Synthesis Of Novel Benzimidazoles Research Articles

Design and synthesis of novel benzimidazoles containing 1,2,3-triazolesas in vitro, anticancer and anti-oxidant agents

A novel series of 2-(1-((1-substitutedphenyl-1H-1,2,3- triazol-4-yl)methoxy)ethyl)-1-((1-substituted phenyl- 1H-1,2,3-triazol-4-yl)methyl)-1H-benzo[d]imidazole (3a-j)derivatives was synthesized in moderate to high yields. The structures of all the synthesized compounds were characterized by 1HNMR, 13CNMR and Mass spectroscopic methods. The title compounds were screened for their anti-oxidant activity and anti-cancer activity. The cancer activity results reveal that the compounds 3j, 3b and 3f are showing promising activity and remaining compounds exhibited moderate activity against all the tested cancer cell lines. The anti-oxidant activity also shows that the compounds 3c and 3d have shown excellent activity and remaining compounds were also found to exhibit moderate activity against the test organisms employed.

Synthesis of novel benzimidazoles and benzothiazoles via furan‐2‐carboxaldehydes, o‐phenylenediamines, and 2‐aminothiophenol using Cu(II) Schiff‐base@SiO2 as a nanocatalyst

2‐(5‐Substituted phenyl)furan‐2‐carboxaldehyde derivatives were prepared by using an efficient copper(II) complex of tetradentate Schiff‐base ligand immobilized onto silica as a heterogeneous nanocatalyst [Cu(II) Schiff‐base@SiO2] (5.0 mol%) using anilines, sodium nitrite, and furan‐2‐carboxaldehyde. Furthermore, attractive di‐heteroaryl benzo‐fused systems such as benzimidazole and benzothiazole derivatives were synthesized using this nanocatalyst (5.0 mol%) via the reaction of o‐phenylenediamines and 2‐aminothiophenol with 2‐(5‐substituted phenyl)furan‐2‐carboxaldehydes in EtOH. The catalyst was characterized by Fourier transform infrared (FT‐IR), field emission scanning electron microscope (FESEM), energy‐dispersive X‐ray spectroscopy (EDX), X‐ray powder diffraction (XRD), and inductively coupled plasma (ICP) techniques. The advantages of the present catalytic system are short reaction times, mild conditions, good to excellent yields, and low amount of nanocatalyst. Moreover, to the best of our knowledge, this is the first time of using the same catalyst in two steps including synthesis of 2‐(5‐substituted phenyl)furan‐2‐carboxaldehyde and benzimidazole or benzothiazole derivatives. In addition, the synthesized catalyst was recycled very well and reused several times without significant loss of its catalytic activity.

One‐pot synthesis of novel benzimidazoles with a naphthalene moiety as antimicrobial agents and molecular docking studies

AbstractIn an attempt to design a greener approach for the synthesis of a potent class of antimicrobials, 1,2‐phenylenediamine derivatives were reacted with various 1/2‐carboxylic acid‐substituted naphthalene derivatives to generate a series of naphthyl‐substituted benzimidazole derivatives (11–19) using polyphosphoric acid as catalyst under microwave irradiation and conventional synthesis method. This is an eco‐friendly and swift reaction method for a synthetic approach to diverse benzimidazoles. Structures of the synthesized compounds were established on the basis of spectral data and they were screened for their antimicrobial activity. Compound 18 showed maximum potency against all Gram‐positive and Gram‐negative bacterial strains with a minimum inhibitory concentration (MIC) value in the range of 7.81–62.50 μg/ml. Only compound 17 was found to be the most active against all fungal strains with a MIC value of 15.62 μg/ml. In this study, we performed molecular docking experiments to understand the interactions between compounds 17 and 18 and E. coli topoisomerase I, and we compared the results obtained with that of 2‐(3,4‐dimethoxyphenyl)‐5‐[5‐(4‐methylpiperazin−1‐yl)‐1H‐benzimidazol‐2‐yl]‐1H‐benzimidazole (DMA). Compounds 17 and 18 demonstrated strong interactions with important active site residues, similar to DMA. As a result, the compounds obtained from this study can be used in designing new potent inhibitors of E. coli topoisomerase I.

