Monoaza[5]helicenes. Part 2: Synthesis, characterisation and theoretical calculations

The synthesis of four different monoaza[5]helicenes is reported, to complete the whole series of these compounds, so that systematic studies on their properties can be carried out. They were fully characterised via NMR. A theoretical approach to explain why ring closure occurs to give the most crowded compound is reported, in comparison with earlier calculation methods.     

Synthesis of carbazole derived aza[7]helicenes

Synthesis of four derivatives of symmetrical aza[7]helicenes is achieved by I₂-THF mediated photocyclization of corresponding bis-styryl derivatives. The cyclization furnished the desired angularly fused aza-helicene in moderate yields. The structures are established by NMR spectroscopy and single crystal X-ray analysis for the difluoro derivative. The series of synthesized aza[7]helicenes showed remarkable thermal stability as indicated by DSC analysis.     

Tricarbonylchromium complexes of [5]- and [6]metacyclophane: an experimental and theoretical study

Tricarbonylchromium complexes of [5]- and [6]metacyclophane were prepared and the interaction between the Cr(CO)₃ tripod and the cyclophane fragment was evaluated by both an experimental and a theoretical study. The tricarbonylchromium complex of [5]metacyclophane could only be obtained in solution and was characterized by its ¹H NMR spectrum. The tricarbonylchromium complex of [6]metacyclophane was isolated and an X-ray crystal structure was obtained, which reveals that no significant geometric changes occur upon coordination of the severely distorted aromatic ring. Computations on the tricarbonylchromium complexes of m-xylene, [5]- and [6]metacyclophane furthermore demonstrate that the corresponding complexation energy is remarkably unaffected by the degree of distortion of the aromatic ring. Theoretical analyses of the above model systems as well as complexes of planar and artificially deformed benzene with Cr(CO)₃ show that this is primarily the result of two counteracting effects: (i) a stabilization due to an increased back-donation from the metal center to the benzene and (ii) a destabilization due to the increasing strain in the aromatic ring.     

Self-assembly and two-dimensional spontaneous resolution of cyano-functionalized [7]helicenes on cu(111)

Birds of a feather flock together: STM and DFT studies provide the first example of spontaneous chiral resolution of a helicene on a surface. Racemic 6,13-dicyano[7]helicene forms fully segregated domains of pure enantiomers (2D conglomerate) on Cu(111). The propensity of the system to optimize intermolecular CN???HC(Ar) hydrogen bonding and CN???CN dipolar interactions translates into chiral recognition with preferential assembly of homochiral molecules.     

Structure and vibrational spectra of some 8-oxa[5]helicenes

A systematic study has been conducted on the geometrical and electronic structure, heliomeric conformations of a series of 8-oxa[5]helicenes based on density functional theory (DFT) computations. A complete vibrational analysis has also been attempted for one of the 8-oxa[5]helicenes (molecule 5) on the basis of experimental infrared spectra in the far and mid infrared regions (60-3100 cm(-1)) and density functional theory computations using B3LYP/6-31G** method characteristic bands of the molecule identified. The approximate mean plane angle between the terminal rings A and E in the presently studied molecules are found to have values between 48.64° and 59.46°. This angle is much larger than the corresponding angle between the terminal rings in benzo[c]phenanthrene (～27°) and partially reduced benzo[c]phenanthrene (34.6-46.0°) and indicates that the presence of oxygen-containing six-membered ring provides a greater helicity to the molecules. Detailed quantum chemical study on molecule 4 shows the existence of two enantiomeric forms M- and P- of almost equal energy separated by a potential barrier of 15.55 kcal/mol. It is expected that similar 8-oxa[5]helicines (molecules 3, 5 and 6) may also exist in two enantiomeric forms.     

Theoretical and experimental studies on circular dichroism of carbo[n]helicenes

The chiroptical properties of a series of carbo[n]helicenes (n = 4-10) were investigated by the state-of-the-art approximate coupled cluster and density functional theory calculations. The theoretical calculation at the RI-CC2/TZVPP//DFT-D2-B97-D/TZVP level nicely reproduced the experimental CD spectra in both excitation energy and rotational strength without any shift or scaling. These calculations afforded the electric and the magnetic transition dipole moment vectors in [n]helicenes, allowing us to discuss the observed rotational strengths as a function of the number of benzene rings. Although the observed CD intensity was not immediately correlated to any of the calculated parameters, the anisotropy (g) factor of the (1)B(b) band and the specific rotation were found inversely proportional to n and nicely correlated with the helical pitch, but discontinuous at n = 6, where the aromatic rings start to overlap. In contrast, the g factor at the (1)B(a) band was rather insensitive to n. It was also revealed that the excitation energies of the (1)B(b) and (1)B(a) bands are inversely proportional to n over the entire range of n examined. The theoretical predictions also enabled us to rectify the erroneous experimental CD spectra of [5]- and [6]helicenes reported earlier, by using the enantiopure samples resolved by chiral HPLC.     

