Substituted Imidazole Derivatives Research Articles

ChemInform Abstract: Erbium Triflate Promoted Multicomponent Synthesis of Highly Substituted Imidazoles.

The synthesis of highly substituted imidazole derivatives has been achieved from various α-azido chalcones, aryl aldehydes, and anilines. This multicomponent protocol employs erbium triflate as a catalyst resulting in excellent yield of the imidazoles.

Tuning the adsorption interactions of imidazole derivatives with specific metal cations.

In this work, we report a computational study of the interactions between metal cations and imidazole derivatives in the gas phase. We first performed a systematic assessment of various density functionals and basis sets for predicting the binding energies between metal cations and the imidazoles. We find that the M11L functional in combination with the 6-311++G(d,p) basis set provides the best compromise between accuracy and computational cost with our metal···imidazole complexes. We then evaluated the binding of a series of metal cations, including Li(+), Na(+), K(+), Co(2+), Ni(2+), Cu(2+), Zn(2+), Cd(2+), Ba(2+), Hg(2+), and Pb(2+), with several substituted imidazole derivatives. We find that electron-donating groups increase the metal-binding energy, whereas electron-withdrawing groups decrease the metal-binding energy. Furthermore, the binding energy trends can be rationalized by the hardness of the metal cations and imidazole derivatives, providing a quick way to estimate the metal···imidazole binding strength. This insight can enable efficient screening protocols for identifying effective imidazole-based solvents and membranes for metal adsorption and provide a framework for understanding metal···imidazole interactions in biological systems.

A concise synthesis of highly substituted imidazoles via copper-mediated oxidative C–H functionalization

We herein report a simple and concise route for the synthesis of highly substituted imidazole derivatives via copper-mediated oxidative C–H functionalization in good to high yields. The advantage of the reaction lies in its mild reaction conditions and readily available starting materials.

Erbium Triflate Promoted Multicomponent Synthesis of Highly Substituted Imidazoles

The synthesis of highly substituted imidazole derivatives has been achieved from various α-azido chalcones, aryl aldehydes, and anilines. This multicomponent protocol employs erbium triflate as a catalyst resulting in excellent yield of the imidazoles.

Effect of 1-substituted imidazole derivatives for the curing process of epoxy- -isocyanate composition

Abstract The kinetics of the curing process of isocyanate-epoxy materials hardened in the presence of 1- substituted imidazole derivatives was studied by the Coast-Redfern method. The extent of a conversion parameter of the curing process in two ways was calculated: DSC (peak area integration) and rheology (viscosity changes). The activation energy values were determined for epoxy-isocyanate cured in the presence of 0.5; 1.0 and 2.0 phr 1-substituted imidazole derivatives respectively. Increasing of accelerators amount results in decreasing the activation energy and other kinetic parameters.

A combined experimental and theoretical investigation of imidazole–carbazole fluorophores

Two different tri and tetra substituted imidazole derivatives connected with carbazole moiety were synthesized by using Vilsmeier–Haack formylation followed by multicomponent cyclisation reaction. Results obtained from spectroscopic (1H NMR, 13C NMR, Mass) and single crystal X-ray diffraction analysis of synthesized compound revealed its chemical structure. UV–vis and photoluminescence studies in various solvents with different polarity demonstrated that these compounds were sensitive to the polarity of the microenvironment in the excited state. Results of TGA and AFM analysis demonstrated that the compounds exhibited good thermal and morphological stabilities over very harsh conditions. DFT calculations were performed to elucidate the structural and electrochemical properties of these compounds. The computed result revealed the ground state of the molecules was majorly stabilized by σ→σ⁎ interaction and the natural hybrid orbital compositions and occupancies predict that the bonding interactions between C and N centers possess pure σ bond with sp2 hybridization.

