Breaking thiacalix[4]arene into pieces – a novel synthetic approach to higher calixarenes bearing mixed (–S–, –CH2–) bridges

A novel approach to calix[5–7]arenes possessing mixed (S and CH₂) bridges within the skeleton is based on the reaction of thiacalix[4]arene monosulfoxide with BuLi leading to a linear phenolic tetramer in essentially quantitative yield. This key intermediate is then cyclized with suitable building blocks to give macrocyclic calixarene analogues. Compared to the traditional stepwise construction of similar systems, this procedure based on thiacalixarene cleavage represents a scalable, robust, and straightforward synthesis and enables the preparation of larger calixarenes on a gram scale. As shown by ¹H NMR and UV-vis titration experiments, the mixed-bridge calix[7]arene is able to recognize fullerenes C₆₀ and C₇₀, thus showing possible applications of such systems. The structures of the mixed bridge systems were confirmed by single crystal X-ray analysis, and the behavior of novel macrocyclic skeletons in solution was studied using dynamic NMR techniques.

A novel approach is based on the cleavage of thiacalix[4]arene monosulfoxide with BuLi providing a linear tetramer in an essentially quantitative yield which is used as a building block for further cyclization.     

Highly functionalized calix[4]arenes via multicomponent reactions: synthesis and recognition properties

Multicomponent reactions (MCRs) include several aspects of green chemistry principles, so it is obvious that chemists in different areas are increasingly interested in providing their product by multicomponent approaches. MCRs can be very useful in supramolecular chemistry, especially to produce novel supramolecular derivatives. Therefore, there are several reports of highly-functionalized calix[4]arene derivatives obtained by MCRs instead of conventional stepwise protocols during the last decade. In this paper, we have particularly focused on the exploitation of upper rim and lower rim substituted calix[4]arenes in multicomponent approaches as a facile and convenient synthetic strategy. The value of this method lies in its operational simplicity, mild reaction conditions and structural diversity of the products. Interestingly, in most cases the products afforded by this method offer unique features and applications which are highlighted in the following sections.

Multicomponent reactions (MCRs) include several aspects of green chemistry principles, so it is obvious that chemists in different areas are increasingly interested in providing their product by multicomponent approaches.     

Synthesis of a novel resorcin[4]arene–glucose conjugate and its catalysis of the CuAAC reaction for the synthesis of 1,4-disubstituted 1,2,3-triazoles in water

The Cu(i)-catalyzed azide–alkyne cycloaddition (CuAAC) in aqueous media using resorcin[4]arene glycoconjugate (RG) is reported. The eight β-d-glucopyranoside moieties constructed on the resorcin[4]arene upper rim provide a pseudo-saccharide cavity that offers a suitable host environment for water-insoluble hydrophobic azido and/or alkyne substrates in water. The utility of RG was established as an efficient inverse phase transfer catalyst for the CuAAC in water as a green approach for the synthesis of 1,4-disubstituted 1,2,3-triazole species. The catalytic utility of RG (1 mol%) was demonstrated in a multicomponent one-pot CuAAC for various azido/alkyne substrates. The RG acts as a molecular host and a micro-reactor resulting in the 1,4-disubstituted 1,2,3-triazoles in excellent yield.

The Cu(i)-catalyzed azide–alkyne cycloaddition (CuAAC) in aqueous media using resorcin[4]arene glycoconjugate (RG) is reported.     

Heterometallic cobalt(ii) calix[6 and 8]arenes: synthesis,structure and electrochemical activity

Heterometallic cobalt p-tert-butylcalix[6 and 8]arenes have been generated from the in situ reaction of lithium reagents (n-BuLi or t-BuOLi) or NaH with the parent calix[n]arene and subsequent reaction with CoBr₂. The reverse route, involving the addition of in situ generated Li[Co(Ot-Bu)₃] to p-tert-butylcalix[6 and 8]arene, has also been investigated. X-ray crystallography reveals the formation of complicated products incorporating differing numbers of cobalt and lithium or sodium centers, often with positional disorder, as well as, in some cases, the retention of halide. The electrochemical analysis revealed several oxidation events related to the subsequent oxidation of Co(ii) centers and the reduction of the metal cation at negative potentials. Moreover, the electrochemical activity of the phenol moieties of the parent calix[n]arenes resulted in dimerized products or quinone derivatives, leading to insoluble oligomeric products that deposit and passivate the electrode. Preliminary screening for electrochemical proton reduction revealed good activity for a number of these systems. Results suggest that [Co₆Na(NCMe)₆(μ-O)(p-tert-butylcalix[6]areneH)₂Br]·7MeCN (6·7MeCN) is a promising molecular catalyst for electrochemical proton reduction, with a mass transport coefficient, catalytic charge transfer resistance and current magnitude at the catalytic turnover region that are comparable to those of the reference electrocatalyst (Co(ii)Cl₂).

