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.     

Synthesis of two new crown ethers containing selenium and the complexation of one of them with silver and lead

Two new macrocyclic crown ethers containing one or two selenium donor atoms have been prepared. Diselena-18-crown-6 (2) was found to transport silver ions through a methylene chloride bulk membrane at about the same rate as the analogous dithia- (3) and diaza-18-crown-6 (4) compounds and transported lead ions about the same as dithia-18-crown-6 but better than diaza-18-crown-6.     

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⁺.     

Syntheses of diazadithiacrown ethers containing appended coumarin or 1‐aminonaphthalene sidearms

Six crown ethers containing two coumarin ( 11, 13,14,16,17 and 19 ) or two 1‐aminonaphthalene ( 15 and 20 ) fragments as sidearms and two crown ethers bearing one coumarin ( 12 and 18 ) arm were synthesized by a nucleophilic substitution of the secondary macrocyclic amine function on the alkyl halide. The major products of these reactions were the diazadithiacrown ethers containing two sidearms. In some cases, one‐armed diazadithiacrown ethers were separated as minor products, although more than 2.5 mmoles of alkyl halide were used for 1.0 mmole of macrocyclic diamine.     

Specific features of the chemical behavior of acetylenic derivatives of benzocrown ethers

4"-Ethynylbenzo-12-crown-4 (8), 4"-ethynylbenzo-15-crown-5 (9), and 4"-ethynylbenzo-18-crown-6 (10) were synthesized by cross-coupling of the corresponding aryl iodides 1—3 with 2-methylbut-3-yn-2-ol (4a) followed by the retro-Favorsky cleavage of the resulting carbinols. Unlike the corresponding benzo-12-crown-4 derivative (5a), the cleavage of tertiary acetylenic alcohols of benzo-15-crown-5 (6a) and benzo-18-crown-6 (7a) requires more than one molar equivalent of KOH. Aminoalkylation of crown ether 8 gives Mannich bases, independently of the reaction conditions and the nature of amine. The aminomethylation of acetylenic crown ethers 9 and 10 with paraform—piperidine (morpholine) in the presence of CuCl yields 1,4-disubstituted buta-1,3-diynes (19, 20) rather than Mannich bases.     

Complexation of silver(I) with different substituted diaza-18-crown-6 ethers in methanol

A large number of derivatives of the diaza-18-crown-6 ligand have been synthesized and characterized. These derivatives have different alkyl or aryl side arms at the nitrogen donor atoms of the macrocyclic diazacrown ether. In some side chains additional donor atoms are available. These diazacrown ethers are used as ligands for the complexation of Ag^I in MeOH. The complexation reactions have been studied using potentiometric and calorimetric methods. The thermodynamic data show the absence of a lariat effect. The increase of the values of the reaction enthalpies are due only to changes in solvation of the different ligands.     

Convenient preparation of bifunctional pybox ligands

Starting from a common easily available pybox derivative, chiral ditopic ligands with pendant Lewis basic sites consisting of amine or phosphine oxide functions attached in the 4-positions of the oxazoline rings were prepared by simple synthetic procedures. From the same pybox derivative, a macrocyclic ligand containing a diaza-18-crown-6-ether ring linked via triazole groups was obtained employing ‘click’ chemistry.     

Application of crown ethers as modifiers for the separation of amines by capillary electrophoresis

The separation of amines with capillary electrophoresis (CE) was made possible by applying crown ethers such as 18-crown-6 and 15-crown-5 as modifiers. Crown ether 18-crown-6 performed better as a modifier than 15-crown-5. The mobility change of primary amines with 18-crown-6 was larger than that for secondary and tertiary amines. The mobility change of various amines with 18-crown-6 were in the order: 1-aminobutane>2-aminobutane>2-amino-2-methylpropane. Effects of crown ether concentration, pH and cations in the eluent of CE were also investigated and discussed. Some neurotransmitters such as dopamine, serotonin, epinephrine, isoproterenol and phenylalanine were separated successfully by using crown ethers in CE analysis.     

含有冠醚基团的有机硅化合物(Ⅱ)——烯基氮杂冠醚的硅氢化和固载化氮杂冠醚的一些性能

本文报道了N-烯丙基、N-(10-十一碳烯基)氮杂15-冠-5与氨杂18-冠-6的合成、硅氢化、固载化,以及所得气相法二氧化硅固载的氮杂冠醚对苦味酸钠、钾的络合容量和正溴己烷碘代反应的相转移催化活性。     

A Convenient and Efficient Method for the Preparation of Unique Fluorophores of Lariat Naphtho‐Aza‐Crown Ethers

New naphtho‐aza‐crown ethers containing different phenolic side‐arms attached through the ortho‐position of the phenol have been prepared under solvent‐free conditions. The starting macrocyclic naphtho‐aza‐crown ether 2 was obtained by treatment of naphthalene dicarboxylic acid diester 1 with diethylenetriamine in EtOH at room temperature for two days without stirring in 77% yield (Scheme 1). Phenolic ligands ( 3 – 14 ) were synthesized by the Mannich reaction of the secondary macrocyclic amine 2 with the substituted phenols using nontoxic and inexpensive CaCl₂. This procedure was applied successfully for the synthesis of Mannich bases from simple secondary amines. The CaCl₂ powder can be reused up to three times after simple washing with dry acetone.     

