Synthesis and Inclusion Properties of a Novel Thiacalix[4]arene-Based Hard–Soft Receptor with 1,3-Alternate Conformation

A novel ditopic receptor possessing two complexation sites and bearing 1,3-alternate conformation based on thiacalix[4]arene was prepared. The binding behaviors with alkali metals and silver ion have been examined by ¹H NMR titration experiment. Although the formation of the heterogeneous dinuclear complexes was not observed, the exclusive formation of mononuclear complexes of 1,3-alternate-3 with metal cations is of particular interest in negative allosteric effect in the thiacalix[4]arene family. These findings demonstrate that preorganization, subtle conformational changes and affinity have a pronounced effect on the complexation process between the two different arms placed at the two edges of the thiacalix[4]arene cavity.     

新型多重氮杂杯[4]芳烃衍生物的合成

对叔丁基杯[4]芳烃-1,3-二醛基衍生物1与水杨酰肼、烟酰肼、异烟酰肼反应, 合成了具有开链结构新型杯[4]多重氮杂衍生物2a～2c, 产率分别为88%, 85%和90%. 化合物1与乙二酰肼、丙二酰肼、己二酰肼反应, 得到具有桥联结构的新型杯[4]多重氮杂衍生物3a～3c, 产率分别为86%, 89%和90%. 新化合物的结构经元素分析、质谱、核磁共振谱等表征证实, 杯[4]芳烃单元均为1,3-取代且采取锥式构象.     

Synthesis,crystal structure and complexation behaviour of a thiacalix[4]arene bearing 1,2,3-triazole groups

The structure and complexation behaviour of 1,3-alternate-1,2,3-triazole based on thiacalix[4]arene,1,3-alternate-1 and 2 have been determined by means of X-ray analysis, fluorescence and ¹H NMR spectroscopy. The X-ray results suggested that the nitrogen atom N3 on triazole ring can act as hydrogen bond acceptors in the self-assembly of a supramolecular structure. The fluorescence spectra changes indicated that the thiacalix[4]arene bearing 1,2,3-triazole groups were highly selective for Ag⁺ in comparison with other tested metal ions by enhancement of the monomer emission of pyrene. The ¹H NMR results suggested that Ag⁺ can be strongly bonded by the triazole groups with the cooperation of the ionophoric cavity formed by the two inverted benzene rings and the sulfur atoms of the thiacalix[4]arene.     

Synthesis and Structure of a 1,3-alternate-Thiacalix[4]arene diamide Derivative

A novel receptor possessing two complexation sites and bearing 1,3-alternate conformation based on thiacalix[4]arene, confirmed by single crystal X-ray analysis, was prepared. The tetrathiacalix[4]arene diamide shows strong intramolecular hydrogen bonding. The binding behavior towards K⁺ and halides has been examined by ¹H NMR titration experiments.     

Hard–Soft Receptors, Tetrakis[(N,N-diethylaminocarbonyl)methoxy] thiacalix[4]arene Derivatives with cone and 1,3-alternate Conformation

Direct O-alkylation of p-tert-butyltetrathiacalix[4]arene with N,N-diethylchloroacetamide afforded two conformational isomers (1,3-alternate and cone) of tetrakis[(N,N-diethylaminocarbonyl)methoxy]thiacalix[4]arene and 1,3-disubstituted bis[(N,N-diethylaminocarbonyl)methoxy]thiacalix[4]arene, depending on the base used. The complaxation behaviors of the tetrakis isomers were assessed by ¹H NMR titration experiments. Evidence of 1:2 (homo- and hetero-dinuclear) complexes formation of 1,3-alternate-tetrakis[(N,N-diethylaminocarbonyl)methoxy]thiacalix[4]arene with alkali (K⁺ and Na⁺) or transition (Ag⁺) metal ions was obtained. Interestingly, it was found that the cone-tetrakis[(N,N-diethylaminocarbonyl)methoxy]thiacalix[4]arene required a prior Ag⁺ complexation to form 1:2 heterodinuclear complex. Received in final form: 26 January 2005     

Improvement of selective d-cation binding by tetrathiacalix[4]arene hydrazides: synthesis and extraction properties

