Diester intrabridging of p-tert-butylcalix[8]arene and unexpected formation of the monospirodienone derivative

Reaction of p-tert-butylcalix[8]arene 1 with adipoyl chloride in the presence of NaH as the base yielded singly and doubly intrabridged esters 2-4 and 6. Surprisingly, calix[8]arene monospirodienone derivative 7 was also isolated, which was originated by O₂ oxidation. The conditions of this oxidation were optimized leading to a novel synthetic approach to calixarene monospirodienones based on the O₂/NaH/acyl-chloride oxidizing system. Xantheno calix[8]arenes 8-8a were obtained by rearrangement of 7.     

CMPO-substituted calix[6]- and calix[8]arene extractants for the separation of An/Ln from radioactive waste

Three calix[6]arene derivatives (1a-c) and two calix[8]arene derivatives (2a,b), with six and eight CMPO residues, respectively, attached to the narrow/lower rim via ether links, were synthesised. Preliminary liquid-liquid extraction studies for Eu(III) and Am(III) from aqueous nitric acid to o-nitrophenylhexyl ether reveal remarkable properties with respect to efficiency and selectivity, especially for the tert-butylcalix[6]arene derivative with a -(CH₂)₃- spacer.     

Dioxamethylene intramolecular bridging of p-tert-butylcalix[8]arene

The first examples of dioxamethylene bridged calix[8]arenes 2-6 have been obtained by Cs₂CO₃-promoted direct O-alkylation of p-tert-butylcalix[8]arene with BrCH₂Cl. Assignment of the 1,2-, 1,2:3,4-, 1,2:3,4:6,7-, 1,4:2,3:5,6:7,8-, and 1,2:3,4:5,6:7,8-bridging pattern of 2-6, respectively, was mainly based on chemical shift of OH groups and chemical correlations. Dynamic ¹H NMR studies and MM3 calculations indicated that in these compounds the dioxocine subunit adopts a boat-chair conformation.     

Phosphite ligands derived from distally and proximally substituted dipropyloxy calix[4]arenes and their palladium complexes: Solution dynamics, solid-state structures and catalysis

Two bisphosphite ligands, 25,27-bis-(2,2′-biphenyldioxyphosphinoxy)-26,28-dipropyloxy-p-tert-butyl calix[4]arene (3) and 25,26-bis-(2,2′-biphenyldioxyphosphinoxy)-27,28-dipropyloxy-p-tert-butyl calix[4]arene (4) and two monophosphite ligands, 25-hydroxy-27-(2,2′-biphenyldioxyphosphinoxy)-26,28-dipropyloxy-p-tert-butyl calix[4]arene (5) and 25-hydroxy-26-(2,2′-biphenyldioxyphosphinoxy)-27,28-dipropyloxy- p-tert-butyl calix[4]arene (6) have been synthesized. Treatment of (allyl) palladium precursors [(η³-1,3-R,R′-C₃H₄)Pd(Cl)]₂ with ligand 3 in the presence of NH₄PF₆ gives a series of cationic allyl palladium complexes (3a-3d). Neutral allyl complexes (3e-3g) are obtained by the treatment of the allyl palladium precursors with ligand 3 in the absence of NH₄PF₆. The cationic allyl complexes [(η³-C₃H₅)Pd(4)]PF₆ (4a) and [(η³-Ph₂C₃H₃)Pd(4)]PF₆ (4b) have been synthesized from the proximally (1,2-) substituted bisphosphite ligand 4. Treatment of ligand 4 with [Pd(COD)Cl₂] gives the palladium dichloride complex, [PdCl₂(4)] (4c). The solid-state structures of [{(η³-1-CH₃-C₃H₄)Pd(Cl)}₂(3)] (3f) and [PdCl₂(4)] (4c) have been determined by X-ray crystallography; the calixarene framework in 3f adopts the pinched cone conformation whereas in 4c, the conformation is in between that of cone and pinched cone. Solution dynamics of 3f has been studied in detail with the help of two-dimensional NMR spectroscopy.The solid-state structures of the monophosphite ligands 5 and 6 have also been determined; the calix[4]arene framework in both molecules adopts the cone conformation. Reaction of the monophosphite ligands (5, 6) with (allyl) palladium precursors, in the absence of NH₄PF₆, yield a series of neutral allyl palladium complexes (5a-5c; 6a-6d). Allyl palladium complexes of proximally substituted ligand 6 showed two diastereomers in solution owing to the inherently chiral calix[4]arene framework. Ligands 3, 6 and the allyl palladium complex 3f have been tested for catalytic activity in allylic alkylation reactions.     

