The use of immobilized crown ethers as in-situ N-protecting groups in organic synthesis and their application under continuous flow

In addition to their high affinity for inorganic cations, crown ethers have been shown to efficiently sequester ammonium ions, forming a stable adduct via hydrogen bonding. Using this principle, several authors have reported the use of crown ethers as protecting groups for amines however to date, their widespread use has been somewhat precluded by the difficulties associated with removal of the crown ether from the resulting reaction mixture. In order to address this problem, we report the preparation of an immobilized 18-crown-6 ether derivative and its incorporation into a flow reactor, demonstrating the ability to use and recycle the reagent for the chemoselective O-acylation and alkylation of bifunctional compounds such as 4-(2-aminoethyl)phenol and 4-nitrophenol. (C) 2009 Elsevier Ltd. All rights reserved.