Synthesis of neutral and proton-ionizable crown ethers

Cyclization studies show that the CS2CO3 instigated reaction of the dimesylate of triethyleneglycol with 2,2'-bis[4(5)-tert-butyl-6- hydroxyphenoxy]-ethyl ether in MeCN is the best available method for preparation of sym-di[4(5)-tert-butylbenzo]-21 -crown-7. The lipophilicity and substitution pattern of hydrocarbon substituents are varied in a series of novel lipophilic 18-crown-6 compounds. Two synthetic methods are used. The first involves cyclization of a functionalized primary bis-hydroxy intermediate with its ditosylate. The second method implements a DMF-THF(4:1) solvent mixture to facilitate the cyclization of functionalized vicinal diols with the ditosylates of polyethylene glycols.

The synthesis of a series of proton-ionizable crown ethers is described, lonizable pendant arms are attached by alkylation and subsequent hydrolysis, if appropriate, of hydroxy- and (hydroxymethyl)crown alkoxides with BrCH2C02H, BrCH2C02Et and CH2=CHCN. The (hydroxymethyl)crown ethers are derived by hydroboration-oxidation of novel vinylidene crown ethers, which are produced by cyclization of methallyl dichloride and bisphenols.

A series of proton-ionizable azacrown ethers are synthesized by incorporation of a tosylaza group into a bisphenol that is cyclized with epichlorohydrin. The N-tosyl hydroxycrown ethers are then alkylated with BrCH2C02H or BrCH2C02Et. The ring nitrogen is alkylated with bromodecane in one compound and with BrCH2C02Et in another.

Two di(proton-ionizable) crown ethers are prepared by alkylation of a primary amine substituted dibenzo-16-crown-5 with 2 equivalents of BrCH2C02Et followed by basic hydrolysis.