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Micro reactors: industrial results

Posted on 24. April, 2012.

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Micro reactors and flow reactors have many advantages as tools in organic synthesis. A review in the April issue of Journal of Chemical Research describes how small reactor volumes enable reactions to be performed on an industrial scale more efficiently and safely than when using batch processes.

Micro reactors, flow reactors and continuous flow synthesis.

This review article explains the advantages of micro reactors and flow reactors as tools for conducting organic synthesis and describes how the technology may be used in research and development as well as production.  A selection of examples is taken from the literature to illustrate how microreactors enable chemists to perform their reactions more efficiently than when using batch processes.

Organic chemists have traditionally used batch reactors (test tubes, round bottomed flasks, stirred tanks etc) to conduct all synthetic organic chemistry.  Although automated equipment, such as combinatorial synthesisers for example, has started to be used in modern research laboratories, fundamentally the reaction is still conducted in batch mode.  However from a process chemistry perspective, a major problem observed with conventional batch technology is the failure to scale-up successful reactions; this is particularly problematic for highly exothermic processes.  In industry this often means redevelopment of synthetic routes on several occasions when transferring from laboratory, to pilot scale and then finally to production.  This is a both a time consuming and costly process.

More recently the chemistry community has introduced ‘continuous flow’ synthesis as an alternative to batch processing; however it should be noted that the petrochemical industry has always manufactured using continuous flow, albeit on a substantially larger scale.  A key advantage of flow reactor technology for the organic chemist is the ability to very accurately control reaction parameters.  For instance, the regulation of temperature and concentration is crucial in maintaining control over a reaction, not only to ensure selective product formation, but also from a safety perspective.  Due to the excellent heat and mass transfer, and predictable flow properties exhibited by flow reactors a high degree of reaction control is attainable.  For example, in traditional large-scale batch reactor vessels, fluctuations in temperature are difficult to correct, as any alterations made take time to have an effect on the reactor as a whole; in comparison, changes are observed almost instantaneously within flow reactors.  Along with increasing the rate of mixing, decreasing the channel diameter of the reactor results in an inherently high surface to volume ratio, allowing rapid dissipation of any heat generated over the course of a reaction.

The original term used to describe this research field was ‘micro reactor technology’ (MRT), however for newcomers this does not clearly enable one to assess what type of equipment is best suited for their application.  Consequently this review is split into sections on micro reactors, meso and flow reactors and finally production systems, to illustrate how MRT may be used in different applications ranging from small scale synthesis as well as research and development, all the way to production.  In each case selected chemical examples are used to illustrate the advantages of the technology; more detailed information is cited in review articles and books.

It is now well established that flow reactors enable reactions to be performed more rapidly, efficiently and selectively than batch reactions.  By optimising the residence time within the reactor, chemists are able to perform reactions that are very difficult to control in batch.  In addition, compared with conventional reaction methodology, the inherent safety associated with the use of small reactor volumes enables users to employ reaction conditions previously thought to be too hazardous for use within a production environment; such as extreme reaction conditions or the use/generation of ‘hazardous’ compounds.  Consequently, the types of reactions available to the R&D chemist increases through the use of this technology.   Over the last 20 years, micro reaction technology has progressed from proof of concept to the mainstream, where continuous flow processing is now being implemented at research, process and production stages by many pharmaceutical and fine chemical companies.  With the advent of commercially available micro and flow reactor equipment, there is now the opportunity for researchers to investigate how the technology can be implemented in a range of different applications.

Paul Watts(a)* and Charlotte Wiles(b)
a()Department of Chemistry, University of Hull, Cottingham Road, Hull HU6 7RX, UK
(b)Chemtrix BV, Burgemeester Lemmensstraat 358, 6163 JT, Geleen, The Netherlands
Doi: 10.3184/174751912X13311365798808

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Keywords: micro reactor, flow reactor, continuous synthesis, scale-up, photochemistry, electrochemistry, process chemistry