Synthesis and Properties of 5-Chloro-8-hydroxyquinoline-Substituted Azacrown Ethers: A New Family of Highly Metal Ion-Selective Lariat Ethers

New 5-chloro-8-hydroxyquinoline (CHQ)-substituted aza-18-crown-6 (4), diaza-18-crown-6 (1), diaza-21-crown-7 (2), and diaza-24-crown-8 (3) ligands, where CHQ was attached through the 7-position, and aza-18-crown-6 (11) and diaza-18-crown-6 (10) macrocycles, where CHQ was attached through the 2-position, were prepared. Thermodynamic quantities for complexation of these CHQ-substituted macrocycles with alkali, alkaline earth, and transition metal ions were determined in absolute methanol at 25.0 degrees C by calorimetric titration. Two isomers, 1 and 10, which are different only in the attachment positions of the CHQ to the parent macroring, exhibit remarkable differences in their affinities toward the metal ions. Compound 1 forms very stable complexes with Mg(2+), Ca(2+), Cu(2+), and Ni(2+) (log K = 6.82, 5.31, 10.1, and 11.4, respectively), but not with the alkali metal ions. Ligand 10 displays strong complexation with K(+) and Ba(2+) (log K = 6.61 and 12.2, respectively) but not with Mg(2+) or Cu(2+). The new macrocycles and their complexes have been characterized by means of UV-visible and (1)H NMR spectra and X-ray crystallography. New peaks in the UV spectrum of the Mg(2+)-1 complex could allow an analytical determination of Mg(2+) in very dilute solutions in the presence of other alkali and alkaline earth metal cations. (1)H NMR spectral and X-ray crystallographic studies indicate that ligand 10 forms a cryptate-like structure when coordinated with K(+) and Ba(2+), which induces an efficient overlap of the two hydroxyquinoline rings. Such overlapping forms a pseudo second macroring that results in a significant increase in both complex stability and cation selectivity.     

The interaction between ketamine and some crown ethers in common organic solvents studied by NMR: the effect of donating atoms and ligand structure

1H NMR spectroscopy was used to investigate the stoichiometry and stability of the drug ketamine cation complexes with some crown ethers, such as 15-crown-5 (15C5), aza-15-crown-5 (A15C5), 18-crown-6 (18C6), aza-18-crown-6 (A18C6), diaza-18-crown-6 (DA18C6), dibenzyl-diaza-18-crown-6 (DBzDA18C6) and cryptant [2,2,2] (C222) in acetonitrile (AN), dimethylsulfoxide (DMSO) and methanol (MeOH) at 27 degrees C. In order to evaluate the formation constants of the ketamine cation complexes, the CH3 protons chemical shift (on the nitrogen atom of ketamine) was measured as function of ligand/ketamine mole ratio. The formation constant of resulting complexes were calculated by the computer fitting of chemical shift versus mole ratio data to appropriate equations. A significant chemical shift variation was not observed for 15C5 and 18C6. The stoichiometry of the mono aza and diaza ligands are 1:1 and 1:2 (ligand/ketamine), respectively. In all of the solvents studied, DA18C6 formed more stable complexes than other ligands. The solvent effect on the stability of these complexes is discussed.     

Synthesis of New Crown Ethers Containing Appended Pyridine, 10-hydroxybenzoquinoline, 8-hydroxyquinoline and 2-amino-1-hydroxybiphenyl Sidearms

Twelve crown ethers containing one or two arms were synthesized. Two methods were used to attach arms to the azacrown ethers. Ligands 4 - 12 were prepared by a nucleophilic substitution of secondary macrocyclic amine functions on RX ( X=bromide or tosylate groups). Ligands 13 - 15 were obtained via a Mannich reaction of secondary macrocyclic amines with 5-chloro-8-hydroxyquinoline or a substituted-phenol. Diaza-18-crown-6 was treated with 2-bromomethyl-9-methyl-1,10-phenanthroline at the same conditions in which 4 - 8 and 10 - 12 were prepared. In this case, the main product was the diazacrown ether containing one arm. Twelve new aza-crown ethers bearing aromatic and aliphatic side arms were prepared by nucleophilic substitution by secondary macrocyclic amine functions on halide or tosylates or via a Mannich reaction of the macrocyclic secondary amines with phenolic compounds. R=derivatives of pyridine, 8-hydroxyquiniline, and 1-hydroxybiphenyl. Crown ether include aza-15-crown-5 diaza-18-crown-6 diazatrithia-15 (and 16)-crown-6 and diaza-21-crown-7     

Preparation of N,N′-di pivot lariat 1,4-diaza-15-crown-5 and 18-crown-6 macrocycles

Twelve diaza-15-crown-5 and 18-crown-6 macrocycles containing different side arms on the nitrogen atoms have been prepared. These diaza-N,N'-di pivot lariat crown ethers were prepared either from N,N'-bishydroxyethyl-1,4-diaza-15-crown-5 or 18-crown-6 ligands or from the corresponding unsubstituted diaza-crowns.     

