Selective TEMPO-Oxidation of Alcohols to Aldehydes in Alternative Organic Solvents

The TEMPO-catalyzed oxidation of alcohols to aldehydes has emerged to one of the most widely applied methodologies for such transformations. Advantages are the utilization of sodium hypochlorite, a component of household bleach, as an oxidation agent and the use of water as a co-solvent. However, a major drawback of this method is the often occurring strict limitation to use dichloromethane as an organic solvent in a biphasic reaction medium with water. Previous studies show that dichloromethane cannot easily be substituted because a decrease of selectivity or inhibition of the reaction is observed by using alternative organic solvents. Thus, up to now, only a few examples are known in which after a tedious optimization of the reaction dichloromethane could be replaced. In order to overcome the current limitations, we were interested in finding a TEMPO-oxidation method in alternative organic solvents, which is applicable for various alcohol oxidations. As a result, we found a method for N-oxyl radical-catalyzed oxidation using sodium hypochlorite as an oxidation agent in nitriles as an organic solvent component instead of dichloromethane. Besides the oxidation of aromatic primary alcohols also aliphatic primary alcohols, secondary alcohols as well as dialcohols were successfully converted when using this method, showing high selectivity towards the carbonyl compound and low amounts of the acid side-product.