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.     

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.     

p-tert-Butylcalix[4]arene Derivatives Containing Azathiol Receptors and Their Recognition towards Hg(II)

25,27(2,2'-bis(ethoxybenzyl))-1,9-diimine-3,7-dithianonane-p-tert-butylcalix[4]arene (3),25,27(4,4'-bis(ethoxybenzyl))-1,9-diimine-3,7-dithianonane-p-tert-butylcalix[4]arene (4),25,27(2,2'-bis(ethoxybenzyl))-1,8-diimine-3,6-dithianonane-p-tert-butylcalix[4]arene (5) and25,27(4,4'-bis(ethoxybenzyl))-1,8-diimine-3,6-dithianonane-p-tert-butylcalix[4]arene (6) havebeen synthesized by condensation reactions between25,27(2,2'-bis(ethoxybenzaldehyde))-p-tert-butylcalix[4]arene (1) and25,27(4,4'-bis(ethoxybenzaldehyde))-p-tert-butylcalix[4]arene (2) and appropriateamines. Reduction of 3 and 4 withNaBH₄ and subsequent protonation byHCl/CH₃OH resulted in25,27(2,2'-bis(ethoxybenzyl))-1,9-diaza-3,7-dithianonane-p-tert-butylcalix[4]arenedihydrogenchloride (7) and25,27(4,4'-bis(ethoxybenzyl))-1,9-diaza-3,7-dithianonane-p-tert-butylcalix[4]arenedihydrogenchloride (8), respectively. Complexation studies of 7 and 8 withZn(II), Cd(II) and Hg(II) ions were carried out bypotentiometric titration. Compounds 7 and8 selectively form 1 : 1 complexes with Hg(II), andtheir stability constants (log Ks) were estimated tobe 4.47 ± 0.08 and 3.20 ± 0.13, respectively. From spiecies distribution plots, 7 and 8were found to form the highest amount of 1 : 1 complexes with Hg(II) at pH 8.7 and 9.1, respectively.     

A Schiff basep-tent-butylcalix[4]arene. Synthesis and metal ion complexation

This communication describes the synthesis of Schiff base calix[4]arene (1) in which the Schiff base unit bridges two opposite hydroxy groups ofp-tert-butylcalix[4]arene. The synthesis of (1) has been achieved by refluxing in acetonitrile-methanol the appropriate 1,3-dicarbaldehyde-p-tert-butyl-calix[4]arene (4) with 1,3-diaminopropane. The yield of the reaction is 19%. Ligand (1) possesses a compartment containing two nitrogen atoms, four ether-type oxygen atoms, and two ionizable hydroxy groups likely to complex metal cations.     

Synthesis of Oligomer and Styrene Polymer-supported Calix[4]arene Derivatives and Selective Extraction of Fe3+

Five new polymeric compounds containing more than one calix[4]arene have been synthesized by reacting an oligomer with 5,11,17,23-tetrakis[(diethylamino)methyl]-25,26,27,28-tetrahydroxycalix[4]arene (L1), 25,27-dimethyl-26,28-dihydroxy-p-tert-butylcalix[4]arene diketone (L2), and p-nitrocalix[4]arene (L3), and chloromethylated polystyrene with 25,27-dimethyl-26,28-dihydroxy-p-tert-butylcalix[4]arene diketone (L4) and p-nitrocalix[4]arene (L5). These compounds were studied by the selective extraction of Fe³⁺ cation from the aqueous phase into the organic phase and was carried out by using compounds L1–L5. It was observed that the polymer support attached to the lower rim of p-nitrocalix[4]arene was the most efficient carrier of Fe³⁺ in the extraction process.     

Synthesis and conformation studies of multiple bridged p-tert-butylcalix[7]arene diphosphates

p-tert-Butylcalix[7]arene reacting with phosphorus pentachloride and then with water afforded two stereoisomers p-tert-butylcalix[7]arene diphosphates 2a and 2b, representing the first phosphorus multiple bridged calix[7]arene. The more accurate structure of 2a was investigated with the aid of Gaussian03 calculations.     

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.     

