When Solids Stop Flow Chemistry in Commercial Tubing

Flow chemistry has emerged as the enabling field of high-throughput, data-driven discovery, and process chemistry, yet solids handling remains its key challenge. Insoluble salt by-products can stop flow, fluctuate reagent concentrations in reactors, and cost unexpected time and materials consumptions. The clogging of perfluoroalkoxy (PFA) tubing, stainless steel (SS) tubing, and a silicon microreactor by NaCl during a Pd-catalyzed amination using XPhos ligand was each studied. Our goal of understanding the appropriate reactor design provides in-depth analyses of constriction and mechanical entrapment. Calculations of Stokes number (St)>1 revealed that NaCl particle depositions were independent of the reactor materials. Analyses of the clogging time's dependence on the residence time (tau) and particle volume fraction (phi) discovered commercial tubing to be inadequate for the decoupling of the kinetics. The results prescribe why fabricated microreactors with on-chip analytics, particle formations and dissolutions, and without fluidic connections are solutions to discover and develop ubiquitous reactions that form inorganic salt by-products.