Trisubstituted Imidazoles Research Articles

Silver-Catalyzed Isocyanide-Isocyanide [3+2] Cross-Cycloaddition Involving 1,2-Group Migration: Efficient Synthesis of Trisubstituted lmidazoles.

Imidazole ring is an important five-membered aromatic heterocycle that is widely present in natural products and synthetic molecules. The isocyanide-isocyanide [3+2] cross-cycloaddition reaction constitutes a straightforward method to access imidazoles starting from the easily available chemicals. So far, only three successive reports are known and all lead to the formation of 1,4-disubstituted imidazoles. Here, we report the first isocyanide-isocyanide [3+2] cross-cycloaddition reaction allowing for the formation of 1,4,5-trisubstituted imidazoles under silver catalysis. An unexpected 1,2-migration of sulfonyl, alkoxycaybonyl, and carbamoyl groups took place during the cyclization process that is responsible for the formation of trisubstituted imidazoles. This report displayed a mechanistically novel synthetic method toward a variety of imidazole derivatives, which are otherwise difficult to access by conventional methods.

Selective Recognition of Zn2+ Ion Using 2,4‐Bis(2‐pyridyl)‐5‐(4‐pyridyl)imidazole: Spectra and Molecular Structure

AbstractA trisubstituted imidazole, 2,4‐bis(2‐pyridyl)‐5‐(4‐pyridyl)imidazole (LH) in presence of other cations, selectively binds Zn2+ ion by exhibiting characteristic absorption and fluorescence spectral behaviors. Upon gradual addition of ZnCl2 to DMSOsolution of LH, intensity of peak at 318 nm decreased. A new peak appeared at 364 nm along with an isosbestic point at 337 nm. The DMSOsolution of LH upon irradiation with λ=320 nm exhibited an emission peak at 391 nm, which decreased gradually with increase in Zn2+ ion concentrations. A new emission peak also appeared at 445 nm along with a quasi isoemissive point at 413 nm. The HEPES buffered aqueous DMSO solution (2:8 v/v, pH=7.4) of free LH, upon excitation with 320 nm radiation gave emission at 396 nm which shifted to 445 nm during incremental additions of Zn2+ ion. The red shift is due to binding of Zn2+ ion to LH. The binding is accompanied by deprotonation of acidic hydrogen in imidazole ring and orientation of two 2‐pyridyl rings in near‐planarity with imidazolate ring. The Zn2+ ion can be detected with a calculated limit of 6.5×10−7 M. The Job's plot revealed that ligand binds Zn2+ ion in 1:2 ratios and was further confirmed by single crystal X‐ray diffraction method.

BF3/nano-sawdust as a green, biodegradable and inexpensive catalyst for one-pot synthesis of tri-substituted imidazoles under solvent free conditions

BF3/nano-sawdust as a green, inexpensive, natural, biodegradable and readily available biopolymer solid acid catalyst was synthesized and characterized. This catalystwas used successfully for the synthesis of various tri-substituted imidazoles in high yields under solvent free conditions.

One-Pot Synthesis of 2,4,5-Trisubstituted Imidazoles via [2 + 2 + 1] Cycloannulation of 1,3-Bishet(aryl)-monothio-1,3-diketones, α-Substituted Methylamines and Sodium Nitrite through α-Nitrosation of Enaminones

An efficient one-pot synthesis of a series of diversely functionalized trisubstituted 4(5)het(aroyl)-2,5(4)-het(aryl)/alkylimidazoles from readily available 1,3-bishet(aryl)monothio-1,3-diketones has been reported. This novel sequential one-pot, three step protocol, wherein three new carbon nitrogen bonds are formed in contiguous fashion, involves in situ generation of enaminones by reaction of monothio-1,3-diketones with α-substituted methylamines, followed by their α-nitrosation with sodium nitrite and subsequent base mediated intramolecular heterocyclization of the resulting α-hydroxyiminoimines to trisubstituted imidazoles in high yields under mild conditions. These newly prepared 4(5)-het(aroyl)-5(4)-het(aryl)/alkylimidazoles are shown to exist as tautomeric mixture, however, their subsequent alkylation with methyl iodide in the presence of potassium carbonate affords 1-N-methy-2,5-bishet(aryl)-4-het(aroyl)imidazoles in highly regioselective fashion in most of the cases. Synthesis of few 4(5)-(2-hydroxyphenyl)-2,5(4)-substituted imidazoles, which are known to be good coordinating ligands, has also been reported. A probable mechanism for the formation of these imidazoles from hydroxyiminoimine intermediates has also been suggested.

