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 fluorescent properties of thiacalix[4]arenes containing terpyridyl fragments at the lower rim

New thiacalix[4]arenes tetrasubstituted by terpyridyl fragments at the lower rims in the 1,3-alternate stereoisomeric form were synthesized. The molecules interact with Eu^III and Tb^III in the DMF solution to form highly luminescent nanoscale (21–26 nm) metal-organic structures with the 2: 1 metal-to-ligand stoichiometry and a narrow particle size distribution.     

Calix[4]arenes containing ferrocene amide as carboxylate anion receptors and sensors

Calix[4]arene derivatives containing amide ferrocene units at the wide rim and ethyl ester groups at the narrow rim, L1-L3, were synthesized and their anion binding and sensing properties were investigated. It was found from (1)H NMR titrations that L1-L3 were able to bind selectively with carboxylate anions. Moreover, cyclic voltammetry and square wave voltammetry showed that L1-L3 were able to act as electrochemical sensors for carboxylate anions. [structure: see text]     

Supramolecular self-assemblies of stereoisomers of p-tert-butyl thiacalix[4]arenes functionalized with hydrazide groups at the lower rim with some metal cations

Novel p-tert-butyl thiacalix[4]arenes functionalized with hydrazide groups at the lower rim in cone, partial cone and 1,3-alternate conformations were synthesized and their receptor properties toward metal ions of p- (Al³⁺, Pb²⁺) and d- (Fe³⁺, Co³⁺, Ni²⁺, Cu²⁺, Ag⁺, Cd²⁺) elements were investigated by picrate extraction and dynamic light scattering (DLS). It was shown that the p-tert-butyl thiacalix[4]arenes functionalized with hydrazide groups are effective extractants of soft metal cations. The complex stoichiometry depended on the receptor configuration. All the p-tert-butyl thiacalix[4]arene derivatives with hydrazide fragments were able to form nanoscale aggregates but did not show self-association abilities.     

p-tert-butylcalix[4]arenes containing azacrown ether substituents at the lower rim as potential polytopic receptors

A series of disubstituted p-tert-butylcalix[4]arenes with N-methoxycarbonylmonoazacrown ether and N-ethoxymonoazacrown ether residues at the lower rim has been prepared via the reaction of di(carboxymethoxy)-p-tert-butylcalix[4]arene with azacrown ethers and subsequent reduction of the resulting amide derivatives. Using UV titration and ¹H NMR spectroscopy we have demonstrated the ability of the calixarene with two N-carbonylmonoaza-18-crown-6-ether substituents to form the 1:3 complexes with K⁺ and Na⁺ and the 1:2 complexes with Cs⁺, Sr²⁺, Cu²⁺, and Zn²⁺. The calixarene with two fragments of N-ethoxymonoazo-18-crown ether has formed binuclear complexes with alkali metals cations and mononuclear complexes with transition metals cations.     

Monosubstituted lower rim thiacalix[4]arene derivatives

A clean and partially green route to monoalkyled thiacalix[4]arenes has been demonstrated. We have discovered that tetraalkylammonium halide can cleave selectively one of the two aryl alkyl ethers of dialkylated para-tert-butylthiacalix[4]arenes. Thus, p-tert-butyl thiacalix[4]arenes differently monoalkyled at the lower rim with acetyl, propyl, and benzyl group were synthesized in good yield.     

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.     

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.     

Calix[4]arenes containing benzodiazepinone fragments at the lower rim

A series of p-tert-butylcalix[4]arene derivatives containing 1,4(1,5)-benzodiazepinone fragments as substituents were prepared. The biological activity of the compounds, namely, their antispasmodic activity in mice, was evaluated by antagonism with a spasmodic agent, Corazol, upon transdermal administration. According to the data obtained, benzodiazepine derivatives of calixarenes show higher antispasmodic activity compared to 3-hydroxyphenazepam, taking into account their considerably higher molecular weight.     

Thiacalix[4] arenes with terminal thiol groups at the lower rim: synthesis and structure

Methods were developed for the synthesis of ω-mercaptoalkoxy derivatives of thiacalix[4]-arenes in the 1,3-alternate conformation containing different numbers (2–5) of methylene spacers at the lower rim. The hydrazinolysis of the corresponding thioacetates is the most efficient method for the synthesis of these compounds.     