Synthesis of novel p-tert-butyl-calix[4]arene derivatives and their cation binding ability: chromogenic effect upon side arms binding

A series of novel double-armed calix[4]arene derivatives, i.e. 5,11,17,23-tetra-tert-butyl -25,27-bis[2-[(2-hydroxy-5-(4-nitroazo)benzylidene)amino]ethoxy]-26,28-dihydroxy-calix[4]-arene (4), 5,11,17,23-tetra-tert-butyl-25,27-bis[2-[(2-hydroxy-5-(2-nitroazo)benzylidene) amino]ethoxy]-26,28-dihydroxycalix[4]arene (5), 5,11,17,23-tetra-tert-butyl-25,27-bis[2-[(2-hydroxy-5-(4-chloroazo)benzylidene)amino]ethoxy]-26,28-dihydroxycalix[4]arene (6), have been synthesized as an selective chromoionophore for Na⁺. The complexation behavior of ligands 4-6 with alkali metal ions Na⁺, K⁺, Rb⁺and Cs⁺ has been evaluated by using UV-Vis spectrometry in CH₃CN-H₂O (99:1/V:V) solution at 25°C. The UV-Vis spectra show that the complexation of 4-6 with Na⁺exhibits obvious bathochromic shifts (λ_max 379→480 nm) and there is a unique color change in the solution from yellow to red upon complexation. The binding constants for Na⁺ are higher than that of other alkali metal ions, giving the highest cation selectivity up to 7 for Na⁺/K⁺. The binding ability and photophysical behavior of alkali cations by calix[4]arene derivatives 4-6 are discussed from the point of view of substituted effects at the lower rim of parent calix[4]arene and size-fit concept between host calix[4]arenes and guest cations.     

Calix[4]quinones. Part 4: The ClO2 oxidation of calix[4]arene dialkyl ethers

Except for the special case of calix[4]arene diethyl ether 1, the chlorine dioxide oxidation of dialkyl ethers 2-5 yielded only the corresponding calix[4]diquinone dialkyl ethers 8-11. Chlorine dioxide oxidation of calix[4]arene diethyl ether 1 produced two isomeric products 6 and 7, which were stable enough to be isolated by column chromatography. However, a slow conformational interconversion between isomeric pair 6 and 7 was observed at room temperature, and the equilibrium was reached after 400 h at 18 °C with an amount of 5:3 in favor of syn-isomer.     

Synthesis and self-assembly of novel calix[4]arenocrowns: formation of calix[4]areno[2]catenanes

A series of novel calix[4]arenocrowns 1a-c were efficiently synthesized by a one-pot reaction of calix[4]monohydroquinone diacetate 5 with ditosylate 6 and its analogues in the presence of sodium hydroxide. It was found that the calix[4]arenocrowns could form stable pseudorotaxane-type complexes 2a-c with paraquat, and further self-assemble into calix[4]areno[2]catenanes 3a-c with dicationic salt 8 and p-bis(bromomethyl)benzene.     

Synthesis of di-substituted calix[4]arene-based receptors for extraction of chromate and arsenate anions

The article describes the synthesis of a family of novel calix[4]arene ionophores, 25,27-bis-(2-aminomethylpyridine-propoxy)-26,28-dihydroxycalix[4]arene (5a), 25,27-bis-(3-aminomethylpyridine-propoxy)-26,28-dihydroxycalix[4]arene (5b) and two chromogenic calix[4]arenes, 5,17-dinitro-25,27-bis-(2-aminomethylpyridine-propoxy)-26,28-dihydroxycalix[4]arene (5c), 5,17-dinitro-25,27-bis-(3-aminomethylpyridine-propoxy)-26,28-dihydroxycalix[4]arene (5d) bearing pyridinium units. In the synthesis, the upper and lower rims of p-tert-butylcalix[4]arene were modified in order to acquire binding sites for the recognition of arsenate and dichromate anions. It has been observed that protonated alkylammonium forms of the ionophores showed high affinity toward dichromate and arsenate anions.     

Polymer-supported calix[4]arenes for sensing and conversion of NO2/N2O4

The use of simple calix[4]arenes 1a,b for NO₂/N₂O₄ sensing and conversion is demonstrated, both in solution and in the solid state. Upon reacting with these gases, compounds 1a,b encapsulate reactive NO⁺ cations within their cavities with the formation of deeply colored (λ_max∼570 nm) charge-transfer complexes 2a,b. Further functionalization of the calix[4]arene platform is reported for attachment to solid supports. Polymer-supported calixarene material 3 was prepared, which reversibly traps NO₂/N₂O₄ with the formation of nitrosonium storing polymer 4. Material 4 was effectively used for nitrosation of amides.     

