Teaching Organic Chemistry with Microwave Speed

Teaching Organic Chemistry with Microwave Speed

by Marsha R. Baar, PhD

About 7 years ago, articles in Chemical & Engineering News and the Journal of Chemical Education, peeked my interest about incorporating microwave heating as a time saver in the undergraduate organic chemistry laboratory. The fact that it was also a green technology based on its energy efficiency was a bonus.  Lengthy refluxes not only test ingenuity of teachers in keeping their students occupied but also try the students’ patience, as well. There is no pedagogical benefit from watching a reaction cook for 1 ½ hours; the chemistry involved and the interpretation of results should be the main focus of an experiment. With the students’ safety as my primary concern, I knew that a domestic oven, although inexpensive, would limit chemistry options or require a major redesign of the experiments to avoid unsafe pressure buildup. I did not want to devote time reworking tried and true experiments. I simply wanted to speed them up. Therefore, I investigated laboratory grade microwave ovens that came equipped with temperature monitoring and appropriate safety features. I purchased CEM’s MARS™ System because it was designed for the academic lab. Depending on the carousel selected, 14-24 samples could be run simultaneously at various power settings in reusable glass reaction vessels and on a scale typically performed in the sophomore lab.    

The first reaction tested for rate acceleration was a Diels-Alder cycloaddition that required 2.5 hours of reflux to produce yield >90% (although we only refluxed for 1.5 hours in the lab obtaining ~ 75% yield). Heating in the MARS for10 minutes at 130 oC matched the high yield. The rate enhancement enabled the reaction, its workup, and analysis to be completed in one lab period, where previously one period had been devoted just for the reflux. This time saving feature allowed another experiment to be added to the lab sequence.     

Highly encouraged by this first success, two SN2 reactions were tested; a Williamson ether synthesis and Wittig salt formation. These reactions, which were allowed to reflux for 1.5 hours (nowhere near completion), gave much higher yields with 10 minutes of heating at 130 oC. An added benefit was the improved yield of the ether product that made scale down possible and an easier purification. The time saved in forming the Wittig salt allowed an expanded NMR analysis to include the effects of phosphorus.     

Currently, my research group is attempting the rate accelerations of reactions illustrating alkyne chemistry, rarely described in lab texts. The dehydrohalogenation of dibromoalkanes to alkynes is usually performed in an open sand bath to achieve temperature in excess of 200 oC. Splattering and charring occurs, so safety issues are significant coupled with poor yields. To hydrate the resultant alkyne, mercury salts or other expensive catalysts are needed, prohibiting their use in the sophomore lab. Both reactions were successfully accelerated by microwave energy. Our first dehydrohalogenation proceeded quantitatively within 10 minutes. One hydration took minutes using a dilute acid catalyst instead of poisonous mercury. Hence, another benefit of microwave acceleration, access to chemistry whose toxic reagents or harsh reaction conditions precluded their use.      

The advantages of microwave heating have been such a boon to the sophomore organic chemistry laboratory that I have to remember to expose my students to a traditional reflux, albeit a short one. The efficiency of microwave heating has permitted the scale down from grams to milligrams, so I also teach miniscale techniques along side microscale.     

Outside the teaching lab, having research students develop these experiments provides an excellent experience. Muhlenberg College must agree with me because they have funded all my students who worked on microwave acceleration with undergraduate research stipends. Rate acceleration of a specific reaction makes for a focused student project; one that fits well within the confines of the academic semester. Within one afternoon, the research student can perform the reaction in the oven, work it up, and analyze it. Thus, by the end of the day, they have their answer and are prepared to alter conditions to optimize results on their next attempt.        

Microwave technology has also informed my synthetic research, as well. About 4 years ago, I began utilizing microwave heating in a research project that involved a multi-step synthesis. Two steps involved hydroxyethylations and two others were ring closures through SN2 amine alkylations. These reactions were known in the literature and required days, even weeks, of reflux. All have been accelerated by microwaves to be completed within 2 hours.  The faster turn around allows for greater flexibility in synthetic design; new ideas can be tested quickly.     

This past summer due to a generous donor, I was able to purchase two Discover® microwave ovens.  These mono-mode units have a greater density microwave field. This type of oven has traditionally been used in research labs for method development since it introduces more energy to the reaction, permitting scale down and increased reaction rates. Mono-mode units have not been extensively used in the teaching laboratory because they run one sample at a time. Even coupled with a computerized robotic system which automatically retrieves and loads samples, the turnover time would have to be approximately 2 minutes to make it comparable to the time it takes the MARS to run the same number of samples. The multi-mode MARS oven retains all samples through heat up, cook, and cool down, usually 30 minutes. However, the advantage of the Discover is that as each sample is done, it is available for workup. My research group is currently experimenting with the Discover to see if rate accelerations are significant enough to allow its use in the organic chemistry lab. This should reduce the frustration of more efficient students and spread out demand on equipment.     

In the past few years, my research group has rate-accelerated six reactions that have been incorporated into the lab sequence. Although the cost of an oven is on the same order as an FT-IR spectrometer, I now think of microwave heating as being as integral to the lab experience as IR analysis. The time savings for additional chemistry and greater in-depth analyses; the cost savings associated with scale down; and the reduced waste disposal, electricity, and water consumption coupled with easier set up and clean up make microwave technology worth the investment. If you are thinking about adopting microwave technology and would appreciate some practical information, I refer you to a soon to a book from Taylor and Francis Publishers entitled, Green Organic Chemistry in Lecture and Laboratory.  I have contributed a chapter on greener reactions under microwave heating that provides information on the pros and cons of the different types of microwave ovens, guidance on how to develop your own rate accelerated reaction, various microwave techniques, and scores of microwave-enhanced reactions appropriate for the undergraduate laboratory, all with associated references.  

Marsha R. Baar, PhD is a Professor of Chemistry at Muhlenberg College in Allentown, Pennsylvania. She can be reached at baar@muhlenberg.edu.