I received both my undergraduate (1989) and graduate education (Ph.D. 1992) in synthetic organic chemistry at the University of Graz, Austria. After periods of postdoctoral research work on reactive intermediates and matrix isolation spectroscopy with Curt Wentrup at the University of Queensland in Brisbane, Australia (1993-1994), and on synthetic methodology/alkaloid synthesis with Albert Padwa at Emory University in Atlanta, USA (1994-1996), I moved back to the University of Graz as an assistant professor in 1996 to start my independent academic career. At that time my group was working in the field of combinatorial chemistry, in particular on multicomponent reactions.

  What sparked your interest in this particular field of study?

After obtaining my "Habilitation" at the University of Graz and being promoted to a tenured position as associate professor in 1999, I was looking for new areas of research in the general field of organic synthesis. At that time microwave chemistry (the first applications were reported in 1986) was not taken seriously by the synthetic community and most people didn’t really understand the basic concepts either. In addition, there was virtually no dedicated equipment available to do serious research; almost everybody still used domestic kitchen microwave ovens where you could not control such important parameters as, for example, the reaction temperature.

“...the current belief is that most reactions requiring heat to run at efficient speed can benefit from microwave heating.”

Although we did run some early—not very successful—experiments before 1998 using kitchen microwaves, the real eye opener for me came in May of 1998 attending a lecture on microwave-assisted synthesis by one of the pioneers in the field, Rajender Varma, in Hungary. From that time on I was hooked and thought that we should focus our efforts on better understanding the fundamental principles of microwave dielectric heating for organic synthesis and on exploring new applications.

In contrast to most other groups working in this area at the time I made the conscious decision not to work with kitchen microwave ovens but to look for alternatives. We bought our first dedicated microwave reactor for organic synthesis in 1999 and shortly thereafter started a collaboration with another instrument manufacturer to help develop new instrumentation.

  Would you please sum up your paper, "Controlled microwave heating in modern organic synthesis" for our readers?

This paper is actually a review article in which I summarized the published reports on microwave-assisted organic synthesis from 2000-2003 (ca 400 references). Although several highly cited review articles in this field have been published before, this review is different as it only includes transformations carried out in dedicated microwave reactors where the reaction temperature can be clearly defined. Before that time, microwave chemistry had a bad reputation because not all of the published work was reproducible, often as a consequence of using kitchen microwave ovens (a practice now banned by most journals).

I think this review, published in Angewandte Chemie in November of 2004 and subsequently voted "best review article" by the readers of that journal, ultimately convinced a lot of synthetic chemists to take this technology seriously, and to apply it to their own projects and problems.

In the article, I first briefly discuss the basic principles of microwave dielectric heating and the available equipment and processing techniques. Most of the review, however, is dedicated to highlighting published reports of controlled microwave-assisted heating in the field of organic synthesis. Examples include applications in transition-metal catalysis, natural product synthesis, the formation of heterocycles, use in solid-phase synthesis, and many more applications. In fact, the current belief is that most reactions requiring heat to run at an efficient speed can benefit from microwave heating.

  Why has the use of microwave energy become so popular in academia and industry?

The simple fact that you can perform a reaction that requires many hours under conventional heating in a few minutes using microwave technology is attractive to most people. In many cases, this acceleration effect is additionally accompanied by higher product yields and a cleaner reaction profile, also important factors in a chemical synthesis.

It is not only the pharmaceutical industry ("time equals money") where this enabling technology today is almost standard practice. Microwave chemistry is also heavily used in academic labs across the world. An additional incentive for academic groups to get involved in this field is the fact that the exact reason why irradiating reaction mixtures with microwave energy speeds up the reaction is not fully understood. Arguments rationalizing this and other effects range from a simple thermal phenomenon (rapid heating), to hot-spot theories and the presumed orientation of polar reaction species in the electric field (non-thermal microwave effects).

In any event, this technology has proven extremely popular in the past few years, the number of publications on controlled microwave heating in organic synthesis is nearly doubling every year. I think this year we will see 1,000 papers being published using this heating method.

We are using microwave heating in all of our projects. We have projects running where we do more fundamental work, investigating, for example, the infamous "non-thermal microwave effect," looking at scale-up options or the energy balance of microwave heating versus conventional heating. In other projects microwave reactors are simply used as a tool to drive the desired chemistry.

In my research group the oil baths and heating mantles have been virtually abandoned. All the chemistry is done under microwave conditions and we are constantly looking for new applications, also outside the field of organic synthesis. Last year we obtained a seven-year grant from the Austrian government to establish a center-of-excellence facility in Graz with the purpose of investigating the fundamental principles behind this technique¹. This will allow us to significantly increase our scientific output in this field in the future.

In my opinion there are many more applications of controlled microwave heating in the chemical sciences that will come to the forefront in the next few years. We have only seen the beginning of this efficient heating method penetrating other fields. Polymerization reactions, the materials science field, the controlled formation of nanoparticles, biochemical applications such as protein digestion and polymerase chain reaction, or peptide synthesis are just some of the areas were exciting research has been published in the past few months and years.

One serious drawback that needs to solved, however, is scale-up. Due to the restricted penetration depth of microwaves into absorbing media (a few centimeters) it is inherently difficult to build larger reactors that can provide products on a kg or higher scale.

Prof. C. Oliver Kappe
Christian Doppler Laboratory for Microwave Chemistry
Institute of Chemistry
Karl-Franzens-University Graz
Graz, AUSTRIA