Synthesis of sulfur containing analogues of the soluble guanylate cyclase inhibitor 8-bromo-4H-[1,2,4]oxadiazolo[3,4-c][1,4]benzoxazin-1-one NS2028

Sulfur analogues of the soluble guanylate cyclase (sGC) inhibitor NS2028 1a are synthesized. Treating 8-bromo-2H-benzo[b][1,4]oxazin-3(4H)-one oxime (6) with 1,1′-thiocarbonyldiimidazole (1.1 equiv) gave the carbamothioate 8-bromo-4H-[1,2,4]oxadiazolo[3,4-c][1,4]benzoxazine-1-thione (3a) in 83% yield. Alternatively reacting NS2028 1a with P₂S₅ (0.5 equiv) affords the carbamothioate 3a in 80% yield. Similar treatment of 8-aryl substituted NS2028 analogues 1b-d with P₂S₅ gave the carbamothioates 3b-d in 64-91% yields. Although quite stable, the carbamothioates 3a-d could be thermally isomerized in the presence of Cu (10 mol %) to afford the thiocarbamates 4a-d in high yields. Interestingly, in the case of carbamothioate 3a Pd and In metals also facilitated the isomerization. Furthermore, treatment of the thiocarbamates 4a-d with P₂S₅ (0.5 equiv) affords the carbamodithioates 5a-d in 72-89% yields. All new compounds are fully characterized including single crystal X-ray data for carbamothioate 3a and thiocarbamate 4a. Finally, a mechanism is proposed for the carbamothioate to thiocarbamate isomerization.     

Synthesis of novel calix[4]arenes containing organosilicon groups

Metalation of (RSiMe₂)₃CH (1a R = H, 1b R = Me, 1c R = Ph) with lithium diisopropylamide (LDA) or methyllithium in THF gave organolithium reagents (RSiMe₂)₃CLi, which reacted with the formylated calixarene (2), to give the corresponding 5,17-bis[2,2-bis(organosilyl)-1-ethenyl]-25,26,27,28-tetrapropoxycalix[4]arenes (3a, 3b and 3c) via the Peterson olefination. The compounds (RSiMe₂)₃CLi were treated with 25,26,27,28-tetrakis(4-bromobutoxy)calix[4]arene (4) to give 25,26,27,28-tetrakis[4-(tris(dimethylsilyl)methyl)butoxy] calix[4]arene (5a) and 25,26,27,28-tetrakis[4-(tris(trimethylsilyl)methyl)butoxy] calix[4]arene (5b) via nucleophilic substitution reactions. However the compound 25,26,27,28-tetrakis[4-(tris(dimethylphenylsilyl)methyl)butoxy] calix[4]arene (5c) was not obtained, presumably because (PhSiMe₂)₃C- is highly sterically hindered and the reactivity of its derivatives is low. The compound 5a has potential as a core for dendrimers.     

Syntheses of two diamine substituted 1,3-distal calix[4]arene-based magnetite nanoparticles for extraction of dichromate, arsenate and uranyl ions

The synthesis of two new calixarene derivatives 4 and 5, functionalized at the lower rim with 4-amino-1-benzylpiperidine to give diamide and diamine derivatives of p-tert-butylcalix[4]arene, is described. They were obtained by the reaction of both the diester derivative of p-tert-butylcalix[4]arene (2) and the dialkyl bromide derivative of p-tert-butylcalix[4]arene (3) with 4-amino-1-benzylpiperidine. The ¹H NMR spectra of calixarene derivatives show that 4 and 5 exist in the cone conformation. Moreover, these diamide and diamine derivatives of p-tert-butylcalix[4]arene (4 and 5) have been immobilized onto [3-(2,3-epoxypropoxy)-propyl]-trimethoxysilane-modified Fe₃O₄ magnetite nanoparticles to obtain calixarene-based magnetic nanoparticles M-DADBP-Calix (6) and M-DABP-Calix (7). The calix[4]arene immobilized materials were characterized by a combination of Fourier Transform Infrared Spectroscopy (FTIR), Transmission Electron Microscopy (TEM) and Thermogravimetric Analyses (TGA) and elemental analysis. Additionally, the studies regarding the removal of As(V)/Cr(VI) ions as well as U(VI) ion from aqueous solutions were also carried out by using these compounds in liquid-liquid/solid-liquid extraction experiments.     

