In the Laboratory
A Discovery-Based Experiment Involving Rearrangement in the Conversion of Alcohols to Alkyl Halides Permanent Magnet
13C
NMR in the First-Semester Organic Chemistry Lab
Richard A. Kjonaas* and Ryand J. F. Tucker Department of Chemistry, Indiana State University, Terre Haute, IN 47809, *
[email protected] Several advantages, including low maintenance and low cost, make permanent magnet FT-NMR attractive for hands-on use in introductory organic chemistry laboratory courses. It is especially convenient that these instruments can be used for 13C NMR because 13C NMR is easier for students to understand and is therefore more suitable than 1H NMR for early use in the course. A few minutes of discussion in a prelab lecture is sufficient to give students enough understanding to allow them to use this technique for the first time. For permanent magnet 13C NMR, however, fast sample turnaround requires that these samples be neat or nearly neat. So hands-on use of permanent magnet 13C NMR in large-section first-semester organic lab courses is limited by the availability of experiments that not only hinge on firstsemester lecture topics, but that also produce at least 0.5 mL of neat liquid sample. For the past few years we have been using three alcohol-toalkyl halide reactions along with permanent magnet 13C NMR as a discovery-based experiment in our large-section (i.e., up to 27 students) first-semester organic lab course. Students detect rearranged or unrearranged products by comparing the number of 13C resonances in the recorded spectrum with the number of resonances predicted for each possible product. The choice of alcohols, the experimental conditions, and the results are shown in Table 1. We found that the well-known and widely used NaBr∙H2SO4 procedure (1, 2) for alcohol to
alkyl halide conversion is the best choice for 1-propanol and 2-pentanol (entries 1 and 2), but that a ZnCl2∙HCl (Lucas’ reagent) procedure (3), which is the faster and easier of the two procedures, can be used successfully with 2,4-dimethyl-3pentanol (entry 3). These three reactions allow students to observe no rearrangement (entry 1), partial rearrangement (entry 2), and complete rearrangement (entry 3). Over a dozen lab sections ranging from 18 to 27 students have now carried out these three reactions in our lab. In most of those sections we have divided the three reactions into two one-day experiments. In the first of these two experiments, half of the students use 1-propanol and half use 2-pentanol. Each student runs the reaction, records the 13C NMR spectrum (with the instructor sitting by to assist), and then exchanges data with a student who used a different alcohol. All of this, along with a prelab lecture, is easily carried out in a three-hour lab period. During the second lab period, all of the students carry out the reaction of 2,4-dimethyl-3-pentanol with HCl∙ZnCl2 and record the 13C NMR spectrum. GC analysis of the product mixture could easily be incorporated into the experiment, but we have chosen to not do so. We have, however, carried out GC analysis of each of the three reactions. This has shown that the reactions in entries 1 and 3 of Table 1 give a trace of the product that is not detected by 13C NMR, and the reaction in entry 2 gives a 2-bromopentane:3bromopentane ratio of about 3:2.
Table 1. Starting Materials, Experimental Conditions, and Results in the Conversion of Three Alcohols to Alkyl Halides Entry
Reactions and the Number of 13C Resonances Expected for Each Product OH
1
a
NaBr / H2SO4
2
a
NaBr / H2SO4
3
b
Br
Br
8
Cl
(no rearrangement)
2
Br
HCl / ZnCl2
Br
3
5 OH
Conclusion (explanation)
Br
Br
3 OH
Number of Observed Resonances
3
and
Br
(partial rearrangement) Cl
Cl
5 4
5
(complete rearrangement)
aHeat under reflux 20 min followed by codistillation from the same flask and then aqueous workup. bHeat in a 50º C water bath 5 min followed by aqueous workup.
