Tetrasubstituted Imidazoles Research Articles

Magnetic nanoparticle-supported sulfonic acid as a green catalyst for the one-pot synthesis of 2,4,5-trisubstituted imidazoles and 1,2,4,5-tetrasubstituted imidazoles under solvent-free conditions

Abstract In this work, magnetic nanoparticle-supported sulfonic acid (γ-Fe2O3-SO3H) is used as an efficient catalyst in the synthesis of 2,4,5-trisubstituted imidazoles and 1,2,4,5-tetrasubstituted imidazoles in a short time (40–70 min for trisubstituted imidazoles and 30–40 min for tetrasubstituted imidazoles) and high-purity products were obtained (92–98% for trisubstituted imidazoles and 94–98% for tetrasubstituted imidazoles) in simple multicomponent reactions. The structure of these products was confirmed via FT-IR and NMR. Green and recyclable catalysts, eco-friendly and solvent-free conditions, high catalytic activity, shorter reaction time, easy recovery by an external magnet, high purity, and excellent yields are some features of these reactions.

Facile fabrication of porous magnetic covalent organic frameworks as robust platform for multicomponent reaction

AbstractThe design of cheap yet efficient nanoporous magnetic catalysts for the environmentally benign process's widespread application is an extremely attractive, challenging chemical research field. A novel porous magnetic covalent organic framework was prepared by the condensation reaction of melamine and terephthaladehyde on the surface of 3,4‐dihydroxybenzaldehyde coated magnetic Fe3O4 nanoparticles COF@Fe3O4 under hydrothermal conditions for the first time. The high surface area magnetic COF could exhibit superior catalytic activity for sustainable synthesis of trisubstituted and tetrasubstituted imidazoles and pyrroles in good to excellent yields in PEG as solvent under environmentally friendly, ambient conditions and making the overall process economical, efficient, and green. The retrievable catalyst in PEG is general and applicable to a broad substrate scope and functional group compatibility. The structure and morphology of the COF@Fe3O4 were characterized by FTIR, XRD, EDX, and SEM spectroscopy. The COF@Fe3O4 magnetic catalyst was recovered by an external magnet and used for several cycles without significant catalytic activity loss.

Tetrasubstituted imidazoles as incognito Toll-like receptor 8\u2009a(nta)gonists

Small-molecule modulators of TLR8 have drawn much interests as it plays pivotal roles in the innate immune response to single-stranded RNAs (ssRNAs) derived from viruses. However, their clinical uses are limited because they can invoke an uncontrolled, global inflammatory response. The efforts described herein culminate in the fortuitous discovery of a tetrasubstituted imidazole CU-CPD107 which inhibits R848-induced TLR8 signaling. In stark contrast, CU-CPD107 shows unexpected synergistic agonist activities in the presence of ssRNA, while CU-CPD107 alone is unable to influence TLR8 signaling. CU-CPD107’s unique, dichotomous behavior sheds light on a way to approach TLR agonists. CU-CPD107 offers the opportunity to avoid the undesired, global inflammation side effects that have rendered imidazoquinolines clinically irrelevant, providing an insight for the development of antiviral drugs.

Unlocking the catalytic potency of a magnetic responsive CoFe2O4/Ni-BTC MOF composite for the sustainable synthesis of tri- and tetra-substituted imidazoles

A CoFe2O4/Ni-BTC hybrid composite has been synthesized for the one-pot multicomponent synthesis of 2,4,5-trisubstituted and 1,2,4,5-tetrasubstituted imidazoles.

Synthesis, Characterization, and Catalytic Properties of Magnetic Fe3O4@FU: A Heterogeneous Nanostructured Mesoporous Bio-Based Catalyst for the Synthesis of Imidazole Derivatives.

