Hexasubstituted Benzene Research Articles

Regioselective [2 + 2 + 2] Alkyne Cyclotrimerizations to Hexasubstituted Benzenes: Syntheses of Fomajorin D and Fomajorin S.

Hexasubstituted benzenoids are prepared by regioselective bimolecular [2 + 2 + 2] alkyne cyclotrimerizations of diynes with alkynes. These convergent and efficient benzannulations are directed toward and lead to the first total syntheses of the illudalane sequiterpenes fomajorin D and S, in 10 and 7 steps, respectively, from commercially available dimedone. Control experiments suggest that hydrogen bonding may play a role in preorganizing the diyne and alkyne coupling partners for establishing the desired regioselectivity, but other factors are likely involved in the selective formation of other regioisomers.

Ni0-Catalyzed Regioselective [2 + 2 + 2] Cyclotrimerization of 1,3-Diynes: An Expeditious Synthesis of Hexasubstituted Alkynyl Benzenes.

In the present work, we demonstrate a regioselective [2 + 2 + 2] cyclotrimerization of 1,3-diynes catalyzed by Ni0 to provide hexasubstituted benzenes (HSBs). HSBs have significant applications as functional materials and pharmaceuticals. The present protocol exhibited remarkable versatility, transforming 1,3-diynes with diverse alkyl, aryl, and heterocyclic groups to the corresponding HSBs. With the help of control experiments and density functional theory (DFT), the mechanism of the reaction and the origin of regioselectivity were elucidated.

Synthesis of O- and N-substituted pentaiodobenzenes bearing σ-symmetric delocalized orbitals using site-selective nucleophilic aromatic substitution reactions

Abstract We report the synthesis of oxygen- and nitrogen-substituted (O- and N-substituted) pentaiodobenzenes using site-selective nucleophilic aromatic substitution (SNAr) reactions. Single-crystal X-ray diffraction analysis and theoretical calculations of thus synthesized pentaiodobenzenes reveal that their highest occupied molecular orbital (HOMOs) are composed of circularly delocalized σ-symmetric orbitals, as found in hexa-substituted benzenes bearing heavy atoms such as selenium and iodine.

Supramolecular Weaving by Halogen-Bonding in Functionality-Rich Hexasubstituted Aromatic Synthons.

Hexasubstituted benzenes are interesting platforms for the generation of functional materials, whose applications span from supramolecular recognition to organic electronics. Their synthesis is difficult to achieve by controlling multiple substitution steps of all hydrogen atoms on the aromatic benzene skeleton, so, often, cycloaddition reactions from disubsituted alkynes are used. In this work, we report a novel, straightforward route to C3-symmetrical hexasubstituted aromatic synthons with a diverse and rich pattern of functionalities, and we report about their packing mode in the crystals, in which, unprecedentedly, directional, strong halogen bonding interactions are capable of forming bidimensional supramolecular weaving.

The Influence of the Intramolecular 2D Interactions on the Physicochemical Properties of Hexasubstituted Benzene Derivatives

This paper contains a comprehensive study regarding the synthesis and physicochemical properties of new hexasubstitued benzene derivatives. In this work, three compounds of this type (including two electropolymerisable monomers) were synthesized in a one-step reaction with good yields ranging from 34% to 56%. A thermal investigation shows that this type of compound is stable up to 360 °C (10% weight loss temperature). The influence of the substituents in the first and second position of the central benzene on the stability, luminescence, and (spectro)electrochemical behavior was thoroughly studied with the aid of theoretical calculations. In each case, strong blue shifting of the π-π* transition (according to 1,4-disubstitued analogs) was observed, proving this moieties’ orthogonal orientation. In the case of derivatives with a Bt-core-Bt formula (where Bt = 2,2′-bithiophene-5-yl), an electrochemical oxidation process transformed them into conducting polymers. The polymer presents extraordinary stability during multiple p-doping; thus, spectroelectrochemical measurements of polymeric films were also performed.

