Optimisation of the Suzuki-Miyaura-coupling and conversion from batch to continuous flow with microwaves as energy source

Abstract

The use of microwave radiation as an energy source for chemical reactions is the last few years a popular method for fast and efficient syntheses. This master's thesis, in collaboration with Lab4U and Janssen Pharmaceuticals, has two objectives. First, the influence of microwave energy on the Suzuki-Miyaura coupling is investigated, and second, the Suzuki reaction carried out in a microwave-assisted flow process is compared with batch processing. The Suzuki-Miyaura reaction in this study combines iodobenzene and phenylboronic acid to form biphenyl. In order to investigate the influence of microwave energy, the reaction kinetics and biphenyl yields are examined in a conventional reactor and microwave reactor. In addition, a microwave-assisted flow system and a conventional flow system are designed to compare the conversions between both flow systems and also with batch processing. At the same temperature profile and residence time, the conversions in batch with conventional energy are 1.20 times higher than the conversions obtained in the microwave reactor. A possible explanation, is a different mechanism in the transmetalation step when using microwaves. Although microwaves are less suitable for the reaction kinetics of the Suzuki-Miyaura reaction, the conversions obtained in the microwave-assisted flow are 3.15 times higher than in the conventional flow. This is due to the rapid heating effect of microwaves so a higher temperature is achieved within the same residence time, which is favorable for the reaction kinetics.