Sie sind auf Seite 1von 218

Introduction to Spectroscopy

Spectroscopy is the study of the interaction of matter with the


electromagnetic (EM) spectrum

1. EM radiation displays the properties of both particles and waves

2. This packet of wave and particle properties is called a photon

The term photon is implied to mean a small, massless particle that


contains a small wave-packet of EM radiation/light

3. The energy E component of a photon is proportional to the frequency


n

E = hn

The constant of proportionality is Planks constant, h

CHEM 430 NMR Spectroscopy 2


Introduction to Spectroscopy

4. Because the speed of light (c ) is constant, the frequency (n)


(number of cycles of the wave per second) can complete in the
same time, must be inversely proportional to how long the
oscillation is, or wavelength (l):
c
___ hc
n= ___
D E = hn =
l l
5. Amplitude describes the wave height, or strength of the oscillation

6. Because the atomic particles in matter also exhibit wave and


particle properties (though opposite in how much) EM radiation
can interact with matter in two ways:
Collision particle-to-particle energy is lost as heat
and movement

Coupling the wave property of the radiation matches


the wave property of the particle and couple to the
next higher quantum mechanical energy level

CHEM 430 NMR Spectroscopy 3


Introduction to Spectroscopy

8. Remember atoms and molecules are quantum mechanical particles

9. Where a photon is a wave with some particle character, matter is made of particles
with some wave character wave/particle duality

10. As a result of this, the energy of these particles can only exist at discrete energies
we say these energy levels are quantized

11. It is easy to understand if we visualize the


wave property of matter as an oscillating
string in a boxonly certain energy levels

Energy
can exist as the string is bound at both ends:

CHEM 430 NMR Spectroscopy 4


The Spectroscopic Process

2. Absorption: Molecule takes on


the quantum energy of a photon
excited state
that matches the energy of a
transition and becomes excited 5. Detection: Relaxation as
hn photons are reemitted.
Spectrometers differ whether
they measure actual emission or
absorbance
Energy

rest state rest state

1. Irradiation: Molecule is
bombarded with photons of
hn hn hn various frequencies over
the range
CHEMdesired
430 NMR Spectroscopy 5
5
Types of Spectroscopy

core
nuclear electron electronic Nuclear Magnetic
excitation excitation excitation molecular molecular Resonance
(PET) (X-ray cryst.) (p to p*) vibration rotation NMR & MRI

g-rays

Visible
X-rays UV IR Microwave Radio

Frequency, n (Hz) ~1017 ~1015 ~1013 ~1010 ~105

Wavelength, l ~0.01 nm 10 nm 1000 nm 0.01 cm 100 m

Energy (kcal/mol) > 300 300-30 300-30 ~10-4 ~10-6

CHEM 430 NMR Spectroscopy 6 6


NMR Spectroscopy

NMR spectroscopy has emerged as the ultimate spectroscopic


method for organic structural analysis

Currently, the development of novel NMR methods is in its


golden age with some of the 2-D methods entering their
maturation period as routine spectroscopic methods

A typical NMR sample consists of 1-10 mg of sample, with which


a full analysis of 1H, 13C, DEPT, COSY, HMBC, HSQC and NOESY
could be done in a few hours on a high-field instrument

Important spin-offs of NMR spectroscopy include a host of


medical and security imaging equipment

CHEM 430 NMR Spectroscopy 7


Brief History of NMR
First NMR spectrum of H2O, 1946:

Bloch, F.; Hansen, W. W.; Packard,


M. Phys. Rev. 1946, 70 474-85.

CHEM 430 NMR Spectroscopy 8


Brief History of NMR

First observation of chemical shift


1H spectrum of ethanol 1951 vs. 2011

Arnold, J.T., S.S. Dharmatti, and M.E.


Packard, J. Chem. Phys., 1951, 19, 507.

CHEM 430 NMR Spectroscopy 9


Brief History of NMR

Fourier transform NMR by Ernst - 1966

CHEM 430 NMR Spectroscopy 10


Brief History of NMR

2D NMR 1975 Jeener and Ernst

CHEM 430 NMR Spectroscopy 11


Brief History of NMR (MRI)

First magnetic resonance image 1973


Lauterbur and Mansfield

2011

CHEM 430 NMR Spectroscopy 12


Brief History of NMR

First 3-D spectrum of small protein - 1985 Wthrich

CHEM 430 NMR Spectroscopy 13


Brief History of NMR

Nobel Prizes for NMR


1944 Physics Rabi (Columbia)
1952 Physics Bloch (Stanford), Purcell (Harvard)
1991 Chemistry Ernst (ETH)
2002 Chemistry Wthrich (ETH)
2003 Medicine Lauterbur (University of Illinois in Urbana ) and
Mansfield (University of Nottingham)

CHEM 430 NMR Spectroscopy 14


Basis of NMR Spectroscopy
2.1 Magnetic Properties of Nuclei
The sub-atomic particles within atomic nuclei possess a spin
quantum number just like electrons

Just as when using Hunds rules to fill atomic orbitals with


electrons, nucleons must each have a unique set of quantum
numbers

The spin quantum number of a nucleus is a physical constant, I

For each nucleus, the total number of spin states allowed is given
by the equation:
2I + 1

CHEM 430 NMR Spectroscopy 15


Basis of NMR Spectroscopy
Spin Quantum Numbers of Common Nuclei
Element 1H 2H 12C 13C 14N 16O 17O 19F 31P 35Cl

Nuclear Spin 1 0 1 0 5/2 3/2


Quantum Number
# of spin states 2 3 0 2 3 0 6 2 2 4

Observe that for atoms with no net nuclear spin, there are zero
allowed spin states

Nuclear Magnetic Resonance can only occur where there are


allowed spin states

Note that two nuclei, prevalent in organic compounds have


allowed nuclear spin states 1H and 13C, while two others do not
12C and 16O

CHEM 430 NMR Spectroscopy 16


Basis of NMR Spectroscopy
2.1 Magnetic Properties of Nuclei
There are three types of nuclei:
No spin: I = O
12C, 16O

Cannot be observed by NMR

Spinning sphere: I =
1H, 13C, 15N, 19F, 29Si, 31P)

Easiest to observe by NMR

Spinning ellipsoid I = 1, 3/2, 2


2H, 11B, 14N, 17O, 33S, 35Cl

Difficult to observe by NMR

CHEM 430 NMR Spectroscopy 17


Basis of NMR Spectroscopy
2.1 Magnetic Properties of Nuclei
A nucleus contains protons, which each bear a +1 charge

If the nucleus has a net nuclear spin, and an odd number of


protons, the rotation of the nucleus will generate a magnetic field
along the axis of rotation

m
I = + H H I = -
m
A hydrogen atom with its lone proton making up the nucleus, can
have two possible spin statesdegenerate in energy

CHEM 430 NMR Spectroscopy 18


Basis of NMR Spectroscopy
2.1 Magnetic Properties of Nuclei
The magnitude of m varies from atom to atom :

m = gI

is Plancks constant divided by 2p

g is the characteristic gyromagnetic ratio of the nucleus

The larger g is, the greater the magnetic moment

CHEM 430 NMR Spectroscopy 19


Nuclear Magnetic Resonance

When a large
In the absence
magnetic field
of stimulus all As B0 increases,
B0 is applied the
nuclear spin the larger DE
two spin states
sates are becomes
become non-
degenerate
degenerate

CHEM 430 NMR Spectroscopy 20


Basis of NMR Spectroscopy
2.1 Magnetic Properties of Nuclei
The large external magnetic field is defined as B0 in units of Tesla, T

The axis of B0 is defined as the z-direction

Splitting of spins into quantized groups is called the Zeeman effect

DE

CHEM 430 BNMR


0 +z Spectroscopy
direction 21
Basis of NMR Spectroscopy
2.1 Magnetic Properties of Nuclei
The force of B0 causes m to move in a circular motion about the z-
direction precession

B0 field in z-direction operates on the x component of m to create a


force in the y-direction (F = m X B0)

This occurs with an angular frequency w0 known as the Larmor


frequency (rad s-1)

CHEM 430 NMR Spectroscopy 22


Basis of NMR Spectroscopy
2.1 Magnetic Properties of Nuclei
A quantum mechanical particle can absorb a photon of energy
equal to DE and become promoted to a higher state
spectroscopic process

As B0 increases so does w0 (B0 w); the constant of


proportionality is g:
w0 = g B0

By equating w0 with Plancks relationship:


DE = hn0 = w0 = g B0

CHEM 430 NMR Spectroscopy 23


Basis of NMR Spectroscopy
2.1 Magnetic Properties of Nuclei
What does this mean for the NMR experiment (observing DE)?

Solving for the frequency of EM radiation we are observing:


For a bare hydrogen nucleus (H+), g = 267.53 (106 rad/Ts)
In a B0 of 1.41 Tesla:
DE = 60 MHz
DE corresponds to the highly weak radio region of the EM spectrum:
l > 5 meters and energies of < 0.02 calmol-1

This causes technical challenges to observing NMR

CHEM 430 NMR Spectroscopy 24


Basis of NMR Spectroscopy
2.1 Magnetic Properties of Nuclei
Boltzmann distribution more problems with NMR observation
DE at 60 MHz (DE = hn) is 2.39 x 10-5 kJ mol-1 (tiny) thermal energy at room
temperature (298 oK) is sufficient to populate both energy levels

DE is small, so rapid exchange is occurring between the two populations, but


there is always a net excess of protons in the lower energy state

From the Boltzmans Law we can calculate the population of each energy
state:
Nupper/Nlower = e-DE/kT = e-hn/kT

@ 298 oK the ratio is 1,000,000 / 1,000,009 !

There is an excess population of 9 nuclei in the lower energy state!


