2-substituted Benzimidazoles Research Articles

H2O2/Fe(NO3)3-Promoted Synthesis of 2-Arylbenzimidazoles and 2-Arylbenzothiazoles

A new, convenient synthesis of 2-substituted benzimidazoles and benzothiazoles is described. Short reaction time, easy and quick isolation of the products, environmentally friendly procedure, excellent chemoselectivity and excellent yields are main advantages of this procedure.

Ammonium metavanadate: A novel catalyst for synthesis of 2-substituted benzimidazole derivatives

Ammonium metavanadate (10 mol%) was found to be a useful catalyst for the synthesis of various 2-substituted aryl benzimidazoles. It was used as an oxidizing agent for the condensation of o-phenylenediamine with different substituted aryl aldehydes at room temperature in ethanol. The method was proved to be simple, convenient and the product was isolated with good yields (79–91%).

Synthesis of novel biaryl 2-benzimidazoles and 2-benzothiazoles

Herein, we describe the synthesis of the novel 4-(1 H-benzo[ d]imidazol-2-yl)isoxazol-5-amine ( 7) and 4-(1 H-benzo[ d]thiazol-2-yl)isoxazol-5-amine scaffolds ( 8). Initial attempts following literature procedures for the synthesis of similar compounds did not yield the desired product. Instead we obtained the ring-opened adduct 2-(1 H-benzo[ d]imidazol-2(3 H)-ylidene)-2-cyanoacetamide ( 5). We were able to modify reaction conditions and successfully synthesize the desired product. We also describe a convenient one-pot microwave-assisted relay reaction for the synthesis of novel and reported 2-substituted benzimidazoles and benzothiazoles from inexpensive, commercially available reagents, 2-benzothiazole acetonitrile ( 2) and 2-benzimidazole acetonitrile ( 1). In all cases, good yields of products were obtained and reaction times were significantly reduced.

Remarkable influence of substituent in ionic liquid in control of reaction: simple, efficient and hazardous organic solvent free procedure for the synthesis of 2-aryl benzimidazoles promoted by ionic liquid, [pmim]BF4

A simple and efficient procedure for the synthesis of 2-substituted benzimidazoles has been developed by a one-pot reaction of o-phenylenediamine with aromatic aldehydes in the presence of an ionic liquid, 1-methyl-3-pentylimidazolium tetrafluoroborate, [pmim]BF4 at room temperature in open air without any organic solvent. The ionic liquid is recycled. A remarkable influence of the substituent on the imidazolium unit of the ionic liquid on the outcome of the reaction is observed.

Water-Mediated Synthesis of 2-Substituted Benzimidazoles by Boric Acid and Glycerol

A very simple, mild, and highly efficient green catalyst has been developed for the synthesis of 2-substituted benzimidazoles by treatment of substituted ortho-phenylenediamines and aldehydes in water at 80°C in the presence of boric acid (5 mol-%) and glycerol (0.05 mL). This methodology has been standardized on 55 substrates, and nine new compounds have been synthesized.

Parallel Synthesis of 2-Aryl-4-aminobenzimidazoles and Their Evaluation as Gonadotropin Releasing Hormone Antagonists

2-Trifluoromethyl-4-aminobenzimidazoles were previously identified by screening to be active antagonists of the gonadotropin releasing hormone receptor (GnRH-R). Structure activity relationships and diversity oriented synthesis are shown here in greater detail. 2-Substituted benzimidazoles were synthesized in parallel by the coupling of carboxylic acids with a latent intermediate diamine monomer to yield the desired benzimidazoles in fair yields. A catch and release strategy was employed as a product isolation technique, followed by RP-HPLC to obtain products of desired purity for biological evaluation. Two libraries were prepared and screened to determine the optimal substitution for inhibitory activity against GnRH-R. The initial library focused on substituted phenyl, pyridine, and thiophenes. The follow-up library focused on substitution patterns observed in the initial library members and generated compounds with IC(50) values lower than 100 nM at the GnRH-R.

