Laboratory Experiment pubs.acs.org/jchemeduc
A Discovery-Based Hydrochlorination of Carvone Utilizing a GuidedInquiry Approach To Determine the Product Structure from 13C NMR Spectra Michael W. Pelter* and Natalie M. Walker Department of Chemistry and Physics, Purdue University Calumet, Hammond, Indiana 46323, United States S Supporting Information *
ABSTRACT: This experiment describes a discovery-based method for the regio- and stereoselective hydrochlorination of carvone, appropriate for a 3-h second-semester organic chemistry laboratory. The product is identified through interpretation of the 13C NMR and DEPT spectra are obtained on an Anasazi EFT-60 at 15 MHz as neat samples. A guided-inquiry approach is used to aid the students with the interpretation of the NMR spectra.
KEYWORDS: Second-Year Undergraduate, Laboratory Instruction, Organic Chemistry, Inquiry-Based/Discovery Learning, Problem Solving/Decision Making, Addition Reactions, Alkenes, Constitutional Isomers, NMR Spectroscopy, Thin Layer Chromatography
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product. The oxalyl chloride and alumina procedure was used for several semesters, but the students were only able to recover unreacted starting material. The desire to include this reaction in our curriculum led us to explore alternatives to the procedures listed above. We report herein the adaptation of a reported method using acetyl chloride in ethanol for the regioselective and chemoselective hydrochlorination of carvone6 (Scheme 1). Although the yields
arvone (5-isopropenyl-2-methyl-2-cyclohexenone, 1) is a simple but interesting monoterpene. Both naturally occurring enantiomers of carvone are used extensively in the food and flavor industries. Although either enantiomer will work in this experiment, the less expensive (R) isomer is used. The investigative aspect of this experiment comes from the fact carvone has two alkenes that can be differentiated: one is terminal and disubstituted in the isopropenyl group attached to the asymmetric carbon at position 5 and the other constitutes the α,β-unsaturated ketone of the cyclohexenone moiety. Chemoselectivity is an important concept in organic synthesis and has been the subject of numerous papers in this Journal.1−4 This experiment has been typically utilized in the secondsemester organic chemistry laboratory course, although it could be appropriately incorporated into the first semester. To further investigate the concept of chemoselectivity, students also perform a chemoselective epoxidation of carvone,2 which shows different reactivity than the hydrochloroination reaction. In each of these experiments, students obtain the FT-IR and 13 C NMR spectra and use these spectra to identify the structure of the product. The 13C NMR and DEPT spectra are obtained on an Anasazi EFT-60 at 15 MHz as neat samples. Experiments investigating the regioselective and chemoselective hydrochlorination of carvone have been previously reported in this Journal. The first utilizes oxalyl chloride and alumina for the in situ generation of HCl.3 The second procedure utilizes chlorotrimethylsilane in water for the in situ generation of HCl.4 Both methods give carvacrol5 as a side © 2012 American Chemical Society and Division of Chemical Education, Inc.
Scheme 1. Regioselective and Chemoselective Hydrochlorination of Carvone
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obtained by students are similar to the other reported methods; the overall average was slightly higher. Additionally, acetyl chloride is less expensive than oxalyl chloride or chlorotrimethylsilane and also commonly used in the organic teaching laboratory in the Friedel−Crafts acylation.7 To develop the student’s problem solving skills, a guidedinquiry approach to the interpretation of the carbon NMR spectral data has been adapted.8 Students are often baffled by the spectral data they generate in the laboratory and, therefore, do not fully grasp the intended goals of the experiment, which is to identify the structure of their product. The guided-inquiry approach to spectral interpretation has greatly improved the student’s attitude toward this experiment. The students are introduced to 13C NMR in the firstsemester organic laboratory course. They are required to interpret a paper unknown as part of a dry-lab exercise and then use 13C NMR to identify the product of an acetate ester synthesis.9 The experiment described herein was performed early in the second semester to reintroduce 13C NMR.
5. How many peaks are present in the 100−150 ppm range? Describe each in terms of its appearance in the DEPT spectrum. 6. How many peaks are present above 150 ppm? 7. How many CH3 groups are present? 8. How many CH2 groups are present? 9. How many CH groups are present? 10. How many carbons have no hydrogen attached? The students are also required to predict what the 13C NMR and DEPT spectra of compounds 2, 3, and 4 (Scheme 1) should be with regard to the above questions, as well as to address the following: • In which two areas of the 13C NMR and DEPT spectra do you expect to see the biggest differences between carvone and the product? • Explain the expected differences for each region. The prelab assignments are collected at the beginning of the laboratory period, graded, and returned to the students during the laboratory period. The students are then asked to discuss their answers with each other. In this way, students with incorrect answers can understand how to correctly answer the questions. Alternatively, the prelab assignment could be done as part of a prelab discussion. Regardless, it is important for the students to understand how to determine the correct answers before completing the experiment. Typically, students obtain the product (Scheme 1, product 2) in greater than 75% yield and of sufficient purity to acquire NMR spectra of a neat sample. To guide the students through the interpretation of the NMR spectra, they are given the following questions: 1. How many signals are present in the 13C NMR spectrum of your product? 2. How many peaks are present in the 0−50 ppm range? Describe each in terms of its appearance in the DEPT spectrum. 3. How many peaks are present in the 50−100 ppm range? Describe each in terms of its appearance in the DEPT spectrum. 4. How many peaks are present in the 100−150 ppm range? Describe each in terms of its appearance in the DEPT spectrum. 5. How many peaks are present above 150 ppm? Which carbon gives rise to this peak? 6. By comparing your answers to questions 1−5 with the information in the prelab assignment, you should be able to easily eliminate TWO of the possible product structures at this time. Show the structure and explain why they can no longer be considered possibilities. 7. Describe two pieces of evidence that support one of the remaining structures and allow you to exclude the other. 8. Show the structure of the product you obtained in this reaction.