CHEM 430 NMR Spectroscopy 25
Basis of NMR Spectroscopy
2.1 Magnetic Properties of Nuclei
As the applied B0 increases, exchange becomes more difficult and the excess
increases:
Field, B0 Frequency Excess nuclei
T MHz
1.41 60 9
1.88 80 12
7.05 300 48
9.40 400 64
14.1 600 96

6. In each case, it is these few nuclei that allow us to observe NMR

7. When radio radiation is applied to a sample both transitions upward and


downward are stimulated if too much radiation is applied both states
completely equilibrate a state called saturation no observed NMR signal
CHEM 430 NMR Spectroscopy 26
Basis of NMR Spectroscopy
2.2 Commonly Studied Nuclides

CHEM 430 NMR Spectroscopy 27


Basis of NMR Spectroscopy
2.2 Commonly Studied Nuclides

Remember that the greater DE the easier it is to detect NMR active


nuclei and have greater S/N ratios:

CHEM 430 NMR Spectroscopy 28


Basis of NMR Spectroscopy
2.2 Commonly Studied Nuclides
1. Spin
In general spin nuclei are the easiest to observe

Quadrapolar (I > ) nuclei are more difficult to observe


Unique mechanism for relaxation gives very short relaxation time

Heisenberg uncertainty principle dictates:


DE Dt ~

As relaxation times become very short, the uncertainty in


energies becomes large and peaks broaden greatly

CHEM 430 NMR Spectroscopy 29


Basis of NMR Spectroscopy
2.1 Magnetic Properties of Nuclei
2. Natural Abundance
Remember from Boltzmans Law we have only a small excess of nuclei
we can observe: 60 MHz, 1.41 T: 1,000,000 / 1,000,009 for 1H

1H is 99.985% of natural hydrogen - only 9 excess nuclei

Consider the excess population when the nuclei we are observing is 13C
1.11% of natural carbon
Spin couplings between low-abundant nuclei are also hampered:
Chance of two 1H-1H on adjacent Cs: 99.985 x 99.985 = 99.97%
Chance of two 13C-13C adjacent to one another: 1.11 x 1.11 = 0.1%

CHEM 430 NMR Spectroscopy 30


Basis of NMR Spectroscopy
2.2 Commonly Studied Nuclides
3. Natural Sensitivity - g
Remember - DE = hn0 = w0 = g B0
NMR signal a function of only B0 and g

The larger DE the greater the excess population for observation


(Boltzmann distribution)

1H is best followed by 19F in routine observations

CHEM 430 NMR Spectroscopy 31


Basis of NMR Spectroscopy
2.2 Commonly Studied Nuclides
4. Receptivity
Mathematical product of abundance and g

Good quick measure of amenable a nuclei is for observation

Your text uses 13C as a guidepost rather than 1H

Quick survey:
1H is 5680 times easier to observe than 13C
15N is 2.2% as easy to observe as 13C

19F is 4730 times easier to obersve than 13C; 31P is 2 times easier

CHEM 430 NMR Spectroscopy 32


Basis of NMR Spectroscopy
2.3 The Chemical Shift
Observation of the NMR phenomenon would be of little use if all
protons resonated at the same frequency

In organic compounds protons are not bare nuclei, they are


surrounded by an s-orbital of containing an e- shared with an e- in
a hybridized orbital of another atom to form a covalent bond

In the presence of an external magnetic field, an induced


circulation of electrons opposite to that of a proton is observed
since the two are of opposite charges

This induced circulation generates a magnetic field in opposition to


the applied magnetic field a local diamagnetic current
CHEM 430 NMR Spectroscopy 33
Basis of NMR Spectroscopy
2.3 The Chemical Shift
Since the magnetic field felt by the proton within this electron cloud is
lowered, the resonance condition frequency is also lowered

This effect of lowering the energy of transition by a cloud of electrons is


called diamagnetic shielding or shielding - represented as s

The opposite effect if electron density is removed from the vicinity of


the proton is called deshielding

The actual field around the nucleus becomes B0(1 s); substitution in the
energy equation gives:

CHEM 430 NMR Spectroscopy 34


Basis of NMR Spectroscopy
2.3 The Chemical Shift
Since the magnetic field felt by the proton within this electron cloud is
lowered, the resonance condition frequency is also lowered

This effect of lowering the energy of transition by a cloud of electrons is


called diamagnetic shielding or shielding

The opposite effect if electron density is removed from the vicinity of


the proton is called deshielding

DE

CHEM 430 BNMR


0 +z Spectroscopy
direction 35
NMR Spectroscopy -
2-6
Introduction
Basis of NMR Spectroscopy
In acetic acid, the CH3 protons
are in an e- rich environment
relative to the OH proton.

Shielding of the electrons


opposes B0 and therefore DE is
lower than that observed for
the OH proton. Here DE is
large as the full effect of B0 is
felt

DE CH3

DE OH

CHEM 430 BNMR


0 +z Spectroscopy
direction 36
DE

CHEM 430 NMR Spectroscopy


B0 37
Basis of NMR Spectroscopy
The effect of electrons on a 1.41 T magnetic field is negligible, but
measurable

Compare the resonance frequencies for the protons in fluoromethane vs.


chloromethane
CH3F CH3Cl

The stronger inductive w/d of electrons by fluorine reduces the resonance


frequency by 72 Hz (not MHz) compared to an operating frequency of the
instrument at 60 MHz @ 1.41 T barely 1 part per million (ppm)

Using units of 60000072 vs. 60000000 is clunky at best

There needs to be a reference proton by which these chemical shifts


can be related - the best candidate would be a completely deshielded
proton (H+) which does not exist in the solution phase

CHEM 430 NMR Spectroscopy 38


Basis of NMR Spectroscopy
NMR spectroscopists chose the other end of the spectrum- a proton that
was more shielded than any other known proton (at the time) those in
tetramethylsilane (TMS)

The 12 chemically identical protons in TMS were used as the standard zero
for an NMR spectrum

The resonance frequency of any proton to be studied (since all were less
shielded) would be at parts per million of the operating frequency of the
instrument greater than this zero

This allowed NMR instruments of varying field (and thus operating


frequency) strengths to use the same scale

Heres how:

CHEM 430 NMR Spectroscopy 39


Basis of NMR Spectroscopy
In an applied field of 1.41 T, the resonance frequency for a typical proton is
60 MHz, at 2.35 T it is at 100 MHz a ratio of 5/3

Thus, for a given proton, the shift in Hz from the TMS standard should be 5/3
greater in the 100 MHz instrument compared to the 60 MHz

Since these are simple ratios, we can simply factor out the effect of field
strength by defining d, or chemical shift to be

d = (shift from TMS in Hz)


(spectrometer frequency in MHz)

or ppm of the instruments operating frequency

CHEM 430 NMR Spectroscopy 40


Basis of NMR Spectroscopy

90 Mhz spectrum 300 MHz spectrum

90 Hz 300 Hz
CHEM 430 NMR Spectroscopy 41
Basis of NMR Spectroscopy
In an applied field of 1.41 T, the resonance frequency for a typical proton is
60 MHz, at 2.35 T it is at 100 MHz a ratio of 5/3

Thus, for a given proton, the shift in Hz from the TMS standard should be 5/3
greater in the 100 MHz instrument compared to the 60 MHz

Since these are simple ratios, we can simply factor out the effect of field
strength by defining d, or chemical shift to be

d = (shift from TMS in Hz)


(spectrometer frequency in MHz)

or ppm of the instruments operating frequency

CHEM 430 NMR Spectroscopy 42


Basis of NMR Spectroscopy
A detailed study of chemical shifts is the basis of Chapter 3
CH3

H Si
O
H3C CH
C H
C CH3 3
O
C
O H
S H H
O R C R
O H
O R
H C H R = H or alkyl
C
O
H C
C EWG
Ph

15 10 9 8 7 6 5 4 3 2 1 0.0

downfield d (ppm) upfield


deshielded shielded
higher DE lower DE

CHEM 430 NMR Spectroscopy 43


Spectrometer Design
Basis of NMR Spectroscopy
Continuous-Wave (CW) Instrument
An NMR spectrometer needs to perform several functions:
Generate a high (>1 Tesla) magnetic field to split the energy levels of the
spin states enough to:
Create an excess nuclei population large enough to observe
Make the radio n that correspond to the transition be
observable

Ensure that the field is homogeneous (shimming)

Vary either the applied field or the radiofrequency (RF) to observe


different nuclei at their various energies of transition

Receive the faint signal of the relaxation of the excited nuclei to their
ground state

Process the signal into a usable spectrum vs. a reference


CHEM 430 NMR Spectroscopy 44
Basis of NMR Spectroscopy
Continuous-Wave (CW) Instrument:

RF Detector
RF (60 MHz)
oscillator

Permanent
Magnet

Variable magnetic field 1.41 T few millionths of T


CHEM 430 NMR Spectroscopy 45
Basis of NMR Spectroscopy
How it works (CW NMR):
The sample is placed in a 5 mm solution cell or tube (experimental aspects
we will cover shortly) in the center of a large permanent or electromagnet

A RF oscillator coil at 90 to the sample generates a radio signal at the


operating frequency of the instrument (60 MHz for a 1.41 T field)

The overall magnetic field is varied by a small electromagnet capping the


poles of the larger field magnet

Remember: DE = n = (g/2p) B0, so variations of either magnetic field or


frequency will cover the observed spectral width if the other is held
constant

As with older dispersive IR instruments, the sweep of magnetic fields is


simultaneous with the movement of the chart paper

CHEM 430 NMR Spectroscopy 46


Basis of NMR Spectroscopy
How it works (CW NMR):
As a particular proton population comes into resonance, a second receiver
coil at 90 to the transmitter coil will pick up the change in orientation of
nuclear spin

This is recorded by the chart as a voltage response, proportional to the


size of the proton population that generated the resonance

One artifact of CW instruments is that the relaxation of the protons is


slower than the movement (sweep) of the chart paper

This causes the ringing effect a decreasing oscillation of the signal after
the spectrometer has moved past a given resonance

CW instruments operate by bringing each individual population of protons


into resonance individually.