Tungstophosphoric acid supported on core-shell polystyrene-silica microspheres or hollow silica spheres catalyzed trisubstituted imidazole synthesis by multicomponent reaction

Materials based on tungstophosphoric acid supported on core-shell polystyrene-silica microspheres or hollow silica spheres were prepared, characterized and used as catalysts in the synthesis of trisubstituted imidazoles by a multicomponent reaction under solvent-free conditions.For the preparation of the two different silica-based structures, silica was synthesized using tetraethylorthosilicate (TEOS) as precursor in an ethanol-ammonium solution and polystyrene spheres as template or core. The formation and growth of the silica layer to obtain the core-shell microspheres were followed by 24h. Then, the hollow spheres were obtained by calcination of the core-shell material at 500°C for 3h. Both supports were impregnated with tungstophosphoric acid (TPA) solutions.A smooth appearance of the spheres was observed by scanning electron microscopy (SEM). Mesoporous materials were obtained, without important microporosity, as determined from N2 adsorption-desorption isotherms. The Fourier transform infrared (FT-IR) spectra confirmed that complete removal of the polystyrene core can directly be achieved by calcination at 500°C, and also that Keggin undegraded TPA species are present in the impregnated solids. The acidic characteristics of the solids were evaluated by potentiometric titration, showing that they exhibit very strong acid sites. Moreover, peaks assigned to crystalline forms of TPA were observed by XRD.The yields obtained in the solvent-free synthesis of 2,4,5-triphenyl-1H-imidazole and other eight trisubstituted imidazoles were high, without formation of by-products resulting from competitive reactions or decomposition products, so the prepared materials are highly selective catalysts.

ChemInform Abstract: Base‐Mediated Syntheses of Di‐ and Trisubstituted Imidazoles from Amidine Hydrochlorides and Bromoacetylenes.

AbstractA new transition metal‐free method for the preparation of title compounds (III), (V) and (VII) is reported.

Zinc sulfamate catalysed synthesis of trisubstituted imidazole

Numerous imidazole derivatives are reported as pharmacological agents like azomycin, clotrimazole, Miconazole, ergothionine, clonidine and moxonidine. One of the most important applications of imidazoles derivatives are treatment for denture and cancer therapy. Imidazoles are in general, well known to possess, anti-cancer activity. These compounds are 5 membered planar ring, soluble in water and other polar solvents. Radziszewski and Jaapproposed the first synthesis of the imidazole corein 1882, starting from 1,2-dicarbonyl compounds, aldehydes and ammonia to obtain 2,4,5-triphenylimidazole [1, 2].

Isocyanurate-based periodic mesoporous organosilica (PMO-ICS): a highly efficient and recoverable nanocatalyst for the one-pot synthesis of substituted imidazoles and benzimidazoles

Isocyanurate bridging periodic mesoporous organosilica (PMO-ICS) was shown to be a highly active and efficient recyclable nanocatalyst for three-component synthesis of trisubstituted imidazole as well as benzimidazole derivatives in EtOH.

Doping of copper (I) oxide onto a solid support as a recyclable catalyst for acetylation of amines/alcohols/phenols and synthesis of trisubstituted imidazole

A study of copper-mediated C–heteroatom especially C–N and C–O bond formations using simpler methodologies has been carried out. In the present work, acetylation of various substrates such as amines, phenols and alcohols; synthesis of 2,4,5-trisubstituted imidazole is done using simple and easily available starting materials. Copper (I) oxide was synthesized in situ by the reduction of Fehling’s solution with glucose followed by its anchoring onto different supports like silica, HAP, basic alumina and cellulose. Comparison and contrasts between the reactivity of copper (I) oxide supported onto different supports for these reactions are made. The reactivity of copper (I) oxide seems to be largely dependent on the nature of support and the most active catalyst for a particular reaction was further characterized by different spectroscopic techniques such as FTIR, XRD, TGA, XPS, SEM, TEM and AAS. The catalysts were found to be stable, easily recyclable without any significant loss in activity. Applications of solid supported copper (I) oxides (where solid support is silica, HAP, cellulose and basic alumina) are studied for various organic transformations with special emphasis on C–N and C–O bond formation reactions.

Base‐Mediated Syntheses of Di‐ and Trisubstituted Imidazoles from Amidine Hydrochlorides and Bromoacetylenes

A new transition metal-free method for the preparation of substituted imidazoles from easy-to-handle amidine hydrochlorides and bromoacetylenes has been developed. The reactions proceed in air and use inexpensive K2 CO3 as base. Additions of 2,2'-bipyridine and water have beneficial effects on the product yields. Various di- and trisubstituted imidazoles have been prepared in good yields (up to 88 %).

ChemInform Abstract: Graphene Oxide—Chitosan Bionanocomposite: A Highly Efficient Nanocatalyst for the One‐Pot Three‐Component Synthesis of Trisubstituted Imidazoles under Solvent‐Free Conditions.