Reactions between p-tert-butylcalix[6 and 8]arenes and lithium or sodium reagents led to complex structures often with positional disorder. Such systems are capable of electrochemical proton reduction.     

Robust hydrophobic gold,glass and polypropylene surfaces obtained through a nanometric covalently bound organic layer

The (electro)chemical grafting of a polyfluorinated calix[4]arene on gold, polypropylene and glass is reported. The modified surfaces were characterized by ellipsometry, atomic force microscopy (AFM), and by X-ray photoelectron spectroscopy (XPS). A nanometric, robust and uniform monolayer of covalently surface-bound calix[4]arenes was obtained on the three different materials. For all surfaces, contact angles higher than 110° were recorded, highlighting the hydrophobic character given by this ∼2 nm thin organic monolayer. Remarkably, the contact angle values remained unchanged after 18 months under a laboratory atmosphere. The results presented herein thus present an attractive and sustainable strategy for bringing hydrophobic properties to the interface of a wide range of materials.

The grafting of a polyfluorinated calix[4]arene-tetradiazonium derivative on various surfaces led to the formation of very robust and stable hydrophobic monolayers.     

Meso-functionalization of calix[4]arene with 1,3,7-triazapyrene in the design of novel fluorophores with the dual target detection of Al3+ and Fe3+ cations

A meso-functionalization strategy has successfully been applied to the synthesis of novel 1,3,7-triazapyrene derivatives of calixarenes. The key synthetic step in these transformations providing the direct C–C bond formation is nucleophilic substitution of hydrogen (S_N^H) in 1,3,7-triazapyrene. General photophysical characteristics for these macrocyclic compounds, as well as features in emission properties upon addition of various metal cations have been elaborated. Studies using NMR spectroscopy have also shown a mutual effect of both calix[4]arene and 1,3,7-triazapyrene moieties on the coordination process. The complex stoichiometry and binding constants for Al³⁺ and Fe³⁺ guests have been explored with titration experiments.

Novel bifunctional fluorophores with the dual target detection of Al³⁺ and Fe³⁺ cations were synthesized in yields up to 70% via bridge-functionalization of calix[4]arenes with the 1,3,7-triazapyrene scaffold.     

Viologen–cucurbituril host/guest chemistry – redox control of dimerization versus inclusion

Two calix[4]arene systems, C23⁴⁺ and C24⁴⁺ – where 2 corresponds to the number of viologen units and 3–4 corresponds to the number of carbon atoms connecting the viologen units to the macrocyclic core – have been synthesized and led to the formation of [3]pseudorotaxanes when combined with either CB[7] or CB[8]. The [3]pseudorotaxanes spontaneously dissociate upon reduction of the bipyridinium units as the result of intramolecular dimerization of the two face-to-face viologen radical cations. CB[7] and CB[8]-based [2]pseudorotaxanes containing monomeric viologen guest model compounds, MC3²⁺ and MC⁴⁺, do not undergo decomplexation and dimerization following electrochemical reduction of their bipyridinium units.

Two calix[4]arenes with two viologen units separated by 3 or 4 carbon atoms from the macrocyclic core were synthesized and led to the formation of [3]pseudorotaxanes when combined with CB[7] or CB[8].     