CHEM 430 NMR Spectroscopy 47


Basis of NMR Spectroscopy
Limitations- CW NMR:
Since the spectrum is collected once, the sample must possess enough
protons to give a suitable excess population that can be observed need a
concentrated sample

Due to the limitations of the relatively low magnetic field (CW instruments
top out at 60-90 MHz) the coupling constants for JHH are relatively large
compared to the spectral width so only simple molecules can be
observed and their structures elucidated

For nuclei of lower magnetogyric ratios, g, or natural abundance (13C most


specifically) the ratio of radio noise to signal is high

CHEM 430 NMR Spectroscopy 48


Basis of NMR Spectroscopy
2.4 Excitation and Relaxation FT-NMR
Lets revisit the NMR experiment we considered earlier

Recall that at even a high applied B0 only a small excess of nuclei are in
the lower spin state (+ ) as per the Boltzman distribution

Ex: @ 7.04 T an excess of 50 spins per million

It is important to also note that 298 K imparts enough energy to the


system such that all spins are interchanging rapidly:

CHEM 430 NMR Spectroscopy 49


Basis of NMR Spectroscopy
2.4 Excitation and Relaxation FT-NMR
So when we are discussing an NMR sample we have quadrillions of
protons creating a net magnetization M in the z direction (B0)

The xy components are distributed randomly, and we can think of


the rest state as M = Mz
z z

M
y y Bo

x x

M precesses at the Larmor frequency. We are using the rotating


frame of reference to make the visualization easier.
CHEM 430 NMR Spectroscopy 50
Basis of NMR Spectroscopy
2.4 Excitation and Relaxation FT-NMR
Important note:
Each individual spin can only exist in either quantized state (
) separated by DE

The bulk magnetization however can exist at a continuum of states

M
y Bo

CHEM 430 NMR Spectroscopy 51


Basis of NMR Spectroscopy
2.4 Excitation and Relaxation FT-NMR
If a RF (w0 = w) is applied that creates a magnetic oscillation along
the x-axis a torque is applied to M rotating it towards y

z z

Mo B1
y y
B1
(or off-resonance) Mxy
wo
x x
wo

With the application of energy, a small amount of the excess


population has flipped spins. Mxy < M0

CHEM 430 NMR Spectroscopy 52


Basis of NMR Spectroscopy
2.4 Excitation and Relaxation FT-NMR
If RF energy continues to be applied the excess of + nuclei
disappears sample at saturation no NMR signal can be
detected

Natural mechanisms return an excess population to equilibrium

Any process that returns the z-magnetization to equilibrium with


an excess of + spins is called spin-lattice or longitudinal
relaxation

It is usually a first-order process and with a time constant of T1

CHEM 430 NMR Spectroscopy 53


Basis of NMR Spectroscopy
2.4 Excitation and Relaxation FT-NMR
Other magnetic nuclei in the NMR sample tumble, generating a
field from its motion

If the field is at w, excess spin energy can pass to this motional


energy as nuclei become + nuclei

For this process to be effective the nuclei need to be spatially


proximate to the tumbling molecule.

Most H-atoms are on the outside of molecules and have roughly


equal probability to relax by this process - #1Hs ~ signal

CHEM 430 NMR Spectroscopy 54


Basis of NMR Spectroscopy
2.4 Excitation and Relaxation FT-NMR
C-atoms differ substantially in their contact with external
molecules T1 relaxation usually by attached protons

Therefore T1 relaxation is more efficient for a 13CH3 rather than a


quaternary carbon or 13C=O.

CHEM 430 NMR Spectroscopy 55


Basis of NMR Spectroscopy
2.4 Excitation and Relaxation FT-NMR
T1 relaxation is responsible for generating the excess of + nuclei
in the first place!

When the sample is first placed in the B0 field, all spins are
degenerate

Magnetization builds up as spins flip from the effect of interactions


with surrounding magnetized nuclei

CHEM 430 NMR Spectroscopy 56


Basis of NMR Spectroscopy
2.4 Excitation and Relaxation FT-NMR
Any process that returns xy magnetization to its equilibrium position of
zero is called spin-spin or transverse relaxation

It is a first order process with time constant T2

By definition T2 < T1

For T2 relaxation the phases of nuclear spins must become randomized

The mechanism for this is when spin is transferred between nuclei of


opposite spin

CHEM 430 NMR Spectroscopy 57


Basis of NMR Spectroscopy
2.4 Excitation and Relaxation FT-NMR
When one spin goes from +1/2 to -1/2 while the other goes from -1/2 to
+1/2 there is no net change in z magnetization

However switches in spin cause dephasing; as the process continues xy


magnetization disappears

CHEM 430 NMR Spectroscopy 58


Basis of NMR Spectroscopy
2.4 Excitation and Relaxation FT-NMR
Detection as xy magnetization dephases the vectors begin to rotate
about z in the rotating frame of reference

A second coil 90o to the transmitter coil detects the decay in the xy

Mxy wo
x

Receiver coil (x) NMR signal

CHEM 430 NMR Spectroscopy 59


Basis of NMR Spectroscopy
2.4 Excitation and Relaxation FT-NMR
The NMR process:

CHEM 430 NMR Spectroscopy 60


Basis of NMR Spectroscopy
2.4 Excitation and Relaxation FT-NMR
Introduction to Pulse Sequences

Shorthand:

90x
Detection
Mixing time

Pulse

CHEM 430 NMR Spectroscopy 61


Pulsed Fourier Transform (FT) Instrument

First, what is a Fourier Transform?

Fourier transforms interconvert mathematical functions in the frequency domain to the


time domain:

f(n) = f(t) e-int dt
-

f(t) = p f(n) eint dt
-
For purposes of this discussion, we will black box the actual calculations and derivations
of these functions, but we need to understand what they do

CHEM 430 NMR Spectroscopy 62


Spectrometer Design

Pulsed Fourier Transform (FT) Instrument

If we feed two simple oscillating equations into a FT, here are the results:

f (t) = cos (nt)

FT
-n +n

f (t) = sin (nt)

FT
+n

-n
CHEM 430 NMR Spectroscopy 63
Spectrometer Design NMR Spectroscopy

Pulsed Fourier Transform (FT) Instrument


In the FT instrument, all proton populations are excited simultaneously by a short,
intense burst of RF energy

Due to a variation of the Heisenberg Uncertainty Principle, even if the RF generator


is set at 90 MHz, if the duration of the pulse is short, the radio waves do not have
time to establish a solid fundamental frequency

This can be illustrated by the following cartoon, showing the combination of a short
pulse being added to a step function:

on on

+ =
off off off off

tp = pulse duration

CHEM 430 NMR Spectroscopy 64


Spectrometer Design

Pulsed Fourier Transform (FT) Instrument


4. If this short pulse is converted into the frequency domain by a FT:

on

FT

off off

tp
n
Observe that we have a continuum of frequency content centered at the
operating frequency of the instrument

We will talk more about the effects of pulse time and width when we
discuss advanced 1-D and 2-D NMR

CHEM 430 NMR Spectroscopy 65


Spectrometer Design

Pulsed Fourier Transform (FT) Instrument


5. For now, if a sample containing one unique population of hydrogens was excited
over tp by a pulse, it would then relax back to its original spin state

6. As each nuclei relaxes it will emit RF radiation of a given frequency; since different
nuclei will relax at different rates, the signal decays over time

7. This emission is recorded by the spectrometer as a free-induction decay or FID

off off

CHEM 430 NMR Spectroscopy 66


Spectrometer Design

Pulsed Fourier Transform (FT) Instrument


8. The actual frequency of the FID is the interference signal of the relaxing protons
superimposed with the frequency of the RF source

9. Conversion of this decay signal by FT back into the frequency domain gives us the
actual n of resonance for the proton being observed

Proton signal Pulse n


FT

time n

10.Again to due Heisenburg and other factors, NMR signals are not single lines, but a
Lorentzian shaped continuum of lines centered at the n of the signal

CHEM 430 NMR Spectroscopy 67


Spectrometer Design

Pulsed Fourier Transform (FT) Instrument


Advantages:
Since all nuclei are excited and observed simultaneously, the pulse can be repeated
after each relaxation period (for 1H, about 10 seconds) and the resulting signals
added together

Because we are observing weak radiofrequency signals in a sea of RF noise for dilute
samples (or those observed once as in CW NMR) noise becomes an issue

If several to hundreds of FIDs are added together, signals will tend to constructively
add together and become more pronounced; since noise is random, it will tend to
destructively add and become less pronounced

Signal to noise ratio improves as a function of the square root of the scans (FIDs)
performed: S/N = f (n)

CHEM 430 NMR Spectroscopy 68


Basis of NMR Spectroscopy
2.4 Excitation and Relaxation FT-NMR
Back to Pulse Sequences
Standard 1-D observation of 1H or other nuclei

90x
Detection Delay

Pulse
n = scans
Delay must be longer than T1 (and T2 < T1)

Scans are repeated until S/N ratio is high enough

CHEM 430 NMR Spectroscopy 69


Basis of NMR Spectroscopy
2.4 Excitation and Relaxation FT-NMR
How can you know what T1 is?
We cannot measure it directly in the z-axis
Pulse sequence is used called inversion recovery:

180y (or x) 90y

tD

CHEM 430 NMR Spectroscopy 70


NMR
Spectroscopy 2-6 Basis of NMR Spectroscopy
2.4 Excitation and Relaxation FT-NMR

tD = 0 z z

x x FT

y y

tD > 0 z z

x x FT

y y

tD >> 0 z z

x x FT

y y
CHEM 430 NMR Spectroscopy 71
NMR
Spectroscopy 2-6 Basis of NMR Spectroscopy
If we plot the intensity versus time we get the following curve:

Intensity, (I)

time

I(t) = I * ( 1 - 2 * e - t / T1 )

It is an exponential with a time constant equal to the T1 relaxation


time.

Most 1Hs decay in less than 10 seconds no need to run routinely


CHEM 430 NMR Spectroscopy 72
NMR
Spectroscopy 2-6 Basis of NMR Spectroscopy
2.4 Excitation and Relaxation FT-NMR
How can you know what T2 is?
We cannot measure it directly like T1
Pulse sequence is used called spin-echo sequence

90y 180y (or x)

tD tD

CHEM 430 NMR Spectroscopy 73


NMR
Spectroscopy 2-6 Basis of NMR Spectroscopy
2.4 Excitation and Relaxation FT-NMR
What it does:
z y y

x tD
x
x
y

y y dephasing

tD
x
x 180y (or x)

refocusing

CHEM 430 NMR Spectroscopy 74


NMR
Spectroscopy 2-6 Basis of NMR Spectroscopy
2.4 Excitation and Relaxation FT-NMR
If we acquire the FID right after the spin-echo sequence, the intensity of
the signal after FT will only be affected by T2 relaxation and not by
dephasing due to B0 imperfections.

Upon repetition for different tD values, we plot the intensity versus 2 * tD


and get a graph similar to the one we got for inversion recovery, but in this
case the decay rate will be equal to T2.

CHEM 430 NMR Spectroscopy 75


NMR
Spectroscopy 2-6 The Coupling Constant
Consider the spectrum of ethyl alcohol:
Why does each resonance split into smaller peaks?

