13C-NMR,

2D-NMR, and MRI

Lecture Supplement: Take one handout from the stage

Midterm Exam 2
Date: Monday May 21 Time: 5:00-6:50 PM Topics: All of spectroscopy (mass spectrometry today) Location: last name A-La in Haines 39 last name Le-Z in Moore 100 Calculators not allowed Question and Answer Session Lecture time, Monday May 21 Submit questions to harding@chem.ucla.edu Label as Question for Q&A Deadline for possible inclusion: noon Sunday May 20 Extra Office Hours Saturday 3-5 PM, Young Hall 3077F (Steve Joiner) Sunday ???

13C-NMR
Is NMR limited to 1H? Any nucleus with I 0 can be observed 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 Easily observed by NMR 31P: 15 protons, 16 neutrons; 100% natural abundance Limited value for organic structure analysis 13C-NMR Carbon is backbone of organic molecules so 13C-NMR has high potential, but... Low natural abundance: 13C = 1.1% (12C = 98.9% but has 6 protons and 6 neutrons) Low probability that photon absorption causes spin flip: 1.6% compared to 1H Result: 13C spin flip much harder to observe than 1H spin flip Modern NMR spectrometers have overcome these problems; 13C-NMR now routine

13C-NMR
What can we deduce about molecular structure from 13C-NMR spectrum?

NMR fundamentals are the same regardless of nucleus

Information from carbon NMR spectrum

Number of signals: equivalent carbons and molecular symmetry

Chemical shift: presence of high EN atoms or pi electron clouds Integration: ratios of equivalent carbons 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

Symmetry exists when # of 13C-NMR signals < # of carbons in formula

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 Downfield shifts caused by electronegative atoms and pi electron clouds Example: HOCH2CH2CH2CH3 OH does not have carbon no 13C-NMR OH signal

13C-NMR:

Position of Signals
CDCl3 (solvent) = 77.0 ppm (triplet) benzene ring C=O ester C=O amide C=O carboxylic acid C=O aldehyde, keto ne 110 16 0 160 18 0 165 18 0 175 18 5 180 21 0

Characteristic Carbon NMR Chemical Shifts (ppm) (CH3)4Si = TMS = 0.00 ppm (singlet) RCH3 RCH2R R3CH RCH2I RCH2Br 0 40 15 55 20 60 0 40 25 - 65 RCH2Cl R3COH R3COR RCCR R2C=CR2

35 80 40 80 40 - 80 65 85 100 - 150

Trends RCH3 < R2CH2 < R3CH EN atoms cause downfield shift Pi bonds cause downfield shift C=O 160-210 ppm

It is not necessary to memorize this table. It will be given on an exam if necessary.

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13C-NMR:
1H-NMR:

Integration

Integration reveals relative number of hydrogens per signal Integration reveals relative number of carbons per signal

13C-NMR:

Rarely useful due to slow relaxation time for 13C time for nucleus to relax from excited spin state to ground state 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 with 1H, 1H with 13C, 13C with 13C 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 observed
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

Conclusions Carbon signal split by attached hydrogens (one bond coupling) No other coupling important

12C

13C-NMR:
1H-13C

Spin-Spin Coupling
H C H H
H C H

Splitting Patterns Carbon signal split by attached hydrogens N+1 splitting rule obeyed Example

H C
C

Quartet

Triplet

Doublet

Singlet

How can we simply this?

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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

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13C-NMR:

Spin-Spin Coupling

Distortionless Enhancement by Polarization Transfer (DEPT) Assigns each 13C-NMR signal as CH3, CH2, CH, or C
O

Example

CH3

All carbons

CH2 only 3only

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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
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2D-NMR
COSY: Correlation of 1H-1H coupling
3 H HO HO OH 1CH2 5 H 6 H OH 10 H CH2OH 12

Sucrose 1H-NMR

9 H HO H 2 O O H 4 8 HO CH2OH H 11 7

Sucrose 1H-NMR

Dots = correlations Ignore dots on diagonal

H8

Examples H6 and H5 are coupled Identify H8 by its coupling with H9

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2D-NMR
HMQC: Correlation of spin-spin coupling between 1H and nuclei other than 1H such as 13C
3 H HO HO OH 1CH2 5 H 6 H OH 10 H CH2OH 12

Sucrose 1H-NMR
O

9 H HO H 2 O O H 4 8 HO CH2OH H 11 7

No diagonal Example Which carbon bears H6?

92 ppm

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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 excitation 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

2002: 22,000 MRI instruments in use; 6 x 107 MRI exams performed

2003: Nobel Prize in Physiology or Medicine: to Paul Lauterbur and Peter Mansfield for their discoveries concerning magnetic resonance imaging http://nobelprize.org
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Magnetic Resonance Imaging (MRI)

NMR and MRI Use Similar Instruments Powerful magnets

An NMR spectrometer

An MRI instrument

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Magnetic Resonance Imaging (MRI)

MRI Images: Quite Different from NMR Spectra!

MRI image: a foot

MRI image: a head

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