(446h) Identification of Reaction Pathways Using in-Line Process Analytical Technology (PAT): UV-Vis Spectroscopic Approach

Metal nanoparticle-catalyzed reactions such as hydrogenation, cross-coupling, carbonylation, and hydroformylation reactions are the most widely used reactions in the pharmaceutical and fine chemical industries. The nanocatalysts experience specific catalytic pathways (i.e., homogeneous versus heterogeneous pathway) and considerable amount of leaching in the given reaction conditions. It has been challenging, however, to characterize the catalytic pathway. As of today, there is no operando spectroscopic technique that exists to monitor the size of functioning nanocatalyst. By exploiting localized surface plasmon resonance of catalytically relevant nanostructures, such as monometallic (e.g., Pd, Pt, Ni, Rh, Au, and Cu) nanoparticles and bimetallic core-shell (e.g., Ag-Pd) nanoparticles, we show that localized surface plasmon resonance (LSPR) spectroscopy can be used as platform to distinguish homogeneous and heterogeneous pathways and monitor the size of functioning nanocatalysts in nano-metal catalyzed reactions. This work is fundamental in providing a new method through which nanocatalystsstability can be traced and elucidate the catalytic pathway for a spectrum of pharmaceutical reactions. Furthermore, this sensitive, inexpensive, and robust spectroscopic approach can be potentially used as in-line process analytical technology (PAT) in pharmaceutical development and manufacturing.