DFT-B3LYP and SMD study on the interactions between aza-, diaza-, and triaza-12-crown-4 (A n -12-crown-4, n = 1, 2, 3) with Na+ in the gas phase and acetonitrile solution

B3LYP/6-311G level of theory is used to study the interactions between aza-, diaza-, and triaza- 12-crown-4 ligands as host molecules and Na⁺ ion as a guest species. Minimum energy structures, complexes binding energies, basis set superposition errors, and various thermodynamic parameters of free ligands, ion, and complexes have been calculated based on the proposed level of theory. A simple thermodynamic cycle with and without different acetonitrile cluster sizes inside the cavity of Na⁺, has been used to calculate the stability constants of aza-12-crown-4 complex. All solvation free energy estimations have been done with using SMD model. Results show that with introducing more acetonitrile molecules in the cavity of guest species, the absolute deviation is reduced. In addition, a good linear correlation between experimental complex formation constants and binding energies of complexes has been obtained. Calculated results, which are in agreement with the experimental data, predict that the interaction energy of triaza- is more than diaza-12-crown-4, which in turn is greater than aza-12-crown-4 with Na⁺ ion.     

Lanthanide crown ether complexes of p-sulfonatocalix[5]arene

Two types of arrays are formed in water involving aza-crown ethers, p-sulfonatocalix[5]arene and europium(III) ions. One is a co-ordination polymer connecting calixarenes, sodium ions and lanthanide ions based on "ferris wheel" moieties incorporating aza-18-crown-6 and sodium ions. The second structure is a host-guest arrangement with di-protonated diaza-18-crown-6 in the cavity of the calixarenes as part of secondary coordination spheres of aquated europium(iii) ions.     

DFT calculation of benzoazacrown ethers and their complexes with calcium perchlorate

The complexation constants of several azacrown ethers with Ca(ClO₄)₂ were determined and turned out to be the higher, the large the macrocycle. The structures of free ligands and their complexes and the complexation energies were calculated by the DFT method. In the aza-12(15)-crown-4(5) ether complexes with Ca(ClO₄)₂, the metal cations lie outside the averaged plane of heteroatoms of the macrocycle, and the coordination of both counterions is V-like. In the complexes of aza-18-crown-6 ethers, the counterions are in the axial position relatively to the macrocycle in the center of which the Ca²⁺ ion is localized. The complexation energies increase with an increase in the size of the azacrown ether macrocycle. The involvement of the nitrogen atom in binding with the Ca²⁺ ion decreases with the expansion of the macrocycle. Two methods for quantitative estimation of the degree of pre-organization of ligands to complexation were considered: geometric and energetic methods. Benzoaza-15-crown-5 ether is a ligand which is more pre-organized to complexation than N-phenylaza-15-crown-5 ether.     

Syntheses of diaza-18-crown-6 ligands containing two units each of 4-hydroxyazobenzene,benzimidazole, uracil,anthraquinone, or ferrocene groups

Six new diaza-18-crown-6 ligands each containing two aromatic side arms with responsive functions were prepared. Diaza-18-crown-6 containing two 4-hydroxyazobenzene ( 3 ) or two 4 -hydroxy- 4′ -(dimethyl-amino)azobenzene ( 4 ) substituents were prepared via a one-pot Mannich reaction. Diaza-18-crown-6 containing two benzimidazole ( 5 ), two uracil ( 6 ) or two 9,10-anthraquinone ( 7 ) substituents were prepared by treating the diazacrown with the appropriate chloromethyl-containing compound. Reductive amination using sodium triacetoxyborohydride, diaza-18-crown-6 and ferrocenecarboxaldehyde was used to prepare bisferrocene-substituted diaza-18-crown-6 ( 8 ). Interactions of compounds 3 , 5 , and 6 with Na⁺, K⁺, Ba²⁺, Ag⁺, and Cu²⁺ were evaluated by a calorimetric titration technique at 25° in methanol. All three ligands form more stable complexes with Ag⁺ and Cu²⁺ ( 5 forms a precipitate with Ag⁺) than with Na⁺ and K⁺. Ligand 5 also forms a highly stable complex with Ba²⁺.     

