One‐Pot Synthesis of Benzimidazoles from o‐Nitroanilines under Microwaves via a Reductive Cyclization

An efficient microwave irradiation synthesis of 2‐substituted benzimidazoles in one step via the Na₂S₂O₄ reduction of o‐nitroanilines in the presence of aldehydes is described. The method is simple and a good option to obtain the title compounds in a very short time.     

A fluorine scan of non-peptidic inhibitors of neprilysin: Fluorophobic and fluorophilic regions in an enzyme active site

This article describes the synthesis and in vitro biological affinities of (poly)fluorinated neprilysin inhibitors. Two series of inhibitors with F-substitution of the central benzimidazole platform of the ligands and the benzylic vector to fill the S1’ pocket of NEP were investigated. The S1’ pocket was found to be highly fluorophobic, and F-substitution led to significantly decreased binding affinities of inhibitors. This result is explained by electrostatically unfavorable close contacts of organic fluorine with the negatively polarized π-surfaces of surrounding aromatic amino acid side chains. In contrast, the protein environment around the benzimidazole platform, with three electropositive guanidinium side chains of Arg residues, was found to provide a fluorophilic environment. Overall, the data support that organic fluorine, with its high negative charge density prefers to orient into electropositive regions of receptor sites. pK_a measurements of fluorinated ligands provided several simple patterns for the prediction of pK_a values of benzimidazoles, important building blocks in medicinal chemistry.     

One-pot synthesis of benzimidazoles from gem-dibromomethylarenes using o-diaminoarenes

A one-pot synthesis of benzimidazoles from gem-dibromomethylarenes is described. The reaction shows the method to prepare a variety of benzimidazole analogues with excellent yield.     

Simple but efficient synthesis of novel substituted benzimidazoles over ZrO2-Al2O3

Solid-acid catalytic materials such as ZrO₂-Al₂O₃ containing 80?mol% of ZrO₂ were prepared by the solution combustion method (SCM) using different fuels such as urea, hexamethylene tetramine, glycine, and sucrose. All the prepared solid acid catalytic materials were characterized for their physico-chemical properties like crystalinity, acidity, functionality and morphology. These materials were evaluated for their catalytic activity in the synthesis of a series of novel substituted benzimidazoles. The reaction conditions were optimized by varying the solvents, reaction temperature, weight of solid acid catalyst, molar ratio of the reactants, and reaction time. The ZrO₂-Al₂O₃ solid acid catalytic material prepared by urea as a fuel was found to be highly active, recyclable, and reusable in the synthesis of benzimidazoles. A possible reaction mechanism for the synthesis of benzimidazoles is also proposed.     

Synthesis of Benzimidazoles and Benzoxazoles Using Palladium Bis(2,2,6,6-tetramethyl-3,5-heptanedionate) as a Novel Catalyst

Structurally well-defined palladium bis(2,2,6,6-tetramethyl-3,5-heptanedionate) complex is reported to be an efficient catalyst for the synthesis of benzimidazole and benzoxazole derivatives in good yields. A novel approach for one-pot synthesis of benzimidazoles via direct reductive amination and N-arylation followed by hydrogenation–cyclization methodology is also described.     

Microwave‐Assisted Solid‐Phase Synthesis of a 1,2‐Disubstituted Benzimidazole Library by Using a Phosphonium Linker

An efficient and rapid microwave‐assisted solid‐phase method for the synthesis of 5‐methyl‐1,2‐disubstituted benzimidazoles derivatives has been developed. The phosphonium linker, obtained by reaction between polymer‐supported triphenylphosphine and 4‐fluoro‐3‐nitrobenzyl iodide, underwent aromatic substitution with primary amines, followed by one‐pot reaction with aldehydes in the presence of SnCl₂·2H₂O, yielded the benzimidazole system under microwave irradiation. The final products were released from the resin with NaOH under microwave irradiation and were obtained in high purity and good overall yield.     

A simple conversion of azlactones into indenones via H3PW12O40/Al2O3 catalyzed intramolecular Friedel-Crafts reaction

A rapid and simple procedure for the synthesis of the indenone derivatives, N-(1-oxo-1H-inden-2-yl)benzamides, via intramolecular Friedel-Crafts (IFC) reaction of (Z)-4-arylidene-2-phenyl-5(4)-oxazolones (azlactones) catalyzed by H₃PW₁₂O₄₀ supported on neutral alumina under microwave irradiation has been developed. The reaction is straightforward and allows easy isolation of the product. The catalyst could be re-used up to four times after simple filtration.     

