Copper-Catalyzed Aerobic Alcohol Oxidation Into Nitriles And Aldehydes

The selective oxidation of alcohol into nitriles and aldehydes is one of the most important reactions in organic synthesis.Two new protocols for the copper-catalyzed alcohol oxidation into nitriles and aldehydes with the promotion of ligands have been developed to resolve the problems existed in the field of alcohol oxidation currently.The employments of the efficient ligands such as N-phenylglycine and ammonia make the oxidations of aromatic primary alcohols,allyl alcohols and heterocyclic aromatic alcohols with high yields and selectivity in organic and aqueous phase,using molecular oxygen or air as the terminal oxidants.Initially,the N,O-bidentate ligands amino acids are selected as alternatives of conventional N,N-bidentate ligands to evaluate the effects for the copper-catalyzed alcohols ammoxidation into nitriles.By systematic screening the various of natural amino acids,functionalized amino ac ids,copper catalysts,solvents,reaction temperature in the presence of aqueous ammonia(4.0 equiv.),the optimum reaction conditions are obtained as: substrates(1.0 mmol),CuI(5 mol%),TEMPO(5 mol%),N-phenylglycine(5 mol%),NaOH(10 mol%),NH3(aq.25-28% w/w,300 ?L,4.0 mmol),CH3OH(2.0 mL).The system shows excellent functional groups compatibility for a wide range of testing substrates and the nitriles can be obtained with hight selectivity.What'more,the present approach can be smoothly scaled up under laboratory conditions.Combining the preliminary results and related published researches,a possible reaction mechanism is proposed.Subsequently,a new system for copper-catalyzed selective alcohol oxidation has been explored,using aqueous ammonia as the simplest N-containing ligand in neat water.By systematic screening the reaction conditions,it can be found that the selective oxidation of alcohol into nitriles or aldehydes is achieved by changing the amoumt of aqueous ammonia.Under the optimum reaction conditions,the testing substrates undergo selective conversions to aldehydes in the presence of 7.9 mol% aqueous ammonia,while nitriles are obtained in aqueous ammonia(8 equiv.).The results of excessive ammonia reused experiments show that the conversion and selectivity do not deteriorate even decreasing the ammonia consumption to 3 equiv.after five circulations.