Substituted Benzene Rings Research Articles

Pentafluoroethylation of Carbonyl Compounds Using HFC-125 in a Flow Microreactor System.

The protocol of micro-flow nucleophilic pentafluoroethylation using pentafluoroethane (HC2F5, HFC-125), a nontoxic, inexpensive, and commercially available greenhouse gas, is described. The micro-flow pentafluoroethylation by HFC-125 proceeded smoothly at room temperature or at -10 °C in DMF or toluene in the presence of a potassium base, namely, t-BuOK or KHMDS. A broad range of ketones, aldehydes, and chalcones with various substituted benzene rings were successfully converted to the corresponding pentafluoroethyl carbinols instantly with good to high yields.

The effect of ring aromaticity on ESIPT behavior and photophysical properties of 2-(2′-hydroxyphenyl)- 4-chloromethylthiazole derivatives: A TD-DFT study

By using density functional theory (DFT) and time-dependent DFT (TD-DFT) methods, the effect of ring aromaticity on the excited state intramolecular proton transfer (ESIPT) process and photophysical properties of HCO, HCSe, HPDCT and HPZCT compounds were explored in detail. The strengthened excited state intramolecular hydrogen bonds (Hbonds) of the studied compounds were confirmed by analysis of the structure, infrared vibration frequency, electron density and reduced density gradient. The stronger Hbond is favorable to ESIPT process. Frontier molecular orbitals evidently showed that the proton transfer was induced by the rearrangement of electronic density. The HOMO-LUMO energy gap (Egap) correlated with the Stokes shift in the enol form. A smaller Egap would produce a larger Stokes shift. The heteroatom substitution in thiazole ring and nitrogen substitution in benzene ring of HCT molecule affected the ring aromaticity, and then had an obvious effect on the intramolecular Hbond. The stronger the ring aromaticity, the stronger the intramolecular Hbond, and the easier the ESIPT process to occur.

Synthesis and Biological Activity of Some [(5-oxazolyl)-phenyl]-thiourea Derivatives

Aims:Synthesis and biological evaluation of some [(5-oxazolyl)-phenyl]-thiourea derivatives as potential antiviral agents.Background:(5-Oxazolyl)-phenyl derivatives were derived from the design of mycophenolic acid structurally related analogues. The (5-oxazolyl)-phenyl fragment is an excellent composition for many novel structure compounds having good pharmaceutical properties, such as immunosuppressive, antiviral and anticancer. In the present study, we present combinations of thiourea group and (5-oxazolyl)-phenyl fragment. The antiviral activity, cytotoxicity and IMPDH activity of the title compounds were evaluated in vitro bioassay.Objective:[(5-Oxazolyl)-phenyl]-thiourea derivatives containing different substituted benzene rings were synthesized by introducing thiourea linker. All the synthesized derivatives were screened for their in vitro antiviral evaluation and inosine monophosphate dehydrogenase activity.Methods:A series of [(5-oxazolyl)-phenyl]-thiourea derivatives were synthesized by the reaction of thiocarbonyldiimidazole with amines. This was an effective method for introducing the thiourea group in the (5-oxazolyl)-phenyl structure. All of the synthesized derivatives were screened for their in vitro antiviral activity against influenza A virus, coxsackievirus B3, herpes simplex virus type 1 and inosine monophosphate dehydrogenase activity.Result:The results of the screening revealed that compounds 4i, 4j, 4k, 7m, 7n and 7o showed comparable activity towards IMPDH as compared to the control drug. Compounds 4k, 4l, 7m and 7n exhibited potent activity towards both RNA virus influenza A virus, coxsackievirus B3 and DNA virus HSV-1 at low micromolar concentrations. The activities of most compounds directly linked to the substituted benzene ring by the thiourea group were superior to those of the compounds which had the methylene linkage.Conclusion:The in vitro biological assays indicated that most of target molecules having combinations of thiourea group and (5-oxazolyl)-phenyl fragment exhibited antiviral activity and IMPDH activity compared the control drugs.

Solvent-Resistant Lignin-Epoxy Hybrid Nanoparticles for Covalent Surface Modification and High-Strength Particulate Adhesives.

