Selectivity engineering in synthesis of 4-benzyloxy propiophenone using liquid–liquid–liquid phase-transfer catalysis

Abstract

4-Benzyloxy propiophenone is an important active pharmaceutical intermediate (API) used in the production of drugs such as Ifenprodil (N-methyl-d-aspartate receptor antagonist) and Buphenine (or nylidrin, a sympathomimetic and beta-adrenergic agonist). The synthesis of this molecule involves cumbersome and highly polluting routes. In the current work, synthesis of 4-benzyloxy propiophenone was achieved by reacting benzyl chloride with 4-hydroxy propiophenone and sodium hydroxide in liquid–liquid–liquid (L-L-L) phase-transfer catalysis (PTC) with tetra butyl ammonium bromide (TBAB) as the catalyst. The novelty of the L-L-L PTC over L-L PTC is that the catalyst forms a separate phase and can be separated easily and reused several times. L-L-L PTC intensifies the rates of reaction and is 100% selective toward 4-benzyloxy propiophenone. Thus, the goal of green chemistry—waste minimization—was achieved. The effects of various parameters on the rate of reaction were studied. A mechanistic model was proposed to deduce the kinetics.