HO CH3
C
H2

CHEM 430 NMR Spectroscopy 76


NMR
Spectroscopy 2-6 The Coupling Constant
The magnetic effects of nuclei in close proximity to those being observed
have an effect on the local magnetic field, and therefore DE

Two examples of close proximity are geminal and vicinal protons


(homonuclear) and protons attached to 13C (heteronuclear):

On any one of the 108 of these molecules in a typical NMR sample, there is
an equal statistical probability each proton is either spin + or

CHEM 430 NMR Spectroscopy 77


NMR
Spectroscopy 2-6 The Coupling Constant
This creates two different magnetic environments for a proton being
observed one where its neighbor is + the other where its neighbor is

If there is more than one proton on an adjacent carbon all the statistical
probabilities exist that each one is either + or in spin

The summation of these effects over all of the observed nuclei in the
sample is observed as the spin-spin splitting of resonances

CHEM 430 NMR Spectroscopy 78


NMR
Spectroscopy 2-6 The Coupling Constant
Consider 1-chloro-4-nitrobenzene

If we are observing the resonance for the HA proton,


in half the molecules in the sample HX would be
in the other half the spin would be +

We would see the resonance of HA split into two


different resonances (energy states):

CHEM 430 NMR Spectroscopy 79


NMR
Spectroscopy 2-6 The Coupling Constant
Consider 1-chloro-4-nitrobenzene

Likewise, if we are observing the resonance for the


HX proton, in half the molecules in the sample HA
would be in the other half the spin would be +

We would see the resonance of HX split into two


different resonances (energy states):

CHEM 430 NMR Spectroscopy 80


NMR
Spectroscopy 2-6 The Coupling Constant
Consider 1-chloro-4-nitrobenzene

The observed 1H NMR spectrum shows two doublets,


one for HA the other for HX

HA and HX are described as a spin-system

CHEM 430 NMR Spectroscopy 81


NMR Spectroscopy 2-6 The Coupling Constant
The influence of neighboring spins on peak multiplicity is called spin-spin
coupling, indirect coupling or J-coupling

The difference between the component peaks of a resonance is a measure


of how strong the interaction is between adjacent nuclei

This difference is called the coupling constant, J, measured in Hz

# of bonds
separating nuclei 3J
H-cis Nuclei that are coupled
and stereochemistry where
appropriate

CHEM 430 NMR Spectroscopy 82


NMR Spectroscopy -
Introduction 2-6 The Coupling Constant
60 MHz propyl bromide
Since J is a measure of J-values are =

interaction between two


nuclei, it must be the same for
both nuclei

J-values are =
Similarly, J is independent of
the applied B0 and will have
the same value regardless of
the field strength of the NMR

300 MHz propyl bromide

CHEM 430 NMR Spectroscopy 83


NMR Spectroscopy -
Introduction 2-6 The Coupling Constant
60 MHz propyl bromide
Since J is a measure of J-values are =

interaction between two


nuclei, it must be the same for
both nuclei

J-values are =
Similarly, J is independent of
the applied B0 and will have
the same value regardless of
the field strength of the NMR

300 MHz propyl bromide

CHEM 430 NMR Spectroscopy 84


NMR
Spectroscopy 2-6 The Coupling Constant
Recall, we are observing the frequency (E = hn) where a proton goes into
resonance

Any change in B0 will cause a change in


energy at which the resonance condition will
occur for a proton of a given chemical shift

CHEM 430 NMR Spectroscopy 85


NMR
Spectroscopy 2-6 The Coupling Constant
In solution we are not looking at a single molecule but about 108

On some molecules the proton being observed may be next to another


proton of spin + 1/2 :

CHEM 430 NMR Spectroscopy 86


NMR
Spectroscopy 2-6 The Coupling Constant
On some molecules the proton being observed may be next to another
proton of spin 1/2 :

CHEM 430 NMR Spectroscopy 87


NMR Spectroscopy -
Introduction 2-6 The Coupling Constant
Mechanism for coupling: usually oversimplified in early studies of
NMR - If molecules can rotate in solution any spatial effect of one
protons magnetic field on another is averaged to zero

The most common mechanism involves the interaction of electrons


along the bonding path between the nuclei.

Electrons, like protons, act like spinning particles and have a


magnetic moment. The X proton ( HX) influences, or polarizes, the
spins of its surrounding electrons, making the electron spins favor
one Iz state very slightly.
CHEM 430 88
NMR Spectroscopy -
Introduction 2-6 The Coupling Constant
Thus, a proton of spin + polarizes the electron to . The electron in
turn polarizes the other electron of the bond, and so on, finally
reaching the resonating A proton (HA).

Because J normally represents an interaction through bonds, it is a


useful parameter for drawing conclusions about molecular bonding,
such as bond order and stereochemistry.

CHEM 430 89
NMR
Spectroscopy 2-6 The Coupling Constant
Observe what effect this has on an isolated ethyl group:

The two methylene Ha protons have three neighbors, Hb, on the adjacent
methyl carbon

Each one of these hydrogens can be + or , and since we are not


looking at one molecule, but billions, we will observe all combinations

CHEM 430 NMR Spectroscopy 90


NMR
Spectroscopy 2-6 The Coupling Constant
The first possibility is that all three Hb protons have a + spin; in this case the
three protons combine to generate three small magnetic fields that aid B0 and
deshield the protons pushing part of the resonance for Ha slightly downfield (the
magnetic field of a proton is tiny compared to B0)

All 3 Hb
protons +

+++
Resonance, n, in absence of coupling

CHEM 430 NMR Spectroscopy 91


NMR
Spectroscopy 2-6 The Coupling Constant
The second possibility is that two Hb protons have a + spin and the third a - ;
in this case the two protons combine to enhance B0 and the other against it, a net
deshielding; there are 3 different combinations that generate this state

or or

3 combinations of
+, + , - -++
+-+
+++ ++-

Resonance, n, in absence of coupling

CHEM 430 NMR Spectroscopy 92


NMR
Spectroscopy 2-6 The Coupling Constant
The third possibility is that two Hb protons have a spin and the third +; here,
the two protons combine to reduce B0 and the other enforce it, a net shielding
effect; there are 3 different combinations that generate this state

or or

3 combinations of
+, - , - -++ --+
+-+ -+-
+++ ++- +--

Resonance, n, in absence of coupling

CHEM 430 NMR Spectroscopy 93


NMR
Spectroscopy 2-6 The Coupling Constant
The last possibility is that all three Hb protons have a spin; in this case the three
protons combine to oppose B0, a net shielding effect; there is one combination
that generates this state:

All 3 Hb
protons - -++ --+
+-+ -+-
+++ ++- +-- ---

Resonance, n, in absence of coupling

CHEM 430 NMR Spectroscopy 94


NMR
Spectroscopy 2-6 The Coupling Constant
The result is instead of one resonance (peak) for Ha, the peak is split into four, a
quartet, with the constituent peaks having a ratio of 1:3:3:1 centered at the d (n)
for the resonance :

-CHa2- is split
into a quartet by
three adj. Hbs

-++ --+
+-+ -+-
+++ ++- +-- ---

Resonance, n, in absence of coupling

CHEM 430 NMR Spectroscopy 95


NMR
Spectroscopy 2-6 The Coupling Constant
Similarly, the Hb protons having two protons, on the adjacent carbon each
producing a magnetic field, cause the Hb resonance to be split into a triplet

-CHb3- is split
into a triplet by two
adj. Has

-+
++ +- --
Resonance, n, in absence of coupling

CHEM 430 NMR Spectroscopy 96


NMR
Spectroscopy 2-6 The Coupling Constant
Rather than having to do this exercise for every situation, it is quickly
recognized that a given family of equivalent protons (in the absence of
other spin-coupling) will have its resonance split into a multiplet
containing n+1 peaks, where n is the number of hydrogens on carbons
adjacent to the carbon bearing the proton giving the resonance this is
the n + 1 rule
# of Hs on Multiplet # of The relative ratios of the peaks are a mathematical
adj. Cs peaks progression given by Pascals triangle:
0 singlet 1 1
1 doublet 2 1 1
2 triplet 3 1 2 1
3 quartet 4 1 3 3 1
4 quintet 5 1 4 6 4 1
5 sextet 6 1 5 10 10 5 1
6 septet 7 1 6 15 20 15 6 1

CHEM 430 NMR Spectroscopy 97


NMR
Spectroscopy 2-6 The Coupling Constant
Common patterns:

methyl - singlet tert-butyl - singlet


ethyl quartet - triplet

n-propyl triplet - quintet - triplet

iso-propyl septet - doublet

CHEM 430 NMR Spectroscopy 98


NMR
Spectroscopy 2-6 The Coupling Constant

CHEM 430 NMR Spectroscopy 99


NMR
Spectroscopy 2-6 The Coupling Constant

CHEM 430 NMR Spectroscopy 100


NMR
Spectroscopy 2-6 The Coupling Constant
Heteronuclear coupling between 1H and 13C are not apparent in 1H spectra
(13C low abundance - 1.1%), In 99 of 100 cases, 1H are attached to
nonmagnetic 12C atoms.

In the 13C spectrum, carbon nuclei are coupled to 1H directly (99%


abundant) attached to the carbon.

Thus, the 13C resonance of a methyl carbon is split into a quartet, that of a
methylene carbon CH2 into a triplet, and that of a methine carbon CH into a
doublet. A quaternary carbon is not split by one bond coupling.

CHEM 430 101


NMR
Spectroscopy 2-6 The Coupling Constant
Shown here (top) the 13C spectrum
of 3- hydroxybutyric acid which
contains a carbon resonance with
each type of multiplicity.
undecoupled
From right to left are seen a quartet
CH3 , a triplet CH2 , a doublet CH ,
and a singlet CO2H (C=O)

Instrumental procedures, called


decoupling, are available by which
spin spin split-tings may be decoupled
removed. These methods, discussed
in Section 5- 3, involve irradiating
one

CHEM 430 102


NMR
Spectroscopy 2-6 The Coupling Constant
Instrumental procedures, called
decoupling, are available by which
spin spin splittings are removed for
clarity.
undecoupled
These methods involve irradiating
one nucleus with an additional field
B2 while observing another nucleus
resonating in the B1 field.

13C spectra are usually run decoupled


as other spectral techniques are decoupled
used to establish 1H-13C connectivity
more rapidly and with more clarity

CHEM 430 103


The NMR Spectrum - 1H NMR Spectroscopy

Spin-spin splitting 1H NMR

The next level of complexity (which we will cover in detail in Chapter 4) is when protons on
adjacent carbons exert different Js than one another.