双冠醚研究(Ⅳ)——Schiff碱型和仲胺型双-(苯并15冠-5)对碱金属苦味酸盐的萃取行为

仲胺型双冠醚与四苯硼酸碱金属盐在丙酮溶液中。25℃下的电导说明它们与Na~+可能形成1∶1络合物(冠醚单元∶金属离子),而与K~+、Rb~+、Cs~+离子则形成2∶1络合物。用Schlff碱型和仲胺型双-(苯并15-冠-5)在水-氯仿体系中进行萃取,测量了分配比D和萃取平衡常数K,发现后者的K值均大于前者。双冠醚F_2对K~+的萃取能力最强,选择性最佳。     

Supramolecular complex of cytochrome c with lariat ether: solubilization, redox behavior and catalytic activity of cytochrome c in methanol

A variety of lariat ethers were employed to solubilize water-soluble cytochrome c in methanol, in which alcohol, ether, ester, amine, and amide functionalities were attached as cation-ligating side arms to 18-crown-6, 15-crown-5, and 12-crown-4 rings. Among these lariat ethers, the alcohol-armed 18-crown-6 derivative offered the highest solubilization efficiency for cytochrome c via supramolecular complexation. The resulting cytochrome c-lariat ether complexes were electrochemically and spectroscopically characterized and confirmed to have redox-active heme structures of 6-coordinate low-spin population in methanol. Some of them catalyzed the oxidation of pinacyanol chloride with hydrogen peroxide in methanol and exhibited higher activities than unmodified cytochrome c and its poly(ethylene glycolated) derivative. Since the supramolecular complexation between lariat ether and cytochrome c includes extremely simple procedures, it provides a facile preparation method of effective biocatalysts working in organic solvents from metalloproteins.     

Bis-8-hydroxyquinoline-armed diazatrithia-15-crown-5 and diazatrithia-16-crown-5 ligands: possible fluorophoric metal ion sensors.

The synthesis and preliminary photophysical properties of a series of diazatrithia-15-crown-5 and diazatrithia-16-crown-5 ligands containing two 8-hydroxyquinoline sidearms are reported. The ligands were prepared by a two-step process. First, diazatrithiacrown ethers 11 and 12 were prepared by treating bis(alpha-chloroamide) 5 with various dimercaptans followed by reduction using a boron-THF complex. Hydroxymethyl-substituted macrocycle 12 was rearranged to hydroxy-substituted diazatrithia-16-crown-5 in refluxing aqueous HCl. Macrocyclic diamines 11-13 were converted to either 5-chloro-8-hydroxyquinolin-7-ylmethyl-substituted diazatrithiacrown ethers 14-16 by a Mannich aminomethylation reaction or to 8-hydroxyquinolin-2-ylmethyl-substituted diazatrithiacrown ethers 17-19 by reductive amination using 8-hydroxyquinoline-2-carboxaldehyde. Preliminary photophysical studies show that ligands 16 and 19 exhibit increased fluorescence in the presence of Zn(2+), indicating that these ligands could be chemical sensors for Zn(2+).     

Enantioselective separation of racemic secondary amines on a chiral crown ether-based liquid chromatography stationary phase

The first general enantioselective separation of racemic secondary amines on a crown ether-based liquid chromatography chiral stationary phase (CSP) is presented. The CSP is based on (+)- or (-)-(18-crown-6)-2,3,11,12-tetracarboxylic acid covalently bonded to silica gel. A mobile phase containing methanol, acetonitrile, triethylamine and acetic acid was employed in these separations of secondary amines with crown ether CSPs. The separation mechanism is believed to be the secondary amine forming a complex which includes crown ether coordination and electrostatic interaction of the positively charged amine with a carboxylate anion of the immobilized crown ether.     

