title: 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 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.
authors.affiliation: Department of Fine Chemicals, East China University of Science & Technology, Meilong Rd. 130, Shanghai, 200237, China. ; Tel: 86-21-64252390.
authors.forename: Nan
authors.initials: N
authors.lastname: Wang
authors.forename: Ronghua
authors.initials: R
authors.lastname: Wang
authors.forename: Xia
authors.initials: X
authors.lastname: Shi
authors.forename: Gang
authors.initials: G
authors.lastname: Zou