Synthesis of new proton-ionizable and neutral macrocyclic,macrobicyclic and macrotricyclic crown compounds containing dibenzo-16-crown-5 units

Fifteen new macrocyclic, macrobicyclic and macrotricyclic crown ether compounds with sym-dibenzo-16-crown-5 units have been prepared. The series includes macrocyclic polyether and bis(crown ether) compounds with proton-ionizable carboxylic or phosphonic acid monoethyl ester groups and bis(crown ether) and macrotricyclic polyether compounds with two sym-dibenzo-16-crown-5 units linked by amide, diamide, or diester functions.     

Synthesis of dibenzocrown ethers with pendent amide groups

Synthetic routes to twenty six crown ether compounds with pendent amide, N-alkylamide, or N,N-dialkyl-amide groups are reported. The new crown ether compounds are based on sym-dibenzo-16-crown-5-oxyacetamide and sym-(propyl)-dibenzo-16-crown-5-oxyacetamide and are obtained in high yields.     

Synthesis of dibenzocrown ethers with pendant thioamide groups

The synthesis of eighteen crown ether compounds with pendant thioamide, N-alkylthioamide, and N,N-dialkylthioamide groups is reported. The new crown ether compounds are obtained by one-step reactions from the corresponding sym-dibenzo-16-crown-5-oxyacetamides and sym-(propyl)dibenzo-16-crown-5-oxyacetamides with Lawesson's reagent.     

Synthesis of macrocyclic polyethers with partially fluorinated side arms

Different types of macrocyclic polyethers with partially fluorinated side arms are prepared. These new macrocyclic ligands are based on sym‐dibenzo‐16‐crown‐5 and sym‐dicyclohexano‐16‐crown‐5 scaffolds.     

Lariat ether alcohols based on dibenzo‐16‐crown‐5

Synthetic routes to forty‐four dibenzocrown ether alcohols are reported. The new crown ether com pounds are based on a sym‐dibenzo‐16‐crown‐5 platform. Most have a hydroxy group and an alkyl, aryl, aralkyl, alkenyl, alkynyl, or perfluoroalkyl group on the central carbon of the three‐carbon bridge. Others have substituted benzene rings and either a hydroxy or ‐O(CH₂)_nOH group attached to the central carbon of the three‐carbon bridge.     

Characteristics of Lariat Crown Ether‐Copper (II) Ion‐Selective Electrodes

An ion‐selective electrode using ionophore 2′‐picolyl sym‐dibenzo‐16‐crown‐5 ether as membrane carrier, sodium tetraphenylborate (NaTPB) as an anion excluder, and 2‐nitrophenyl‐octyl ether (NOPE) as the plasticing solvent mediator has been successfully developed. This electrode exhibits al in ear response with a slope of 42 mV/decade in concentration ranging from 10^?5 molL^?1 to 10^?1 molL^?1, slightly larger than the 30 mV expected from the one‐to‐one complex. The reason for the super‐Nernstain slope is the partial dimmer formation in side the membrane of the electrode, because this dimmer [Cu(C₂₅H₂₇NO₆)₂(H₂O)₂] 2ClO₄, has been isolated and confirmed by single crystal X‐ray crystallography. The detection limit for the cop per (II) ion was estimated to be 1 × 10^?6 molL^?1. Electrades composed of other plasticing solvent mediators such as tris(2‐ethylhexyl) phosphate (TOP), bis (2‐ethylhexyl) sebacate (DOS) and dibutyl phthalate (DBP) were also investigated. Stability constants (logKs) of the two to one and the one to one 2‐picolylsym‐dibenzo‐16‐crown‐5 ether‐Cu (II) complexes have been determined by potentiometric titration in methanol.     

