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Green Chemistry in the Organic Teaching Laboratory: An Environmentally Benign Synthesis of Adipic Acid Scott M. Reed and James E. Hutchison* Department of Chemistry, University of Oregon, Eugene, OR 97403-1253; *
[email protected] Chemical synthesis that takes into account environmental considerations in the selection of reactants and reaction conditions is growing in importance as both industrial and academic researchers become aware of the environmental and economic advantages of an environmentally benign or “green” approach. In the teaching laboratory, introduction of greener experiments improves safety, allows for the routine use of macroscale techniques, and provides an ideal context for the discussion of chemical safety. The use of greener reactions and reagents also introduces state-of-the-art methods and gives students a glimpse of the frontiers of chemical research. While many chemistry courses now cover environmental issues as a part of their curriculum (1), few integrate such concepts into their laboratory sections, owing in part to a lack of published material in this field. We know of no published green experiments designed for use in the organic teaching laboratory. The scarcity of such experiments occurs because green synthesis is in its infancy and modification of existing experiments can be difficult. The lack of experiments is a major obstacle to providing a greener organic laboratory curriculum. Because of the potential benefits of such a curriculum, our aim was to develop experiments for use in a new green organic chemistry laboratory course taught at the University of Oregon.1 Here we report an experiment from that course in which the students synthesize adipic acid by oxidation of cyclohexene under environmentally benign conditions. This reaction serves as an example of the types of experiments that introduce green concepts while teaching hands-on green laboratory techniques.
The experiment reported here has a number of these attributes. They are described below. This experiment, An Environmentally Benign Synthesis of Adipic Acid, was carried out during the third laboratory session of the first term of the green organic chemistry laboratory sequence. The experiment, adapted from an article in the recent literature (2), was conducted during a 4-hour period that was preceded by a 1-hour lecture, although the experiment can be accomplished in a 3-hour period. The experiment introduces important laboratory techniques (recrystallization and phase-transfer catalysis) and provides an opportunity to introduce polymer chemistry in the lecture course (adipic acid is used in the synthesis of Nylon 6,6, a polymer commonly synthesized in labs and in classroom demos). Synthesis of adipic acid typically involves hazardous reagents or by-products and is thus a good candidate for developing greener chemical methods. Industrial production of adipic acid involves the oxidation of cyclohexanol, cyclohexanone, or both by nitric acid (2). An inevitable by-product of this reaction is nitrous oxide, which has been implicated in global warming and ozone depletion (2). Student laboratory experiments have utilized potassium permanganate and dichromate to oxidize cyclohexanol to adipic acid (3). In both cases the oxidant used is a hazard to both the environment and the students. A number of research groups have been studying the use of hydrogen peroxide as a milder oxidant of alkenes using various catalysts in a variety of solvents (4 ). An alternative process for adipic acid synthesis has recently been described that uses sodium tungstate–catalyzed oxidation of cyclohexene by hydrogen peroxide in water (2):
Discussion Our goal in designing this course was twofold. We sought to teach students the core organic synthesis laboratory skills while demonstrating, first hand, the benefits of an approach that uses greener reagents, reaction conditions, and products. Our criteria for identifying green experiments for this new curriculum are that each experiment should: 1. Illustrate green chemical concepts (e.g., recycling, hazard reduction, solvent reduction). 2. Teach modern reaction chemistry and techniques. 3. Complement the lecture course and provide a platform for discussion of environmental issues in the classroom. 4. Be accomplished by students within the time (3 hours) and material constraints of a typical student organic laboratory. 5. Be adaptable to either macroscale or microscale methods. 6. Use inexpensive, greener solvents and reagents. 7. Reduce laboratory waste and hazards.
Na2WO4 H2O2
KHSO4 Aliquat 336
O HO OH O
This process, which we have adapted to a teaching laboratory setting, substitutes an environmentally benign oxidizing agent for a hazardous one, uses water as the solvent, and teaches the benefits of recycling. One of the green messages that can be taught from this experiment is the advantage of using a recyclable catalyst. Because the sodium tungstate and the phase-transfer reagents are not consumed in the reaction, it is possible to recycle the aqueous reaction mixture that contains them for use in subsequent reactions. It is only necessary to add fresh olefin (cyclohexene) and oxidant (hydrogen peroxide) to the recycled catalyst solution to repeat the reaction. A second opportunity for conveying the benefits of recycling of materials arises because during a first-term laboratory experiment students
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commonly prepare a cyclohexene starting material, which can be used as a substrate in this experiment.2 Results The experimental procedure is a modification of the adipic acid synthesis described by Sato et al. (2), shown in the scheme above. The modifications are as follows: (i) a reduction of the reaction time from 10 to 2 hours, so that the experiment can be completed during a normal laboratory session; (ii) a reduction in the scale to one more suitable to a teaching laboratory; (iii) an increase in the ratio of phasetransfer catalyst to alkene reactant; and (iv) a change in the phase-transfer catalyst to one that can be formed in situ from commercially available chemicals. The last alteration, in particular, bears comment. Sato et al. emphasize the importance of using methyltrioctylammonium hydrogen sulfate as a phase-transfer catalyst. As they discuss (2), the commercially available methyltrioctylammonium chloride (Aliquat 336) will not work as a replacement. We felt that the reported synthesis of methyltrioctylammonium hydrogen sulfate (5) was inappropriate for a student laboratory. However, we found that Aliquat 336 can be used if potassium hydrogen sulfate is added to the reaction to provide the hydrogen sulfate counterion. Conclusions This experiment fulfills all the criteria we set forth for a successful green experiment. In addition to the primary goals of teaching green chemical concepts and techniques, we found that the incorporation of green experiments provides other advantages. We were able to reduce the waste that is normally formed from such an experiment, thereby reducing the expense of the experiment, and to switch from microscale to macroscale, exposing students to glassware more common in research laboratories. We found that incorporation of green experiments into the curriculum provides a platform for discussion of environmental issues in the classroom. Student evaluations were positive and indicated that working on a experiment from the recent literature was particularly exciting. The experiment works well in the teaching laboratory and provides opportunities for further modification and development. Students report good to excellent yields using the procedure described. Looking toward further development of this experiment, we see the two obvious opportunities. First, the reaction time could be reduced3 (from the rate at which the organic layer disappears, it appears that the reaction is complete within the first hour). Second, other alkene substrates could be tried,2 with the following caveat: the diacid product obtained from alternative alkene substrates may not recrystallize as easily as adipic acid. If teaching the skill of recrystallization is a primary goal, cyclohexene is the ideal substrate.
