Acid-Catalyzed Hydrolysis of N-Hydroxyacetanilides: Amide Hydrolysis vs N-O Bond Heterolysis

Article abstract of DOI:10.1021/jo00252a003

Although it has been widely assumed that N-hydroxy-N-aryl amides decompose in acidic solution by acid-catalyzed N-O bond heterolysis, we have found that the N-hydroxyacetanilides 1a-e largely decompose by the alternative amide hydrolysis pathway.The immediate products of hydrolysis, the hydroxylamines 2a-e, can be detected by direct or indirect methods, but these materials also decompose via the Bamberger rearrangement under the reaction conditions.Only the p-EtO- and p-MeO-substituted N-hydroxyacetanilides (1a and 1b) exhibit any sign of N-O bond heterolysis, and only as a minor component (ca. 7percent) of the overall hydrolysis.No change in mechanism could be found for 1d in H2SO4 solutions as concentrated as 9 M.The lack of reactivity of 1a-e to N-O bond heterolysis is largely due to unfavorable protonation of the OH group.Protonation of the carbonyl oxygen is favored over the hydroxyl oxygen by ca. 7 orders of magnitude.