Oliver Kappe talks to Marie Cote about scaling-up microwave chemistry

Oliver Kappe

Oliver Kappe is professor of chemistry at the University of Graz in Austria. Research in the Kappe group focuses on enabling technologies for synthesis, including microwave and continuous flow methods.

Can you tell us what inspired you to become a scientist?

In my case it was pretty straightforward since my father was also a professor of organic chemistry at the University of Graz. It's a family affair!

What led you towards microwave chemistry in particular?

At a conference in 1998 in Hungary I heard a lecture by Professor Rajender Varma, now at the US EPA, highlighting the benefits of doing organic chemistry under microwave conditions. At that time it was all kitchen microwaves, there was almost nothing else available. That same year we started our collaboration and the following year published our first joint paper together.

I liked it so much that we continued in many different areas. We studied fundamental issues, such as the occurrence of special microwave effects, as well as the application of microwave chemistry in organic synthesis and fields like peptide chemistry, nanomaterials, polymer synthesis. And of course, finally, we looked at how to scale-up microwave chemistry.

The scale-up question was important for your future work. Can you tell us more about it?

Scaling-up reactions led us to flow chemistry. If a reaction would work on a small scale, many of our industrial collaborators in the field of microwave chemistry were obviously interested in how to make larger quantities of their products. We therefore had to investigate how to scale-up microwave chemistry and initially performed microwave chemistry in larger batches. But as everybody who has defrosted lasagne in a kitchen microwave knows, sometimes it stays cold in the middle but is piping hot on the outside.

Because of penetration depth issues it isn’t possible to have very large tanks or batches of microwave reactors. But, and this is something we also discovered in our regular research, we knew that, in general, microwave chemistry is related to a purely bulk thermal effect – it is just very efficient and more rapid heating. This led us to the idea that we can heat microreactors or continuous flow apparatus very efficiently, and this was the translation of a batch microwave experiment to a continuous flow experiment, using 1mm steel capillaries in which we can heat anything fairly rapidly and efficiently to much higher temperatures and under higher pressures than in a microwave system.

Where do you see the future of flow chemistry going?

Well, people have different opinions and there are different theories. Of course flow chemistry is not new and the petroleum industry in particular has large production plants where many things are flow chemistry, because there is no other way to do things. The pharmaceutical industry and agrochemical industry which do not have such high volumes are starting to look into flow chemistry as well. In particular, for reactions that cannot be done in batch for safety reasons. Flow chemistry can also combine many of the hall marks of green chemistry into continuous flow processes. We've seen examples of lower solvent consumption, higher yield, higher selectivity, meaning that you have to spend less time purifying and therefore use less solvent.

Nothing is perfect, and not all batch chemistry can or should be run in flow, as sometimes batch is just easier. But running something at 200°C under 20 bar pressure is very difficult to do in large batch vessels for safety reasons, and in these cases you are much better off using a continuous flow system.

Can you tell us about a key project you're running in your lab at present?

One key project we've been doing with Swiss company Lonza is to synthesise tetrazoles in continuous flow mode. Tetrazoles are an important structural motif in a number of pharmaceutically interesting molecules and we were able to design a safe way to generate them using the highly explosive reagent, hydrazoic acid. The reason we can do this in continuous flow is because we can generate this reagent in situ in a micro reactor so it is then consumed in the continuous flow reaction. Since hydrazoic acid is completely consumed at the end of the continuous flow process nothing hazardous is going to leave the continuous flow reactor.

What inspires you and where do you look for ideas?

Primarily at conferences: talking to colleagues over a beer sometimes gives me great ideas. It is also very rewarding for me and gives me great pleasure and satisfaction to see my students and post docs come up with great projects too.

What would you say is the best thing about your job?

Freedom! Being in academia, especially with a permanent position, which is rare these days, is something very satisfying because it means that essentially you can do what you want professionally. It is not as easy as it was 10 or 20 years ago, because we need money to do research of course and it is more difficult to secure these funds. But by and large I still prefer to be in academia than in industry because I have this freedom to explore, and if I do not want to do flow chemistry anymore I can change field and do something totally different. This is a freedom you only have in academia. I also love the fact that you travel a lot, you meet a lot of interesting people in many different parts of the world.

What would you like to say to the next generation of scientists?

I think the most important thing is that young people should follow their passion. If you end up in a job doing something you don’t like you will not lead a happy life and it will lead to frustration. Hopefully, my group come to the lab because they enjoy doing what they are doing.

Where can we find you in your spare time?

I like to travel, not only for business but also for pleasure. I like to scuba dive, my favourite spots are the Red Sea and the Great Barrier Reef.

If you weren’t a scientist, what would you be?

I think I’d like to be a writer. Now I only write scientific papers but sometimes I feel I could be tempted to write novels as well. I like to read crime novels. The creativity appeals to me – if you write a scientific paper you're very restricted by the content and format, so it would be fun to write something where I have complete freedom. There are of course examples of people who have turned authors, like Carl Djerassi who writes novels and plays. So that could be for the years to come perhaps.

And finally, do you have a message you’d like to shout out that’s close to your heart?

Scientific honesty and integrity are very important. There have been a couple of recent excellent publications in essay form – one is The seven sins in academic behavior in the natural sciences published in Angewandte Chemie. We see so many irreproducible results and retractions that it is important to teach our students that we have to abide by the rules of what is good science and demonstrate ethical behaviour. The pressure to publish more papers or get into Nature and Science should not overrule the basics of doing good science. We should focus on finding new things, and not only on putting a paper out as fast as possible. That I feel is important.