Stirring Effects in High Throughput Experimentation

• Sydney Ziemba, Biochemistry, University of Delaware

• Jessica Sampson, Department of Chemistry and Biochemistry, University of Delaware

Previous research has looked at stirring as a source of irreproducibility in large scale experimentation, and several groups have noted observing stirring effects in High-Throughput Experimentation (HTE). However, a focused study regarding stirring effects in HTE has yet to be completed. This warrants attention as significant variation in stirring across the plate can falsely “pass” or “fail” a reaction condition, since, when HTE is performed, often only a single replicate of a condition is run. This is done, especially in the pharmaceutical industry, to more rapidly find optimal reaction conditions for making a known product or screen for new products. In order to study stirring effects in HTE, the Buchwald-Hartwig amination was used as a test case due to its prevalence in pharmaceutical HT studies. With the goal of providing a broadly representative set of data, both homogeneous and heterogeneous reaction conditions were chosen, and studies were done on both a tumble stirrer, and a standard magnetic stir plate. Additionally, a variety of stir bar and reactor sizes and shapes were investigated. In order to observe both positive and negative variations in yield, reactions were stopped when, under ideal conditions, they would have achieved partial conversion. Yields were then determined by UPLC/MS, and compared. The resulting data can be used to inform how HT-reactions are set up going forward. When used alongside other techniques, this can help to reduce variability and error in HTE screening, and improve reliability of results.