New de-tert-butyltetrathiacalix[4]arenes with acetylhydrazide substituents in cone and 1,3-alternate conformations have been synthesised with good yield by the hydrazinolysis of calix[4]arene ester derivatives. The recognition ability of synthesised macrocycles towards transition and alkali metals has been investigated by the picrate extraction method. The stoichiometry of complexes and the extraction constants have been determined. It has been found that tetrahydrazides do not extract alkali metal ions, but show an excellent affinity towards transition and heavy metal cations. The 1,3-alternate conformer of de-tert-butyltetrathiacalix[4]arene has revealed a remarkable selectivity for Ni²⁺ and Ag⁺ in the row of d-elements and for Cd²⁺ ion among the toxic heavy metals. The experimental data show that the removal of tert-butyl groups from tetrathiacalix[4]arene framework leads to the drastic improvement of extraction efficiency and selectivity of new tetrahydrazides.     

A Synthetic Cation-Transporting Calix[4]arene Derivative Active in Phospholipid Bilayers

One order of magnitude: The transport of Na⁺ and K⁺ ions through a phospholipid bilayer occurs with much higher conductance levels with 1 and 2 than with typical Na⁺-transporting proteins or gramicidin. However, the cations do not appear to pass through the calix[4]arene ring, which has a rigid 1,3-alternate conformation. diazacrown=10-benyzl-1,10-diaza[18]crown-6 group.     

Synthetic and NMR Studies on Calix[n]Arene (n = 4,6,8) Triflates,Mesylates, and Tosylates

Abstract

The synthesis and full characterization of eight new calix[n]arene sulfonate esters including their conformational analysis were carried out. While p-tBucalix[6]arene and p-tBu-calix[8]arene esters are conformationally labile in the temperature interval of 25–100°C, p-tBu-calix[4]arene mono-and diesters were isolated as stable conformers at ambient temperature. Two 1,3-functionalised compounds of these derivatives, p-tert-butylcalix[4]arene ditriflate (5) and dimesylate (6) were shown unexpectedly high conformational stability up to 100°C by dynamic NMR measurements. The NMR measurements confirm the pinched-cone conformation for both derivatives. For the dealkylated calix[4]arene derivatives the partial cone conformer of the triesters have been obtained as major products in all cases.     

Allosteric bindings of thiacalix[4]arene-based receptors with 1,3-alternate conformation having two different side arms

A novel ditopic receptor possessing two complexation sites such as crown ether and 2-pyridylmethyl groups bearing 1,3-alternate conformation based on thiacalix[4]arene was prepared. The binding behaviors with Li⁺ and Ag⁺ have been examined by ¹H NMR titration experiment. The exclusive formation of mononuclear complexes of 1,3-alternate-5 with Li⁺ and Ag⁺ was observed even though the formation of the heterogeneous dinuclear complexes was expected. The decomplexation of Li⁺ from the crown moiety of 1:1 complex 1,3-alternate-5?Li⁺ to form the Ag⁺?1,3-alternate-5 complex by addition of AgSO₃CF₃ clearly shows that pyridyl moiety works as an efficient switch-off of the recognition ability of the crown moiety. We have also developed the construction of hydrogen-bonding self-assembly heterodimeric systems based on bis(4-pyridyl) and dicarboxylic acid thiacalix[4]arene derivatives in 1,3-alternate conformation. Their supramolecular behaviors are studied by ¹H NMR titration experiments with K⁺ and Ag⁺ ions. Although the values of the dimerization constants are relatively small, the stability of the dimers is strong enough to overcome only small conformational changes upon complex formation.     

Synthesis and heteronuclear inclusion properties of a novel thiacalix[4]arene-based hard-soft receptor with 1,3-alternate conformation

A novel thiacalix[4]arene ditopic receptor with 1,3-alternate conformation and possessing two complexation sites for hard and soft cations, 5,11,17,23-tetra-tert-butyl-25,27-bis[(N,N-diethylaminocarbonyl)methoxy]-26,28-bis[(pyridylmethyl)oxy]-2,8,14,20-tetrathiacalix[4]arene is prepared. Regioselective synthesis of distal-bis[(N,N-diethylaminocarbonyl)methoxy]thiacalix[4]arene is accomplished by a protection-deprotection method using benzyl groups as a protecting group. The deprotection of benzyl group was succeeded in the presence of solid superacid (Nafion-H) under refluxing benzene. Its complexation behavior is examined by ¹H-NMR titration experiments. The formation of 1:2 homo- and heteronuclear complexes demonstrates that the preorganization, subtle conformational changes and affinity have a pronounced effect on the complexation of the receptor.     

