nuclear magnetic resonance -...
TRANSCRIPT
Nuclear Magnetic
Resonance Spectroscopy:
Tools for Structure Determination
Chung-Ming Sun
Department of Applied Chemistry
National Chiao Tung University
Hualien 300, Taiwan
Chapter 13 2
Introduction
• NMR (Nuclear Magnetic Resonance) is the most powerful tool available for organic structure determination.
• It is used to study a wide variety of nuclei:
1H
13C
15N
19F
31P
=>
Chapter 13 3
Nuclear Spin
• A nucleus with an odd atomic number or an odd
mass number has a nuclear spin.
• 1H has a spin quantum number I = 1/2 and has allowed spin states of +1/2 or -1/2
• Other nuclei with I = 1/2 are 13C, 19F and 31P and these also respond to an external magnetic field
• Nuclei with I = 0 do not have spin (12C and 16O) and do not respond to an external magnetic field
Chapter 13 4
The spinning charged nucleus
generates a magnetic field.
Chapter 13 5
External Magnetic Field
When placed in an external field, spinning protons act like bar magnets. The nucleiof NMR-active nuclei behave like tiny bar magnets
=>
Chapter 13 6
• alpha-spin state and beta-spin state
Chapter 13 7
Nuclear Spin: The Origin of the Signal
Chapter 13 8
In the absence of an external
magnetic field, proton magnetic
moments have random orientations.
Chapter 13 9
NMR absortion
The magnetic fields of the spinning nuclei will align either withthe external field, or against the field.
A photon with the right amount of energy can be absorbed and cause the spinning proton to flip.
Chapter 13 10
E and Magnet Strength• Energy difference is proportional to the
magnetic field strength.
• E = h = h B0
2
• Gyromagnetic ratio, , is a constant for
each nucleus (26,753 s-1gauss-1 for H).
• In a 14,092 gauss field, a photon of 60
MHz is required to flip a proton.
• Low energy, radio frequency. =>
Chapter 13 11
NMR involves absorption of energy in the
radiofrequency rang p.510
Chapter 13 12
The stronger the external magnetic field,
the higher the radio frequency energy
required to flip the nuclear spin
Chapter 13 13
Magnetic Shielding
• If all protons absorbed the same
amount of energy in a given magnetic
field, not much information could be
obtained.
• But protons are surrounded by electrons
that shield them from the external field.
• Circulating electrons create an induced
magnetic field that opposes the external
magnetic field. =>
Chapter 13 14
Shielded Protons
Magnetic field strength must be increased for a
shielded proton to flip at the same frequency.
Chapter 13 15
Protons in a Molecule
Depending on their chemical
environment, protons in a molecule are
shielded by different amounts.
=>
Chapter 13 16
NMR Signals
• The number of signals shows how many
different kinds of protons are present.
• The location of the signals shows how
shielded or deshielded the proton is.
• The intensity of the signal shows the
number of protons of that type.
• Signal splitting shows the number of
protons on adjacent atoms. =>
Chapter 13 17
The NMR Spectrometer
=>
Chapter 13 18
Chapter 13 19
The NMR GraphThe absorptions of more shielded protons
appear upfield, toward the right of the spectrum
=>
Chapter 13 20
Tetramethylsilane
• TMS is added to the sample.
• Since silicon is less electronegative than carbon, TMS protons are highly shielded. Signal defined as zero.
• Organic protons absorb downfield (to the left) of the TMS signal.
=>
Si
CH3
CH3
CH3
H3C
Chapter 13 21
Chemical Shift
• Measured in parts per million (ppm).
• Ratio of shift downfield from TMS (Hz) to total spectrometer frequency (Hz).
• Same value for 60, 100, or 300 MHz NMR machine.
• Called the delta (d) scale.
• Each d unit is 1 ppm difference from TMS: 60 Hz at 60 MHz and 300 Hz at 300 MHz
Chapter 13 22
• Table 13-1
• The chemical shift of the methyl protons depends on the electronegativity of the substituent.
• With more electronegative substituents deshielding more and giving larger chemical shifts.
• The effect of an electron-withdrawing substituent decreases with increasing distance.
