Chem 5331:  Advanced Organic (NMR) Spectroscopy

Class Syllabus....Spring, 2008

Class M, W, F, 11:00 to 11:50 am, Room 165 Ekeley (Conference Room)

Course will be taught by :

Dr. Rich Shoemaker, Room 02 Cristol, E-mail:  Richard.Shoemaker@colorado.edu , Phone: (303) 492-7062

Office Hours:  Arranged as needed on an individual basis.

Web-Page:  Look for course materials on the NMR website: http://chemnmr.colorado.edu/class .

Overview:   This course is intended for those who are using (or will be using) NMR  spectroscopy as a primary characterization tool in their research.  There will be two principle areas of emphasis:

1.        How do we determine the structure of a compound, and what is required to say that a compound has been thoroughly characterized?

2.        The “nuts and bolts” of NMR spectroscopy, including how the signals are generated and detected, how the instrumentation works, and a functional understanding of pulse-sequences. 

Textbook:  This year we will be using two texts:  Spectrometric Identification of Organic Compounds, (7^th Ed.) by R. Silverstein, F. Webster, and D. Kiemle, and High-Resoulution NMR Techniques in Organic chemistry, by Timothy D.W. Claridge.  The text by Claridge is more focused on experimental NMR spectroscopy, and the Silverstein text is primarily devoted to understanding the NMR data as it applies to solving structures.  There is far too much information to be covered in lectures, and it is expected that you will read the assigned chapters and work the assigned problems.  The lectures will be intended to supplement/enhance the information in the text, and are not to be a substitute for reading. 

Grading Policy   The course grade will be based on three graded problem sets (10% each), 2 in-class exams (25% each) and a take-home final exam (20%).  Some problems in the book (and supplemental problem sets) will be assigned, and answer keys provided.  Although not every problem set will be graded, every problem set should be approached as if it will be graded.  Prior notice may not be given regarding which problem sets will be turned in for a grade.   Although subject to change, it is planned that the first exam will be a 1-hour, in-class exam, and the second in-class exam will be given at the scheduled time for the final exam (Monday, May 5th at 10:30 am).  The take-home final exam will be distributed on or before the last day of class (May 2), and will be required to be completed and turned in by 5:00 pm on Thursday, May 8.  The specific details of the take-home final exam will be provided before it is distributed.  

Policy for Disputing Grades: If you feel a problem or question was scored unfairly, you may re-submit the entire exam or problem-set for re-grading.  After re-scoring the entire exam or problem set, you will receive the new grade (whether higher or lower than the original score).

Goals and Objectives:  Students in this course should gain an understanding of NMR techniques as applied to molecular structure determination and to the study of molecular dynamics.  In addition to learning to derive structures from spectra, students will gain a basic understanding of NMR spectroscopy in one and two dimensions.  Upon successful completion of the course, students will know what techniques are available to answer specific, key questions about molecular structure.  Concepts including instrumentation, shimming, pulse-sequences, magnetization, relaxation, polarization transfer, coherence transfer will be addressed in this course.  Upon successful completion of this course, students should be prepared to apply modern NMR spectroscopic techniques to their research problems.

Calendar:  Due to Dr. Shoemaker’s responsibilities involving management of the NMR Facility, certain situations might arise that could require class cancellations or rescheduling.  Should this happen, it will be announced as far in advance as possible.    The detailed calendar below includes all class cancellations that are known at the time of this writing.  If it becomes necessary,  Dr. Shoemaker reserves the right to schedule extra, required lectures outside of the normal class time; however, this will be avoided if possible.

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Below is a general overview/outline of the course.  This represents the initial plan, but it is subject to change. Sections  may be added or omitted as necessary to cover the material deemed most important.  The dates are tentative estimates  because one never knows for sure how long it will take to adequately cover each topic.

