Exploring structural and conformational behaviour of cyclophanes incorporating imidazole-2-thiones

New cyclophanes containing two imidazole-2-thione moieties linked by two xylylene groups have been synthesized by the reaction of imidazolium-linked cyclophanes with sulfur in the presence of K₂CO₃. The conformational behaviour of the new cyclophanes was explored by NMR spectroscopy and X-ray diffraction studies. In cyclophanes containing o-xylylene or 2,4,6-trimethyl-m-xylylene linking groups, the imidazole-2-thione groups were mutually syn in both the solid state and in solution, the cyclophanes adopting a conformation reminiscent of the cone conformation of calix[4]arenes. Cyclophanes containing p-xylylene or m-xylylene linking groups exhibited two conformations in solution, one in which the imidazole-2-thione groups are mutually syn, the other in which they are mutually anti, and these conformations did not interconvert on the NMR timescale. Both conformations co-crystallised in the m-xylylene linked cyclophane, while for the p-xylylene-linked cyclophane the anti conformation crystallised separately.     

Azolium-linked cyclophanes: effects of structure, solvent, and counteranions on solution conformation behavior

This paper describes the synthesis, structural characterization, and solution behavior of some xylyl-linked imidazolium and benzimidazolium cyclophanes decorated with alkyl or alkoxy groups. The addition of alkyl/alkoxy chains to the cyclophanes allows for studies in chlorinated solvents, whereas previous solution studies of azolium cyclophanes have generally required highly polar solvents. The azolium cyclophanes may exist in a syn/syn conformation (azolium rings mutually syn, arene rings mutually syn) or a syn/anti conformation (azolium rings mutually syn, arene rings mutually anti). The preferred conformation is significantly affected by (i) binding of bromide (ion pairing) to the protons on the imidazolium or benzimidazolium rings, which occurs in solutions of bromide salts of the cyclophanes in chlorinated solvents, and (ii) the addition of alkoxy groups to the benzimidazolium cyclophanes. These structural modifications have also led to cyclophanes that adopt conformations not previously identified for similar azolium cyclophane analogues. Detailed (1)H NMR studies for one cyclophane identified binding of bromide at two independent sites within the cyclophane.     

The synthesis, characterization and X-ray diffractometry structure of fluorine-containing cyclobis(paraquat-p-phenylene) tetracation

<正>Two novel fluorine-containing cyclophanes 1 and 2 incorporating a 1,4-bismethylfluorophenylene subunits have been synthesized via the template-directed clipping methodology and their structure was characterized by ~1H NMR,~(13)C NMR, MALDI-TOF-MS and elemental analysis.X-ray diffraction analysis of the solid state molecular structure showed that the complex units are linked by non-classical C-H…F hydrogen bonding.     

Dinuclear N-heterocyclic carbene complexes of silver(I), derived from imidazolium-linked cyclophanes

The synthesis of four new silver complexes of bidentate N-heterocyclic carbenes, derived from imidazolium-linked cyclophanes, has been achieved via a simple complexation reaction of the imidazolium-linked cyclophanes with the basic metal source Ag(2)O. The cyclophane structures contain two imidazolyl links between ortho-, meta- and mixed ortho/meta-substituted aromatic rings. The new silver carbene systems are thermally stable and have been characterised by NMR spectroscopy and X-ray crystallography. Three of the complexes have a dimeric structure of the form [L(2)Ag(2)](2+) in the solid state that is rigid on the NMR timescale in solution. The fourth complex has a neutral structure of the form [L(AgBr)(2)], the NMR studies suggesting some lability of the L-Ag bonding in solution.     