Synthesis and electrochemical properties of calix[4]arene derivatives containing ferrocene units in the cone and 1,3-alternate conformation

Two novel calix[4]arene receptors containing ferrocene units in cone (L₁) and 1,3-alternate (L₂) conformations have been synthesized from 25,27-dihydroxy-26,28-bis[(3-aminopropyl)oxy]calix[4]arene 4 or 25,26,27,28-tetra[(3-aminopropyl)oxy]calix[4]arene 6 and ferrocenecarboxaldehyde via condensation, respectively. Their structures have been characterized by ¹H, ¹³C, APT, COSY NMR, FTIR, HSMR, and UV–vis spectral data. The electrochemical behavior of L₁ and L₂ has been investigated in the presence of F^?, Cl^?, Br^?, H₂PO₄^?, CH₃COO^? anions. Electrochemical studies show that these receptors electrochemically recognize CH₃COO^?, H₂PO₄^?, and Cl^?, anions. Using an UV–vis study, the selectivity to these anions in DMSO solution was confirmed.     

Selectively formylated and bridged calix[6]arene derivatives at the upper rim

The strategy of bridging the anisole units at the upper rim of calix[6]arene has been applied to strain the conformations of calix[6]arene. Based on the selective formylation of the 1,3,5-tri-p-tert-butylcalix[6]arene, several new calix[6]arene derivatives with different 1,3-bridged chains or a 1,3,5-tripod bridge at the upper rim have been prepared with moderate yields. The ¹H NMR spectra indicate that these calix[6]arene derivatives adopt a cone conformation, which has also been confirmed by the theoretical calculation at AM1 level. X-ray crystal structure of 1,3,5-tripod bridged compound 5 discloses that the calix[6]arene host stands in a cone conformation with approximate C_3v symmetry, and that a methanol molecule is enclosed in its hydrophobic cavity and stabilized by multi hydrogen bonds.     

Calix[4]arenes with 1,2- and 1,3-upper rim tetrathiafulvalene bridges

Herein we report the synthesis of several calix[4]arene derivatives with tetrathiafulvalene bridges at the upper rim. Calix[4]arene-tetrathiafulvalene (TTF) conjugates 4a–d, fixed in cone conformation and comprising two smaller 1,2-bridges, were prepared by cyclisation of tetrakis-chloromethylated calix[4]arene 1 with 2,3-dithiolates of TTFs. Larger calix[4]arene-TTF macrocycles 14 and 15, also in cone conformation, contain 1,3-bridges and were synthesised by cyclisation of 2,6- and 2,7-dithiolates of TTFs with bis-bromomethylated calix[4]arene 7. Redox properties of new calix[4]arene-TTF conjugates were characterised using cyclic voltammetry.     

Preparation of Calix[4]arene Alkylamine Derivatives by Mannich Reaction and use as Phase-Transfer Catalysts for Esterification Reaction

In this study, 5,11,17,23-tetrakis[(N-ethylpiperazine)methyl]-25,26,27,28-tetrahydroxycalix[4]arene (3) and 5,11,17,23-tetrakis[(4-carboethoxy-N-piperidino) methyl]-25,26,27,28-tetrahydroxycalix[4]arene (4) were synthesized in one step according to the Mannich reaction by the treatment of calix[4]arene with a secondary amine (N-ethylpiperazine, ethyl-4-piperidincarboxylate) and formaldehyde. The calix[4]arene derivatives (3, 4) were characterized by a combination of FTIR, ¹H NMR and elemental analyses. The synthesized compounds were used in an esterification reaction as the phase transfer catalyst. The catalytic efficiency of the calix[4]arenes 3 and 4 was evaluated by carrying out the ester-forming reaction of alkali metal carboxylates (sodium butyrate or sodium caprylate) with p-nitrobenzyl bromide. It was observed that the ester-forming reaction of alkali metal carboxylates with p-nitrobenzyl bromide, using calix[4]arene-based catalyst 3 as a phase-transfer catalyst in dichloromethan, provided the best yields.     

