(497f) Rapid Kinetic Profiling of Copper(I)-Catalyzed Alkyne-Azide Cycloaddition(CuAAC) Click Reactions Utilizing Inline IR, HPLC and MS
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 â??click reactionâ?. Sci. Adv. (2015)
2. J. S. Moore and K. F. Jensen. â??Batchâ? 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)