Cyclophanes of perylene tetracarboxylic diimide with different substituents at bay positions

Cyclophanes of perylene tetracarboxylic diimides (PDIs) with different substituents at the bay positions, namely four phenoxy groups at the 1,7-positions (1), four piperidinyl groups at the 1,7-positions (2), and eight phenoxy groups at the 1,6,7,12-positions (3) of the two PDI rings, have been synthesized by the condensation of perylene dianhydride with amine in a dilute solution. These novel cyclophanes were characterized by (1)H NMR spectroscopy, MALDI-TOF mass spectrometry, electronic absorption spectroscopy, and elemental analysis. The conformational isomers of cyclophanes substituted with four piperidinyl groups at the 1,7-positions (2 a and 2 b) were successfully separated by preparative TLC. The main absorption band of the cyclophanes shifts significantly to the higher energy side in comparison with their monomeric counterparts, which indicates significant pi-pi interaction between the PDI units in the cyclophanes. Nevertheless, both the electronic absorption and fluorescence spectra of the cyclophanes were found to change along with the number and nature of the side groups at the bay positions of the PDI ring. Time-dependent DFT calculations on the conformational isomers 2 a and 2 b reproduce well their experimental electronic absorption spectra. Electrochemical studies reveal that the first oxidation and reduction potentials of the PDI ring in the cyclophanes increase significantly compared with those of the corresponding monomeric counterparts, in line with the change in the energy of the HOMO and LUMO according to the theoretical calculations.     

A combined experimental and theoretical study on the conformation of multiarmed chiral aryl ethers

Four series of multiarmed chiral aryl ethers carrying two, three, five, or eight side-chains on a variety of aromatic core molecules (2-5) were prepared. The structure and conformation of 2 and 3 (in the solid state) were determined by the X-ray crystallographic analyses. While a pair of alternated (anti) conformers (i.e, up-down and down-up) were found in the crystal of 2, three side-arms in 3 were aligned in the same direction to give a C(3)-symmetric syn-conformation. Examinations by dispersion-corrected density functional (DFT-D) calculations revealed that two out of six anti- and two out of four syn-conformers of 2 are energetically most important. Two calculated structures of anti-conformers are in good agreement with those found in the solid state by X-ray analysis. Similarly, relevant conformations of syn-3, fully alternated 4, and C(5)-symmetric 5 were optimized at the DFT-D-B-LYP/TZVP level. The structure and conformation of the side-arms in 2-5 in solution were further studied by temperature dependent (1)H NMR and UV-vis spectroscopy. In addition, comparative experimental and theoretical CD spectral studies were carried out in order to elucidate the contribution of the thermodynamically less-stable minor isomers in solution. The CD spectral changes observed for 2 and 3 at varying temperatures were quite different, while the parent chiral arene 1, as well as 4 and 5, only showed an increased intensity of the negative Cotton effect for the (1)L(b) band. The latter behavior is readily accounted for in terms of the conformational freezing of the chiral groups at low temperatures. The unusual CD spectral behavior observed for 2 and 3 was rationalized by the conformational alteration of the side-arms. Because of attractive van der Waals interactions between the aromatic units of the arms in nonpolar solvents, the syn-conformations become gradually more important for 2 at low temperatures, which eventually results in a weak positive Cotton effect for the (1)L(b) band. This was also supported by the SCS-MP2/TZVPP single-point energy calculations for the relevant conformers of 2. For 3, the contribution of the C(3)-symmetrical conformer becomes more important than the less-symmetrical isomers at low temperatures. The conformations of 2 and 3 in their excited states as well as in the oxidized states were also examined.     

Molecular Pacman: folding, inclusion, and X-ray structures of tri- and tetraamino piperazine cyclophanes

