Development and Application of a Continuous Microwave Reactor for Organic Synthesis

Reproducibility and Scalability of Microwave-Assisted Reactions

“…Thus, the further development of large reactors is required, at least on the pilot plant scale to enable multikilogram production of lead compounds. It was not until the mid-1990s that the issue of scale-up was first investigated (Raner et al, 1995;Cablewski et al, 1994;Roberts & Strauss, 2005). Since that time, a significant number of prototypical and commercial microwave scale-up reactors have been reported, for both batch and continuous operation, and most of these were described by chemical engineering groups.…”

“…It was recognised early on in the development of microwave reactors that flow-based applications offered tremendous advantages in terms of processing capabilities. Two of the early pioneers of microwave chemistry extolled the virtues of continuous microwave reactors as early as the 1990s (Chen et al, 1990;Cablewski et al, 1994). However, such pioneering developments received little recognition or further development due to a combination of inferior technology, poor quality manufacture and the fact that the adoption of continuous flow protocols was in direct contradiction to the emerging, at that time, Combinatorial Chemistry (small scale multiparallel batch processes).…”

“…Additionally, the combination of such processing techniques with the enabling technology of immobilized reagents, scavengers and catalysts to effect multi-step synthetic transformations has allowed the generation of novel pharmaceutical architectures and more complex natural products. One of the first successful examples of scale-up was developed by Strauss (Cablewski et al, 1994). These authors prepared hundred gram quantities of a cyclopentenone intermediate using the continuous microwave reactor that they developed themselves (Scheme 16).…”

Microwave-assisted synthesis of cycloalkanespirohydantoins and piperidylspirohydantoins as precursors of restricted α-amino acids

“…In this sense, microwave irradiation in chemical reactions has been recognized for increased reaction rates, better yields and cleaner products. 9,10 Additionally, working with sealed vessels for shorter times reduces the exposure to toxic substances. Several methods for the preparation of diverse hydantoins have been reported using microwave-assisted conditions, 11 but to the best of our knowledge, the synthesis of cycloalkanespirohydantoins 3 and piperidinespirohydantoins 4 has not been reported under microwave-assisted conditions.…”

Development of Predictive Tools for Optimizing Organic Reactions

“…This limits the choice of solvents and subsequent removal and recycling can create problems. Continuous and batch microwave reactors developed by our group [2,3], enable the use of low-boiling solvents under pressurized conditions to speed reactions and facilitate product isolation. With these systems, processes that are notoriously sluggish by traditional methods have been performed faster and in higher yield.…”