Facile and Efficient Syntheses of a Series of N-Benzyl and N-Biphenylmethyl Substituted Imidazole Derivatives Based on (E)-Urocanic acid, as Angiotensin II AT1 Receptor Blockers

In the present work, a facile and efficient route for the synthesis of a series of N-substituted imidazole derivatives is described. Docking studies have revealed that N-substituted imidazole derivatives based on (E)-urocanic acid may be potential antihypertensive leads. Therefore, new AT1 receptor blockers bearing either the benzyl or the biphenylmethyl moiety at the N-1 or N-3 position, either the (E)-acrylate or the propanoate fragment and their related acids at the C-4 position as well as a halogen atom at the C-5 position of the imidazole ring, were synthesized. The newly synthesized analogues were evaluated for binding to human AT1 receptor. The biological results showed that this class of molecules possesses moderate or no activity, thus not always confirming high docking scores. Nonetheless, important conclusions can be derived for their molecular basis of their mode of action and help medicinal chemists to design and synthesize more potent ones. An aliphatic group as in losartan seems to be important for enhancing binding affinity and activity.

QSAR and pharmacophore approach on substituted imidazole derivatives as angiotensin II receptor antagonists

A QSAR analyses of 32 aminomethyl and acylaminomethyl substituents derivatives were carried out to interpret the relationship between structural properties and angiotensin II AT1 receptor activity. Two-dimensional (2D-QSAR), Group-based (G-QSAR), 3D-QSAR, and pharmacophore mapping studies were performed using partial least square and k-nearest neighbor methodology coupled with various feature selection methods, viz. stepwise, genetic algorithm, and simulated annealing (SA) to derive QSAR models which were further validated for statistical significance and predictive ability by internal and external validation. The activity contributions of whole compounds and their substituents were determined from regression equation. The statistically significant best 2D-QSAR model 1 having r 2 = 0.8754 and q 2 = 0.7231 with $$ {\text{pred}}\_r^{ 2} = \, 0. 8 3 8 9 $$ was developed by GA-PLS with the descriptors like SdssCcount, SssNHcount and SaaaCcount. The best Group-based QSAR model-5 having r 2 = 0.7516 and q 2 = 0.6714 with $$ {\text{pred}}\_r^{ 2} = \, 0. 7 3 0 9 $$ was developed by GA-PLS. The 2D-QSAR results agreed with those from the Group based QSAR model and suggested the structural features of SssOE-index, Mol.Wt and SssNHE-index functionality that would enhance the antihypertensive activity of the imidazole derivatives in this series. The results of two-dimensional, Group-based QSAR showed that a combination of topological indices, hydrophobic properties, and auto-correlation descriptors of different atomic properties could be explored to design potent antihypertensive agents. The k-nearest neighbor approach was used to generate three-dimensional quantitative structure–activity relationship (3D-QSAR) models for these sets of molecules. The present study is an attempt in this direction seeking for the development and comparison of QSAR models of substituted imidazoles by different feature selection methods, which ultimately establishes the superiority of the GA-based models. Statistically genetic algorithm (GA) selection k-nearest neighbor (GA-kNN-MFA) model with respect to both the internal (q 2 = 0.7856) as well as external (pred_r 2 = 0.8193) model validation and correctly predicts the activity of calculated 78.56 % and calculated 81.93 % for the training and test set, respectively. Continuing with the series of substituted imidazoles derivatives, chemical feature-based pharmacophore models with lowest RMSD value (0.1397 A), consisting of one aromatic carbon center, two hydrogen bond acceptor, and one hydrogen bond donor features, was developed. The information rendered by 2D-QSAR, Group-based QSAR, k-nearest neighbor, and pharmacophore identification models may lead to a better understanding of structural requirements of antihypertensive agents and can help in the design of novel potent molecules.

ChemInform Abstract: Microwave Irradiated Synthesis of Some Substituted Imidazole Derivatives (IV) as Potential Antibacterial and Anticancer Agents.