Enantiomeric Separations in Capillary Electrochromatography with Crown Ether‐Capped β‐Cyclodextrin‐Bonded Silica Particles as Chiral Stationary Phase

Two novel types of crown ether capped β‐cyclodextrin (β‐CD) bonded silica, namely, 4′‐aminobenzo‐X‐crown‐Y (X=15, 18 and Y=5, 6, resp.) capped [3‐(2‐O‐β‐cyclodextrin)‐2‐hydroxypropoxy] propylsilyl‐appended silica, have been prepared and used as stationary phases in capillary electrochromatography (CEC) to separate chiral compounds. The two stationary phases have a chiral selector with two recognition sites: crown ether and β‐CD. They exhibit excellent enantioselectivity in CEC for a wide range of compounds. After inclusion of metal ions (Na⁺ or K⁺) from the running buffer into the crown ether units, the stationary phases become positively charged and can provide extra electrostatic interaction with ionizable solutes and enhance the dipolar interaction with polar neutral solutes. This enhances the host‐guest interaction with the solute and improves chiral recognition and enantioselectivity. Due to the cooperation of the anchored β‐CD and the crown ether, this kind of crown ether capped β‐CD bonded phase shows better enantioselectivity than either β‐CD‐ or crown ether bonded phases only. These new types of stationary phases have good potential for fast chiral separation with CEC.     

Synthetic, structural, and theoretical investigations of alkali metal germanium hydrides--contact molecules and separated ions

The preparation of a series of crown ether ligated alkali metal (M=K, Rb, Cs) germyl derivatives M(crown ether)_nGeH₃ through the hydrolysis of the respective tris(trimethylsilyl)germanides is reported. Depending on the alkali metal and the crown ether diameter, the hydrides display either contact molecules or separated ions in the solid state, providing a unique structural insight into the geometry of the obscure GeH₃^? ion. Germyl derivatives displaying M? Ge bonds in the solid state are of the general formula [M([18]crown‐6)(thf)GeH₃] with M=K ( 1 ) and M=Rb ( 4 ). The compounds display an unexpected geometry with two of the GeH₃ hydrogen atoms closely approaching the metal center, resulting in a partially inverted structure. Interestingly, the lone pair at germanium is not pointed towards the alkali metal, rather two of the three hydrides are approaching the alkali metal center to display M? H interactions. Separated ions display alkali metal cations bound to two crown ethers in a sandwich‐type arrangement and non‐coordinated GeH₃^? ions to afford complexes of the type [M(crown ether)₂][GeH₃] with M=K, crown ether=[15]crown‐5 ( 2 ); M=K, crown ether=[12]crown‐4 ( 3 ); and M=Cs, crown ether=[18]crown‐6 ( 5 ). The highly reactive germyl derivatives were characterized by using X‐ray crystallography, ¹H and ¹³C NMR, and IR spectroscopy. Density functional theory (DFT) and second‐order Møller–Plesset perturbation theory (MP2) calculations were performed to analyze the geometry of the GeH₃^? ion in the contact molecules 1 and 4 .     

Synthesis and Optical Properties of 2,13‐Dibenzothiazol‐2′‐yldibenzo[b,k]‐18‐crown‐6

A new crown ether of 2,13‐dibenzothiazol‐2′‐yldibenzo[b,k]‐18‐crown‐6 was synthesized from 2,13‐diformyl‐ dibenzo[b,k]‐18‐crown‐6 with 2‐aminothiophenol. The binding behavior and the optical properties of the crown ether were examined through UV‐visible spectroscopy and fluorescence spectroscopy. When complexed with Na⁺, K⁺, Rb⁺ and Cs⁺ ions, it led to intramolecular charge transfer and caused the changes of the fluorescence spectra. The protonation of the crown ether was also studied.     

Synthesis of lipophilic lariat ethers with pendant N‐(X)sulfonyl carboxamide groups

Synthetic routes to sixteen lipophilic lariat ether N‐(X)sulfonyl carboxamides with X = trifluoromethyl, methyl, phenyl, and p‐nitrophenyl are described. For this new family of proton‐ionizable lariat ethers in which the acidity can be ‘tuned’ by X group variation, the ring size is systematically varied from 12‐crown‐4 to 14‐crown‐4 to 15‐crown‐5 to 18‐crown‐6.     