In this protocol, Fucoidan (FU), a fucose-rich sulfated polysaccharide extracted from brown algae Fucus vesiculosus was used for in situ preparation of magnetic Fe3O4@FU. Nanoco magnetic properties of Fe3O4@FU were investigated by energy dispersive X-ray (EDX) spectroscopy, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), Brunauer–Emmett–Teller (BET) adsorption method, and vibrating sample magnetometer (VSM). The catalytic activity of Fe3O4@FU was employed for the synthesis of tri- and tetra-substituted imidazoles through three- and four-component reactions respectively, between benzyl, aldehydes, NH4OAc and benzyl, aldehydes, NH4OAc, and amine under reflux in ethanol. It is worth nothing that excellent yields, short reaction times, chromatography-free purification, and environmental friendliness are highlighted features of this protocol.

Highly efficient and metal-free synthesis of tri- and tetrasubstituted imidazole catalyzed by 3-picolinic acid

3-Picolinic acid is an efficient organo-catalyst for a one-pot three-component synthesis of 2,4,5-triaryl substituted imidazole. Moreover, the utility of this catalyst has been extended to the four-component synthesis of 1,2,4,5-tetra-substituted imidazole. The pivotal advantages of this process are easy purification, cost-effectiveness, and high yielding, above all environmentally benign protocol.

Green and efficiently synthesized tetrasubstituted imidazole: introduced bismuth oxide co-doped Lu3+, Er3+ as a novel reusable heterogeneous nanocatalyst

Nano-structured Bi1.5(Lu, Er)0.5O3 was synthesized efficiently and utilized as a novel environmentally benign and recyclable heterogeneous catalyst for the synthesis of tetrasubstituted imidazole derivatives in water under ultrasonic irradiation. This synthesis method offers the several advantages such as green and eco-friendly protocol, operational simplicity, mild reaction conditions, short reaction time, higher yields, and easy work-up procedures. For this purpose, nano-structured bismuth oxide and Lu3+, Er3+ co-doped Bi2O3 with different Lu3+, Er3+ loadings (0.1, 0.5%mol) were synthesized by a simple hydrothermal method. The obtained catalysts were characterized by X-ray diffraction, field emission scanning electron microscopy, transmission electron microscope, Fourier-transform infrared spectroscopy, and UV–Vis absorption spectroscopy. X-ray analyses of obtained bismuth oxide were indexed as monoclinic phase and nano co-doped bismuth oxides (Bi2 – x (Lu, Er) x O3, x = 0.1, 0.5%mol) have tetragonal phase.

Design, synthesis and anticonvulsant activity of new imidazolidindione and imidazole derivatives

New imidazolidindiones and tetra-substituted imidazole derivatives were designed, synthesized, and evaluated for the anticonvulsant activity through pentylenetetrazole (PTZ)-induced seizures and maximal electroshock (MES) tests using valproate sodium and phenytoin sodium as reference drugs, respectively. Most of the target compounds showed excellent activity against pentylenetetrazole (PTZ)-induced seizures with fair to no-activity against MES. Compounds 3d, 4e, 11b, and 11e showed higher activity (120%) than that of valproate sodium in PTZ model. Almost all compounds showed no neurotoxicity, as indicated by the rotarod test. Estimation of physicochemical properties and pharmacokinetic profiles of the target compounds were studied. The chemical structures of the target compounds were characterized by different spectrometric methods and elemental analysis.

Bmim]HSO4-Catalyzed Synthesis of Tetrasubstituted Imidazoles as Potential Mutant Isocitrate Dehydrogenase 1 Inhibitors

An ecofriendly, simple, and efficient one-pot protocol has been developed for the synthesis of 1,2,4,5-tetrasubstituted imidazoles by the reaction of benzil, aryl aldehydes, aliphatic or aromatic amines, and ammonium acetate, catalyzed by the acidic halogen-free ionic liquid [bmim]HSO4 under solvent-free conditions. The advantages of the proposed protocol include high yields, short reaction time, operational simplicity, and recyclability of the catalyst. Eight previously unknown tetrasubstituted imidazoles were synthesized, among which those bearing a cyclopropyl substituent on N1 can be considered as potential mutant isocitrate dehydrogenase 1 (IDH1) inhibitors.