Synthesis of Diazadi(and tri)thiacrown Ethers Containing Two 5-Substituent(or 2-methyl)-8-hydroxyquinoline Side Arms

Abstract

Sixteen new diazadi(or tri)thiacrown ethers containing two 5-substituent(or 2-methyl)-8-hydroxyquino-lin-2-ylmethyl side arms have been prepared by a three-step process. First, the appropriate bis(α-chloroamide)s were treated with five dimercaptans in base to form macrocyclic di(or tri)thiadiamides. The macrocyclic diamides were reduced by BH₃-THF to form 1,7-diaza-4-oxa-10,13-dithia-cyclopentadecane (11); 1,7-diaza-4,13-dioxa-10,16-dithiacyclooctadecane (12); 1,7-diaza-4-oxa-10,13,16-trithiacyclooctadecane (13); 1,7-diaza-4,13,16-trioxa-10,19-dithiacycloheneicosane (14); and 1,10-diaza-4,7-dioxa-13,16-dithiacyclooctadecane (15). The diazadi(or tri)thiacrown ethers were then treated with 8-hydroxyquinoline, 8-hydroxy-5-methylquinoline, 5-chloro-8-hydroxyquinoline, and 8-hydroxyquinaldine in the presence of paraformal-delyde in refluxing benzene to form the bis(8-hydroxy-5-substituent(or 2-methyl)quinolin-7-ymethy)-substituted diazadi(or tri)thiacrown ethers 16-31. The crown ethers containing two 8-hydroxyquinoline or 8-hydroxyquinaldine side arms proved to be mixtures of about 90% bis(8-hydroxyquinolin-7-ylmethyl)-substituted crown ethers; 9% mixed (8-hydroxyquinolin-7-ymethyl)-substituted and (8-hydroxyquinolin-5-ylmethyl)-substituted crown ethers; and 1% bis(8-hydroxyquinolin-5-ylmethyl)-substituted crown ethers.     

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.     

Syntheses and Complexing Properties of Polyethers

Diaza-18-crown-6 with two 8-hydroxyquinolines as side arms show high selective complexing ability with metal ions^[1,2] and with two aminophenols exhibit strange property^[3]. 8 diaza-18-crown-6 ethers containing sidearms^[4] and 7 podands were synthesized. Their complexing ability with metal ions were studied, the results show that they present high complexing capability for metal ions. The polyethers containing 8-hydroquinoline fragment show high selectivities for Hg²⁺,Ni²⁺ and their complexes with Eu³⁺ and Tb³⁺ show strong luminescence.     

Synthesis of new enantiopure proton-ionizable crown ethers containing a dialkylhydrogenphosphate moiety

Seven new enantiopure proton-ionizable crown ethers containing a dialkylhydrogenphosphate moiety were prepared starting from optically active dialkyl-substituted oligoethylene glycols and phosphorus oxychloride followed by mild hydrolysis of the resulting macrocyclic chlorophosphates. Pentaethylene glycols having primary hydroxyl groups gave good yields of 17-crown-6 type ethers. Pentaethylene glycols with secondary hydroxyl groups rendered about the same amount of 17-crown-6 ethers and open chain dihydrogenphosphates in low yields. Tetraethylene glycols are reluctant to undergo macrocyclization with phosphorus oxychloride, especially the ones which contain secondary hydroxyl groups.     

Azacrown ethers containing oximic and Schiff base sidearms - potential heteronuclear metal ion receptors

A simple synthetic pathway for the preparation of oxime- and Schiff base-containing aza- and diazacrown ethers is reported. N-Methoxymethyl-substituted aza-15-crown-5 and aza-18-crown-6 as well as N,N′-bis(methoxymethyl)-substituted diaza-18-crown-6 were treated with 5-bromosalicylaldehyde to produce the N-(2′-hydroxy-3′-carbonyl-5′-bromobenzyl)-substituted aza-15-crown-5 (8), aza-18-crown-6 (9) and N,N′-bis(2′-hydroxy-3′-carbonyl-5′-bromobenzyl)-substituted diaza-18-crown-6 (10) compounds. Compounds 8 and 10 were treated with hydroxylamine to give oxime-substituted ligands 12 and 13. A series of bis-Schiff base-containing diaza-18-crown-6 ligands were prepared by reacting 10 with 2-hydroxyaniline (to form 14), 5-nitro-2-hydroxyaniline (15), 2-aminopyridine (16), 2-hydrazinopyridine (17) and N-aminomorpholine (18). Compounds 12–18 are potential complexing agents for simultaneous binding of soft transition and hard alkali or alkaline earth metal ions in one molecule. These new oxime- and Schiff base-containing ligands interacted strongly with Na⁺ and K⁺ in methanol. The interaction of the aromatic portions of 9, 10, and 12–15 with transition metal ions was shown by the UV spectra of the metal ion complexes in 50% aqueous DMF. The X-ray structure of 10 is reported.     

Ion Selectine Crown-Ether Electrdes for Local Anesthetic Cations

Abstract

An electrode selectively sensitive to the cationic species of aromatic amine local anesthetics is described. Poly(viny1 chloride) gel membrane containing dibenzo-24-crown-8 ether was tested for ion selectivity to the cationic forms of local anesthetics. The electrode responded ideally to dibucaine and hexylcaine among eight local anesthetics tested. A dibenzo-18-crown-6 ether electrode also responded to these two anesthetics, although less ideally. Membranes with dicyclohexyl crown ethers were not good sensors for any local anesthetics tested. The relationship between chemical structures and sensitivity is discussed.