Anion receptors based on ureido-substituted thiacalix[4]arenes and calix[4]arenes

The regioselective nitration of 25,27-dipropoxythiacalix[4]arene was carried out as a key step in the synthesis of thiacalix[4]arene derivative bearing two arylureido functions on the upper rim. The preorganisation of ureido units using the thiacalix[4]arene/calix[4]arene moieties as a molecular scaffold gave novel anion receptors. These compounds, albeit based on hydrogen bonding interactions, show good complexation ability even in highly HB-competitive solvent, such as DMSO. Direct comparison of otherwise identical structures 6a and 7a revealed remarkable dominance of the thiacalix[4]arene derivative over its classical analogue in anion binding.     

Synthesis of (thia)calix[4]arene oligomers: towards calixarene-based dendrimers

Thiacalix[4]arenes bearing two or four carboxylic functions on the lower rim served as starting compounds for the synthesis of novel calixarene oligomers connected by amidic functions. The cone conformers react smoothly with four molecules of 5-amino-calix[4]arene to yield the corresponding pentakis-calixarenes. On the other hand, because steric hindrance, the 1,3-alternate condenses only with two molecules leading thus to tris-calixarene, possessing a novel type of inherent chirality based on the 25,26-substitution pattern. The title compounds, which connect together ‘classical’ calixarene and thiacalixarene building blocks, represent a first step towards calixarene-based dendritic structures.     

Synthesis, characterization, and conformational analysis of new perfunctionalized calix[9]arenes

The synthesis of a series of six new per-substituted p-tert-butylcalix[9]arenes derivatives has been achieved. Functions such as ester, nitrile, or carbonate have been grafted on the phenolic oxygens of calix[9]arene: p-tert-butylcalix[9]arene nona-ethyl acetate, p-tert-butylcalix[9]arene nona-carboxylic acid, p-tert-butylcalix[9]arene nona-cyanopropyloxy, p-tert-butylcalix[9]arene nona-tert-butoxycarbonyle, p-tert-butylcalix[9]arene nona-acetyl, and p-tert-butylcalix[9]arene nona-trifluoroacetyl have been obtained in good yields (from 48% to 78%) and fully characterized. The X-ray structures of p-tert-butylcalix[9]arene nona-tert-butoxycarbonyl and p-tert-butylcalix[9]arene nona-ethyl acetate have been determined. A dynamic NMR study has revealed the high conformational mobility of such structures, even at low temperature.     

Synthesis of terpyridine-substituted calix[n]arenes

Calix[n]arenes (n = 4,5) comprising 4-(2,2′:6′,2″-terpyridyl)-phenyl substituents at the upper rim were synthesized for the first time, employing Suzuki-type coupling reactions. All calix[n]arene derivatives were prepared as cone conformers. The single crystal X-ray structure of cone-5,11,17,23-tetra{4-(2,2′:6′,2″-terpyridyl)-phenyl}-25,26,27,28-tetrabutoxycalix[4]arene 4 is analyzed in terms of structural rigidity and potential use of these ligands as novel synthons of cage-type metallosupramolecular assemblies.     

Binding of neutral molecules by p-nitrophenylureido substituted calix[4]arenes

Although originally designed for anion recognition, bis(N′-p-nitrophenylureido)calix[4]arenes immobilised in the 1,3-alternate conformation can act as receptors for small neutral molecules, such as sulfoxides and ketones. Their binding ability was studied both in solution and in the solid state using the combination of UV/vis, NMR, and X-ray crystallography.     

Synthesis of amine, halide, and pyridinium terminated 2-alkyl-p-tert-butylcalix[4]arenes

The synthesis of calix[4]arenes with functional groups tethered to a single methylene bridge has been explored. Mono-lithiated calix[4]arenes react with 1,ω-bromochloroalkanes to give 2-(ω-chloroalkyl)-calix[4]arenes, which function as key intermediates in the synthesis of a variety of tether-functionalized calix[4]arenes. Subsequent reactivity of these chloroalkyl species has allowed for successful synthesis of 2-(ω-iodoalkyl)-calix[4]arenes, 2-(ω-pyridiniumalkyl)-calix[4]arenes, and 2-(ω-aminoalkyl)-calix[4]arenes. This latter group of amine-terminated calix[4]arenes are especially significant as they may serve as useful entries to a wide range of subsequent chemistry, including metal coordination or attachment to a solid support. Both alkyl and aryl amines have been incorporated at the end of the tether, and a 2,6-diisopropylaniline derivative has been analyzed by X-ray diffraction.     