One-Pot Synthesis of Tetra Substituted Imidazoles Catalyzed by Fly Ash Supported Bi2O3-ZnO.

A simple and efficient one pot synthesis of 1,2,4,5-tetra substituted imidazoles is achieved by condensation-cyclization reaction of benzil, aromatic aldehyde, 2-amino ethyl pyrrolidine, ammonium acetate using fly ash loaded Bi₂O₃-ZnO. Different substituted aldehydes have been used in this reaction. The process is operationally simple, environmentally safe and has magnificent yield. Furthermore this catalyst can be recycled at least four times without any loss of activity.

SYNTHESIS, CHARACTERIZATION, AND EVALUATION OF ANTIBACTERIAL AND ANTIDEPRESSANT ACTIVITIES OF NOVEL TETRASUBSTITUTED IMIDAZOLE DERIVATIVES

Objective: The objective of this study is to synthesize 10 novel tetrasubstituted imidazole derivatives and characterizations of them and to evaluate their antibacterial and antidepressant activities.
 Methods: Ten novel tetrasubstituted imidazole derivatives were synthesized on the basis of Radziszewski imidazole synthesis. They were purified by double crystallization, characterized by melting point, thin-layer chromatography, infrared, and nuclear magnetic resonance spectroscopy, and subjected to elemental analysis. They were evaluated for their antibacterial activity by agar disc diffusion method and antidepressant activity by forced swim method and tail suspension method.
 Results: The compounds were synthesized and characterized them, and the structure was confirmed. The compounds were designated as M1 to M10 depending on their substitution. The antibacterial activity was evaluated using disc diffusion test in Bacillus subtilis, Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli using ciprofloxacin 20 μg as standard. All the 10 test drugs show significant antibacterial activity in Gram-positive organism. The antidepressant activity of novel tetrasubstituted derivatives and standard clomipramine using forced swim test and tail suspension method is evaluated in rats. Synthesized novel tetrasubstituted derivatives show a promising antidepressant activity.
 Conclusion: The synthesized compounds find promising antibacterial and antidepressant activities.

A New Tetrasubstituted Imidazole Based Difunctional Probe for UV-spectrophotometric and Fluorometric Detecting of Fe3+ Ion in Aqueous Solution

Two new compounds, 4-(2-bromophenyl-4,5-diphenyl-imidazol-1-yl)aniline(probe 1) and 4-[2,4,5-tris(4-bromophenyl)-1H-imidazol-1-yl]aniline(probe 2), were synthesized via a soft and high-efficiency one-pot microwave- assisted method under solvent-free conditions. Their sensing to different metal ions was detected by UV spectrophotometry and fluorescence spectrometry. Probe 2 revealed highly selective and sensitive UV and fluorescence response to Fe3+ ion. Upon the addition of Fe3+ ion, probe 2 showed obvious color change of the solution, conspicuous absorbance enhancement and relatively quick fluorescence quenching. The detection limit for Fe3+ ion was respectively calculated to be 0.72 μmol/L(fluorescent detection) and 0.48 μmol/L(UV-spectrum detection). Also, probe 2 was bound by Fe3+ ion to form a 1:1 complex. Moreover, preliminary application of probe 2 for detecting Fe3+ ion in aqueous solution was attempted, and satisfying results were obtained.

Experimental and computational study of metal-free Brønsted acidic ionic liquid catalyzed benzylic C(sp3)[sbnd]H bond activation and C[sbnd]N, C[sbnd]C cross couplings

