Midterm 1
• 1 hour exam (in class on Friday, May 25)
• Will cover:
– Mass Spectrometry, IR, 1H-NMR, and 13C-NMR.
– Will NOT cover X-Ray crystallography.
• Last name A-P in CS50
• Last name Q-Z in Franz 1260
•
You will be provided with a periodic table and the information from the inside
cover of the lecture supplement (Natural abundances, IR stretching
frequencies, and characteristic proton NMR shifts)
• Tools
– Pen and/or pencil
– Model kit
– No calculators or cell phone
How should I study?
• Review past “Exam 2”s on Hardinger’s website
http://www.chem.ucla.edu/harding/index.html
(on left frame, click “Ch14C” then in middle frame click
“Current and Past Exam and Keys”)
Note: X-ray
crystallography will not
be on Midterm 2, so
please skip those
questions on the practice
exams
13C-NMR,
2D-NMR, and MRI
Lecture Supplement page 181
An NMR spectrometer
An MRI instrument
13C-NMR
Is NMR limited to 1H?
•Any nucleus with I (spin quantum number)  0 can be studied by NMR
• I  0 when nucleus has odd number of protons or odd number of neutrons
•Includes 1H, 2H, 13C, 19F, 29Si, 31P, 127I, etc.
Examples
•19F: 9 protons, 10 neutrons; 100% natural abundance
•31P: 15 protons, 16 neutrons; 100% natural abundance
•19F, 31P easily observed by NMR, but of limited value for organic structure analysis
13C-NMR
•13C: 6 protons, 7 neutrons; I  0, 1.1% natural abundance
•Carbon is backbone of organic molecules so 13C-NMR very useful
13C-NMR
What can we deduce about molecular structure from 13C-NMR spectrum?
•NMR fundamentals are the same regardless of nucleus
Information from 13C-NMR spectrum
1. Number of signals: Equivalent carbons and molecular symmetry
2. Chemical shift: Presence of high EN atoms or pi electron clouds
3. Integration: Ratios of equivalent carbons
4. Coupling: Number of neighbors
13C-NMR:
Number of Signals
Number of 13C-NMR signals reveals equivalent carbons
•One signal per unique carbon type
•Reveals molecular symmetry
•Examples:
CH3CH2CH2CH2OH No equivalent carbons
Four 13C-NMR signals
CH3CH2OCH2CH3
2 x CH3 equivalent
2 x CH2 equivalent
Two 13C-NMR signals
If # of 13C-NMR signals < # of carbons in formula then molecule has some symmetry
13C-NMR:
Position of Signals
•Position of signal relative to reference = chemical shift
•13C-NMR reference = TMS = 0.00 ppm
•13C-NMR chemical shift range = 0 - 250 ppm
•Deshielding caused by electronegative atoms and pi electron clouds
Example:
HOCH2CH2CH2CH3
OH does not have carbon

no 13C-NMR signal for OH
13C-NMR:
Position of Signals
Trends
It is not necessary to memorize this table.
•EN atoms cause deshielding
It will be given on an exam if necessary.
•RCH3 < R2CH2 < R3CH EN C > EN H
•Pi bonds cause deshielding and shielding
•C=O 160-220 ppm Cross-check with IR zone 4
13C-NMR:
1H-NMR:
Integration
Integration reveals relative number of hydrogens per signal
13C-NMR:
Integration reveals relative number of carbons per signal
•Rarely useful due to slow relaxation time for 13C
Relaxation time: Time for nucleus to relax from excited spin state to ground state
I = - ½ Excited state
I = + ½ Ground state
•1H relaxation time important phenomenon for MRI
13C-NMR:
Spin-Spin Coupling
Spin-spin coupling of nuclei causes splitting of NMR signal
•Only nuclei with I  0 can couple
•Examples: 1H couples with 1H, 1H couples with 13C, 13C couples with 13C
1H does not couple with 12C
•1H NMR: Splitting reveals number of H neighbors
•13C-NMR: Limited to nuclei separated by just one sigma bond; no pi bond “free spacers”
Coupling occurs
Coupling occurs but signal very weak:
Low probability for two adjacent 13C
1.1% x 1.1% = 0.012%
1H
13C
No coupling: Too far apart
13C
No coupling: 12C has I = 0
12C
Conclusions
•Carbon signal split by attached hydrogens only (one bond coupling)
•No other coupling important
13C-NMR:
Spin-Spin Coupling
1H-13C
Splitting Patterns
•Carbon signal split by attached hydrogens
•N+1 splitting rule obeyed
Example
H
C
H
C
C
C
Doublet
Singlet
H
H
Quartet
Triplet
O
Singlet
H
H
How can we simply this?