Organometallic trimacrocyclic hexasubstituted benzenes: Synthesis, structure and properties

Macrocyclization proves a useful strategy for obtaining artificial supramolecular hosts via reducing the degrees of freedom of the corresponding precursors. However, synthesis of receptor containing multiple macrocycles is challenging. In this contribution, we describe the rational design and synthesis of a new class of organometallic trimacrocyclic hexasubstituted benzenes 1 and 2 via either metal–ligand coordination or dynamic covalent chemistry strategies. Such class of constructs feature a benzene core fused by three identical metallomacrocycles with high symmetry and interesting physiochemical property, as inferred from the NMR, mass spectrometry, cyclic voltammetry and DFT calculations. Trimacrocycle 2 bearing one ferrocene unit in each sub–macrocycle was found able to selectively capture bromide and iodide, as evidenced by NMR spectroscopy, DFT calculations, as well as molecular dynamics simulations. Thus, we hope this study will somewhat accelerate the development of complex functional host–guest systems for species of interest.

Trimacrocyclic hexasubstituted benzenes for recognition of guanidinium and their anti-cancer and antimicrobial activities

We report the facile synthesis of two trimacrocyclic hexasubstituted benzenes for selective guanidinium recognition and extraction, along with their anti-cancer and antimicrobial activities.

Trimacrocyclic hexasubstituted benzene linked by labile octahedral [X(CHCl3)6]- clusters.

Crystalline supramolecular architectures mediated by cations, anions, ion pairs or neutral guest species are well established. However, the robust crystallization of a well-designed receptor mediated by labile anionic solvate clusters remains unexplored. Herein, we describe the synthesis and crystalline behaviors of a trimacrocyclic hexasubstituted benzene 2 in the presence of guanidium halide salts and chloroform. Halide hexasolvate clusters, viz. [Cl(CHCl3)6]−, [Br(CHCl3)6]−, and [I(CHCl3)6]−, were found to be critical to the crystallization process, as suggested by the single-crystal structures, X-ray powder diffraction (XRPD), thermogravimetric analysis (TGA), scanning electron microscopy with energy dispersive spectroscopy (SEM-EDS), and NMR spectroscopy. This study demonstrates the hitherto unexpected role that labile ionic solvate clusters can play in stabilizing supramolecular architectures.

Convenient synthesis of hexasubstituted benzene derivatives via DABCO promoted domino reaction of arylidene malononitrile and dialkyl but-2-ynedioate

A convenient synthetic protocol for the hexasubstituted benzene derivatives was successfully developed by DABCO promoted domino reaction of arylidene malononitrile with two molecules of dialkyl but-2-ynedioates. The domino reaction resulted in tetraalkyl 6-cyano-[1,1′-biphenyl]-2,3,4,5-tetracarboxylates in good to high yields. This formal [2 + 2 + 2] cycloaddition was believed to proceed with sequential nucleophilic addition, Michael addition, annulation and aromatization processes.

Para-Selective Arylation of Arenes: A Direct Route to Biaryls by Norbornene Relay Palladation.

Biaryl compounds are extremely important structural motifs in natural products, biologically active components and pharmaceuticals. Selective synthesis of biaryls by distinguishing the subtle reactivity difference of distal arene C-H bonds are significantly challenging. Herein, we describe para-selective C-H arylation, which is acheived by a unique combination of a meta-directing group and norbornene as a transient mediator. Upon direct meta-C-H palladation, one-bond relay palladation occurs in presence of norbornene and subsequently para-C-H arylation is achieved for sulfonates, phosphonates and phenols bearing 2,6-disubstitution patterns. The protocol is amenable to electron-deficient aryl iodides. Multisubstituted arenes and phenols are obtained by postsynthetic modification of the products. The protocol allows the synthesis of hexa-substituted benzene by sequential selective distal C-H functionalization.

Three Queries about the HOMA Index.

