Insights into the Self-Filling Effects of Branched Isopropyl Groups on the Conformational and Supramolecular Properties of Isopropoxyprism[6]arene

In this work, the direct macrocyclization of a prism[6]arene macrocycle bearing branched alkyl chains on the rims is reported. Isopropoxyprism[6]arene adopts in solution and in the solid state a cuboid D₂-conformation in which four isopropyl groups are folded inside the cavity, to give C−H⋅⋅⋅π interactions and filling the internal void. The conformational features of isopropoxyprism[6]arene have been studied by dynamic ¹H NMR experiments. The presence of branched isopropyl chains on the prism[6]arene rims, stabilizes the cuboid D₂-conformation to a greater extent than ethyl or propyl groups in PrS[6]^Et and PrS[6]^nPr. The higher resistance of PrS[6]^iPr to open its cuboid D₂ conformation, with respect to PrS[6]^Et and PrS[6]^nPr, also affected its binding abilities. In fact, alkylammonium-based endo-cavity complexes of PrS[6]^iPr show lower binding constant values than the analogous propoxy/ethoxy-prism[6]arene complexes.     

Bis- and tetracalix[4]arenes in the partial cone conformation: synthesis, structure and RCM reactions

The synthesis, structure and ring-closing metathesis (RCM) reactions of polyether bridged biscalix[4]arenes 6 in the partial cone conformation with upper rim allyl substituents are reported. The RCM reaction modes depend on the length of polyether chain. Diethylene glycolic chain produced the dimer 7a and linear oligomer 7a′ with multi-cavities, whereas triethylene and tetraethylene glycolic chains allowed direct cyclization through intramolecular head-to-tail pattern to yield novel bridged biscalix[4]arenes 7b-c.     

Cooperative intramolecular hydrogen bond and conformations of thiocalix[4]arene molecules

The joint FTIR spectroscopic study and ab initio quantum-chemical calculations (HF/3-21G and PBE/TZ2P methods) showed that thiocalix[4] arene molecules adopt the cone conformation in CCl₄ solutions. The weakening of the cooperative intramolecular H bond in thiocalix[4]arenes compared to the corresponding calix[4]arenes can be due to the larger thiocalixarene macrocycle, bifurcated hydrogen bond in it, and electron density transfer from the bridging S atom to the benzene ring.     

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.     

Stereoselective convergent synthesis of a trans-fused polycyclic ether ring system including a 4-hydroxy-5-methyl-tetrahydropyran ring

[reaction: see text] Stereoselective convergent synthesis of a trans-fused 6-6-6-6-membered tetracyclic ether ring system including 4alpha- or 4beta-hydroxy-5-methyl-tetrahydropyran was achieved. The key reactions involve the acetylide-aldehyde coupling of two tetrahydropyrans, intramolecular hetero-Michael cyclization of enone, stereoselective reduction of enone, hydroboration, intramolecular acetalization, and stereoselective reduction of the acetal with Et(3)SiH-TMSOTf.     

Construction of Hydrocarbon Nanobelts

Linearly fused hydrocarbon nanobelts are a unique type of double‐stranded macrocycles that would serve as not only the powerful hosts in supramolecular science but also the templates to grow zig‐zag carbon nanotubes with defined diameters. Fully conjugated hydrocarbon nanobelts such as belt[n]arenes would also possess unique physical and chemical properties. Despite the importance, both fully conjugated and (partially) saturated hydrocarbon nanobelts remain largely unexplored because of the lack of cyclization methods. Reported here is the construction of nanometer sized H₁₂‐belt[12]arenes based on the strategy to close up all fjords of resorcin[6]arene by means of six‐fold intramolecular alkylation reactions of resorcin[6]arene derivatives. All resulting H₁₂‐belt[12]arenes produce a very similar nanobelt core structure with six benzene rings and six boat 1,4‐cyclohexadiene rings being alternately linear‐fused to give a nearly equilateral hexagonal cylinder. The average long diagonal is around 1 nm and the height of the cylinder is about 0.3 nm. The acquired H₁₂‐belt[12]arenes would be the potential precursors to various hydrocarbon nanobelts including fully conjugated belt[12]arenes.     

Synthesis of tetrahydrobenzoisoquinolinols, tetrahydropyrindines, and hexahydroquinolines from 4-aryltetrahydropyridines

A straightforward synthesis of tetrahydrobenzoisoquinolinols 2, tetrahydropyrindines 3, and hexahydroquinolines 4 from versatile intermediate 6 is reported. Two key transformations were carried out by intramolecular Friedel-Crafts cyclization and ring-closing metathesis in moderate yields. Skeleton 6 was easily prepared from the known starting material 4-aryl-4-methoxypiperidin-3-ones 7 via Wittig olefination with Ph₃P=CHCO₂Et, deconjugation with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), and boron trifluoride etherate (BF₃-OEt₂)-catalyzed addition of the corresponding iminium ion with allyltrimethylsilane.     