Copper-doped silica cuprous sulfate: A highly efficient heterogeneous nano-catalyst for one-pot three-component synthesis of 1-H-2-substituted benzimidazoles from 2-bromoanilines,aldehydes, and [bmim]N3

A facile and highly efficient one-pot three-component synthesis of 1-H-2-substituted benzimidazole derivatives from readily available substrates catalyzed by copper-doped silica cuprous sulfate (CDSCS) is described. In this method, treatment of diverse 2-bromoanilines, aldehydes, and [bmim]N₃ in DMF at 110 °C in the presence of CDSCS as a highly efficient heterogeneous nano-catalyst affords the corresponding 1-H-2-substituted benzimidazoles in good to excellent yields. The CDSCS is an inexpensive and stable nano-catalyst that could be simply prepared, recovered and reused for many consecutive reaction runs without significant loss of its activity.     

TMSCl/Fe(NO3)3-Catalyzed Synthesis of 2-Arylbenzothiazoles and 2-Arylbenzimidazoles Under Ultrasonic Irradiation

A convenient one-pot cyclocondensation method for benzothiazole and benzimidazole syntheses is described. A set of benzothiazoles and benzimidazoles were readily prepared from aromatic ortho-diamines or ortho-aminothiophenol and aldehydes using chlorotrimethylsilane in dimethylformamide as promoter and water scavenger under ultrasonic irradiation in good yields (84–97%).     

Synthesis of seven- and eight-membered [1,2-a] alicyclic ring-fused benzimidazoles and 3-aziridinylazepino[1,2-a]benzimidazolequinone as a potential antitumour agent

Azepino and azocino[1,2-a]benzimidazoles were obtained either by treatment of 1-nitrophenyl-2-azacycloalkanes via a one-pot catalytic hydrogenation/acetylation or by treatment of the acetamides generated in the latter reaction with performic acid. This represents the first facile synthesis of eight-membered [1,2-a] alicyclic ring-fused benzimidazoles. 3-Methoxy-azepino[1,2-a]benzimidazole was elaborated to the novel potential cytotoxin, 3-(N-aziridinyl)-7,8,9,10-tetrahydro-6H-azepino[1,2-a]benzimidazole-1,4-dione. The synthesis included clarification of the reactivity of methoxy-substituted benzimidazoles towards nitration.     

Reusable Nano-Zirconia-Catalyzed Synthesis of Benzimidazoles and Their Antibacterial and Antifungal Activities

In this article, a zirconia-based nano-catalyst (Nano-ZrO₂), with intermolecular C-N bond formation for the synthesis of various benzimidazole-fused heterocycles in a concise method is reported. The robustness of this reaction is demonstrated by the synthesis of a series of benzimidazole drugs in a one-pot method. All synthesized materials were characterized using ¹HNMR, ¹³CNMR, and LC-MS spectroscopy as well as microanalysis data. Furthermore, the synthesis of nano-ZrO₂ was processed using a standard hydrothermal technique in pure form. The crystal structure of nano-ZrO₂ and phase purity were studied, and the crystallite size was calculated from XRD analysis using the Debye–Scherrer equation. Furthermore, the antimicrobial activity of the synthesized benzimidazole drugs was evaluated in terms of Gram-positive, Gram-negative, and antifungal activity, and the results were satisfactory.     

Cp2ZrCl2-catalyzed synthesis of 2-aminovinyl benzimidazoles under microwave conditions

A microwave-assisted general method for the synthesis of 2-aminovinyl benzimidazoles has been developed.Treatment of the 1,2-phenylenediamines and N-arylated/N,N-dialkylated 3-aminoacroleins with bis(cyclopentadienyl)zirconium(IV) dichloride(Cp2Zr Cl2) as the catalyst under microwave irradiation for 3–5 min followed by in situ Mn O2 oxidation afforded thirteen 2-aminovinyl benzimidazoles in good yields.     

New route for the synthesis of benzimidazoles by a one-pot multistep process with mono and bifunctional solid catalysts

One-pot multistep reactions involving a new environmentally friendly catalytic procedure have been developed for the synthesis of benzimidazoles. Benzimidazole derivatives with biological and pharmaceutical interest have been prepared by a one-pot four step process with a solid catalyst containing basic and oxidation sites. The four steps refer to: (a) oxidation of the alcohol; (b) cyclocondensation of the aldehyde formed with ortho-phenylenediamines, (c) oxidation of the carbon-nitrogen bond, (d) N-alkylation reaction. The process is illustrated by the synthesis of 1,2-disubstituted benzimidazole derivative with antiviral activity.     