Synthesis of novel benzimidazoles at room temperature, under solvent-free condition and their biological studies

An efficient and facile synthesis of substituted novel benzimidazoles (3a–3h) mediated by fruit juices viz. Cocos nucifera L. juice, Citrus limetta juice and Citrus sinensis L. juice, via condensation of substituted aldehydes (1a–1h) and o-phenylenediammine (2a) under solvent-free condition at room temperature is presented in this paper. The purity of compounds was confirmed by melting point and thin layer chromatography. All synthesized compounds (3a–3h) were fully characterized via NMR and FTIR spectral data and evaluated for in vitro herbicidal activity against Raphanus sativus L. (Radish) seeds. The compounds (3a–3h) were also evaluated for their antibacterial activity against Erwinia cartovora and Xanthomonas citri by inhibition zone method. Antifungal activity was also determined against Rhizoctonia solani and Colletotrichum gloeosporioides by poisoned food techniques method. From activity data, it was found that compounds 3d and 3e were most active against R. sativus L. (root) and R. sativus L. (shoot), respectively. Compound 3g has shown maximum inhibition zone i.e. 8.00 mm against E. cartovora at 2000 µg/mL concentration. Maximum X. citrii growth was inhibited by compounds 3a showing inhibition zone 5.20 mm at highest concentration. Compound 3f was found most active against R. solani and C. gloeosporioides fungus at 2000 µg/mL concentration. In comparison with the conventional methods, the present method complies with several key requirements of green chemistry principles such as the utilization of renewable feedstock, auxiliary aqueous conditions and reduces waste with the use of nature-derived catalyst. Therefore, the present method offers an attractive option because of its ecological safety, environmental acceptance, cost effective and easy workup process.

Tungstate sulfuric acid: preparation, characterization, and application in catalytic synthesis of novel benzimidazoles

AbstractTungstate sulfuric acid (TSA) was prepared, characterized, and applied for direct synthesis of novel and known benzimidazoles through a condensation reaction of o-phenylenediamines with orthoesters under solvent-free conditions. TSA was characterized by powdered X-ray diffraction (XRD), X-ray fluorescence (XRF), and FTIR spectroscopy. This novel and eco-friendly method is very cheap and has many advantages such as excellent yields, recyclable and eco-friendly catalyst, and simple work-up procedure.

Parallel synthesis of novel benzimidazoles on a soluble polymer support

AbstractLiquid phase combinatorial synthesis using a soluble polyethylene glycol (PEG) polymer support and commercially available 3-nitro-4-fluoro benzoic acid is carried out in order to create a molecular library of trisubstituted benzimidazoles. The PEG-ester conjugate of 3-nitro-4-fluoro benzoic acid is subjected to ipso-fluoro displacement by various primary amines. The nitro group is reduced under neutral conditions using excess zinc and ammonium chloride, producing the polymer-boundo-phenylene diamines. Reaction of the diamines with different aldehydes results in cyclisation to benzimidazoles. The polymer support is cleaved releasing the desired products in high yields and purity. All reactions are performed at room temperature.

Two-step solution-phase synthesis of novel benzimidazoles utilizing a UDC (Ugi/de-Boc/cyclize) strategy

The novel solution-phase synthesis of an array of biologically relevant benzimidazoles in a simple two-step procedure is revealed. Transformations are carried out in excellent yield by condensation of mono-Boc protected ortho-phenylene diamine and supporting Ugi reagents. Subsequent acid treatment and evaporation affords benzimidazoles in good to excellent yield. The described protocol represents a highly attractive solution-phase procedure for the rapid generation of benzimidazole libraries.