Thermodynamic parameters of sublimation of calix[4]arenes

The temperature dependences of the vapor pressure of calix[4]arenes were determined by the Knudsen effusion method. Some calix[4]arenes can form congruently subliming intramolecular compounds with a solvent. The thermodynamic parameters of the sublimation of the compounds were calculated. Molecules of organic solvents incorporated in the cavity of calix[4]arenes stabilize the crystal lattice, increasing the enthalpy of sublimation. The electrostatic interactions presumably make a significant contribution to stabilization of the crystal lattice of stoichiometric complexes of calix[4]arenes with solvents.     

A convergent synthesis of Hexahomotriazacalix

A new, convergent synthesis of hexahomotriazacalix[3]arenes 1a-e is described. The key transformation in this synthesis involves the coupling of the triamines 4a-d with 2, 6-bis(chloromethyl)-4-methylphenol 5 and results in the formation of the hexahomotriazacalix[3]arenes 1a-d in 90-95% yield. The triamines 4a-d were constructed by the one-pot reaction of monochloroaldehyde 3 and a primary amine followed by reduction to yield the triamines 4a-d in 50-55% yield. Deallylation of macrocycle 1d was accomplished by palladium catalysis to obtain the N-unsubstituted macrocycle 1e, which has the potential to be a precursor to a variety of N-substituted hexahomotriazacalix[3]arenes.     

Iron complexes of facially capping triphosphorus macrocycles

Primary and secondary phosphine piano-stool complexes of the type [eta(5)-CpFeL3]+ (L = phenylphosphine, 3, (alpha-methyl)vinylphosphine, 4, allylphosphine, 5, (2-methylpropenyl)phosphine, 5b, allyl(phenyl)phosphine, 6) are described. The alkenyl phosphine complexes, 5 and 6, react by intramolecular hydrophosphination to give the corresponding [eta(5)-CpFe]+ complexes of 1,5,9-triphosphacyclododecane (12-aneP3R3, 2, R = H), 9 and 10 respectively. Alkylation of the secondary phosphines in 9 is achieved by hydrophosphinations with ethene to give the 12-aneP3R3 (R = Et) derivative 11. These complexes are also obtained by reaction of suitable [eta(5)-CpFe]+ containing precursor complexes with the corresponding free 12-aneP3R3 macrocycle as is the related [eta(5)-Cp*Fe]+ derivative, 8. Direct substitution of acetonitrile in [Fe(CH3CN)6][BF4]2 by 12-aneP3Et3, leads to the macrocycle piano-stool complex, [(12-aneP3Et3)Fe(CH3CN)3][BF4]2, 7. The crystal structures of selected primary phosphine, eta(5)-Cp, eta(5)-Cp* complexes and 7, allow a comparison of steric influences upon key macrocycle ring closure reactions and hence an insight into parameters required for the formation of smaller ring sizes by template based methods.     

Synthesis and structure of the calixarene-like phosph(III)azane macrocycle [{P(mu-N(t)Bu)}2{1,5-(NH)2C10H6}]3

The reaction of [ClP(mu-NtBu)]2 with 1,5-diamino-naphthalene [1,5-(NH2)2C10H6] in Et3N-thf gives the trimeric macrocycle [{P(mu-NtBu)}2{1,5-(NH)2C10H6}]3(1); the X-ray structure of the toluene solvate 1.3toluene reveals a cone-shaped (calixarene-like) arrangement in which toluene guest molecules are trapped within the cavity.     

Large Calixarenes: Structure and Conformation of a Calix[16]arene Complexed with Neutral Molecules

A crystal of an inclusion compound between a calix[16]arene and molecules ofacetonitrile and dichloromethane, used as solvents, has been obtained and its X-raystructure studied. The cell is monoclinic, space group C2/c with a = 38.508(8) Å,b = 21.593(4) Å, c = 26.625(5) Å and = 121.34(3)°.The macrocycle is in the form of two superimposed celtic torcs connected by theirextremities.¹ Two acetonitrile molecules are situated in the middleof this double torc, two dichloromethane molecules are encapsulated in the pseudocalix[4]arenes obtained on both extremities of the torcs by the folding of the lastfour phenolic rings. A disorder is observed for the other acetonitrile and dichloromethanemolecules situated outside the macrocycle.     