Fabrication of spherical lignin nanoparticles (LNPs) is opening more application opportunities for lignin. However, dissolution of LNPs at a strongly alkaline pH or in common organic solvent systems has prevented their surface functionalization in a dispersion state as well as processing and applications that require maintaining the particle morphology under harsh conditions. Here, we report a simple method to stabilize LNPs through intraparticle cross-linking. Bisphenol A diglycidyl ether (BADGE), a cross-linker that, like lignin, contains substituted benzene rings, is coprecipitated with softwood Kraft lignin to form hybrid LNPs (hy-LNPs). The hy-LNPs with a BADGE content ≤20 wt % could be intraparticle cross-linked in the dispersion state without altering their colloidal stability. Atomic force microscopy and quartz crystal microbalance with dissipation monitoring were used to show that the internally cross-linked particles were resistant to dissolution under strongly alkaline conditions and in acetone-water binary solvent that dissolved unmodified LNPs entirely. We further demonstrated covalent surface functionalization of the internally cross-linked particles at pH 12 through an epoxy ring-opening reaction to obtain particles with pH-switchable surface charge. Moreover, the hy-LNPs with BADGE content ≥30% allowed both inter- and intraparticle cross-linking at >150 °C, which enabled their application as waterborne wood adhesives with competitive dry/wet adhesive strength (5.4/3.5 MPa).

Synthesis and structure of 4-{[(E)-(7-meth-oxy-1,3-benzodioxol-5-yl)methyl-idene]amino}-1,5-dimethyl-2-phenyl-2,3-di-hydro-1H-pyrazol-3-one.

In the title compound, C20H19N3O4, the dihedral angles between the central pyrazole ring and the pendant phenyl and substituted benzene rings are 50.95 (8) and 3.25 (12)°, respectively, and an intra-molecular C-H⋯O link generates an S(6) ring. The benzodioxolyl ring adopts a shallow envelope conformation with the methyl-ene C atom as the flap. In the crystal, the mol-ecules are linked by non-classical C-H⋯O inter-actions, which generate a three-dimensional network. Solvent-accessible voids run down the c-axis direction and the residual electron density in these voids was modelled during the refinement process using the SQUEEZE algorithm [Spek (2015 ▸). Acta Cryst. C71, 9-18] within the structural checking program PLATON.

Understanding the electro-catalytic effect of benzene ring substitution on the electrochemical oxidation of aniline and its derivatives using BDD anode: Cyclic voltammetry, bulk electrolysis and theoretical calculations

The use of boron doped diamond (BDD) films in environmental applications has been extensively proved. This electrocatalytic material produces higher concentrations of free‑hydroxyl radicals on its surface, favoring a complete mineralization of many organic pollutants. Although efficient degradation levels are achieved using BDD films, effects such as the chemical structure of the contaminant, waste by-products, oxidants produced, weak/strong surface interactions and bulk reactions influence the electro/chemical catalytic reactions as well as on the effectiveness of the process. In this frame, this study aims to investigate the effect of benzene ring substitution on the electrochemical oxidation of aniline and its derivatives using BDD anode. To do that, the electrochemical behavior of aniline, nitro and chloro‑aniline derivatives in aqueous solution on BDD anode using cyclic voltammetry and bulk electrolysis was examined as well as their environmental elimination was explained by quantum mechanics (QM) calculations. The results clearly allowed associating the experimental measurements to theoretical estimations to comprehend the catalytic relationship between the molecular electronic properties of aniline and its derivatives and their elimination from water.