Reaction of piperazine and 1,3-bis(bromomethyl)-2-nitrobenzene under high-dilution conditions yields cyclic trimeric trinitro, tetrameric tetranitro, and pentameric pentanitro piperazine cyclophanes. Reduction of the nitro groups with SnCl(2) under acidic conditions produces the corresponding triamino and tetraamino piperazine cyclophanes. The solution studies of both nitro and amino piperazine cyclophanes at 30 degrees C by (1)H NMR spectroscopy shows symmetrical structures owing to the fast conformational exchange, whereas the low temperature studies of the tetraamino piperazine cyclophane reveals interesting dynamic behavior that indicates additional intramolecular interactions. Careful crystallizations of the trimeric trinitro and triamino and the tetrameric tetraamino cyclophanes resulted in crystals suitable for X-ray diffraction studies. In the crystalline state the amino-functionalized cyclophanes manifest an extraordinary circular intramolecular hydrogen-bonding network that leads to a fixed 3D structure. Hydrogen bonding in the triamino trimer leads to orientation of all three of the amino groups on the same side of the macrocycle, namely, the rcc conformation, whereas the tetraamino tetramer folds into a more compact shell-like conformation. During the crystallization process one acetonitrile guest is enclosed into the cavity of the tetraamino cyclophane, which gives a crystalline inclusion complex with remarkable resemblance to the famous Pacman motif. The folding, which mimics the behavior of some cyclic peptides and pyrroles, is induced by intramolecular hydrogen bonding from the amino groups to the tertiary amine groups of the piperazines. The cavity of the tetraamino tetramer is markedly smaller than in the corresponding, but nonfolded, tetranitro tetramer and the guest/host volume ratio (packing coefficient) for the acetonitrile and the cavity is approximately 50 %, which indicates a good size match for acetonitrile inclusion.     

Encapsulation of small polar guests in molecular apple peels

Three aromatic oligoamides have been prepared that have alternating 1,6-diaminopyridine and 1,6-pyridinedicarboxylic acid units at the center of the sequence and two 8-amino-2-quinolinecarboxylic acid units at each extremity. The three oligomers differ in the number--3, 5, or 7-of pyridine units in the sequence. They were designed to adopt helically folded conformations in solution and in the solid state. The sequence of monomers was chosen so that the diameter of the helix is larger in the center than at each extremity, and hence they resemble helically wrapped apple peels. According to modeling studies, the pyridine units were expected to define a polar hollow within the helix that is large enough to accommodate small polar guests, whereas the quinoline units at each end of the oligomeric sequences were expected to completely cap the hollow and transform the helix cavities into a closed shell that may act as a capsule. Crystallographic studies demonstrate that the oligomers do fold into helices that define a cavity isolated from the surrounding medium in the solid state. Depending on the number of pyridine rings, one or two water molecules are bound within the capsules. The crystal structure of a capsule fragment shows that MeOH can also be hosted by the largest oligomer. Solution NMR studies confirm that binding of water also occurs in solution with the same stoichiometry as observed in the solid state. The capsules have distinct signals depending on whether they are empty, half-full, or full, and these species are in slow exchange on the NMR timescale at low temperature. Indeed, the binding and release of water molecules requires a significant conformational distortion of the helix that slows down these processes. The addition of small polar molecules such as methanol, hydrazine, hydrogen peroxide, or formic acid to the largest capsule leads to the observation of new sets of NMR signals of the capsules that were assigned to complexes with these guests. However, water appears to be the preferred guest.     

New [4.4]cyclophanes: molecular parallelograms, triangles, rhombuses, pentagons, and supramolecular constructions

The fair or good yield synthesis of new [(4.4)(n)]cyclophanes (n = 1-5), starting from 1,4-bis(2-hydroxymethyl-5,5-dimethyl-1,3-dioxan-2-yl)benzene and several diacid-dichlorides, based on monomer and oligomer formation reactions (from 1 + 1 to 5 + 5), is reported. The structure and the complex architectures of the lattices for these cyclophanes are revealed by the X-ray molecular structure for five compounds, NMR investigations, and mass spectrometry measurements. Intramolecular and intermolecular CH-pi, p-pi, and pi-pi interactions are observed, both in solid state and solution.     