Concentration-dependent supramolecular self-assembly of A1/A2-asymmetric-difunctionalized pillar[5]arene

A series of A1/A2-bromoalkoxy-and-hydroxy-difunctionalized pillar[5]arenes were synthesized by the removal of the pillar[5]arene-bearing benzyl group using catalytic hydrogenation. The difunctionalized pillar[5]arene bearing 8-bromooctoxy and benzyloxy substituents at the A1/A2 positions formed pseudo[1]rotaxane at low concentration and double-threaded supramolecular dimer at high concentration. The supramolecular self-assembly behavior has been probed with multiple methods including varying (variable) concentration ¹H NMR spectroscopy, diffusion-ordered spectroscopy (DOSY), dynamic light scattering (DLS) measurements, isothermal titration calorimetry (ITC), and single-crystal X-ray analysis.

Concentration-dependent supramolecular self-assembly of A1/A2-asymmetric-difunctionalized pillar[5]arene was synthesized by co-cyclization strategy. This approach enables wide range of structural manipulations to regulate the supramolecular assembly.     

Influence of water-soluble pillararene hosts on Kemp elimination

Since pillar[5]arene was first discovered in 2008, it has developed into a multifunctional supramolecular host. Its application covers many fields from drug delivery and chemical sensing to the construction of molecular machines, and so on. Supramolecular catalysis based on pillar[n]arenes is one of the hot research topics that has emerged in recent years. In this paper, we have synthesized two water-soluble pillar[5]arenes with peripheral rims bearing opposite charges and investigated their influence on Kemp elimination reaction of 1,2-phenylisoxazole derivatives. It is found that both hosts have a moderate rate acceleration effect on the reaction, and the positively charged host H1 has a greater impact on the reaction rate than the negatively charged host H2.

Water-soluble pillar[5]arenes with different rim charges have been successfully used to catalyze Kemp elimination reaction of 1,2-phenylisoxazole derivatives.     

External-stimulus-triggered conformational inversion of mechanically self-locked pseudo[1]catenane and gemini-catenanes based on A1/A2-alkyne–azide-difunctionalized pillar[5]arenes

Herein, we report a methodology for constructing mechanically self-locked molecules (MSMs) through the efficient intramolecular copper(i)-catalyzed alkyne–azide cycloaddition (CuAAC) of self-threaded A1/A2-azido-propargyl-difunctionalized pillar[5]arenes. The obtained monomeric “pseudo[1]catenane” and dimeric “gemini-catenane” were isolated and fully characterized using mass spectrometry, nuclear magnetic resonance (NMR) spectroscopy, and X-ray crystallography. Upon investigation by ¹H NMR spectroscopy in chloroform, the observed motion for the threaded ring in the pseudo[1]catenane was reversibly controlled by the temperature, as demonstrated by variable-temperature ¹H NMR studies. Two gemini-catenane stereoisomers were also isolated in which the two pillar[5]arene moieties threaded by two decyl chains were aligned in different topologies. Furthermore, the conformational inversion of pseudo[1]catenane and the gemini-catenanes triggered by solvents and guests was investigated and probed using ¹H NMR spectroscopy, isothermal titration calorimetry, and single-crystal X-ray analysis.

Mechanically self-locked molecules (MSMs) through the efficient intramolecular copper(i)-catalyzed alkyne–azide cycloaddition (CuAAC) of self-threaded A1/A2-azido-propargyl-difunctionalized pillar[5]arenes.     

Synthesis of upper rim-double-bridged calix[4]arenes bearing seven membered rings and related compounds

Meta/meta- and meta/para-disubstituted organomercury calix[4]arenes in the cone conformation were transformed into corresponding amino derivatives. Acylation and subsequent intramolecular cyclization using the Bischler–Napieralski reaction provided, in the case of the meta/meta-series, double bridged calixarenes possessing seven membered rings on the upper rim. A similar synthetic strategy applied to meta/para-isomers allowed for the isolation of monobridged compounds bearing an additional trifluoroacetamido group located distally to seven-membered rings. Both series represent inherently chiral systems, which were successfully resolved using preparative chiral HPLC. The pure enantiomers exhibited a recognition ability towards selected chiral guest molecules as documented by the ¹H NMR titration experiments. The absolute configuration of the phenyl-substituted enantiomer (meta/meta-) was confirmed by single crystal structure determination (X-ray).

Calix[4]arenes bearing one or two bridges on the upper rim were prepared as novel inherently chiral derivatives potentially capable of chiral recognition.     