Consider the ethylene fragment:

The influence of the geminal-relationship


is over the shortest distance

The magnetic influence of the trans-


relationship is over the longest distance

The cis-relationship, is over an


intermediate distance
CHEM 430 NMR Spectroscopy 104
The NMR Spectrum - 1H NMR Spectroscopy

Spin-spin splitting 1H NMR

For ethylene we would then observe three chemically distinct resonances with spin-spin
splitting exerted by the other two protons:
The observed
J couplings: multiplet for Ha
is a doublet of
2J = 0 1 Hz
gem doublets

3J
AC

3J = 11- 18 Hz
trans

3J 3J
AB AB

3J = 6 - 15 Hz
cis

CHEM 430 NMR Spectroscopy 105


The NMR Spectrum - 1H NMR Spectroscopy

Spin-spin splitting 1H NMR

Similar behavior is observed with aromatic rings; since the ring structure is fairly rigid and
electronic effects are conducted over a longer distance, J couplings are observed across
the ring system:

In low-field 1H NMR the signal for this proton


3J
would be split into a doublet by the proton
ortho ortho to it.

On a high field instrument one finds this


3J 4 5
4J
meta ortho as well as a Jmeta and a J para from
the effect of the protons meta and para to it
5J
para
Typically:
3J
ortho = 7-10 Hz
4J
meta = 1-3 Hz
5J
para = 0-1 Hz

CHEM 430 NMR Spectroscopy 106


The NMR Spectrum - 1H NMR Spectroscopy

Spin-spin splitting 1H NMR

For our initial treatment of 1H NMR the alkenyl, aromatic and the following J values should
be learned:

3J = 6-8 3J = 11-18 3J = 8-11


trans 3J = 4-8
trans
3J = 6-12
cis

3J = 6-15
cis
3J = 8-14 3J = 5-7
a,a
3J
a,e = 0-7
3J
e,e = 0-5
3J
ortho =
7-10 Hz
4J
meta = 1-3 Hz
3J = 4-10
allyl 3J = 4-8
5J
para = 0-1 Hz
trans
3J = 6-12
cis
CHEM 430 NMR Spectroscopy 107
The NMR Spectrum - 1H

A typical 1H NMR is recorded from -2 to 15 d (ppm); what is typically reported is the


region from 0 to 10 d

Remember, if a proton is shielded (e- circulation reduces felt magnetic field) DE for the
transition is lowered and the signal is near the high field or upfield region of the
spectrum (right)

If the proton is deshielded (e- circulation doesnt reduce the felt magnetic field) DE
for the transition is raised and the signal is near the low field or downfield region of
the spectrum (left)

high DE low DE
deshielded 1H sees full B0 shielded 1H reduces B0
downfield upfield

10 CHEM 430 dNMR


or ppm 0
Spectroscopy 108
The NMR Spectrum - 1H

The number of signals observed will be equal to the number of unique populations of
chemically equivalent protons

To determine if two protons are chemically equivalent, substitute X for that each
respective hydrogen in the compound and compare the structures

If the two structures are fully superimposible (identical) the two hydrogens are
chemically equivalent; if the two structures are different the two hydrogens were not
chemically equivalent
CH3
H
A simple example: p-xylene
CH3 X
H CH3
Same structure
H
CH3 CH3
X

H
CHEM 430 NMR Spectroscopy
CH3 109
The NMR Spectrum - 1H

The position (v) of each resonance is dependant on the electronic environment around
the proton chemical shift as a result of local diamagnetic shielding

There are three principle effects that contribute to local diamagnetic shielding:
1) Electronegativity
2) Hybridization
3) Proton acidity/exchange

CHEM 430 NMR Spectroscopy 110


The NMR Spectrum - 1H

Local Diamagnetic Shielding - Electronegativity

1. Electronegative groups comprise most organic functionalities:

-F -Cl -Br -I -OH -OR -NH2

-NHR -NR2 -NH3+ -C=O -NO2-NO -SO3H

-PO3H2 -SH -Ph -C=C and most others

In all cases, the inductive w/d of electrons of these groups decreases the electron
density in the C-H covalent bond proton is deshielded higher DE of transition

CHEM 430 NMR Spectroscopy 111


The NMR Spectrum - 1H

Local Diamagnetic Shielding - Electronegativity

2. Protons bound to carbons bearing electron withdrawing groups are deshielded based
on the magnitude of the withdrawing effect Pauling electronegativity:

CH3F CH3O- CH3Cl CH3Br CH3I CH4 (CH3)4Si

Pauling 4.0 3.5 3.1 2.8 2.5 2.1 1.8


Electronegativity

d of H 4.26 3.40 3.05 2.68 2.16 0.23 0.0

CHEM 430 NMR Spectroscopy 112


The NMR Spectrum - 1H

Local Diamagnetic Shielding - Electronegativity

3. The magnitude of the withdrawing effect is cumulative:

CH3Cl CH2Cl2 CHCl3


d of H 3.05 5.30 7.27

4. The magnitude of the withdrawing effect is reduced by distance, as the inductive


model suggests

-CH2Br -CH2CH2Br -CH2CH2CH2Br


d of H 3.30 1.69 1.25

CHEM 430 NMR Spectroscopy 113


The NMR Spectrum - 1H NMR Spectroscopy

Local Diamagnetic Shielding - Hybridization

1. The hybridization of the carbon the proton is bound exerts a strong electronic effect

2. The greater the s-character, the more tightly bound the electrons are to carbon, raising
its effective electronegativity (sp = 50% s, sp2, 33% s and sp3 25% s)

Type of H Name of H Chemical Shift, d

R-CH3, R2CH2, R3CH alkyl 0.8-1.7

C=C-CH3 allyl 1.6-2.6

CC-H Acetylenic 2.0-3.0

C=C-H Vinylic 4.6-5.7 Something odd


is happening
Ar-H aromatic 6.5-8.5 here, as we will
discuss
O=C-H aldehydic 9.5-10.1
CHEM 430 NMR Spectroscopy 114
The NMR Spectrum - 1H NMR Spectroscopy

Local Diamagnetic Shielding - Proton Acidity/Exchange

1. If an organic molecule that possesses hydrogen atoms of low pKA are dissolved in a
deuterated solvent that also has a low pKA, the visible protons will exchange with
deuterium from solvent and become invisible to the NMR spectrometer

OH OD
D2O

Such studies are useful, if it is desired to see which H-atoms on an organic are acidic!

CHEM 430 NMR Spectroscopy 115


The NMR Spectrum - 1H NMR Spectroscopy

Local Diamagnetic Shielding - Proton Acidity/Exchange

2. Due to H-bonding effects, the resonance for certain functional groups (esp. OH and
NH2) can change drastically dependent on concentration and the extent of the H-
bonding

3. Just as in IR spectroscopy, peaks corresponding to these resonances are broad and


often undefined observing a continuum of bond strengths/electron densities about
the observed proton

4. The correlation tables for the position of such protons tend to be broad and unreliable:
Acid OH 10.5-12.0 d
Phenol OH 4.0-12.0 d
Alcohol OH 0.5-5.0 d
Amine NH2 0.5-5.0 d
Amide NH2 5.0-8.0 d
Enol CH=CH-OH >15 d
CHEM 430 NMR Spectroscopy 116
NMR Spectroscopy

Some observed 1H resonances can not be fully explained by local diamagnetic shielding
effects

Magnetic Anisotropy literally magnetic dissimilarity

For example, by our hybridization model, a proton bound to an sp2 C should be observed
at lower d than a proton bound to an sp C

Type of H Name of H Chemical Shift, d

R-CH3, R2CH2, R3CH alkyl 0.8-1.7

C=C-CH3 allyl 1.6-2.6

CC-H Acetylenic 2.0-3.0

C=C-H Vinylic 4.6-5.7

Ar-H aromatic 6.5-8.5

O=C-H aldehydic 9.5-10.1

CHEM 430 NMR Spectroscopy 117


The NMR Spectrum - 1H NMR Spectroscopy

Magnetic Anisotropy

1. This effect is primary due to the fact that there is an additional effect of circulating
electrons, observed in p-systems

2. In benzene, the 6-p-orbitals overlap to allow full circulation of electrons; as these


electrons circulate in the applied magnetic field they oppose the applied magnetic field
at the center just like the circulation of electrons in the 1-s orbital about hydrogen
at the middle!:

B0

CHEM 430 NMR Spectroscopy 118


The NMR Spectrum - 1H NMR Spectroscopy

Magnetic Anisotropy

3. On the periphery of the ring, the effect is opposite the magnetic effect reinforces the
applied B0, and DE becomes greater deshielding effect

CHEM 430 NMR Spectroscopy 119


The NMR Spectrum - 1H NMR Spectroscopy

Magnetic Anisotropy

4. This theory can easily be tested by the observation of large aromatic systems that
possess protons inside the ring (now a shielding effect):

-1.8 d
H
8.9 d H

Or over a ring system: 2.0 d


H2
C

CH2 -1.0 d
CHEM 430 NMR Spectroscopy 120
The NMR Spectrum - 1H NMR Spectroscopy

Magnetic Anisotropy

5. In alkynes, a similar situation (to the central protons in large aromatic systems) arises
where the terminal proton is in the region of maximum shielding

CHEM 430 NMR Spectroscopy 121


The NMR Spectrum - 1H NMR Spectroscopy

General Correlation Chart 1H NMR

Due to the three effects on local diamagnetic shielding, in conjunction with the effect of
magnetic anisotropy 1H NMR chemical shifts are variable
Avoid using hard and fast rules (tables of numbers)

Instead, start from the general correlation table and deduce structural features
based on the effects just discussed

After a structural inference has been made, then use the more specific correlation
tables to confirm the analysis

CHEM 430 NMR Spectroscopy 122


The NMR Spectrum - 1H NMR Spectroscopy

General Correlation Chart 1H NMR

Here are the general regions for 1H chemical shifts: CH3

H Si
O
H3C CH
C H
C CH3 3
O
C
O H
S H H
O R C R
O H
O R
H C H R = H or alkyl
C
O
H C C EWG
Ph

15 10 9 8 7 6 5 4 3 2 1 0.0

downfield d (ppm) upfield


deshielded shielded
higher DE lower DE
CHEM 430 NMR Spectroscopy 123
The NMR Spectrum - 1H NMR Spectroscopy

Spin-spin splitting 1H NMR

1. The magnetic effects of nuclei in close proximity to those being observed have an
effect on the local magnetic field, and therefore DE

2. Specifically, when proton is close enough to another proton, typically by being on an


adjacent carbon (vicinal), it can feel the magnetic effects generated by that proton

3. On any one of the 108 of these molecules in a typical NMR sample, there is an equal
statistical probability that the adjacent (vicinal) proton is either in the + or spin
state

4. If there is more than one proton on an adjacent carbon all the statistical probabilities
exist that each one is either + or in spin

5. The summation of these effects over all of the observed nuclei in the sample is
observed as the spin-spin splitting of resonances