Hydrogen-bonding-induced planar, rigid, and zigzag oligoanthranilamides. Synthesis, characterization, and self-assembly of a metallocyclophane

Four oligoanthranilamides 1-4, which are incorporated with three, five, seven, or nine benzene units, respectively, have been synthesized and characterized. X-ray analysis, 1D and 2D (1)H NMR, and IR experiments reveal that all the new oligoamides adopt rigid, planar and zigzagged conformations in both solution and solid state, which are stabilized by intramolecular three-center hydrogen bonding. A 5-mer oligomer 22, which is incorporated with two acetylene groups at the ends, has also been synthesized and utilized for the self-assembly of a rigid hydrogen-bonded metallocyclophane. The new rigid oligoanthranilamides represent useful building blocks for the construction of supramolecular architectures.     

Efficient construction of biaryls and macrocyclic cyclophanes via electron-transfer oxidation of Lipshutz cuprates

An efficient method for the homocoupling of aryl halides by electron-transfer oxidation of Lipshutz cuprates (Ar2Cu(CN)Li2) with organic electron acceptors is disclosed. Thus, various types of Lipshutz cuprates are prepared by successive treatment of aryl or heteroaryl bromides with tert-butyllithium and CuCN. The electron-transfer oxidation of Lipshutz cuprates with p-benzoquinones proceeds smoothly to afford the corresponding homocoupling products in moderate to good yields. Furthermore, it can be applied to the construction of either thiophene- or benzene-fused 10-membered ring cyclophanes. For the synthesis of 10-membered cyclophanes, the linear C-Cu-C structure of Lipshutz cuprates should be maintained in the dimetallacyclic intermediates, producing the large ring cyclophanes efficiently. The X-ray analysis of the cyclophanes reveals that the difference in the bridging atoms results in the different conformations of the macrocyclic rings. Thus, the silicon-bridged cyclophane 5a adopts a D2-symmetric structure with a twisted rhombic arrangement of four thiophene rings, whereas the methylene- and oxygen-bridged cyclophanes 5b and 5c possess C2h- and C2-symmetric structures with chair- and boatlike conformations, respectively. The 1H NMR spectrum of C2-symmetric 5c is temperature-dependent, and the activation energy (DeltaG) for the conformational change is 10.1 kcal/mol.     

Slow anion exchange,conformational equilibria,and fluorescent sensing in venus flytrap aminopyridinium-based anion hosts

The synthesis, anion binding, and conformational properties of a series of 3-aminopyridinium-based, tripodal, tricationic hosts for anions are described. Slow anion and conformational exchange on the (1)H NMR time scale at low temperature, coupled with NMR titration, results in a high level of understanding of the anion-binding properties of the compounds, particularly with respect to significant conformational change resulting from induced fit complexation. Peak selectivity for halides, particularly Cl(-), is observed. The approach has been extended to dipodal and tripodal podands based on 3-aminopyridinium "arms" containing photoactive anthracenyl moieties. The 1,3,5-tripodal host shows a remarkable selectivity for acetate over other anions, in contrast to the analogous unsubstituted tris(3-aminopyridinium) analogue, despite the fact that low-temperature (1)H NMR experiments reveal a total of four acetate-binding conformations. Photodimerization of anthracene units results in the formation of potential fluorescent anion sensors.     

Bis-phenol A Cyclophanes: Synthesis, Crystal Structures and Binding Studies

The synthesis and structural characterisation of three new macrocyclicbis-phenol A cyclophane ethers are described. The solid state structuresof two of the cyclophanes were determined by single crystal X-raydiffraction. Cyclophane 3 crystallises in the orthorhombic spacegroup Pbca with unit cell dimensions of a = 11.533(7), b = 29.383(8),c = 14.927(8) Å and cyclophane 4 in the monoclinic spacegroup P2₁/n with cell dimensions of a = 11.585(4), b = 11.839(2), c = 18.866(2) Å, = 94.48(2)°.The X-ray crystalstructures reveal distorted conformations, thus supporting the weak bindingof quats in solution observed by the NMR studies. In the crystalline state bothmacrocycles were found to form self-complementary dimers held together byweak intermolecular - and CH- interactions. The bindingbehaviour towards a series of tetralkylammonium cations was determinedby ¹H NMR titration in CDCl₃ solution. The interactions between the hosts and the quats were clearly detectable but too weak to be translated into meaningful equilibrium constants.     

