Synthesis of proton-ionizable acyclic, macrocyclic and macrobicyclic compounds containing one or two triazole groups

Abstract

New acyclic, macrocyclic and macrobicyclic compounds containing one or two proton-ionizable triazole groups are prepared and characterized. The series includes six podands, a macrocycle with one triazole and one pyridine unit in the ring, a bis-triazolo macrocycle with four pentafluorobenzyl substitutents, and two bis(crown ethers) with a triazolo group connecting the two polyether rings. The solid-state structure and solubility in supercritical carbon dioxide are determined for the bis-triazolo macrocycle with pendant pentafluorobenzyl groups. Neutral crown ethers and cryptands are widely employed for complexation and selective extraction of alkali metal cations, alkaline earth metal cations and trivalent lanthanide ions [1]. Macrocyclic polyethers with proton-ionizable functional moieties are interesting and important complexing agents for metal ion extraction. Compared with a neutral crown ether extractant, a crown ether with a proton-ionizable group has the advantage that metal ion transport into the organic phase does not require concomitant transfer of an anion from the aqueous phase. Therefore, the extraction efficiency is independent of the identity of the aqueous phase anion. Also, the stability of the cation-macrocycle complex is increased when the macrocycle is ionized [2].Two main strategies have evolved for incorporation of proton-ionizable functions into macrocyclic ligands, incorporation of i) proton-ionizable group(s) on the side arm(s) and ii) proton-ionizable group(s) as part of the macroring. Lariat ethers with pendant carboxylic acid [3], phosphonic acid monoethyl ester [4], hydroxamic acid [5], and, most recently, N-(X)sulfonylcarboxamide [6] groups as the proton-ionizable function on a pendant arm have been mostly developed in our laboratories. Also, Bradshaw and coworkers have reported a series of diaza-18-crown-6 compounds with pendant phenol and hydroxyquinoline units [7]. Macrocycles with 4-hydroxypyridine [8-13] and triazole [13][14][15][16][17] heterocyclic subunits within the macroring have been developed by Brandshaw, Izatt and their coworkers, de Mendoza and Torres and their coworkers [18][19][20][21][22][23][24][25] and others [26][27][28]. Podands [23][24][25][26][27][28][29] and polyaza macrobicyclic cryptands [24] with triazole subunits have been prepared, as well. Macrocycles with a single triazole unit in the macroring exhibit complexation selectivity with univalent metal ions, such as Ag + [30]; whereas macrocycles with two such triazole units form strong complexes with divalent metal ions [21,25]. Chiral dialkyl-substituted triazole-18-crown-6 ligands have been used for enantiomeric recognition of organic ammonium salts [31].