Kinetics of Beckmann rearrangement of 4-hydroxyacetophenone oxime and acetophenone oxime catalyzed by TFA: a clean and reusable organocatalyst for industrial synthesis

Aromatic amides are important industrial and pharmaceutical intermediates and their synthesis via greener processes is an important goal for the industrial research. For Instance, the production of N-(4-hydroxyphenyl) acetamide (acetaminophen or APAP ) via the Hoechst-Celanese process is multistage and the various steps (Fries rearrangement of phenyl acetate, oximation of the 4-hydroxyacetophenone to the corresponding oxime (4HAPO) and the Beckmann rearrangement to the product) employ mineral acid and inorganic bases. A great improvement of the process, from an environmental point of view, could be the use of TFA as reusable acid catalytic system, avoiding the employment of mineral acid. TFA in acetonitrile as a solvent showed practically quantitative conversion and high selectivity in the Beckmann rearrangement of cyclohexanone oxime to caprolactam and the solvent catalytic system CH3CN-TFA is fully reusable. Here we present some results on the kinetic studies of the Beckmann rearrangement of 4HAPO to APAP and of acetophenone oxime (APO) to acetanilide (AA) in TFA. In both cases almost quantitative yield in the desired products are observed, but a different reaction profile can be observed. This behaviors could suggest two reactions with a different pathway but a detailed analysis of the apparent activation energy shows that in both are multistage reaction with different rate determining step. The suggested reaction mechanism is the same of the Beckmann rearrangement of the cyclohexanone oxime in a CH3CN-TFA systems proposed in a previous paper.