2-substituted Benzimidazoles Research Articles

Synthesis,Characterization and Biological studies on Mannich Bases of 2-Substituted Benzimidazole Derivatives

In the present study novel derivatives of 2-substituted benzimidazoles were prepared via Mannich reaction and evaluated for their in vitro antimicrobial activity against two gram negative strains (Escherichia coli and Pseudomonas aeruginosa), two gram positive strains (Bacillus subtilis and Staphylococcus aureus) and fungal strains (Candida albicans and Aspergillus niger).The synthesized compounds were also screened for antioxidant activity.The newly synthesized compounds were characterized by spectral and analytical techniques.The results revealed that all the synthesized compounds have a significant antioxidant and biological activity against the tested microorganisms.

TiO2 nanoparticles catalysed synthesis of 2-arylbenzimidazoles and 2-arylbenzothiazoles using hydrogen peroxide under ambient light

A H2O2/TiO2 P25 nanoparticle system has been examined and applied towards synthesis of a wide range of 2-substituted benzimidazole and benzothiazole derivatives from oxidative coupling of aromatic 1,2-phenylendiamine and 2-aminothiophenol with aromatic aldehydes bearing different types of substituents.

Facile one-pot clean synthesis of benzimidazole motifs: Exploration on bismuth nitrate accelerated subtle catalysis

Abstract In the present letter, an efficient, clean and one-pot synthesis of 2-substituted benzimidazole and 1,2-disubstituted benzimidazole derivatives has been explored by reacting o -phenylenediamine with aromatic aldehydes using bismuth nitrate as a catalyst in ethanol at ambient temperature. This methodology avails with faster reactions, excellent yield, mild reaction conditions, use of inexpensive and non-toxic catalyst compared to literature reported hitherto.

Reaction of 1-substituted benzimidazoles with acylacetylenes and water: ring-opening versus ring-expansion and isotopic effect of deuterium

1-Substituted benzimidazoles react with acylacetylenes and water (reflux in MeCN, 46–120 h) to stereoselectively give functionalized arylaminovinyl ketones, products of the imidazole ring-opening, in up to 75% yield and benzodiazocinones, products of the imidazole ring-expansion, in up to 28% yield. With D2O the yield of benzodiazocinone from 1-methylbenzimidazole and benzoylphenylacetylene is twice as much compared to the same reaction with H2O, thus demonstrating the strong isotopic effect of deuterium. The reaction mechanism, which agrees with deuterium distribution in the products, is discussed.

Highly efficient water-mediated approach to access benzazoles: metal catalyst and base-free synthesis of 2-substituted benzimidazoles, benzoxazoles, and benzothiazoles.

An efficient water-catalyzed method has been developed for the synthesis of 2-substituted benzimidazoles, benzoxazoles, and benzothiazoles in one step. The present method excludes the usage of toxic metal catalysts and bases to produce benzazoles in good to excellent yields. An efficient and versatile water-mediated method has been established for the synthesis of various 2-arylbenzazoles. The present protocol excludes the usage of any catalyst and additive provided excellent selectivities and yields with high functional group tolerance for the synthesis of 2-arylated benzimidazoles, benzoxazoles, and benzothiazoles. Benzazolones were also synthesized using similar reaction protocol.

ChemInform Abstract: Stereoselective Synthesis of N‐[(Z)‐2‐Cyano‐1‐phenylethenyl]benzimidazole‐2‐carbothioamides by a Three‐Component Reaction of 1‐Substituted Benzimidazoles, Phenylcyanoacetylene, and Isothiocyanates.

A new method has been developed for the synthesis of benzimidazole carbothioamides, which have potential pharmacological activity, by a three-component reaction of 1-substituted benzimidazoles, phenylcyanoacetylene, and methyl, allyl, or phenyl isothiocyanates. The reaction of these components proceeds under mild conditions in acetonitrile at 50-55°C for 12-20 h and stereoselectively leads to N-[(Z)-2-cyano-1-phenylethenyl]benzimidazole-2-carbothioamides in 43-82% yield.

Efficient domino synthesis of benzimidazole derivatives: copper catalysis versus transition metal-free conditions

An efficient and facile assembly of 2-substituted benzimidazoles and 2-benzimidazolones has been developed. Under very mild copper catalysis or transition metal-free conditions, a wide range of the 2-alkyl/alkenyl benzimidazole derivatives can be conveniently and selectively synthesized through the domino reactions of o-haloarylcarbodiimides with active methylene species. Interesting complimentary effect was discovered under the two different sets of conditions. Furthermore, a series of 1,3-disubstituted 2-benzimidazolones were facilely assembled from o-haloarylcarbodiimides and α,β-unsaturated esters.

