WSU NMR Project
Principles of Organic Chemistry II - Dr. Nalli
Experiments
Expt #1. Grignard Synthesis of Triphenylmethanol: This standard experiment1 was carried out without modification except that the product was characterized using melting point and 13C NMR (proton decoupled) rather than the usual 1H NMR. Triphenylmethanol shows a broad aromatic singlet at 300 MHz in the 1H NMR spectrum, so in our view, this is very unsatisfying as a method of characterization. The carbon spectrum, however, gives a distinct peak for each of the five chemically distinct carbons. Fairly concentrated NMR samples were used so that the number of scans could be kept to less than 100 allowing all of the students to obtain their spectra in a single lab period. Students processed and printed out the spectra on their laptops, after the laboratory, when writing up their reports.
Expt #2. Redox reactions of alcohols and ketones.; Borneol, Camphor, Isoborneol: This experiment was carried out as described in the Pavia laboratory manual1. However, students were required to process, integrate and print out their own spectra on their own time as described later on this page.
Expt #3. Preparation of an acetate ester: This was the first of the individual problem experiments in the course where each student team of two was assigned their own unique project. In this lab, each team was assigned an alcohol to convert into its acetate ester using acetic anhydride. Products were distilled and characterized by FT-IR as well as 1H and 13C NMR. The team that was assigned 3-ethyl-3-pentanol was confused by the odor, bp and spectra obtained. Consultation with the professor helped them determine that the product was actually not an ester, but instead was the alkene, 3-methyl-2-pentene formed from dehydration of the alcohol. Primary alcohols (2-ethyl-1-hexanol, 1-octanol, 1-propanol, isopentyl alcohol, benzyl alcohol, 2-phenyl-1-ethanol, 3-phenyl-1-propanol, etc) worked very smoothly in all cases to form the desired esters.
Expt #4. Preparation of N,N-Diethyl-m-toluamide (DEET). Molecular modeling and NMR study of amide bond rotation in DEET: DEET was prepared in standard fashion.1 It was characterized by FT-IR and 1H NMR. In the second lab period, the students used HyperChem to determine the rotation barrier of the amide bond by molecular mechanics. Also, one student sample was submitted to Variable Temperature NMR throughout this second lab period. Students observed the VT experiment in progress and later processed and printed out the spectra obtained at the various temperatures and calculated an estimate of the rotation barrier based on the approximate temperature of peak coalescence for the methylene protons and methyl protons respectively.
Expt #5. The Knoevenagel Condensation. Preparation of Coumarins and HETCOR NMR.
Students were given a link to a paper from the 1998 Electronic Conference on Heterocyclic Chemistry.2 This paper describes the microwave-assisted condensation of beta-dicarbonyl compounds with salicyclic acid and derivatives. Students were assigned a specific substituted coumarin from among those described in the paper and asked to carry out the reaction according to the literature. Students were instructed to scale down the published procedure to 0.01 mol (at most 0.002 mol is recommended for future courses) and they ran the reaction in loosely-capped screw-top vials in an ordinary household microwave oven. Products were crystallized from ethanol/water mixtures (best mixture determined by experiment) and characterized by 1H and 13C NMR and pfgHMQC spectroscopy. The pfgHMQC spectrum is a 2-D experiment that gives heteronuclear C-H correlations and is fairly easy for students to interpret. The pulsed-field-gradients (pfg) version of the experiment is quite fast, requiring an acquisition time of about 20 minutes, so we were able to get spectra for all student teams in a reasonable amount of time. Processing of the pfgHMQC spectrum is difficult and was don individually by the instructor for each student group.
Expt #6. Electrophilic aromatic substitution. Analysis by GC-MS and proton NMR: Each student team was assigned their own aromatic substitution reaction to carry out. 1H NMR or GC/MS was used to determine the ortho:meta:para ratios in their crude products and final (recrystallized or distilled) products. Individual team results were submitted to the instructor who tabulated and posted them on line. Students were asked to write a lab report that addressed electrophilic aromatic substitution reactions in general, in addition to reporting on the reaction that they specifically carried out. Substituent effects, both electronic and steric, revealed themselves in the class results, both in terms of reaction regioselectivity (o:m:p) ratios and in the occurrence of polysubstitution.
Operation of spectrometer and processing of spectra
For all of these experiments, students used the Magnetic Resonance Companion (Mest-ReC) software. Each of them downloaded the software and installed it on their personal laptop computers, which all WSU students are required to lease from the University. Procedures for working up the data using this software were demonstrated by the instructor during pre-lab lectures. NMR FID files were exported in NUTS format directly to a networked storage folder reserved for students in this course. Students retrieved and processed the data outside of the laboratory period. Students became quite accomplished at using the software by the end of the semester.
Students were encouraged to man the instrument work station and essentially, obtain their own spectra. The teaching assistant (previously trained on the NMR) or the instructor were usually present to supervise but toward the end of the semester, most students were able to obtain their own spectra with minimal supervision.
Materials Developed:
Please use the links above under the individual experiments to go to the various materials developed for this course.
Link to Course Web Page and Lab Syllabus:
References:
(1) Pavia, D. L.; Lampman, G. M.; Kriz, G. S.; Engel, R. G. Introduction to Organic Laboratory Techniques. A Microscale Approach, 3rd ed, Brooks/Cole - Thomson Learning: Pacific Grove, CA, 1999.
(2) Bogdal, D. http://www.ch.ic.ac.uk/ectoc/echet98/pub/o87/index.htm
