SPECIAL TOPICS IN ANALYTICAL CHEMISTRYIntroduction to NMR

CHEM 991A, Fall 2014MWF 11:30-12:20pm, Rm 133/134 Hamilton Hall

COURSE OUTLINE

Instructor: Dr. Robert Powers Office Labs

Address: 722 HaH 720 HaHPhone: 472-3039 472-5316e-mail:rpowers3@unl.eduweb page: http://bionmr.unl.edu

Office Hours: 10:30-11:30 am MWF or by Special Appointment

Required Items:(i)Text: “NMR and Chemistry: An Introduction to Modern NMR Spectroscopy”, by J. W. Akitt & B. E. Mann; Stanley Thornes, 2000(ii) Calculator for exams (TI-89 style or a simpler model)(iii) Highly Recommended text:

“Structure Determination of Organic Compounds: Tables of Spectral Data”, by Pretsch, E., Bühlmann, P., and Affolter, C., Springer-Verlag, 3rd ed., 2000

“Spin Dynamics – Basics of Nuclear Magnetic Resonance”, by M. H. Levitt, Wiley, 2001.

“Spectrometric Identification of Organic Compounds” Silverstein, Bassler and Morrill

“Organic Structure Determination Using 2-D NMR Spectroscopy:  A Problem-Based Approach” Jeffrey H. Simpson

“Essential Practical NMR for Organic Chemistry” Stephen A. Richards & John C. Hollerton

“Basic One- and Two-Dimensional NMR Spectroscopy” Horst Friebolin

“Modern NMR Techniques for Chemistry Research” Andrew E. Derome

“Nuclear Magnetic Resonance Spectroscopy” R. K Harris

“Experimental Pulse NMR. A Nuts and Bolts Approach” Eiichi Fukushima & Steve B.W. Roeder  

“Two-Dimensional Nuclear Magnetic Resonance in Liquids”, Ad Bax

Some Other Suggested NMR ReferencesSome Other Suggested NMR References

Some NMR Web SitesSome NMR Web Sites

The Basics of NMR by J.P. Hornak The Basics of NMR by J.P. Hornak Hypertext based NMR courseHypertext based NMR course http://www.cis.rit.edu/htbooks/nmr/nmr-main.htm

Spectral DataBase for Organic Compounds (SDBS)http://sdbs.db.aist.go.jp/sdbs/cgi-bin/cre_index.cgi Educational NMR Software All kinds of NMR softwarehttp://deane.bio.ucalgary.ca/EduNMRSoft.html

NMR Knowledge Base A lot of useful NMR linkshttp://www.spectroscopynow.com/

NMR Information Server News, Links, Conferences, Jobshttp://www.spincore.com/nmrinfo/

Technical Tidbits Useful source for the art of shimminghttp://www.acornnmr.com/nmr_topics.htm

NMR Wiki Sharing NMR know-howhttp://nmrwiki.org/wiki/index.php?title=Main_Page

Some More NMR Web SitesSome More NMR Web Sites

Structure Determination Using NMR by H. J. Reich Structure Determination Using NMR by H. J. Reich Web based NMR courseWeb based NMR course http://www.chem.wisc.edu/areas/reich/chem605/index.htm

eNMR NMR Periodic Tablehttp://www.bruker-nmr.de/guide/eNMR/chem/NMRnuclei.html

Web Spectra Example NMR Structure Problemshttp://www.chem.ucla.edu/~webspectra/

Organic Structure Elucidation Another Work Book of Unknownshttp://www3.nd.edu/~smithgrp/structure/workbook.html

NMRShiftDB2 Predict NMR Chemical Shiftshttp://nmrshiftdb.nmr.uni-koeln.de/nmrshiftdb

ChemDoodle Simulate NMR and MS Spectrahttp://web.chemdoodle.com/demos/simulate-nmr-and-ms

NESG Wiki Another NMR Wiki Page, Emphasis in Protein NMRhttp://www.nmr2.buffalo.edu/nesg.wiki/Main_Page

