Ion-exchange-resin-catalyzed adamantylation of phenol derivatives with adamantanols: Developing a clean process for synthesis of 2-(1-adamantyl)-4- bromophenol, A key intermediate of adapalene

Abstract

A clean process has been developed for the synthesis of 2-adamantylphenol derivatives through adamantylation of substituted phenols with adamantanols catalyzed by commercially available and recyclable ion-exchange sulfonic acid resin in acetic acid.The sole byproduct of the adamantylation reaction,namely water,could be converted into the solvent acetic acid by addition of a slight excess of acetic anhydride during the work-up procedure,making the process waste-free except for regeneration of the ionexchange resin,and facilitating the recycling of the resin catalyst.The ion-exchange sulfonic acid resin catalyst could be readily recycled by filtration and directly reused at least ten times without a significant loss of activity.The key intermediate of adapalene,2-(1-adamantyl)-4-bromophenol,could be produced by means of this waste-free process. © 2012 Wang et al. licensee Beilstein-Institut.