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The catalytic activity of heterogeneous catalysts based on noble metals is investigated for the conversion of lignin to precursors of various commodity chemicals. Here we use a model compound containing a β-O-4 ether linkage to understand its cleavage mechanism and kinetics as analogous to that in lignin. Various parameters including temperature, pressure, solvent, and choice of metals and supports have been optimized to obtain the most practical and efficient conditions for industrial applications. It has been found that Pd is the most capable noble metal catalyst tested for β-O-4 cleavage compared to Pt and Ru. The support CeO2 gives the highest selectivity towards acetophenone (rather than hydrogenated products) when compared to other supports including both ‘‘reducible’’ (TiO2) and ‘‘irreducible’’ (Al2O3 and SiO2) metal oxides. The unique support effects of CeO2 when paired with Pd make it the most effective support. To optimize process temperatures, conversion of the model compound, 2-phenoxy-1-phenylethan-1-ol (PPE) was investigated at 50, 70, 90, and 110 °C under 5 bar H2. While the conversion of PPE was found to increase with temperature, we have found that increasing the pressure does not follow the same trend. When varying the hydrogen pressure between 5 and 50 bar at a constant 80 °C, the highest conversion (59%) after 4 hours is achieved at only 10 bar. Here, we propose a pressure (H2) dependent mechanism that involves balancing hydride and PPE on the catalyst surface to cleave the β-O-4 linkage in PPE to selectively form acetophenone, phenol, cyclohexanol, and cyclohexanone. Our results show interesting insights into the various interactions hydrogen has with aromatic substrates on the surface of metal nanoparticles and lead to the design and optimization of a catalytic reaction that can selectively produce commodity chemical precursors from renewable feedstock, such as polystyrene and Nylon-6.