Metal and solvent free synthesis of tetrasubstituted imidazoles and tetrasubstituted pyrazines from 1,2-diketones and aliphatic amines is studied experimentally and computationally. Various ionic liquids (ILs) are taken as a catalyst in 10 mol% for the reaction. The best conversion to products is achieved in the presence of two ILs: [taH4][I4] and[deaH][HSO4]. The low-cost, simple Brønsted acidic IL [deaH][HSO4] catalyzed reaction yields 75% PRO1(1-benzyl-2,4,5-triphenyl-1H-imidazole) and 18% PRO2 (2,3,5,6-tetraphenylpyrazine) at 90 °C in 1 h. Further optimization with the IL shows that the products yield can be tuned with changing parameters: time, catalyst loading, and temperature. Optimization shows that PRO2 formation becomes predominant after 3 h. Density functional calculations show that PRO1 formation occurs via condensation to diimine, and further C(sp3)–H activated cyclization stages. An unusual hydrogen shift transition state (∆G‡ = 29.8 kcal) has a crucial role in the ring closure and subsequent annulation to the five- and six-membered rings (PRO1, PRO2).

Four-Component, One-Pot Synthesis of Novel Conjugated Indole-Imidazole Derivatives

A series of new tetrasubstituted imidazoles 2-phenyl-3-(1, 4, 5-triphenyl-1H-imidazol-2-yl)-1H-indole derivatives substituted with –F, Cl, Br, I,-OCH3 and -NHCOCH3 were synthesized using a multicomponent reaction. The compounds were obtained in good yields by easy workup and with high purity

Unusual formation of novel highly substituted N-(3-indolyl)-imidazoles

Treatment of 3-amidoindoles with phosphoryl chloride leads to a dimerization of the resulting iminochlorides to form tetrasubstituted imidazoles in moderate yield. One indole ring undergoes ring-opening to allow the formation of the imidazole ring. This strategically simple synthesis considerably expands the scope of delivering N-indolylimidazoles.

Synthesis of tetra-substituted phenanthroimidazole derivatives using SBA-Pr-SO3H

A one pot four-component reaction of 9,10-phenanthraquinone, aromatic aldehyde, aniline, and ammonium acetate was designed for the preparation of tetrasubstituted imidazoles (phenanthro[9,10-d]imidazole) derivatives in the presence of SBA-Pr-SO3H as a mesoporous solid acid catalyst. Phenanthro[9,10-d]imidazole derivatives were produced by the use of this technique in short reaction times and good to high yields. SBA-15 (Santa Barbara Amorphous), as a hexagonal mesoporous silica with 6 nm pore diameter, was synthesized and then its internal surface was modified with (3-mercaptopropyl)trimethoxysilane following an oxidation process to gain SBA-Pr-SO3H. The latter was then characterized; SEM image showed uniform particles about 700-900 nm and TEM image demonstrated the presence of parallel channels, which resemble the pores configuration of SBA-15. Additionally, the weight reduction in TGA curve in the temperature range of 200-600 °C (about 20% mass loss) established that the anchored propyl sulfonic acid groups onto the SBA-15 pores is about 1.2 mmol/g. This data was also confirmed by back-titration of SBA-Pr-SO3H with standardized NaOH and HCl solutions.

Elemental Sulfur‐Promoted Aerobic Cyclization of Ketones and Aliphatic Amines for Synthesis of Tetrasubstituted Imidazoles

AbstractElemental sulfur‐promoted cyclization for the one‐pot synthesis of tetra‐substituted imidazoles from benzylamines and ketones is described. Elemental sulfur combined with molecular oxygen as the benign co‐oxidant was found to be the key for the high efficiency of this transformation under metal‐free conditions. A range of tetrasubstituted imidazoles were synthesized from simple ketones and amines with good functional group tolerance.magnified image

Citrate trisulfonic acid: A heterogeneous organocatalyst for the synthesis of highly substituted Imidazoles

Citrate trisulfonic acid (CTSA), as a novel recyclable and eco‐benign organocatalyst, was employed for the efficient and one‐pot synthesis of trisubstituted imidazoles and tetrasubstituted imidazoles using aldehydes, ammonium acetate or aniline, and benzoin, benzyl, or 9,10‐phenanthrenequinone under solvent‐free conditions providing high to excellent yields. CTSA is easily prepared via the reaction of trisodium citrate and chlorosulfonic acid in high purity. Compared to the conventional procedures, the present method offers several advantages, including high yields, easy work‐up, short reaction time, reusability of the catalyst, and simple purification of the products.

