Benzotriazole Derivatives Research Articles

Multichromic benzimidazole‐containing polymers: Comparison of donor and acceptor unit effects

AbstractThis study reports a comparative study on electrochromic properties of two donor–acceptor–donor (DAD)‐type polymers namely poly(2‐heptyl‐4,7‐di(thiophen‐2‐yl)‐1H‐benzo [d]imidazole) (BImTh) and poly(4,7‐bis(2,3‐dihydrothieno[3,4‐b] [1,4]dioxin‐5‐yl)‐2‐heptyl‐1H‐benzo[d]imidazole) (BImEd). DAD‐type monomers were polymerized electrochemically on indium tin oxide‐coated glass slides to determine the optical properties of the polymers. Electrochemical p‐doping experiments were performed to determine the band gap and absorption band values of the polymer films at different redox states. Polymerization of BImTh and BImEd yields multichromic polymers. Donor and acceptor effects are studied by comparing the PBImEd and PBImTh with corresponding benzotriazole derivatives. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012

Long Wavelength Photosensitizers for Diaryliodonium Salts Based on the 2-Benzyl-2H-benzo[d][1,2,3]triazole Skeleton

Two benzotriazole derivatives, 2-benzyl-4,7-di(thiophen-2-yl)-2H-benzo[d][1,2,3]triazole (BBTS) and 2-benzyl-4,7-bis(2,3-dihydrothieno[3,4-b][1,4]dioxin-5-yl)-2H-benzo[d] [1,2,3]triazole (BBTES) were employed as photosensitizers for diaryliodonium salt photoinitiators in photoinitiated cationic polymerization of various epoxide and vinyl ether monomers. Diphenyliodonium hexafluorophosphate (Ph2I+PF6 –) salt was used as the photoinitiator in this study. Extended conjugation and electron-rich moieties of the photosensitizers enabled the use of long wavelength UV and visible light emitting light sources in cationic photopolymerizations. Having low oxidation potentials and good solubility in cationically polymerizable monomers make them efficient photosensitizers for the diphenyliodonium salt in the photoinitiated cationic polymerization. Polymerizations were achieved at room temperature and monitored by optical pyrometry. Moreover, photopolymerization of a diepoxide monomer with ambient solar irradiation in the presence of BBTES and BBTS were examined.

Synthesis and biological evaluation of some novel thiazole substituted benzotriazole derivatives

A series of novel hybrid molecules 4a–y containing thiazole and benzotriazole templates were designed and synthesized. The structures of the synthesized compounds were elucidated by IR, 1H NMR, 13C NMR and mass spectral data. All the synthesized compounds were tested for their antimicrobial activity (zone of inhibition) against Gram-positive, Gram-negative strains of bacteria as well as fungal strains. After that minimum inhibitory concentrations (MICs), minimum bactericidal concentrations (MBCs) and minimum fungicidal concentrations (MFCs) of all the synthesized compounds were determined. The investigation of antimicrobial screening data revealed that most of the tested compounds showed moderate to good microbial inhibitions.

A new class of bioactivable self-immolative N,O-ligands

A hexadentate ligand built on an amine-bis(phenol) skeleton with an aminal, self-immolative moiety is presented. Synthesis of the ligand is convenient and relatively high yielded. Moreover, it enables synthesis of many derivatives, both in the amino-phenol and aminal fragment (various heterocycles). Once the final hexadentate ligand is synthesized via the Katritzky reaction, it becomes prone to hydrolysis. Bioactivation by β-galactosidase cleaves the glycosylic bond and a spontaneous collapse of the aminal fragment occurs, thus leading to a pentadentate chelate. This bioactivation has been shown for pyrazole, 1,2,4-triazole and benzotriazole derivatives.

