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Scaling Up Effects in the Organic Laboratory Anna Persson and Ulf M. Lindström* Bioorganic Chemistry, Center for Chemistry and Chemical Engineering, Lund University, P. O. Box 124, SE-221 00 Lund, Sweden; *
[email protected] Performing a reaction on a 50-mg scale can be quite different from performing the reaction on a 50-g or 500-g scale. For example, special caution often has to be taken in controlling exothermic reactions performed on a larger scale. This is an important practical aspect of organic synthesis. Nevertheless, it is often neglected in chemical education. We describe a simple but effective way of exposing chemistry students to some of the effects of scaling up an organic reaction. The experiment requires only basic training in organic synthetic labwork and was given as a lab assignment to second-year chemical engineering students as part of a class in applied organic chemistry. These students had completed an introductory course in organic chemistry that included 48 hours of laboratory practice. The classic Diels–Alder reaction between maleic anhydride and cyclopentadiene (Scheme I) is well suited for our purposes (1–4). This reaction is exothermic enough to give measurable heat evolution even when performed on a subgram scale but still safe for students to run on a 30-g scale. In addition, the starting materials are inexpensive. The assignment consists of five experiments. Three of these are identical except for the quantity of reagents; small, medium, and large scale, starting with 0.75 g, 7.5 g, and 30 g of maleic anhydride, respectively. The other two experiments demonstrate how the excess heat evolution can be controlled by simple means. In one experiment, the reaction is performed in the presence of glass helices; the helices are added to the reaction flask. The large increase in glass surface has a cooling effect and quenches the heat evolution. In another experiment, one third of the ethyl acetate is replaced with water. Water has a high heat capacity and thus works as an efficient sink for the excess heat generated. This assignment can be adapted to work with both small and large groups of students.
tion is at room temperature and is being stirred vigorously, freshly distilled cyclopentadiene (5) is added in one portion.1 Temperature readings are noted every 30 seconds. Following the last reading (six minutes should be sufficient), the Diels– Alder adduct usually precipitates within a few minutes. If no precipitation occurs spontaneously, cooling the solution should help. The crystals can be recrystallized from methanol to give pure endo-norbornene dicarboxylic anhydride. The reactions with glass helices and water as heat absorbents are performed analogously in the largest of the three scales (see the Supplemental MaterialW for the experimental details). Hazards The experiments should be carried out in a ventilated hood. Ethyl acetate is a skin irritant and flammable liquid. Cyclopentadiene is an irritant and has a foul smell. Maleic anhydride may cause burns and allergic response on inhalation and skin contact. The chemicals should be disposed of by incineration or in accord with local regulations. Results Students plot the temperature versus time for each reaction. A typical set of data is shown in Figure 1. As can be seen, the differences in reaction temperature between the small, medium, and large scale reactions are significant. It is also clear that water and glass helices act as efficient heat
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The Experiments
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T / °C
The Diels–Alder reactions are performed in three-necked flasks, 25 mL, 250 mL, and 1000 mL for the small, medium, and large scale. Maleic anhydride, 0.75 g, 7.5 g, and 30 g, is dissolved in 7.5 mL, 75 mL, and 300 mL of ethylacetate兾 petroleum ether (1:1), respectively. Each flask is fitted with a condenser, a thermometer, and a drying tube. After making sure that the maleic anhydride is dissolved and that the solu-
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O O
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Scheme I. The classic Diels–Alder reaction between maleic anhydride and cyclopentadiene.
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glass helices
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water
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t/s Figure 1. Dependence of reaction temperature on reaction size and the presence of glass helices or water in the Diels–Alder reaction between cyclopentadiene and maleic anhydride.
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In the Laboratory
Summary
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It is our experience that these experiments are useful in conveying to students, in a simple and easily comprehensible fashion, some of the effects of scaling up organic reactions. It provides students with an experience that they may encounter in an industrial setting.
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Acknowledgments
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The authors wish to thank Ulf Ellervik for valuable discussions and the students of Applied Organic Chemistry, Lund Institute of Technology, 2002.
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Figure 2. Dependence of rate of temperature increase (dT/dt) on the volume/area ratio of the reaction flask and on the presence of glass helices or water.
Supplemental Material
Detailed student instructions, instructor notes, calculations, and results are available in this issue of JCE Online. Notes
quenchers to make the heat evolution on a large scale comparable to that observed on a small scale. Dissipation of heat to the reaction flask and the surroundings is inversely dependent on the reaction volume兾flask surface area ratio. Students calculate the dependence of observed rate of heat evolution (dT兾dt) on the ratio of reaction volume and surface area of the flask (V兾A). The results are displayed in Figure 2. For the Diels–Alder reaction there is an almost linear relationship between the three scales. As a final exercise, the students considered a hypothetical analogous reaction performed in a 1-m3 roundbottomed flask.
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1. Cyclopentadiene may be obtained in acceptable quality by cracking dicyclopentadiene in a Claisen distillation setup with a fractionating column, but a superior apparatus is described in ref 5.
Literature Cited 1. Lee, M. J. Chem. Educ. 1992, 69, A172. 2. Nash, E. G. J. Chem. Educ. 1974, 51, 619. 3. Fieser, L. F.; Williamson, K. L. Organic Experiments, 8th ed.; Houghton-Mifflin: Boston, MA, 1998; pp 463–474. 4. Rao, K. R.; Srinivasan, T. N.; Bhanumathi, N. Tetrahedron Lett. 1990, 31, 5959. 5. Magnusson, G. J. Org. Chem. 1985, 50, 1998.
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