Solvent extraction and self-assembly of nanosized aggregates of p-tert-butyl thiacalix[4]arenes tetrasubstituted at the lower rim by tertiary amide groups and monocharged metal cations in the organic phase

New p-tert-butyl thiacalix[4]arenes functionalized with morpholide and pyrrolidide groups at the lower rim in cone, partial cone, and 1,3-alternate conformations were synthesized, and their receptor properties for monocharged cations (alkali metal and silver ions) were studied using the picrate extraction method and dynamic light scattering (DLS). To evaluate the ability of the p-tert-butyl thiacalix[4]arene derivatives to recognize metal ions, liquid-liquid extraction of their picrate salts has been carried out in a mutually saturated water-dichloromethane system. The degrees of extraction and the extraction constants for monocharged metal cations (Li⁺, Na⁺, K⁺, Cs⁺) have been determined. The ability of the systems, consisting of host and guest molecules, to self-assembly was proved by DLS using a Zetasizer Nano ZS particle size analyzer. It was shown that all the investigated thiacalix[4]arenes are able to form nanoscale particles with silver cations under the experimental conditions. The pyrrolidide derivative in the cone conformation showed both self-association and aggregation processes with lithium cations. The degree of extraction for all the investigated systems that formed nanoscale aggregates in the organic phase was more than 67% and the extraction constants, log K_ex determined by the picrate extraction method, more than 6.     

1,3-Alternate calix[4]arenes, selectively functionalized by amino groups

General strategies are described to synthesize calix[4]arenes which are fixed in the 1,3-alternate conformation and substituted selectively by amino groups. These derivatives are useful starting materials for the attachment of various groups via amide bonds, as demonstrated by several examples, but may be converted also to ureas, imides or azomethines. Four amino groups may be attached to the narrow rim via(several) methylene groups as spacer by O-alkylation with omega-bromophthalimides or omega-bromonitriles. From the resulting tetraethers the amino functions are obtained by cleavage with hydrazine or by hydrolysis, allowing a selective functionalisation of both sides of the molecule (phenolic units A, C versus B, D). Amino functions at the wide rim are introduced by ipso-nitration of the respective t-butylcalix[4]arene derivatives and subsequent reduction. Selective ipso-nitration of a 1,3-diether, followed by O-alkylation with allylbromide to obtain the tetraether in the 1,3-alternate conformation, hydrogenation of allyl and nitro groups (in one step), protection of the amino functions as phthalimides followed by ipso-nitration of the remaining t-butyl phenol rings, allows again to distinguish both sides of the molecule (units A, C versus B, D). Reaction of a wide rim tetraamine in the 1,3-alternate conformation by Boc-anhydride allows not only to obtain the mono- and tri-Boc derivative, but also in nearly 60% yield the C2-symmetrical di-Boc derivative, in which two adjacent phenolic units are protected (distinction of A, B from C, D). This paves the way for the preparation of chiral derivatives or assemblies. O-Alkylation with omega-bromophthalimides followed by ipso-nitration leads to precursors for octaamines in the 1,3-alternate conformation, in which the potential amino functions on both rims can be selectively "activated" by reduction or hydrazinolysis. The structures of the newly synthesized molecules were mainly confirmed by their 1H NMR spectra, which allow a distinction from isomeric derivatives in the cone and partial cone conformation. Single crystal X-ray analyses were obtained for two analogous derivatives in the 1,3-alternate conformation (27, n = 3,4), an isomeric compound in the cone conformation (27, n = 3,4), and a derivative in the partial cone conformation (11).     

Novel anion receptors based on thiacalix[4]arene derivatives

Starting from the thiacalix[4]arene tetraacetate, novel derivatives bearing four ureido or thioureido functions on the lower rim have been prepared. As proven by NMR titrations, these compounds can bind anions via hydrogen bonding interactions and represent the first example of anion receptors in the thiacalixarene series.     

Stereoselective dialkylation of the proximal hydroxy groups of calix- and thiacalix[4]arenes

Treatment of p-tert-butylcalix[4]arene (C1) and its sulfur-bridged analog T1 with 1,3-dichloro-1,1,3,3-tetraisopropyldisiloxane in the presence of imidazole gives proximally O,O'-disiloxane-1,3-diyl-bridged calixarenes C2 and T2 in excellent yields, respectively. Subsequent base-catalyzed etherification of the remaining hydroxy groups with alkyl halides gives syn- and anti-O',O'-dialkylated products, the stereoselectivity of which varies depending on the nature of the macrocycle, as well as the metal cation of the base employed. Thus, conventional calixarene C2 preferentially affords syn compounds of 1,2-alternate conformation (C3) with the aid of tert-BuOK and K(2)CO(3) and anti counterparts of partial-cone conformation (C4) with Cs(2)CO(3). On the other hand, thiacalixarene T2 affords syn compounds of 1,2-alternate conformation (T3) with any of the bases. The disiloxanediyl bridge of the resulting products can readily be removed by treatment with tetrabutylammonium fluoride. Thus, the net process provides an efficient method for the regio- and stereoselective synthesis of proximally dialkylated calix[4]arenes.     