Protein kinase CK2 from two higher eukaryotes of economical importance, the mussel Mytilus galloprovincialis and the medfly Ceratitis capitata

Abstract Protein kinase CK2 is a highly conserved Ser/Thr protein kinase involved in cell cycle control, transcription, signal transduction and cell proliferation. It is upregulated in several diseases and by oxidative stress. CK2 is generally composed of two catalytic subunits and two regulatory subunits and utilizes either ATP or GTP as a phosphate donor. CK2 was isolated from the sea mussel Mytilus galloprovincialis, a biomarker of marine pollution, and the Mediterranean fly Ceratitis capitata, an insect capable of wreaking extensive damage to a wide range of fruit crops with great economical importance. The catalytic CK2α and regulatory CK2β subunits of M. galloprovincialis and C. capitata show similar properties. The mussel and fly catalytic subunits and holoenzymes were capable of phosphorylating the recombinant ribosomal stalk P1 protein, implying functional conservation. They also demonstrate the characteristics of a typical CK2: use of ATP and GTP as phosphate donors, inhibition by known modulators of CK2 activity (like benzotriazole derivatives and heparin), and stimulation by polycations. Both organisms seem to be ideal models for the analysis of CK2 in the control of gene expression in response to cellular stress.

Combined effect of hindered amine light stabilizer and ultraviolet absorbers on photodegradation of poly(vinyl chloride)

AbstractThe combined effect of a basic hindered amine light stabilizer (HALS) and ultraviolet absorbers (UVAs) on casted poly(vinyl chloride) (PVC) films, during photodegradation, was studied by color change, ultraviolet‐visible (UV–vis) spectroscopy, Fourier‐transform infrared (FTIR) spectroscopy, and viscosity‐average molecular weight. It was found that the basic amine groups in the HALS (T770) could promote the dehydrochlorination, thereby accelerating the photooxidation of PVC films. Meanwhile, T770 could scavenge the radicals formed and restrain the aging of PVC to some extent. The above‐mentioned aspects were competing factors: the former played a dominant role during the first 100 h, while the latter counteracted the former effect to some extent between 100 and 300 h. A benzotriazole derivative (UV326) absorbs more UV radiation in the UV‐A region (320–400 nm), which mainly causes the photodegradation of PVC samples, than a benzophenone derivative (UV531). Thus, UV326 is a more efficient UV absorber than UV531 in prohibiting the photooxidation and chain scission of PVC films. The combination of T770 and UV326 effectively protected PVC films from dehydrochlorination and photooxidation. The combination of T770 and UV531 accelerated the dehydrochlorination and discoloration of PVC films. J. VINYL ADDIT. TECHNOL., 2012. © 2012 Society of Plastics Engineers

Simultaneous determination of benzotriazole and benzothiazole derivatives in aqueous matrices by mixed-mode solid-phase extraction followed by liquid chromatography–tandem mass spectrometry

An improved selectivity method for the simultaneous determination of four benzotriazoles (benzotriazole, 4-methylbenzotriazole, 5-methylbenzotriazole, and 5,6-dimethyl-1H-benzotriazole) and six benzothiazoles (benzothiazole, 2-hydroxybenzothiazole, 2-benzothiazolamine, mercaptobenzothiazole, 2-methylbenzothiazole, and 2-methylthiobenzothiazole) in aqueous matrices has been developed. Under optimal conditions, analytes are concentrated using a MAX solid-phase extraction (SPE) cartridge, based on divinylbenzene-N-vinylpyrrolidone functionalized with quaternary amine groups, which allows reversed-phase interactions in combination with ionic exchange. Selected compounds are recovered with methanol–acetone 7:3 (v/v) whereas acidic interferences remained attached to the sorbent, and as determined by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), LOQs for surface, urban and industrial wastewater are in the range of 0.002-0.29 ng/mL. Figures of merit of the method revealed good precision (RSD% <12%), linearity (R2 > 0.99) and accuracy (%R = 80-100%) for surface waters and effluents allowing direct external standard quantification. For more complex samples, such as urban and industrial raw wastewater, either the standard addition method or pseudo-external standard calibration using matrix matched standards are recommended. Analysis of different real samples, surface, urban wastewater and, for the first time, metal industry wastewater, reflected concentrations up to 310 ng/mL. The methylbenzotriazole isomers ratio was also determined.

Synthesis of new potential UV-filters

Three new silylated 2-(2´-hydroxyphenyl)benzotriazole derivatives were prepared. Starting with the easily available simple 2-(2´-hydroxyphenyl)benzotriazole, the target compounds were synthesized by a stepwise synthetic protocol, namely alkylation, thermal rearrangement and silylation.