Upper rim tetrathiafulvalene-bridged calix[4]arenes

The synthesis of novel upper rim calix[4]arene-tetrathiafulvalene conjugates 1a-d has been performed by bridging the tetrachloromethylated calix[4]arene derivative 4 with the corresponding tetrathiafulvalene-dithiolates. The cyclic voltammetry of 1a-d shows a two-step oxidation behavior, whereas NMR binding titrations showed their binding affinity to pyridinium salts. X-ray structure of 4 features calixarene fixed in the pinched cone conformation; its crystal packing is defined by the network of C-H···Cl weak hydrogen bonds.     

Synthesis of a novel tetracyclic azaindolo[2,1-c][1,4]benzoxazine ring system

Synthesis of a series of novel fused tetracyclic mono- and diazaindolo[2,1-c][1,4]benzoxazine heterocyclic compounds 3a-o has been achieved in a two-step one-pot reaction set up starting from commercially available or easily accessible inputs. For example, reaction of di-lithiated (N-Boc)-2-amino-3-methylpyridine Li₂-2a with Weinreb amide of 2-(2,4-difluorophenoxy)-2,2-dimethylacetic acid 1a, followed by TFA treatment furnished the tetracyclic compound 3a, which is essentially a fusion of 7-azaindole and 3,4-dihydro[1,4]benzoxazine, in 70% isolated yield. A competitive elimination by-product 4a was also observed (24% isolated yield) in this case. Based on our initial results, a structural basis and molecular mechanism have been suggested to explain these two parallel reactions. Consequently, with appropriate structural tuning of 1, formation of the individual products can be controlled.     

A novel and convenient method for the synthesis of new derivatives of pyrido[3,2-e]pyrrolo[1,2-a][1,4]diazepine-6,11-dione

A novel methodology has been developed for the efficient synthesis of 1,4-pyridopyrrolodiazepine derivatives. The key reaction is the bromination under mild conditions by NBS of compounds resulting via peptide coupling of l-proline methyl ester with 3-aminopyridine-2-carboxylic acid 1, then intramolecular cyclization in the construction of 2-bromo-6a,7,8,9-tetrahydro-5H-pyrido[3,2-e]pyrrolo[1,2-a][1,4]diazepine-6,11-dione 4. This latter is then engaged in cross-coupling reactions to generate 1,4-pyridopyrrolodiazepines derivatives 5a-m, 6a-i, 7, and 8a-c. This strategy provides an efficient method to access a library of compounds based on privileged substructures that are of great interest in drug discovery.     

Naphthyridines. Part 3: First example of the polyfunctionally substituted 1,2,4-triazolo[1,5-g][1,6]naphthyridines ring system

Treatment of 1,2,4-triazoles (1) with diethylmalonate in bromobenzene gave 1,2,4-triazolo-[1,5-a]pyridines 2. Chlorination of 2 using POCl₃/DMF (Vilsmeier reagent) led to the isolation of 7-chloro-6-formyl-1,2,4-triazolo[1,5-a]pyridine derivative 4, which reacted with the stabilized ylid 5 to afford 6-ethoxycarbonylvinyl-1,2,4-triazolo[1,5-a]-pyridines 6. Azidation of 6 yielded the corresponding azido compound 7, (Scheme 2). Reduction of 7 with Na₂S₂O₄ gave the corresponding 7-amino compound 8, which cyclized in boiling DMF to give the novel 1,2,4-triazolo[1,5-g][1,6]naphthyridines 9. On the other hand, reacting 7 with one equivalent of PPh₃ (aza-Wittig reaction) in CH₂Cl₂ gave 7-imino-phosphorane derivative 10, and subsequent cyclization in boiling DMF afforded the new 1,2,4-triazolo[1,5-g][1,6]naphthyridine derivative 11 (Scheme 3). However, treatment of 10 with phenyl isothiocyanate in 1,2-dichlorobenzene at reflux temperature gave the new 1,2,4-triazolo[1,5-g][1,6]naphthyridine derivative 14 (Scheme 4). Refluxing 6 with excess of a primary amines 15a,b in absolute. EtOH yielded the corresponding 7-alkyl-amino-1,2,4-triazolo[1,5-a]pyridines 16a,b. These obtained amines 16a,b underwent intramolecular heterocyclization in boiling DMF to give the novel 9-alkyl-1,2,4-triazolo[1,5-g][1,6]-naphthyridines 17a,b, in excellent yields (Scheme 5).     