Copper-catalyzed one-pot synthesis of benzimidazole derivatives

A simple, efficient, and environmentally benign method has been developed for the synthesis of 2-substituted benzimidazoles through a one-pot reaction of phenylenediamines with aryl aldehydes in excellent isolated yields under mild conditions using Cu(II) complex as the selective, recyclable, and heterogeneous catalyst at ambient temperature. The Cu(II) complex as a heterogeneous catalyst can be reused in further catalytic reactions, and it was found that its activity remained largely unchanged for eight successive runs. No metal-complex leaching was observed after the consecutive catalytic reactions. The salient features of this method include mild conditions, high yields, simple procedure, and good recovery and reusability of the heterogeneous catalyst.Key words: benzimidazole, o-phenylenediamine, arylaldehydes, heterogeneous catalyst, N,N-bis (2-hydroxyphenyl)pyridine-2,6-dicarboxamide.

PEG-mediated catalyst-free expeditious synthesis of 2-substituted benzimidazoles and bis-benzimidazoles under solvent-less conditions

A wide variety of 2-substituted benzimidazoles and bis-benzimidazoles were synthesized in high yields by PEG-mediated catalyst-free synthesis under solvent-less conditions. The products were directly recrystallized from hot methanol. The reaction occurred giving excellent yields with low as well as high molecular weight PEGs.

Mild and Highly Efficient Method for the Synthesis of 2-Arylbenzimidazoles and 2-Arylbenzothiazoles

A new, convenient method for the syntheses of 2-substituted benzimidazole and benzothizole is described. Short reaction times, large-scale synthesis, easy and quick isolation of the products, excellent chemoselectivity, and excellent yields are the main advantages of this procedure.

Synthesis and investigation of mass spectra of some novel benzimidazole derivatives

2-Substituted benzimidazoles (3) and (4a-c) were prepared via condensation of ethyl 2-thionyl-pyruvate (1) and hydrazidoyl derivatives (2a-c) with o-phenylene diamine in acetic acid. Acetylation of compound (4a) with acetic anhydride yielded the corresponding N-acetyl derivative (5). Treatment of compound 4b with hydrazine hydrate gave the corresponding hydrazino derivative (6). Reaction of 2-[(2-thionyl)acetyl)] benzimidazole (3) with hydrazine hydrate gave the pyrazolyl derivative (7) and hydrazino derivative (8). Alkylation of compound 3 with alkyl halide gave the corresponding 2,3-disubstituled benzimidazoles (9a, b). Pyrrolo[1,2-a] benzimidazole derivatives 10 and 11 were prepared via cyclocondensation of compound 3 with acetic anhydride in presence of AcONa and phosphorus oxychloride. The electron impact mass spectra of both of the above series of compounds have also been recorded and their fragmentation patterns are discussed.

Dowex 50W: A highly efficient and recyclable green catalyst for the construction of the 2-substituted benzimidazole moiety in aqueous medium

Abstract Only 10 mol% of Dowex 50W in water proved to be a very efficient catalyst for the synthesis of a wide variety of 2-substituted benzimidazoles. The methodology is mild, high yielding, green and the catalyst could be easily recycled.

Convenient one-pot synthesis of novel 2-substituted benzimidazoles, tetrahydrobenzimidazoles and imidazoles and evaluation of their in vitro antibacterial and antifungal activities

A series of novel 2-substituted benzimidazoles and imidazoles have been synthesized from long-chain alkenoic acids. The reactions occurred under relatively mild conditions and afforded the desired product in good yields. The structures of these compounds have been elucidated by elemental and spectral (IR, 1H NMR, 13C NMR, mass) analyses. Furthermore, compounds were screened for in vitro antibacterial activity against the representative panel of two Gram-positive and two Gram-negative bacteria. All the synthesized compounds were also tested for their inhibitory action against five strains of fungus. The various compounds show potent inhibitory action against test organisms.

An efficient method to access 2-substituted benzimidazoles under solvent-free conditions

An expeditious method to access 2-substituted benzimidazoles was developed. Both aromatic (phenols, anilines, and thiophenols) and alkyl nucleophiles (amines and thiols) react with 2-methylsulfonyl benzimidazole under solvent-free conditions to generate a variety of 2-substituted benzimidazoles.

