Communication pubs.acs.org/jchemeduc
The Isomerization of (−)-Menthone to (+)-Isomenthone Catalyzed by an Ion-Exchange Resin Aurora L. Ginzburg, Nicholas A. Baca,† and Philip D. Hampton* Department of Chemistry, California State University Channel Islands, One University Drive, Camarillo, California 93012, United States
J. Chem. Educ. 2014.91:1748-1750. Downloaded from pubs.acs.org by RICE UNIV on 01/02/19. For personal use only.
S Supporting Information *
ABSTRACT: A traditional organic chemistry laboratory experiment involves the acidcatalyzed isomerization of (−)-menthone to (+)-isomenthone. This experiment generates large quantities of organic and aqueous waste, and only allows the final ratio of isomers to be determined. A “green” modification has been developed that replaces the mineral acid catalyst with an acid-form ion-exchange resin, AMBERLYST 15DRY. This “green” modification dramatically reduces the quantity of waste, eliminates the hazards of concentrated acid, and allows for the isomer ratio to be monitored as a function of time. The pedagogical impact of the experiment has been significantly improved through examination of the effect of catalysis on the position of the equilibrium and on the kinetics of the reaction. As part of the experimental procedure, students generate their own hypothesis regarding the position of the equilibrium using molecular modeling of (−)-menthone and (+)-isomenthone. Students then test their hypothesis by performing the reaction with different catalyst quantities and at different temperatures. By pooling their data, students can examine the effect of both catalyst quantity and temperature on the position of the equilibrium, and the rate of the reaction. KEYWORDS: Laboratory Instruction, Second-Year Undergraduate, Organic Chemistry, Inquiry-Based/Discovery Learning, Catalysis, Conformational Analysis, Equilibrium, Green Chemistry, Kinetics, Thermodynamics ne of the experiments performed in the first semester introductory organic laboratory involved the acidcatalyzed isomerization of (−)-menthone to (+)-isomenthone (Scheme 1) through an enol intermediate.1 The traditional
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reinforce the concepts of isomerization, conformations of cycloalkanes, optically active molecules, catalysis, and reaction kinetics and thermodynamics. AMBERLYST 15DRY catalyzes the conversion of neat (−)-menthone (1 mL) efficiently to an equilibrium mixture of (−)-menthone and (+)-isomenthone within 90 min using 10 mg (1.1 mass %) of resin at 70 °C. In contrast with the traditional conditions that required aqueous workup, this new version of the experiment allows the equilibration process to be monitored as a function of time by simply removing aliquots of the reaction mixture free from the insoluble catalyst. At the end of the experiment, the product mixture can be easily separated from the polymeric resin using a pipet without the need for neutralization and extraction. These conditions dramatically decrease the quantity of waste generated in this organic laboratory experiment and eliminate the use of corrosive acids. Table 1 displays the quantities of reagents and solvents used in the traditional experiment compared with this modified procedure. Using the traditional conditions, an 18-student lab generated over 750 mL of mixed organic waste, a liter of aqueous waste, and 50 g of solid waste. The “green” version of this experiment, in contrast, generates less than 250 mL of total waste for this same lab. The modified laboratory experiment has been successfully implemented for the past 10 semesters in first semester organic
Scheme 1. Isomerization of (−)-Menthone to (+)-Isomenthone
experiment used a mixture of hydrochloric acid and glacial acetic acid to catalyze the isomerization. When implemented as described, this experiment generated considerable quantities of chemical waste as a result of the need to neutralize the acids and to extract the mixture of (−)-menthone and (+)-isomenthone into an organic solvent. This communication describes a substantial improvement to this experiment that involves the use of AMBERLYST 15DRY (dry, hydrogen form) to catalyze the equilibration, resulting in a more environmentally benign and pedagogically valuable experiment. The modified experiment is aimed at students who are enrolled in an introductory organic chemistry course, and it can be used to © 2014 American Chemical Society and Division of Chemical Education, Inc.
Published: July 21, 2014 1748
dx.doi.org/10.1021/ed500124f | J. Chem. Educ. 2014, 91, 1748−1750
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generated in the laboratory. The mixture reached equilibrium within 90 min over the entire range of recommended conditions. At the end of the reaction time, the final product was analyzed by optical rotation measurements. (Note: a polarimeter with an accuracy of thousandths of a degree of rotation was needed to detect the small changes in rotation.) The total experiment time including sample preparation and polarimetry measurements was approximately 3 h. Some of the aliquots/final reaction mixture could be analyzed by gas chromatography during the laboratory period, and the remaining samples were run outside of the laboratory period on a gas chromatograph equipped with an autosampler.
