Novelties of microwave irradiated solid–liquid phase transfer catalysis (MISL-PTC) in synthesis of 2′-benzyloxyacetophenone

Abstract

2′-Benzyloxyacetophenone is an important pharmaceutical intermediate for the manufacture of drugs used as diuretics, antihypertensive, platelet, antiaggregant, lipoxygenase, analgesics and prostaglandin, and for treatment of metabolic disorders. Microwave irradiation has been widely used for the rapid synthesis of a variety of compounds. In the current work, for the first time, novelties of low power microwave irradiated solid–liquid phase transfer catalysis, named as MISL-PTC, has been brought out in enhancements of the rates of selective O-alkylation of sodium salt of o-hydroxyacetophenone (OHAP) with benzyl chloride by using tetra-n-butylammonium bromide as a catalyst. The advantages of solid–liquid (S–L) PTC are that the reaction is conducted at controllable temperatures, the rates of reaction are increased by orders of magnitude and the reaction is 100% selective at 80 °C, in comparison with the liquid–liquid (L–L) PTC which is slow and produces by-products. The microwave irradiation further enhances the rates of reaction. The system elegantly forms a synergistic combination of S–L PTC and microwave irradiation. The mechanism based on homogeneous solubilization of solid resulting in the formation of an active ion pair with the nucleophile was found to prevail in the system. A new theoretical analysis is presented to determine both the rate constant and equilibrium constant from the same set of data. The reaction is intrinsically kinetically controlled. The Gibbs free energy for solid dissolution with anion exchange reaction could be also evaluated.