Os(VIII)-catalyzed mechanistic investigation of oxidation of some benzimidazoles by chloramine-T in alkaline medium: A kinetic approach

Abstract The kinetics of Os(VIII)-catalyzed oxidation of benzimidazole (BzlH) and 2-substituted benzimidazoles viz., 2-methylbenzimidazole (MeBzlH), 2-hydroxybenzimidazole (2-HyBzlH), 2-aminobenzimidazole (2-AmBzlH) and 2-phenylbenzimidazole (2-PhBzlH) by sodium-N chloro- p -toluenesulfonamide (chloramine-T; CAT) in presence of NaOH has been investigated at 303 K. Under comparable experimental conditions, the oxidation reactions follow identical kinetics for all the five benzimidazoles with first order dependence each on [CAT] 0 and [substrate] 0 and fractional order dependence each on [OH − ] and [Os(VIII)]. The reactions were studied at different temperatures and the composite activation parameters have been computed. The calculated isokinetic temperature ( β ) of 380 K obtained from enthalpy-entropy relationships and Exner correlations was much higher than the experimental temperature of 303 K, indicating that the rate is under enthalpy control. Relative reactivity of oxidation of these follow the order: 2-MeBzlH > 2-HyBzlH > 2-AmBzlH > BzlH > IzlH > 2-PhBzlH. This trend may be attributed to inductive effects. Further, the kinetics of Os(VIII)-catalyzed oxidation of these benzimidazoles have been compared with those of their uncatalyzed reactions (in the absence of catalyst) and found that the catalyzed reactions are 10–15 fold faster than the uncatalyzed reactions. The observed results have been explained by a plausible mechanism and the related rate law has been deduced.

Synthesis of 2-substituted benzimidazoles and bis-benzimidazoles by microwave in the presence of alumina-methanesulfonic acid

A microwave-assisted method for the synthesis of 2-substituted benzimidazoles in the presence of alumina-methanesulfonic acid (AMA) is reported. In addition, by this method some new bis-benzimidazoles from the direct reaction of phenylenediamine and dicarboxylic acid under microwave irradiation in good to excellent yields are described.

Coordination behavior of benzimidazole, 2-substituted benzimidazoles and benzothiazoles, towards transition metal ions

Coordination chemistry of benzimidazole and 2-substituted benzimidazole derivatives towards transition metal ions is reviewed. Benzimidazole complexes containing halides or carboxylates derivatives are discussed, as well as the coordination chemistry of 2-substituted benzimidazoles bearing additional nitrogen, oxygen or sulfur atoms as potential binding sites, which may form chelates. The latter ligands give place to a variety of metal-ligand coordination modes. In some cases, these bidentate ligands favour the formation of a six membered ring, by inclusion of a metal ion in a planar delocalized system. Some of the studied 2-substituded benzimidazoles include 2-uroyl, 2-carbamate, 2-benzothiazole, 2-(2-benzothiazolylamino)benzothiazole, 2-(2- aminobenzothiazolyl-amino) benzoxazole, 2-(4'-thiazolyl)benzimidazole, 2-((5-methylpyrazol-3- yl)methyl)benzimidazole, 2-guanidinobenzimidazole, 2-aminomethylbenzimidazole, 1- (benzimidazol-2-yl)phenolato, 2-(2-benzimidazol-2-yl)pyridine-N-oxide-N,O and N- (benzothiazol-2-yl)-dithiocarbamic methyl ester. It is important to mention that benzimidazole and its derivatives promote intra and inter-molecular interactions, such as hydrogen bonding and π- stacking, giving place to the formation of molecular aggregates.

Products from condensation of 1-(3(4)-acetylphenyl)-4-carboxy-2-pyrrolidinones with o-phenylenediamine and their properties

2-Substituted benzimidazoles were synthesized by the reaction of 1-(3(4)-acetylphenyl)-4-carboxy-2-pyrrolidinones with o-phenylenediamine. Their reactions with sodium hydroxide and hydrazine and some of their chemical characteristics were investigated.

A Simple and Efficient One‐Pot Synthesis of 2‐Substituted Benzimidazoles.

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Palladium-catalyzed N-heteroannulation of N-allyl- or N-benzyl-2-nitrobenzenamines: synthesis of 2-substituted benzimidazoles

A palladium-catalyzed reductive N-heteroannulation of N-allyl- or N-benzyl-2-nitrobenzenamines, using carbon monoxide as the ultimate reducing agent, affording 2-substituted benzimidazoles has been developed.

A Simple and Efficient One-Pot Synthesis of 2-Substituted Benzimidazoles

A simple and efficient procedure for the synthesis of substituted benzimidazoles through a one-pot condensation of o-phenylenediamines with aryl aldehydes in the presence of H 2 O 2 /HCl system in acetonitrile at room temperature is described. Short reaction time, large-scale synthesis, easy and quick isolation of the products, and excellent yields are the main advantages of this procedure.