Synthesis of benzoazacrown ethers by transformation of benzocrown macrocycle and preparation of related complexing agents

The results of studies aimed at producing and developing a new methodology of synthesis of functional derivatives of benzoazacrown ethers by stepwise transformation of the benzocrown macrocycle are generalized. The comprehensive study of the spatial structure and complexation properties of the starting benzocrown ethers, target benzoazacrown ethers, and their nearest structural analogs shows that the N-alkylbenzoazacrown derivatives exhibit a much higher ability to bind metal and ammonium cations compared to the corresponding N-phenylazacrown ethers. They are comparable with benzocrown ethers in complexation properties and exceed them in some cases. A new approach to the synthesis of dinitrodibenzodiazacrown ethers is proposed based on the one-step transformation of the macrocycle of the dinitrodibenzo18-crown-6 cis-isomer under the action of aliphatic diamines. The synthesis of styryl dyes containing the N-methylbenzoazacrown fragment is described. The detailed studies by electron spectroscopy, NMR spectroscopy, and X-ray diffraction analysis revealed a high potential of these dyes as optical molecular sensors for alkaline and alkaline-earth metal cations.     

Macrocycle opening in formyl derivatives of benzocrown ethers under the action of methylamine

A new method for synthesizing nitrogen-containing podands by nucleophilic regioselective cleavage of the macrocycle in formyl derivatives of benzocrown ethers by heating with methylamine and methylammonium chloride has been developed. This reaction is the first example of crown ether opening by a nitrogen-containing nucleophile.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 950–953, May, 1995.     

New approach to the synthesis of dibenzodiazacrown ethers by ring transformation of dibenzocrown ether

Opening of the macrocycle of 4′,4″(5″)-dinitrodibenzo-18-crown-6 ethers under the action of MeNH₂ or MeONa to give podands was studied. Structure of the aza podands was confirmed by X-ray diffraction. A new approach to the synthesis of previously unknown dinitrodibenzodiazacrown ethers based on one-step ring transformation of the cis isomer of dinitrodibenzo-18-crown-6 ether on treatment with aliphatic diamines was proposed.     

Macrocycle opening in crown ethers

Macrocycle opening in derivatives of benzocrown ethers under the action of amines is affected by the nature of the heteroatoms in the macrocycle, the nature of the functional group in the benzene ring of the crown ether, and the length, branching, and number of hydrocarbon radicals at the amine nitrogen atom. A distinguishing feature of this reaction is the template effect of MeNH₃ ⁺, Me₂NH₂ ⁺, Na⁺, and K⁺ ions.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 687–692, March, 1996.For Part I see Ref. 1.     

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.     

Macrocycle opening in crown ethers

A method for the synthesis of nitrogen-containing podands from 4′-nitrobenzocrown ethers was developed. It involves nucleophilic regioselective cleavage of the macrocycle upon heating with MeNH₂. For Communication 2 see Ref. 1. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 540–543, March, 1997.     

Inclusion compounds: The products of the interaction of silicon,germanium and boron fluorides with crown ethers

This review deals with the problem of the interaction of Si(IV), Ge(IV) and B(III) fluorides with crown ethers and their aza analogues. The crystallographic structures have been determined of the stable products obtained by the interaction of H₂SiF₆ solution with the following crown ethers: 18-crown-6 (18C6), monoaza-18C6 (MA18C6), 1,10-diaza-18C6 (DA18C6) and 1,7-diaza-15C5 (DA 15C5). The complexes obtained are stabilized by a system of H-bonds of the O-H... O, N-H. ... O, N-H...F and O-H ... F types. For H₂GeF₆ the adducts obtained are similar to those obtained using H₂SiF₆. The crystal structures of three new boron fluoride-containing complexes with 18-membered crown ethers are also described. During macrocycle complexation the guest entities undergo chemical transformations which are stabilized by creation of the H- bond system. The results of vibrational and NMR spectra are also discussed.Presented at the Sixth International Seminar on Inclusion Compounds, Istanbul, Turkey, 27–31 August, 1995.     

Synthesis of thiaazapodands from 4′-nitrobenzothiacrown ethers

A series of thiaazapodands were synthesized from 4′-nitrobenzothiacrown ethers by nucleophilic regioselective opening of the macrocycle on heating with methylamine in up to 94% yield. Dedicated to Academician V. A. Tartakovsky on his 75th birthday. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1479–1481, August, 2007.     

