GEN How scalable is microwave chemistry?
Dr. Kappe A major weakness of microwave heating is the limited scalability. The penetration depth of microwaves into organic solvents at the typical frequency used in the laboratory is in the order of only a few centimeters. This means that it is difficult to construct and operate batch-type reactors that are able to process several hundred liters of volume, in particular, in the temperature/pressure regime of a typical small-scale microwave experiment.
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?
Dr. Kappe Most, if not all, pharmaceutical companies globally are using the technology on a discovery scale from mg to kg. I am not aware of a successful large-scale API production route that uses microwave technology so far, although, clearly attempts have been made and we may see significant progress over the next few years.
GEN Who are some of the leading suppliers of microwave reactors? Do you partner with them in any way?
Dr. Kappe Essentially, there are four globally active suppliers of laboratory-scale microwave equipment for synthetic chemistry: Anton Paar, Biotage, CEM, and Milestone. They share a competitive and still-expanding worldwide market that includes industry, academia, and government laboratories.
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?
Dr. Kappe Despite having achieved the status of an almost standard and routine technology in the past few years, the number of microwave users in synthetic chemistry laboratories is still comparatively small. There are probably several reasons for this, one certainly being equipment cost. More importantly, perhaps, is the fact that people like to keep doing things that they know work. Change, and trying something new, is always difficult and often requires a high activation barrier. It is imperative, therefore, that a new generation of scientists is exposed to this technology early on in their careers.
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.