含酚醚中心功能基的大二环型穴醚的合成及配位性能

4-氯-2, 6-二羟基苯甲醚(2)与氯乙酸钠缩合, 制得4-氯-2, 6-二(羟甲氧基甲基)苯甲醚(4), 由4经酰氯化生成4-氯-2, 6-二(3-氯甲酰基-2-氧杂丙基)苯甲醚(5)后, 再与相应的二氮杂冠醚3a, 3b和3c反应制备标题化合物1a~1c。用1^H NMR法研究了1a~1c对碱金属离子的配位性能, 讨论了分子内的中心功能基和底环大小对其IR, 1^H NMR和配位行为的影响。     

Solvent extraction of divalent metal ions with azacrown ether substituted acylpyrazolones

Novel 4-acyl-5-pyrazolones having aza-15-crown-5 (HPMP-A15C5) and aza-18-crown-6 (HPMP-A18C6) moieties as an intramolecular synergist have been synthesized by simple coupling reactions between 1-phenyl-3-methyl-4-chloroacetyl-5-pyrazolone and the corresponding azacrown ethers. The solvent extraction of the divalent metal ions (Mn(2+), Co(2+), Ni(2+), Cu(2+), Zn(2+), Cd(2+) and Pb(2+)) were examined. Synergistic extractions with 1-phenyl-3-methyl-4-benzoyl-5-pyrazolone (HPMBP) and benzocrown ethers were also examined for a comparison. Extractions with the novel acylpyrazolones were unique and quite different from those with HPMBP and benzocrown ethers. The synergistic effect with benzocrown ethers was low, and an obvious difference brought by the ring size was not observed. The extractions of the divalent metal ions with HPMP-A18C6 were generally enhanced, as compared to those alone with HPMBP; on the contrary, the extractions with HPMP-A15C5 were relatively poor.     

Design, synthesis and evaluation of diazadibenzocrown ethers as Pb(2+) extractants and carriers in plasticized cellulose triacetate membranes

The ligands 4,7-diaza-2,3,8,9-dibenzo-15-crown-5 (L1), 4,10-diaza-2,3,11,12-dibenzo-18-crown-6 (L2), 4,10-diaza-2,3,11,12-di(4′-tert-butylbenzo)-18-crown-6 (L3) and N,N-di(methylenecarboxyethoxy) 4,10-diaza-2,3,11,12-dibenzo-18-crown-6 (L4) have been prepared. Partition coefficients and acid dissociation constants for these four diazadibenzocrown ether compounds were determined in water-chloroform. Their effectiveness was assessed in solvent extraction of Pb²⁺ from aqueous solutions into toluene. Ligands L3 and L4 provide high selectivity for Pb²⁺ over Cd²⁺ and Zn²⁺ in transport across plasticized cellulose triacetate membranes.     

Complex Formation Between Crown Ethers and Urea and Some Guanidinium Derivatives in Methanol

The complexation of urea and some guanidinium derivatives by the ligands 15-crown-5, 18-crown-6, benzo-18-crown-6 and diaza-18-crown-6 in methanol has been studied by means of calorimetric titrations. The complex formation is mainly favored by entropic contributions. The number of solvent molecules released during the complex formation is responsible for the stability of the complexes formed.This revised version was published online in November 2005 with corrections to the Cover Date.     

Molecular Complex Formation between Some Azacrown Ethers and 2,4,6-Trinitrophenol

The formation of molecular complexes with 1 : 1 stoichiometry between 2,4,6-trinitrophenol and aza-12-crown-4, aza-15-crown-5 and aza-18-crown-6 in chloroform solution was investigated spectrophotometrically. The resulting complexes were isolated and characterized by microchemical analysis, IR and NMR spectroscopy. The equilibrium constants of the 1 : 1 adducts were evaluated from the non-linear least-squares fitting of the absorbance-mole ratio data. The overall stability of the 2,4,6-trinitrophenol complexes was found to vary in the order aza-15-crown-5 > aza-18-crown-6 aza-12-crown-4. The kinetics of complex formation between 2,4,6-trinitrophenol and the aza-substituted crown ethers used were investigated and in all cases the results showed the occurrence of an oscillating chemical reaction in solution.     

