Design and Synthesis of New Chiral Calix[4]arenes as Liquid Phase Extraction Agents for α-Amino Acid Methylesters and Chiral α-Amines

The article describes the synthesis and extraction properties of new (S)-(-)-1-phenylethylamine substituted p-tert-butylcalix[4]arene/calix[4]arene. These compounds have been synthesized via nucleophilic substitution reactions involving 5,11,17,23-tetra-tert-butyl-25,26,27,28-tetra(2-hydroxyethoxy)calix[4]arene (4a), or 5,11,17,23-tetra-H-25,26,27,28-tetra(2-hydroxyethoxy)calix[4]arene (4b) with (S)-(-)-1-phenylethylamine in dry THF. The extraction properties of ligands 5a and 5b towards the some selected α-amino acid methylesters and chiral α-amines are also reported. It has been observed that receptor 5a was an excellent ionophore for α-amino acid methylesters/α-amines and good extractant than 5b. However, both of the ligands did not display any selectivity towards the configurations of this species. in final form: 17 January 2005     

Calixarene-based highly efficient primary amine–thiourea organocatalysts for asymmetric Michael addition of aldehydes to nitrostyrenes

The synthesis of calix[4]arene-based chiral bifunctional primary amine–thiourea catalysts has been described from p-tert-butylcalix[4]arene for the first time. The calix[4]arene-based catalysts were successfully applied to promote Michael addition of aldehydes with nitroalkenes affording preferentially the (R)- or (S)-adducts in high yields (up to 95%) and excellent enantioselectivities (up to 99% ees).     

Synthesis of novel chiral Schiff base and amino alcohol derivatives of calix[4]arene and chiral recognition properties

In the present study, the synthesis and liquid phase extraction properties towards some amino acid methylesters and amino alcohols of Schiff base and amino alcohol substituted calix[4]arene are reported. The Schiff base substituted calix[4]arene 5 has been synthesized via condensation reaction involving 5,17-diformyl-11,23-di-tert-butyl-25,27-di[3-(4-formylphenoxy)propoxy]-26,28 dihydroxycalix[4]arene 4 and (R)-(?)-2-phenylglycine methyl ester in CHCl₃:MeOH. To give the amino alcohol substituted calix[4]arene 6, the synthesized chiral compound 5 was reduced by LiAlH₄. The new chiral Schiff base and amino alcohol derivatives of calix[4]arene have been characterized by a combination of FT-IR, ¹H NMR, ¹³C NMR, FAB-MS and elemental analysis. Also, the extraction behaviors of 5 and 6 towards some selected amino acid methylesters and amino alcohols have been studied by liquid–liquid extraction.     

Tetra(diethyl)amide-p-tert-butyl-thiacalix[4]arene in Cone Conformation: Synthesis and Binding Properties with Alkali,Alkaline Earth,Heavy and Transition Metal Ions

Tetra(diethyl)amide-p-tert-butylthiacalix[4]arene 1a in the cone conformation was synthesized and its binding properties towards a large variety of metal ions were established on the basis of liquid–liquid and solid–liquid extraction as well as complexation experiments. This compound is a less efficient and selective compound than the “classical” tetra(diethyl)amide-p-tert-butylcalix[4]arene 3 in the cone conformation for alkali and alkaline earth metal ions. However, Pb²⁺ is selectively extracted and complexed within heavy and transition metal ions.     

