(616e) Overcoming the Challenges of Bridging and Constriction During Pd-Catalyzed C-N Bond Formation In Microreactors Conference: AIChE Annual MeetingYear: 2010Proceeding: 2010 AIChE Annual MeetingGroup: Food, Pharmaceutical & Bioengineering DivisionSession: Reaction Engineering in API Synthesis Time: Monday, November 8, 2010 - 2:10pm-2:35pm Authors: Hartman, R. L., The University of Alabama Naber, J. R., Massachusetts Institute of Technology Buchwald, S. L., Massachusetts Institute of Technology Jensen, K. F., Massachusetts Institute of Technology The transition from traditional batch to continuous-flow production in fine chemical manufacturing requires a comprehensive understanding of how to handle solids. Solids can participate in chemical reactions as reactants, products, by-products, and/or catalysts. Strategies for dealing with solids are necessary in both the laboratory and production environments covering the range from micro- to macro-scales. In this study, we investigated 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 important class of reactions. Based on these observations, several approaches were engineered to overcome the challenge of plugging and to enable the continuous-flow synthesis of a biaryl amine. We found that bridging could be eliminated with acoustic irradiation while constriction was managed via fluid velocity and the prediction of growth rates. Consequently, the present work establishes the groundwork for further continuous-flow studies on both the mechanisms responsible for clogging and synthetic applications of Pd-catalyzed cross-coupling reactions. Although the handling of solids in microsystems offers new opportunities for chemical reactions that were previously difficult or not attainable, moving forward is not without challenges. Many of the routes to APIs involve solids, and strategies for handling other types will prove useful for developing efficient flow-based syntheses. Furthermore, the need to operate in both the micro and macro scale reactors warrants a deeper understanding of solids handling. Additionally, deposition and growth on peripheral equipment, reactors, instruments, and transfer tubing surfaces is an important consideration that needs to be addressed when flowing salts suspended in organic solvents. Strategies and techniques to remove such deposits will find utility on all scales.