A scalable, continuous-flow process has been developed to implement a homogeneous Cu I /TEMPO catalyst system for aerobic oxidation of primary alcohols to aldehydes. This catalyst system is compatible with a wide range of alcohols bearing diverse functional groups. A dilute oxygen source (9% O 2 in N 2 ) is used to avoid flammable oxygen/organic mixtures. Residence times in the heated reaction zone can be as low as 5 min with activated (e.g., benzylic) alcohols. The method has been demonstrated with nine different alcohols, including one up to 100 g scale. This flow-based catalytic method exhibits significant advantages for aerobic oxidation of alcohols, including substantially shorter residence times and broader substrate scope relative to a Pd-catalyzed method that we reported recently.

A "tube-in-shell" membrane flow reactor has been developed for aerobic oxidation reactions that permits continuous delivery of O 2 to a liquid-phase reaction along the entire length of the flow path. The reactor uses inexpensive O 2 -permeable PTFE ("Teflon") tubing that is compatible with elevated pressures and temperatures and avoids hazardous mixtures of organic vapor and oxygen. Several polymeric materials were tested, and PTFE exhibits a useful combination of low cost, chemical stability and gas diffusion properties. Reactor performance is demonstrated in the aerobic oxidation of several alcohols with homogeneous Cu/TEMPO and Cu/ABNO catalysts (TEMPO = 2,2,6,6-tetramethyl-1-piperidinyl-N-oxyl and ABNO = 9-azabicyclo[3.3.1]nonane N-oxyl). Kinetic studies demonstrate regimes where the overall rate is controlled by the kinetics of the reaction or the transport of oxygen through the tube wall. Near-quantitative product yields are achieved with residence times as low as 1 min. A parallel, multitube reactor enables higher throughput, while retaining good performance. Finally, the reactor is demonstrated with a heterogeneous Ru(OH) x /Al 2 O 3 catalyst packed in the tubing.