keep emphasizing that this pattern only holds
for when the neighboring protons are equivalent.
Why is that? The answer is two slides away.
19
More About Coupling
Earlier we said that protons couple to each other
because they feel the magnetic field of the
neighboring protons. While this is true, the
mechanism by which they feel this field is
complicated and is beyond the scope of this class
(they dont just feel it through space, its
transmitted through the electrons in the bonds).
It turns out that when two protons appear at the
same chemical shift, they do not split each
other. So, in EtBr, we have a CH3 next to a CH2,
and each proton of the CH3 group is only coupled
to the protons of the CH2 group, not the other
CH3 protons because all the CH3 protons come at
the same chemical shift.
20
Not all Couplings are Equal--Non-equivalence
When protons couple to each other, they do so
with a certain intensity. This is called the
coupling constant. Coupling constants can vary
from 0 Hz (which means that the protons are not
coupled, even though they are neighbors) to 16
Hz. Typically, they are around 7 Hz, but many
molecules contain coupling constants that vary
significantly from that. So, what happens when a
molecule contains a proton which is coupled to
two different protons with different coupling
constants?
21
Non-Equivalence and Stereochemistry
So, if the protons are not equivalent, they can
have different coupling constants and the
resulting pattern will not be a triplet, but a
doublet of doublets. Sometimes, nonequivalent
protons can be on the same carbon as described on
the next slide. Topicity describes the symmetry
relationship of two or more groups (or atoms) in
a molecule that have identical connectivities
(i.e., they are connected to the molecule in the
same way). Two or more groups (or atoms)
are homotopic if the groups (or atoms) are in
identical environments, they are called
homotopic. Homotopic groups are related to each
other either by a bond rotation or an axis of
rotation in the molecule. enantiotopic if the
groups (or atoms) are in mirror image
environments. Enantiotopic groups are related to
each other by a reflective symmetry element (the
most common being a mirror plane within the
molecule). diastereotopic if the groups (or
atoms) are in different environments.
Diastereotopic groups are not related by any
symmetry elements or bond rotations.
22
Coupling Constants in Alkenes
Coupling constants in alkenes can also differ
depending on whether the protons are cis or trans
to each other. Note that in a terminal alkene
(i.e., an alkene at the end of a carbon chain),
the cis and trans protons are NOT equivalent.
One is on the same side as the substituent, the
other is on the opposite side. The coupling of
trans protons to each other is typically very
large, around 16 Hz, while the coupling of cis
protons, while still large, is a little smaller,
around 12 Hz. This leads to the pattern shown
below, and an example of a molecule with this
splitting pattern is shown on the next slide.
23
(No Transcript)
24
Some Things to Consider
Since molecules are fluxional, we are allowed to
rotate about s- bonds (but not p- bonds) and
place the molecule in whatever conformation
provides the highest symmetry. For example, the
molecule shown in the conformation below has no
symmetry elements in that conformation
But, we can rotate about the central C-C bond
By rotating about the central C-C bond and
placing the methyl groups eclipsed, we now have a
conformation with a mirror plane running through
the central C-C bond which interconverts the blue
Hs, the Me groups and the Cls, rendering them
all enantiotopic.
25
Diastereotopic Protons in an NMR Spectrum
There are several important features to this
spectrum. Notice that the protons marked Ha and
Hb are diastereotopic and that they appear at
different d. We cant assign which is Ha and
which is Hb, but we know they are different.
Also, notice that the lines for Ha and Hb are not
of equal heights the outside lines are smaller
than the inside lines. Such leaning of NMR
lines is common and is described on the next
slide.
26
The Roof Effect--leaning of NMR lines
Recall that if we have two protons, Ha and Hb,
and they are coupled to each other, Ha will be
split into two lines by Hb, and Hb will be split
into two lines by Ha. So, we should see a
spectrum where there are four lines, two for
each proton. But, it turns out that the patterns
lean towards each other in that the outside
lines of the pattern are smaller than the inside
How much leaning we have depends on how close to
each other the signals are in the spectrum, and
how strongly they are coupled to each other. The
closer they are, the greater the leaning, the
stronger the coupling, the greater the leaning as
shown on the next slide
27
Leaning NMR lines
How much leaning we have depends on how close to
each other the signals are in the spectrum, and
how strongly they are coupled to each other. The
closer they are, the greater the leaning, the
stronger the coupling, the greater the leaning
28
Examples of Leaning in Some Spectra Weve Already
Seen
29
Notice the appearance of the OH peak in this
spectrum its broad and not coupled to its
neighbors. This is common with OH peaks. OH
peaks are unusual in that their appearance is
variable for the same molecule, sometimes they
are coupled sometimes they are not, sometimes
they are sharp, sometimes they are broad. In
fact, sometimes they are very broad, so broad
that you cant even see them! This is due to OH
groups undergoing exchange with each other and
with traces of water in the solvent. This
process is catalyzed by traces of acid or base in
the solvent which effects the rate of the
exchange and the appearance of the OH.
30
More on this NMR Spectrum
Now lets consider the appearance of the Ph
group. Its a mess! Note that there are more
couplings than we would expect based on a nearest
neighbor analysis. Thats because all the
protons come at similar d, and overlap with each
other. In general, whenever there are a lot of
signals coupled to each other that are bunched up
in a portion of the spectrum, we get complex
patterns with extra lines. The reason for this
is called virtual coupling, and an explanation of
this is beyond the scope of this class, but you
should be aware when you are solving spectra that
sometimes, this causes the patterns to be more
complex than you would initially expect.
31
Helpful Links

