Microchemical systems for rapid optimization of organic synthesis

Abstract

In the chemistry laboratory, the desire to use smaller quantities of material to minimize both reagent cost and waste generation has driven chemists to develop new experimental techniques. The current approach to small scale experimentation has mostly been a simple reduction in the size of batch reaction apparatus. Working with these smaller volumes has increased the efficiency of experiments by accelerating the typically time consuming processes of heating, filtration, and drying. Furthermore, when working with hazardous materials, smaller scales minimize the exposure of a chemist to toxic materials and enable easier containment of potentially flammable or explosive systems. The use of microfluidic devices has shown several improvements when compared to traditional batch synthesis. The precise control of reaction conditions enabled within the microreactor format has proved advantageous for a wide range of single and multiphase reactions. Also, unlike conventional bench-top batch reactions, continuous microreactors are capable of producing both analytical and preparative quantities of material by simply changing the amount of reactor effluent collected.

(cont.) The aim of this work was to harness the microsystem advantages of improved safety and process intensification while demonstrating both improved quality and speed of data collection, especially for chemistries that were challenging to explore using standard laboratory techniques. This work required improvements to reactor design, packaging technologies, and experimental techniques in order to use microreactors as a platform for rapidly determining optimum reaction conditions as well as reaction kinetics. Three model reactions were selected to highlight the advantages of microchemical laboratory tools. The synthesis of oligosaccharides served as an example of rapid profiling of the effects of temperature and reaction time. Microreactors improved reaction optimization by reducing waste and dramatically increasing the rate of data collection. High-pressure carbonylation of aryl halides was also explored to characterize the effects of pressure, temperature, and various substrates on product yields. With microreactors, previously inaccessible reaction conditions were explored thus obtaining improved insights into the reaction mechanism.

(cont.) Finally, the production of sodium nitrotetrazolate was used to demonstrate the improved flexibility and safety of a modular microchemical system. The kinetics and pH effects for each step of the synthesis of this energetic compound were measured. This system was also optimized so that the microreactors used to characterize the reaction could be run in parallel as a production method.