Scale-up in microwave-accelerated organic synthesis.

Abstract

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 1 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 1-1 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.