A base-free hydroxylaminolysis protocol promoted by ZnO in deep eutectic solvents

Abstract

There are many protocols for the preparation of hydroxamic acids from their corresponding carboxylic esters or carboxylic acids, but as for ester precursors, strong bases are usually indispensable. Herein, an environmentally benign and scalable protocol was developed to prepare hydroxamic acids from their ester precursors in deep eutectic solvents (DESs). The distinguishing features of this method were a base-free process and promotion by zinc oxide which then also facilitated the separation of the product via chelating with it to form precipitates. The work-up was designed as an integrated solution of product purification and reagent recovery, which improved resource efficiency and reduced PMI and WI. Various hydroxamic acids, including enantiomerically pure hydroxamic acids, were prepared in good to excellent yields via the protocol and the recyclability of both zinc oxide and DESs was proved via the preparation of vorinostat at the gram scale for at least four consecutive runs.