Design, synthesis and antitumor evaluation of novel 5-methylpyrazolo[1,5-a]pyrimidine derivatives as potential c-Met inhibitors

A series of novel 5-methylpyrazolo[1,5-a]pyrimidine derivatives (10a–10x) were designed, synthesized, and evaluated for their in vitro inhibitory activities against c-Met kinase and antiproliferative activities against the SH-SY5Y, MDA-MB-231, A549, and HepG2 cell lines. Most of the compounds remarkably inhibited c-Met kinase and showed moderate to good cytotoxicity and selectivity toward the four cancer cell lines. Among them, compounds 10b and 10f were the two most potent selective c-Met inhibitors with half-maximal inhibitory concentration (IC50) values of 5.17 ± 0.48 nM and 5.62 ± 0.78 nM, respectively, and suppression abilities comparable with the positive control cabozantinib. Cell proliferation assay further demonstrated that the two most promising compounds 10a and 10b also showed good cytotoxicity and selectivity toward MDA-MB-231 cells, with IC50 values of 26.67 ± 2.56 μM and 26.83 ± 2.41 μM, respectively. Compounds 10f and 10g showed cytotoxicity and selectivity toward A549 cells, with IC50 values of 20.20 ± 2.04 μM and 21.65 ± 1.58 μM, respectively. All antiproliferative activities were within the range of those of cabozantinib. Notably, these compounds presented relatively low hepatotoxicity compared with reference drugs. Moreover, the preliminary structure–activity relationship and docking studies revealed that replacement of a nitrogen-containing heterocycle on the R2 (block A) group might improve the c-Met kinase inhibitory and antiproliferative effects in MDA-MB-231 cells, whereas displacement by a substituted benzene ring, especially for the p-fluorophenyl or 4-fluoro-3-methoxyphenyl moiety, on the R2 group enhanced cytotoxicity toward A549 cells. Together, these results suggest that 10b and 10f are promising compounds and provide a basis for their development as new antitumor agents.

Flavonoid glycosides from the rhizomes of Pronephrium penangianum

Six flavonoid glycosides jixueqisus A-F, together with nine known flavonoids, were isolated from the rhizomes of the fern Pronephrium penangianum. Among them, two red pigments jixueqisus A and B possess the same rare 6,8-dimethyl-2-phenyl-7H-1-benzopyran-7-one skeleton (a long conjugated system). Jixueqisu Cwas a dihydrochalcone glycoside, jixueqisu D was a chalcone glycoside, jixueqisu E was an aurone glycoside, and jixueqisu F was a flavonone glycoside. Interestingly, jixueqisus D-F, (2S)-5,2′,5′-trihydroxy-7-methoxyflavanone and 5,2′,5′-trihydroxy-7-methoxyflavone possessed a 2,5-dihydroxy substituted benzene ring (B-ring). Their structures were elucidated by various spectroscopic and chemical methods. Furthermore, the plausible biosynthetic pathways of jixueqisus A-F were discussed, respectively. All isolated compounds were evaluated for their activities against the proliferation of MCF-7, HepG-2, HCT-116 and BGC-823 tumor cell lines, four known flavane-4-ol glycosides, abacopterins A and C, eruberin B and triphyllin A, exhibited moderate activities to various cell lines.

Simple dithienosilole-based nonfused nonfullerene acceptor for efficient organic photovoltaics

Two simple dithienosilole unit (DTS)-based nonfused small molecular acceptors (SiOC2C6–4F and SiOC2C6–4Cl) using two DTS moieties linked alkoxyl substituted benzene ring as the central core (D) and bis(5,6-difluro-3-oxo-2,3-dihydro-1H-indene-2,1-diylidene)dimalononitrile or bis(5,6-dichloro-3-oxo-2,3-dihydro-1H-indene-2,1-diylidene)dimalononitrile as the end groups have been synthesized. The optical, electrochemical properties and device photovoltaic performance of these two molecules were investigated in detail. DFT results indicates S⋯O interactions involving alkoxyl groups of benzyl rings and thienyl S atoms of DTS can act as conformational “locks” to enhance molecular planarity. when the polymer PBDB-T was chosen as the donor, the PBDB-T:SiOC2C6–4F-based device provided a high PCE of 9.68% with a Voc of 0.90 V, a Jsc of 17.02 mA/cm2 and an FF of 63.00%, while the PBDB-T:SiOC2C6–4Cl-based device exhibited a PCE of 11.29% with a Voc of 0.87V, a Jsc of 20.35 mA/cm2 and an FF of 63.73%, which is so far the best performance reported for organic photovoltaic using silole-based small-molecule acceptors.

