NMR

Nuclear Magnetic Resonance

NMR
NMR - Basics
Nuclei can be characterised based on their
so-called nuclear spin quantum number I.
I = 0 These nuclei have no interaction with
the magnetic field and are therefore not visible
in a NMR. These nuclei have an even number of
protons and electrons, such as
12
C,
16
O and
32
S.
I = These nuclei have a magnetic moment
and are visible in a NMR. Mainly
1
H and
13
C are
used.
I > These nuclei are difficult to observe in
a NMR. Examples are
2
H,
14
N and
79
Br.
NMR
NMR - Basics
The number of different states of a
nucleus is described by (2I + 1), as an
integer value.
All these states have the same energy,
except when the nucleus is placed in a
magnetic field.
NMR
NMR - Basics
magnetic field B
o
no magnetic
field
AE = hv
|
o
-
+
NMR
NMR - Basics
The Lamor equation
h = Planck constant
= Magnetogyric ratio, dependent on the nucleus
H
0
= magnetic field
AE = energy difference between spin states
h
E A
= v
0
2
H
t

v =
t

2
0
H h
E = A
NMR
NMR - Basics
For example for
1
H (proton):
H
0
= 1.4093 T v = 60 MHz
H
0
= 2.3488 T v = 100 MHz
H
0
= 9.3950 T v = 400 MHz
And for
13
C:
H
0
= 2.3488 T v = 25.2 MHz
NMR
NMR - Basics
energy
magnetic field B
o
AE
AE
60 MHz 200 MHz
NMR
NMR - Instrumentation
NMR spectra are recorded in solution.
Special equipment is required for solids.
Of importance for the solvent are:
Solubility of the sample
No strong sample - solvent interactions
Additionally, solvents for proton NMR
should not contain protons.
CCl
4
is a suitable, but is not a good solvent.
Deuterated solvents are used when samples are
insoluble in CCl
4
, but some of these are
expensive.
NMR
NMR - Instrumentation
A NMR instrument basically consists of: a
magnet, a radiofrequency (RF) transmitter
and receiver , a recorder, a calibrator, a
integrator and a sample holder.
NMR
NMR - Instrumentation
The magnet is an important part of the
NMR spectrometer.
The magnetic field should be:
Homogeneous
Strong
Stable
To improve the homogeneity of the
magnetic field, the sample is rotated in the
magnetic field.
NMR
NMR - Instrumentation
NMR spectra can be obtained in different
ways.
Two different types of NMR instruments
are the continuous wave (CW) and the
fourier transform (FT) instruments.
NMR
NMR - Instrumentation
CW instruments can be operated in two
ways:
Constant magnetic field, varying radiofrequency
Constant frequency, varying magnetic field
A CW instruments therefore scans the
resonance frequency range and excite
nuclei separately.
NMR
NMR - Instrumentation
When comparing FT with CW:
FT is more sensitive
FT needs less sample: 5 g for FT versus 0.2
20 mg for CW
NMR
Chemical Shift
The resonance frequency is influenced by
the electron-density surrounding the
proton, the Lamor equation :
Where o represent the shielding
The variation in the resonance frequency
due to the shielding is called chemical shift
and means that different protons in the
same molecule can have resonance at
different frequencies.
) 1 (
2
0
o
t