Jan 14:  Review the relationships between NMR spectral data and structure (Chemical Shifts, J-couplings, and the basic concepts of NMR that should have been learned in undergraduate organic chemistry). {Read Silverstein, Ch.3, and Claridge, Ch.1 & 2}

Jan 16 – 25 (no class Mon. 1/21):  Introduction to experimental NMR spectroscopy {If you haven’t read Ch. 1-2 in Claridge & Ch. 3 in Silverstein, do it now}  Nuts and Bolts of NMR: magnetization, relaxation, pulsed-excitation.  Introduce the “rotating frame of reference”, as it applies to the net magnetization, excitation, and detection.  Pulse Sequences to measure relaxation, and the concept of “refocusing”, also introduce the concept of Pulsed Field Gradients (PFGs).

Jan 28 – Feb 1:  Detecting the NMR signal:  Dynamic Range, Spectral width vs. Dwell Time, Signal Averaging, and Signal:Noise ratio. {Read Ch. 3 in Claridge }.

Feb 4 - 8:  The time-frequency connection: understanding the FFT, its uses and consequences.  Understanding the principles of the Fourier-transform, and the relationship between time-domain and frequency-domain in 1D NMR is crucial to understanding 2D NMR concepts. {Review Section 2.3 and 3.2 in Claridge}

Feb 11-15:  Instrumentation:  getting to know your NMR spectrometer.  We will hopefully shine some light into the traditional “Black Box” called the NMR spectrometer.  We’ll cover superconducting magnets, pulse generation, signal detection, probe design/performance issues, probe-tuning, shimming. {Chapter 3 in Claridge, Section 3.4, 3.5}

Feb 18-25:  Interpreting 1D NMR spectra:  Chemical Shifts, J-couplings, and structure.   Interpretation/prediction of chemical shifts, and interpretation of first-order J-coupling patterns coupling constants as related to structure. Chemical Equivalence & Structure, including symmetry, chirality, and the use of chiral shift reagents and other methods for enantiomeric resolution. {Silverstein Ch. 3, 4, & 6 }

Feb 27-29: Dynamic NMR & Advanced J-Coupling.  Understanding simple chemical exchange, and introduce complex spin systems, recognizing first-order coupling vs. strong-coupling.  Common spin-systems, and “magnetic equivalence” vs. “chemical equivalence” (i.e. AX, AB, AMX, ABX, …etc.)  {Ch. 3, Silverstein, sections 3.5 – 3.11 }. 

March 3-7:  More on NMR Relaxation, NOE:  Quantitation in NMR:  getting reliable peak integrations.   The Nuclear Overhauser Effect (NOE), how we measure it.  Through-space proximity via cross-relaxation {Review Claridge, 2.4 & 2.5, and READ Sections 8.1-8.6 in Claridge}. Note: we’ll introduce Transient 1D NOE concepts now, and address 2D-NOE experiments later in the course.

March 10-14 No Class:  Read Chapter 4 in Claridge. No Class this week due to the 49^th Experimental NMR Conference in Pacific Grove, CA.  Expect a literature assignment {Look up and read paper by Reynolds, et. al: J. Natural Products, 65, 221-224 (2002) }, and/or a problem set to keep everyone happy and occupied this week.  . 

March 17-19: Advanced 1-Dimensional NMR: Having read chapter 4 in Claridge, we will discuss the important points including polarization transfer (INEPT), spectral editing (DEPT/APT), and important aspects of decoupling.  And, by the way, yes… this will likely be on the Exam on Friday.

March 21:  Exam #1 (tentative, the exact day will be announced at least 1 week prior to the Exam).  The exam will cover basic experimental NMR spectroscopy, and interpretation of 1D-NMR spectra.

March 24-28:  Spring Break, No Classes… No Assigned Homework

March 31-Apr. 4:  Introduction to 2D-NMR, experimental concepts and applying the FFT in two dimensions. {READ Claridge, Chs. 5 & 6}.  We’ll start with 2D-COSY, then move to heteronuclear experiments (HETCOR, HMQC/HSQC, HMBC, …etc.).