Effect of structural variations of dibenzocrown ether resins and their acyclic analogues upon ion-pair sorption of alkali metal salts from aqueous and aqueous methanol solutions

Abstract

Ion-pair sorption of alkali metal salts from aqueous and aqueous methanol solutions by acyclic and cyclic dibenzopolyether resins possessing different side arm groups such as hydroxy, methoxy and carboxy has been investigated. The results reveal that both sorption selectivity and efficiency are influenced by: (1) the methanol content of the aqueous sample solution; (2) the acyclic or cyclic nature of the polyether unit; (3) the conformational positioning of the side arm group with respect to the crown ether cavity; and (4) the identity of the counteranion species of the alkali metal salt. For sym-(C₃H₇)(R′)dibenzo-16-crown-5 resins, the sorption selectivity and efficiency increased as the R′ group was varied: -OCH₃ < -OH < -OCH₂CO₂H. The highest sorption efficiency and Na⁺ selectivity was obtained for sym-(propyl)dibenzo-16-crown-5-oxyacetic acid resin (7) in which the pendent carboxylic acid group is oriented over the crown ether cavity. The use of a less hydrated anion in the alkali metal salt species enhances the ion-pair efficiency: SO₄ ^2- < NO₃ ^?, Cl^?, Br^? < I^? < SCN^?. Monovalent metal selective sorption was noted for competitive ion-pair sorption of NaCl, KCl, MgCl₂ and CaCl₂ by resin 7.     

Transport of trivalent lanthanides in a H2O-CHCl3H2O liquid membrane system containing a crown ether carboxylic acid

Neutral crown ethers do not transport trivalent lanthanide cations in a H₂O-CHCl₃-H₂O liquid membrane system. With the addition of a carboxylate group to a macrocyclic polyether, as in the case of sym-dibenzo-16-crown-5-oxyacetic acid, high efficiencies of transporting trivalent lanthanides were observed across the H₂O-CHCl₃-H₂O liquid membrane. The crown ether carboxylic acid also showed significant selectivity for the lanthanides studied in this system.     

Natural p‐Menthene Monoterpenes: Synthesis of the Enantiomeric Forms of Wine Lactone,Epi‐wine Lactone,Dill Ether,and Epi‐dill Ether Starting from a Common Intermediate

A concise synthesis of the enantiomeric forms of wine lactone ( 5 ), epi‐wine lactone ( 14 ), dill ether ( 6 ), and epi‐dill ether ( 15 ) was accomplished starting from the enantiomeric forms of p‐mentha‐1,8(10)‐diene‐3,9‐diol ( 8 ) (Scheme 3). The latter compounds were previously prepared in high optical purity by means of lipase‐mediated kinetic resolution, and they were the common building blocks for this divergent synthesis. The key steps were a number of chemo‐ and diastereoselective reactions of which the oxidation of 8 to the lactone 7 (see Table 1), the diastereoselective reduction of 7 to the lactones 14 and 5 (see Table 2), and the reduction of enol‐ether 16 to ether 15 were studied comprehensively. The effectiveness of this new synthetic approach allows the preparation of the title p‐menthane monoterpenes, which are of considerable interest to the perfume industry, in high yield and in a few simple experimental steps.     

DFT Study for a Series of Less-Symmetrical Crown Ethers and Their Complexes with Alkali Metal Cations

A series of ring‐contracted (14‐crown‐5, 17‐crown‐6) and ring‐enlarged (16‐crown‐5, 17‐crown‐5, 19‐crown‐6, 20‐crown‐6) crown ethers and their complexes with alkali‐metal cations Na⁺ and K⁺ had been explored using density functional theory (DFT) at B3LYP/6‐31G* level in order to reveal the effects of the methylene‐chain length in a crown ether. The nucleophilicity of all crown ethers had been investigated by the Fukui functions. The quantum chemistry parameters, such as the energy gap (ΔE), the highest occupied molecular orbital energy (E_HOMO) and the lowest unoccupied molecular orbital energy (E_LUMO) for less‐symmetrical crown ethers and symmetrical frameworks (15‐crown‐5, 18‐crown‐6) had been calculated. In addition, the thermodynamic energies of complexation reactions had also been studied. The results of the DFT calculations show that the methylene‐chain length plays an important role in determining the structure characters of the crown ethers and also strongly influences the properties of the ethers. Some of the calculated results are in a good agreement with the experimental values.     

Extraction of Co(II) and Ni(II) ammine cations from aqueous solutions into chloroform by highly lipophilic crown carboxylic acids

The proton-ionizable crown ethers, 2-[(sym-dibenzo-14-crown-4)oxy]-decanoic acid (1), 2-[sym-dibenzo-16-crown-5)oxy]decanoic acid (2), and 2-[sym-dibenzo-19-crown-6)oxy]decanoic acid (3) efficiently extract Co(II) and Ni(II) ammine cations from highly alkaline aqueous solutions (pH>10) into chloroform. For extractions of the individual metal species,2 is more efficient than1 or3. In competitive extraction systems, good selectivity for Co(II) ammine cations over Ni(II) ammine cations is observed.     