Syntheses and properties of enantiomerically pure higher (n > or = 7) [n-2]triangulanedimethanols and sigma-[n]helicenes

(P)-(+)-Hexaspiro[2.0.0.0. 0.0.2.1.1.1.1.1]pentadecane [(P)-17] as well as (M)-(-)- and (P)-(+)-octaspiro[2.0.0.0.0.0.0.0.2.1.1.1.1.1.1.1]nonadecanes [(M)- and (P)-25]-enantiomerically pure unbranched [7]- and [9]triangulanes-have been prepared starting from racemic THP-protected (methylenecyclopropyl)methanol 6. The relative configurations of all important intermediates as well as the absolute configurations of the key intermediates were established by X-ray crystal structure analyses. This new convergent approach to enantiomerically pure linear [n]triangulanes for n=7, 9 was also tested in two variants towards [15]triangulane. Some of the most prominent and unexpected features of the newly prepared compounds are the remarkable modes of self-assembly of the diols (P)-14, (E)-(3S,3'S,4S,4'S,5R,5'R)-21, (P)-(+)-22, and (E)-31 in the solid state through frameworks of intermolecular hydrogen bonds leading to, depending on the respective structure, nanotube- [(P)-14, (P)-(+)-22, and (E)-31], honeycomb-like structures [(E)-(3S,3'S,4S,4'S,5R,5'R)-21] or a supramolecular double helix [(P)-(+)- and (M)-(-)-22]. Liquid crystalline properties of the esters and ethers of the diols (P)-14, (P)-, and (M)-22 have also been tested. Although all of these [n]triangulanes have no chromophore which would lead to significant absorptions above 200 nm, they exhibit surprisingly high specific rotations even at 589 nm with [alpha](20)(D)=+672.9 (c=0.814 in CHCl(3)) for (P)-(+)-17, +909.9 (c=0.96 in CHCl(3)) for (P)-(+)-25, -890.5 (c=1.01 in CHCl(3)) for (M)-(-)-25, and -1302.5 (c=0.36 in CHCl(3)) for (M)-(-)-39, and the specific rotations increase drastically on going to shorter wavelengths. This outstanding rotatory power is in line with their rather rigid helical arrangement of sigma bonds, and accordingly these helically shaped unbranched [n]triangulanes may be termed "sigma-[n]helicenes", as they represent the sigma-bond analogues of the aromatic pi-[n]helicenes. Density functional theory (DFT) computations at the B3 LYP/6-31+G(d,p) level of theory for the geometry optimization and time-dependent DFT for determining optical rotations with a triplet-zeta basis set (B3 LYP/TZVP) reproduce the optical rotatory dispersions (ORD) very well for the lower members (n=4, 5) of the sigma-[n]helicenes. For the higher ones (n=7, 9, 15) the computed specific rotations turn out increasingly larger than the experimental values. The remarkable increase of the specific rotation with an increasing number of three-membered rings is proportional neither to the molecular weight nor to the number of cyclopropane rings in these sigma-[n]helicenes.     

SnAr Reactions of 2,4-Diazidopyrido[3,2-d]pyrimidine and Azide-Tetrazole Equilibrium Studies of the Obtained 5-Substituted Tetrazolo[1,5-a]pyrido[2,3-e]pyrimidines

A straightforward method for the synthesis of 5-substituted tetrazolo[1,5-a]pyrido[2,3-e]pyrimidines from 2,4-diazidopyrido[3,2-d]pyrimidine in SnAr reactions with N-, O-, and S- nucleophiles has been developed. The various N- and S-substituted products were obtained with yields from 47% to 98%, but the substitution with O-nucleophiles gave lower yields (20–32%). Furthermore, the fused tetrazolo[1,5-a]pyrimidine derivatives can be regarded as 2-azidopyrimidines and functionalized in copper(I)-catalyzed azide-alkyne dipolar cycloaddition (CuAAC) and Staudinger reactions due to the presence of a sufficient concentration of the reactive azide tautomer in solution. In total, seven products were fully characterized by their single crystal X-ray studies, while five of them were representatives of the tetrazolo[1,5-a]pyrido[2,3-e]pyrimidine heterocyclic system. Equilibrium constants and thermodynamic values were determined using variable temperature ¹H NMR and are in agreement of favoring the tetrazole tautomeric form (ΔG₂₉₈ = −3.33 to −7.52 (kJ/mol), ΔH = −19.92 to −48.02 (kJ/mol) and ΔS = −43.74 to −143.27 (J/mol·K)). The key starting material 2,4-diazidopyrido[3,2-d]pyrimidine presents a high degree of tautomerization in different solvents.     