Lecture TopicsTopic Chapters in NMR & Chemistry

I. BASIC NMR TheoryI. Introduction to NMR Theory 1

a. Quantum and classical descriptionII. Obtaining an NMR Spectra 5

a. Data acquisition and processingb. Instrumentation

III. Chemical Shifts () 2a. Select examples of chemical shift trendsb. Predicting chemical shifts

IV. Coupling Constants (J) 3a. Simulation of second-order spin systems

II. One and Two Dimensional NMRI. NMR Pulses 6II. 1D NMR 8

a. NOE, J modulation, INEPT, DEPT, INADEQUATEIII. 2D NMR 9

a. Theoryb. COSY,TOCSY,NOESY,HMQC,HMBC

IV. Examples of Spectral Interpretation 8III. NMR Dynamics

• Relaxation 4I. T1,T2,Dipole-Dipole,CSA,Quadrupolar

I. Exchange 7a. NMR time scale

IV. Solid State NMR (as time permits) 11

Course OutlineDate Chapter Topic

I. Basic NMR TheoryAug 25 Course Overview & SchedulingAug 27 Software LabAug 29 Software LabSep 3 Software LabSep 5 Chap 1 Introduction to NMR Theory Sep 8 Chap 1Sep 10 Chap 1 Sep 12 Chap 5 Obtaining an NMR SpectrumSep 15 Chap 5Sep 17 Chap 5Sep 19 Chap 5Sep 22 Chap 5Sep 24 Chap 2 Chemical Shifts (d)Sep 26 Chap 2Sep 29 Chap 2Oct 1 Chap 2Oct 3 Chap 3 Coupling Constants (J)Oct 6 Chap 3Oct 8 Chap 3Oct 10 Midterm ExamOct 13 Chap 6 NMR PulsesOct 15 Chap 6

II. One and Two Dimensional NMROct 17 Chap 8 1D NMR

Date Chapter Topic Oct 20 to Oct 21 Fall BreakOct 22 Chap 8Oct 24 Chap 8Oct 27 Chap 8Oct 29 Chap 9 2D NMROct 31 Chap 9Nov 3 Chap 9Nov 5 Chap 9Nov 7 Examples of Spectral Interpretations

III. NMR DynamicsNov 10 Chap 4 & 7 Relaxation & ExchangeNov 12 Chap 4 & 7Nov 14 Chap 4 & 7Nov 17 Chap 4 & 7

IV. Solid State NMRNov 19 Chap 11 Solid State NMRNov 21 Chap 11

V. Presentations of NMR PapersNov 24 Oral PresentationsNov 26 to Nov 28 Thanksgiving BreakDec 1 Oral PresentationsDec 3 Oral PresentationsDec 5 Oral PresentationsDec 8 Oral Presentations Dec 10 Oral PresentationsDec 12 Review Structure Problem Sets DueDec 16 Final Exam

Course Outlined (cont.) Course Work:

Midterm Exam: 100 pts. (Fri., Oct. 10)Final Exam: 100 pts. (Tues., Dec. 16)Structure Problems (3): 150 pts. (Fri., Dec. 12)Oral Presentation: 50 pts. (various due dates)

Total: 400 pts.

ALL PowerPoint presentations, grades, and answer keys for the structure problem sets and exams will be posted on BlackBoard.

Grading scale: A+=95%; A=90%; A-=85%; B+=80%; B=75%; B-=70%; C+=65%; C=60%; C-=55%; D=50%; D-=45%; F=40%

Class Participation•Reading assignments should be completed prior to each lecture.

•You are expected to participate in ALL classroom discussions

Exams

•The MidTerm Exam will take place at 6 pm on Fri. Oct. 10 in Rm 133/134 Hamilton Hall. The Final Exam will take place at 10 am on Tues. Dec. 16 in Rm 133/134.

•The length of each exam will be two hours. The Final Exam WILL NOT be cumulative, it will only cover new material since the MidTerm Exam.

•Bring TI-89 style calculator or a simpler model, and a approved translator if needed.

•A review session will take place during the normal class time.

•ALWAYS SHOW ALL WORK!!!!

Course Outlined (cont.)

STRUCTURE PROBLEMS• Using NMR Data to Determine the Structure of an

Unknown Organic Compound

• Total of 3 unknown structures to solve

• Structures will be randomly assigned to you today

• NMR data sets for unknowns will be available in the NMR computer lab (832 HaH)

• Each unknown will include the following data:– Chemical formula– 1D 1H & 13C spectra – 2D 1H COSY, 2D 1H NOESY, 2D 1H-13C HSQC, 2D 1H-13C HMBC, 2D

HSQC-TOCSY

• Each Structure Problem Sets Increase in Difficulty– First unknown – easy– Second unknown – moderately challenging– Third unknown – difficult

• Do Not Wait! Start Working on the Problem Sets Now!

• Using NMR Data to Determine the Structure of an Unknown Organic Compound

• Assign Each Student Their Three Unknowns

STRUCTURE PROBLEMS (cont.)

STRUCTURE PROBLEMS (cont.)

• The Goal of the Structure Problem Sets is to Develop Your Skills in Analyzing NMR Data

• These are Individual Projects

• Do Not Work Together on the Assignments

• Do Not Share Your Results with Other Students

• Answer Keys will be Posted after Class on Fri. Dec 12

• The Due Date for the Three Structure Problems is the beginning of class on Friday, Dec. 12

• Please Hand-in Your Answers as Soon as You Complete the Assignment

• Problems Sets will be Graded as they are turned-in and Grades will be Immediately Posted on BlackBoard

• A Significant Component of Your Grade is Your Performance on these Problem Sets.