HOMA (Harmonic Oscillator Model of Aromaticity) is a simple, successful, and widely used geometrical aromaticity index. However, HOMA can also be used as a general molecular descriptor appropriate for any type of molecule. It reaches the global maximum for benzene, whereas the potent magnetic aromaticity NICS index has no lower or upper limits. Hence, questions arise and go beyond mere differences between the geometric and magnetic aspects of aromaticity: (1) Does a molecule of aromaticity greater than that of benzene, but undisclosed by the HOMA definition, exist? (2) Can the Kekuléne cyclohexatriene moiety with HOMA = 0 exist as a part of a larger system? (3) Can the geometrical aromaticity index be defined better? Our answer to the first query is “It is not likely enough”, to the second, “Why not define HOMA using a less mysterious molecule than cyclohexatriene?”, and to the third, “It is possible to construct another fair geometrical index, but is it better for evaluating aromaticity?” To find these answers, we have studied: (1) the HOMA and NICS indices of over 50 hexahomosubstituted benzenes, (2) the HOMA, as well as EN and GEO, indices of over 100 triply fused hexasubstituted benzenes, and (3) the HOMA and new Geometrical Auxiliary Index (GAI) , of different unsaturated and saturated, aromatic and aliphatic hydrocarbons including all alkane constitutional isomers composed of up to nine carbon atoms.

Synthesis, Isolation, and Characterization of Mono- and Bis-norbornene-Annulated Biarylamines through Pseudo-Catellani Intermediates.

A palladium-catalyzed C-H functionalization of an external ring of N-acyl 2-aminobiaryl with bicyclo[2.2.1]hept-2-ene (norbornene) via multiple C-H bond activations was developed. This study is the first report of the formation of bis-norbornene annulated biarylamines isomers ( syn-3a'/ anti-3a' = 36:64) from multiple C-H bond functionalizations. Additionally, nondirected C-H bond functionalization at the C-4' position with alkenes rendered complete C-H functionalization of five C-H bonds that formed a stable hexasubstituted benzene ring.

Facile synthesis of mixed O, S or Se bearing hexasubstituted benzenes and their potential as Cu(ii) ion probe.

The present study offers a facile route for the synthesis of unsymmetrical hexasubstituted benzenes bearing alternate heteroatoms (O, S and Se) with the formula [1,3,5-(RSeCH2)3-2,4,6-(R'ECH2)3C6] (E = O, S or Se). The synthetic protocol involves the use of an in situ generated tris(selenonium) ion followed by treatment with another nucleophile affording the targeted species in >70% yields. The unsymmetrical hexasubstituted derivatives were characterized on the basis of physicochemical and spectroscopic data and in a representative case with single crystal X-ray study. The current work assumes great significance as the potential of these species as "turn-off" chemical sensors for Cu2+, which is a biologically and environmentally crucial metal ion, was also successfully demonstrated by 5a which bears alternate oxygen and selenium centres.

Iron-catalyzed regioselective cyclotrimerization of alkynes to benzenes

We report the synthesis and characterization of simple di(aminomethyl)pyridine ligated iron-pincer complexes, which catalyzed the regioselective [2+2+2] cyclotrimerization of terminal aryl and alkyl alkynes to provide the 1,2,4-trisubstituted benzene molecules. Interestingly, internal alkynes also exhibited similar cyclization and resulted in hexa-substituted benzene compounds. Increased steric bulk on pincer ligands diminished the selectivity for cycloaddition. Cyclotrimerization reactions proceeded at room temperature upon activation of catalyst by a Grignard reagent. EPR studies indicated thermally induced spin crossover effect in catalyst.

Hexa-substituted benzene derivatives as hole transporting materials for efficient perovskite solar cells

Two low cost hexa-substituted benzene derivatives, namely HFB-OMeDPA and HPB-OMeDPA, have been successfully utilized as hole transporting materials (HTMs) for efficient perovskite solar cells (PSCs). The relationships between molecular structure, electronic properties of the semiconductor and eventually the photovoltaic performance are investigated. The planar PSCs employing HPB-OMeDPA as HTM exhibit excellent power conversion efficiencies exceeding 16% under AM 1.5G illumination conditions, which are comparable to the reference cells based on spiro-OMeTAD.

A New Multicomponent Reaction MCR4 for the Synthesis of Analogs of Staurosporine

Background: We report a novel MCR4 useful for generating chiral analogs of staurosporine a promiscuous and potent protein kinases inhibitor. Method: Our strategy introduces the use of substituted tetramic acids as chiral precursors which together with an aldehyde, an isocyanide, a dienophile and a Lewis acid lead to hexa-substituted benzenes in one pot. Conclusion: Interestingly, the use of chiral precursors not only allowed obtaining a stereo- controlled reaction, but also observing unusual atropo-diastereomers with axial chirality. The reaction can be carried out both under thermal or microwave conditions. The methodology is demonstrated for a panel of aldehydes, tetramic acids, isocyanides and dienophiles. Keywords: Staurosporine, multicomponent reaction, Ugi, isocyanide, tetramic acid, hexa-substituted benzene, Meldrum's acid.

