Rapid Lewis Acid Screening and Reaction Optimization using 3D Printed Catalyst Impregnated Stirrer Devices in the Synthesis of Heterocycles

Abstract

We describe the development of Lewis Acid catalyst-impregnated 3D printed stirrer devices and demonstrate their ability to facilitate the rapid screening of reaction conditions to synthesize heterocycles. The SLA 3D printed stirrer devices were designed to fit round-bottomed flasks and Radleys carousel-tubes using our recently reported solvent resistant resin and using CFD modelling studies and experimental data, we demonstrated that the device design leads to rapid mixing and rapid throughput over the device surface. Using a range of Lewis Acid 3D printed stirrers, the reaction between a diamine and an aldehyde was optimized for catalyst and solvent and we demonstrated that use of the 3D printed catalyst embedded devices led to higher yields and reduced reaction times. A library of benzimidazole and benzothiazole compounds were synthesized and use of devices led to efficient formation of the product as well as low levels of catalyst in the resultant crude mixture. The use of these devices makes the process of setting up multiple reactions simpler by avoiding weighing out of catalysts and the devices, once used, can be simply removed from the reaction, making the process of compound library synthesis more facile.