Synthesis and alkaline earth metal cation extraction by proton di-ionizable p-tert-butylcalix[4]arene-crown-5 compounds in cone, partial-cone and 1,3-alternate conformations

Synthetic strategies for novel, proton di-ionizable p-tert-butylcalix[4]arene-crown-5 compounds in cone, partial-cone and 1,3-alternate conformations are reported. Selective linkage of the two diametrical phenolic oxygens in p-tert-butylcalix[4]arene with tetraethylene glycol ditosylate gave 1,3-bridged p-tert-butylcalix[4]arene-crown-5. The two remaining phenolic units were alkylated using NaH and KH as the bases to give the cone and partial-cone conformers, respectively. Preparation of the 1,3-alternate conformers utilized a different sequence in which O-alkylation was followed by crown ether ring formation. Structures of these new ligands were elucidated by (1)H and (13)C NMR spectroscopy. These proton-ionizable ligands were tested for their solvent extraction properties toward alkaline earth metal cations. Surprising differences in their extraction behaviors are noted compared to those reported previously for di-ionizable p-tert-butylcalix[4]arenecrown-6 analogues.     

Effect of para-substituents on alkaline earth metal ion extraction by proton di-ionizable calix[4]arene-crown-6 ligands in cone, partial-cone and 1,3-alternate conformations

Two carboxylic acid or N-(X)sulfonyl carboxamide groups were incorporated into calix[4]arene-crown-6 compounds to afford di-ionizable ligands for use in divalent metal ion separations. Acidities of the N-(X)sulfonyl carboxamide groups were tuned by variation of the electron-withdrawing properties of X. Cone, partial-cone and 1,3-alternate conformations were obtained by different synthetic strategies and their structures verified by NMR spectroscopy. Competitive solvent extractions of alkaline earth metal cations from aqueous solutions into chloroform were performed and the results compared with those reported previously for di-ionizable p-tert-butylcalix[4]arene-crown-6 analogues to probe the influence of the para-substituent on the calix[4]arene scaffold on extraction selectivity and efficiency.     

Di-ionizable calix[4]arene-1,3-crown-4 ligands in 1,3-alternate,cone, and partial-cone conformations: synthesis and metal ion extractions

Di-ionizable calix[4]arene-1,3-crown-4 compounds locked in 1,3-alternate, cone, and partial-cone conformations are synthesized for evaluation in metal ion separations. The ionizable functions include carboxylic acid and N-(X)sulfonyl carboxamide groups in which the acidity is tuned by variation of the electron-withdrawing ability of X. Similar synthetic routes were employed for preparation of the cone and 1,3-alternate ligand series. A different preparative route utilizing protection and deprotection was required to obtain the partial-cone analogues. Ligand conformations were confirmed by their proton and/or carbon NMR spectra. X-ray diffraction verified an unusual 1,2-alternate conformation in the solid-state for one synthetic intermediate. Effects of ligand conformation and ionizable group variations on competitive solvent extractions of alkali and alkaline earth metal cations from aqueous solutions into chloroform were assessed. Single species solvent extractions of Hg²⁺ and Pb²⁺ were also performed.     

Di-ionizable p-tert-butylcalix[4]arene-1,2-crown-5 and -crown-6 compounds in the cone conformation: synthesis and alkaline earth metal cation extraction

Di-ionizable p-tert-butylcalix[4]arene-1,2-crown-5 and -crown-6 ethers in the cone conformation were prepared and their conformations and regioselectivities were verified by NMR spectroscopy. The metal ion-complexing properties of these ligands were evaluated by competitive solvent extractions of alkaline earth metal cations from water into chloroform. The ligands were found to be efficient extractants with selectivity for Ba(2+). The maximal loadings were 95-100% as calculated for formation of 1 : 1 ionized ligand-metal ion complexes. With the variation of proton-ionizable groups, which were oxyacetic acid moieties and N-(X)sulfonyl oxyacetamide units with X = methyl, phenyl, 4-nitrophenyl, and trifluoromethyl, "tunable" acidity was obtained.     

Di-ionizable p-tert-butylcalix[4]arene-1,2-crown-3 ligands in cone and 1,2-alternate conformations: synthesis and metal ion extraction

Novel di-ionizable p-tert-butylcalix[4]arene-1,2-crown-3 ligands in cone and 1,2-alternate conformations were prepared as potential metal ion extractants. Selective bridging of proximal hydroxyl groups of the calix[4]arene platform by a crown-3 polyether unit was achieved under Mitsunobu reaction conditions. In addition to the carboxylic acid group, the acidity tunable N-(X)sulfonyl oxyacetamide functions [OCH(2)C(O)NHSO(2)X] with X group variation from methyl to phenyl to p-nitrophenyl to trifluomethyl were used as the proton-ionizable groups. Conformations and regioselectivities of the new ligands were established by (1)H and (13)C NMR spectroscopy. Competitive solvent extractions of alkali metal cations and of alkaline earth metal cations from aqueous solutions into chloroform were performed, as were single species extractions of lead(ii) and mercury(ii).     