CHEM 430 NMR Spectroscopy 124


Intensity of SignalsIntegration

The area under an NMR signal is proportional to the number of absorbing


protons

An NMR spectrometer automatically integrates the area under the peaks, and
prints out a stepped curve (integral) on the spectrum

The height of each step is proportional to the area under the peak, which in
turn is proportional to the number of absorbing protons

Modern NMR spectrometers automatically calculate and plot the value of


each integral in arbitrary units

The ratio of integrals to one another gives the ratio of absorbing protons in a
spectrum; note that this gives a ratio, and not the absolute number, of
absorbing protons
CHEM 430 NMR Spectroscopy 125
The NMR Spectrum - 1H NMR Spectroscopy

Integration 1H NMR

1. Like instrumental chromatography, in NMR spectroscopy, the area under a peak (or
multiplet) is proportional to the number of protons in the sample that generated that
particular resonance

2. The NMR spectrometer typically will print this information on the spectrum as an
integral line (stepped line on the spectrum below)

3. The height of the integral is proportional to that proton population; by comparing the
ratios of the integrals on an NMR spectrum you can determine the number of protons
as a least common multiple of these ratios

CHEM 430 NMR Spectroscopy 126


The NMR Spectrum - 1H NMR Spectroscopy

Integration 1H NMR

4. For example observe the integration of the ethanol spectrum below:

HO CH3
C -CH3
H2
3.75 units high

-OH
1.25 units high

2.5 units high

CHEM 430 NMR Spectroscopy 127


Intensity of SignalsIntegration

CHEM 430 NMR Spectroscopy 128


Intensity of SignalsIntegration

CHEM 430 NMR Spectroscopy 129


Nuclear Magnetic Resonance

When a nuclei of
spin + The nuclei tips The nuclei
encounters a its spin state and relaxes and
photon where is now opposed returns to the
n = E/h, the two to B0 + spin state
couple

CHEM 430 NMR Spectroscopy 130


Basis of NMR Spectroscopy
2.1 Excellent Simulators for NMR Phenomenon
2-D compass needle analogy:

http://www.drcmr.dk/JavaCompass/

3-D Bloch equation simulator

http://www.drcmr.dk/BlochSimulator/

CHEM 430 NMR Spectroscopy 131


General Theory NMR Spectroscopy

Nuclear Spin States


The sub-atomic particles within atomic nuclei possess a spin quantum number just
like electrons

As with electrons, the nucleons are organized in energy levels

Just as when using Hunds rules to fill atomic orbitals with electrons, nucleons must
each have a unique set of quantum numbers

The total spin quantum number of a nucleus is a physical constant, I

For each nucleus, the total number of spin states allowed is given by the equation:
2I + 1

CHEM 430 NMR Spectroscopy 132


General Theory NMR Spectroscopy

Nuclear Spin States

Spin Quantum Numbers of Common Nuclei

Element 1H 2H 12C 13C 14N 16O 17O 19F 31P 35Cl

Nuclear Spin 1 0 1 0 5/2 3/2


Quantum Number
# of spin states 2 3 0 2 3 0 6 2 2 4

6. Observe that for atoms with no net nuclear spin, there are zero allowed spin states

7. All the spin states of a given nucleus are degenerate in energy

CHEM 430 NMR Spectroscopy 133


General Theory NMR Spectroscopy

Nuclear Magnetic Moments


A nucleus contains protons, which each bear a +1 charge

If the nucleus has a net nuclear spin, and an odd number of protons, the rotation of
the nucleus will generate a magnetic field along the axis of rotation

Thus, a nucleus has a magnetic moment, m, generated by its charge and spin

A hydrogen atom with its lone proton making up the nucleus, can have two possible
spin states, degenerate in energy

m m

+ H H -

CHEM 430 NMR Spectroscopy 134


General Theory

Nuclear Spin States


5. In the presence of an externally applied magnetic field, these two spin states are no
longer degenerate in energy

6. The spin opposed orientation is slightly higher in energy than the spin aligned
orientation

m
H -

DE B0 externally applied magnetic field

m
+ H
CHEM 430 NMR Spectroscopy 135
General Theory

Absorption of Energy
The energy difference between the two non-degenerate spin states in the presence
of an applied magnetic field is quantized

At low B0 is easy to surmise that the potential energy of the spin opposed state
would be low, and as B0 grows in strength, so would the potential energy

Thus, with increasing strength of B0, DE between the two spin states also increases

-1/2

-1/2 +1/2
DE

+1/2

CHEM 430 BNMR


0 increasing
Spectroscopy 136
General Theory NMR Spectroscopy

Absorption of Energy
4. From theory we have already discussed, we say that a quantum mechanical particle
can absorb a photon of energy equal to DE and become promoted to the higher
state

5. This energy is proportional to the frequency of the photon absorbed, and in the
case of nuclear spin, is a function of the magnetic field applied:

DE = hn = f (B0)

6. Every nucleus has a different ratio of m to angular momentum (each has a different
charge and mass) this is referred to as the magnetogyric ratio, g

DE = hn = f (gB0)

Angular momentum is quantized in units of h/2p, thus:

DE = hn = g (h/2p)B
CHEM
0 430 NMR Spectroscopy 137
General Theory

Absorption of Energy
7. Solving for the frequency of EM radiation we are observing:

DE = n = (g/2p) B0

8. For a bare hydrogen nucleus (H+), g = 267.53 (106 radians/Tsec)

9. In a field strength of 1 Tesla, DE = 42.5 MHz (for our discussion, at 1.41 T, DE = 60


MHz)
DE = hn = f (B0)

This energy difference corresponds to the highly weak radio frequency region of the
EM spectrum with wavelengths of >5 meters equal to < 0.02 calmol-1

g-rays X-rays UV IR Microwave Radio

CHEM 430 NMR Spectroscopy 138


General Theory

Mechanism of absorption nuclear magnetic resonance


What we are actually observing for DE is the precessional or Larmor frequency (w)
of the spinning nucleus this is analogous to a spinning toy top precessing as a
result of the influence of the earths magnetic field:

B0

CHEM 430 NMR Spectroscopy 139


General Theory NMR Spectroscopy

Mechanism of absorption Nuclear Magnetic Resonance


2. When a photon of n = 60 MHz encounters this spinning charged system (a bare
proton) the two can couple and change the spin state of the proton

This state is called nuclear DE w


magnetic resonance, and the
nucleus is said to be in
resonance with the incoming
radio wave

B0
n=w
w

CHEM 430 NMR Spectroscopy 140


General Theory NMR Spectroscopy

Mechanism of absorption Nuclear Magnetic Resonance


3. The energy difference corresponding to 60 MHz (DE = hn) is 2.39 x 10-5 kJ mol-1
(tiny) thermal energy at room temperature (298 oK) is sufficient to populate both
energy levels

4. The energy difference is small, so rapid exchange is occurring between the two
populations, but there is always a net excess of protons in the lower energy state

5. From the Boltzman distribution equation we can calculate the population of each
energy state:

Nupper/Nlower = e-DE/kT = e-hn/kT

@ 298 oK the ratio is 1,000,000 / 1,000,009 !

There is an excess population of 9 nuclei in the lower energy state!

CHEM 430 NMR Spectroscopy 141


General Theory

Mechanism of absorption Nuclear Magnetic Resonance


6. As the applied B0 increases, exchange becomes more difficult and the excess
increases:
Frequency (MHz) Excess nuclei
60 9
80 12
100 16
200 32
300 48
600 96

7. In each case, it is these few nuclei that allow us to observe NMR

8. When radio radiation is applied to a sample both transitions upward and downward
are stimulated if too much radiation is applied both states completely equilibrate
a state called saturation no NMR signal can be observed

CHEM 430 NMR Spectroscopy 142


General Theory NMR Spectroscopy

Chemical Shift
6. Spectroscopic observation of the NMR phenomenon would be of little use if all
protons resonated at the same frequency

7. The protons in organic compounds are not bare nuclei, they are surrounded by an s
-orbital of containing an electron shared with an electron in a hybridized orbital of
another atom to form a covalent bond

8. In the presence of an external magnetic field, an induced circulation of electrons


opposite to that of a proton is observed since the two are of opposite charges

9. This induced circulation generates a magnetic field in opposition to the applied


magnetic field a local diamagnetic current

CHEM 430 NMR Spectroscopy 143


Basis of NMR Spectroscopy

2.1 Magnetic Properties of Nuclei


The magnitude of m from atom to atom varies:

m = gI

is Plancks constant divided by 2p

g is the characteristic gyromagnetic ratio of the nucleus

The larger g is, the greater the magnetic moment

CHEM 430 NMR Spectroscopy 144


Nuclear Magnetic Resonance

For the 1H nucleus (proton) this resonance condition occurs at low


energy (lots of noise) unless a very large magnetic field is applied

Early NMR spectrometers used a large permanent magnet with a


field of 1.4 Teslaprotons undergo resonance at 60 MHz (1 MHz =
106 Hz)

Modern instruments use a large superconducting magnetour


NMR operates at 9.4 T where proton resonance occurs at 400 MHz

In short, higher field gives cleaner spectra and allows longer and
more detailed experiments to be performed

CHEM 430 NMR Spectroscopy 145


Origin of the Chemical Shift

Electrons Deshieding Shielding


surrounding the Factors which lower e- Factors which raise
nucleus are density allow the e- density reduce
opposite in charge nucleus to see more the amount of B0
to the proton, of the B0 being the nucleus sees
therefore they applied resonance resonance
generate an occurs at higher condition occurs at
opposing b0 energy lower energy

CHEM 430 NMR Spectroscopy 146


The Proton (1H) NMR Spectrum

CHEM 430 NMR Spectroscopy 147


The 1H NMR Spectrum

A reference compound is neededone that is inert and does not


interfere with other resonances

Chemists chose a compound with a large number of highly shielded


protonstetramethylsilane (TMS)

No matter what spectrometer is used the resonance for the protons on


this compound is set to d 0.00

CH3

Si
H3C CH
CH3 3

CHEM 430 NMR Spectroscopy 148


The 1H NMR Spectrum

The chemical shift for a given proton is in frequency units (Hz)

This value will change depending on the B0 of the particular spectrometer

By reporting the NMR absorption as a fraction of the NMR operating


frequency, we get units, ppm, that are independent of the spectrometer

CHEM 430 NMR Spectroscopy 149


The 1H NMR Spectrum

We need to consider four aspects of a 1H spectrum:

a. Number of signals
b. Position of signals
c. Intensity of signals.
d. Spin-spin splitting of signals

CHEM 430 NMR Spectroscopy 150


The Number of Signals

The number of NMR signals equals the number of different types of


protons in a compound

Protons in different environments give different NMR signals

Equivalent protons give the same NMR signal

CHEM 430 NMR Spectroscopy 151


The Number of Signals

To determine if two protons are chemically equivalent, substitute X for


that each respective hydrogen in the compound and compare the
structures

If the two structures are fully superimposible (identical) the two


hydrogens are chemically equivalent; if the two structures are different
the two hydrogens were not equivalent

CH 3
A simple example: p-xylene H

CH 3 Z
H CH 3
Same Compound
H
CH 3 CH 3
Z

CHEM 430 NMR Spectroscopy H


152
CH 3
The Number of Signals

Examples

Important: To determine equivalent protons in cycloalkanes and alkenes, always draw


all bonds to show specific stereochemistry:

CHEM 430 NMR Spectroscopy 153


The Number of Signals

In comparing two H atoms on a ring or double bond, two protons are


equivalent only if they are cis or trans to the same groups.

