The Development Of Simplified Microreactors For Use In Multi-Step Reaction Sequences

Abstract

This dissertation describes the development of simplified microreactors to be used in multi-step reaction sequences. Microreactors are a developing technology with numerous benefits and whose modular design permits multi-step reaction sequences to be performed in a continuous flow process. The first chapter discusses the physical properties of microreactors and describes how performing reactions in these miniaturized reactors leads to safer, more efficient and more selective chemical transformations. A brief discussion of multi-step reaction sequences already performed in flow will also be presented. These multi-step reaction sequences, however, rarely rely on catalysis to facilitate chemical transformations. This area therefore has room for great improvement. The next two chapters discuss the development and application of solid-supported catalysts to be used in flow. In the first of these two chapters, two catalysts are immobilized on a solid-support and used in a simplified flow reactor. These reactions proved to be more efficient than similar batch reaction and the catalysts were highly recyclable. The next chapter presents a supported TEMPO catalyst used to oxidize alcohols to carbonyl species. These three catalysts set the foundation for multi-step flow reaction to be potentially performed in the group. The ensuing chapter uses a flow reactor to facilitate a two-step click reaction starting from an alkyl halide, sodium azide and a terminal acetylene. This process proved to be high throughput and rapidly synthesized vast libraries of compounds to be submitted for biological testing. The next two chapters discuss the synthesis of the ibuprofen and atropine in flow. Initial studies were carried out to synthesize both of these drugs in flow as part of a project geared toward synthesizing drugs on-demand. Later, a continuous flow synthesis of ibuprofen was realized using a series of reactions in which excess reagents and byproducts were compatible with downstream reactions. Finally, on-going work to develop asymmetric, multi-step reaction sequences in flow will be discussed in which the majority of reaction steps utilize solid-supported catalysts.