Microwave Flow Advancements

I have spoken about this area in the recent past, but some of the enhancements for flow chemistry has put some pressure on microwave engineers to push the envelope for large production scale chemistry. While batch has taken precedent, and there certainly is a place and need for that (med chem, kilo labs, scoping, etc), most will agree that microwave flow reactor development has been most discussed. With that, C-Tech industries has developed and put together some trials of their contribution to these developments. A quick look at their site will help you understand the thinking: 0.3 to 1l/hour flow with the capability of handling 250C and 30 bar of pressure and a production rate of >100 kg of product/day with an innovative way of delivering the required power to maintain a transfer over solvent and reactants moving through the piped system.

Examples of their work are easily downloadable from the website and include an article from Specialty Chemicals magazine, a case study from lab to plant, and a collaborative poster illustrating improvements in production scale and impurity profiles in Pd-mediated coupling reactions and a supported project aimed at process scale-up while minimizes and chemical method development. Developments of this nature will help sustain the technology as a choice in today’s chemical research and development. C-Tech in addition to development, has set opportunities for collaborative partnerships.

Microwave scale-up and scale-out: Feasible?

A number of commercial vendors and engineering groups have developed large scale batch reactors — so it always gets me thinking about the challenges with microwave technology in general: 1) penetration depth limits its’ usage 2) how to build a continuous flow microwave reactor and 3) transfer of technology. I value the field a great deal – it has offered a sustainable way to speed up and make a number of transformations doable. For small scale research and discovery, the ability to make large libraries quickly will always make this a preferred technology, and let’s face it, it has been around for awhile now.

Challenges: The penetration depth issue has been overcome in a couple of different ways (and I am sure there are more solutions out there that I don’t know about. 915 MHz can be used in batch and flow process, enabling the capability of having much larger reactor volumes. Sairem offers batch reactors up to 500L with a proprietary INTLI microwave transmission technology with both 900 MHz and 2.45 GHz frequencies for microwave synthesis — not sure what the specs are, but to be effective, the size isn’t the only factor which needs addressed — temperature and pressure also need to be high enough to cover the scope of the majority of the chemistry. Sairem isn’t the only game in town: Upscale microwave, out of Pennsylvania, has a couple of large batch reactor microwaves in the 20-50L range and is operating at a custom manufacturer (I have have posted feasibility studies on them before, see example below).

Kilo scale reactors are also available from Milestone and Anton Paar, which would make an excellent addition into CROs and kilo process groups in pharma and biotech chemistry research groups. As I mentioned, the value on the research side still lies in the small-scale approach, but the need to be able to produce kilos of material quickly is often stumbling block for traditional chemistry.

Continuous flow: One way to overcome microwave batch technology is to look into continuous flow. Easier said than done — the engineering, materials for the reactor design, temperature and pressure capabilities present some obstacles. For homogeneous organic synthesis, the have been a number of small scale approaches with glass, quartz or pyrex tubes inside a multimode cavity and even some reinforced Teflon reactors inside as well. I can think of 2 examples where proof-of-concept studies resulted in a viable, working microwave reactor that can be used in full scale production. The first example comes from the Cambrex Corporation and their reactor developed for in-house custom synthesis and manufacturing — you can read an announcement from early 2010 in Manufacturing Chemist. The capability of the instrument is a little on the low side for some chemistries but I am sure they put this to good use — and if you read through their material the big thing that stands out is the capability of running heterogenous metal-catalyzed reactions in full scale capacity. A separate intriguing design was published in Green Processing and Synthesis 2012, and involved a number of companies along with Oliver Kappe and his technology research team, coming together with the design, construction and implementation of a safe, high-capability flow reactor – again pictures are below — and the key features include an Al2O3 microwave reactor tube (310C/60 bar) and the ability to transfer microwave power efficiently through the tube. To illustrate some of the chemistry is shown below:

Clariant Produkte Deutschland GmbH, Innoturn GmbH, Püschner GmbH and Christian Doppler Laboratory for Microwave Chemistry (CDLMC) – University of Graz

Cambrex Continuous Flow CaMWave

UpScale Microwave – Floor large mw batch reactor

Pilot scale continuous flow mw reactor

Technology Transfer: The ‘scale-out’ from small scale to multi kg/day has been published and be a topic for another day. But it does mean that we can reflect on the need to continue to use small scale single mode and parallel and added-capability multimode instrumentation, because we can take the method and information and apply it to larger batch and mw flow without the problems of the past – and although, I shouldn’t mention it here I have to — there are a number of examples where a microwave method has been transferred back to conventional heating on a production scale level.

An upcoming post will include several microwave methods which have been easily tranferred to flow reactors – there will be some comparisons and thoughts on what we do with the studies with both technologies doing so well today. Happy Reading!