AbstractAll the new aryl‐substituted imidazole derivatives (IV) (10 examples) show good antibacterial activity against gram‐negative bacterial strains and significant cytotoxicity against DLA and EAC cell lines.

Convenient Synthesis of Highly Substituted Imidazole Derivatives

A one-pot synthesis of the trisubstituted imidazole derivatives from α-acetoxy-α-chloro-β-keto-esters, aldehydes, and ammonium acetate has been developed.

SBA-15/TFE (SBA-15/2,2,2-trifluoroethanol) as a suitable and effective metal-free catalyst for the preparation of the tri- and tetra-substituted imidazoles via one-pot multicomponent method

Adduct of unfunctionalized SBA-15 mesoporous and 2,2,2-trifluoroethanol (SBA-15/TFE) acts as a catalyst for the reaction between of an aldehyde, amine and ammonium acetate with benzil to provide an entry in the synthesis of high substituted imidazole derivatives as a synthetic potential and a pharmaceutical interest compound via one-pot multicomponent method. The present method carries the advantages of being performed under the neutral conditions and requires no activation or modification of the substrates. The catalyst can be reused without an obvious loss of the catalytic activity.

Studies on interaction between an imidazole derivative and bovine serum by spectral methods

The interaction between a trifluoromethyl substituted imidazole derivative 2-(4-(trifluoromethyl)phenyl)-1-phenyl-1H-imidazo[4,5-f] [1,10] phenanthroline (tfmppip) and bovine serum albumin (BSA) was investigated by solution spectral studies. The observed experimental result shows that the imidazole derivative has strong ability to quench the fluorescence of BSA by forming complex which is stabilized by electrostatic interactions. The effective quenching constants (ksv) were 2.79×104, 2.51×104, and 2.32×104 at 301, 310 and 318K respectively. The Stern–Volmer quenching constant (Ksv), binding site number (n), apparent binding constant (KA) and corresponding thermodynamic parameters (ΔG, ΔH and ΔS) were calculated. The distance between the donor (BSA) and acceptor (tfmppip) was obtained according to fluorescence resonance energy transfer (FRET). Conformational changes of BSA were observed from synchronous fluorescence technique. The effect of metal ions such as Cu2+, Zn2+, Ca2+, Mg2+, Ni2+, Co2+ and Fe2+ on the binding constants between the imidazole derivative and BSA were also studied.

The interaction between heteroditopic pyridine–nitrogen NHC with novel sulfur NHC ligands in palladium(0) derivatives: Synthesis and structural characterization of a bis-carbene palladium(0) olefin complex and formation in solution of an alkene–alkyne mixed intermediate as a consequence of the ligands hemilability

We have synthesized a new class of heteroditopic chelating ligands bearing the phenylthiomethyl group and variously substituted imidazole derivatives and the corresponding complexes [Pd(η2-ma)(R-NHC-CH2-SPh) (ma=maleic anhydride; R=methyl, mesityl, di-i-propylphenyl). We have compared their chemical characteristics and reactivity with those of similar palladium(0) complexes bearing the R-NHC-CH2-Py ligands.The hemilability of the above-mentioned moieties is apparent when their palladium derivatives react with an excess of the same or different heteroditopic ligands. In these cases, we obtained complexes bearing maleic anhydride and two mono-coordinated heteroditopic ligands bound to the same metal center. However, at variance with the generally accepted opinion, precipitation of AgBr does not warrant the quantitative formation of the bis-heteroditopic Pd(0) derivative and in some cases, a reaction involving a heterogeneous equilibrium is observed.The reaction of the palladium(0) carbene–sulfur or carbene–nitrogen complexes with the alkyne dimethyl-2-butynedioate (dmbd) to give palladacyclometallate derivatives is not always warranted and formation of the intermediate [Pd(η2-ma)(η2-dmdb)(κ1-Mes-NHC-CH2-SPh)] is detected only in one case.Finally, we have carried out a diffractometric study on the solid-state structures of two derivatives and in particular we describe the configurations of the complex [Pd(η2-ma)(κ1-Me-NHC-CH2-SPh)2] and of [Pd(η2-ma)(Me-NHC-CH2-SPh)].