Synthesis of some Novel Imidazoles Catalyzed by Co3O4 Nanoparticles and Evaluation of their Antibacterial Activities.

The multi-component condensation of benzil, primary amines, ammonium acetate and various aldehydes was efficiently catalyzed using cobalt oxide nanoparticles under ultrasonic irradiation. This approach describes an effective and facile method for the synthesis of some novel 1,2,4,5-tetrasubstituted imidazole derivatives with several advantages such as high yields and short reaction times and reusability of the catalyst. Moreover, the prepared heterocyclic compounds showed high antibacterial activity against some pathogenic strains. The facile and efficient approaches for the preparation of Co3O4 nanoparticles were carried out by one step method. The synthesized heterogeneous nanocatalyst was characterized by spectroscopic analysis including EDX, FE-SEM, VSM, XRD and FT-IR analysis. The as-synthesized cobalt oxide nanoparticles showed paramagnetic behaviour in magnetic field. In addition, the catalytic influence of the nanocatalyst was examined in the one-pot reaction of primary amines, benzil, ammonium acetate and diverse aromatic aldehydes under ultrasonic irradiation. All of the 1,2,4,5-tetrasubstituted imidazoles were investigated and checked with m.p., 1H NMR, 13C NMR and FT-IR spectroscopy techniques. The antibacterial properties of the heterocycles were evaluated in vitro by the disk diffusion against pathogenic strains such as Escherichia coli (EC), Bacillus subtillis (BS), Staphylococcus aureus (SA), Salmonellatyphi (ST) and Shigella dysentrae (SD) species. In this research cobalt oxide nanostructure was used as a robust and green catalyst in the some novel imidazoles. The average particle size measured from the FE-SEM image is found to be 20-30 nm which confirmed to the obtained results from XRD pattern. Various electron-donating and electron-withdrawing aryl aldehydes were efficiently reacted in the presence of Co3O4 nanoparticles. The role of the catalyst as a Lewis acid is promoting the reactions with the increase in the electrophilicity of the carbonyl and double band groups. To investigate the reusability of the catalyst, the model study was repeated using recovered cobalt oxide nanoparticles. The results showed that the nanocatalyst could be reused for five times with a minimal loss of its activity. We have developed an efficient and environmentally friendly method for the synthesis of some tetrasubstituted imidazoles via three-component reaction of benzil, primary amines, ammonium acetate and various aldehydes using Co3O4 NPs. The present approach suggests different benefits such as: excellent yields, short reaction times, simple workup procedure and recyclability of the magnetic nanocatalyst. The prepared 1,2,4,5-tetrasubstituted imidazoles revealed high antibacterial activities and can be useful in many biomedical applications.

Synthesis of Highly Sensitive Fluorescent Probe Based on Tetrasubstituted Imidazole and Its Application for Selective Detection of Ag+ Ion in Aqueous Media

A small molecule fluorescent probe, 4-[2-(4-chlorophenyl)-4,5-diphenyl-1H-imidazol-1-yl]aniline(L) for detecting Ag+ ion was gently synthesized via one-pot multi-component reaction catalyzed by H3[PW12O40] under solvent-free microwave irradiation. When the concentration of Ag+ ion changed from 0 to 8.0×10−6 mol/L in the solution of H2O/CH3OH(19:1, volume ratio), the fluorescence emission spectrum was blue-shifted and accompanied by a gradual increase in fluorescence intensity with a low detection limit of 3.0×10−11 mol/L. Moreover, UV-Vis absorption titration experiment demonstrated a 1:1 stoichiometric ratio and an association constant of (9.95±0.44)×105 L/mol between probe L and Ag+ ion, and thus their complexation mechanism was also proposed and verified. More importantly, this fluorescent probe was remarkably specific for Ag+ ion under the interference of other metal ions and exhibited a wide pH application range of 4.0―8.0. Additionally, preliminary application of this probe was also carried out and satisfactory results were shown.