Inherently chiral biscalixarene cone–cone conformers consisting of calix[4]arene and calix[5]arene subunits

Inherently chiral biscalixarenes with hetero-cavities were synthesized by a covalent assembly of p-tert-butylcalix[5]arene with a 1,3-substituted calix[4]arene via 1,3-alkylation reaction and subsequent desymmetrization. The racemates were resolved by chiral HPLC method. ¹H NMR spectra, VT-NMR spectra, and theoretical calculations support that the calix[5]arene subunit of the inherently chiral calix[4][5]arene ester adopts a cone-in conformation, with the aromatic ring bearing the CH₂CO₂Et group tilting inward the calix[5]arene cavity. By contrast, such a cone-in structural feature of the calix[5]arene subunit disappears for the corresponding inherently chiral calix[4][5]arene carboxylic acid, due to the intramolecular hydrogen bonding between the carboxyl group and an ethereal oxygen of the glycolic chain.     

1,3-Disubstituted p-tert-Butylcalix[4]arenes as Cholinesterase Inhibitors

The inhibitory effect of 1,3-substituted p-tert-butylcalix[4]arenes on butyrylcholinesterase from horse serum has been discovered and kinetically investigated with photometric microassay techniques. The interaction of calix[4]arene with the enzyme is described in accordance with the formal kinetics of competitive reversible inhibition. The inhibition constants calculated depend on the substituent in the lower rim of the calix[4]arene and vary in the range of (5–110) × 10^-6 M. The proposed mechanism of inhibition involves the cooperative interaction of indophenyl acetate used as a substrate, calix[4]arene and the enzyme without any covalent or electrostatic binding of the functional groups in the active site of cholinesterase. This results in the coordination of the calixarene on the enzyme surface in the proximity of the enzyme active site. Such interaction prevents the substrate from entering the enzyme active site.     

Endo-cavity Complexes between Calix[6]arene Dianions and Aliphatic Ammonium Cations: Structure of a Hexylammonium Complex by X-ray Crystallography

The interactions of calix[6]arene and p-tert-butylcalix[6]arene with aliphatic amines in acetonitrile solution were studied by spectrophotometric titrations in the UV region and ¹H NMR spectrometry. Calix[6]arenes can undergo two deprotonations by aliphatic amines and the extent of the second proton transfer is mainly governed by the size of the α-substituent of the amine. ¹H NMR spectra show that the macrocycle adopts a 1,2,3-alternate conformation and that the α-hydrogens of the ammonium ions are shielded by the π-clouds of the aromatic rings. The X-ray crystal structure of the dihexylammonium complex of the p-tert-butylcalix[6]arene dianion, reported here, confirms the 1,2,3-alternate conformation and shows one of the two ammonium moieties encapsulated in the inner cavity of the macrocycle.     

Stereochemical control of calixarenes useful as rigid and conformationally diversiform platforms for molecular design

Stereochemical problems and related functions of calix[4]arenes, calix[6]arenes and their chiral derivatives have been reviewed. In p-tert-butylcalix[4]arene (1H₄) and its mono-, di-, tri-, and tetra-O-alkyl derivatives (1H₃R, 1H₂R₂,1HR₃, and 1R₄, respectively), 23 different homologues can exist (including 1H₄). We found that the OH group in the unmodified phenol unit is permeable through the calix[4]arene ring. Thus, several conformational isomers become equivalent after the ‘oxygen-through-the-annulus’ rotation of the OH group and the number of possible homologues is reduced to 13 (including 1H₃). We report in this paper the syntheses of all of these possible conformational isomers using a protection-deprotection method with a benzyl group and metal template effects. On the other hand, all possible chiral isomers that can be derived from calix[4]arene by modification of the OH groups have been systematically classified. Molecular asymmetry can be generated not only by different substituents but also by conformational isomerism. The numbers of chiral isomers are 17 for tetra-O-substituted calix[4]arenes, 9 for tri-O-substituted calix[4]arenes, 3 for di-O-substituted calix[4]arenes, and 0 for mono-O-substituted calix[4]arenes. Chiral calix[4]arenes can also be designed by the introduction of a substituent into the m-position of a phenol unit or by the use of a dissymmetric ‘stapling reaction’ in proximal phenol units. In p-tert-butylcalix[6]arene, the conformational behaviour is totally different from that in p-tert-butylcalix[4]arene. A large degree of conformational freedom remains in the framework, and both ‘oxygen-through-the-annulus rotation’ and ‘para-substituent-through-the-annulus rotation’ can take place. However, when metal cations are bound to calix[6]aryl esters, the conformation is changed to a cone type. Bridging and capping are powerful methods to immobilize the conformation of calix[6]arenes. In addition, definitive evidence for ring immobilization was obtained from the absence of racemization in the chiral calix[6]arene. A successful example of chiral recognition for α-amino acid derivatives was achieved by using chiral homooxacalix[3]arene which has ‘pseudo C₂ symmetry’. These examples indicate that calixarenes serve as rigid and conformationally diversiform platforms for the design of novel functional supramolecules.     