Investigating partitioning of free versus macrocycle bound guest into a model POPC lipid bilayer

We report on the permeation of free and macrocycle-bound avobenzone across a POPC lipid bilayer through combined neutron reflectometry experiments and molecular dynamics simulations. Results indicate that the p-phosphonated calix[8]arene macrocycle limits the avobenzone penetration into the upper leaflet of the membrane. Hence, it could serve as a useful vehicle for safer formulations.

We report on the permeation of free and macrocycle-bound avobenzone across a POPC lipid bilayer through combined neutron reflectometry experiments and molecular dynamics simulations.     

A selective and easily recyclable dimer based on a calix[4]pyrrole derivative for the removal of mercury(ii) from water

A recyclable mercury(ii) selective dimer based on a calix[4]pyrrole derivative has been synthesised and characterised by mass and FT-IR spectrometry, Scanning Electron Microscopy (SEM) and Energy Dispersive X-ray (EDX). Information regarding the ability of the dimer to interact with metal cations was obtained from FTIR and SEM-EDX analyses. A striking feature of micrographs of the loaded dimer is the change of morphology with the cation. Based on these results, optimal conditions for removing cations from water were assessed under different experimental conditions. Results obtained demonstrate that the removal process is fast. Capacity values and selectivity factors show that the dimer is selective for Hg(ii) in single and multiple component metal solutions relative to other cations. Single-ion transfer Gibbs energies from water to a solvent containing common functionalities to those of the dimer were used to assess the counter-ion effect on the removal process. Agreement is found between these data and energy calculations derived from molecular simulation studies. Studies on polluted water in the presence of normal water components in addition to toxic metal cations are reported. Further experimental work on wastewater from the mining industry is in progress.

A recyclable mercury(ii) selective dimer based on a calix[4]pyrrole derivative has been synthesised and characterised by mass and FT-IR spectrometry, Scanning Electron Microscopy (SEM) and Energy Dispersive X-ray (EDX).     

Performance and selectivity of lower-rim substituted calix[4]arene as a stationary phase for capillary gas chromatography

This work presents the investigation of p-tert-butyl(tetradecyloxy)calix[4]arene (C4A-C10) as stationary phase for capillary gas chromatographic (GC) separations. The statically-coated C4A-C10 capillary column showed weak polarity and column efficiency of 2566 plates per m determined by n-dodecane at 120 °C. Impressively, the C4A-C10 column exhibited extremely high resolving capability for a wide range of analytes from nonpolar to polar, including n-alkanes, esters, ketones, aldehydes, alcohols and bromoalkanes. Most importantly, the C4A-C10 column exhibited an excellent separation performance for positional, structural and cis-/trans-isomers. Among them, the column displayed advantageous resolving capability over the commercial polysiloxane stationary phase for aromatic amine isomers. Moreover, the C4A-C10 column showed good column repeatability with RSD values below 0.06% for run-to-run, 0.12–0.27% for day-to-day and 2.8–5.3% for column-to-column.

This work presents the investigation of p-tert-butyl(tetradecyloxy)calix[4]arene (C4A-C10) as stationary phase for capillary gas chromatographic (GC) separations.     

New insights into the reactivity of aminomethylene derivatives of resorc[4]arene: amine group transfer,conformational analysis,reaction mechanism

Using the example of aminomethylene derivatives of resorc[4]arene and their Michael reaction with 4-hydroxycoumarin, the possibility of transferring an amine molecule from substrate to product is demonstrated. The conformation of the aminocoumarin derivatives of resorc[4]arene formed is controlled by the polarity of the solvent. For one of the products, conformational analysis was performed by kinetic sampling using metadynamics (MTD). The energies of the final set of conformers were calculated by DFT (r2scan-3c). A reaction mechanism based on multiscale (ONIOM) Nudged Elastic Band (NEB-TS) reaction profile calculations is discussed.

Using the example of aminomethylene derivatives of resorc[4]arene and their Michael reaction with 4-hydroxycoumarin, the possibility of transferring an amine molecule from substrate to product is demonstrated.     

One-pot three component synthesis of 5-allyl-1,2,3-triazoles using copper(i) acetylides

One-pot three-component reactions using copper(i) acetylide, azide, allyl iodide, and NaOH have been developed. The reactions proceed smoothly at room temperature to afford 5-allyl-1,2,3-triazoles, which can be further transformed into a variety of 1,2,3-triazole-fused bi-/tricyclic scaffolds. This method offers the most efficient, convenient, and practical route towards useful polycyclic scaffolds in moderate to excellent yields.