Multiple Stimuli-Responsive Conformational Exchanges of Biphen[3]arene Macrocycle

Conformational exchanges of synthetic macrocyclic acceptors are rather fast, which is rarely studied in the absence of guests. Here, we report multiple stimuli-responsive conformational exchanges between two preexisting conformations of 2,2′,4,4′-tetramethoxyl biphen[3]arene (MeBP3) macrocycle. Structures of these two conformations are both observed in solid state, and characterized by ¹H NMR, ¹³C NMR and 2D NMR in solution. In particular, conformational exchanges can respond to solvents, temperatures, guest binding and acid/base addition. The current system may have a role to play in the construction of molecular switches and other stimuli-responsive systems.     

NMR studies of conformations and dynamic processes—1 : [24]cyclophanes with ethylene bridges

The conformations and dynamic processes in a series of relatively unstrained [2₄]paracyclophanes (with one, two or four -CH₂-CH₂-bridges) and some closely related compounds have been analysed. Their ¹NMR spectra have been recorded at low temperatures and the temperature dependence rationalised as being due to essentially two types of dynamic process-the torsional motion around the sp³-sp³ C-C bonds in the bridges, and the rotation around the sp²-sp³ C-C bonds adjacent to the benzene rings. The barriers to the former process are similar for the series of cyclophanes 1–6 and are due to steric and electronic interactions in the syn-oriented transition states. In cyclophanes 7–9, in which anti-orientations of the aromatic rings are possible, the barriers are lower. The latter process, involving the rotation of the benzene rings, becomes important at temperatures below 150 K and has not been further analysed.     

Conformational Studies by Dynamic NMR. 71.(1) Stereodynamics of Triisopropyl(aryl)silanes in Solution and in the Solid State

A study has been carried out of the conformations of triisopropyl(aryl)silanes (i-Pr)(3)SiAr, (Ar = phenyl, 1-naphthyl, and 2-naphthyl) both as to the orientation of the three isopropyl groups and the conformation about the silicon-aromatic bonds. The report comprises dynamic NMR studies of conformational interconversions in solution and in the solid state as well as molecular mechanics calculations. The barriers for the stereomutation processes measured in the crystalline state were found significantly higher than those in solution.     

Rhodium and iridium complexes of an asymmetric bicyclic NHC bearing secondary pyridyl donors

A tridentate N^C^N ligand, 1, containing a bicyclic central NHC ring and two flanking pyridyl groups has been coordinated to Rh(I) and Ir(I) to give complexes of the type [M(κ(3)-1)(1,5-COD)]PF(6) (2 M = Rh; 3 M = Ir). In contrast to our earlier study with this ligand, the complexes have been shown to approximate to a trigonal bipyramidal geometry in the solid state and exist as an isomeric mixture in solution as determined by (1)H and (13)C NMR spectroscopy. Electrochemical studies revealed that both complexes undergo a 1-electron oxidation with the potential of the Rh complex 0.1 V less than that of the Ir complex in CH(2)Cl(2). Preliminary DFT studies confirm the lowest energy conformations as those seen in the solid state and show the location and energy of the HOMOs to be identical in 2 and 3. Partial charge analysis shows a greater positive charge on the Ir in 3 compared to the Rh in 2. Some preliminary studies of hydrogenation reactivity have shown the complexes to be efficient for both transfer and direct hydrogenation of prochiral ketones and alkenes at moderate temperatures but without any discernible enantioselectivity.     

