Highly Selective Synthesis of Primary Amines via Self-Propagative Lossen Rearrangement

In 1872, Wilhelm Lossen discovered the rearrangement bearing his name when he observed that pyrolysis of O-benzoylbenzohydroxamic acid affords phenyl isocyanate. Since that report, it has been believed over the years that this rearrangement requires the preliminary activation of primary hydroxamic acids (RCO-NHOH) by using an equivalent or more amount of activating agents except harsh reaction conditions. In this account, our recent research on base-mediated self-propagative Lossen rearrangement of primary hydroxamic acids for the efficient and facile synthesis of primary aromatic and aliphatic amines is described. This rearrangement has several features including no external activating agents to be needed for promoting the rearrangement, less than one equivalent of base to be used, and a clean reaction in which only carbon dioxide is produced as a by-product. A self-propagating mechanism through activation of a hydroxamic acid by an isocyanate intermediate is proposed and elementary reaction steps, namely, chain propagation reactions are supported by experiments.