A one-pot three-component synthetic route toward 5-allyl-1,2,3-triazoles using copper(i) acetylide has been developed, which allows further transformation to important tricyclic scaffolds.     

Synthesis of a coumarin derivative of resorcin[4]arene with solvent-controlled chirality

This paper presents the synthesis of a coumarin derivative of resorcin[4]arene (1) using a cascade thermolysis/Michael reaction. The influence of the hydrogen bonding system on the conformational rigidity and cyclochirality of the coumarin derivative of resorcin[4]arene was discussed; these properties depended on the proton-donor–acceptor properties of the solvent. Significant differences, which depended on the environment, in the coumarin derivative of resorcin[4]arene fluorescence were observed and discussed.

This paper presents the synthesis of a coumarin derivative of resorcin[4]arene (1) using a cascade thermolysis/Michael reaction.     

Polymerization of a biscalix[5]arene derivative

Recent decades have seen an increased interest in the preparation of polymers possessing host or guest moieties as the end group, which has enabled new polymeric materials such as self-healable, shape-memory, and stimuli-responsive materials. Such polymers are commonly synthesized by tethering the host or guest moieties to polymers. On the other hand, there are limited reports demonstrating the preparation of host- or guest-appended polymers by directly polymerizing the corresponding host- or guest-appended monomers, which is valuable for easy access to diverse polymers from single molecular species. However, reactive host and/or guest moieties of the monomer interfere with the polymerization reaction. Here, we report that a biscalix[5]arene host-appended molecule can be polymerized with various monomers to form the corresponding host-appended polymers. The host–guest complexation behavior of calix[5]arene-appended polymers with fullerene derivatives was studied by ¹H NMR and UV/Vis spectroscopic techniques, which revealed that the long polymer chains did not prevent host–guest complexation even when the fullerene derivative was equipped with a polymer chain. Thus, the present study shows the potential for developing polymers that have various combinations of polymer chains.

A calix[5]arene appended monomer molecule was subjected to polymerization reaction to yield corresponding methacrylate polymers. The calix[5]arene appended polymers showed excellent encapsulation capability for fullerene molecules.     

Enantioselective Michael reaction of anthrone catalyzed by chiral tetraoxacalix[2]arene[2]triazine derivatives

A highly enantioselective Michael addition reaction of anthrone with nitroalkenes by chiral tetraoxacalix[2]arene[2]triazine catalysts was investigated as a novel topic. The stereoselective conversion progressed smoothly by employing 10 mol% of the catalyst and afforded the corresponding Michael adducts with acceptable to high enantioselectivities (up to 97% ee) and very high yields (up to 96%).

A highly enantioselective Michael addition reaction of anthrone with nitroalkenes by chiral tetraoxacalix[2]arene[2]triazine catalysts was investigated as a novel topic.     

Supported l-tryptophan on Fe3O4@SiO2 as an efficient and magnetically separable catalyst for one-pot construction of spiro[indene-2,2′-naphthalene]-4′-carbonitrile derivatives

In this work, l-tryptophan functionalized silica-coated magnetic nanoparticles were readily prepared and evaluated as a recyclable magnetic nanocatalyst for the synthesis of spiro[indene-2,2′-naphthalene]-4′-carbonitrile derivatives through the one-pot four-component reaction of malononitrile, cyclohexanone, aromatic aldehydes, and 1,3-indandione. This novel magnetic nanocatalyst was confirmed to be effective and provide products in moderate to excellent yields under reflux conditions. The structure of obtained nanoparticles was characterized using FT-IR, XRD, VSM, EDX, elemental mapping, FE-SEM, and TGA. This synthetic protocol provides several benefits such as excellent yields in short reaction times (64–91%), saving costs, reusability of the catalyst using an external magnet (seven runs), and low catalyst loading.

l-Tryptophan functionalized silica-coated magnetic nanoparticles were prepared and evaluated as a magnetic nanocatalyst for the synthesis of spiro[indene-2,2′-naphthalene]-4′-carbonitrile derivatives through the one-pot four-component reaction.