CHEM 430 NMR Spectroscopy 154


The Number of Signals

Proton equivalency in cycloalkanes can be determined similarly:

CHEM 430 NMR Spectroscopy 155


The Number of Signals

Enantiotopic Protons when substitution of two H atoms by Z forms


enantiomers:
a. The two H atoms are equivalent and give the same NMR signal
b. These two atoms are called enantiotopic

CHEM 430 NMR Spectroscopy 156


The Number of Signals

Diastereotopic Protons - when substitution of two H atoms by Z forms


diastereomers
a. The two H atoms are not equivalent and give two NMR signals
b. These two atoms are called diastereotopic

CHEM 430 NMR Spectroscopy 157


Chemical Shift Position of Signals

Remember:

Electrons Deshieding Shielding


surrounding the Factors which lower Factors which raise
nucleus are e- density allow the e- density reduce the
opposite in charge nucleus to see amount of B0 the
to the proton, more of the B0 being nucleus sees
therefore they applied resonance resonance condition
generate an occurs at higher occurs at lower
opposing b0 energy energy
CHEM 430 NMR Spectroscopy 158
Chemical Shift Position of Signals

The less shielded the nucleus becomes, the more of the applied magnetic
field (B0) it feels

This deshielded nucleus experiences a higher magnetic field strength, to it


needs a higher frequency to achieve resonance

Higher frequency is to the left in an NMR spectrum, toward higher


chemical shiftso deshielding shifts an absorption downfield

Downfield, deshielded Upfield, shielded

CHEM 430 NMR Spectroscopy 159


Chemical Shift Position of Signals

There are three principle effects that contribute to local


diamagnetic shielding:
a. Electronegativity
b. Hybridization
c. Proton acidity/exchange

CHEM 430 NMR Spectroscopy 160


Chemical Shift Position of Signals

Electronegative groups comprise most organic functionalities:

-F -Cl -Br -I -OH -OR -NH2

-NHR -NR2 -NH3+ -C=O -NO2-NO -SO3H

-PO3H2 -SH -Ph -C=C and most others

In all cases, the inductive WD of electrons of these groups


decreases the electron density in the C-H covalent bond
proton is deshielded signal more downfield of TMS

CHEM 430 NMR Spectroscopy 161


Chemical Shift Position of Signals

Protons bound to carbons bearing electron withdrawing groups are


deshielded based on the magnitude of the withdrawing effect Pauling
electronegativity:

CH3F CH3O- CH3Cl CH3Br CH3I CH4 (CH3)4Si

Pauling 4.0 3.5 3.1 2.8 2.5 2.1 1.8


Electronegativity

d of H 4.26 3.40 3.05 2.68 2.16 0.23 0.0

CHEM 430 NMR Spectroscopy 162


Chemical Shift Position of Signals

3. The magnitude of the deshielding effect is cumulative:

CH3Cl CH2Cl2 CHCl3


d of H 3.05 5.30 7.27

As more chlorines are added d becomes larger

3. The magnitude of the deshielding effect is reduced by distance, as the


inductive model suggests

-CH2Br -CH2CH2Br -CH2CH2CH2Br


d of H 3.30 1.69 1.25

CHEM 430 NMR Spectroscopy 163


Chemical Shift Position of Signals

Hybridization
Increasing s-character (sp3 sp2 sp) pulls e- density closer to nucleus
effectively raising electronegativity of the carbon the H atoms are bound
to a deshielding effect

We would assume that H atoms on sp carbons should be well downfield


(high d) and those on sp3 carbons should be upfield (low d)

CHEM 430 NMR Spectroscopy 164


Chemical Shift Position of Signals

What we observe is slightly different:

Type of H Carbon Name of H Chemical Shift, d


hybridization
R-CH3, R2CH2, R3CH sp3 alkyl 0.8-1.7

C=C-CH3 sp3 allyl 1.6-2.6

CC-H sp acetylenic 2.0-3.0

C=C-H sp2 vinylic 4.6-5.7

Ar-H sp2 aromatic 6.5-8.5

O=C-H sp2 aldehydic 9.5-10.1

Chemists refer to this observation as magnetic anisotropy


CHEM 430 NMR Spectroscopy 165
Chemical Shift Position of Signals

Magnetic Anisotropy Aromatic Protons


a. In a magnetic field, the six p electrons in benzene circulate around
the ring creating a ring current.
b. The magnetic field induced by these moving electrons reinforces the
applied magnetic field in the vicinity of the protons.
c. The protons thus feel a stronger magnetic field and a higher
frequency is needed for resonance. Thus they are deshielded and
absorb downfield.

CHEM 430 NMR Spectroscopy 166


Chemical Shift Position of Signals

Similarly this effect operates in alkenes:

CHEM 430 NMR Spectroscopy 167


Chemical Shift Position of Signals

In alkynes there are two perpendicular sets of p-electronsthe molecule


orients with the field lengthwiseopposing B0 shielding the terminal H atom

CHEM 430 NMR Spectroscopy 168


Chemical Shift Position of Signals

CHEM 430 NMR Spectroscopy 169


Chemical Shift Position of Signals

CHEM 430 NMR Spectroscopy 170


Intensity of SignalsIntegration

The area under an NMR signal is proportional to the number of


absorbing protons

An NMR spectrometer automatically integrates the area under the


peaks, and prints out a stepped curve (integral) on the spectrum

The height of each step is proportional to the area under the peak,
which in turn is proportional to the number of absorbing protons

Modern NMR spectrometers automatically calculate and plot the value


of each integral in arbitrary units

The ratio of integrals to one another gives the ratio of absorbing


protons in a spectrum; note that this gives a ratio, and not the absolute
number, of absorbing protons

CHEM 430 NMR Spectroscopy 171


Intensity of SignalsIntegration

CHEM 430 NMR Spectroscopy 172


Intensity of SignalsIntegration

CHEM 430 NMR Spectroscopy 173


Spin-Spin Splitting

Consider the spectrum of ethyl alcohol:


Why does each resonance split into smaller peaks?

HO CH3
C
H2

CHEM 430 NMR Spectroscopy 174


Spin-Spin Splitting

The magnetic effects of nuclei in close proximity to those being


observed have an effect on the local magnetic field, and therefore DE

Specifically, when proton is close enough to another proton, typically


by being on an adjacent carbon (vicinal), it can feel the magnetic
effects generated by that proton

On any one of the 108 of these molecules in a typical NMR sample,


there is an equal statistical probability that the adjacent (vicinal)
proton is either in the + or spin state

If there is more than one proton on an adjacent carbon all the


statistical probabilities exist that each one is either + or in spin

The summation of these effects over all of the observed nuclei in the
sample is observed as the spin-spin splitting of resonances

CHEM 430 NMR Spectroscopy 175


Spin-Spin Splitting

Recall, we are observing the frequency (E = hn) where a proton goes


into resonance

Any change in B0 will cause a change in


energy at which the resonance condition will
occur for a proton of a given chemical shift

CHEM 430 NMR Spectroscopy 176


In solution we are not looking at a single molecule but about 108
On some molecules the proton being observed may be next to another
proton of spin + 1/2 :

CHEM 430 NMR Spectroscopy 177


Spin-Spin Splitting

On some molecules the proton being observed may be next to


another proton of spin 1/2 :

CHEM 430 NMR Spectroscopy 178


Spin-Spin Splitting

Observe what effect this has on an isolated ethyl group:

The two methylene Ha protons have three neighbors, Hb, on the


adjacent methyl carbon

Each one of these hydrogens can be + or , and since we are not


looking at one molecule, but billions, we will observe all combinations

CHEM 430 NMR Spectroscopy 179


Spin-Spin Splitting

The first possibility is that all three Hb protons have a + spin; in this
case the three protons combine to generate three small magnetic fields
that aid B0 and deshield the protons pushing the resonance for Ha
slightly downfield (the magnetic field of a proton is tiny compared to B0)

All 3 Hb
protons +

CHEM 430 NMR Spectroscopy 180


resonance for Ha in absence of spin-spin splitting
Spin-Spin Splitting

The second possibility is that two Hb protons have a + spin and the third
a - ; in this case the two protons combine to enhance B0 and the other
against it, a net deshielding;
there are 3 different combinations that generate this state

or or

2 Hb
protons +

CHEM 430 NMR Spectroscopy 181


resonance for Ha in absence of spin-spin splitting
Spin-Spin Splitting

The third possibility is that two Hb protons have a spin and the third
+; here, the two protons combine to reduce B0 and the other enforce
it, a net shielding effect;
there are 3 different combinations that generate this state

or or

2 Hb
protons -

CHEM 430 NMR Spectroscopy 182


resonance for Ha in absence of spin-spin splitting
Spin-Spin Splitting

The last possibility is that all three Hb protons have a spin; in this case
the three protons combine to oppose B0, a net shielding effect;
there is one combination that generates this state

All 3 Hb
protons -

CHEM 430 NMR Spectroscopy 183


resonance for Ha in absence of spin-spin splitting
Spin-Spin Splitting

The result is instead of one resonance (peak) for Ha, the peak is split
into four, a quartet, with the constituent peaks having a ratio of 1:3:3:1
centered at the d (n) for the resonance

CHEM 430 NMR Spectroscopy 184


resonance for Ha in absence of spin-spin splitting
Spin-Spin Splitting

Similarly, the Hb protons having two protons, on the adjacent carbon each
producing a magnetic field, cause the Hb resonance to be split into a
triplet