Dibutylphosphinoylmethyloxythiacalix[4]arenes. Synthesis,structure, americium,europium and technetium extraction

A series of thiacalix[4]arenes bearing one, two or four chelating dibutylphopshinoylmethoxy groups have been synthesised and studied in the context of this paper. The synthesis consisted of precise Williamson alkylation of thiacalixarene tetrols with tosylate of dibutylhydroxymethyl phosphine oxide in the presence of alkali metal carbonates or sodium hydride. Stereochemical yield of the reaction (cone or 1,3-alternate conformer) depends on the nature of alkali metal. Small-sized ‘hard’ sodium cation organises the macrocyclic platform in the cone conformation, but larger and ‘soft’ potassium and cesium cations stabilise the macrocycle in the 1,3-alternate conformation. All synthesised compounds (except monophosphine monoxide) possess either moderate or high extraction ability towards pertechnetate ion. The cone-shaped thiacalix[4]arene tetraphosphine tetraoxide due to cooperative (macrocyclic) effect of eight oxygen atoms of the phosphinoylmetoxy-binding groups effectively extract spherical americium, europium cations due to cooperative (macrocyclic) effect of eight oxygen atoms of the phosphinoylmetoxy-binding groups. The extraction ability is very similar to that of calix[5]arene pentaphosphine pentaoxide existing in the cone conformation.     

Regioselective Synthesis and Inclusion Properties of distal-Bis[(2-pyridylmethyl) oxy]tetrathiacalix[4]arenes

Regioselective synthesis of bis[(2-pyridylmethyl)oxy]tetrathiacalix[4]arenes was accomplished by a protection–deprotection method using benzyl groups as a protecting group. The conformational studies of distal-bis[(2-pyridylmethyl)oxy]thiacalix[4]arenes in solution and solid state are described. The two-phase solvent extraction data indicated that bis[(2-pyridylmethyl)oxy]tetrathiacalix[4]arenes show strong Ag⁺ (E%, 97%) affinity. In contrast, no significant E% is observed for K⁺. A good Job plots proves 1:1 coordination of 1,3-alternate -3 with Ag⁺ cation. ¹H-NMR Titration of 1,3-alternate- 3 with AgSO₃CF₃ also clearly demonstrates that a 1:1 complex is formed with retention of the original symmetry. The conformational changes of pyridine moiety from the original outward orientation of the ring nitrogen to the inside orientation toward the thiacalixarene cavity were observed in the process of Ag⁺ complexation. The down-field shifts of the benzene protons of the benzyl group were also observed and attributed to the conformational deviation from the original face to face overlapping.     

On the importance of the pore inner cavity for the ionophoric activity of 1,3-alternate calix[4]arene/steroid conjugates

1,3-Alternate calix[4]arenes, decorated with four nonpolar ‘all-trans’ tetracyclic nuclei and cation-stabilizing β-methoxyethoxy appendages, were synthesized from commercially available starting materials and through straightforward functional groups transformations/couplings. Their Na⁺-transport activities, when compared with those exerted by the known conformationally-rigidified 1,3-alternate calix[4]arene AB/cis cholic acid conjugates, suggest that the cation conductance is related to the morphology of the pendant steroids.     

Synthesis of new chiral calix[4]arene diamide derivatives for liquid phase extraction of α-amino acid methylesters

The synthesis of chiral diamide derivatives of calix[4]arene from the reaction of p-tert-butylcalix[4]arene diester 1a and calix[4]arene diester 1b with various amino alcohols were reported. The ¹H and ¹³C NMR, data showed that the compounds synthesized exist in the cone conformation. The extraction study properties of these new compounds 3a,b–4a,b towards some selected α-amino acid methylesters are also reported.     

Mercury(II) and silver(I) receptors based on tetrathiacalix[4]arene hydrazones

The extraction ability of phenyl hydrazone derivatives of cone- and 1,3-alternate tetrathiacalix[4]arenes towards to some alkali, alkaline earth, transition and heavy metal ions has been investigated by picrate extraction method. The synthesized cone-tetrathiacalix[4]arene hydrazones show a high efficiency coupled with an excellent selectivity towards for Ag⁺ and Hg²⁺ ions. The stoichiometry of complexes and the extraction constants have been determined. The influence of calix[4]arene platform’s structure and the electron donor substituents in phenyl fragments on the extraction efficiency has been discussed.     

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.