Che 440/540 Proton Nuclear Magnetic Resonance (NMR) Spectroscopy
Fundamental NMR EquationsNumber of energy levels = 2I + 1I = the spin quantum number (1/2 for 1H and 13C)Therefore, there are two possible spin states for these nuclei.
E = h; h = Planck’s constant, = resonant frequency, Hz
= Bo/2Bo = applied magnetic field = gyromagnetic ratio (unique for each NMR active nucleus)
E = hBo/2
IsotopeNatural %Abundance
Spin (I)MagneticMoment (μ)*
MagnetogyricRatio (γ)†
1H 99.9844 1/2 2.7927 26,753
2H 0.0156 1 0.8574 4,107
11B 81.17 3/2 2.6880 --
13C 1.108 1/2 0.7022 6,728
17O 0.037 5/2 -1.8930 -3,628
19F 100.0 1/2 2.6273 25,179
29Si 4.700 1/2 -0.5555 -5,319
31P 100.0 1/2 1.1305 10,840
* μ in units of nuclear magnetons = 5.05078•10-27 JT-1 † γ in units of 107 rad T-1 sec-1
Characteristics of Some NMR Active Nuclei
no magnetic field present Bo magnetic field present
Nuclear Spins in the Absence and Presence of a Magnetic Field
Slide by Joanna LeFevre
spin state
spin state(slight excess)
N/N = e-E/kT
For a 300 MHz instrument, N/N = 1,000,000/1,000,048.Therefore, for every two million nuclei, there are only 48 excess nuclei in the spin state!! Therefore NMR is an
inherently insensitive technique.http://teaching.shu.ac.uk/hwb/chemistry/tutorials/molspec/nmr1.htm
magnetic moment, μ
http://www.cem.msu.edu/~reusch/VirtualText/Spectrpy/nmr/nmr2.htm#nmr12b
A spinning gyroscope
in a gravitational field A spinning charge
in a magnetic field
I = +1/2
I = -1/2
http://www.cem.msu.edu/~reusch/VirtualText/Spectrpy/nmr/nmr2.htm#nmr12b
Net Macroscopic Magnetization of a Sample in an External Magnetic Field Bo
Excitation by RF Energy and Subsequent Relaxation
T1 = spin-lattice relaxation time; establishes the z axis equilibrium. T1’sare usually short (<1 sec) in 1H NMR. They can be quite long (>1 min) in 13C NMR.
T2 = spin-spin relaxation time; causes a decrease in magnetization in the x-y plane.For a good magnet, T2 = 1-2 sec.
http://www.cem.msu.edu/~reusch/VirtualText/Spectrpy/nmr/nmr2.htm#nmr12b
http://www.cem.msu.edu/~reusch/VirtualText/Spectrpy/nmr/nmr2.htm#pulse
Four different frequencies
Complex summation wave (FID)
Fourier transformation
Generation and Fourier Transformation (FT) of a Free Induction Decay (FID) Pattern
http://www.cem.msu.edu/~reusch/VirtualText/Spectrpy/nmr/nmr2.htm#pulse
seconds0 1 2 3 4 5
Free Induction Decay (FID) Signal: A Decaying Cosine Curve
5 Hz signalAssume T2 = 2 secIt = Ioe-t/T2
~35% of signal remains after 2 sec.
0.020.02 0.040.04 0.060.06 0.080.08 0.100.10
Time (sec)
0.02 0.04 0.06 0.08 0.1
Portion of the FID of BetulinH
H
H
OH
HO
H
0.50.51.01.01.51.52.02.02.52.53.03.03.53.54.04.04.54.55.05.0
H
H
H
OH
HO
H
1H Spectrum of Betulin after Fourier Transformation
Presentation of NMR Data
= chemical shift (Hz) – shift of tetramethyl silane (TMS; 0 Hz) = ppm spectrometer frequency (MHz)
For example, in CH2Cl2 a sharp singlet occurs at 1,590 Hz using a 300 MHz spectrometer frequency.