Probing the Dynamic Covalent Chemistry Behavior of Nitrogen-Centered Di- and Triurazole Radicals.

Dynamic covalent chemistry (DCvC) describes systems in which readily reversible bond formation allows for control of product distributions by straightforward manipulation of reaction conditions (e.g., changes in temperature, solvent, concentration, etc). Nitrogen-centered 1-aryl urazole radicals reversibly form tetrazane dimers in solution via N-N bond formation. When two such urazole units are attached to a single, appropriately substituted benzene ring, the resulting diradical system engages in DCvC. At room temperature, a polymeric network of units is created that exhibits gel-like properties, while at higher temperatures, near quantitative dimerization to form a molecular cage is observed.However, attaching three such urazole units to a single appropriately substituted benzene ring inhibits DCvC behavior.

(Z)-5-(4-Bromo-phen-yl)-3-{[(3,5-di-chloro-phen-yl)amino]-methyl-idene}furan-2(3H)-one.

The title compound, C17H10BrCl2NO2, crystallizes in the monoclinic space group C2/c with a large cell volume of 6207 (3) Å3. The asymmetric unit of the title compound investigated at 120 K contains two crystallographically independent mol-ecules (Z' = 2). Each mol-ecule demonstrates slight non-planarity in the solid state and a Z-configuration for the exocyclic C=C bond. The crystal packing reveals the presence of π-π stacking inter-actions between the substituted benzene rings [centroid-centroid distances of 3.836 (5) Å, shift distances in the range 1.272-1.843 Å].

A competition between hydrophobic and electrostatic interactions in protein-ligand systems. Binding of heterogeneously halogenated benzotriazoles by the catalytic subunit of human protein kinase CK2.

A series of chlorine-substituted benzotriazole derivatives, representing all possible substitution patterns of halogen atoms attached to the benzotriazole benzene ring, were synthetized as potential inhibitors of human protein kinase CK2. Basic ADME parameters for the free solutes (hydrophobicity, electronic properties) together with their binding affinity to the catalytic subunit of protein kinase CK2 were determined with reverse-phase HPLC, spectrophotometric titration, and Thermal Shift Assay Method, respectively. The analysis of position-dependent thermodynamic contribution of a chlorine atom attached to the benzotriazole ring confirmed the previous observation for brominated benzotriazoles, in which substitution at positions 5 and 6 with bromine was found crucial for ligand binding. In all tested halogenated benzotriazoles the replacement of Br with Cl decreases the hydrophobicity, while the electronic properties remain virtually unaffected. Supramolecular architecture identified in the just resolved crystal structures of three of the four possible dichloro-benzotriazoles shows how substitution distant from the triazole ring affects the pattern of intermolecular interactions. Summarizing, the benzotriazole benzene ring substitution pattern has been identified as the main driver of ligand binding, predominating the non-specific hydrophobic effect.

Non-planar core-modified dibenzi expanded isophlorin

The role of aromatic subunits is crucial to the structural and electronic properties of isophlorin and its expanded derivatives. Herein we describe the effect of benzene ring substitution in a 32[Formula: see text] expanded isophlorin core, which is at the crossroads of hexaphyrin and octaphyrin. Synthesis, structural characterization and electronic properties of a non-planar 32[Formula: see text] core-modified expanded isophlorin resembles that of a hexaphyrin like macrocycle. Dibenzi hexaphyrin is known to retain a planar structure; however, the dibenzi expanded isophlorin reported here loses its planarity and is found to adopt a unique V-shaped structure. The non-antiaromatic nature observed from spectroscopic analysis is ably supported by computational studies. Electronic absorption studies and mass spectrometry support a two-electron ring oxidation as expected of antiaromatic macrocycles.

Synthesis, Characterization, Antibacterial and Antioxidant Potency of NSubstituted- 2-Sulfanylidene-1,3-Thiazolidin-4-one Derivatives and QSAR Study.