April 7-11: Using 2D NMR to determine structures, and assigning NMR resonances.  the “alphabet soup” of NMR acronyms {Claridge Ch. 9, Silverstein Ch. 5.}

April 14-18:  2D-NOESY/ROESY & Dynamic Exchange measurements in 2-Dimensions (NOESY/ROESY/EXCHSY) {Claridge, 8.7 through 8.10}.

April 21-25: Using Pulsed Field Gradients (PFGs) and selective pulses in 2D NMR experiments… basic principles and practical applications, including measuring diffusion (DOSY), coherence selection, and artifact suppression.  \

1D Analogues to 2D NMR experiments (Using selective pulses), 1D-COSY/TOCSY, 1D-NOESY/GOESY.

April 28-May 2:   More Structure Determination and Assignment, bringing it all together.  We will work though an example problem (possibly a previous final exam problem), using NMR data from a variety of NMR experiments to assign the structure and all NMR resonances. {We may refer to Chapter 6 in Silverstein… “Other Nuclei”}

Additional Topics, possibly including Solid-State NMR concepts and techniques, semi-solid phase (gel phase), Diffusion-NMR/DOSY, BioMolecular NMR concepts… depending upon time availability.

Final Examination Information:

Take-Home Final Exam to be distributed on (or before) May 2 (Last Day of Class).

University Required Syllabus Information:

If you qualify for accommodations because of a disability, please submit to me a letter from Disability Services in a timely manner so that your needs may be addressed.  Disability Services determines accommodations based on documented disabilities.  Contact: 303-492-8671, Willard 322, and http://www.Colorado.EDU/disabilityservices.

Campus policy regarding religious observances requires that faculty make every effort to reasonably and fairly deal with all students who, because of religious obligations, have conflicts with scheduled exams, assignments or required attendance.  In this class, please see me if you need to miss any class due to a resigious observance, and we will make the appropriate arrangements.  See full details at http://www.colorado.edu/policies/fac_relig.html .

Students and faculty each have responsibility for maintaining an appropriate learning environment. Students who fail to adhere to such behavioral standards may be subject to discipline. Faculty have the professional responsibility to treat all students with understanding, dignity and respect, to guide classroom discussion and to set reasonable limits on the manner in which they and their students express opinions.  Professional courtesy and sensitivity are especially important with respect to individuals and topics dealing with differences of race, culture, religion, politics, sexual orientation, gender, gender variance, and nationalities.  Class rosters are provided to the instructor with the student's legal name. I will gladly honor your request to address you by an alternate name or gender pronoun. Please advise me of this preference early in the semester so that I may make appropriate changes to my records.  See polices at:

http://www.colorado.edu/policies/classbehavior.html    and at http://www.colorado.edu/studentaffairs/judicialaffairs/code.html#student_code  

The University of Colorado at Boulder policy on Discrimination and Harassment, the University of Colorado policy on Sexual Harassment and the University of Colorado policy on Amorous Relationships apply to all students, staff and faculty.  Any student, staff or faculty member who believes s/he has been the subject of discrimination or harassment based upon race, color, national origin, sex, age, disability, religion, sexual orientation, or veteran status should contact the Office of Discrimination and Harassment (ODH) at 303-492-2127 or the Office of Judicial Affairs at 303-492-5550.  Information about the ODH, the above referenced policies and the campus resources available to assist individuals regarding discrimination or harassment can be obtained at  http://www.colorado.edu/odh .

All students of the University of Colorado at Boulder are responsible for knowing and adhering to the academic integrity policy of this institution. Violations of this policy may include: cheating, plagiarism, aid of academic dishonesty, fabrication, lying, bribery, and threatening behavior.  All incidents of academic misconduct shall be reported to the Honor Code Council (honor@colorado.edu; 303-725-2273). Students who are found to be in violation of the academic integrity policy will be subject to both academic sanctions from the faculty member and non-academic sanctions (including but not limited to university probation, suspension, or expulsion). Other information on the Honor Code can be found at http://www.colorado.edu/policies/honor.html  and at  http://www.colorado.edu/academics/honorcode/ .