Overcoming the challenges of solid bridging and constriction during Pd-catalyzed C-N bond formation in microreactors

We investigate the mechanisms that govern plugging in microreactors during Pd-catalyzed amination reactions. Both bridging and constriction were shown to be important mechanisms that lead to clogging in our system and greatly limited the utility of microsystems for this class of reactions. On the basis of these observations, several approaches were engineered to overcome the challenge of plugging and to enable the continuous-flow synthesis of a biarylamine. Bridging could be eliminated with acoustic irradiation while constriction was managed via fluid velocity and the prediction of growth rates.