v = H
NMR
Chemical Shift
Example:
The introduction of an electron withdrawing
group in a molecule reduces the electron
density around a proton.
This will result in reduced shielding and
therefore increase in resonance frequency.
CH
3
F CH
3
OCH
3
CH
3
Cl CH
3
HC=O CH
4
Increase in electron withdrawing effect of X on CH
3
X
Less shielding, higher resonance frequency
NMR
Chemical Shift
Tetramethylsilane, (CH
3
)
4
Si, (TMS) was chosen
when NMR was first introduced, because the
protons in the methyl groups are more shielded
than in any other compound and would thus
mark the one end of the scale.
The peak positions are given as parts per million
(ppm) relative to TMS which is defined as the
zero point:
6
10
Hz in frequency er spectromet
Hz in TMS from shift chemical
) ( shift chemical x = o
NMR
1
H NMR Chemical Shift
The chemical shift increases form right to
left in a NMR spectrum.
In general, the chemical shift observed for
the majority of the protons is in the 0 10
range.
NMR
Chemical Equivalence - Examples
H H
H H
H H
CH
2
CH
2
CH
2
CH
2
CH
2
C CH
3
O
CH
3
NMR
Chemical Equivalence - Examples
H
H H
H CH
3
CH
3
CH
2
CH
2
C
C
OCH
3
OCH
3
O
O
C CH
3
OCH
3
O
CH
3
O CH
2
Cl
NMR
Chemical Equivalence - Examples
CH
3
O CH
2
C CH
3
CH
3
CH
3
CH
3
C CH
2
O CH
3
O
NMR
Integrals
48 . 1
0 . 22
5 . 32
00 . 1
0 . 22
0 . 22
52 . 2
0 . 22
5 . 55
= = =
NMR
Chemical Environment and Chemical
Shifts
NMR
Trends Influencing Chemical Shift
The chemical shift is dependent on how
much the proton is shielded from the
magnetic field.
Three important factors for this shielding
are:
Electronegativity: Electrons are withdrawn by
neighbouring electronegative atoms
Hybridisation: Protons attracted to sp
2
carbon atom are less shielded
Hydrogen bonding: Shielding is reduced by
hydrogen bonding
NMR
Electronegativity
( C H
3
)
3
S i
C H
3
C H
3
( C H
3
)
3
N
( C H
3
)
2
O
C H
3
F
0.00
0.86
2.20
3.20
4.20
3.47
1.31
1.06
C H
3
Cl C H
2
C l
2
C H Cl
3
7.24 5.33 3.05
o
(ppm)
| | | | | | | | |
8 7 6 5 4 3 2 1 0
2 3
1
C H
2
Cl
C H
2
C H
3
1
2
3
NMR
Hybridisation
Effect of hybridisation, of the atom to
which the proton is attached, on chemical
shift:
0.86
5.23
1.80
sp
2
sp sp
3
H
2
C CH
2
HC CH
CH
3
CH
3
O
H
5.23
H
2
C CH
2
o
(ppm)
10 9 8 7 6 5 4 3 2 1 0
| | | | | | | | | | |
9.5
7.29
variation among sp
2
hybridised molecules
NMR
Anisotropy
NMR
Hydrogen Bonding
1. H-bonding increases with concentration
Common NMR solvents such as CDCl
3
and CCl
4
do not form H-bonds. When a sample
containing OH or NH groups is dissolved in
these solvents, the chemical shift of the OH
or NH protons changes with the concentration
of the sample.
o (ppm)
| | | | | | | | |
8 7 6 5 4 3 2 1 0
100%
20%
5%
2%
1%
O H
O
H
NMR
Hydrogen Bonding
2. H-bonding decreases with temperature
When a sample containing OH or NH groups is
heated, H-bonding is disrupted, and as a result
the chemical shift of the OH and NH protons
changes with temperature
o (ppm)
| | | | | | | | |
8 7 6 5 4 3 2 1 0
heating cooling
.......
H O
CH
3
H O
CH
3
heat
cool
CH
3
O
H
CH
3
O
H
NMR
Hydrogen Bonding
3. H-bonding may occur between sample and
solvent
While CDCl
3
and CCl
4
do not form H-bonds to
OH or NH in a sample, some other solvents
such as water, d
6
-acetone and d
6
-
dimethylsulfoxide do. Such H-bonds result in
downfield shifts. In particular, the position of
water (a common impurity peak) is strongly
affected.
CDCl
3
o (ppm)
| | | | | | | | |
8 7 6 5 4 3 2 1 0
water in
acetone
pure water
water in