Dicobalt octacarbonyl-catalyzed cationic polymerization of allylic and enolic ethers

In the presence of silanes bearing Si H groups, dicobalt octacarbonyl [Co₂(CO)₈] efficiently catalyzes the cationic polymerization of a wide variety of enol ether and other related monomers including vinyl ethers, 1-propenyl ethers, 1-butenyl ethers, 2,3-dihydrofuran, 3,4-dihydro-2H-pyran, ketene acetals, and allene ethers. In addition, this catalyst system is also effective for the polymerization of complimentary allylic and propargylic ethers by a process involving tandem isomerization and cationic polymerization. This latter process occurs by a stepwise mechanism in which the allylic or propargylic ether is first isomerized, respectively, to the corresponding enol ether or allenic ether and then this latter compound is rapidly cationically polymerized in the presence of the catalyst. In accord with this mechanism, it has been shown that the structure of the polymers prepared from related enol and allyl ethers using the above catalyst system are identical. © 1997 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 35: 1579–1591, 1997     

Antifungal activity of crown ethers

Some crown ethers were found to show significant antifungal activity against some wood-decay fungi, phytopathogenic fungi and eumycetes,Trichophytons for dermatomycosis. Their toxicity was evaluated by the paper disc method as well as by determining the values of ED₅₀, i.e., the concentration which inhibits the mycelium growth by 50%. The fungi examined areTyromyces palustris, Picnoporous coccineus, Coriolous versicolor, Pyricularia filamentosa, Fusarium sp., Trichophyton rubrum, Trichophyton sp., etc. Among the 26 crown ethers tested, 3,5-di-t-butyl-benzo-15-crown-5 showed relatively high activity, the highest ED₅₀ value of which being 8 M or 3 ppm. Other alkylbenzocrown ethers, dicyclohexyl crown ethers and Kryptofix 22DD also showed considerable activity. On the other hand, unsubstituted crown ethers, benzocrown ethers with a polar substituent, Kryptofix 222B and Kryptofix 221 were inactive.     

Synthesis of 3-nitro-3-azalk-2-yl ethers

PrimaryN-nitramines react with vinyl ethers to give 3-nitro-3-azalk-2-yl ethers. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 621–623, March, 1999.     

Properties of monolayers of crown ethers bearing an azo and azoxy group in the macrocycle

Two methods are described for preparing monomolecular layers of crown ethers with an azo or azoxy group in the macrocycle. When the molecules used to build the monolayer are soluble in aqueous solutions, adsorptive preconcentration on mercury electrodes was used to prepare the monolayer coating. The monolayer was electroactive due to the presence of the azo or azoxy unit in the molecules. Monolayers of crown ethers bearing an azo group in the macrocycle were shown to recognize alkali metal cations present in the solution. Changes of the parameters of the voltammetric reduction peaks - peak potential and peak width, served as an indication of specific interactions of the monolayer of 13-membered and 16-membered azocrown ethers with Na⁺ and K⁺ cations, respectively.The monolayers capable of recognizing cations have also been prepared on the aqueous solution-air interface, using the Langmuir technique. In this approach, amphiphilic derivatives of the azocrowns were synthesized and the monolayer has been assembled on the subphase containing metal cations. Binding of the cation by the macrocycle has a stabilizing effect on the monolayer and higher collapse pressures are achieved than on the pure water subphase. The monolayer was transferred from the air-water interface on the solid substrate using the Langmuir-Blodgett technique. Thin mercury film electrodes on the Ag substrate, or An films evaporated on glass slides were employed as the electrode substrates. The former gave monolayer modified electrodes of higher stability.Presented at the Sixth International Seminar on Inclusion Compounds, Istanbul, Turkey, 27–31 August, 1995.     

Comparative photophysical behaviour of naphthalene-linked crown ethers and aza crown ethers of varying cavity dimensions

A comparative time-resolved emission studies of several naphtho-crown ethers I–V, where metal ions can be complexed in a predetermined orientation with respect to the naphthalene (Naph) π-plane and naphthalene-linked aza crown ethers (L1 and L2) have been presented. In both the systems, crown ethers and aza crown ethers, naphthalene fluorescence gets quenched. In the systems I to V, the quenching is mainly due to efficient spin-orbit coupling (SOC) leading to greater population of the lowest triplet state of naphthalene. This SOC depends on the orientation of the crown ring with respect to the Naph-π-plane. However, in the systems L1 and L2, the quenching is due to photoinduced electron transfer (PET) from nitrogen lone pair of the aza crown ring to naphthalene moiety and consequent exciplex formation. The results have been interpreted using the time-resolved emission studies of all the compounds in various solvents, their alkali metal ion complexes, and protonated ligands.     

Synthesis of nitro and amino derivatives of benzothiacrown ethers

The condensation reaction of 1,2-bis(2-haloethoxy)-4-nitrobenzenes with acyclic α,ω-(oxa)alkanedithiols in the presence of alkali metal carbonates produced a series of nitrobenzodithiacrown ethers with macrocycles of different size. The structures of three ethers were established by X-ray diffraction. A new method was developed for the synthesis of nitrobenzomonothia-15-crown-5 ether. Nitro derivatives of benzodithiacrown ethers were tested as reagents for extraction of palladium(II), platinum(IV), and rhodium(III) from hydrochloric acid solutions. Extraction of Pd^II salts was found to be highly selective compared to that of Pt^IV and Rh^III salts. Benzodithia-15-crown-5 ether is the most efficient extractant for palladium(II). Reduction of nitrobenzothiacrown ethers with hydrazine hydrate in the presence of a platinum catalyst afforded their amino derivatives. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 958–966, May, 2007.     

