Application of Ionic Liquid Halide Nucleophilicity for the Cleavage of Ethers:  A Green Protocol for the Regeneration of Phenols from Ethers

Abstract

We have used the high nucleophilicity of bromide ion in the form of the ionic liquid, 1-n-butyl-3-methylimidazolium bromide ([bmim][Br]), for the nucleophilic displacement of an alkyl group to regenerate a phenol from the corresponding aryl alkyl ether. Using 2-methoxynaphthalene (1) as a model compound, we found that the combination of ionic liquid [bmim][Br] and p-toluenesulfonic acid with warming effected demethylation in 14 h, affording the desired product 2-naphthol (2) in good yield (97%). Various other protic acids (MsOH, hydrochloric acid (35%), dilute sulfuric acid (50%)) could be used as a proton source in this demethylation reaction. Under the same conditions, cleavage of alkyl alkyl ether 2-(3-methoxypropyl)naphthalene yielded mixture of corresponding 2-(3-bromopropyl)naphthalene and 2-(3-hydroxypropyl)naphthalene. Dealkylation of various aryl alkyl ethers could also be achieved using significantly reduced (i.e., stoichiometric) amounts of concentrated hydrobromic acid (47%) in the ionic liquid. Both procedures afforded the desired products in moderate to good yield; however, cleavage of aryl alkyl cyclic ether, 2,3-dihydrobenzofuran, resulted in low yield of the desired product o-2-bromoethylphenol. The convenience of this method for ether cleavage and its effectiveness using only a moderate excess of hydrobromic acid make it attractive as a green chemical method.

Michael Additions of Methylene Active Compounds to Chalcone in Ionic Liquids without any Catalyst: The Peculiar Properties of Ionic Liquids

“…It is of interest to note that the higher nucleophilicity of halide anions in IL than in conventional solvents was described by Chi et al, [38][39][40] and for water by Kim. [41] The higher nucleophilicity of halide anions in ionic liquids was made questionable in papers by Welton [42,43] and Landini. [44] Landini [44] proved that the nucleophilicities of halide ions and the azide ion in [hexmim]PF 6 are comparable with their nucleophility in methanol and is slightly lower than in DMSO.…”

Synthesis and Evaluation of Estrogen Receptor β -Selective Ligands: Fluoroalkylated Indazole Estrogens

“…The ether-protected fluoropropyl compound 10a was prepared from the tosylated precursor 9a, using TBAF· 3H 2 O. However, when we tried to deprotect methyl ether groups using various demethylation reagents such as BF 3 17 as well as others (Scheme 1), we were unable to obtain the desired fluorobisphenol without also cleaving the C-F bond. This necessitated a change to a more easily cleaved protecting group.…”

Halogenation of organic compounds in ionic liquids

“…This observation seems contradictory to the findings of Chi et al, namely that the increased nucleophilicity of bromide ion in imidazolium-based ILs enabled nucleophilic displacement of an alkyl group from the corresponding aryl alkyl ethers to form phenols. 125 …”