was added. This was followed by 0.50 g of Aliquat 336, 11.98 g of 30% hydrogen peroxide, and 0.37 g of KHSO4. This mixture was stirred and then 2.00 g of cyclohexene was added. A drying tube with calcium chloride was fitted to the top of the condenser to minimize odors and the reaction was heated on a sand bath to a reflux for 2 hours. The progress of the reaction was monitored by stopping the stirring and observing whether the layers separated. As the liquid cyclohexene is converted to the water-soluble adipic acid, the mixture no longer separates into two layers. After two hours of heating, the round-bottom flask was removed from the sand bath. However, it was not allowed to cool completely because this causes co-precipitation of the phase-transfer catalyst with the product. While the reaction mixture is still hot the aqueous layer was transferred by pipet into a clean flask. Upon cooling, crude adipic acid precipitated. Students reported yields ranging from 42 to 87%, with an average of 68%. The crude samples were easily recrystallized from a minimal amount of hot water to yield pure samples that melted sharply at the temperature expected for adipic acid. Students also performed mixture melting point determinations and some samples were checked by IR and NMR spectroscopy to confirm identity and purity. Hazards Aliquat 336 is toxic and should be handled with gloves. Hydrogen peroxide at 30% concentration causes severe contact burns on the skin or in the eyes. Protective gloves and goggles must be worn when handling this substance. Potassium hydrogen sulfate and solutions containing it are acidic and should be handled appropriately. Recycling and Waste Disposal It is possible to recycle the waste from this experiment for use in further reactions. The material that remains in the round-bottom flask should contain the phase-transfer catalyst, and the aqueous filtrate from the collection of the crystals should contain the tungstate catalyst. If these materials are not recycled, they should be disposed of with caution, as the phase-transfer catalyst is toxic and the aqueous solution will be acidic owing to the potassium hydrogen sulfate. Acknowledgments We thank Marvin G. Warner and the members of the fall-term CH337G at the University of Oregon for their assistance in optimizing and testing this experiment. SMR acknowledges support from a Department of Education GAANN fellowship. JEH is an Alfred P. Sloan Research Fellow and a Camille Dreyfus Teacher/Scholar Award recipient. This work was supported by the University of Oregon and the National Science Foundation CAREER program (CHE9702726 to JEH).
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All materials were purchased from Aldrich and used as received. To a 50-mL round-bottom flask fitted with a water condenser and a stir bar, 0.50 g of sodium tungstate dihydrate
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Supplemental Material
A student handout is available as supplemental material in this issue of JCE Online.
Journal of Chemical Education • Vol. 77 No. 12 December 2000 • JChemEd.chem.wisc.edu
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Literature Cited
1. This curriculum is being developed in collaboration with Kenneth M. Doxsee. 2. In our laboratory sequence, students have synthesized 4-methylcyclohexene in a previous lab session. The product obtained from oxidation of this material, however, is much more difficult to isolate and recrystallize than the product obtained from cyclohexene. 3. We have conducted this laboratory experiment a second time since our initial writing. We increased the number of students to 28 and reduced the lab time from four hours to three hours. Of the 28 students, 23 successfully completed the experiment with an average reported yield of 39%. While this supported our belief that it is possible to complete the experiment in three hours, we feel that the longer lab section allows the students to focus more on the technique of recrystallization.
1. Aram, R. J.; Manahan, S. E. J. Chem. Educ. 1995, 72, 977. Collins, T. J. J. Chem. Educ. 1995, 72, 965. Swan, J. A.; Spiro, T. G. J. Chem. Educ. 1995, 72, 967. Amato, I. Science 1993, 259, 1538. 2. Sato, K.; Aoki, M.; Noyori, R. Science 1998, 281, 1646. 3. Fieser, L. F.; Williamson, K. L. Organic Experiments, 6th ed.; Heath: Lexington, MA, 1987; p 188. 4. Schwegler, M.; Floor, M.; van Bekkum, H. Tetrahedron Lett. 1988, 29, 823. Antonelli, E.; D’Aloisio, R.; Gambaro, M.; Fiorani, T.; Venturello, C. J. Org. Chem. 1998, 63, 7190. Sakata, Y.; Katayama, Y.; Ishii, Y. Chem. Lett. 1992, 671. Ishii, Y.; Yamawaki, K.; Ura, T.; Yamada, H.; Yoshida, T.; Ogawa, M. J. Org. Chem. 1988, 53, 3587. 5. Sato, K.; Aoki, M.; Ogawa, M.; Hashimoto, T.; Noyori, R. J. Org. Chem. Soc. 1996, 61, 8310.
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