AbstractImidazoles (III) are rapidly, conveniently, and eco‐friendly obtained by reaction of benzil (I) or benzoin with various aromatic aldehydes and ammonium acetate.

Ion Chromatography of Tri-Substituted Imidazolium Ionic Liquid Cations: Method and Application for Octanol–Water Partition Coefficient (KOW) Determination

A method was developed for simultaneous determination of four trisubstituted imidazolium ionic liquid cations (1-ethyl-2,3-dimethylimidazolium, 1-propyl-2,3-dimethylimidazolium, 1-butyl-2,3-dimethylimidazolium, 1-pentyl-2,3-dimethylimidazolium) by ion chromatography using a carboxylic acid cation exchanger bonded to a silica-based column and direct (nonsuppressed) conductivity detection. The effects of the type of eluents, organic acid concentration, acetonitrile volume fraction, and column temperature on the cations retention were investigated. The optimal conditions for the method were 5 mmol L−1 methanesulfonic acid +10% acetonitrile as an eluent, 1.0 mL min−1 flow rate, and a column temperature of 30°C. The detection limit (S/N = 3) were 0.82–2.39 mg L−1 for the cations. The method was validated, accurate, and reproducible. This method was successfully applied to determine trisubstituted imidazolium ionic liquid cations in spiked tap water. The octanol–water partition coefficients (Kow) of these four trisubstituted imidazole substances were also reported in this study.

ChemInform Abstract: Nano Copper and Cobalt Ferrites as Heterogeneous Catalysts for the One‐Pot Synthesis of 2,4,5‐Tri Substituted Imidazoles.

AbstractA simple one‐pot synthesis is presented for the synthesis of trisubstituted imidazoles using magnetic recyclable spinel nano copper and cobalt ferrites by the condensation of benzil, different aromatic aldehydes, and ammonium acetate in ethanol.

ChemInform Abstract: Triorganoindium Reagents in Selective Palladium‐Catalyzed Cross‐Coupling with Iodoimidazoles: Synthesis of Neurodazine.

AbstractThe cross‐coupling sequence is used for preparation of neurodazine (VI) and analogs.

ZnO nanorods: Efficient and reusable catalysts for the synthesis of substituted imidazoles in water

A simple procedure has been developed for the synthesis of ZnO nanorods (ZnO NRs). The newly synthesized crystals were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM). Moreover, the catalytic activity was examined in the one-pot, three-component synthesis of 2,4,5-triaryl-1H-imidazoles in water under reflux conditions. The results confirmed ZnO NRs to be mild, benign and effective catalysts for the preparation of tri-substituted imidazoles in high yield via an operationally simple and environmentally friendly procedure. Furthermore, the catalyst can be conveniently recovered and reused for at least three runs without any activity loss.

Graphene oxide–chitosan bionanocomposite: a highly efficient nanocatalyst for the one-pot three-component synthesis of trisubstituted imidazoles under solvent-free conditions

An eco-friendly and clean GO–biopolymer heterogeneous nanocatalyst was prepared and characterized, which efficiently promoted an important organic reaction.

Trisubstituted Imidazole Synthesis: A Review

Trisubstituted Imidazole Synthesis: A Review

Triorganoindium reagents in selective palladium-catalyzed cross-coupling with iodoimidazoles: synthesis of neurodazine.

Triorganoindium reagents (R3In, R = aryl, heteroaryl, alkynyl) react selectively under palladium catalysis with N-benzyl-2,4,5-triiodoimidazole to afford the C-2 monocoupling products. The reaction proceeds efficiently for a variety of aryl- and heteroarylindium reagents with the transfer of all three organic groups attached to the metal. The coupling products can be used in a subsequent two-fold cross-coupling to give trisubstituted imidazoles in good yields. This approach was employed to synthesize neurodazine and analogues in good yields.

ChemInform Abstract: Synthesis of Trisubstituted Imidazoles via a Convergent Reaction Network from Methyl Ketones and Benzoins.

Abstract A novel method for constructing trisubstituted imidazoles has been created using simple and readily available aromatic ketones, benzoins, and ammonium acetate as starting materials. The new synthetic strategy utilized a convergent integration of two self-labor domino sequences, providing a typical example for logical self-organization synthesis.

ChemInform Abstract: An Expedient One‐Pot Synthesis of Highly Substituted Imidazoles Using Supported Ionic Liquid‐Like Phase (SLLP) as a Green and Efficient Catalyst and Evaluation of Their anti‐Microbial Activity.

AbstractAn efficient one‐pot multicomponent route for the synthesis of trisubstituted imidazole derivatives (III) (9 examples) and (V) (5 examples) under ultrasonic irradiation or classical thermal conditions is developed using a supported ionic liquid‐like phase as catalyst.