385710 Palladium Theory for Aqueous-Phase Catalyzed Cu-Free Sonogashira Couplings

Wednesday, November 19, 2014: 9:30 AM
304 (Hilton Atlanta)
Ria C. Domier1, Spencer Alaniz2, Jane N. Moore2, Kevin H. Shaughnessy2 and Ryan L. Hartman1, (1)Department of Chemical and Biological Engineering, The University of Alabama, Tuscaloosa, AL, (2)Department of Chemistry, The University of Alabama, Tuscaloosa, AL

Flow chemistry, important to the global chemicals and materials sectors, depends on the symbiosis between chemical reaction engineering and organic synthesis.  Chemistry and engineering principles are needed to design therapeutics and microscale devices for a broad cross-section of society problems.  Studying chemical reactions on-chip has advantages in fine chemicals and pharmaceuticals research and manufacturing. Engineering their continuous manufacture with microchemical systems reduces discovery times, solvent waste consumption, and the energy requirements for their preparation at laboratory and production scales, as compared to conventional batch-wise processing.  Significant quantities of chemical waste are generated in fine chemicals and pharmaceuticals manufacture relative to the mass of the reaction products formed that ultimately save lives and improve quality of life.  Most reactions involve solids as starting materials or products.  Handling solids in microsystems, perhaps the grandest challenge in the field, unveils opportunities for innovations of active particle handling techniques.  Alternatively, designing reactions that ensure solubility potentially avoids solids handling challenges.  Synthesis by aqueous-phase catalyzed couplings of aryl heteroatoms using palladium and hydrophilic ligand is a broad, versatile, and growing science.  As an example, the kinetics of an aqueous phase Pd-catalyzed, Cu-free Sonogashira coupling were investigated.  Evaluating the multiphase aqueous-organic reaction requires understanding of liquid-liquid transport, which was accomplished by assessing the relative ratio of the reaction rate to the diffusion rate through thin films: the Hatta number.  Our discovery that both deprotonation and carbopalladation mechanisms accurately describe the kinetics undergirds the importance of considering transport phenomena via reactor design principles in laboratory-scale batch and flow synthetic chemistry.  Discovery of ligand theory for such reactions not only enables accurate kinetic predictions, but it also broadly impacts ligand-transition metal interactions.  The palladium to ligand ratio and its magnitude relative to substrates is a global quantity in cross-coupling reactions.  Activation barriers similar in magnitude to density functional theory calculations of purely organic synthesis support that water as a reaction solvent could revolutionize the continuous flow manufacture of fine chemicals and pharmaceuticals by accelerating the kinetics and reduce solvent consumptions, while maintaining the solubility of inorganic salt by-products.  Partnerships between scientists and engineers are needed to drive innovations in flow chemistry using microchemical systems and chemical reaction engineering is key.

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See more of this Session: Multiphase Reaction Engineering I
See more of this Group/Topical: Catalysis and Reaction Engineering Division