Supramolecular Fullerene Chemistry: A Comprehensive Study of Cyclophane‐Type Mono‐ and Bis‐Crown Ether Conjugates of C70

The covalently templated bis‐functionalization of C₇₀, employing bis‐malonate 5 tethered by an anti‐disubstituted dibenzo[18]crown‐6 (DB18C6) ether, proceeds with complete regiospecificity and provides two diastereoisomeric pairs of enantiomeric C₇₀ crown ether conjugates, (±)‐ 7a and (±)‐ 7b , featuring a five o'clock bis‐addition pattern that is disfavored in sequential transformations (Scheme 1). The identity of (±)‐ 7a was revealed by X‐ray crystal‐structure analysis (Fig. 6). With bis‐malonate 6 containing a syn‐disubstituted DB18C6 tether, the regioselectivity of the macrocylization via double Bingel cyclopropanation changed completely, affording two constitutionally isomeric C₇₀ crown ether conjugates in a ca. 1 : 1 ratio featuring the twelve ( 16 ) and two o'clock ((±)‐ 15 ) addition patterns, respectively (Scheme 3). The X‐ray crystal‐structure analysis of the twelve o'clock bis‐adduct 16 revealed that a H₂O molecule was included in the crown ether cavity (Figs. 7 and 8). Two sequential Bingel macrocyclizations, first with anti‐DB18C6‐tethered ( 5 ) and subsequently with syn‐DB18C6‐tethered ( 6 ) bis‐malonates, provided access to the first fullerene bis‐crown ether conjugates. The two diastereoisomeric pairs of enantiomers (±)‐ 28a and (±)‐ 28b were formed in high yield and with complete regioselectivity (Scheme 9). The cation‐binding properties of all C₇₀ crown‐ether conjugates were determined with the help of ion‐selective electrodes (ISEs). Mono‐crown ether conjugates form stable 1 : 1 complexes with alkali‐metal ions, whereas the tetrakis‐adducts of C₇₀, featuring two covalently attached crown ethers, form stable 1 : 1 and 1 : 2 host‐guest complexes (Table 2). Comparative studies showed that the conformation of the DB18C6 ionophore imposed by the macrocyclic bridging to the fullerene is not particularly favorable for strong association. Reference compound (±)‐ 22 (Scheme 4), in which the DB18C6 moiety is attached to the C₇₀ sphere by a single bridge only and, therefore, possesses higher conformational flexibility, binds K⁺ and Na⁺ ions better by factors of 2 and 20, respectively. Electrochemical studies demonstrate that cation complexation at the crown ether site causes significant anodic shifts of the first reduction potential of the appended fullerene (Table 3). In case of the C₇₀ mono‐crown ether conjugates featuring a five o'clock functionalization pattern, addition of 1 equiv. of KPF₆ caused an anodic shift of the first reduction wave in the cyclic voltammogram (CV) by 70 to 80 mV, which is the result of the electrostatic effect of the K⁺ ion bound closely to the fullerene core (Fig. 14). Addition of 2 equiv. of K⁺ ions to C₇₀ bis‐crown ether conjugates resulted in the observation of only one redox couple, whose potential is anodically shifted by 170 mV with respect to the corresponding wave in the absence of the salt (Fig. 16). The synthesis and characterization of novel tris‐ and tetrakis‐adducts of C₇₀ are reported (Schemes 5 and 6). Attempts to prepare even more highly functionalized derivatives resulted in the formation of novel pentakis‐ and hexakis‐adducts and a single heptakis‐adduct (Scheme 7), which were characterized by ¹H‐ and ¹³C‐NMR spectroscopy (Fig. 10), as well as matrix‐assisted laser‐desorption‐ionization mass spectrometry (MALDI‐TOF‐MS). Based on predictions from density‐functional‐theory (DFT) calculations (Figs. 12 and 13), structures are proposed for the tris‐, tetrakis‐, and pentakis‐adducts.     