Bentonite clay: an efficient catalyst for the synthesis of 2-substituted benzimidazoles

Benzimidazoles have been reported to have a wide range of biological and therapeutic properties. For this reason a variety of methods for their synthesis has been described, following one of the two general routes: the coupling of o-phenylenediamine and carboxylic acids or their derivatives using a strong acid and high temperature, or a two-step sequence that involves oxidative cyclodehydrogenation of Schiff’s bases, obtained by the reaction of o-phenylenediamines and aromatic aldehydes. A simple, efficient, and environmentally friendly procedure for the synthesis of substituted 2- and 2,5(6)-substituted benzimidazoles is herein described. The procedure is carried out by treatment of o-phenylenediamine or 4-chloro-o-phenylenediamine with aryl or heteroaryl aldehydes. Bentonite clay is used as catalyst in dry acetonitrile at room temperature. This procedure has several important advantages, including short reaction times, large-scale preparations, easy isolation of the products, and good to excellent yields.

Synthesis and characterization of 2-substituted benzimidazoles and their evaluation as anticancer agent

In this work, we report a series of benzimidazole derivatives synthesized from benzene-1,2-diamine and aryl-aldehydes at room temperature. The synthesized compounds have been characterized on the basis of elemental analysis and various spectroscopic studies viz., IR, 1H- and 13C-NMR, ESI-MS as well by X-ray single X-ray crystallographic study. Interaction of these compounds with CT-DNA has been examined with fluorescence experiments and showed significant binding ability. All the synthesized compounds have been screened for their antitumor activities against various human cancer cell lines viz., Human breast adenocarcinoma cell line (MCF-7), Human leukemia cell line (THP-1), Human prostate cancer cell lines (PC-3) and adenocarcinomic human alveolar basal epithelial cell lines (A-549). Interestingly, all the compounds showed significant anticancer activity.

Synthesis of 2-substituted benzimidazoles and benzothiazoles using Ag2CO3/Celite as an efficient solid catalyst

An efficient and simple approach for the synthesis of 2-substituted benzimidazoles and benzothiazoles through a coupling of 1,2-phenylenediamines and 2-aminothiophenols with variety of aryl aldehydes in ethanol at 70 °C using Ag2CO3/Celite as solid catalyst is described. The procedure features short reaction time, excellent yields and simple workup.

Grindstone chemistry: protic ionic liquid-substrate tuned green synthesis of 1,2-disubstituted and 2-substituted benzimidazoles with outstanding selectivity

An environmentally benign and highly substrate-protic ionic liquid controlled synthesis of 1,2-disubstituted and 2-substituted benzimidazoles with outstanding selectivity is demonstrated through grinding a mixture of OPD, aldehydes and catalyst.

An efficient one-pot two catalyst system in the construction of 2-substituted benzimidazoles: synthesis of benzimidazo[1,2-c]quinazolines.

The benzimidazole core is a common moiety in a large number of natural products and pharmacologically active small molecules. The synthesis of novel benzimidazole derivatives remains a main focus in medicinal research. In continuation of the efforts towards Ce(III) catalysts for organic transformations, we observed for the first time the activity of the iodide ion and copper cation in activating CeCl3·7H2O in the selective formation of prototypical 2-substituted benzimidazoles. The one-pot CeCl3·7H2O-CuI catalytic system procedure includes the cyclo-dehydrogenation of aniline Schiff's bases, generated in situ from the condensation of 1,2-phenylenediamine and aldehydes, followed by the oxidation with iodine, which works as a hydrogen sponge. Mild reaction conditions, good to excellent yields, and clean reactions make the procedure a useful contribution to the synthesis of biologically active fused heterocycles containing benzimidazoquinazolines.

Iron(III) Tetranitrophthalocyanine Chloride Immobilized on Activated Carbon: Efficient, Excellent Chemoselectivity and Recyclable Catalyst for Synthesis of 2-Substituted Benzimidazoles

Iron(III) Tetranitrophthalocyanine Chloride Immobilized on Activated Carbon: Efficient, Excellent Chemoselectivity and Recyclable Catalyst for Synthesis of 2-Substituted Benzimidazoles

Synthesis of 2-substituted benzoxazoles and benzimidazoles from 3-phenoxyphenyl-containing acrylonitriles

The synthesis was carried out via stirring the reactants in ethanol in the presence of sodium hydroxide at room temperature (20–25°C) during 1 h (3-phenoxyphenylacetonitrile:aldehyde = 1 : 1.2 mol/mol). Yields of nitriles II and III were of 84–90% (Scheme 1). When selecting the optimal reaction temperature, we took into account that at T > 30°C a competitive Cannizzaro reaction and disproportionation of the starting aldehyde could occur. On top of that, at 20– 30°C the formed 3-phenoxyphenyl acrylonitriles readily crystallized and precipitated, thus greatly facilitating the product isolation.

