Rate intensive and selective etherification of vanillin with benzyl chloride under solid–liquid phase transfer catalysis by aqueous omega phase

Abstract

The alkylation of vanillin, containing three reactive groups, with benzyl chloride is challenging and can lead to both C- and O-alkylated products, particularly when liquid–liquid (L–L) phase transfer catalysis (PTC) is used. In the current studies, solid–liquid (S–L) PTC has been employed in the reaction of solid sodium salt of vanillin and benzyl chloride in toluene at 90 °C to make 4-benzyloxy vanillin, an ether, which is used as a perfume and also as a starting material for the synthesis of thalifoline, ephedradine as alkaloids and in synthesis of flavonoid compounds. The selectivity towards the desired product under S–L PTC is 100%. The rates of reaction are enhanced greatly by using trace quantities of water (the so-called omega phase (ω)) with 100% selectivity to the ether. Efficacy of various phase transfer agents such as TBAB (tetra-n-butyl ammonium bromide), TBAHS (tetra-n-butyl ammonium hydrogen sulfate), TPAB (tetra-n-propyl ammonium bromide), TEAB (tetraethyl ammonium bromide) and ETPB (ethyl triphenyl phosphonium bromide) was evaluated under otherwise similar conditions at 90 °C and explained. The order of activity was as follows: TBAB (maximum) > TBHS > TPAB > TEAB > ETPB (minimum). A theoretical model is developed to account for the enhancements in rates of reaction and selectivity to the ether. The kinetic constants have been evaluated and the apparent activation energy is determined as 9.64 kcal/mol. The results are novel.