1. 1 13 C-NMR, 2D-NMR, and MRI Lecture Supplement: Take one handout from the stage

2. 2 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.eduharding@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 ???

3. 3 13 C-NMR Is NMR limited to 1 H? Any nucleus with I  0 can be observed I  0 when nucleus has odd number of protons or odd number of neutrons Includes 1 H, 2 H, 13 C, 19 F, 29 Si, 31 P, 127 I, etc. Examples 19 F: 9 protons, 10 neutrons; 100% natural abundance 31 P: 15 protons, 16 neutrons; 100% natural abundance } Easily observed by NMR Limited value for organic structure analysis 13 C-NMR Carbon is backbone of organic molecules so 13 C-NMR has high potential, but... Low natural abundance: 13 C = 1.1% ( 12 C = 98.9% but has 6 protons and 6 neutrons) Low probability that photon absorption causes spin flip: 1.6% compared to 1 H Result: 13 C spin flip much harder to observe than 1 H spin flip Modern NMR spectrometers have overcome these problems; 13 C-NMR now routine

4. 4 13 C-NMR What can we deduce about molecular structure from 13 C-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

5. 5 13 C-NMR: Number of Signals Number of 13 C-NMR signals reveals equivalent carbons One signal per unique carbon type Reveals molecular symmetry Examples CH 3 CH 2 CH 2 CH 2 OHCH 3 CH 2 OCH 2 CH 3 Two 13 C-NMR signals 2 x CH 3 equivalent 2 x CH 2 equivalent No equivalent carbons Four 13 C-NMR signals Symmetry exists when # of 13 C-NMR signals < # of carbons in formula

6. 6 13 C-NMR: Position of Signals Position of signal relative to reference = chemical shift 13 C-NMR reference = TMS = 0.00 ppm 13 C-NMR chemical shift range = 0 - 250 ppm Downfield shifts caused by electronegative atoms and pi electron clouds OH does not have carbon  no 13 C-NMR OH signal Example: HOCH 2 CH 2 CH 2 CH 3

7. 7 13 C-NMR: Position of Signals It is not necessary to memorize this table. It will be given on an exam if necessary. Trends RCH 3 < R 2 CH 2 < R 3 CH EN atoms cause downfield shift Pi bonds cause downfield shift C=O 160-210 ppm

8. 8 13 C-NMR: Integration 1 H-NMR : Integration reveals relative number of hydrogens per signal 13 C-NMR : Integration reveals relative number of carbons per signal Rarely useful due to slow relaxation time for 13 C Relaxation time important phenomenon for MRI time for nucleus to relax from excited spin state to ground state

9. 9 13 C-NMR: Spin-Spin Coupling Spin-spin coupling of nuclei causes splitting of NMR signal Only nuclei with I  0 can couple Examples: 1 H with 1 H, 1 H with 13 C, 13 C with 13 C 1 H NMR: splitting reveals number of H neighbors 13 C-NMR: limited to nuclei separated by just one sigma bond; no pi bond “free spacers” Conclusions Carbon signal split by attached hydrogens (one bond coupling) No other coupling important 1H1H 13 C 12 C Coupling observed Coupling occurs but signal very weak: low probability for two adjacent 13 C 1.1% x 1.1% = 0.012% No coupling: too far apart No coupling: 12 C has I = 0

10. 10 13 C-NMR: Spin-Spin Coupling Carbon signal split by attached hydrogens N+1 splitting rule obeyed Quartet TripletDoublet Singlet Example 1 H- 13 C Splitting Patterns How can we simply this?

11. 11 Proton decoupled 13 C-NMR: Spin-Spin Coupling Broadband decoupling: all C-H coupling is suppressed All split signals become singlets Signal intensity increases; less time required to obtain spectrum Simplification of Complex Splitting Patterns

12. 12 13 C-NMR: Spin-Spin Coupling Distortionless Enhancement by Polarization Transfer (DEPT ) Example All carbons Assigns each 13 C-NMR signal as CH 3, CH 2, CH, or C CH 3 onlyCH 2 onlyCH only

13. 13 Two-Dimensional NMR (2D-NMR) Basis: interaction of nuclear spins ( 1 H with 1 H, 1 H with 13 C, 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

14. 14 2D-NMR COSY: Correlation of 1 H- 1 H coupling Dots = correlations Ignore dots on diagonal Sucrose 1 H-NMR Examples H 6 and H 5 are coupled Identify H 8 by its coupling with H 9 H8H8

15. 15 2D-NMR HMQC: Correlation of spin-spin coupling between 1 H and nuclei other than 1 H such as 13 C Sucrose 13 C-NMR Sucrose 1 H-NMR No diagonal Example Which carbon bears H 6 ? 92 ppm

16. 16 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 1 H 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 10 7 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

17. 17 Magnetic Resonance Imaging (MRI) NMR and MRI Use Similar Instruments Powerful magnets An NMR spectrometerAn MRI instrument

18. 18 Magnetic Resonance Imaging (MRI) MRI Images: Quite Different from NMR Spectra! MRI image: a foot MRI image: a head