Direct Synthesis of 3-Arylphthalides Promoted by Eaton's reagent

A rapid method has been developed for the synthesis of 3-arylphthalides from readily available starting materials. We describe herein a direct approach based on a simple Friedel-Crafts condensation between an aromatic ester and an aldehyde promoted by a mixture of phosphorus pentoxide and methanesulfonic acid (Eaton's reagent) under metal and solvent-free conditions. Due to their similarity to cytosporone E (a natural antibacterial phthalide), some of the synthesized compounds were tested as antibacterial agents against methicillin-resistant strain of Staphylococcus aureus. A convenient solvent and metal-free approach for the synthesis of a large variety of 3-arylphthalides from aromatic esters and aldehydes, combined with the antibacterial activity evaluation of selected analogues of natural phthalides against methicillin-resistant strains of Staphylococcus aureus (MRSA). image