Diverse synthesis of pyrimido[1,2-a]benzimidazoles and imidazo[2,1-b]benzothiazoles via CuI-catalyzed decarboxylic multicomponent reactions of heterocyclic azoles,aldehydes and alkynecarboxylic acids

We have developed a straightforward approach to diverse synthesis of 2,3-, 2,4-disubstituted pyrimido [1,2-a]benzimidazoles, 2,4,10-trisubstituted 2,10-dihydropyrimido [1,2-a]benzimidazoles and 2,3-disubstituted imidazo [2,1-b]benzothiazoles via multicomponent reactions (MCRs) of heterocyclic azoles, aldehydes with easily storable and handling alkynecarboxylic acids. In the presence of a catalytic amount of CuI and K₂CO₃, the pyrimido [1,2-a]benzimidazole or imidazo [2,1-b]benzothiazole scaffold could be rapidly constructed through a 6-endo-dig or 5-exo-dig cyclization, respectively. The preliminary mechanistic study suggested that the formation of 2,3- disubstituted pyrimido [1,2-a]benzimidazoles, which completes the assembly of the scaffold and its C-3 position functionalization in one pot, undergoes a novel cascade process involving a decarboxylation, A [3] coupling, 6-endo-dig cyclization, nucleophilic addition and dehydration.     

Zn3(BTC)2 as a Highly Efficient Reusable Catalyst for the Synthesis of 2‐Aryl‐1H‐Benzimidazole

Zn₃(BTC)₂ metal‐organic frameworks as recyclable and heterogeneous catalysts were effectively used to catalyze the synthesis of benzimidazole derivatives from o‐phenylendiamine and aldehydes in ethanol. This method provides 2‐aryl‐1H‐benzimidazoles in good to excellent yields with little catalyst loading. The catalyst was characterized using different techniques such as X‐ray diffraction (XRD), energy dispersive X‐ray (EDX) analysis, scanning electron microscopy (SEM), and Fourier transform infrared (FT‐IR) spectroscopy.     

CN bond formation and cyclization: A straightforward and metal-free synthesis of N-1-alkyl-2-unsubstituted benzimidazoles

A straightforward and metal-free synthesis of N-1-alkyl-2-unsubstituted benzimidazoles from the corresponding o-fluoro aryl formamidines and primary amines using microwave irradiation is described. The displacement of -F by the primary amine and cyclization to form the corresponding benzimidazoles took place in one pot.     

Microwave‐mediated synthesis and antibacterial activity of some novel 2‐(substituted biphenyl) benzimidazoles via Suzuki‐Miyaura cross coupling reaction and their N‐substituted derivatives

A series of some novel 2‐(substituted biphenyl) benzimidazoles and their N‐substituted derivatives were synthesized via microwave‐mediated Suzuki‐Miyaura coupling of 2‐(4‐iodophenyl)‐1H‐benzimidazole or 2‐(4‐iodophenyl)‐6‐amino‐1H‐benzimidazole and arylboronic acids. The method reported herein offers advantageous shorter reaction times, higher yields and is applicable to a large set of substrates. All the synthesized compounds were screened for their antibacterial activity against Staphylococcus aureus and Salmonella typhimurium bacterial species. J. Heterocyclic Chem., (2011).     

Synthesis of one-pot pyrazolo[4′,3′:5,6]pyrano[2,3-c]phenazin-15-yl) methanone derivatives via a multi-component using Fe3O4@TiO2-SO3H as a recoverable magnetic catalyst under microwave irradiation

ABSTRACT

A new one-pot method for the synthesis four-component of pyrazolo[4′,3′:5,6]pyrano[2,3-c]phenazin-15-yl)methanone derivatives has been developed in the presence of nano Fe₃O₄@TiO₂-SO₃H catalysts (heterogeneous acid) under microwave conditions and in a solvent-free environment at 180?W. One of the benefits of using this catalyst was its re-use in subsequent stages of its reaction without much loss in its activity, which was carried out by an external magnet and recovered. The catalyst was synthesized and characterized by XRD, EDX, TEM, FESEM, TGA-DTA, BET, VSM and AFM. The productivity of the products obtained from this protocol (MAOS) is significantly high and the shorter reaction time in the synthesis process over the reflux method. These results showed advantages for synthesis, such as mild reaction conditions, no use of toxic catalysts in the laboratory, solvent-free environment, low energy consumption and Economically Affordable.     

Green synthesis of benzimidazole derivatives catalyzed by ionic liquid under microwave irradiation

An efficient synthesis of benzimidazole derivatives from o-phenylene diamine and substituted aromatic aldehyde catalyzed by ionic liquid under microwave irradiation was reported. The synthesis conditions were first optimized by single factor experiments. Then, a central composite design combined with response surface methodology was used to study the most effective factors. Optimal conditions were synthesis time 1 h, the reactant/catalyst molar ratio 1:1:0.200, the temperature 50 °C and the microwave power 500 W. Under optimized conditions, the yields of benzimidazole derivatives were 78.55–97.66 %. This method offered the outstanding advantages, such as faster reaction rate, higher yields, recyclable catalyst, environmental friendliness, and simple workup procedure.