Cu-Catalyzed Aerobic Oxidation of Diphenyl Sulfide to Diphenyl Sulfoxide within a Segmented Flow Regime: Modeling of a Consecutive Reaction Network and Reactor Characterization

A continuous flow homogeneous Cu-catalyzed aerobic oxidation of diphenyl sulfide to diphenyl sulfoxide was investigated. The protocol utilized copper sulfate pentahydrate as catalyst, pyridine as ligand, molecular oxygen as oxidant, 2,2,6,6-tetramethyl-1-piperidinyl oxidanyl (TEMPO) as co-oxidant, and methanol as solvent. The continuous flow reactor system was characterized through a residence time distribution (RTD) study, showing that the flow reactor could be modeled as a plug flow reactor. The hydrodynamics of the system were simulated using computational fluid dynamics (CFD). The liquid slug length, bubble length and bubble frequency from the simulation closely corresponded to the experimentally-observed values. The volumetric mass transfer coefficient (k _La) was estimated by applying Higbie's penetration model for micro-scale diffusion. A reaction profiling approach was applied within continuous flow to generate experimental data to fit a consecutive reaction network for the monooxidation of diphenyl sulfide to the diphenyl sulfoxide and then the subsequent overoxidation to the diphenyl sulfone. The reaction network comprised of four kinetic parameters (A ₁, E _a1, A ₂ and E _a2). Three out of four of the fitting parameters could be estimated with less than 7% uncertainty and the fitted model closely correspond to the experimental data, with R ² = 0.994. The fit-for-purpose model was then used to explore the experimental design space in silico. The models were successfully validated in a scale-out experiment which was operated over 4 h collection time to give 72% conversion and 65% sulfoxide yield, corresponding to a selectivity of 91% and a throughput of 0.61 g·h ⁻¹.