Comparative macrocycle binding of the anticancer drug phenanthriplatin by cucurbit[<Emphasis Type="Italic">n</Emphasis>]urils, β-cyclodextrin and <Emphasis Type="Italic">para</Emphasis>-sulfonatocalix[4]arene: a <Superscript>1</Superscript>H NMR and molecular modelling study

The potential anticancer drug phenanthriplatin, [cis-(NH₃)₂(phenanthridine)Cl]⁺, forms supramolecular complexes with cucurbit[n]urils (CB[n], n?=?7 or 8), β-cyclodextrin and para-sulfonatocalix[4]arene (sCX[4]) as determined by ¹H NMR spectroscopy and molecular modeling. The results show that cucurbit[7]uril binds over the long arm of the drug, where hydrophobic effects and two hydrogen bonds stabilise binding. For cucurbit[8]uril, two phenanthriplatin molecules can bind simultaneously within the macrocycle’s cavity. Unfortunately, Na⁺ was able to displace the drug from both CB[7] and CB[8] making the macrocycles unsuitable as delivery vehicles for phenanthriplatin. Drug binding to β-cyclodextrin occurs at the portal of the macrocycle with no part of the phenanthriplatin located within the cavity. Phenanthriplatin binding to sCX[4] occurs in a 2-to-1, macrocycle-to-drug, ratio with the formation of a capsule-like complex where each sCX[4] binds over opposing ends of the drug. The results indicate that para-sulfonatocalix[4]arene is the only suitable macrocycle of the four studied for further research into phenanthriplatin drug delivery.     

Fullerene encapsulation with calix[5]arenes

This paper presents the synthesis of the fullerene hosts based on the calix[5]arenes and their binding properties. Calix[5]arenes 1a, 2, 3a bind C₆₀ or C₇₀ in organic solvents. The solvent effect of the fullerene complexation was clearly observed; the association constant decreases in a solvent with high solubility for C₆₀. Covalently linked double-calix[5]arenes 4-6 were also investigated on their binding properties for fullerenes in organic solvents. Their binding abilities for both C₆₀ and C₇₀ are extremely high in toluene solution. Higher binding selectivity toward C₇₀ is observed by all the double-calix[5]arenes. The selectivity of 5a toward C₇₀/C₆₀ is highest in toluene with a value of 10. The structures of the supramolecular complexes of the calix[5]arene hosts and C₆₀ or C₇₀ were investigated by using ¹H and ¹³C NMR studies. The molecular mechanics calculation and X-ray structure reveal that the interior of the calix[5]arene is complementary to the exterior of C₆₀ molecule. In contrast, the host-guest complexes of C₇₀ with the simple calix[5]arenes take many conformational options due to its less symmetric shape. The molecular mechanics calculation and our chemical shift simulation nicely worked to estimate the reliable structures; the calix[5]arene cavity takes up C₇₀ molecule, and the C₇₀ molecule tilts significantly from the C5 axis of the calix[5]arene. In the case of the host-guest complex of C₇₀ with the double-calix[5]arene, the molecular dynamics simulation of the host-guest complex represented the realistic movement of the bound C₇₀ inside the cavity. The combination of the molecular dynamics simulation and the chemical shift simulation of the host-guest complex suggested that the C₇₀ molecule rapidly moves inside the cavity.     

Ullmann coupling reaction of 1,3-bistriflate esters of calix[4]arenes: facile syntheses of monoaminocalix[4]arenes and 4,4′:6,6′-diepithiobis(phenoxathiine)

Treatment of 1,3-bistriflate esters of thiacalix- (6a) and calix[4]arenes 6b with benzylamine in the presence of CuI and K₃PO₄ results in the displacement of a TfO moiety with a benzylamino group, which provides an easy access to monoaminothiacalix[4]arene 4a and its methylene-bridged counterpart 4b. On the other hand, the reaction of 6a in the absence of benzylamine leads to intramolecular dietherification, giving 4,4′:6,6′-diepithiobis(phenoxathiine) 7a.     

Ultramacrocyclization in water via external templation

Condensing a dihydrazide and each of a series of cationic bisaldehyde compounds bearing polymethylene chains in weakly acidic water produces either a macrocycle in a [1 + 1] manner or its dimer namely a [2]catenane, or their mixture. The product distribution is determined by the length of the bisaldehydes. Addition of cucurbit[8]uril (CB[8]) drives the catenane/macrocycle equilibria to the side of macrocycles, by forming ring-in-ring complexes with the latter. When the polymethylene unit of the bisaldehyde is replaced with a more rigid p-xylene linker, its self-assembly with the dihydrazide leads to quantitative formation of a [2]catenane. Upon addition of CB[8], the [2]catenane is transformed into an ultra-large macrocycle condensed in a [2 + 2] manner, which is encircled by two CB[8] rings. The framework of this macrocycle contains one hundred and two atoms, whose synthesis would be a formidable task without the external template CB[8]. Removal of CB[8] with a competitive guest leads to recovery of the [2]catenane.