Regioselective intramolecular bridging of p-tert-butylcalix[10]arene

The synthesis and characterization of a series of regioselective intramolecular bridging of calix[10]arene are described for the first time. Reacting p-tert-butylcalix[10]arene with tri-ethylene glycol ditosylate using K₂CO₃ as a base in toluene, 1,2-calix[10]crown-4 2a, 1,4-calix[10]crown-4 2b and 1,6-calix[10]crown-4 2c were obtained in yields of 9%, 14% and 7%, respectively. While using Cs₂CO₃/acetone instead of K₂CO₃/toluene, the 1,4-calix[10]crown-4 2b was obtained selectively in good yield up to 50%.     

The synthesis of metallocene calix[4]arenes

The condensation of 1,1-bis(chlorocarbonyl)metallocenes andp-tert-butylcalix[4]arene in toluene leads to novel metallocene calix[4]arenes in which the metallocene subunit bridges the opposite hydroxy groups of the parent calixarene.Presented at the Fourth International Symposium on Inclusion Phenomena and the Third International Symposium on cyclodextrins, Lancaster, U.K., 20–25 July 1986.     

Calix[4]Arene Cavitands: A Solid State Study on the Interactions of their Aromatic Cavity with Neutral Organic Guests Characterised by Acid CH3 or CH2 Groups

Abstract

To gain information on CH-π aromatic interactions involved in the formation of host-guest adducts, the geometrical parameters which define the solid state structures of the complexes of calix[4]arenes in the cone conformation with guests having acid CH₃ or CH₂ groups have been studied. Most of the data have been obtained from the CH₃CN and CH₂Cl₂ calix[4]arene complexes retrieved from the literature. To understand the effect of the acidity on these parameters, p-cyclohexylcalix[4]arene-biscrown-3 ? CH₃CN, p-tert-butylthiacalix[4]arene ? CH₃CN, p-tert-butylthiacalix[4]arene ? CH₃NO₂, 1,3-dipropoxy-p-tert-butylcalix[4]arene ? ClCH₂CN and 1,3-dipropoxy-p-tert-butylcalix[4]arene ? CH₂(CN)₂ complexes were prepared, crystallised and investigated in the solid state. CH₃X guests are bound preferentially by hosts having a C₄ symmetry. The interaction is directional, but it is independent from the basicity of the host and acidity of the guest, indicating that classic hydrogen bond do not play a major role. On the contrary CH₂XY guests find the best matching with hosts having a C_2v symmetry, interacting specifically with two diametrical aromatic rings. These interactions are directional and show a correlation between the acidity of the guest and the CH-π aromatic distance, thus supporting a stronger contribution of “classic” hydrogen bond in these latter complexes. These results are in agreement with the hypothesis that CH-π aromatic interactions derive from the superimposition of different types of intermolecular forces, whose contribution depends on several factors as the nature of the interacting partners.     

Structures and properties of solvated and unsolvated isopropyl functionalised calix[4]arenes

The tetra-isopropyl ethers of calix[4]arene and p-t-butylcalix[4]arene have been isolated in the cone conformation, and structurally characterised as chloroform solvates. Thermogravimetric analysis demonstrated that the parent isopropylcalix[4]arene solvate is significantly more stable than the p-t-butylcalix[4]arene analogue, retaining the solvent up to a temperature of 125°C. It was found that the calix[4]arene ether sublimes at atmospheric pressure, and solvent-free crystals appropriate for structure determination were produced at reduced pressure. The p-t-butylcalix[4]arene ether was also isolated without solvent in the lattice, but in this case the calixarene was crystallised from acetone, as sublimation did not produce crystals of sufficient quality.     