New receptors for anions in water: Synthesis, characterization, X-ray structures of new derivatives of 5,11,17,23-tetraamino-25,26,27,28-tetrapropyloxycalix[4]arene

Syntheses and characterization of ten new compounds from the calixarene family, cone - 5,11,17,23- tetrakis(2-pyridylmethylamino)-25,26,27,28-tetrapropyloxycalix[4]arene 4a; cone - 5,11,17,23-tetrakis(3-pyridylmethylamino)-25,26,27,28-tetrapropyloxycalix[4]arene 4b; cone - 5,11,17,23-tetrakis(4-pyridylmethylamino)-25,26,27,28-tetrapropyloxycalix[4]arene 4c; cone - 5,11,17,23-tetrakis(ferrocenylmethylamino)-25,26,27,28-tetrapropyloxycalix[4]arene 4d; cone - 5,11,17,23-tetrakis(2-pyridylmethimino)-25,26,27,28-tetrapropyloxycalix[4]arene 3a; cone - 5,11,17,23-tetrakis(3-pyridylmethimino)-25,26,27,28-tetrapropyloxycalix[4]arene 3b; cone - 5,11,17,23-tetrakis(4-pyridylmethimino)-25,26,27,28-tetrapropyloxycalix[4]arene 3c; cone - 5,11,17,23-tetrakis(ferrocenylmethimino)-25,26,27,28-tetrapropyloxycalix[4]arene 3d; cone - 5,11,17,23-tetrakis(2-thienylmethimino)-25,26,27,28-tetrapropyloxycalix[4]arene 3e and cone - 5,11,17,23-tetrakis(2-pyrrolylmethimino)-25,26,27,28-tetrapropyloxycalix[4]arene 3f are reported. The target compounds 4a-4d were designed to form complexes with anions based on hydrogen bonds and electrostatic interactions in acidic aqueous solutions and the interaction constant 1770 mol⁻¹ dm³ of a 1:1 complex was obtained for the interaction of 4c with sulfate anion in 5 × 10⁻³ M aqueous HCl. The solid state structures of the compounds 3b, 3e and 3f were determined, their stereochemistry and the stereochemistry of the calix[4]arene frame is generally discussed. Raman, infrared and UV-vis spectra of the target compounds and some intermediates are reported, too.     

Short-step syntheses and complexation properties of Z,Z-tribenzodidehydro- and all-Z-tribenzo[12]annulenes

Syntheses of all-Z-tribenzo[12]annulenes (1a-c) and Z,Z-tribenzodidehydro[12]annulenes (2a-c) by the reduction of the corresponding tribenzohexadehydro[12]annulenes 3a-c were carried out using a low valent titanium complex generated from Ti(O-i-Pr)₄ and i-PrMgCl. The unique structure of the first reduction products 2a-c as well as 1a-c was fully characterized. Complexation of these annulenes with silver(I) ions produces the corresponding silver complexes. Among them, the silver complexes of 2a-c exhibit interesting monomer-dimer equilibrium.     

Azobenzene-bridged calix[8]arenes

An azobenzene bridge was introduced into the lower (or smaller) rim of p-tert-butylcalix[8]arene (1) and 1,5-calix[8]crown-3 (2) to form 1,4-singly bridged (3) and 1,5:3,7-doubly bridged (4) calix[8]arene derivatives, respectively. Trans and cis isomers of conformationally rigid 4 were isolated. The quantum yields of the trans-cis photoisomerisation reactions have been measured.     

Functionalisation of the upper rim of calix[4]arene via alcoholysis and hydrosilylation reactions

Metalation of 5,17-dibromo-25,26,27,28-tetra propoxy calix[4]arene (1) with n-BuLi in THF at −78 °C gave organolithium reagent, which reacted with Me₂HSiCl to give 5,17-bis(dimethylsilyl)-25,26,27,28-tetra propoxy calix[4]arene (2). The Si-H groups of calixarene 2 were treated with methanol, ethanol, propanol, butanol, pentanol, hexanol, 2-propanol and 2-methyl propanol in the presence of Karstedt catalyst (platinum(0)-1,3-divinyl-1,1,3,3-tetramethyl disiloxane complex, solution in xylene) to give the corresponding 5,17-bis(alkoxydimethylsilyl)-25,26,27,28-tetra propoxy calix[4]arene (3). Moreover, calixarene 2 was easily functionalized with a variety of alkenes using Karstedt catalyst to give the corresponding organosilylated calix[4]arene (4).