Coordination Chemistry of Lipoic Acid and Related Compounds V [1]. New Heteroditopic Ligands Derived from Monoazacrown Ethers and Lipoic Acid

Summary.  Lipoyl imidazolide reacts with aza-15-crown-5 (1,4,7,10-tetraoxa-13-azacyclopentadecane) or aza-18-crown-6 (1,4,7,10,13-pentaoxa-16-azacyclooctadecane) to afford new N-lipoylated azacrown compounds in good yields. These compounds can be transformed into 1,3-dithiols and amines by reduction with complex hydrides of the disulfide and/or amide group of the lipoyl chain. The new pendant-arm macrocycles react as heteroditopic ligands by forming dithiolate and disulfide complexes with the ‘soft’ metal ions Ni²⁺ and Pd²⁺, respectively, and an amine complex with the ‘hard’ Li⁺ ion. Semiempirical and DFT calculations on the complexation of a lithium ion give a most favourable structure in which the azacrown and two solvent molecules are in contact with the metal but not the pendant arm. Received January 29, 2002; accepted (revised) March 25, 2002     

Synthesis of actinomycin D analogs: XXIII. Actinocin derivatives containing azacrown fragments

A number of actinocin amides containing residues of aza-15-crown-5 and aza-18-crown-6 where crown fragments were separated from the heterocyclic chromophore by the residues of ω-amino acids were obtained as actinomycin D models.     

Complexes of sodium and lithium borohydrides with macrocyclic polyethers

A method for the synthesis of complexes of sodium and lithium borohydrides with crown ethers is proposed. The complexes of sodium borohydride with benzo-15-crown-5, 4′-aminobenzo-15-crown-5, dibenzo-18-crown-6, and diaza-18-crown-6 and the complexes of lithium borohydride with benzo-15-crown-5 and dibenzo-18-crown-6 are synthesized. These complexes can be used for the preparation of hydrogen in their reactions with methanol. The complex formation does not affect the purity of hydrogen formed.     

Chromo- and Fluoroionophores Based on Diaza-Crown Ethers for Alkaline Earth Metal Ions

Abstract

Two new metal-selective dyes were synthesized and used to develop methods for determining Ca²⁺ and Mg²⁺. A chromogenic diaza-18-crown-6 with an alizarin group at each crown nitrogen is a calcium-selective ionophore used for extraction-spectrophotometry. The detection limit for the technique is 1 × 10^?5 M Ca²⁺. Fluorometric determination of Mg²⁺ is performed using a diaza-15-crown-5 derivatized with two methyiumbelliferone groups. This method allows for the one-phase determination of Mg²⁺ down to 7 × 10^?6 M.     

Acylation of aza crown ethers with N-substituted isophthalimides

Acylated aza crown ethers containing fragments of N-substituted phthalamic acids in the side chain were obtained by the reaction of monoaza-15-crown-5, monoaza-18-crown-6, and diaza-18-crown-6 with N-substituted isophthalimides.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 536–539, April, 1987.     

Synthesis of new functionalized 1,10-phenanthrolines

Styrylphenanthroline derivatives containing the fragments dithia-18-crown-6, aza-18-crown-6, and azadithia-15-crown-5 were obtained for the first time. The conditions for their synthesis were optimized.     

Synthesis, structures and reactivity of triosmium clusters containing terminal pyrazines, bridging hydroxy and methoxycarbonyl ligands

Four triosmium carbonyl clusters bearing terminal pyrazines, bridging hydroxy and methoxycarbonyl ligands of general formula [Os₃(CO)₉(μ-OH)(μ-OMeCO)L] (1, L = pyrazine; 2, L = 2-methylpyrazine; 3, L = 2,3-dimethylpyrazine; 4, L = 2,3,5-trimethylpyrazine) were synthesized by the reactions of [Os₃(CO)₁₂] with the corresponding pyrazine derivatives and water in the presence of a methanolic solution of Me₃NO in moderate yields. Compounds [Os₃(CO)₉(μ-OH)(μ-OMeCO)L] react with a series of two electron donor ligands, L′ at ambient temperature to give [Os₃(CO)₉(μ-OH)(μ-OMeCO)L′] (5, L′ = PPh₃; 6, L′ = P(OMe)₃; 7, L′ = ^tBuNC; 8, L′ = C₅H₅N) in good yields by the displacement of the pyrazine ligands. This implies that the pyrazine ligands in 1–4 are relatively labile. Compounds 2, 3, 4, and 8 were characterized by single crystal X-ray diffraction analyses. All the four compounds possess two metal–metal bonds and a non-bonded separation of two osmium atoms defined by Os(1)Os(3), which are simultaneously bridged by OH and MeOCO ligands and a heterocyclic ligand is terminally coordinated to one of the two non-bonded osmium atoms.