NMR
13
C NMR
Carbon 13 spectra are used to determine the
number of nonequivalent carbons and to identify
the types of carbon atoms (methyl, methylene,
aromatic, carbonyl, etc.)
Structural determination is often easier with
carbon 13 NMR then with proton NMR.
However, mostly proton NMR and carbon 13 NMR
are used together to determine the structure of
an unknown compound.
NMR
13
C NMR
Carbon 13 resonances are about 6000
times weaker than proton resonances.
The reason for this is:
Natural abundance of
13
C is very low: some
molecules have no carbon 13, other have only
one carbon 13 atom.
The magnetogyric ratio of carbon 13 is lower
than for a protons. The resonance frequency
will therefore be lower. At lower frequencies,
the population excess is lower and therefore
reducing the sensitivity.
NMR
Chemical Environment and Chemical
Shift
NMR
Spin - Spin Coupling
1
H NMR
C C Br Br
Cl Cl
H
a
H
b
C C
Cl
H
a
H
b
Cl
OCH
3
OCH
3
NMR
Spin - Spin Coupling
1
H NMR
1 1 2 1
1 2 1 3 2
1 3 3 1 4 3
1 4 6 4
1
5 4
1 1 0
Relative peak
areas
Multiplicity
(n+1)
Number of
magnetically
equivalent protons
Relative peak areas in multiplets due to spin-spin
coupling (I = )
Pascals triangle
NMR
Spin - Spin Coupling
1
H NMR
triplet quartet
an ethyl group
-CH
3
-CH
2
-
area = 3 area = 2
- CH
2
-CH
3
1 : 2 : 1 1 : 3 : 3 : 1
NMR
Spin - Spin Coupling
1
H NMR
quartet
area = 3
CH
CH CH
3
-CH
3
area = 1
1 : 1 1 : 3 : 3 : 1
doublet
1 : 2 : 1
area = 2
X CH
2
CH
2
Y
CH
2
1 : 2 : 1
triplet
area = 2
CH
2
triplet
NMR
Spin - Spin Coupling
1
H NMR
doublet
septet
-(CH
3
)
2
CH
area = 6
area = 1
CH
CH
3
CH
3
an isopropyl group
1 : 6 : 15 : 20 : 15 : 6 : 1 1 : 1
NMR
Spin-Spin Coupling
13
C NMR
NMR
Spin - Spin Coupling
13
C NMR
The probability of finding 2 or more carbon 13
atoms in the same molecule is very low.
This means that homonuclear (carbon - carbon)
spin-spin coupling is rarely observed.
Heteronuclear spin-spin coupling, however, does
occur. Here, the carbon 13 atom interacts with
protons that are attached directly to the carbon
13 atom (to more remote protons only minor
interaction is observed).
With
13
C NMR, we generally observed splitting that
arises from protons directly attached to the carbon atom
being studied (one-bond coupling). In proton NMR,
homonuclear (proton - proton) splittings are common and
are three bond couplings.
NMR
Spin - Spin Coupling
13
C NMR
13
C H
H
H
13
C H
H
13
C H
13
C
3 protons 2 protons 1 proton 0 protons
13
C NMR quartet triplet doublet singlet
1
H NMR The peak splitting is as discussed previously.
NMR
Spin - Spin Coupling
13
C NMR
Remember:
We do not observe carbons in a proton NMR
spectrum, since the chemical shifts for carbons
are outside the proton NMR spectrum range.
We do not observe protons in carbon NMR
spectra, again since proton resonances occur
outside the range used to obtain carbon 13
spectra.
We do not observe
12
C in a carbon spectrum.
NMR
Spin - Spin Coupling
13
C NMR
The spectra in which spin-spin coupling of
carbon 13 with protons takes place are
called proton-coupled spectra.
NMR
Spin - Spin Coupling
13
C NMR
The proton-coupled carbon 13 spectra are
often difficult to interpret.
The multiplets from different carbons
often overlap each other, because the
coupling constants are often larger than
the differences in chemical shift between
the carbons. This makes the spectra
rather complicated.
Proton-decoupled spectra are therefore
often applied to avoid this problem.
NMR
Spin - Spin Coupling
13
C NMR