High-resolution 13C NMR study of free and metal-complexed ionophores in the solid state: Conformation and dynamics of the macrocyclic ring and the effect of intermolecular short contact of methyl groups on spin–lattice relaxation times and displacements of chemical shifts

High-resolution ¹³C NMR spectra of 15 samples of uncomplexed and metal-complexed tetranactin and nonactin were recorded in the solid state, revealing characteristic displacements of peaks due to complex formation and the effect of crystalline packing on the ¹³C chemical shifts and spin–lattice relaxation times of the methyl groups. The C-1 ¹³C chemical shifts of uncomplexed and complexed tetranaction and nonactin are well related to the variation of nearby torsion angles characteristic of the macrocyclic conformation, as determined by x-ray diffraction. The existence of short intermolecular contact of methyl groups (<3.8 Å) at the surface of the molecules results in either prolonged ¹³C spin–lattice relaxation times in the laboratory frame (T₁^C) or substantial upfield displacement of peaks (up to 6 ppm). In addition, significantly reduced T₁^C values in uncomplexed nonactin (one order of magnitude smaller than those of other compounds) was ascribed to the presence of a puckering motion of the tetrahydrofuran ring and fluctuation of the macrocyclic ring in the solid state (with a time scale of 10⁻⁸ _s). Finally, how the conformations of these compounds in the solid are retained in chloroform solution was examined in view of the differences in the ¹³C chemical shifts between the solid and solution.     

Missing-link macrocycles: hybrid heterocalixarene analogues formed from several different building blocks

The synthesis and structural characterization of hybrid heterocalix[4]arene analogues containing pyrrole, benzene, methoxy-substituted benzene, and pyridine subunits is described. Macrocycles 1 and 2, examples of calix[2]benzene[2]pyrrole and calix[1]benzene[3]pyrrole systems, respectively, are synthesized by the condensation of pyrrole and an appropriate phenylbis(carbinol). Macrocycles 3 and 7, examples of calix[2]benzene[1]pyridine[1]pyrrole and calix[1]pyridine[3]pyrrole, respectively, are synthesized by the use of a carbene-based pyrrole-to-pyridine ring-expansion procedure. Single-crystal X-ray analysis reveals that compounds 1a, 1b, and 2b adopt 1,3-alternate conformations in the solid state, whereas compounds 3 and 7 display structures that are best described as "flattened partial cones" in terms of their conformation. (Series a refers to pure benzene-derived systems, whereas series b indicates macrocycles containing 5-methoxyphenyl subunits). In the solid state, the methoxy-functionalized macrocycles 1b and 2b, and the chloropyridine-containing macrocycle 7 exist as dimers. In the case of 1a and 7, these compounds interact with neutral solvent in the solid state. The conformations of the macrocycles in solution were explored by temperature-dependent proton NMR and NOESY spectral analysis. At 188 K, macrocycles 1a and 2a adopt flattened 1,3-alternate conformations, whereas macrocycles 3 and 7 exist in the form of flattened partial-cone conformations. Standard proton NMR titration analyses were carried out in the case of macrocycles 1a and 2a, and reveal that at least the second of these systems is capable of binding fluoride and chloride anions in CD(2)Cl(2) solution at room temperature (K(a)=571 and 17M(-1) in the case of 2a and F(-) and Cl(-), respectively).     

Polycationic Redox-Active Cyclophanes with Integrated Electron-Rich Diboron Units

Cationic cyclophanes are widely used in a variety of applications in supramolecular chemistry and materials science. In this work the authors systematically study the integration of electron-rich diboron units with B^II atoms into polycationic cyclophanes with viologen-like electron-acceptor units. They also report a first hexacationic cage-compound in which three diboron units connect two tris(4-pyridyl)triazine acceptor units. Moreover, di- and tetracationic open-structure compounds, in which one diboron unit connects two bispyridyl groups, were synthesized and the properties compared to those of the corresponding closed structures (cyclophanes). The combination of diboron electron-donor units and bi- or oligopyridyl electron-acceptor units leads to intriguing optical and redox properties.