Rhodanine is known for its potential and important role in the medicinal chemistry since its derivatives exhibit a wide range of pharmacological activities such as antibacterial, antifungal, antidiabetic, antitubercular, anti-HIV, antiparasitic, antioxidant, anticancer, antiproliferative and anthelmintic agents. Since N-substituted rhodanine synthons are rarely commercially available, it is desirable to develop a straightforward synthetic approach for the synthesis of these key building blocks. The objective was to synthesize a series of rhodanine derivatives and to investigate their antimicrobial and antioxidant activity. Also, in order to obtain an insight into their structure-activity relationship, QSAR studies on the antioxidant activity were performed. 1H and 13C FTNMR spectra were recorded on Bruker Avance 600 MHz NMR Spectrometer, mass analysis was carried out on ESI+ mode by LC-MS/MS API 2000. 2,2-Diphenyl-1- picrylhydrazyl radical scavenging activity (% DPPH) was determined in dimethylsulfoxide (DMSO) as a solvent. The antibacterial activity was assessed against Bacillus subtilis, Staphylococcus aureus (Gram positive) and Escherichia coli, Pseudomonas aeruginosa (Gram negative) bacteria in terms of the minimum inhibitory concentrations (MICs) by a modified broth microdilution method. A series of N-substituted-2-sulfanylidene-1,3-thiazolidin-4-ones were synthesized and characterized by 1H NMR, 13C NMR, FTIR, GC MS, LCMS/MS and C,H,N,S elemental analysis. Most of the synthesized compounds showed moderate to excellent antibacterial activity (MIC values from 125 μg/ml to 15.62 μg/mL) and DPPH scavenging activity (from 3.60% to 94.40%). Compound 2-thioxo-3- (4-(trifluoromethyl)-phenyl)thiazolidin-4-one showed the most potent activity against Escherichia coli (3.125 μg/mL), equivalent to antibiotic Amikacin sulphate and against Staphylococcus aureus (0.097 μg/ml), 100 times superior then antibiotic Amikacin sulphate. It has also shown a potent antioxidant activity (95% DPPH scavenging). Two best QSAR models, obtained by GETAWAY descriptor R7p+, Balabans molecular connectivity topological index and Narumi harmonic topological index (HNar), suggest that the enhanced antioxidant activity is related to the presence of pairs of atoms higher polarizability at the topological distance 7, substituted benzene ring and longer saturated aliphatic chain in N-substituents. A series of novel N-substituted-2-thioxothiazolidin-4-one derivatives were designed, synthesized, characterized and evaluated for their antibacterial and antioxidant activity in vitro. Majority of the compounds showed excellent antibacterial activity compared to ampicillin and few of them have an excellent activity as compared to Chloramphenicol standard antibacterial drug. The QSAR study has clarified the importance of presenting a pairs of atoms higher polarizability, such as Cl and S at the specific distance, as well as the substituted benzene ring and a long saturated aliphatic chain in N-substituents for the enhanced antioxidant activity of 2-sulfanylidene-1,3- thiazolidin-4-one derivatives.

Designing difluoro substituted benzene ring based fullerene free acceptors for small Naphthalene Di-Imide based molecules with DFT approaches

Herein current research work, we designed four new acceptor materials for small solar cell molecules with Naphthalene Di-Imide central unit by employing the wB97xd/6-31 G (d,p) and TD-wB97xd/6-31 G (d,p) level of density functional theories. Absorption properties of designed materials are excellent between the 400 nm to 510 nm with chloroform solvent and 340 nm to 490 nm in gas phase, small reorganization energy values 0.0163–0.0172 eV for electron (λe) and 0.0205–0.0257 eV for hole transfer (λh), large expected open circuit voltages (Voc) from 3.60 to 4.53 eV with respect to [6, 6]-phenyl-C61-butyric acid methyl ester (PCBM), high dipole moment strength ranging from 4.0199 to 8.9647 Debye in excited state and 3.3847 Debye to 7.2632 Debye in ground state which are very helpful for the further construction of organic solar cell (OSC) devices with improved and better power conversion efficiencies (PCEs).