Table 1. Comparison of the Conditions Used in the Traditional versus Green Experiment Activity Synthesis
Traditional Experiment 2 mL of (−)-menthone 10 mL of glacial acetic acid
Polarimetry GC analysis Waste (per 18 students)
10 mL of 1 M HCl 40 mL of 1 M NaOH 25 mL of dichloromethane 1−3 g of CaCl2 10 mL of ethanol 1 mL of organic solvent 750 mL of mixed organic waste, 1 L of aqueous waste, 50 g of solid waste
Green Experiment 1 mL of (−)-menthone 10−40 mg of AMBERLYST 15DRY
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10 mL of ethanol 3 mL of organic solvent Less than 250 mL of total waste
HAZARDS Students and the instructor wore personal protective equipment consisting of nitrile gloves, a lab coat, and goggles at all times during the lab experiment. The experiment was conducted in a fume hood with adequate ventilation. As part of the prelab assignment, students reviewed the MSDS forms to determine the hazards of (−)-menthone, acetone, and ethanol (all are flammable solvents). Students were advised to avoid skin and eye contact with all chemicals used in this experiment. Liquid waste was disposed into a labeled hazardous waste bottle.
chemistry laboratory to a total of 420 students. It has been extremely successful as an experiment based on the dramatic reduction in chemical waste generated, and the improved pedagogical opportunity for students to observe how a catalyst influences the rate of a reaction, but not the position of the equilibrium and how rates increase with increasing reaction temperature.
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EXPERIMENTAL RESULTS Figure 1 shows how the ratio of (+)-isomenthone to (−)-menthone, as measured by gas chromatography peak
METHODOLOGY
Molecular Modeling
Prior to the laboratory period, students performed molecular modeling and made molecular models to generate a hypothesis regarding the position of the equilibrium between (−)-menthone and (+)-isomenthone. MarvinSketch, a free molecular modeling software available on the Internet and accessible to students from any location, generated a lower energy for (+)-isomenthone. In contrast, molecular models and Chem3D and CAChe software correctly predicted that (−)-menthone is the more stable isomer.1c The conflicting results provided an opportunity to explain the limitations of computational approaches, and it also allowed students to examine the differences between theory and experimentation. A discussion of the minimization using MarvinSketch is provided in the Supporting Information. Students compared the MarvinSketch energy difference between the two isomers with experimental values obtained from equilibrium constants determined by gas chromatography and polarimetry. MarvinSketch indicated that the most stable conformer of (+)-isomenthone has an axial isopropyl group and an equatorial methyl group, consistent with an NMR and theoretical study.2
Figure 1. Student-generated data comparing two different quantities of AMBERLYST 15DRY catalyst at 90 °C. Ratio of peak areas = area of (+)-isomenthone/area of (−)-menthone.
areas, changed as a function of time with two different quantities of the catalyst. The displayed graph was generated from data obtained by two groups of introductory organic chemistry undergraduate students who performed this experiment; however, a similar graph could be plotted for the other assigned temperatures or catalyst quantities. Students observed that the initial slopes of the curves were strongly dependent upon the quantity of catalyst used, but the final equilibrium position was identical for the two reactions. The final ratio at equilibrium was used as a measure of the equilibrium constant for the reaction. From an analysis of pooled data for the lab section, students saw that the quantity of catalyst did not affect the overall thermodynamics of the reaction, but did influence the rate at which equilibrium was attained. The reaction temperature dramatically affected the rate at which the reaction reached equilibrium and, to a much lesser
Experimental Conditions
Each student weighed the desired quantity of AMBERLYST 15DRY catalyst (10−40 mg) into a 20 mL scintillation vial, added a small stir bar, and delivered (−)-menthone (1 mL) to the vial. The vial was placed in an equilibrated water bath at a known temperature (70−90 °C). A detailed experimental procedure is provided in the Supporting Information. Instructors should note that static electricity prevented direct weighing of the resin and, instead, a dispensing tool was used (described in the Supporting Information). The reaction was stirred for 90 min, and small aliquots were removed at 15 min intervals by using capillary action to pull a sample into a glass pipet, followed by dilution with acetone. Samples were analyzed by gas chromatography as they were 1749
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obtained at 25 °C compared with a laboratory temperature of approximately 19 °C.
extent, the position of the equilibrium. Figure 2 displays the results of student-generated data using the same quantity of
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CONCLUSION The introduction of this “green” version of the isomerization of (−)-menthone improved the value of the experiment in numerous ways. First, implementing a polymer catalyst dramatically reduced the quantity of chemicals used and waste generated, as well as the hazards associated with them. Second, the use of a polymeric catalyst, rather than aqueous acid, was advantageous because it allowed the time dependence of the equilibration to be observed, as well as how it depended on the reaction conditions. Finally, students were able to collaborate with their classmates to examine how different reaction conditions affected both the thermodynamics and the kinetics of the equilibration.
