465076 Rapid Kinetic Profiling of Copper(I)-Catalyzed Alkyne-Azide Cycloaddition(CuAAC) Click Reactions Utilizing Inline IR, HPLC and MS

Wednesday, November 16, 2016: 10:10 AM
Franciscan A (Hilton San Francisco Union Square)
Kosi Aroh, Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA and Klavs F. Jensen, Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA

Since their discovery, a great deal of interest has been placed in understanding the CuAAC reaction mechanism. Early focus was on the number of copper atoms involved in the reaction pathway, but recent studies have shown under various circumstances that only unique copper centers catalyze the reaction1. To develop a mechanistic understanding of the reaction pathways and quantitatively describe the kinetics, it is essential to systematically scan a wide, multidimensional parameter space as efficiently as possible.

In this work, prior techniques for data collection in continuous flow systems2,3 are expanded upon to develop a robust method for rapid and efficient reaction monitoring. Rapid MS, HPLC and IR analytics provide inline means to generate a comprehensive quantitative understanding of the mechanism for most organic reactions. This new method is validated with the Paal-Knorr reaction before further application toward describing the click reaction. Various substrates were reacted and the kinetic contributions from several ligands were elucidated while limiting reagent consumption and overall experimental time. The results of this study demonstrates a robust, general method for systematic mechanistic studies in continuous flow systems.

1. L. Jin, D. R. Tolentino, M. Melaimi, G. Bertrand. Isolation of bis(copper) key intermediates in Cu-catalyzed azide-alkyne “click reaction”. Sci. Adv. (2015)

2. J. S. Moore and K. F. Jensen. “Batch” Kinetics in Flow: Online IR Analysis and Continuous Control. Angew. Chem. Int. Ed. (2014)

3. C. J. Welch, X. Gong, W. Schafer, E. C. Pratt, T. Brkovic, Z. Pirzada, J. F. Cuff, B. Kosjek. MISER chromatography (multiple injections in a single experimental run): the chromatogram is the graph. Tetrahedron Asymmetry (2010)

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