The mechanism of acylation of neutral Oalkyl benzohydroxamates. The formation of (Z)-acetic O-benzylarylhydroximic anhydrides and their conversion to O-benzyl N-acetylarylhydroxamates

Abstract

The acetylation of O-benzyl benzohydroxamates by acetic anhydride and pyridine in organic solvents is shown to proceed by the primary formation of (Z)-acetic O-benzylhydroximic anhydrides which rearrange, either in the presence of the acetylation reagent or in the presence of tertiary nitrogen bases, AcO^–, or Br^–, to the more stable O-benzyl N-acetylbenzohydroxamate isomers: AcO^– is a better catalyst than pyridine for this reaction by a factor of ca. 1 300.

The formation of (Z)-acetic O-benzylbenzohydroximic anhydrides follows the equation Rate =k₃[hydroxamate]-[Ac₂O][pyridine], and probably involves S_N2 attack of the hydroxamate on the acylpyridinium ion. The nucleophilic catalysed conversion of the (Z)-acetic O-benzylhydroximic anhydrides to the corresponding N-acetyl isomers follows Rate =k₂[anhydride][nucleophile], and proceeds by a two-step intermolecular S_N2 process involving O-benzyl benzohydroxamate anions and an acetylation reagent as intermediates. The corresponding conversion in the presence of the acetic anhydride–pyridine acetylation reagent results principally from catalysis by the pyridine component, but for (Z)-acetic O-benzylhydroximic anhydrides bearing electron-donating substituents in the benzene ring electrophilic catalysis by the acetylating agent is also apparent. The (Z)-acetic O-benzylbenzohydroximic anhydride obtained from the acetylation of O-benzyl benzohydroxamate is considered to be the kinetically controlled product and the N-acetyl isomer the thermodynamically controlled product.