Synthesis of lipophilic crown ethers with pendant carboxylic acid groups

Abstract

Synthetic routes to thirteen highly lipophilic crown ether carboxylic acids are described. Seven contain 12–15‐membered crown ether units with four ring oxygens and are designed for lithium ion complexation. Three others possess large ring 24‐crown‐8, 27‐crown‐9, and 30‐crown‐10 units. Six new hydroxymethyl crown ethers are prepared as synthetic intermediates.

Synthesis of C‐pivot lariat ethers

“…Hydroxymethyl 19‐crown‐6 81 was obtained by cyclization of diol 68 ( m = 1) and ditosylate 80 with potassium t ‐butoxide in THF, followed by debenzylation [45]. …”

“…Bartsch et al . [45, 53] used route 1 (Incorporation of the pivot carbon via a glycerol unit, Section 5.1.1.1) for the synthesis of hydroxymethylbenzo‐12‐crown‐4, 14‐crown‐4 [45] and hydroxymethylbenzo‐18‐crown‐6 [53] by reaction of the appropriate benzyloxymethy diol with the corresponding ditosylates and subsequent debenzylation.…”

Synthesis of Lipophilic Lariat Ethers with Pendant N‐(X)‐Sulfonyl Carboxamide Groups.

“…1 H NMR (CDCl 3 ): δ 0.88 (t, 3H), 1.26 (m, 16H), 2.59 (t, 2H), 3.70-4.05 (m, 17H), 6.94-6.98 (d, 1H), 7.27 (dd, 1H), 7.97,7.98 (d, 1H). 1,22.7,29.1,29.3,29.4,29.5,29.6,31.3,31.9,34,7,68.9,69.4,69.8,70.3,71.7,113.1,118.1,120.6,132.5,136.0,137.0,155.4,162.2. A solution of the appropriate sulfonamide (1.2 eq) in 30 ml of tetrahydrofuran was added over a 10-min period and the mixture was stirred at room temperature for 1.5 h. A solution of the lariat ether acid chloride (1.0 eq) in 45 ml of tetrahydrofuran was added over a 10-min period and the mixture was stirred overnight at room temperature.…”

“…Previously we have reported the synthesis of lipophilic crown ethers with a pendant carboxylic acid group or phosphonic acid monoethyl ester group, 1 and 2, respectively [7,8]. The selectivity in competitive alkali metal cation extractions by these ligands was found to be influenced both by the size of the crown ether ring (CE) and the identity of the acidic group [9,10].…”

Ion Extraction and Transport by Proton-Ionizable Crown Ethers

“…The proton-ionizable crown ethers with side arms that have been synthesized thus far have utilized largely carboxylic acid units (e.g., XXIU-XXVI) [12,22,23,26,28,30,33,36,38,40,[43][44][45][46][47][48]50,53,55,58,60], phenolic OH groups (~, LXXIV-LXXXIU) [31,35,39,42,56,57,65,66] or amine nitrogens (~, X-XVIII) [25,31,32,34,52,54,65] to provide the acidic proton. A few have been synthesized with phosphonic acid functions (~, XLV~L) [24,36,51,59,61,62] and others have a sulfonic acid group (XXI,XLIV) [36,61].…”