Engineering selectivity in novel synthesis of 3-(phenylmethoxy)phenol from resorcinol and benzyl chloride under liquid–liquid−liquid phase transfer catalysis

Abstract

Monobenzyl ether of resorcinol, namely, 3-(phenylmethoxy)phenol is used as an intermediate for the synthesis of various chemically and biologically active molecules. The synthesis of 3-(phenylmethoxy)phenol can be accomplished by using phase transfer catalysis (PTC), either as liquid–liquid (L−L) or solid–liquid (S−L) PTC. Creation of a third phase in a biphasic reaction leads to several advantages in this type of reaction. A catalyst rich middle phase is formed between the other two phases wherein the main reaction takes place in the liquid–liquid−liquid (L−L−L) PTC and this offers a number of advantages over L−L PTC in terms of intensification of rate, higher selectivity and the possibility to reuse the catalyst. It is an excellent way for waste reduction and improving profitability. The catalyst rich phase is recovered and reused to up to six times with little impact to reactivity. This also helps in waste minimization which is a major theme of Green Chemistry. In the current work, synthesis of 3-(phenylmethoxy)phenol was accomplished by the reaction of resorcinol with benzyl chloride using tetrabutylammonium bromide (TBAB) under liquid–liquid−liquid phase transfer catalysis (L−L−L PTC) at 90 °C. The studies cover the effects of various kinetic and process parameters which lead to enhancement in rates and selectivities. A theoretical model was developed and validated against experimental data. It follows zero-order kinetics in the mono-O-benzylation of resorcinol. There is 100% selectivity for 3-(phenylmethoxy)phenol with no discernible amount of bis-alkylated product detectable. O-Alkylation of hydroquinone and catechol were also studied using the same technique to realise the same high selectivity. The order of reactivity and apparent activation energy is as follows: hydroquinone > resorcinol> catechol.