Atom-efficient benzoin condensation in liquid–liquid system using quaternary ammonium salts: pseudo-phase transfer catalysis

Abstract

Benzoin condensation is a reaction of great commercial interest wherein two aromatic aldehydes are condensed to give benzoin (2-hydroxy-2-phenylacetophenone) product. Theoretically it is 100% atom economical. Several routes are used amongst which the metal cyanide catalysed reaction in homogeneous medium using alcohols as solvent is very popular. In the current work, benzoin condensation (dimerization) of two benzaldehyde molecules was carried out to give 2-hydroxy-2-phenylacetophenone (i.e., benzoin), in a biphasic catalytic system containing sodium cyanide and a phase transfer catalyst at 80 °C. Efficacy of various phase transfer agents such as tetra-n-butylammonium bromide (TBAB), tetramethylammonium bromide (TMAB), ethyltriphenylphosphonium bromide (ETPB), and tetrabutylammonium hydrogensulfate (TBAHS) was evaluated under otherwise similar reaction conditions. Use of two immiscible phases keeps contamination of cyanide ion in the organic phase negligible, and hence workup procedures are simpler. Under standard reaction conditions, with TBAB as catalyst, 75% conversion with >95% selectivity was obtained. Also, the aqueous phase was found to be reusable up to three times with good activity. An insight is provided as regards the actual mechanism. A kinetic model is developed on the basis of the experimental findings. Hitherto unknown facets of benzoin condensation are discussed with proper theoretical and experimental proof. This reaction is not the so-called phase transfer catalysis since there is no transfer of ion pairs once the reaction is initiated by the quaternary ion pair. The overall reaction is second order in benzaldehyde and first order in the quaternary ammonium salt of the cyanide ion. This is the first example of pseudo-phase transfer catalysis. The aqueous phase is reusable, unlike the traditional phase transfer catalysis procedures.