Tetrazolecalix[4]arenes as new ligands for palladium(II)

The synthesis of new calix[4]arenes bearing two or four tetrazole liganting groups at the upper rim is decribed. The structures of tetrakis-tetrazolecalix[4]arene and its palladium dichloride (2:2) complex are examined by X-ray crystallography.     

Synthesis of new calix[4]arenes containing nucleoside bases

A family of novel calix[4]arene derivatives containing nucleoside bases were designed and synthesized. Coupling reaction between para mono- or bis-amino calix[4]arenes 5, 6 or 7 and thymin-1-ylacetic acid in the presence of DCC afforded mono- or bis-thymine-substituted calix[4]arenes 8, 9 or 10 in over 70% yield. Owing to the low solubility of adenine-N⁹-ylacetic acid in DMF and DMSO and the weak nucleophilicity of aminocalix[4]arene derivatives, alternatively, the substitution reaction of bromoacetylated aminocalix[4]arenes derivatives 11, 12, 13 with adenine in the presence of sodium hydride was carried out to synthesize mono- or bis-adenine-substituted calix[4]arenes. Two kinds of isomers 15 and 16 or 17 and 18 were obtained due to the non-regiospecific alkylation of adenine, and their structures have been confirmed by ¹³C NMR and ¹H NMR spectra.     

Aramidocalix[4]arenes as new anion receptors

Calix[4]arenes bearing aromatic amide (aramid) moieties at the upper rim display interesting recognition properties toward anions and in particular versus planar trigonal nitrate and Y-shaped benzoate. Molecular modeling and DFT calculations indicate that the high affinity displayed by aramidocalix[4]arenes 3 and 4 for nitrate anion is likely due to the planar arrangement of the NH groups, which form an unusual six-hydrogen-bond scheme with nitrate anion.     

Conformational behaviour of tetramethoxythiacalix[4]arenes: solution versus solid-state study

The conformational behaviour of simple thiacalix[4]arene derivatives was studied using a combination of NMR spectroscopy and X-ray diffraction analysis. The 25,26,27,28-tetramethoxythiacalix[4]arene was found to adopt an unprecedented solid-state structure, where the cone and 1,3-alternate conformers co-exist in the crystal lattice in the 3:1 ratio. This phenomenon reflects the basically distinct conformational behaviour of thiacalix[4]arene skeleton as compared with classical calixarenes.     

Efficient divalent metal cation extractions with di-ionizable calix[4]arene-1,2-crown-4 compounds

Di-ionizable calix[4]arene-1,2-crown-4 ethers in the cone conformation were synthesized and their conformation and regioselectivity verified by NMR spectroscopy. These new ligands exhibited high Ba²⁺ selectivity in competitive solvent extraction of alkaline earth metal cations from aqueous solutions into chloroform. The selectivity order was Ba²⁺>>Sr²⁺>Ca²⁺>Mg²⁺ with Ba²⁺/Sr²⁺ selectivity exceeding 100. The ligands also exhibited high extraction ability for Pb²⁺ and for Hg²⁺ in single species extraction. With variation of proton-ionizable groups, which are oxyacetic acid moieties and N-(X)sulfonyl oxyacetamide units with X=methyl, phenyl, 4-nitrophenyl, and trifluoromethyl, ‘tunable’ ligand acidity was obtained.     

