In the Laboratory edited by
Green Chemistry
Mary M. Kirchhoff ACS Education Division Washington, DC 20036
Acylation of Ferrocene: A Greener Approach Kurt R. Birdwhistell,* Andy Nguyen, Eric J. Ramos, and Robert Kobelja Department of Chemistry, Loyola University, New Orleans, LA 70118; *
[email protected] A number of laboratory experiments and articles involving ferrocene and acylation of ferrocene have been published (1–7). A green procedure for the acylation of ferrocene was recently reported (8). The acylation of ferrocene experiment nicely demonstrates an aromatic electrophilic substitution or Friedel–Crafts acylation reaction. This experiment is usually the first introduction for undergraduates to the area of metal–arene complexes (9–11). Frequently, this experiment is employed to illustrate the use of column chromatography for the purification of complex mixtures (4, 5, 12). All of the complexes and derivatives of ferrocene are highly colored, which allows students to see the separation of the various components. We have used the above acylation reaction in our secondsemester organic lab for several years. In an effort to introduce more green chemistry into our curriculum we have modified the acylation of ferrocene experiment in two ways to make it greener: (i) we replaced the mineral acid with a polymeric sulfonic acid (Nafion,1 Figure 1); and (ii) we have switched from conventional thermal heating to microwave heating of the reaction. We believe this green modified experiment will be of interest to many instructors who have used the conventional acylation of ferrocene experiment in their laboratories and want to include more green chemistry. Our modified experiment uses the polymeric sulfonic acid (Nafion) as an acid catalyst for the acylation of ferrocene (Scheme I). As noted by Doyle (13), Nafion can be handled without the safety hazards associated with concentrated mineral acids (14). Using Nafion applies at least two principles of green chemistry: (i) “it is better to prevent waste than to treat or clean up waste after it is formed” and (ii) “substances and the form of a substance used in a chemical reaction should be chosen to minimize the potential for chemical accidents” (15). Using microwave energy to accelerate the organic reaction, thereby reducing the energy requirements of the reaction, is another application of green chemistry principles (15).
extracts are decanted from the Nafion strips. The Nafion strips from the class are collected and combined for later regeneration.2 Compared to the conventional heating method, the microwave procedure produces less tarry black byproduct. The diethyl ether extracts are combined and washed with 3 × 5 mL of 5% NaHCO3(aq). The combined diethyl ether extracts are dried over magnesium sulfate and filtered. The solvent is removed in vacuo and the resulting residue is purified by column chromatography. Purification Although purification by column chromatography is not a particularly green operation, column chromatography is an important technique. The bright orange and yellow colors of the components of this reaction mixture make for a colorful column and provide a visual illustration of the utility of column chromatography. The students determine which mobile phase to use by separating ferrocene and their product on thin-layer chromatography (TLC) by using a range of solvents. The mobile phase (20:1) petroleum ether: ethyl acetate used by Davis (12) works well. The students make up the silica chromatography column, purify their mixture, and collect the fractions in tared round-bottom flasks. The solvent is removed from the fractions. The resulting crystalline residues are analyzed by TLC, IR, 1H NMR, and GC–MS. Students record the yield. We ask the students to determine a percent yield and calculate the atom economy. Student percent yields from this procedure range from 40–60%. Hazards Protective clothing, gloves, and eye protection should be worn at all times and all manipulations should be done in a fume hood. Petroleum ether, diethyl ether, and ethyl acetate are volatile and flammable. Acetic anhydride produces skin irritation. Ferrocene and acetylferrocene are volatile organometallic solids and exposure should be minimized by the above procedures. It
Equipment A MARS model commercial microwave from CEM Corp. equipped with 50 mL Teflon express microwave vessels was used for this experiment. Experiment A 50 mL Teflon microwave vessel is charged with 1.0 g of ferrocene, 5 mL of acetic anhydride, 1.0 g of Nafion sheet (cut into 2 cm × 1 cm strips), and a stir bar. The vessel is closed with a screw cap and placed in the microwave. These vessels have a self-venting cap for pressure release. The microwave program is set to monitor the temperature in the vessels and moderate the microwave input, accordingly. The microwave program ramps the temperature to 100 °C over 1 minute, holds at 100 °C for 10 minutes, and cools for 10 minutes or until the vessels cool to 50 °C. The vessel is cooled in an ice bath before continuing. After cooling, the reaction mixture is extracted with 4 × 5 mL of diethyl ether and the
CF2CF2 n
CF
CF2
OCF2CF
x
OCF2CF2 SO3 H
CF3 Figure 1. Nafion, a polymeric sulfonic acid made with a perfluoro ethylene backbone.
