Silver nanoparticle-catalysed phenolysis of epoxides under neutral conditions: Scope and limitations of metal nanoparticles and applications towards drug synthesis

Abstract

Chemo- and regio-selective epoxide phenolysis is reported for the first time under neutral condition catalysed by silver nanoparticles. Other metal nanoparticles (e.g., Au, Pd, Cu, In, and Ru) are less effective. The choice of solvent is critical with 2-propanol being the best followed by DEF. Amongst various stabilisers used (surfactants, PEGs, tetra-alkylammonium halides) the tetra-alkylammonium halides are found to be the most effective (TBAF > TBAB > TBACl > TBAI). The role of the silver nanoparticles is envisaged as synchronous mode epoxide-phenol dual activation via a cooperative network of coordination, anion–π interaction, and hydrogen bond. The silver nanoparticles are recovered and reused for five consecutive times. The reaction has been used for the synthesis of propranolol and naftopidil as a few representative cardiovascular drugs.