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Feature Articles : Jun 1, 2010 ( )
Microwave Chemistry Speeds Up Discovery
Heating Technology Establishing a Niche in Key Academic and Commercial Activities!--h2>
It turns out that almost the same process you use to warm your Stouffers Macaroni and Cheese dinner might also help your research team find novel therapeutics. In addition, it looks like microwaves can accelerate peptide synthesis as well. GEN’s interview with C. Oliver Kappe, Ph.D., explores the realm of microwave chemistry. Dr. Kappe is an associate professor at Karl-Franzens-University in Graz, Austria, where his research interests include microwave-enhanced synthesis and continuous flow processing.
GEN What is microwave chemistry and how does it apply to the pharmaceutical industry?
Dr. Kappe Microwave chemistry is the process of using efficient dielectric heating mechanisms—similar to kitchen microwaves—to heat reaction mixtures directly, rather than heating the reaction vessel via conduction mechanisms as in a conventional synthesis.
Microwave chemistry is typically performed in a sealed vessel under carefully controlled reaction conditions (temperature/pressure), allowing superheating of the reaction mixture to temperatures far above the boiling point of the solvent. Based on the well-known relationship between temperature and reaction speed (Arrhenius equation), this can lead to dramatic enhancements in reaction rate.
Converting your chemistry from round-bottom flasks to sealed vessel microwave conditions has been shown to reduce reaction times from many hours down to a few minutes and also improve product purity and/or selectivity.
Not surprisingly, this enabling technology is now used extensively in discovery research programs in the pharmaceutical industry. It is perhaps fair to say that most, if not all, pharmaceutical companies globally, are users of microwave chemistry.
GEN Is there a biotech angle to microwave chemistry?
GEN With what types of organic molecules does microwave chemistry work best?
It has become difficult to identify reactions that have not been performed using microwave technology. In addition, transformations that traditionally were carried out at room temperature have, in some cases, been successfully translated to high-speed microwave reactions.
GEN What are some of the advantages compared with initiation of organic reactions with heat or light?
It took the scientific community quite some time to come to that conclusion, and there may still be people that believe in the existence of nonthermal microwave effects or related phenomena, however, the evidence from recent investigations points to a strictly thermal effect for the overwhelming majority of cases relevant to synthetic organic chemistry.
Photochemistry, such as ultrasound or mechanochemistry, is something completely different and should not be mixed up with microwave heating phenomena.
GEN How scalable is microwave chemistry?
The solution around this is continuous flow processing, either applying microwave or conventional heating principles. Since only a small section of the reaction volume needs to be heated, penetration depth is not an issue.
It should be stressed, however, that at this stage microwave-assisted flow processes on production scale have not been realized, at least not for the preparation of pharmaceuticals. This is probably related to issues such as energy efficiency, engineering/construction cost, regulatory, and safety problems. Multikilogram product quantities can be produced in currently available, larger batch-style microwave instruments.
GEN Are any pharmaceutical companies using microwave chemistry, and what types of reactions or processes are they using it for?
GEN Who are some of the leading suppliers of microwave reactors? Do you partner with them in any way?
Over the years, we had various partnerships with several of the instrument vendors. Right now, we do have a good collaboration with Anton Paar, in which we are developing instrumentation and technology that is expected to improve on currently available microwave reactors. We are also interested in finding new applications for microwave technology in the analytical, materials, and biosciences fields.
GEN What does the future look like for microwave-assisted synthesis? Has it reached its limits?
Chemistry-wise, I predict that we will see a significant increase in applications in the material-, nano-, and biosciences fields in the next few years.
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