The chemical shift is:(1,590 – 0) Hz = 5.3 ppm 300 MHz
Shielding vs Deshielding
Increasing deshielding
Increasing shielding, Bo
ClCH2 C CH2Cl
CH3
CH3
Downfield Upfield
Compound, CH3X CH3F CH3OH CH3Cl CH3Br CH3I CH4 (CH3)4Si
X F O Cl Br I H Si
Electronegativity of X 4.0 3.5 3.1 2.8 2.5 2.1 1.8
Chemical shift, / ppm 4.26 3.4 3.05 2.68 2.16 0.23 0
Electronegative groups attached to the C-H system decrease the electron density around the protons, and there is less shielding (i.e. deshielding) so the chemical shift increases.
These effects are cumulative, so the presence of more electronegative groups produce more deshielding and therefore, larger chemical shifts.
Compound CH4 CH3Cl CH2Cl2 CHCl3
/ ppm 0.23 3.05 5.30 7.27
http://www.chem.ucalgary.ca/courses/351/Carey/Useful/nmr1.gif&imgrefurl
Anisotropic Shielding and Deshielding
1H NMR Spectrum of 4-Methylbezaldehyde
CH3
O
H
H
H
deshieldedprotons
ppm
TMS
CH3CH3
RONR2
CH3OCH3
RO
HR
R R
HH
RO
Ph CH3
HR
Cl
CH3
Ph
OH
OH
R
NHR
Upfield regionof the spectrum
Downfield regionof the spectrum
TMS = Me Si
Me
Me
Me
012345678910
CH3HO(R)
http://orgchem.colorado.edu/hndbksupport/nmrtheory/NMRtutorial.html
Chemical Shifts of Various Protons
Integrations: Relative Numbers of Protons
H3C
O
O
CH3
CH3CH3
3
1
CH3
H3C O
O
CH3
1H NMR Spectrum of Isopentyl Acetate
6H
2H
1H
3H
2H
Spin-Spin Splitting: The n+1 rule in Vicinal Coupling (HA-C-C-HB)
Equivalent nuclei do not couple each other.
The number of lines in a multiplet is determined by the number of equivalent protons on neighboring atoms plus one, i.e. the n + 1 ruleThe distance between the peaks is called the coupling constant (3J).
The coupling constant is not dependent on the applied field strength.
A
B
B
B
JAB = 7 Hz
JAB = 7 Hz
http://teaching.shu.ac.uk/hwb/chemistry/tutorials/molspec/nmr1.htm
The Origin of Spin-Spin Splitting
CH3 CH2 OH
Some Common Splitting Patterns
Condition for Applying the n+1 Rule
CC
HA
C
HB HA'
If JHA-HB = JHA’-HB then the n+1 rule applies and HB appears as a 1:2:1 triplet.
However, if the relevant J values are not the same, the splitting is more complex.
HA
HX
HM
O16 Hz
12 Hz
Example: Cis and Trans Coupling in a Carbon-Carbon Double Bond
HA
HX
HM
OCH2CH2Cl
The Karplus Relationship
The vicinal coupling constant (3J) is dependent upon the dihedral angle, .
http://www.cem.msu.edu/~reusch/VirtualText/Spectrpy/nmr/nmr2.htm#nmr12b
3.103.103.203.203.303.303.403.403.503.503.603.603.703.70
H3C CH3
OH
CH3
CH3
H3CHO
CH3
H2(ax)
H6(eq)
H6(ax)
H1
Menthol
H1
Some Alkene Splitting Patterns
http://www.cem.msu.edu/~reusch/VirtualText/Spectrpy/nmr/nmr2.htm#nmr12b
Typical 1H-1H Coupling Constants
http://www.cem.msu.edu/~reusch/VirtualText/Spectrpy/nmr/nmr1.htm
First-Order CouplingThe splitting pattern shown below displays the ideal or"First-Order" arrangement of lines. This is usually observedif the spin-coupled nuclei have very different chemical shifts.