The Photochemistry of Benzotriazole Derivatives. Part 2: Photolysis of 1-Substituted Benzotriazole Arylhydrazones: New Route to Phenanthridin-6-yl-2-phenyldiazines

Irradiation of 1-substituted benzotriazole arylhydrazones 3a–c, 4a,b and 5a,b with a 16 W low pressure mercury arc-lamp (254 nm) for 24 h gave phenanthridin-6-yl-2-phenyldiazines 9a–c, phenanthridin-6(5H)-ones 10a–c, 1-anilinobenzimidazoles 11a–c, 2-aryl-1H-benzimidazoles 12a–c, 1-arylamino-1H-benzimidazol-2-carboxylic acid ethyl esters 14a,b, 1-aryl-1H, 9H-benzo [4,5][1,2,3] triazolo[1,2-a]tetrazole-3-carboxylic acid ethyl esters 16a,b, 1-arylamino-2-benzoylbenzimidazoles 18a,b and 2-benzoylbenzoxazole 21.

Synthesis and oxidation of some azole-containing thioethers

Pyrazole and benzotriazole-containing thioethers, namely 1,5-bis(3,5-dimethylpyrazol-1-yl)-3-thiapentane, 1,8-bis(3,5-dimethylpyrazol-1-yl)-3,6-dithiaoctane and 1,3-bis(1,2,3-benzotriazol-1-yl)-2-thiapropane were prepared and fully characterized. Oxidation of the pyrazole-containing thioether by hydrogen peroxide proceeds selectively to provide a sulfoxide or sulfone, depending on the amount of oxidant used. Oxidation of the benzotriazole derivative by hydrogen peroxide is not selective, and sulfoxide and sulfone form concurrently. Selenium dioxide-catalyzed oxidation of benzotriazole thioether by H2O2, however, proceeds selectively and yields sulfoxide only.

Performance Assessment of Semiempirical Molecular Orbital Methods in Describing Halogen Bonding: Quantum Mechanical and Quantum Mechanical/Molecular Mechanical-Molecular Dynamics Study

The performance of semiempirical molecular-orbital methods--MNDO, MNDO-d, AM1, RM1, PM3 and PM6--in describing halogen bonding was evaluated, and the results were compared with molecular mechanical (MM) and quantum mechanical (QM) data. Three types of performance were assessed: (1) geometrical optimizations and binding energy calculations for 27 halogen-containing molecules complexed with various Lewis bases (Two of the tested methods, AM1 and RM1, gave results that agree with the QM data.); (2) charge distribution calculations for halobenzene molecules, determined by calculating the solvation free energies of the molecules relative to benzene in explicit and implicit generalized Born (GB) solvents (None of the methods gave results that agree with the experimental data.); and (3) appropriateness of the semiempirical methods in the hybrid quantum-mechanical/molecular-mechanical (QM/MM) scheme, investigated by studying the molecular inhibition of CK2 protein by eight halobenzimidazole and -benzotriazole derivatives using hybrid QM/MM molecular-dynamics (MD) simulations with the inhibitor described at the QM level by the AM1 method and the rest of the system described at the MM level. The pure MM approach with inclusion of an extra point of positive charge on the halogen atom approach gave better results than the hybrid QM/MM approach involving the AM1 method. Also, in comparison with the pure MM-GBSA (generalized Born surface area) binding energies and experimental data, the calculated QM/MM-GBSA binding energies of the inhibitors were improved by replacing the G(GB,QM/MM) solvation term with the corresponding G(GB,MM) term.

Synthesis and structural characterization of 1′-(diphenylphosphino)ferrocene-1-carboxamide, its corresponding hydrazide, some heterocycles derived from the hydrazide and palladium(II) complexes with these functional phosphinoferrocene ligands

