TEMPO-functionalized mesoporous silica particles as heterogeneous oxidation catalysts in flow

Abstract

Organocatalysts immobilized on inorganic porous substrates possess fundamental benefits, e.g., a high catalyst/reactant ratio, easy scalability as well as work-up, and continuous processing. Here we report the development of a heterogeneous (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO) catalyst immobilized on mesoporous SiO₂ and demonstrate its feasibility in the oxidation of benzyl alcohol to benzaldehyde. Our catalyst system is based on commercially available mesoporous silica particles that are optimized for flow applications (LiChrospher® Si 100 from Merck). The transition from well-known silica materials like MCM-41 and SBA-15 to specialized high-performance materials such as the used LiChrospher® particles is of great value for getting closer to industrial applications on large scale. We functionalized the material by applying click-chemistry and employed a packed HPLC column for the investigation of the catalyst performance and stability in continuous flow. The material shows the best performance with low catalyst loadings. The catalytic activity can be improved significantly by conversion of the TEMPO radical to an oxoammonium salt prior to the reaction. The material is well suited for applications in continuous flow syntheses, as the spherical shape of the particles results in low back pressures. The organic catalyst produces yields up to 89% with a flow rate of 0.05 mL min⁻¹. The mild reaction conditions allow the use of the material in multi-step reactions. This option was demonstrated by combining the TEMPO-functionalized column with an aminopropyl-functionalized column and performing a TEMPO-mediated oxidation followed by a Knoevenagel condensation in a continuous flow setup for the first time. Long-term tests and post-catalytic analysis show a previously neglected decomposition pathway of TEMPO due to the co-catalyst.