Theoretical study of the second-order nonlinear optical properties of [N]helicenes and [N]phenylenes

The second-order nonlinear optical properties of helicenes and phenylenes have been theoretically investigated at the time-dependent Hartree-Fock level using the Austin model 1 semiempirical Hamiltonian. Both the antisymmetric isotropic component of the first hyperpolarizability (beta) and its projection on the dipole moment (beta(parallel)) have been determined for increasingly large helical systems as well as for their analogs substituted by donor/acceptor pairs. It is found that (i) in nonsubstituted helicenes and phenylenes, beta increases monotonically with the size of the system and slightly depends on the nature of the helix; (ii) the corresponding beta(parallel) is mostly determined by the radial component of the first hyperpolarizability vector; (iii) in helicenes, beta(parallel) is positive and presents quasiperiodic oscillations with the helix; (iv) in phenylenes, beta(parallel) depends upon the size of the helix and it can be either positive or negative as a result of the differences in evolution with N of the radial components of the dipole moment and first hyperpolarizability. Substituting the helicenes and phenylenes by the prototypical NH2/NO2 donor/acceptor pair provides a diversity of effects on beta and beta(parallel) that encompasses decrease, increase, and change in sign.     

Azo-hydrazo conversion via [1,5]-hydrogen shifts. A combined experimental and theoretical study

Azoalkenes 6e, 6g, 6h, and 8c underwent an easy azo-hydrazo conversion via a [1,5]-hydrogen shift yielding α,β-unsaturated hydrazones. The isomerization products were characterized through spectroscopic and spectrometric techniques. In order to understand the nature of the mechanism of these [1,5]-hydrogen shifts, the transition state structures of the reactions were theoretically studied at the B3LYP/6-31G(d,p) level. Substitution effects in the propenylazo system on the kinetic and thermodynamic parameters were analyzed. An electron localization function (ELF) analysis of the electronic structure of the transition state structure associated with the azo-hydrazo conversion of the simplest 1-azopropene 6a indicates that these [1,5]-hydrogen shifts have a two-stage one-step mechanism via pseudodiradical transition states, in which a formal hydrogen atom is transferred. This finding allows us to reject the pericyclic reaction model for these [1,5]-hydrogen shift reactions.     

A combined experimental and theoretical study on the conformational behavior of a calix[6]arene

An experimental and theoretical study on the conformational behavior of the 1,3,5-OMe-2,4,6-OCH(2)CONHOH-p-tert-butylcalix[6]arene has been carried out. In particular, semiempirical (AM1) and density functional theory (DFT) calculations have been performed in order to identify the possible conformers. The obtained results show that the cone structure is the most stable conformer at any level of theory, even if significant differences have been obtained for the other species. The inclusion of solvent effect, through a continuum model, also points out the relevant role played by the solvent in the stabilization of the cone structure in solution. These latter results have been confirmed by NMR experiments, which clearly show the presence of only the cone conformer in a polar solvent, such as DMSO. Finally, (1)H and (13)C NMR spectra on model systems, i.e., two successive phenol rings (Ar(1)-CH(2)-Ar(2)), have been computed at the DFT level and compared with the experimental spectra of the complete molecule. The results show an overall good agreement with the experimental data, thus leading to an unambiguous assignment of the experimental spectra.     

A quantum chemical study of racemization pathways in substituted chrysene derivatives

The potential-energy surfaces of 5,11-disubstituted 6,12-dimethoxychrysene and chrysene-6,12-dione derivatives were investigated by means of density functional calculations. We report relative energies of all conformers and an identification of the racemisation pathways of the chiral equilibrium structures. By analysis of homodesmotic reactions we were able to obtain an estimate for the strain energy of the substituted compounds. This strain energy can be used as a means of measuring the steric effects exerted by the substituents.     

A regioselective and convenient one-pot multicomponent synthesis of 9-amino-3,5-diaryl-4,9-dihydro-5H-[1,2,4]triazolo[5,1-c][1,2,4]triazepine-8-thiol

An efficient and environment-friendly procedure for the synthesis of a new series of nitrogen bridge-head [1,2,4]triazolo[5,1-c][1,2,4]triazepine derivatives through one-pot three-component reaction of polyfunctional triazole with aromatic aldehydes and acetophenone derivatives using alcoholic sodium hydroxide solution. The same new products were prepared in classical route through reaction of triazole with the corresponding chalcones under the same conditions.     