Alkali metal cation complexation by 1,3-alternate,mono-ionisable calix[4]arene-benzocrown-6 compounds

Alkali metal cation extraction behaviour for two series of 1,3-alternate, mono-ionisable calix[4]arene-benzocrown-6 compounds is examined. In Series 1, the proton-ionisable group (PIG) is a substituent on the benzo group of the polyether ring that directs it away from the crown ether cavity. In Series 2, the PIG is attached to one para position in the calixarene framework, thereby positioning it over the crown ether ring. Competitive solvent extraction of alkali metal cations from aqueous solutions into chloroform shows high Cs⁺ efficiency and selectivity. Single-species extraction pH profiles of Cs⁺ for Series 1 and 2 ligands with the same PIG are very similar. Thus, association of Cs⁺ with the calixcrown ring is more important than the position of the PIG relative to the crown ether cavity. Solid-state structures of two unionised ligands from Series 2 are presented. Also described is a crystal containing two different ionised ligand–Cs⁺ complexes.     

Di-ionizable p-tert-butylcalix[4]arene-1,3-crown-4 ligands: synthesis and alkaline earth metal cation extraction

A series of di-ionizable calix[4]arene-1,3-crown-4 compounds has been synthesized. The ionizable groups are oxyacetic acid and N-(X)sulfonyl oxyacetamide groups with X=methyl, phenyl, 4-nitrophenyl and trifluoromethyl, which ‘tunes’ the acidity of the latter. The efficiency and selectivity of these novel ligands are assessed with competitive solvent extractions of alkaline earth metal cations from aqueous solutions into chloroform. The results are compared with those reported previously for calix[4]arene-crown analogues with crown-6 and crown-5 rings.     

Mono-ionizable calix[4]arene-benzocrown-6 ligands in 1,3-alternate conformations: synthesis, structure and silver(I) extraction

Two series of novel mono-ionizable calix[4]arene-benzocrown-6 ligands in 1,3-alternate conformations are synthesized. In one series, the proton-ionizable group (PIG) is attached to the para position of one aromatic ring in the calixarene framework, thereby positioning it over the polyether ring cavity. In the other series, the PIG is a substituent on the benzo group in the polyether ring. This orients the PIG away from the crown ether cavity. In addition to carboxylic acid functions, the PIGs include N-(X)sulfonyl carboxamide groups. With X group variation from methyl to phenyl to 4-nitrophenyl to trifluoromethyl, the acidity of the PIG is ‘tuned’. Solvent extraction of Ag⁺ from aqueous solutions into chloroform is used to probe the influence of structural variation within the mono-ionizable calixcrown ligand on metal ion extraction efficiency, including the identity and acidity of the PIG and its orientation with respect to the polyether ring.     

Comparison of upper and lower rim-functionalized,di-ionizable calix[4]arene-crown-6 structural isomers in divalent metal ion extraction

Upper rim-functionalized, di-ionizable calix[4]arene-crown-6 ligands are synthesized and compared with structural isomers having the two acidic side arms attached to the lower rim. Solvent extractions of selected divalent metal cations (alkaline earth metal cations, Pb²⁺, and Hg²⁺) from aqueous solutions into chloroform by the upper and lower rim-functionalized, di-ionizable calix[4]arene-crown-6 isomers are utilized to assess the effects of this structural modification on metal ion complexation abilities of the ligands. The observed effects are compared with those reported for analogous di-ionizable calix[4]arene-crown-5 structural isomers.     

Lower-rim versus upper-rim functionalization in di-ionizable calix[4]arene-crown-5 isomers. Synthesis and divalent metal ion extraction

Two series of di-ionizable calix[4]arene-crown-5 isomers in the cone conformation are synthesized to probe the effect of the pendant acidic group location on their metal ion extraction properties. In one series, the ionizable groups are attached to the lower rim of the calix[4]arene scaffold, which orients them near the crown ether cavity. In the second series, the ionizable groups are connected to the upper rim positioning them away from the crown ether ring, but close to the hydrophobic pocket of the calix[4]arene unit. The metal ion extraction behaviors of the two series of ligands are compared in extractions of alkaline earth metal cations, Hg²⁺, and Pb²⁺.     

Protonation of 25,27-bis(1-octyloxy)calix[4]arene-crown-6 in the 1,3-alternate conformation

From extraction experiments in the two-phase water-nitrobenzene system and γ-activity measurements, the stability constant of protonated 1,3-alternate-25,27-bis(1-octyloxy)calix[4]arene-crown-6 in nitrobenzene saturated with water was determined. By using DFT calculations, the most probable structure of the 1,3-alternate-25,27-bis(1-octyloxy)calix[4]arene-crown-6 · H₃O⁺ complex species was derived. Correspondence: Emanuel Makrlík, Faculty of Applied Sciences, University of West Bohemia, Pilsen, Czech Republic.     

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.     