• http//web.centre.edu/muzyka/organic/jmol10/table/
  JcampIndex.htm
• http//www.chem.ucla.edu/webspectra/
• http//www.chemguide.co.uk/analysis/nmrmenu.htmlt
  op

32

• How to approach IR Spectral Problems
• Calulate the degrees of unsaturation (rings or
  double bonds) to limit the number of possible
  structures. The degree of unsaturation indicates
  whether or not the compound has one or more
  double bonds or rings.
• degree of unsaturation 2 (C) 2 - H -
  Hal N/2
• Look at the IR spectrum, especially the region
  greater than 1500 cm-1. Look for likely
  functional groups (O-H, sp2 C-H, sp3 C-H, CO,
  CC, and C-O), working in conjunction with the
  calculated number of degree of unsaturation and
  the molecular formula. For instance, if there is
  one degree of unsaturation, and an oxygen, it
  could be a carbonyl compound if there are no
  degrees of unsaturation and an oxygen, it will be
  either an alcohol or an ether. if there are four
  degrees of unsaturation, there might be an
  aromatic ring, etc.
• AVOID THE TEMPTATION TO TRY TO ASSIGN EVERY
  PEAK!!! Look for absorptions that are common in
  organic compounds that will allow you to
  differentiate between functional groups.

33

• How to approach NMR spectral problems.
• 1.        Calculate the degrees of unsaturation
  using the molecular formula (can tell you if
  there are any rings or double bonds)
• 2.        Count the number of signals to
  determine how many different kinds of
  hydrogens/carbons there are
• 3.        The line of integration with the
  molecular formula can determine the number of
  hydrogens in each set
• 4.        Look at signals in spectrum that are
  characteristic of different types of
  hydrogens/carbons using chemical shift
  correlation tables
• 5.        Use multiplicity of peaks to determine
  the number of nonequivalent neighboring protons
  in 1H NMR
• Important terms.
•    Equivalent hydrogens The same chemical
  environment
• Ex Propane CH3CH2CH3 The methyl hydrogens
  are equivalent, and resonate at the same chemical
  shift. They show up as a triplet that integrates
  for 6H.
• Line of Integration Proportional to the area
  under the signal. This is proportional to the
  of Hs represented by the signal.
• Chemical Shift each type of H and C has only a
  certain range of chemical shift values in which
  it resonates. Correlation tables can be used.
• Things to think about.
• From the number of signals, we can tell the
  number of sets of equivalent hydrogens/carbons,
  describing the symmetry of the molecule.
• From integration, we can tell the relative number
  of hydrogens per signal.
• From chemical shift, we can tell info about the
  types of hydrogens/carbons they are.
• Multiplicity in H NMR occurs when two
  nonequivalent hydrogens are on adjacent carbons.
  The signal of a H or set of equivalent hydrogens
  splits into (n 1) peaks by neighboring
  nonequivalent hydrogens.
• Most signals are between 0-12 ppm in H NMR.
• Most signals are between 0-220 ppm in C NMR.
• Integration and multiplicity are only applicable
  to H NMR.

Calculate degree of unsat from MF
5o unsat
0 unsat
1o unsat
alcohol
ketone
Aromatic ester
IR
IR
IR
C-O Sp3 CH OH
Sp3 CH CO
C-O Sp3 CH Sp2 CH CO OH
NMR
NMR
NMR
Look for 1H singlet 2.5-5.0ppm
Look for small CO signal 180-220 ppm
Look for small CO signal 180-220 ppm, also look
for aromatic carbons and hydrogens
Exp. 14 Spectroscopy flow chart
34
Table 13.7 Regions of the 13C NMR Spectrum