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EXPERIMENTAL OVERVIEW A solution of carvone and absolute ethanol was stirred in a round-bottom flask with an attached air condenser. The flask was heated in a 40−45 °C sand bath in a fume hood. Acetyl chloride was added to the heated reaction mixture dropwise through the condenser. The reaction mixture darkened on addition of the acetyl chloride. Progress of the reaction was monitored at 15 min intervals using thin-layer chromatography until the presence of the carvone starting material was no longer evident. This required less than 90 min. Once the reaction was complete, the reaction mixture was allowed to cool to room temperature and the solvent was removed under reduced pressure using a rotary evaporator to give the product as an oil (>75% yield). Spectra (IR, 13C NMR, DEPT) were recorded for characterization of the product.10
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HAZARDS Acetyl chloride is flammable, corrosive, and reacts with water. Avoid contact. Acetyl chloride must be measured out carefully in a fume hood. Ethanol is highly flammable. Carvone may cause eye, skin, and respiratory tract irritation and is combustible. Eye protection must be worn at all times. Hydrochloric acid is generated in the reaction. Removal of solvent should be carried out in a fume hood. Hexanes and ethyl acetate are highly flammable. The aqueous potassium permanganate solution is an eye and skin irritant.
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DISCUSSION As a prelab assignment, the students are provided with the 13C NMR and DEPT spectra of carvone and required to answer the following questions: 1. How many different types of chemically distinct carbons are in carvone? 2. How many signals are present in the 13C NMR spectrum of carvone? 3. How many peaks are present in the 0−50 ppm range? Describe each in terms of its appearance in the DEPT spectrum. 4. How many peaks are present in the 50−100 ppm range? Describe each in terms of its appearance in the DEPT spectrum.
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CONCLUSIONS We started using this experiment in the spring semester of 2008 and added the guided-inquiry spectral interpretation activity in 2010 (∼40 students per semester). By incorporating a guidedinquiry approach to this experiment, over 90% of our students are able to successfully determine the correct structure of the product. This guided-inquiry approach is highly adaptable to other discover-based experiments involving spectral interpreta1184
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tion. We also use this approach with the epoxidation of carvone experiment and plan to adapt additional experiments to a guided-inquiry approach. Most importantly, students have increased confidence in their abilities and improved attitude toward organic chemistry laboratory and spectral interpretation.
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ASSOCIATED CONTENT
S Supporting Information *
Student handout with a detailed experimental procedure; instructor’s notes; product spectra. This material is available via the Internet at http://pubs.acs.org.
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AUTHOR INFORMATION
Corresponding Author
*E-mail:
[email protected]. Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS We thank Betty Bunkowske and the students of CHM 25601 for their participation in the development of this new laboratory experiment and the reviewers for their helpful comments that aided in the refinement of the manuscript.
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REFERENCES
(1) For other articles illustrating chemoselectivity see: (a) Cunningham, A. D.; Ham, E. Y.; Vosburg, D. A. J. Chem. Educ. 2011, 88, 322− 324 and references cited therein. (b) Pelter, M. W.; Macudzinski, R. M.; Passarelli, M. E. J. Chem. Educ. 2000, 77, 1481. (2) Mak, K. K. W.; Lai, Y. M.; Siu, Y.-H. J. Chem. Educ. 2006, 83, 1058−1061. (3) Miles, W. H.; Nutaitis, C. F.; Berreth, C. J. Chem. Educ. 1994, 71, 1097. (4) Boudjouk, P.; Kim, B.-K.; Han, B.-H. J. Chem. Educ. 1997, 74, 1223−1224. (5) Kjonaas, R. A.; Mattingly, S. P. J. Chem. Educ. 2005, 82, 1813− 1814. (6) Yadav, V. K.; Babu, K. G. Eur. J. Org. Chem. 2005, 425−456. (7) For example see: (a) Pavia, D. L.; Lampman, G. M.; Kriz, G. S.; Engel, R. G. Introduction to Organic Laboratory Techniques: A Small Scale Approach; Brooks/Cole-Thomson Learning: Belmont, CA, 2005; pp 530−537. (b) Schoffstall, A. M.; Gaddis, B. A.; Druelinger, M. L. Microscale and Miniscale Organic Chemistry Laboratory Experiments; McGraw Hill: Boston, MA, 2004; pp 310−316. (8) For an example of using this approach in the interpretation of the 1 H NMR spectra of aspirin see: Parmentier, L. E.; Lisensky, G. C.; Spencer, B. J. Chem. Educ. 1998, 75, 470−471. (9) Pavia, D. L.; Lampman, G. M.; Kriz, G. S.; Engel, R. G. Introduction to Organic Laboratory Techniques: A Small Scale Approach; Brooks/Cole-Thomson Learning: Belmont, CA, 2005; pp 518−520. (10) Students are required to acquire an IR spectrum of all products obtained in the lab. In this case, no structural information can be obtained from the IR spectrum of the product. It makes a good contrast to other experiments that the students perform where the product identity is determined from the IR spectrum.
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