Process Development of CuI/ABNO/NMI-Catalyzed Aerobic Alcohol Oxidation

An improved Cu/nitroxyl catalyst system for aerobic alcohol Oxidation has been developed for th e Oxidation of functionalized primary and secondary alcohols to aldehydes and ketones, suitable for implementation in batch and flow processes. This catalyst, mhich, has been deinonstratednr a >50 g scale batch reaction, addresses al-lumber of process limitations associated with a previously reported ((MeO)bpy)Crit/MNO/NIVII, catalyst system ((MeO)bpy = 4,4'-Cinnethoxy-2,2'-bipyridine, ABNO = 9-azabicyclo[3.3.1]noriane NMI = N-methylimidazole). Iinportairt catalyst iiodiflcations include the replacement of [Cu(MeCN)4]()Tf with alower-cost Cu source, CriI, reduction of the ABNO loading to 0.05-0.3 mol%, and use of NMI as the only ligand/additive (i.e, without a need for (MeO)bpy). Use of high flash point solvent, N-methylpyrrolidone, enables safe operation in batch reactions with air as the oxidant For continuous-flow applications compatible with elevated gas pressures, better performanCe is observed With acetonitrile as the solvent.