Phosphite ligands derived from distally and proximally substituted dipropyloxy calix[4]arenes and their palladium complexes: Solution dynamics, solid-state structures and catalysis

Two bisphosphite ligands, 25,27-bis-(2,2′-biphenyldioxyphosphinoxy)-26,28-dipropyloxy-p-tert-butyl calix[4]arene (3) and 25,26-bis-(2,2′-biphenyldioxyphosphinoxy)-27,28-dipropyloxy-p-tert-butyl calix[4]arene (4) and two monophosphite ligands, 25-hydroxy-27-(2,2′-biphenyldioxyphosphinoxy)-26,28-dipropyloxy-p-tert-butyl calix[4]arene (5) and 25-hydroxy-26-(2,2′-biphenyldioxyphosphinoxy)-27,28-dipropyloxy- p-tert-butyl calix[4]arene (6) have been synthesized. Treatment of (allyl) palladium precursors [(η³-1,3-R,R′-C₃H₄)Pd(Cl)]₂ with ligand 3 in the presence of NH₄PF₆ gives a series of cationic allyl palladium complexes (3a-3d). Neutral allyl complexes (3e-3g) are obtained by the treatment of the allyl palladium precursors with ligand 3 in the absence of NH₄PF₆. The cationic allyl complexes [(η³-C₃H₅)Pd(4)]PF₆ (4a) and [(η³-Ph₂C₃H₃)Pd(4)]PF₆ (4b) have been synthesized from the proximally (1,2-) substituted bisphosphite ligand 4. Treatment of ligand 4 with [Pd(COD)Cl₂] gives the palladium dichloride complex, [PdCl₂(4)] (4c). The solid-state structures of [{(η³-1-CH₃-C₃H₄)Pd(Cl)}₂(3)] (3f) and [PdCl₂(4)] (4c) have been determined by X-ray crystallography; the calixarene framework in 3f adopts the pinched cone conformation whereas in 4c, the conformation is in between that of cone and pinched cone. Solution dynamics of 3f has been studied in detail with the help of two-dimensional NMR spectroscopy.The solid-state structures of the monophosphite ligands 5 and 6 have also been determined; the calix[4]arene framework in both molecules adopts the cone conformation. Reaction of the monophosphite ligands (5, 6) with (allyl) palladium precursors, in the absence of NH₄PF₆, yield a series of neutral allyl palladium complexes (5a-5c; 6a-6d). Allyl palladium complexes of proximally substituted ligand 6 showed two diastereomers in solution owing to the inherently chiral calix[4]arene framework. Ligands 3, 6 and the allyl palladium complex 3f have been tested for catalytic activity in allylic alkylation reactions.     

Synthesis and structure of lower rim C-linked tetra-N-tosyl peptidocalix[4]arenes

Chiral p-tert-butylcalix[4]arenes perfunctionalised at the lower rim with amino acid residues have been prepared. The ¹H and ¹³C NMR spectra indicate that the macrocycles adopt a cone conformation. Calix[4]arenes bearing amino acid moieties 5a shows strong complexation towards Cl⁻, Br⁻, HSO₄⁻, H₂PO₄⁻ and N-tosyl-(l)-alaninate.     

Synthesis and pH-dependent self-assembly of semifluorinated calix[4]arenes

A new series of highly fluorinated calix[4]arene-based amphiphilic molecules was designed and synthesized. Using the calix[4]arene scaffold, four perfluorinated hyper-hydrophobic groups and four water solubilizing chains were introduced in the same molecule and also segregated in space following the scaffold directionality. Upon solubilization in aqueous solutions, these amphiphilic molecules form microscopic fluorous domains that drive the formation of various self-assembly patterns. We found that the self-assembly of these semifluorinated calix[4]arenes is dependent on external stimuli, such as changes in the polarity of the solvent or pH. As a consequence, by changing the pH of the solutions, it is possible to shift the aggregation pattern of these molecules, by a regular change either in the shape or in the size of the initially formed ordered aggregates. These are examples of the variety of structures and possibilities in nano-engineering offered by fluorous-phase driven molecular recognition.     

A new calix[4]arene based nucleobase for cation recognition

A novel calix[4]arene linked nucleobase molecular receptor bearing two adenine moieties has been synthesized and characterized by UV, IR, NMR and ESI–MS analyses. The synthesized receptor can recognize biologically important Zn²⁺ and Mn²⁺ ions through 1:1 binding stoichiometry. The evaluation of binding constants suggests that adenine alone, in an appropriate supramolecular network, can exhibit efficient binding for Zn²⁺ ions without the presence of any phosphate or sugar unit.     