Two polar phosphinoferrocene ligands, 1′-(diphenylphosphino)ferrocene-1-carboxamide ( 1) and 1′-(diphenylphosphino)ferrocene-1-carbohydrazide ( 2), were synthesized in good yields from 1′-(diphenylphosphino)ferrocene-1-carboxylic acid (Hdpf) via the reactive benzotriazole derivative, 1-[1′-(diphenylphosphino)ferrocene-1-carbonyl]-1 H-1,2,3-benzotriazole ( 3). Alternatively, the hydrazide was prepared by the conventional reaction of methyl 1′-(diphenylphosphino)ferrocene-1-carboxylate with hydrazine hydrate, and was further converted via standard condensation reactions to three phosphinoferrocene heterocycles, viz 2-[1′-(diphenylphosphino)ferrocen-1-yl]-1,3,4-oxadiazole ( 4), 1-[1′-(diphenylphosphino)ferrocen-1-carbonyl]-3,5-dimethyl-1,2-pyrazole ( 5), and 1-[1′-(diphenylphosphino)ferrocene-1-carboxamido]-3,5-dimethylpyrrole ( 6). Compounds 1 and 2 react with [PdCl 2(cod)] (cod = η 2:η 2-cycloocta-1,5-diene) to afford the respective bis-phosphine complexes trans-[PdCl 2(L-κ P) 2] ( 7, L = 1; 8, L = 2). The dimeric precursor [(L NC)PdCl] 2 (L NC = 2-[(dimethylamino-κ N)methyl]phenyl-κ C 1) is cleaved with 1 to give the neutral phosphine complex [(L NC)PdCl( 1-κ P)] ( 9), which is readily transformed into a ionic bis-chelate complex [(L NC)PdCl( 1-κ 2 O,P)][SbF 6] ( 10) upon removal of the chloride ligand with Ag[SbF 6]. Pyrazole 5 behaves similarly affording the related complexes [(L NC)PdCl( 5-κ P)] ( 12) and [(L NC)PdCl( 5-κ 2 O,P)][SbF 6] ( 13), in which the ferrocene ligand coordinates as a simple phosphine and an O,P-chelate respectively, while oxadiazole 4 affords the phosphine complex [(L NC)PdCl( 4-κ P)] ( 11) and a P,N-chelate [(L NC)PdCl( 4-κ 2 N 3 ,P)][SbF 6] ( 14) under similar conditions. All compounds were characterized by elemental analysis and spectroscopic methods (multinuclear NMR, IR and MS). The solid-state structures of 1⋅½AcOEt, 2, 7⋅3CH 3CN, 8⋅2CHCl 3, 9⋅½CH 2Cl 2⋅0.375C 6H 14, 10, and 14 were determined by single-crystal X-ray crystallography.

ChemInform Abstract: Unprecedented Formation of Benzo[d][1,2,3,6]oxatriazocine Derivatives via Diazo‐Oxygen Bond Formation and Synthesis of Enantiomerically Pure 1‐Alkyl Benzotriazole Derivatives.

AbstractA series of an entirely new kind of amino acid‐derived benzo[d][1,2,3,6]oxatriazocine derivatives (II) is prepared via an one‐pot three step sequence, (i) diazotation, (ii) Tbs‐deprotection, and (iii) cyclization.

Benzotriazoles and Indazoles Are Scaffolds with Biological Activity against Entamoeba histolytica

Parasitic infections caused by Entamoeba histolytica are still major threats against public health, especially in developing countries. Although current therapies exist, the problems associated with parasite resistance and negative side effects make it imperative to search for new therapeutic agents. A systematic scaffold analysis reported herein of a public database containing 474 antiamoebic compounds reveals that benzimidazole is the most active scaffold reported thus far. To gain insights into the antiamoebic activity of novel compounds, the authors report herein the biological activity of 12 compounds, including benzotriazole and indazole derivatives, scaffolds not previously tested against E. histolytica. Compounds with the benzotriazole and indazole scaffolds showed low micromolar activity (IC(50) = 0.304 and 0.339 µM) and are more active than metronidazole, which is the drug of choice used for the treatment of amebiosis. The novel compounds have similar properties to approved drugs. Compounds with novel scaffolds represent promising starting points of an optimization program against E. histolytica.

Alkynylation of Benzotriazole with Silylethynyliodonium Triflates. Regioselective Synthesis of 2-Ethynyl-2H-benzotriazole Derivatives

Phenyl(trimethylsilylethynyl)iodonium and tert-butyldimethylsilylethynyl(phenyl)iodonium triflates were applied to alkynylation of benzotriazole. Treatment of the silylethynyliodonium triflates with the potassium salt of benzotriazole ion in (t)BuOH and CH(2)Cl(2) gave 2-(trimethylsilylethynyl)-2H-1,2,3-benzotriazole and 2-(tert-butyldimethylsilylethynyl)-2H-1,2,3-benzotriazole in 74% and 76% yields, respectively. The regioisomers, 1-silylethynyl-1H-1,2,3-benzotriazole derivatives, were minor. In both cases of the silyl-substitued ethynyliodonium salts, novel regioselective alkynylation of benzotriazole at the 2 position was observed.