Condensing a bisaldehyde and a bisacylhydrazide in water in the presence of cucurbit[8]uril, produced an ultra-large ring whose framework contains more than one hundred atoms.     

Corona[5]arenes Accessed by a Macrocycle‐to‐Macrocycle Transformation Route and a One‐Pot Three‐Component Reaction

Corona[5]arenes, a novel type of macrocyclic compound that is composed of alternating heteroatoms and para ‐arylenes, were synthesized efficiently by two distinct methods. In a macrocycle‐to‐macrocycle transformation approach, S₆‐corona[3]arene[3]tetrazine underwent sequential S_NAr reactions with HS‐C₆H₄‐X‐C₆H₄‐SH (X=S, CH₂, CMe₂, SO₂, and O) to produce the corresponding corona[3]arene[2]tetrazines. Different corona[3]arene[2]tetrazine compounds were also constructed in a straightforward manner by a one‐pot three‐component reaction of HS‐C₆H₄‐X‐C₆H₄‐SH (X=S, CH₂, CMe₂, SO₂, and O) with diethyl 2,5‐dimercaptoterephthalate and 2 equiv of 3,6‐dichlorotetrazine under very mild conditions. All corona[5]arenes adopted 1,2,4‐alternate conformational structures in the crystalline state yielding similar nearly regular pentagonal cavities. Both the cavity size and the electronic property of the acquired macrocycles were fine‐tuned by the nature of the bridging element X.     

Synthesis of new methylated thieno[2,3‐a] and [3,2‐b]carbazoles by reductive cyclization of 6‐(2′‐Nitrophenyl)benzo[b]thiophenes obtained by palladium‐catalyzed cross‐coupling isabel

The synthesis of new methylated thieno[2,3‐a] and [3,2‐b]carbazoles (5) (R=H) was achieved by a palladium‐catalyzed cross‐coupling, intramolecular reductive cyclization sequence of reactions. The cyclization precursors 6‐(2′‐nitrophenyl)benzo[b]thiophenes (3) were obtained by Suzuki cross‐coupling of 6‐boronated methylbenzo[b]thiophenes intermediates (2) with 2‐bromo or iodonitrobenzene. The boronated intermediates (2) were prepared via bromine‐lithium exchange followed by boron transmetalation and coupled in situ using Pd(OAc)₂ giving thus a “one‐pot” three steps reaction from the 6‐bromobenzo[b]thio‐phenes (1) to the cyclization precursors (3) . In the reductive cyclization step, N‐ethylthienocarbazoles (5) (R=Et) were also obtained. Several experiments have been made varying the amount of triethylphosphite and the time of reaction, to avoid their formation.     

Phosphorus-bridged calixarene phosphites: dramatic influence of a tert-butyl group at the upper rim of the macrocycle upon anion binding

New cyclic phosphite derivatives of calix[4]arenes in 1,2-alternate configuration were obtained by the interaction of calix[4]arenes with ethylene chlorophosphite; the influence of a tert-butyl group at the upper rim of the macrocycle upon anion binding was shown     

Cucurbit[n]uril analogues: synthetic and mechanistic studies

[reaction: see text] The synthesis of cucurbit[n]uril analogues (18, 19, (+/-)-20, 33, 34, 35, 36, and 37) is presented. These CB[5], CB[6], and CB[7] analogues all contain bis(phthalhydrazide) walls that are incorporated into the macrocycle. The tailor-made synthesis of these CB[n] analogues proceeds by the condensation of the appropriate bis(electrophile) (4, 7, or 9) with bis(phthalhydrazide) (17), which delivers the CB[6] and CB[7] analogues in good yield, whereas the CB[5] analogue is formed in low yield. To improve the solubility characteristics of the CB[n] analogues for recognition studies in water or organic solution, the CO2Et groups were transformed to CO2H and CO2(CH2)9CH3 groups. On the basis of the results of product resubmission experiments, we conclude that these macrocycles are kinetic products. To help rationalize the good yields obtained in the CB[6] and CB[7] analogue macrocyclization reactions, we performed mechanistic studies of model methylene bridged glycoluril dimers, which suggest an intramolecular isomerization during CB[n] analogue formation.