Synthesis of mono- and 1,3-diaminocalix[4]arenes via Ullmann-type amination and amidation of 1,3-bistriflate esters of calix[4]arenes

Practical methods are described for the preparation of monoamines 4 and 1,3-diamines 5, bearing one or two amino group(s) instead of the hydroxy group(s) at the 28-position or at both the 26- and 28-positions of p-tert-butylcalix[4]arene (1a) and p-tert-butylthiacalix[4]arene (1b), via the Ullmann-type amination or amidation. Thus, the copper-catalyzed or mediated amination of the 1,3-bistriflate ester (2a) of 1a with benzylamine affords either mono(benzylamino) triflate 7a or 1,3-bis(benzylamine) 8 in a high yield, depending on the reaction conditions. On the other hand, the 1,3-bistriflate ester (2b) of 1b resists disubstitution and produces, under stoichiometric conditions, mono(benzylamino) triflate 7b. The disubstitution of 2b is achieved by amidation with tosylamide, giving 1,3-bis(tosylamide) 17b. The hydrogenolysis of the benzylamino moiety of 7a, followed by the hydrolysis of the Tf moiety, affords monoamine 4a, while the hydrogenolysis of 8 affords 1,3-diamine 5a. The amino moiety of 7b can be deprotected under acidic conditions to give, after hydrolysis, monoamine 4b. The hydrolysis of 17b affords 1,3-diamine 5b. The overall yields of compounds 4a, 4b, 5a, and 5b are 72%, 45%, 78%, and 24%, respectively, based on commercially available compounds 1 and are much higher than the ones previously reported in the literature.     

Upper rim substituted thiacalix[4]arenes

The synthesis and structure of new tetrahydroxythiacalix[4]arenes, existing in the cone conformation and possessing reactive bromide, chloromethyl or diorganylphosphoryl groups on the upper rim of the macrocycle are described. The molecular structure of tetrakis(diisopropoxyphosphorylmethyl)thiacalix[4]arene was examined by X-ray crystallography.     

Synthesis and properties of novel calix[4]arene derivatives bearing fluorogenic coumarin units

Four novel calix[4]arene derivatives 5-8 bearing four fluorogenic coumarin units attached via imino group acting also as binding sites at the upper rim have been prepared and characterized by IR, IH NMR and MS. Compounds 5-8 adopt a cone conformation. Their complexation properties to different heavy and transition metal ions have been studied by UV-vis spectroscopy. Compounds 5, 6, 8 show selective recognition to Fe^3＋ and Cr^3＋.     

Anion responsive TTF-appended calix[4]arenes. Synthesis and study of two different conformers

Two new cone- and 1,3-alternate-calix[4]arenes (cone-1 and 1,3-alt-1), bearing four modified TTF (tetrathiafulvalene) substituents on the upper rim, have been synthesized. The binding ability of these two sets of conformers for various anions, including F(-), Cl(-), Br(-), I(-), PF6(-), ClO4(-), HSO4(-), CH3COO(-), H2PO4(-), and HP2O7(3-), was tested in organic media by monitoring the changes in their UV/vis and (1)H NMR spectra as a function of added anion, as well as via cyclovoltammetry (CV) (all anions studied as their respective TBA salts). On the basis of the present findings, we propose that incorporation of four TTF units within an overall calix[4]arene-based recognition framework produces a preorganized receptor system that displays a modest preference for the pyrophosphate (HP2O7(3-)) anion.     

CMPO-substituted calix[6]- and calix[8]arene extractants for the separation of An/Ln from radioactive waste

Three calix[6]arene derivatives (1a-c) and two calix[8]arene derivatives (2a,b), with six and eight CMPO residues, respectively, attached to the narrow/lower rim via ether links, were synthesised. Preliminary liquid-liquid extraction studies for Eu(III) and Am(III) from aqueous nitric acid to o-nitrophenylhexyl ether reveal remarkable properties with respect to efficiency and selectivity, especially for the tert-butylcalix[6]arene derivative with a -(CH₂)₃- spacer.