Recognition Studies of a Pyridine-Pendant Calix[4]arene with Neutral Molecules: Effects of Non-covalent Interactions on Supramolecular Structures and Stabilities

A new calix[4]arene derivative containing hydrogen bond acceptors,5,11,17,23-tetra-tert-butyl-25,27-bis[(4-pyridylmethyl)oxy]-26,28-dihydroxycalix[4]arene (L), has been synthesized. ¹H-NMR titrations in chloroform-d werecarried out to investigate the host–guest chemistry ofL towards neutral molecules containing a widevariety of hydrogen bond donor groups such as aldehydederivatives of p-tert-butylcalix[4]arenes(compounds 3 and 4), acetylacetone,1,2-diaminoethane, 2,6-diaminopyridine, catechol,resorcinol, hydroquinone, phthalic acid, isophthalicacid and terephthalic acid. L can formcomplexes with resorcinol, phthalic acid and catecholin 1 : 1 (log K = 3.13), 1 : 1 (log K = 5.41) andpolymeric fashions, respectively. In addition, thesolution structures of these complexes have beenrevealed by NOESY experiments. L forms a 1 : 1complex with resorcinol by hydrogen bonding and vander Waals interactions resulting in a supramolecularframework. The phthalic acid molecule interacts withL via hydrogen bonding and is included into thelower rim cavity of L.     

Molecular Design of Calixarene 5. Syntheses and Cation Selectivities of Novel Schiff's Base p‐tert‐Butylcalix[4]arenes

Five novel Schiff's bases p‐tert‐butylcalix[4]arenes have been synthesized in high yields by the reaction of 1,3‐distally disubstituted p‐tert‐butylcalix[4]arene amine (1) with the corresponding aromatic aldehydes, and their cation binding abilities and selectivities with alkali and heavy metal ions have been evaluated by solvent extraction of aqueous metal picrates to show the highest Ag⁺ extractability for Schiff's base p‐tert‐butylcalix[4]arene (6) and the best Na⁺/Li⁺ and Ag⁺/Ti⁺ selectivities for Schiff's base p‐tert‐butylcalix[4]arene (4 and 2) over any other calix[4]arene derivatives, respectively.     

Synthesis and chiral recognition abilities of new calix[6]arenes bearing amino alcohol moieties

Herein the synthesis and recognition abilities towards amino acids and amino alcohols of new d-/l-phenylalaninol substituted p-tert-butylcalix[6]arenas are reported. These compounds, 6 and 7 have been synthesized via nucleophilic substitution reactions involving 5,11,17,23,29,35-tert-butyl-37,38-dimethoxy-39,40,41,42-(p-tosylethoxy)calix[6]arene 5 with d-/l-phenylalaninol in dry THF. The extraction properties of 6 and 7 towards some selected amino acid methylesters and amino alcohols have been studied by liquid–liquid extraction. These results show that chiral calix[6]arene derivatives exhibit a good affinity towards all amino acids and amino alcohols.     

Enantioselective Recognition of Calix[4]arene Derivative Bearing Bicyclic Guanidinium for D/L Amino Acid Zwitterions

The p‐tetra‐tert‐butyl calix[4] arene derivatives (3 and 4) with (5,5) chiral bicyclic guanidinium, as the receptors of amino acid zwitterions, have been synthesized via a O‐alkylation reaction of p‐tetra‐tert‐butyl calix [4] arene with cbJoromethyl chiral bicyclic guanidinium 2 in the presence of anhydrous K₂CO₃ in acetonitrile. The results obtained from liquid‐liquid competitive extraction experiments indicate that the two receptors may selectively recognize L‐aromatic amino acids, and that the enantioselective recognizability of the receptor 4 with two chiral bicyclic guanidinium units reachs up to about 90% for L‐Phe.     

Novel Triphenylamine Appended 1,3-Alternate-Calix[4]arenes: Synthesis and Characterization

In the present study, two novel calix[4]arene receptors containing triphenylamine units in 1,3-alternate conformation have been synthesized and characterized in detail. First, the 25,27-dipropoxy-26,28-bis[(3-aminopropyl)oxy]-calix[4]arene 4 and 25,26,27,28-tetra[(3-aminopropyl)oxy]-calix[4]arene 7 were prepared by using convenient reagents. Then, these amino derivatives of calix[4]arene were converted to Schiff base derivatives appended to triphenylamine of calix[4]arene (5 and 8) using 4-formyltriphenylamine via condensation. The 1,3-alternate conformation of the synthesized calix[4]arenes was determined by ¹H and ¹³C NMR analyses. Also, their structures have been characterized by using ¹H and ¹³C NMR, infrared, and elemental analyses.

Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications® to view the free supplemental file.     

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.     

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.     

Liquid–liquid extraction and transport through membrane of amino acid methylesters by calix[n]arene derivatives

The extractability together with the transport through liquid membrane of some amino acid methylesters by using p-tert-butylcalix[4]arene as extractant or carrier was studied. In this context, p-tert-butylcalix[n]arenes (n = 6, 8) were found to act as useful carriers or extractant reagents for l-tryptophan methylester and l-tyrosine methylester. The calix[n]arene derivatives used in experiments extracted amino acids methylesters from the aqueous phase into chloroformic phase in the presence of tropaeolin 00 ([4(4′-anilinophenylazo)benzenesulphonic acid]) as counterion at . The extraction and the transport depend on the structure of calixarenes, the structure of amino acids, the pH, and the nature of anion used as ion pair for cation-receptor complexes. The properties of solvent involved in liquid membrane play an important role in membrane stability and also in selecting membrane systems. The results demonstrated that the inclusion properties of the investigated hosts are correlated with their structural properties and also they suggest further possibilities for optimal separation of amino acids derivatives.     

Unprecedented cyclisations of calix[4]arenes with glycols under the Mitsunobu protocol. Part 1: A new perspective for the synthesis of calixcrowns

Selective ring closures of p-tert-butylthiacalix[4]arene and p-tert-butylcalix[4]arene with oligoethylene glycols were performed under the Mitsunobu protocol using the DEAD/TPP system. The method opens a new perspective for the syntheses of 1,3-calixcrowns.     

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.     

One‐Step Synthesis of Singly Bridged Biscalix[4]arenes with Oligooxyethyleneethyl Spacers

Here we describe the one‐step synthesis of a series of singly bridged biscalix[4]arene derivatives connected by ethylene or oligooxyethyleneethyl chain through the reaction of calix[4]arene with corresponding ethylene or oligoethylene glycol ditosylates in the presence of sodium hydride in toluene. A 1,2‐bis(ethylene) doubly bridged bis‐p‐tert‐butylcalix[4]arene was also obtained as a by‐product.     

Sulphur-enriched thiacalix[4]arenes in the cone conformation: synthesis, crystal structures and cation binding properties

The synthesis and crystal structure of p-tert-butylthia- and p-tert-butylcalix[4]arene derivatives 1–7 substituted at the narrow rim by diethylthiophosphate ester groups, -PS(OEt)₂ are reported. In these compounds the phosphorus atoms are directly attached to the phenolic O atoms of the calix units and the S atoms of the thiophosphate may serve as a two-electron donor to a metal ion. Their crystal structures were solved, which revealed their cone conformation. Their cation-binding properties have been established by liquid-liquid extraction of metal picrates from water into dichloromethane and stability constant determination in acetonitrile using UV-absorption spectrophotometry. Quantitative extraction was achieved for Ag⁺ (%E = 99) with the tetra-substituted thiacalix[4]arene derivative. The complexes were found to be of 1:1 stoichiometry and the location of the metal cations was shown to be nearby the sulphur atoms by ¹H NMR.     

Anion influence on extraction and transport of amino acid methyl esters by functionalised calix[4]arene

The liquid–liquid extraction of a series of amino acid methyl esters has been carried out with functionalised calix[4]arene (5,11,17,23-tetrakis(N-methylpiperazino)-25,26,27,28-tetrahydroxycalix[4]arene) from an aqueous phase into a chloroform phase as ion pairs in the presence of picrate ion or tropaeolin 00 as counter ion in order to study the molecular recognition properties of this receptor. The active transport assisted by pH gradient of amino acids as ion pairs through liquid membrane employing the functionalised calix[4]arene as carrier has been investigated. The results showed that the receptor exhibits good extractability towards amino acids and it can also act as carrier through liquid membrane aiming to the separation of amino acids. It was highlighted that the anion nature used as counter ion, the structure of calix[4]arene, and the structure of amino acids are responsible for the experimental results obtained. High yields in both amino acids extraction and transport were obtained for picrate ion used as counter ion.     

