Microreactors in Organic Chemistry and Catalysis, Second Edition (2013)
11. Industrial Microreactor Process Development up to Production
Ivana Dencic and Volker Hessel
This chapter discusses industrial applications of microprocess technology. Industry is not very active in publishing because of confidentiality reasons and, even besides this, has also no direct need for and benefit from creating such public profile in the same way as academics. Thus, one cannot expect that the ongoing developments can be shown with a similar degree of completeness, clarity, and detailedness, as this is possible for reviewing scientific contributions from academy with a wealth of peer-reviewed papers. Especially the information of major interest, what has been transferred to production and how do the companies make profit with the new technology, is usually kept secret. Thus, it has to be accepted that in the following some major information is missing among the chapters and that this is only the tip of the iceberg. Also, the sources of information are not as validated as the refereed literature, since in some cases one has to rely on interviews and other information given in a magazine format.
Knowing these shortcomings, the contents were grouped in sections on industrial mission statements, laboratory process development, pilot plants, and chemical production. For the process development issue papers were also considered with industrial coauthors, assuming that the work was (partly) done under industrial perspective and reflects fields of interest and activity of industry.
11.1. Mission Statement from Industry on Impact and Hurdles
Fine chemistry is the current major application area of microprocess technology. Lonza in Visp, Switzerland, a leading company in life science markets, has a goal to pursue microreactor technology and bring this technology as a standard method for large-scale production: “The question of whether microreactors are going to be used in the future, I think this is already answered ‘yes’ [1]. The open question is what per cent of the market in fine chemicals they will take.”
“The question of whether microreactors are going to be used in the future, I think this is already answered ‘yes’.”
Dominique Roberge, Lonza
Georg Markowz, Senior Process Engineer at Evonik Degussa, says “We believe in the potential of microchannel process technology both as a development tool in the lab and for production technology.” Ralf Pfirmann, Business Director at Clariant Pharmaceutical Fine Chemical Business, summarizes some of the primary effects of microreaction engineering and adds “Use of microreactors in pharmaceutical synthesis...much higher yields, with higher selectivities, and with economics therefore not possible.” [2]. Fabian Wahl, Global Director Corporate Development Analytical Business at Sigma-Aldrich, comes to the secondary effects and adds “...allowing far more precise reaction control and far better product quality control than can be achieved with conventional reactors” [3]. Wahl adds that about 800 out of the 2000 reactions in Sigma-Aldrich's portfolio are suited for microreactor processing, with no or only minor process modification. For the microreactor cases studied so far, reduction of reaction time and cost were major drivers. An application is especially seen in the Sigma-Aldrich's custom synthesis business with fast process development as prime goal. Wahl expects a 40% reduction in process development time by using microreaction technology. Tony Wood, Vice President and Worldwide Head of Medicinal Chemistry for Pfizer, Sandwich, UK, adds “What's interesting to me is the opportunity to pursue fields such as electrochemistry or photochemistry. That would enable us to functionalize molecules in a quite different way from mainstream transformations.” [1]. Former Dow corporate leader Jon Siddall points out: “Microchannel technology may allow us to reduce costs or otherwise improve the process for making an essential commodity of world commerce...the irony of making large-volume chemicals in small-volume reactors is unmistakable.” [4].
Besides the technical challenges, one still has to take care of the soft factors, which is the human personnel that requires a change of mindset. “You are in a small, innovative team in an established company that has more than 100 years' experience in chemical production and you want to change things – there are some barriers beyond the technical,” says Dominique Roberge from Lonza [1]. Luca Mantovani, President of the Division's Pharmaceuticals and Exclusive Synthesis Unit at DSM, explains the customers-based need for microreactor technology: “Outsourcing trends favor companies with specialized technologies, which for DSM include microreactors, biocatalysis, and energetic reactions. DSM has invested in sophisticated technologies that have gained credibility...” [5].
Proving the potential of microprocess technology for large-scale and bulk chemical production, in the past 3 years a number of large-scale projects have started with the aim of realizing “new, intensified process and plant concepts for speeding up market penetration, enhancing the product life cycle, and improving sustainable production.” PILLS (process intensification methodologies applied to liquid–liquid systems in structured equipment), INVITE (innovation, vision, technology), and F3 factory (future–fast–flexible factory) are some of them [6]. “Today we witness a moment of innovation for sustainable chemistry. A dream of many of you sitting here has finally come true,” said BTS CEO Dr. Dirk Van Meirvenne during the opening of the F3 project [7].
A facility incorporating continuous-flow and microreactor technology, “Factory of Tomorrow,” is being constructed at Lonza's main site in Visp, Switzerland. The plant offers expedited development and technology transfer compared with standard batch-based production. The plant feautures Lonza's FlowPlate™ microreactors enabling faster changeover of processes and efficiencies in production and cleaning and is planed to operate from mid 2012 [8].
A Canadian firm, SBI Fine Chemicals, is out to prove that continuous microreactor techniques can also be used on a larger scale. For that purpose, SBI is building a biodiesel demonstration plant in Edmonton, Alberta, that can make 20 l of the fuel per minute from a variety of vegetable oils [9].
Sigurd Buchholz, in his presentation at IPIT Symposium 2011, explained the development from microreaction technology to flow chemistry: Continuous processing is an enabling technology for the preparation of tricky molecular targets and scalability must be implemented at early stage into the whole process development. According to him, innovative modular engineering at Bayer Technology Services leads to significant progress for chemical products [10].
“Chemical production need not always take place in huge plants...Because small is profitable – not only for new products and volatile markets, but whenever time-to-market is the key to success.” is a good introductory statement from the Evonik magazine [11].