A Mild and Simple One‐pot Synthesis of 2‐Substituted Benzimidazole Derivatives Using DDQ as an Efficient Oxidant at Room Temperature

AbstractA series of 2‐substituted benzimidazoles were prepared through one‐pot reaction of o‐phenylenediamine with various aryl aldehydes in the presence of 2,3‐dichloro‐5,6‐dicyano‐1,4‐benzoquinone (DDQ) in acetonitrile as solvent at room temperature. The reactions were smoothly preceded in excellent yields and short reaction times with an easy work‐up. The pure benzimidazoles as products were confirmed and characterized by physical and spectral data.

Biomimetic Synthesis of Benzimidazoles, Benzoxazoles, and Benzothiadazole via the Group Transfer of Tetrahydrofolate Models

By an efficient biomimetic synthetic method, several novel 2-substituted benzimidazoles, benzoxazoles, and benzothiadazole were readily prepared in good yields under mild conditions with 2-substituted imidazolinium iodides as the tetrahydrofolate model compounds at the oxidation level of formate. The reaction is probably involved in a nucleophilic addition to the C=N bond at the imidazolinium ring, followed a 1,3-H migration at an imidazolidine intermediate and a salt elimination. Keywords: Benzimidazole, benzoxazole, benzothiadazole, biomimetic synthesis, imidazolinium iodide, transfer reaction, tetrahydrofolate model.

Synthesis of 2-Substituted Benzimidazoles Using 25 % Co/Ce-ZrO2 as a Heterogeneous and Nanocatalyst

25 % Co/Ce-ZrO2 nano fine particles are reported as a new catalyst for the efficient synthesis of 2-arylbenzimidazoles. A simple and convenient procedure, reusable catalyst, easy purification and shorter reaction times are the advantageous features of this method. Also prepared catalyst according to the coprecipitation method was characterized by common techniques such as SEM, XRD, FTIR and so on analysis. The catalyst is reusable and, reusable catalyst was characterized by XRD and FTIR techniques.

New highlights of the syntheses of pyrrolo[1,2-a]quinoxalin-4-ones.

The one-pot three-component reactions of 1-substituted benzimidazoles with ethyl bromoacetate and electron-deficient alkynes, in 1,2-epoxybutane, gave a variety of pyrrolo[1,2-a]quinoxalin-4-ones and pyrrolo[1,2-a]benzimidazoles. The influence of experimental conditions on the course of reaction was investigated. A novel synthetic pathway starting from benzimidazoles unsubstituted at the five membered ring, alkyl bromoacetates and non-symmetrical electron-deficient alkynes in the molar ratio of 1:2:1, in 1,2-epoxybutane at reflux temperature, led directly to pyrrolo[1,2-a]quinoxalin-4-ones in fair yield by an one-pot three-component reaction.

Novel 1,2,3-Triazole Derivatives as Antimicrobial Agents

2-Substituted benzimidazoles 3a-c was prepared via condensation of ethyl pyruvates 2a-c with 2-phenylenediamine in glacial acetic acid. Pyrrolo[1,2- a ]benzimidazole derivatives 5 and 8 were prepared via cyclocondensation of compounds 3a,b with phosphorus oxychloride or acetic anhydride in presence of sodium acetate respectively. Reactivity of pyruvate 2 towards 2-aminophenol, hydroxylamine and cyanothioacetamide was also investigated. They exhibited potent antimicrobial activity comparable to clinical drugs such as ciprofloxacin and ketoconazole. Compounds 3a , 11 and 13 showed excellent antimicrobial activity against all the tested microbes, and Compound 11 showed lower MIC values against all the tested organisms.

Saccharose as a new, natural, and highly efficient catalyst for the one-pot synthesis of 4,5-dihydropyrano[3,2-c]chromenes, 2-amino-3-cyano-4H-chromenes, 1,8-dioxodecahydroacridine, and 2-substituted benzimidazole derivatives

Saccharose was applied as a green and natural catalyst for the one-pot, three-component condensation between aromatic aldehydes, malononitrile, and resorcinol, or 4-hydroxycoumarine to afford the corresponding pyran-annulated heterocyclic systems. This green methodology offers several advantages such as the use of a non-hazardous catalyst, easy access, clean work-up, excellent yields, short reaction time, and environmentally mild conditions. In addition, 1,8-dioxodecahydroacridine and 2-substituted benzimidazole derivatives have been synthesized from commercially available starting materials, arylaldehydes, dimedone, amines, or ammonium acetate and o-phenylenediamine using the mentioned catalyst.