Resolution of inherently chiral calix[4]arenes with AABB and CDCD substitution patterns on the upper and lower rims,respectively

Proximal di-tert-butylcalix[4]arene (5,11-di-tert-butylcalix[4]arene-25,26,27,28-tetrol) 1b, obtained by direct partial removal of tert-butyl groups from p-tert-butylcalix[4]arene, gave high yields of inherently chiral derivatives upon ‘symmetry breaking’ by syn-distal di-O-alkylation or di-O-acylation in the presence of K₂CO₃. The chirality of these compounds was proven by the splitting of ¹H NMR signals in the presence of Pirkle's reagent and in some cases by HPLC enantiomeric resolution using chiral stationary phases and corroborated by mirror-image CD spectra.     

Synthesis and photochemical reaction of cyclic oligomers: Synthesis and photopolymerization of novel C‐methylcalix[4]resorcinarene and p‐alkylcalix[n]arene derivatives containing spiro ortho ether groups

New photoreactive calixarene derivatives containing spiro ortho ester groups (calixarenes 3a–3c ) were synthesized by the reaction of 2‐bromomethyl‐1,4,6‐trioxaspiro[4.4]nonane with 2,8,14,20‐tetramethyl‐4,6,10,12,16,18,22,24‐octakis(carboxymethoxy)calix[4]resorcinarene, 5,11,17,23,29,35‐hexamethyl‐37,38,39,40,41,42‐hexakis(carboxymethoxy)calix[6]arene, and 5,11,17,23,29,35,41,47‐octa‐tert‐butyl‐49,50,51,52, 53,54,55,56‐octakis‐(carboxymethoxy)calix[8]arene, which were prepared by the reaction of C‐methylcalix[4]resorcinarene, p‐methylcalix[6]arene, and p‐tert‐butylcalix[8]arene, respectively. The thermal stability of the obtained calixarene derivatives containing spiro ortho ester groups was examined with thermogravimetric analysis, and it was found that these calixarene derivatives had good thermal stability. The photoinitiated cationic polymerization of spiro ortho ester groups in calixarene derivatives 3a–3c was examined with certain photoacid generators in the film state. Interestingly enough, the reaction of calixarene derivatives did not proceed with only photoirradiation; however, the reaction proceeded smoothly when the photoirradiation was followed by heating. Furthermore, calixarene 3a , composed of a C‐methylcalix[4]resorcinarene structure, showed the highest photochemical reactivity in this reaction system. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 1293–1302, 2002     

Synthesis and Structure of Novel Double Flexible Spacer Bridged Biscalix[4]arenes

25, 25′, 27, 27′‐Bis(1,3‐dioxypropane)‐bis(5, 11, 17, 23‐tetra‐tert‐butylcalix[4]arene‐26,28‐diol) (4) and 25, 25′, 27, 27′‐bis(1, 4‐dioxybutane)‐bis (5, 11, 17, 23‐tetra‐tert‐butylcalix‐[4]arene‐26, 28‐diol) (5) were synthesized by the reaction of p‐tert‐butylcalix[4]arene (1) with preorganized 25, 27‐bis(3‐bromoproxyl)calix[4]arene‐26, 27‐diol (2) and 25, 27‐bis(3‐bromobutoxyl)calix[4]arene‐26, 27‐diol (3) in the presence of K₂CO₃ and KI. Compounds 4 and 5 were characterized with X‐ray analysis and the selectivity of 4 and 5 toward K⁺ over other alkali metal ions, alkaline metal ions as well as NH₄⁺ were investigated with an ion‐selective electrode.