Anaerobic oxidation of non-activated secondary alcohols over Cu/Al 2 O 3 Federica Zaccheria, a Nicoletta Ravasio,* b Rinaldo Psaro b and Achille Fusi a Received (in Cambridge, UK) 6th September 2004, Accepted 1st October 2004 First published as an Advance Article on the web 19th November 2004 DOI: 10.1039/b413634a A liquid phase, transfer dehydrogenation reaction promoted by an 8% Cu/Al 2 O 3 catalyst allows complete conversion of secondary alcohols into ketones under very mild conditions and in short times without any additives. The development of catalytic methods for alcohol oxidation has been one of the most pursued targets in the last few years, due to the urgency of substituting stoichiometric oxidants used in the fine chemicals industry, often based on toxic metals, with oxygen or air. Very active copper based homogeneous systems have been set up, 1 whereas the heterogeneous ones mainly rely on the use of noble metals. 2 An interesting alternative to aerobic conditions is represented by the use of a readily available organic molecule instead of oxygen as hydrogen acceptor, thus overcoming safety concerns linked with the use of flammable solvents. However, only a few cases of liquid phase alcohols transfer dehydrogenation promoted by heterogeneous catalysts are known. 3 Recently two palladium based systems have been reported by Hayashi 4 and Baiker, 5 both active only in the oxidation of aromatic or allylic alcohols. Here we wish to report that a low loading supported copper catalyst (namely 8% Cu/Al 2 O 3 ) is very effective in selective oxidation of non-activated aliphatic secondary alcohols under transfer dehydrogenation conditions. Copper catalysts prepared with a non-conventional chemisorp- tion–hydrolysis technique have been shown to be active and very selective in a wide range of reductions, not only under catalytic hydrogenation conditions but also in hydrogen transfer from secondary alcohols. 6 In particular, a detailed study of the reduction of 4-tert-Bu-cyclohexanone exploring especially the effect of the donor alcohol, revealed the existence of a two-step mechanism based on the donor alcohol dehydrogenation followed by the substrate reduction. 7 These results and the need for heterogeneous and simple systems for the oxidation of hydroxyl groups, prompted us to investigate the activity of copper catalysts, in particular Cu/SiO 2 and Cu/Al 2 O 3 in alcohols dehydrogenation reactions. Both catalysts revealed very promising performances (Table 1) although in the absence of an acceptor an equilibrium situation between dehydrogenation and hydrogenation was reached. On the other hand if hydrogen is removed by venting the reactor at regular times (entries 2 and 4) it is apparent that the dehydrogenation reaction can go to completion. It seemed thus more effective to adopt transfer dehydrogenation conditions by exploiting a pivotal feature of these catalytic systems already expressed in other synthetic applications, 6,8 that is their specificity towards hydro- genation of a conjugated system in the presence of an isolated one. Thus, by adding styrene into the reaction mixture as hydrogen acceptor in equimolar ratio with respect to the substrate, complete oxidation of the desired alcohol was obtained in very short reaction times (entries 3 and 5), particularly over Cu/Al 2 O 3 . The by-product ethylbenzene is easily removed from the reaction mixture together with the solvent. A remarkable activity is observed for non-activated secondary alcohols, whereas under these conditions 1-octanol and 2-phenyl- ethanol were not oxidized nor did they give any secondary reaction. Competitive oxidation of cyclooctanol and 1-octanol gave . 97% cyclooctanone, 1-octanol being recovered unchanged, thus showing that this system can selectively oxidize secondary alcohols also in the presence of primary ones. Selected results obtained in the oxidation of aliphatic alcohols are reported in Table 2. *n.ravasio@istm.cnr.it Table 1 Dehydrogenation of 3-octanol under different conditions a Entry Catalyst t (h) Conv. % Selectivity % 1 Cu/SiO 2 48 60 100 2 b Cu/SiO 2 20 100 100 3 c Cu/SiO 2 3 100 100 4 b Cu/Al 2 O 3 12 84 100 5 c Cu/Al 2 O 3 1.5 100 100 6 Al 2 O 3 24 0 — a Alcohol (100 mg), catalyst (100 mg), untreated toluene (8 mL), 363 K, N 2 . b Reaction carried out by venting the reactor. c Reaction carried out by using styrene as H 2 acceptor. Table 2 Oxidation of of different aliphatic alcohols over Cu/Al 2 O 3 a Entry Substrate t (h) Conv. % Selectivity % 1 3-octanol 1.5 100 100 2 b 3-octanol 2.5 96 100 3 2-octanol 4 100 100 4 1-octanol 24 4 — 5 2,4-dimethylpentan-3-ol 6 100 100 6 Cyclohexanol 3 99 98 7 2-Me-cyclohexanol 3.5 99 100 8 3-Me-cyclohexanol 3 100 100 9 4-Me-cyclohexanol 1.5 100 100 10 4-tert-Bu-cyclohexanol 1.5 97 100 11 (2)-menthol 48 80 100 c 12 Neomenthol 6 97 100 c 13 Carveol 2.5 100 88 14 Cyclooctanol 0.5 100 100 15 Cyclododecanol 2 97 100 16 Adamantanol 1.5 100 100 17 2-phenylethanol 24 0 — a Alcohol (100 mg), styrene/substrate 5 mol/mol, catalyst (100 mg), untreated toluene (8 mL), 363 K, N 2 . b Catalyst pretreated at 453 K. c Menthone/isomenthone mixture. COMMUNICATION www.rsc.org/chemcomm | ChemComm This journal is ß The Royal Society of Chemistry 2005 Chem. Commun., 2005, 253–255 | 253