Upper rim guanidinocalix[4]arenes as artificial phosphodiesterases

Calix[4]arene derivatives, blocked in the cone conformation and functionalized with two to four guanidinium units at the upper rim were synthesized and investigated as catalysts in the cleavage of the RNA model compound 2-hydroxypropyl p-nitrophenyl phosphate. When compared with the behavior of a monofunctional model compound, the catalytic superiority of the calix[4]arene derivatives points to a high level of cooperation between catalytic groups. Combination of acidity measurements with the pH dependence of catalytic rates unequivocally shows that a necessary requisite for effective catalysis is the simultaneous presence, on the same molecular framework, of a neutral guanidine acting as a general base and a protonated guanidine acting as an electrophilic activator. The additional guanidinium (guanidine) group in the diprotonated (monoprotonated) trifunctional calix[4]arene acts as a more or less innocent spectator. This is not the case with the tetrasubstituted calix[4]arene, whose mono-, di-, and triprotonated forms are slightly less effective than the corresponding di- and triguanidinocalix[4]arene derivatives, most likely on account of a steric interference with HPNP caused by overcrowding.     

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

Chiral p-tert-butylcalix[4]arenes functionalized at the lower rim with amino acid residues have been prepared. The (1)H and (13)C NMR spectra indicate that the macrocycles preferably adopt a cone conformation. Calix[4]arenes bearing amino acid moieties were prepared as a class of receptors selective for anions that are bound through hydrogen bonding with the NH group. The association constants are dependent on the nature of the substituents at the lower rim. Derivative 9 shows the strongest complexation and the largest selectivity for N-tosyl-(L)-alaninate. Finally, a preliminary X-ray crystal study of the difunctionalized receptor 6f shows the "flattened cone" conformation in the solid state.     

Delayed lanthanide luminescent Tb(III) complexes formed from lower rim amide functionalised calix[4]arenes

The synthesis and the photophysical studies of a new generation of time resolved luminescent systems based on calix[4]arenes alkylated at the lower rim, capable of hosting lanthanide (III) ions such as terbium and sensitising its emission, are described. Two series of ligands were designed to provide an ideal cavity to host terbium (Tb(III)) and were synthesised in high yields following two novel approaches. The tetra-alkylation, which was achieved in one step using with piperidino- and morpholino-acetamide pendant arms, provides eight donor atoms forming a binding ‘pocket’ at an ideal distance from the metal core to favour the sensitisation via the antenna effect. Of the two ligand series developed, compounds 3 and 4 possess a short spacer between the calix and the amide receptor site. The second series of ligands 6–7, designed with longer pendant amide arms, was synthesised from 2 in two steps through the ester analogue 5. The crystal structure of 3 (and 6 as shown in Supporting Information, available online) is presented. The synthesis and the photophysical studies of the four resulting complexes 3.Tb, 4.Tb, 6.Tb and 7.Tb are described in detail and in each case, successful sensitisation of the terbium emission occurred upon excitation of the phenolic scaffold of the calixarene.     

New artificial receptors from selectively functionalized calix[4]arenes

Abstract

The development of new synthetic methods for the monoalkylation of calix[4]arenes at the lower rim allows the synthesis of a new class of trihydroxamate siderophores. Three chelating hydroxamic acid units are introduced through a sequence of reactions which blocks the macrocycle in the cone conformation. The new ligands obtained form neutral 1:1 complexes (FeL) with iron (III), which are stable in EtOH/H₂O 9:1 at pH 2–7. Calix[4]arene bis-crown ethers are prepared by exploiting the selective 1,2-(proximal) functionalization of calix[4]arenes at the lower rim. These ligands are, however, less effective in complexing alkali metal cations compared with the 1,3-calix[4]arene crown-ethers which, in their partial cone structure, offer a better shielding for the complexed cations. Rigid upper rim-bridged calix[4]arenes potentially useful for the inclusion of neutral molecules are prepared by exploiting the selective 1,3-diformylation of calix[4]arene at the upper rim. Finally a new chloromethylation method for calix[4]arenes blocked in the cone conformation is described together with the synthesis of new cavitands.     

Pyrrolamidocalix[4]arenes: new receptors for anion recognition

Pyrrolamidocalix[4]arenes 1-4, members of a new class of anion receptors bearing pyrrolic units at the upper rim of calix[4]arene macrocycle, have been readily synthesized in good yields. Derivatives 1 and 3, with unsubstituted pyrrole units, show a good selectivity for over F⁻ and AcO⁻, while the presence of electron-withdrawing NO₂ substituents in 2 and 4 inverts the selectivity favoring more basic AcO⁻ and F⁻. In addition, it is demonstrated that the flexibility of calix[4]arene skeleton, present in 1 but absent in 3, is very important in the fitting process that leads the amidopyrrole moieties to wrap the tetrahedral guest.