Chapter 13 23
Delta Scale
=>
Chapter 13 24
Location of Signals
• More electronegative
atoms deshield more and
give larger shift values.
• Effect decreases with
distance (< four bonds).
• Additional electronegative
atoms cause increase in
chemical shift about 2-3
ppm each time.
Chapter 13 25
Typical Values
=>
Chapter 13 26
Aromatic Protons, d7-8 ppm
=>
Chapter 13 27
Chapter 13 28
Vinyl Protons, d5-6 ppm
=>
Chapter 13 29
Acetylenic Protons, d2.5
=>
Chapter 13 30
Aldehyde Proton, d9-d10
=>
Electronegative
oxygen atom
Chapter 13 31
O-H and N-H Signals
• Chemical shift depends on concentration.
• Hydrogen bonding in concentrated
solutions deshield the protons, so signal is
around d 3.5 for N-H and d 4.5 for O-H.
• Proton exchanges between the molecules
broaden the peak.
Chapter 13 32
Carboxylic Acid
Proton, d10+
=>
Chapter 13 33
Number of SignalsEquivalent hydrogens have the same
chemical shift.
=>
Chapter 13 34
Intensity of Signals• The area under each peak is
proportional to the number of protons.
• Shown by integral trace.
=>
Chapter 13 35
How Many Hydrogens?
When the molecular formula is known, each integral rise can be assigned to a particular number of hydrogens (p.575).
Chapter 13 36
Spin-Spin Splitting
• Nonequivalent protons on adjacent carbons
have magnetic fields that may align with or
oppose the external field.
• This magnetic coupling causes the proton
to absorb slightly downfield when the
external field is reinforced and slightly
upfield when the external field is opposed.
• All possibilities exist, so signal is split.
Chapter 13 37
1,1,2-Tribromoethane
Nonequivalent protons on adjacent carbons.
=>
Chapter 13 38
Doublet: 1 Adjacent Proton
=>
Chapter 13 39
Triplet: 2 Adjacent Protons
=>
Chapter 13 40
The N + 1 Rule
If a signal is split by N equivalent protons,
it is split into N + 1 peaks.
=>
Chapter 13 41
Range of Magnetic
Coupling (p.579)
• Equivalent protons do not split each other.
• Protons bonded to the same carbon will split each other only if they are not equivalent- 2J(geminal coupling)
• Protons on adjacent carbons normally will couple- 3J(vicinal coupling)
• Protons separated by four or more bonds will not couple( 距離太遠)- 4J~0
=>
Chapter 13 42
Chapter 13 43
Splitting for Ethyl Groupsp.579
=>
Chapter 13 44
Roof effect
• A multiplet often lean upward toward the
protons that are causing the splitting
Chapter 13 45
Splitting for
Isopropyl Groups (p.581)
=>
Chapter 13 46
Coupling Constants (J)
• Distance between the peaks of multiplet
• Measured in Hz
• Not dependent on strength of the external
field
• Multiplets with the same coupling constants
may come from adjacent groups of protons
that split each other (p.581).
Chapter 13 47
Values for
Coupling Constants
=>
Chapter 13 48
Para, ortho and meta isomers of
nitrotoluene
Chapter 13 49
• Cis coupling constant of two vinyl
protons is J = 9 Hz.
Chapter 13 50
• trans coupling constant of two vinyl
protons is J = 15 Hz. (p.584)
Chapter 13 51
Complex Splitting
• Signals may be split by adjacent
protons, different from each other, with
different coupling constants.
• Example: Ha of styrene which is split by
an adjacent H trans to it (J = 17 Hz) and
an adjacent H cis to it (J = 11 Hz).
=>
C C
H
H
Ha
b
c
Chapter 13 52
Splitting TreeC C
H
H
Ha
b
c
=>
Chapter 13 53
Spectrum for Styrene
=>
Chapter 13 54
Stereochemical Nonequivalence
• Usually, two protons on the same C are
equivalent and do not split each other.
• If the replacement of each of the protons of
a -CH2 group with an imaginary “Z” gives
stereoisomers, then the protons are non-
equivalent and will split each other.