Experimental study of relaxation dynamics in solid solutions of benzene, hexa-substituted benzenes. I

The NMR study revealed that the 60° reorientational jumps in non-polar crystalline benzene do not give to a new configuration, and therefore benzene behaves as orientationally ordered system from thermodynamic perspective. All the non-polar symmetric crystalline hexa-substituted benzenes, such as hexachlorobenzene, hexamethylbenzene, etc., are supposed to be characteristically similar like benzene. We selectively probed solid solutions of these non-polar crystalline matrices with polar crystalline species employing dielectric spectroscopy, and differential scanning calorimetry. An additional process, close to Debye in nature, was observed in dielectric spectroscopy with higher activation energy, which was absent in NMR, and based on spectral behaviour we designate it as α-relaxation. Moreover, the single strong process that appears in NMR study of non-polar benzene, hexachlorobenzene, and hexamethylbenzene matrices is identical to a relatively weak process observed in dielectric spectroscopy, which we designate as secondary relaxation. In all the cases, the temperature dependence of the relaxation rates follow Arrhenius equation.

Experimental study of relaxation dynamics in solid solutions of benzene, hexa-substituted benzenes. II

In continuation with Part I of current study, we present here the orientationally disordered materials pentachloroaniline (PCA), bromopentamethylbenzene (BPMB), and their solid solutions with hexachlorobenzene (HCB) and hexamethylbenzene (HMB), respectively, encompassing the entire concentration range, studied employing dielectric spectroscopy, differential scanning calorimetry, and powder X-ray spectroscopy. The α- relaxation in these systems gets closer to Debye behaviour on non-polar rich side and is analyzed employing Havriliak-Negami equation, whereas the β- relaxation is found to be symmetric everywhere and follows Cole–Cole equation. In both the systems studied here, the temperature dependence of relaxation rates could be described by Arrhenius equation. The β- relaxation evidenced in these two binary systems appears to originate from the different microscopic mechanism that is discussed based on their spectral behaviour. Further, we probe the liquid glasses of very dilute concentrations of dipolar HSB solutes in OTP matrix, and compare it with the spectral features of the dilute dipolar solid solutions of HSBs.

Zirconium-mediated selective synthesis of 1,4-dialkyl(aryl)-hexa-substituted benzenes from two silyl-substituted alkynes and one internal alkyne

Based on the formation of 2,5-bis(trimethylsilyl)-zirconacyclopentadienes from two silylalkynes with Cp2ZrBu2 and the Cu-mediated formation of 1,4-disilylbenzene via the cycloaddition of zirconacyclopentadienes to disubstituted alkynes, a selective synthesis of 1,4-dialkyl(aryl)-hexa-substituted benzenes was achieved followed by iodination and coupling reaction. The coupling reactions were carried out with either organolithium reagent or organozinc reagent(Negishi coupling), depending on the electrophilic species.

Lopsided Benzene’s Big Moment

Chemists have made a new set of hexasubstituted benzenes in which electron-withdrawing cyano groups on one side of the ring and electron-donating amino groups on the other combine to pull and push the molecule’s electron density in the same direction. These compounds are remarkable for being the most polar neutral molecules now known to exist (Angew. Chem. Int. Ed. 2016, DOI: 10.1002/anie.201508249). Organic molecules with large dipole moments are desirable for their ability to enhance the efficiency of polymer films in electronic devices such as lasers, microchips for smart cards, and solar cells. Multisubstituted benzenes have long been synthetic targets, but chemists have been limited in their ability to prepare them using standard electrophilic substitutions. A research team led by Klaus Müllen of the Max Planck Institute for Polymer Research has now devised a new synthesis of hexasubstituted benzenes and dialkyldihydrobenzimidazoles via a new dibromo intermediate they prepared. The most