Design, Synthesis and Antifungal Activity of Some New Imidazole and Triazole Derivatives

Triazole and imidazole are incorporated into the structures of many antifungal compounds. In this study a novel series of 1,2,4-triazole, imidazole, benzoimidazole, and benzotriazole derivatives was designed as inhibitors of cytochrome P450 14α-demethylase (14DM). These structures were docked into the active site of MT-CYP51, using Autodock program. Sixteen compounds with the best binding energy were synthesized. The chemical structures of the new compounds were confirmed by elemental and spectral ((1) H-NMR and Mass) analyses. All compounds were investigated for antifungal activity against Candida albicans, Candida tropicalis, Candida glabrata, Candida parapeilosis, Candida kruzei, Candida dubliniensis, Aspergillus fomigatus, Aspergillus flavus, Microsporum canis, Microsporum gypseum, Trichophyton mentagrophyte, Epidermophyton floccosum. Some compounds showed excellent in-vitro antifungal activity against most of the tested fungi. Compounds 2, 9, and 10 had antifungal activity against several resistant fungi against fluconazole and itraconazole.

Multisite-directed inhibitors of protein kinase CK2: new challenges

New 4,5,6,7-tetrabromo benzotriazole derivatives have been synthesized, and their activities against CK2 have been tested. A click chemistry approach based on the copper-catalyzed azide-alkyne cycloaddition has been utilized to connect benzotriazoles, which efficiently interact with the ATP-binding site, to other subunits designed to simultaneously bind to the active and the substrate-binding sites of the enzyme. Docking studies allowed us to identify key interactions between CK2 and the designed ligands, which will be useful to optimize this series of multisite-directed inhibitors.

Two-Step Synthesis of Hexaammonium Triptycene: An Air-Stable Building Block for Condensation Reactions to Extended Triptycene Derivatives

A simple two-step synthesis of an air-stable hexaammoniumtriptycene is introduced, which can be used for a variety of transformations by condensation reactions, e.g., to benzimidazole, benzotriazole, and quinoxaline derivatives in high yields.

Molecular mechanical study of halogen bonding in drug discovery

A halogen bond is a noncovalent bond between a halogen atom (X) and a Lewis base (Y). This type of bond is attributed to the anisotropic distribution of the charge density on the halogen atom, resulting in the formation of a positive cap (called the σ-hole) centered on the A-X axis. The current research is the first reported molecular mechanical study of halogen bonding, the positive region centered on the halogen atom was represented by an extra-point (EP) of charge. The correlation between the X-EP distance and the X…Y bond length was explored to determine the optimal position of the EP. A test set of 27 halogen-containing molecules complexed to various Lewis bases was studied using molecular mechanical potentials. The molecular mechanical minimized halogen bond lengths and binding energies were in good agreement with the corresponding quantum mechanical values. The EP inclusion on the halogen atom resulted in an improvement in the accuracy of the electrostatic-potential derived charges. The solvation free energies of halobenzene molecules relative to benzene were calculated with and without EP inclusion to assess the accuracy of the developed approach. Molecular mechanical study of halo derivatives of benzotriazole complexed to cyclin-dependent protein kinase 2 (CDK2) was performed, and MM-PB(GB)SA binding energies were calculated as a case study in finding potent halogenated inhibitors that can serve as antitumor drugs.

Synthesis and Application of New Benzotriazole Derivatives as UV Absorbers for Polyester Fabrics

2-(2′-Hydroxyphenyl)-5-amino-2H-benzotriazole was synthesized and subjected to acylamidation to yield three new ultraviolet (UV) absorbers. The largest absorption wavelength and the relationship between the concentration and the maximum absorbance of the UV absorbers were measured in dimethylsulfoxide. Then the four benzotriazole type UV absorbers were dispersed and applied onto polyester fabrics with the high temperature and pressure dyeing method. The stabilizing effect against UV light of the finished fabrics was studied by ultraviolet protection factor (UPF) and UV transmittance measurement.