Quartet
13C-NMR:
Spin-Spin Coupling
Simplification of Complex Splitting Patterns
•Broadband decoupling: All C-H coupling is suppressed
•All split signals become singlets
•Signal intensity increases; less time required to obtain spectrum
Proton decoupled
Singlet
O
Singlet
Singlet
13C-NMR:
Spin-Spin Coupling
Distortionless Enhancement by Polarization Transfer (DEPT)
•Assigns each 13C-NMR signal as CH3, CH2, CH, or C
O
Example
All carbons
CH3
CH3 only
13C-NMR:
O
Spin-Spin Coupling
CH2 only
CH3
All carbons
CH only
Two-Dimensional NMR (2D-NMR)
•Basis: Interaction of nuclear spins (1H with 1H, 1H with 13C, etc.) plotted in two dimensions
•Applications:
Simplifies analysis of more complex or ambiguous cases such as proteins
Obtain structural information not accessible by one-dimensional NMR methods
•Techniques include:
Correlation Spectroscopy (COSY)
Heteronuclear Correlation Spectroscopy (HETCOR)
Heteronuclear Multiple-Quantum Coherence (HMQC)
Nuclear Overhauser Effect Spectroscopy (NOESY)
Incredible Natural Abundance Double Quantum Transfer Experiment (INADEQUATE)
Many others
2D-NMR
COSY: Correlation of 1H-1H coupling
Sucrose 1H-NMR
OH
1 CH2
5
H
6
H OH
O
HO
HO
H
4 H 2
HO
O
H 10
9
H
CH2OH
O
8
12
HO
CH2OH
7
H 11
•Dots = 1H-1H coupling
•Ignore dots on diagonal
Sucrose 1H-NMR
3H
Examples
•H6 and H5 are coupled
•Identify H10 by coupling with H9
H10
2D-NMR
HMQC: Correlation of spin-spin coupling between 1H and nuclei other than 1H such as 13C
Sucrose 1H-NMR
OH
3H
1 CH2
5
H
6
H OH
O
HO
HO
H
4 H 2
HO
O
H 10
9
H
CH2OH
O
8
12
HO
CH2OH
7
H 11
•Dot = H bonded to C
•No diagonal
Example
Which carbon bears H6?
92 ppm
Magnetic Resonance Imaging (MRI)
Basis: Spin-excited nuclei relax at a rate dependent on their environment
•Environmental factors = bonding to other atoms, solvent viscosity, etc.
•Photons released upon relaxation are detected
•1H relaxation times varies with tissue type (brain, bone, etc.)
•Therefore tissues may be differentiated by NMR
Timeline
1971: First MRI publication: “Tumor Detection by Nuclear Magnetic Resonance”
Science, 1971, 171, 1151
2003: Nobel Prize in Physiology or Medicine - Paul Lauterbur and Peter Mansfield
for “their discoveries concerning magnetic resonance imaging”
http://nobelprize.org
2010: ~6800 MRI instruments in use; ~3 x 107 MRI scans performed
Magnetic Resonance Imaging (MRI)
NMR and MRI use similar instruments
Powerful magnets
An NMR spectrometer
An MRI instrument
Magnetic Resonance Imaging (MRI)
MRI Images: Quite different from NMR spectra!
2D MRI image: A head
3D MRI Image: A brain