=>
Chapter 13 55
Some Nonequivalent
Protons
C C
H
H
Ha
b
cOH
H
H
H
a
b
c
d
CH3
H Cl
H H
Cl
a b =>
Chapter 13 56
Chapter 13 57
Chapter 13 58
Chapter 13 59
Hc (He) are diastereotopic to Hd (Hf) and two sets
of protons absorb at different magnetic field and
are capable of splitting each other
Chapter 13 60
The two protons on the –CH2Cl
group are diastereotopic
Chapter 13 61
Diastereotopic protons in 1,2-
dichloropropane
Chapter 13 62
Time Dependence
• Molecules are tumbling relative to the
magnetic field, so NMR is an averaged
spectrum of all the orientations.
• Axial and equatorial protons on
cyclohexane interconvert so rapidly that
they give a single signal.(p.591)
• Proton transfers for OH and NH may occur
so quickly that the proton is not split by
adjacent protons in the molecule.
=>
Chapter 13 63
Chapter 13 64
Hydroxyl Proton
• Ultrapure samples
of ethanol show
splitting.
• Ethanol with a small
amount of acidic or
basic impurities will
not show splitting.=>
Chapter 13 65
N-H Proton
• Moderate rate of exchange.
• Peak may be broad.
=>
Chapter 13 66
Identifying the O-H
or N-H Peak• Chemical shift will depend on
concentration and solvent.
• To verify that a particular peak is due to
O-H or N-H, shake the sample with D2O
• Deuterium will exchange with the O-H
or N-H protons.
• On a second NMR spectrum the peak
will be absent, or much less intense.
Chapter 13 67
Common chemical shifts in the 1H NMR spectrum(p-594)
Chapter 13 68
Carbon-13
• 12C has no magnetic spin.
• 13C has a magnetic spin, but is only 1% of
the carbon in a sample.
• The gyromagnetic ratio of 13C is one-
fourth of that of 1H.
• Signals are weak, getting lost in noise.
• Hundreds of spectra are taken, averaged.
=>
Chapter 13 69
Fourier Transform NMR• Nuclei in a magnetic field are given a
radio-frequency pulse close to their
resonance frequency.
• The nuclei absorb energy and precess
(spin) like little tops.
• A complex signal is produced, then
decays as the nuclei lose energy.
• Free induction decay is converted to
spectrum. =>
Chapter 13 70
Hydrogen and Carbon
Chemical Shifts
=>
Chapter 13 71
Combined 13C
and 1H Spectra
=>
Chapter 13 72
Differences in 13C Technique
• Resonance frequency is ~ one-fourth,
15.1 MHz instead of 60 MHz.
• Peak areas are not proportional to
number of carbons.
• Carbon atoms with more hydrogens
absorb more strongly.
=>
Chapter 13 73
Spin-Spin Splitting
• It is unlikely that a 13C would be adjacent to another 13C, so splitting by carbon is negligible.
• 13C will magnetically couple with attached protons and adjacent protons.
• These complex splitting patterns are difficult to interpret.
=>
Chapter 13 74
Proton Spin Decoupling
• To simplify the spectrum, protons are continuously irradiated with “noise,” so they are rapidly flipping.
• The carbon nuclei see an average of all the possible proton spin states.
• Thus, each different kind of carbon gives a single, unsplit peak.
=>
Chapter 13 75
Off-Resonance Decoupling
• 13C nuclei are split only by the protons
attached directly to them.
• The N + 1 rule applies: a carbon with N
number of protons gives a signal with
N + 1 peaks.
=>
Chapter 13 76
Interpreting 13C NMR
• The number of different signals indicates
the number of different kinds of carbon.
• The location (chemical shift) indicates the
type of functional group.
• The peak area indicates the numbers of
carbons (if integrated).
• The splitting pattern of off-resonance
decoupled spectrum indicates the number
of protons attached to the carbon. =>
Chapter 13 77
Two 13C NMR Spectra
=>
Chapter 13 78
Chapter 13 79
MRI
• Magnetic resonance imaging, noninvasive
• “Nuclear” is omitted because of public’s
fear that it would be radioactive.
• Only protons in one plane can be in
resonance at one time.
• Computer puts together “slices” to get 3D.
• Tumors readily detected.
=>