Beilstein Journal of Organic Chemistry 2012-01-01

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.

Nan Wang, Ronghua Wang, Xia Shi, Gang Zou

Index: Beilstein J. Org. Chem. 8 , 227-33, (2012)

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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 ion-exchange 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.