Scale-Up in Microwave-Accelerated Organic Synthesis
Microwave-assisted organic chemistry has received strong exposure in the literature over the last decade, and nowadays more and more research chemists are successfully applying microwave technology to organic reactions on a small scale. However, the efficient application of this technology to cover the specific needs of larger-scale preparations, e.g., in a kilo lab, remains to be shown. We therefore initiated a study to investigate the scalability of microwave technology. Two different microwave systems designed for large-scale operation were evaluated in order to characterize strengths and weaknesses of each instrument with regard to scale-up. Special focus was directed on temperature/pressure limits, handling of suspensions, ability to rapidly heat and cool, robustness, and overall processing time. Based on the results of this study, a batch microwave reactor with a reaction volume of approximately 1.1 l was purchased and installed in the kilo lab. Several reactions have been performed successfully on a 50- to 100-g scale in our laboratory, showing that a scale-up from a 15 ml scale to a 1-l scale is feasible. In general, a significant reduction of reaction time was achievable, in some cases yields and selectivity were also improved. Nevertheless, a major weakness of the available systems is the limited vessel size, which is, in most cases, far below a suitable reaction volume required for work in a kilo lab.
KeywordsModel Reaction Microwave Heating Conventional Heating Microwave Device Additional Optimization
The author thanks Biotage (Uppsala, Sweden), Anton Paar (Graz, Austria), and CEM Corp. (Matthews, NC, USA) for their support and for the possibility to test their microwave reactors in the kilolab. He also thanks all the colleagues and people who were involved in this project for their input and the challenging discussions.
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