Di-ionizable calix[4]arene-1,2-crown-5 and -crown-6 ethers in cone conformations: synthesis and divalent metal ion extraction

Two series of di-ionizable calix[4]arene-1,2-crown-5 and -crown-6 ethers in cone conformations are synthesized. The ionizable groups are oxyacetic acid moieties and N-(X)sulfonyl oxyacetamide units with X=methyl, phenyl, 4-nitrophenyl, and trifluoromethyl, which ‘tunes’ their acidity. For competitive solvent extraction of alkaline earth metal cations from aqueous solutions into chloroform, the new ligands with N-(X)sulfonyl carbamoyl groups are efficient extractants with Ba²⁺ selectivity. On the other hand, the dicarboxylic acid analogues exhibit little selectivity in extraction of alkaline earth metal cations. For single species extractions of Pb²⁺, the ligands with both types of ionizable groups show very good extractions abilities. In single species extractions of Hg²⁺, the N-(X)sulfonyl carboxamide ligands are highly efficient, in contrast to the dicarboxylic acid compounds. Influences of the ionizable group identity, the crown ether ring size, and the presence of upper-rim p-tert-butyl groups on divalent metal ion extraction are explored.     

Mercuration of calix[4]arenes immobilized in the 1,2- and 1,3-alternate conformations

Calix[4]arenes immobilized in the 1,2-alternate and 1,3-alternate conformations were directly mercurated using Hg(TFA)₂. The reaction regioselectivity was compared with the thermodynamic stability of the corresponding products obtained by theoretical calculations (wB97XD/def2tzvp method). Both experimental and theoretical data suggest that para substitution is slightly preferred over meta attack for the 1,2-alternate conformer, while in the case of the 1,3-alternate conformation the situation is reversed. The usefulness of the mercury intermediates was demonstrated by the synthesis of a rigid upper-rim-bridged calixarene in the 1,2-alternate conformation possessing a highly distorted cavity. A simple transformation of the organomercury compounds afforded the corresponding iodo derivatives, which are potentially applicable as building blocks for further synthesis. Moreover, many products are inherently chiral representing unique substitution patterns inaccessible by common “mercury-free” chemistry.     

Selective metal detection in an unsymmetrical 1,3-alternate calix[4]biscrown chemosensor

Calix[4]crown-based chemosensors 1, 2, and reference 3 have been synthesized. The weak fluorescence intensity of 1,5-naphthalene of 1 suggests that the benzene rings of the calix[4]arene as well as the oxygen atoms of the crown-5 ring take part in PET. The complexation of two K⁺ ions by both crown-5 and 1,5-naphthalene-crown-6 loops of 1 caused fluorescence enhancement of the naphthalene unit by CHEF. Pb²⁺ acted as a quenching metal ion.     

Complexation of the cesium cation with 1,3-alternate-25,27-bis(1-octyloxy)calix[4]arene-crown-6

From extraction experiments and γ-activity measurements, the extraction constant corresponding to the equilibrium Cs⁺(aq) + I^?(aq) + 1(nb) ? 1·Cs⁺(nb) + I^?(nb) taking place in the two–phase water–nitrobenzene system (1 = 1,3-alternate-25,27-bis(1-octyloxy)calix[4]arene-crown-6; aq = aqueous phase, nb = nitrobenzene phase) was evaluated as log K _ex (1·Cs⁺, I^?) = 2.9 ± 0.1. Further, the stability constant of the 1·Cs⁺ complex in nitrobenzene saturated with water was calculated for a temperature of 25 °C: log β_nb (1·Cs⁺) = 8.8 ± 0.1. Finally, by using quantum–mechanical DFT calculations, the most probable structure of the resulting cationic complex species 1·Cs⁺ was derived.     

Aminolysis of p-tert-butyltetrathiacalix[4]arene tetraethylacetates in cone, partial cone and 1,3-alternate conformation: synthesis of amide based receptors for oxyanions

Cone, partial cone and 1,3-alternate conformers of tetrathiacalix[4]arene tetraethylacetate were synthesized and subjected to aminolysis with alkyl amines [CH₃(CH₂)_nNH₂; n=2, 3, 5] to yield mono-, di-, tri- or tetrasubstituted p-tert-butyltetrathiacalix[4]arene amides which were characterized by detailed analysis of their NMR spectral and single crystal X-ray crystallography. It has been observed that while the 1,3-alternate and cone conformers of the tetrathiacalix[4]arene tetraethylacetate gave corresponding tetrathiacalix[4]arene tetraamides under different experimental conditions, the corresponding partial cone conformer undergoes a cascade of regioselective reactions with the same amines. Variable temperature ¹H NMR experiments allowed the determination of relative stability of different conformers within the temperature range of 298-333 K. The synthesized derivatives were evaluated as molecular extractants for cations and anions and were determined to facilitate extraction of oxyanions (CrO₄²⁻ and Cr₂O₇²⁻) from aqueous to the organic phase. The studies have a significance in the design of tetrathiacalix[n]arene based molecular receptors for innovative applications.