New pentamethylene-bridged bis-imidazolium dication ligands and its palladium(II) complexes: Synthesis, characterization, and catalysis

Two new pentamethylene-bridged bis-imidazolium dication ligands (L1=1,5-bis(1-(4-cyanophenyl)-imidazolium-1-yl)pentane dibromide) and L2=1,5-bis(1-(4-methoxyphenyl)-imidazolium-1-yl)pentane dibromide) bearing CPI (1-(4-cyanophenyl)-imidazole) and MPI (1-(4-methoxyphenyl)-1H-imidazole)-functionality have been prepared via the reaction of 1,5-dibromopentane with a substituted imidazole derivative. The imidazolium ligand L1 and L2 on reaction with [PdBr2(C6H5CN)2] led to the formation of neutral bis-imidazolium dication palladium(II) complexes [L1] [PdBr4] [1] (L1=1,5-bis(1-(4-cyanophenylimidazolium-1-yl)pentane) and [L2] [PdBr4] [2] (L2=1,5-bis(1-(4-methoxyphenyl) imidazolium-1-yl)pentane), respectively. The new ligands as well as their palladium(II) complexes, has been characterized by elemental analysis, electronic, IR, 1H and 13C NMR, FAB–MS and ESI–MS spectroscopy. The molecular structure of the representative complex [L2] [PdBr4] [2] have been determined by single crystal X-ray analysis. Complex 2 exhibits the strong intra- and inter-molecular C–H···X (X=Br, O, π) weak interactions, which plays an important role in stabilizing the crystal packing. Furthermore, the C–H···O interactions in 2 lead to a single-helical motif. The complexes 1 and 2 exhibited good activity in a model Suzuki–Miyaura coupling reaction.

ChemInform Abstract: Palladium‐Catalyzed Three‐Component Reaction of 2,3‐Allenyl Amines, Isocyanates, and Organic Halides: A Diversified Assembly of Imidazolidinones.

AbstractVarious substituted imidazole derivatives are efficiently synthesized by the present new three‐component reaction of allenyl amines with isocyanates and organic iodides under mild conditions.

ChemInform Abstract: Substituted Imidazole Derivatives as Novel Cardiovascular Agents.

AbstractA variety of novel substituted imidazole derivatives are prepared and evaluated in vivo for their hypotensive activities and acute toxicities.

Substituted imidazole derivatives as novel cardiovascular agents

A series of novel substituted imidazole derivatives were synthesized and have been screened in vivo for their hypotensive and acute toxicity activities. Out of seventeen compounds eight compounds (2b, 2c, 3b, 3c, 3f, 4a, 4b and 4c) have shown good hypotensive and bradycardiac responses. Compounds 3b, 3c, 3f and 4c have shown better activity than reference drug clonidine. All the compounds have shown ALD50>1000 mg/kg with maximum in 2e and 4c (>1200 mg/kg).

ChemInform Abstract: Synthesis, Antimicrobial and Antiviral Evaluation of Substituted Imidazole Derivatives.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: Tandem Oxidation Process Using Ceric Ammonium Nitrate: Three‐Component Synthesis of Trisubstituted Imidazoles under Aerobic Oxidation Conditions.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Tandem Oxidation Process Using Ceric Ammonium Nitrate: Three-Component Synthesis of Trisubstituted Imidazoles Under Aerobic Oxidation Conditions

By combining a ceric ammonium nitrate (CAN)–catalyzed aerobic oxidation of α-hydroxy ketones with a subsequent three-component condensation reaction using aldehydes and ammonium acetate, highly substituted imidazole derivatives can be assembled. This reaction is an important approach for the synthesis of highly substituted imidazole derivatives and was carried out in good to excellent yields in ethanol as an environmentally benign solvent.