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Jun 1, 2010 (Vol. 30, No. 11)

Microwave Chemistry Speeds Up Discovery

Heating Technology Establishing a Niche in Key Academic and Commercial Activities

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    C. Oliver Kappe, Ph.D.

    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?
    Dr. Kappe
    There is a biotech angle of some sort since biotech firms are also involved in making small molecule compound libraries. In addition, the field of peptide synthesis has seen dramatic growth in the use of microwave technology. There is extensive published research that demonstrates that controlled microwave heating can not only speed-up solid-phase peptide synthesis but also—perhaps more importantly—increase peptide purity significantly. This allows the generation of peptide sequences that otherwise would be difficult to synthesize. There are several microwave peptide synthesizers commercially available today.


    GEN With what types of organic molecules does microwave chemistry work best?
    Dr. Kappe
    In general, many organic transformations that require high temperatures and/or long reaction times have benefited the most from the use of microwave heating. These include condensation reactions for making heterocycles, transition-catalyzed cross couplings, and a whole variety of other transformations.

    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?
    Dr. Kappe
    Microwave chemistry essentially boils down to applying an efficient direct-heating principle to your reaction mixture in the flask. Although it works much faster and is more efficient than regular heating, it is essentially still heat that drives the chemistry. Because of the more rapid heating, the higher temperatures, and the better process control in a dedicated microwave reactor (operating up to 300°C and 30 bar of pressure), you can do more things faster and better.

    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.

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