Photoredox [4+2] Annulation to Construct Substituted Benzene Rings

Key words photoredox reaction - [4+2] annulation - thiophenes - alkynes - benzene rings

Experimental and theoretical study of planar small molecule acceptor for organic solar cells

A planar small molecule acceptor (IDTT-BO-MN) with 6,12-dihydro-dithieno[2,3-d:2′,3′-d']-s-indaceno[1,2-b:5,6-b']dithiophene (IDTT) as a central core, bis(alkoxy)-substituted benzene ring as conformational control moieties and malononitrile as end-capping units was designed and synthesized. Non-covalent interactions successfully controlled the rotation to make planar backbone. When IDTT-BO-MN was paired with cheapest polymer donor (P3HT), it achieved 5.75% power conversion efficiency and 9.06 × 10−4 cm2V–1S−1 electron mobility. A detailed quantum chemical analysis was performed to understand the electronic and structural behavior of synthesized acceptor. Non-covalent interactions were also studied through the analysis of partial atomic charges and binding energy between participating atoms. Transition dipole moment was calculated that can be simple descriptor for the short circuit current (Jsc). Molecular Packing behavior was also examined and intermolecular binding energy was calculated.

Formation of Amidinyl Radicals via Visible-Light-Promoted Reduction of N-Phenyl Amidoxime Esters and Application to the Synthesis of 2-Substituted Benzimidazoles.

We have developed a new method for the synthesis of 2-substituted benzimidazoles via amidinyl radicals generated by visible-light-promoted reduction of N-phenyl amidoxime esters in the presence of an iridium photocatalyst. This is the first report of the use of N-phenyl amidoxime esters as amidinyl radical precursors, and the first use of substituted benzene rings as amidinyl radical acceptors. This method widens the application range of substrates and overcomes the shortcomings of the traditional methods for the synthesis of 2-substituted benzimidazoles, which requires harsh reaction conditions, involves difficult-to-prepare substituted o-phenylenediamine substrates, and produces acidic waste.

Packing Rearrangements in 4-Hydroxycyanobenzene Under Pressure

4-hydroxycyanobenzene (4HCB) is a dipolar molecule formed of an aromatic substituted benzene ring with the CN and OH functional groups at the 1 and 4 positions. In the crystalline state, it forms spiral chains via hydrogen bonding, which pack together through interactions. The direct stacking of benzene rings down the a- and b-axes and its interactions throughout the structure gives rise to its semiconductor properties. Here, high-pressure studies are conducted on 4HCB in order to investigate how the packing and intermolecular interactions, related to its semiconductor properties, are affected. High-pressure single-crystal X-ray diffraction was performed with helium and neon as the pressure-transmitting mediums up to 26 and 15 GPa, respectively. The pressure-dependent behaviour of 4HCB in He was dominated by the insertion of He into the structure after 2.4 GPa, giving rise to two phase transitions, and alterations in the interactions above 4 GPa. 4HCB compressed in Ne displayed two phase transitions associated with changes in the orientation of the 4HCB molecules, giving rise to twice as many face-to-face packing of the benzene rings down the b-axis, which could allow for greater charge mobility. In the He loading, the hydrogen bonding interactions steadily decrease without any large deviations, while in the Ne loading, the change in 4HCB orientation causes an increase in the hydrogen bonding interaction distance. Our study highlights how the molecular packing and interactions evolve with pressure as well as with He insertion.

Effect of crosslinking patterns on the properties of conjugated microporouspolymers

Syntheses and detailed spectroscopic characterizations of two similar conjugated microporous polymers formed by A4 $+$ B2 and A2 $+$ B3 type functional monomers via Sonogashira--Hagihara polycondensation are presented in this report. The two porous polymeric networks possess mono-, di-, and tri- (1-, 1,4-, and 1,3,5-, respectively) substituted benzene rings and fused thiophenic moieties (dithienothiophenes). Because of the different conjugation patterns, their solid state nuclear magnetic resonance, infrared, and ultraviolet/visible light absorption analyses indicated significant differences. Besides the discussions on the porous properties of the obtained polymeric networks, the presented spectroscopic investigations can be useful for identifying the structure-property relationship of the novel conjugated porous polymeric structures, since the characterization of such nonsoluble compounds by using fundamental techniques is always a challenge.