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Journal of Chemical Education • Vol. 85 No. 1 January 2008 • www.JCE.DivCHED.org • © Division of Chemical Education
In the Laboratory
This experiment is an example of the discovery (or guidedinquiry) approach to laboratory instruction (4, 5). The characteristics of this type of experiment along with those of three other types—expository, inquiry, and problem-based—have been described in this Journal (6). Our students are introduced to carbocations in the lecture course shortly before carrying out the experiment described here, and their only exposure to 13C NMR is in the experiment preceding this one. In the prelab lecture the students and the instructor mechanistically rationalize the possible products shown in Table 1. Then the instructor and students jointly explore the possibility of using 13C NMR to determine the actual outcome of the reactions. The students find no difficulty in doing this, except that all of them (and understandably so) expect 3-chloro-2,4-dimethylpentane to have only three signals rather than four. When asked to predict the results, the students are virtually unanimous in predicting the correct outcome for entry 3 in the table, but are nearly clueless in predicting the outcome of entries 1 and 2. They seem to show special interest in a question suggested by entry 2—“do secondary-to-secondary carbocation rearrangements occur to a noticeable extent?” That interest quickly turns into a personal challenge when told that they will find out for themselves before the lab period is over. In this experiment, more than in any other one in the course, the students take personal responsibility for learning, and they express satisfaction in having done so. Hazards A tremendous quantity of heat is generated when 18 M H2SO4 is diluted to a 9.0 M solution, so it is recommended that this solution be prepared for the students. Lucas’ reagent should also be prepared for the students as it is highly corrosive and gives off hydrogen chloride, which presents an inhalation hazard. For this reason, the HCl∙ZnCl2 procedure directs students to have a balloon over the reaction mixture until it is returned to the fume hood for workup. The three starting materials and four products are low molecular weight alcohols or alkyl halides, and each is a skin, eye, and respiratory irritant. Those same seven compounds are also flammable. Secondary alcohols are highly prone to peroxide formation so 2-pentanol and 2,4-dimethyl3-pentanol should be checked before use.
Literature Cited 1. (a) Kamm, O.; Marvel, C. S. Organic Synthesis Coll. Vol. 1; Gilman, H., Blatt, A. H., Eds.; J. Wiley & Sons: New York, 1941; pp 25–35. (b) Smith, M. B.; March, J. March’s Advanced Organic Chemistry, 5th ed; Wiley-Interscience: New York, 2001; pp 518–519. 2. For examples of the NaBr/H2SO4 (or hydrogen halide) procedure adapted to the teaching laboratory see (a) Fieser, L. F. Organic Experiments; D. C. Heath: Boston, 1964; pp 76–79. (b) Williamson, K. L.; Minard, R. D.; Masters, K. M. Macroscale and Microscale Organic Experiments, 5th ed; Houghton Mifflin: Boston, 2007; pp 329–330. (c) Lehman, J. W. Multiscale Operational Organic Chemistry; PrenticeHall: Upper Saddle River, NJ, 2002; pp 213–222. (d) Warren, H. W.; Newton, T. A. J. Chem. Educ. 1980, 57, 747. (e) Cooley, J. H.; McCown, J. D.; Shill, R. M. J. Chem. Educ. 1967, 44, 280–281. 3. (a) Lucas, H. J. J. Am. Chem. Soc. 1930, 52, 802–804. (b) Kjonaas, R. A.; Riedford, B. A. J. Chem. Educ. 1991, 68, 704–706. 4. (a) Pavelich, M. J.; Abraham, M. R. J. Chem. Educ. 1979, 56, 100–103. (b) Allen, J. B.; Barker, L. N.; Ramsden, J. H. J. Chem. Educ. 1986, 63, 533–534. (c) Ricci, R. W.; Ditzler, M. A. J. Chem. Educ. 1991, 68, 228–231. 5. For some representative examples of discovery (guided-inquiry) type experiments designed for the organic laboratory see (a) Vittimberga, B. M.; Ruekberg, B. J. Chem. Educ. 2006, 83, 1661–1662. (b) Mak, K. K. W.; Lai, Y. M.; Yuk-Hong, S. J. Chem. Educ. 2006, 83, 1058–1061. (c) Baru, A. R.; Mohan, R. S. J. Chem. Educ. 2005, 82, 1674–1675. (d) Garner, C. M. J. Chem. Educ. 2005, 82, 1686–1688. (e) Reeve, A. M. J. Chem. Educ. 2004, 81, 1497–1499. (f ) Montes, I.; Lai, C.; Sanabria, D. J. Chem. Educ. 2003, 80, 447–449. (g) Horowitz, G. J. Chem. Educ. 2003, 80, 1039–1041. (h) Pelter, M. W.; Macudzinski, R. M.; Passarelli, M. E. J. Chem. Educ. 2000, 77, 1481. (i) Shadwick, S. R.; Mohan, R. S. J. Chem. Educ. 1999, 76, 1121–1122. 6. Domin, D. S. J. Chem. Educ. 1999, 76, 543–547.
Supporting JCE Online Material
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Spectra of the products
© Division of Chemical Education • www.JCE.DivCHED.org • Vol. 85 No. 1 January 2008 • Journal of Chemical Education
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