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Figure 2. Student-generated data comparing the effect of temperature on the equilibrium at two reaction temperatures (70 and 90 °C) and with 30 mg (3.4 mass %) of AMBERLYST 15DRY. Ratio of peak areas = area (+)-isomenthone/area (−)-menthone.
Student laboratory manual procedure including molecular modeling instructions for MarvinSketch, and instructor notes consisting of background information, gas chromatography conditions and data, answers to prelab questions, and CAS registry numbers. This material is available via the Internet at http://pubs.acs.org.
catalyst at two different temperatures. Again, a similar graph was obtained for other temperatures, but only two are plotted here for the sake of clarity. It should be noted that a much larger range of temperatures would be necessary to observe a temperature dependence of the equilibrium constant. Sand baths could be used to achieve temperatures greater than 100 °C; however, they require long equilibration times and have an inhomogeneous temperature distribution. Results obtained using sand baths, including graphs over a wide temperature range, can be found in the Supporting Information. Table 2 compares student-generated equilibrium constants obtained from both optical rotation and gas chromatography
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*E-mail:
[email protected]. Present Address †
N.A.B.: PETNET Solutions, 4050 East Cotton Center Boulevard, Building 7, Suite 79, Phoenix, AZ 85040. Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS We would like to acknowledge the Chemistry Program at CSU Channel Islands for providing support for the development of this experiment. We thank Nancy Deans and Ahmed Awad for providing student-generated data, and we thank Nancy Deans for contributing to the prelab questions for this experiment.
Keq Catalyst Quantity (mg)
From GCa
From Optical Rotationb
70 70 90 90
20 30 10 30
0.473 0.487 0.491 0.496
0.498 0.532 0.385 0.540
AUTHOR INFORMATION
Corresponding Author
Table 2. Comparison of Experimentally Determined Equilibrium Constants Temperature (°C)
ASSOCIATED CONTENT
S Supporting Information *
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a
Equilibrium constants were calculated using the ratio of (+)-isomenthone and (−)-menthone as measured using the peak areas obtained by gas chromatography. bEquilibrium constants were calculated using the final optical rotation of the samples according to ref 1.
REFERENCES
(1) (a) Lehman, J. W. Operational Organic Chemistry, 3rd ed.; Prentice Hall: Upper Saddle River, NJ, 1999; pp 136−142. (b) Barry, J. Determination of the Relative and Absolute Configurations of (−)Menthol and (+)Neomenthol. J. Chem. Educ. 1973, 50 (4), 292. (c) Currie, J. Evaluations of Conformations of Menthone and Isomenthone. In Teaching with CAChe: Exercises on Molecular Modeling in Chemistry; Wong, C., Currie, J., Eds.; Fujitsu Limited: Forest Grove, OR, 2001; pp 4-1−4-6. (2) Smith, W. B.; Amezcua, C. NMR versus Molecular Modeling: Menthone and Isomenthone. Magn. Reson. Chem. 1998, 36 (S1), S3− S10. (3) Kukula, P.; Č ervený, L. Stereoselective Hydrogenation of (−)-Menthone and (+)-Isomenthone Mixture Using Nickel Catalysts. Res. Chem. Intermed. 2000, 26 (9), 913−922. (4) Rickborn, B. Conformational Analysis in Symmetrically Substituted Cyclohexanones. The Alkyl Ketone Effects. J. Am. Chem. Soc. 1962, 84 (12), 2414−2417.
measurements. The measured equilibrium constants were consistent with published values (0.433 and 0.4104). Studentobtained values typically ranged from 0.47 to 0.56 with GC analysis and from 0.39 to 0.61 with polarimetric analysis. The equilibrium constants from optical rotation data were highly variable. This is likely due to instrument difficulties in accurately measuring the observed rotation at equilibrium, which was between zero and one degree. Student error in measuring the mass of product transferred from the scintillation vial to the 10 mL volumetric flask was also a significant problem. The optical rotation calculation used literature specific rotation values for (+)-isomenthone and (−)-menthone 1750
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