Relative thermodynamic stabilities of allyl vinyl and propenyl vinyl ethers

The relative thermodynamic stabilities of a number of isomeric allyl vinyl and propenyl vinyl ethers were determined by chemical equilibration in DMSO solution with KOBu-t as catalyst. From the temperature dependence of the values of the equilibrium constant the parameters G _m , H _m and S _m of isomerization at 298.15 K were evaluated. Propenyl vinyl ethers, owing to their low enthalpy contents, are much more stable than the isomeric allyl vinyl ethers. It appears that in the parent propenyl vinyl ether, the Me group attached to C- of the divinyl ether skeleton has a strong stabilizing effect, comparable to that of alkyl groups in ordinary olefins, on the unsaturated system. In more heavily alkyl-substituted divinyl ethers, however, the stabilizing effects of alkyl groups are less prominent, being comparable to the low stabilization energies of alkyl groups in vinyl ethers, and depend moreover, on the pattern of substitution.     

Synthesis,crystal structure,and alkali metal picrate extraction capabilities of molecular clips based on diphenylglycoluril and benzocrown ethers

A convenient method for the synthesis of a series of molecular clips based on the diphenylglycoluril framework and benzocrown ether moieties by the reaction of bis(cyclomethoxymethylene)diphenylglycoluril with benzocrown ethers in polyphosphoric acid is proposed. X-ray diffraction analysis of molecular clips with the benzo-12-crown-4 and benzo-15-crown-5 fragments showed that both compounds are chloroform solvates with the stoichiometry clip:chloroform 1:1. By theoretical and experimental methods the existence of obtained clips in an anti–anti conformation was proved. The complexation properties of the obtained molecular clips were examined toward alkali metal and ammonium ions by FABMS spectrometry and extraction experiments.     

Direct heterocyclization of benzocrown ethers

The synthesis of novel 3,3‐dialkyl‐3,4‐dihydroisoquinoline derivatives via direct heterocyclization of benzocrown ethers is described. © 2005 Wiley Periodicals, Inc. Heteroatom Chem 16:192–195, 2005; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20092     

Dipropargyl ethers possessing nitramine units

The syntheses and characterization of novel propargyl ethers of N-(hydroxymethyl)nitramines that contain from one to four nitramine units are reported. All nitramine-functionalized ethers were well characterized by IR and multinuclear NMR spectroscopy as well as CHN analysis, and the X-ray crystal structures of two of them are described. For ethers bearing two or three nitramine units, the standard molar enthalpies of formation at 298.15 K were determined from the experimental standard molar energies of combustion in oxygen measured by static bomb combustion calorimetry     

Sodium and potassium benzeneazophosphonate complexes with crown ethers: Solid-state microwave synthesis, characterization and biological activity

The eco-friendly synthesis, spectroscopic (IR, MS, ¹H and ¹³C NMR) study and biological (cytostatic, antiviral) activity of sodium and potassium benzeneazophosphonate complexes, obtained by reaction in the solid state under microwave irradiation of the alkali salts of ethyl [α-(4-benzeneazoanilino)-N-benzyl]phosphonic acid and [α-(4-benzeneazoanilino)-N-4-methoxybenzyl]phosphonic acid with crown ethers containing 18-membered (dibenzo-18-crown-6 and bis(4′-di-tert-butylbenzo)-18-crown-6), 24-membered (dibenzo-24-crown-8) and 30-membered (dibenzo-30-crown-10) macrocyclic rings, have been described. The simple work-up solvent free reaction is an efficient green procedure for the formation of mononuclear crown ether complexes in which the sodium/potassium ion is bound to oxygen atoms of the macrocycle and the phosphonic acid oxygen. The free crown ethers, alkali benzeneazophosphonate salts and their complexes were evaluated for their cytostatic activity in vitro against murine leukemia L1210, murine mammary carcinoma FM3A and human T-lymphocyte CEM and MT-4 cell lines, as well as for their antiviral activity against a wide variety of DNA and RNA viruses. The investigated compounds showed no specific antiviral activity, whereas all the free crown ethers and their complexes demonstrated cytostatic activity, which was especially pronounced in the case of bis(4′-di-tert-butylbenzo)-18-crown-6 and its complexes.     

Access to functionalized cyclopropylcarbinyl compounds from homoallylic ethers via zirconocene intermediates

Cyclopropylcarbinylzirconium complexes were generated from homoallylic ethers and zirconocene (Cp₂ZrCl₂/2n-BuLi). They underwent further in situ transformations that is, bromination-substitution, transmetallation-functionalization and insertion reactions to afford various cyclopropylcarbinyl derivatives. In contrast, ring-opening products could be selectively obtained by treating the zirconium complex with MeLi, prior to functionalization.