The condition that must be met is /J > 6. Consider ethyl acetate.
HA = 1.26 ppm x 90 Hz/ppm = 113.4 HzHC = 4.11 ppm x 90 Hz/ppm = 369.9 Hz
/J = (369.9 – 113.4)Hz/7.2 Hz = 35.6
http://www.cem.msu.edu/~reusch/VirtualText/Spectrpy/nmr/nmr2.htm#nmr12b
However, if the ratio of Δν to J decreases to less than 10 a significant distortion of the expected pattern will take place.
Second-Order Coupling
First-order
http://www.cem.msu.edu/~reusch/VirtualText/Spectrpy/nmr/nmr2.htm#nmr12b
Example of a Second-Order Coupling Pattern
http://www.cem.msu.edu/~reusch/VirtualText/Spectrpy/nmr/nmr2.htm#nmr12b
Magnetic Non-equivalence
H(A) and H(B) are magnetically non-equivalent.H(A) and H(A)* couple differently to H(B) [and to H(B*)].
*
*
Para and Meta-Disubstituted Benzene RingsNO2
Cl
NO2
Cl
Increasing the field strength leads to greater dispersion of signals.
Mono-Substituted Benzene Ring
http://www.cem.msu.edu/~reusch/VirtualText/Spectrpy/nmr/nmr2.htm#nmr12b
Chemical Shift Equivalence
C
H
H
H’s are homotopic:Related by a 180o rotational axis, Cn.They have the same chemical shift.
Chemical Shift Equivalence
C
H
H
NH2
H’s are enantiotopic:Related by a mirror plane, .They have the same chemical shift.
Chemical Shift EquivalenceHA and HB are diastereotopic: They are not related by a rotational axis or a mirror plane. They have different chemical shifts, and they split each other.
C HAHB
NH2
CO2HH
Homotopic Methyl Groups
These methyls are homotopic: they arerelated by a 180o rotational axis, Cn.They have the same chemical shift.
CH3
CH3
ClCl
Enantiotopic Methyl Groups
CH3
CH3
HO
These methyls are enantiotopic:They are related by a mirror plane, .They have the same chemical shift.
Diastereotopic Methyl Groups
CH3
CH3
C H
H
OH
CH3O
These methyls are diastereotopic: They are not related by a rotational axis or a mirror plane. They have different chemical shifts.Notice that a chiral center* is present.
CH3
CH3
H3CCOCH2CH2 H
O
Compare with isopentyl acetate(enantiotopic methyls)
For the following molecules label any groups that are homotopic, enantiotopic, or diastereotopic.
H3C
CH3
O
CH3
OH
CH3
Br Br
NH
OCH3OCCH3
O
HO
http://www.cis.rit.edu/class/schp740/docu/avance/noediff.pdf
NOE Difference Spectra of Pamoic Acid
CH2Ha
Hb
Hc
Hd
OH
CO2H
OH
CO2H
He
NOE
NOE
Ha
Hd
NOE Difference Spectrum of Betulin
4.404.504.604.704.804.90
NOE difference spectrum
normal spectrum
NOE
H
OH
H3C
Hcis Htrans
Pople Notation: Describes sets of spins
If /J > 8, the pattern is called AX (i.e. ethyl acetate).
A3
X2
CH3CO2CH2CH3:A3X2
If /J < 8, the pattern is called AB (i.e. 2-chloroacrylonitrile)
H
H Cl
CN
A
B
Three weakly coupled sets are designated AMX; (i.e. styrene)
HX
HA
HM
A
M
X
CO2H
Cl
AA’XX’ pattern
AA’BB’ pattern
*
*
A compound whose 1H NMR spectrum appears below has a molecularformula of C7H14O2. The IR spectrum shows a strong absorbance at1739 cm-1. Suggest a structure for this compound.
15 mm
15 mm
15 mm
15 mm
23 mm
23 mm