CHEM 430 NMR Spectroscopy 185


resonance for Ha in absence of spin-spin splitting
Spin-Spin Splitting

Rather than having to do this exercise for every situation, it is quickly


recognized that a given family of equivalent protons (in the absence of other
spin-coupling) will have its resonance split into a multiplet containing n+1
peaks, where n is the number of hydrogens on carbons adjacent to the carbon
bearing the proton giving the resonance this is the n + 1 rule

# of Hs Multiplet # of The relative ratios of the peaks are a


on adj. peaks mathematical progression given by Pascals
Cs triangle:
0 singlet 1 1
1 doublet 2 1 1
2 triplet 3 1 2 1
3 quartet 4 1 3 3 1
4 quintet 5 1 4 6 4 1
5 sextet 6 1 5 10 10 5 1
6 septet 7 CHEM 430 NMR Spectroscopy 1 6 15 20 15 6 1 186
1H NMRSpin-Spin Splitting

Common patterns:

methyl - singlet tert-butyl - singlet


ethyl quartet - triplet

n-propyl triplet - quintet - triplet

iso-propyl septet - doublet

CHEM 430 NMR Spectroscopy 187


1H NMRSpin-Spin Splitting

CHEM 430 NMR Spectroscopy 188


1H NMRSpin-Spin Splitting

Another Example:
Br
Br C
Br = Br
Br C
Br Ha
Hb Hb

CHEM 430 NMR Spectroscopy 189


1H NMRSpin-Spin Splitting

Another Example:

CHEM 430 NMR Spectroscopy 190


1H NMRSpin-Spin Splitting

Three general rules describe the splitting patterns commonly


seen in the 1H NMR spectra of organic compounds:
1.Equivalent protons do not split each others signals
2.A set of n nonequivalent protons splits the signal of a
nearby proton into n + 1 peaks
3.Splitting is observed for nonequivalent protons on the same
carbon or adjacent carbons
If Ha and Hb are not equivalent, splitting is observed when:

CHEM 430 NMR Spectroscopy 191


1H NMRSpin-Spin Splitting

Magnetic influence falls off dramatically with distance

The n + 1 rule only works in the following situations:

H H
Aliphatic compounds that have free
rotation about each bond
H H

G
H Ha
Aromatic compounds where each proton is
H Hb held in position relative to one another
Hc CHEM 430 NMR Spectroscopy 192
1H NMRSpin-Spin Splitting

The amount of influence exerted by a proton on an adjacent


carbon is observed as the difference (in Hz) between component
peaks within the multiplet it generates. This influence is
quantified as the coupling constant, J

Two sets of protons that split one another are said to be coupled

J for two sets of protons that are coupled are equivalent


therefore on complex spectra we can tell what is next to what

This J Is equal to this J

-CH2- CHEM 430 NMR Spectroscopy -CH3 193


1H NMRSpin-Spin Splitting

The next level of complexity (which at this level, is only introduced) is


when protons on adjacent carbons exert different Js than one another.

Consider the ethylene fragment:


The influence of the geminal-relationship is
over the shortest distance

The magnetic influence of the trans-


relationship is over the longest distance

The cis-relationship, is over an


intermediate distance
CHEM 430 NMR Spectroscopy 194
1H NMRSpin-Spin Splitting

For this substituted ethylene we see the following spectrum:

The observed multiplet


for Ha is a doublet of
2J = 0 1 Hz
gem doublets

3J
AC

3J = 11- 18 Hz
trans

3J 3J
AB AB

3J = 6 - 15 Hz
cis

CHEM 430 NMR Spectroscopy 195


1H NMRSpin-Spin Splitting

In general, when two sets of adjacent protons are different from each
other (n protons on one adjacent carbon and m protons on the other),
the number of peaks in an NMR signal = (n + 1)(M + 1)

In general the value of J falls off with distance; J values have been
tabulated for virtually all alkene, aromatic and aliphatic ring systems

CHEM 430 NMR Spectroscopy 196


1H NMRSpin-Spin Splitting

Some common J-values

3J = 6-8 3J = 11-18 3J = 8-11


trans 3J = 4-8
trans
3J = 6-12
cis

3J = 6-15
cis
3J = 8-14 3J = 5-7
a,a
3J
a,e = 0-7
3J
e,e = 0-5
3J
ortho = 7-10 Hz
4J
meta = 1-3 Hz
3J = 4-10 5J
allyl 3J
trans= 4-8 para = 0-1 Hz
3J = 6-12
cis
CHEM 430 NMR Spectroscopy 197
1H NMRSpin-Spin Splitting

We can now tell stereoisomers apart through 1H NMR:

CHEM 430 NMR Spectroscopy 198


1H NMRSpin-Spin Splitting

A combined example:

CHEM 430 NMR Spectroscopy 199


1H NMRSpin-Spin Splitting

Under usual conditions, an OH proton does not split the NMR signal
of adjacent protons
Protons on electronegative atoms rapidly exchange between
molecules in the presence of trace amounts of acid or base (usually
with NH and OH protons)

CHEM 430 NMR Spectroscopy 200


Structure Determination

CHEM 430 NMR Spectroscopy 201


Structure Determination

CHEM 430 NMR Spectroscopy 202


Structure Determination

CHEM 430 NMR Spectroscopy 203


Structure Determination

CHEM 430 NMR Spectroscopy 204


13C NMR

The lack of splitting in a 13C spectrum is a consequence of the low


natural abundance of 13C
Recall that splitting occurs when two NMR active nucleilike two
protonsare close to each other. Because of the low natural
abundance of 13C nuclei (1.1%), the chance of two 13C nuclei being
bonded to each other is very small (0.01%), and so no carbon-
carbon splitting is observed
A 13C NMR signal can also be split by nearby protons. This 1H-13C
splitting is usually eliminated from the spectrum by using an
instrumental technique that decouples the proton-carbon
interactions, so that every peak in a 13C NMR spectrum appears as a
singlet
The two features of a 13C NMR spectrum that provide the most
structural information are the number of signals observed and the
chemical shifts of those signals

CHEM 430 NMR Spectroscopy 205


13C NMR

CHEM 430 NMR Spectroscopy 206


13C NMR

The number of signals in a 13C spectrum gives the number of different


types of carbon atoms in a molecule.
Because 13C NMR signals are not split, the number of signals equals the
number of lines in the 13C spectrum.
In contrast to the 1H NMR situation, peak intensity is not proportional to
the number of absorbing carbons, so 13C NMR signals are not integrated.

CHEM 430 NMR Spectroscopy 207


13C NMR

In contrast to the small range of chemical shifts in 1H NMR (1-10


ppm usually), 13C NMR absorptions occur over a much broader range
(0-220 ppm).
The chemical shifts of carbon atoms in 13C NMR depend on the same
effects as the chemical shifts of protons in 1H NMR.

CHEM 430 NMR Spectroscopy 208


13C NMR

CHEM 430 NMR Spectroscopy 209


13C NMR

CHEM 430 NMR Spectroscopy 210


Shoolery Tables

After years of collective observation of 1H and 13C NMR it is possible to


predict chemical shift to a fair precision using Shoolery Tables

These tables use a base value for 1H and 13C chemical shift to which are
added adjustment increments for each group on the carbon atom

H H H
X C H X C Y X C Z
H H Y
methyl methylene methine

CHEM 430 NMR Spectroscopy 211


Shoolery Values for Methylene

X or Y Substituent X or Y Substituent
Constant Constant
-H 0.34 -OC(=O)OR 3.01
-CH3 0.68 -OC(=O)Ph 3.27
-CC 1.32 -C(=O)R 1.50
-CC- 1.44 -C(=O)Ph 1.90
-Ph 1.83 -C(=O)OR 1.46
-CF2- 1.12 -C(=O)NR2 or 1.47
H2
-CF3 1.14 -CN 1.59
-F 3.30 -NR2 or H2 1.57
-Cl 2.53 -NHPh 2.04
-Br 2.33 -NHC(=O)R 2.27
-I 2.19 CHEM 430 NMR Spectroscopy
-N 1.97 212
3

-OH 2.56 -NO2 3.36


Shoolery Values for Methine

X ,Y or Z Substituent X, Y or Z Substituent
Constant Constant
-F 1.59 -OC(=O)OR 0.47
-Cl 1.56 -C(=O)R 0.47
-Br 1.53 -C(=O)Ph 1.22
-NO2 1.84 -CN 0.66
-NR2 or H2 0.64 -C(=O)NH2 0.60
-NH3+ 1.34 -SR or H 0.61
- 1.80 -OSO2R 0.94
NHC(=O)R
-OH 1.14 -CC- 0.79

-OR 1.14 -C=C 0.46

-C(=O)OR 2.07 -Ph 0.99


CHEM 430 NMR Spectroscopy 213
-OPh 1.79
Shoolery Tables

For methyluse methylene formula and table


using the H value

For methyleneuse a base value of 0.23 and


add the two substituent constants for X and Y
In 92% of cases experimental is within 0.2 ppm

For methineuse a base value of 2.50 and add


the three substituent constants for X, Y and Z
Error similar to methylene
CHEM 430 NMR Spectroscopy 214
Shoolery Tables

Work for aromatics as well (.pdf posted)

CHEM 430 NMR Spectroscopy 215


Running an NMR Experiment

Sample sizes for a typical high-field NMR (300-600 MHz):


1-10 mg for 1H NMR
10-50 mg for 13C NMR

Solution phase NMR experiments are much simpler to run; solid-


phase NMR requires considerable effort

Sample is dissolved in ~1 mL of a solvent that has no 1H hydrogens

Otherwise the spectrum would be 99.5% of solvent, 0.5% sample!

CHEM 430 NMR Spectroscopy 216


Running an NMR Experiment

Deuterated solvents are employedall 1H atoms replaced with 2H


which resonates at a different frequency

Most common: CDCl3 and D2O

Employed if necessary: CD2Cl2, DMSO-d6, toluene-d8, benzene-d6,


CD3OD, acetone-d6

Sample is contained in a high-tolerance


thin glass tube (5 mm)

CHEM 430 NMR Spectroscopy 217


Running an NMR Experiment

IMPORTANTno deuterated solvent is 100% deuterated, there is


always residual 1H material, and this will show up on the spectrum

CHCl3 in CDCl3 is a singlet at d 7.27

HOD in D2O is a broad singlet at d 4.8

No attempt is made to make solvents for 13C NMR free of 13C, as the
resonances are so weak to begin with

13C NMR using CDCl3 shows a unique 1:1:1 triplet at d 77.00 (+1, 0, 1
spin states of deuterium coupled with 13C)

CHEM 430 NMR Spectroscopy 218