Synthesis of nonsteroidal drugs with anti-inflammatory and analgesic activities with zeolites and mesoporous molecular sieve catalysts

A series of molecules with nonsteroidal anti-inflammatory and analgesic properties were synthesized through a chemical route involving the oximation of acetophenone derivatives, followed by the solid acid-catalyzed Beckmann rearrangement to give the corresponding amides. Microporous and mesoporous molecular sieves, as well as a delaminated (ITQ-2) zeolite, were studied as catalysts, and excellent activity and selectivity for amides were achieved when accessibility of the reactants to the active sites and the surface polarity of the catalyst were optimized. When the number and size of ring substituents increase in the product, only ITQ-2 and MCM-41 give high activities and selectivities. The order of activity observed, when the size of the oxime increases, can be reversed with respect to the obtained conventionally, because of a transition-state shape selectivity in the pores, where the bulkier substituents in the anti-position are impeded from migrating.