TEMPO-Catalyzed Continuous-Flow Aerobic Oxidations of Alcohols on Silica

Abstract

2,2,6,6′-Tetramethylpiperidine-N-oxyl (TEMPO) is a highly efficient oxidation catalyst, valued for its environmentally benign nature, particularly in comparison to transition-metal catalysts. Despite their merits, TEMPO-based catalysts are not notably cost-effective. Immobilization of TEMPO onto supports offers a promising strategy to overcome this limitation. In this work, we present the synthesis and application of immobilized TEMPO catalysts 2–5, prepared via a straightforward condensation reaction, for the aerobic oxidation of alcohols. These catalysts demonstrate remarkable activity for alcohol oxidations under continuous-flow conditions, employing nitric acid as the co-catalyst. Notably, catalyst 2 immobilized by COOH silica gel exhibits outstanding performance for the oxidation of benzyl alcohol by oxygen gas, achieving a turnover frequency (TOF) of 15 h⁻¹ and a turnover number (TON) exceeding 300. Catalyst 2 further demonstrates broad substrate scope, effectively oxidizing primary, secondary, and benzylic alcohols. Post-reaction analysis of spent catalyst 2 reveals that deactivation primarily stems from nitrosation of the N−O bond. Interestingly, the amide moiety remains intact despite the harsh acidic reaction conditions.