• Don’t Wait Until the End of Class to Determine If you Are Having Problems! - Seek Help and Visit Me during My Office Hours

• Grading (50 points/structure; 150 total points)

STRUCTURE PROBLEMS (cont.)

• Completed Reports for the Unknown Structure Determination will contain:

• Your Name

• Unknown Number

• Chemical Structure of the Unknown

Grade will Simply be Based on the Accuracy of Your Identified Structure

- Any partial credit awarded for an incorrect structure is strictly subjective and is not open to a re-grade

• Software Training• In order to complete the structure problem sets, you will need to

know how to use NMR software to analyze the NMR data.

• The software training will take place in the NMR computer lab (Rm 832)

• For the next THREE lectures (Aug 27 to Sept. 3) Please go to HaH 832 for Software Training.

• Dr. Martha Morton will oversee the software training.

• Questions on the MidTerm Exam Will Cover Material Discussed During the Software Training Sessions.

STRUCTURE PROBLEMS (cont.)

SP FT PS TPInput data (ser file) ZF

STRUCTURE PROBLEMS (cont.) • NMR Training

• The application of two-dimensional (2D) NMR will be a major focus of the course and an important component of the structure problems

• In addition to the software training, you will also receive one hour of hands-on training with Dr. Morton on an NMR spectrometer.

• The training will involve practical information for setting-up and executing 2D NMR experiments.

• The training will occur in groups of 3-4 students on various dates based on Dr. Morton’s availability

• Questions on the MidTerm Exam Will Cover Material Discussed During the NMR Training Session.

STRUCTURE PROBLEMS (cont.)

• NMR Training (cont.)

• SCHEDUAL NMR TRAINING

• Doodle poll – First come, First Serve.

ORAL PRESENTATION OF AN NMR PAPER

– One 20 minute Oral Presentation in Class • Last Two Weeks of the Semester (Nov. 24 to Dec. 10)

• Audience Participation is Expected (like a journal club)

• Presentation Dates Randomly Assigned Today

• Grading: 50 points

– Paper of Your Choice (two options):• Paper Describes an NMR method (i.e., pulse sequence, software, or

strategy) to Determine the Structure of an Organic Molecule CAN NOT be a Method Discussed in Class

or

• Paper Describes the Determination of the Structure of an Organic Molecule or Natural Product that Primarily Used NMR

– Some Other Considerations:• The Paper Topic Should be of General Interest and of Significant Impact

• Send an Electronic Copy of the Paper to the Class Prior to Your Presentation

ORAL PRESENTATION OF AN NMR PAPER (cont.)

SCHEDUAL ORAL PRESENTATIONS

– Some Recommended Sources• JACS, J. Mag Res., Concepts in Magnetic Resonance,

Progress in Nuclear Magnetic Resonance Spectroscopy, Anal. Chem., J. Med. Chem. PNAS, Journal of Organic Chemistry, Organic Letters, Angewandte Chemie, and Angewandte Chemie International Edition, ChemMedChem, and Natural Products Reports.

– Presentation Goals NMR Method Paper

• Present a Clear Understanding of the NMR Method(s) to the Class

• How is the Method Used to Solve a Structure?

• What are the Advantages and/or Limitations of the Method?

• How Does the Method Compare to Alternative Approaches?

• Why Did You Choose the Paper?

Structure Paper• Explain to the Class, in Detail, How NMR was Used to Determine

the Structure

• Explain the NMR Experiments Used and the Information the Experiments Provided.

• Why is the Compound of Interest?

• What were Challenges to Solving the Structure?

• What Other Analytical Techniques were Used to Solve the Structure and Why?

ORAL PRESENTATION OF AN NMR PAPER (cont.)

– Grading• Combination of My Assessment and the Other Students’ Assessment

• Each Student will be Limited to Giving Approximately 30% As, 55% Bs, and 15% Cs

• Default Grade is a B, a A or C will Require Justification

• All the assessments will be averaged together to determine the number of points

– Assessing the Presenter • How well did the presenter understand the material?

• How clearly did the presenter discuss the material?

• Was the chosen paper of general interest and significant?

• Were the NMR experiments relevant and important to the paper?

• How well did the presenter answer questions?

• Did the paper lead to an interesting discussion?

Average Assessed Grade: A to A-: 50pts, B+: 45pts, B to B-: 40pts, C+: 35pts, C: 30pts

ORAL PRESENTATION OF AN NMR PAPER (cont.)