O
Fe
O CH3C 2O
Nafion microwave
Fe
CH3C O2H
Scheme I. Nafion catalyzed acylation reaction of ferrocene.
© Division of Chemical Education • www.JCE.DivCHED.org • Vol. 85 No. 2 February 2008 • Journal of Chemical Education
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In the Laboratory
is not recommended that household microwaves be used for experiments involving volatile organic chemicals. Discussion The traditional acylation of ferrocene experiment has elements of green chemistry. Due to the reactive nature of the cyclopentadienyl rings in ferrocene, a strong Lewis acid, such as aluminum chloride, is not necessary for the acylation to occur (16). In the traditional acylation experiment, aluminum chloride is replaced by phosphoric acid removing any aluminum salts from the waste stream. The traditional acylation experiment is also green because no additional solvents are needed in this experiment. The acetic anhydride reagent is used as the solvent. Our use of the polymeric sulfonic acid, Nafion, to replace the phosphoric acid is another green option. Replacing phosphoric acid with Nafion reduces the hazards associated with handling concentrated mineral acids and reduces the waste stream produced upon neutralization of the phosphoric acid. The polymeric Nafion can be reclaimed and regenerated.1 Our attempts to use regenerated Nafion have met with limited success. The yields of acetylferrocene using regenerated Nafion are lower (5–20%). There are environmental concerns about perfluorinated materials persisting in the environment (17). Because Nafion is polymeric, it is less likely to be dispersed in the environment (18). For those instructors not wanting to use Nafion, a molar equivalent amount of phosphoric acid can be used in the microwave with identical parameters resulting in a similar yield. Another aspect of green chemistry is the minimization of energy requirements for reactions. Examples of decreasing the energy requirements of organic reactions by using microwave energy to increase the rate of reaction are found in the literature (19). In particular, combining microwave-assisted heating with solid reagents such as Nafion has shown significant rate enhancement in many reactions (20). In many cases the use of microwave energy results in a greater yield or cleaner reaction. In our case, microwave heating of the acylation of ferrocene substantially reduced the quantity of tarry black byproduct. Although column chromatography is not a very green process, we have retained its use in this experiment because it is an important technique for undergraduates to learn. We believe the vivid illustration of chromatography is one reason the traditional acylation experiment has been so popular. If the instructor was not interested in the chromatography portion of the laboratory, we believe the microwave and catalyst parameters could be optimized to preclude use of chromatography for purification. Conclusions This report illustrates the application of several principles of green chemistry to the acylation of ferrocene. We talk to students about the iterative procedure used in developing this experiment that allows the students to see that green chemistry is an active ongoing process of assessment and reengineering of a chemical process. Green chemistry recognizes the value of incremental improvements. The development of this experiment mimics the type of process optimization that occurs in many manufacturing operations. This article incorporates the use of solid recyclable reagents and microwave energy to illustrate the application of green chemistry principles to the Friedel–Crafts reaction. We are working on increasing the greenness of this reaction by trying new solid acid catalysts and new methods for regenerating Nafion. 262
Acknowledgments We thank the National Science Foundation CCLI A&I program (Grant No. # DUE-0535957) for support in purchasing our CEM microwave system and Loyola University’s College of Humanities and Natural Science for support of this work. KRB would like to thank Earl and Gertrude Vicknair for support of this work. Notes 1. Nafion is a registered trademark of the DuPont Company. 2. The Nafion can be regenerated by stirring in 25% nitric acid, washing with water, and drying in vacuo, see ref 13 for details.
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Journal of Chemical Education • Vol. 85 No. 2 February 2008 • www.JCE.DivCHED.org • © Division of Chemical Education