Competitive transport of alkali metal ions from aqueous media into toluene solutions of 2-(sym-dibenzo-16-crown-5-oxy)-decanoic acid. A comparative study

Competitive permeation of alkali metal ions from an alkaline source phase into or through a toluene phase facilitated by the lipophilic crown ether carboxylic acid 2-(symdibenzo-16-crown-5-oxy)-decanoic acid is studied in liquid—liquid extraction, bulk liquid membrane transport, and emulsion liquid membrane transport. Most rapid transport was obtained in emulsion liquid membrane experiments. Some differences in selectivity orders for alkali metal permeation were observed for the three separation techniques.     

[Rb4Sn9] — A Low Dimensional Arrangement of Zintl Ions in [Rb(18‐crown‐6)]2Rb2[Sn9](en)1.5

The compound [Rb(18‐crown‐6)]₂Rb₂[Sn₉](en)_1.5 ( 1 ) was synthesized from an alloy of formal composition K₂Rb₂Sn₉ by dissolving in ethylenediamine (en) followed by the addition of 18‐crown‐6 and toluene. 1 crystallizes in the monoclinic space group P2₁/n with a = 10.557(2), b = 25.837(5), c = 20.855(4)Å, β = 102.39°, and Z = 4. The structure consists of [Sn₉]^4— cluster anions, which are connected via Rb atoms to infinite [Rb₄Sn₉] layers. The layers of binary composition are separated by the crown ether molecules. The crown ether molecules are bound by one side via the Rb atoms to the [Sn₉]^4— anions. The other side, which is turned away from the Rb atoms, shows only weak van der Waals interactions to the crown ether molecules of the next layer. Comparison with other compounds of similar composition shows, that the variation of the alkali metals and the complexing organic molecules leads to the low dimensional arrangement of the clusters.     

Synthesis of Novel Dibenzo‐18‐crown‐6‐ ether‐Functionalized Benzimidazoles and its Applications in Colorimetric Recognition to Hg2+ and as Antifungal Agents

New crown ether‐functionalized benzimidazoles was designed and synthesized via formylation of dibenzo‐18‐crown‐6 followed by condensation with different o‐phenylene diamines. The complexation properties of crown ether‐functionalized benzimidazoles with various metals (K⁺, Ca²⁺, Ba²⁺, Co²⁺, Hg²⁺) were examined using UV–vis spectroscopy. Hg²⁺ showed a well‐defined peculiar absorption maximum at 366 nm exclusively. All these newly synthesized compounds were screened for antifungal activity against Aspergillus niger and Aspergillus oryzae, respectively.     

Synthesis,Supramolecular Behavior,and In Vitro Photodynamic Activities of Novel Zinc(II) Phthalocyanines “Side‐strapped” with Crown Ether Bridges

Two new tetra‐ or di‐α‐substituted zinc(II) phthalocyanines 5 and 6 have been prepared through a “side‐strapped” method. In the molecules, the adjacent benzene rings of the phthalocyanine core are linked at α‐position through a triethylene glycol bridge to form a hybrid aza‐/oxa‐crown ether. The tetra‐α‐substituted phthalocyanine 5 shows an eclipsed self‐assembly property in CH₂Cl₂ and the effect on the di‐α‐substituted analogue 6 is significantly weakened. Furthermore, the crown ethers of these compounds can selectively complex with Fe³⁺ or Cu²⁺ ion in DMF, leading to formation of J‐aggregated nano‐assemblies, which can be disaggregated in the presence of some organic or inorganic ligands, such as triethylamine, tetramethylethylenediamine, CH₃COO^?, or OH^?. In addition, both compounds are efficient singlet oxygen generators with the singlet oxygen quantum yields (Φ_Δ) of 0.54‐0.74 in DMF relative to unsubstituted zinc(II) phthalocyanine (Φ_Δ=0.56). They exhibit photodynamic activities toward HepG2 human hepatocarcinoma cells, but the compound 6 , which has more than 40‐fold lower IC₅₀ value (0.08 μM ) compared to the analogue 5 (IC₅₀=3.31 μM ), shows remarkablely higher in vitro photocytotoxicity due to its significantly higher cellular uptake and singlet oxygen generation efficiency. The results suggest that these compounds can serve as promising multifunctional materials both in (opto)electronic field and photodynamic therapy.