A study on theoretical predictive model and experimental findings of melt-electrospinning process

The current study extends a previous work published by the authors in which an analytical predictive model is proposed to simulate the melt-electrospinning process. The analytical model is specifically designed to predict the various behaviors of the melt-electrospun fiber under different material and processing conditions. A brief discussion of this model is presented here to establish context and help the reader capture the modeling philosophy employed. The current study complements the previous work by focusing on the experimental aspects of the research. Correlations between the independent process parameters and the topological attributes of the melt-electrospun fibers are investigated and compared with findings from the theoretical model. The effects of changes in the process parameters on average fiber diameters and the collection diameter are experimentally analyzed using the design of experiments (DOE) techniques. Toward this end, polylactic acid (PLA) is melt-electrospun at different treatment levels of the processing parameters in a controlled environment. Two regression-based models—one for predicting the collection diameter and the other for the fiber diameter—are derived from the DOE data for benchmarking and quantitative evaluation of the predictive performance of the theoretical model. The theoretical model is run based on the same treatment levels as the experiment. The elastic parameter values used in the theoretical simulation are extracted from rheological tests. Comparison between the simulated and the observed fiber characteristics revealed that the collector diameter predictions by the theoretical model exhibited approximately a 16.7% difference compared to 24.2% for the average fiber diameter. Finally, a discussion is presented on the challenges and potential factors contributing to the observed differences. Overall, given the identified challenges and gaps in material characterization, the results of the theoretical predictive model are encouraging.     

An experimental and computational study of calamitic and bimesogenic liquid crystals incorporating an optically active [2,2]-paracyclophane

Two liquid-crystalline materials containing an optically active (R)-4-hydroxy-[2,2]-paracyclophane group were prepared, one in which the chiral group is a bulky terminal unit and one in which it forms part of a terphenyl-like mesogenic unit. Both materials exhibit monotropic chiral nematic phases. Partial phase diagrams were constructed for mixtures of both materials with 5CB, allowing us to extrapolate pitch lengths and helical twisting power values (HTP) for each material. The HTP value of the material with a ‘locked’ paracyclophane is 70% higher than that of a ‘free’ paracyclophane and this is rationalised as being due to the reduction in conformational freedom of the former material relative to the later.     

High‐Yield Diastereoselective Synthesis of Planar Chiral [2]‐ and [3]Rotaxanes Constructed from per‐Ethylated Pillar[5]arene and Pyridinium Derivatives

Planar chiral [2]‐ and [3]rotaxanes constructed from pillar[5]arenes as wheels and pyridinium derivatives as axles were obtained in high yield using click reactions. The process of rotaxane formation was diastereoselective; the obtained [2]rotaxane was a racemic mixture consisting of (pS, pS, pS, pS, pS) and (pR, pR, pR, pR, pR) forms of the per‐ethylated pillar[5]arene ( C2 ) wheel, and other possible types of the [2]rotaxane did not form. Isolation of the enantiopure [2]rotaxanes with one axle through (pS, pS, pS, pS, pS)‐ C2 or (pR, pR, pR, pR, pR)‐ C2 wheels was accomplished. Furthermore, pillar[5]arene‐based [3]rotaxane was successfully synthesized by attachment of two pseudo [2]rotaxanes onto a bifunctional linker. [3]Rotaxane formed in a 1:2:1 mixture with one axle threaded through two (pS, pS, pS, pS, pS)‐ C2 , one (pS, pS, pS, pS, pS)‐ C2 and one (pR, pR, pR, pR, pR)‐ C2 (meso form), or two (pR, pR, pR, pR, pR)‐ C2 wheels. The [3]rotaxane enantiomers and the meso form were successfully isolated using appropriate chiral HPLC column chromatography. The procedure developed in this study is the starting point for the creation of pillar[5]arene‐based interlocked molecules.     

A convergent approach to synthesis of bortezomib: the use of TBTU suppresses racemization in the fragment condensation

Bortezomib is a first-in-class therapeutic antineoplastic agent used for treating patients with multiple myeloma and mantle cell lymphoma. In this paper we report an improved method for synthesis of the title compound using a convergent approach. TBTU was found to efficiently suppress racemization in the fragment condensation. In comparison with the original synthesis, the presented one is shorter by two steps, higher in yield, and provides better atom economy.