Selectivity Engineering of Phase Transfer Catalyzed Alkylation of 2‘-Hydroxyacetophenone:  Enhancement in Rates and Selectivity by Creation of a Third Liquid Phase

Enhancements in rate of reaction and selectivity of the desired product in biphasic reactions are achieved by creating a third liquid phase, under appropriate conditions, where the third liquid phase is the locale of the main reaction, having a dramatic effect on product distribution in complex chemical reactions. Thus, in the case of phase transfer catalysis (PTC), conversion of liquid−liquid (L−L) PTC into liquid−liquid−liquid (L−L−L) PTC is of considerable techno-commercial interest resulting in waste minimization which is a major theme of green chemistry. Etherification of 2‘-hydroxyacetophenone with 1-bromopentane, under traditional liquid−liquid phase transfer catalysis, results in loss of catalyst. However, the transformation of two liquid phases into three liquid phases (L−L−L) PTC leads enhancement in rates by orders of magnitude, with 100% conversion of the limiting reactant 1-bromopentane and 100% selectivity to 2‘-pentyloxyacetophenone. This strategy eliminates separation problems and results in high reaction rates reducing the total reaction time. Moreover, the catalyst-rich third phase is recycled more than 7 times without loss in activity. The kinetics of the reaction are studied in great detail. There is a substantial reduction in activation energy under L−L−L PTC vis-à-vis L−L PTC, where the locale of the reaction is shifted from the organic phase to the third phase.