New Bis- and Tris-Ferrocenoyl and Tris-Benzoyl Lower-rim Substituted Calix[5]arene Esters: Synthesis,Electrochemistry and X-ray Crystal Structures

Abstract

New tris-benzoyl-, tris-ferrocenoyl- and bis-ferrocenoyl p-tert-butylcalix[5]arene esters have been synthesised (1–3 respectively) by reaction of the parent calixarene with the appropriate acid chloride. X-ray crystal structures of all three compounds have been determined with the structure of 2 revealing an ethanol guest molecule bound deep in the cavity of the calix[5]arene. The electrochemical properties of 2 have been extensively investigated using rotating disk electrode, cyclic and square wave voltammetric techniques. Electrochemical evidence is presented suggesting 2 has the capability of detecting neutral polar guest molecules, such as dimethylformamide, in dichloromethane solutions.     

Thermo gravimetric analysis of supramolecular complexes of p-tert-butylcalix[6]arene and ammonium cations: crystal structure of diethylammonium complex

Thermo gravimetric analysis of ammonium-p-tert-butylcalix[6]arene salts were carried out to determine the stoichiometry of the inclusion compounds and the temperature of leaving of the ammonium cation, as amine, from the solid phase by a reverse proton transfer reaction to calixarene. The chain length of the amine molecules and their relative basicity order are the main factors which determine the decomplexation temperatures for the ammonium salts of piperidinium, diethylammonium, ethylenediammonium, morpholinium, s-butylammonium, butylammonium, hexylammonium and triethylammonium salts of p-tert-butylcalix[6]arene anion. The solid state structure of bis-diethylammonium-p-tert-butylcalix[6]arene dianion is reported. The calix moiety adopts a 1,2,3 alternate conformation, with one ammonium as exo-calix and other as endo-calix, with an intricate array of hydrogen bonds between phenol, phenolate and ammonium cations.     

Preparation and characterisation of thiol functionalised p-tert-butylcalix[4]arene-embedded polymer inclusion membranes: performance and selectivity

ABSTRACT

Here in we report the syntheses of the thiol functionalised p-tert-butylcalix[4]arene from the reaction of p-tert-butylcalix[4]arene-dialkylbromide derivative with thiourea. The structure of the thiol functionalised p-tert-butylcalix[4]arene was determined by using ¹HNMR, ¹³CNMR and elemental analysis techniques. Furthermore, the thiol functionalised p-tert-butylcalix[4]arene, cellulose triacetate (CTA) and 2-nitrophenyl octyl ether (o-NPPE) in dichloromethane were used to make a new calixarene-embedded polymer inclusion membrane (Bu^t-C@PIM). The surface and structure morphology of Bu^t-C@PIM was detected using thermogravimetric analysis, elemental analysis techniques and scanning electron microscopy. The affinity (the percentage of metal ion transferred from the source solution) of a PIM towards a range of divalent cations was found to follow the order Pb²⁺ > Zn²⁺ > Ni²⁺ > Cu²⁺ > Cd²⁺ > Co²⁺. The results also indicated that the transport efficiency of Bu^t-C@PIM was repeatable and may be beneficial in the development of a simplistic and highly influential trace metal recovery method from aqueous solution.     

Inclusion of multi-ring compounds byp-tert-butylcalix[5]arene

The inclusion complex ofp-tert-butylcalix[5]arene with tetralin has been characterized in the solid state by a single crystal X-ray diffraction study and by¹³C CP/MAS NMR experiments. A crystallographic mirror plane bisects the calix[5]arene and contains the tetralin molecule (which is dynamically disordered). The guest penetrates the upper rim of the calixarene and the experimental results indicate the saturated ring is imbedded most deeply.p-tert-Butylcalix[5]arene (tetralin) · 2 EtOH belongs to the monoclinic space group C2/m witha = 22.187(6),b = 15.823(6),c = 18.168(5) Å, = 99.70(2)°, andD _c = 1.09 g cm^–3 forZ = 4. Refinement based on 1652 observed reflections led to a finalR value of 0.081. Supplementary Data relating to this article are deposited with the British Library as supplementary publication No. SUP 82/82129 (19 pages).     

Two Stabilized Calix[6]Cryptand Stereo Isomers used as Stationary Phases for Capillary Gas Chromatography

ABSTRACT

A couple of stabilized calix[6]cryptand steroisomers were synthesized by capping 1,3,5-trimethoxy-p-tert-butylcalix[6]arene with 1,1,1-tri(tosyloxyethoxyethoxymethyl)-propane and used as stationary phases for capillary gas chromatography. Their chromatographic characteristics and separation mechanism for aromatic positional isomers and polycyclic aromatic hydrocarbons are discussed.