Azolium Salts Research Articles

(Benz)imidazo[1,2-a]quinolinium Salts: Access via Unprecedented Regiospecific non-AAIPEX Strategy and Study of Their Tunable Properties.

An unprecedented non-AAIPEX protocol has been developed to access diverse monosubstituted cationic polycyclic heteroaromatic compounds (cPHACs) from the readily available azolium salts and phenacyl bromides via Ru(II)-catalyzed tandem annulation cum aromatization. This atom-economic protocol executes a range of intermediate steps e. g. double C-H activation, nucleophilic addition, annulation, and dehydration cum aromatization in one-pot manner under the generation of H2O as the sole byproduct. Moreover, the systematic tunability of photo-physical and electrochemical properties of these new class of cPHACs can be authenticated from the DFT calculated frontier molecular orbital energies that might be beneficial for their potential applications in optoelectronics and DNA intercalation.

Photo-Catalyzed Acyl Azolium Promoted Selective α-C(sp3 )-H Acylation of Acetone via HAT: Access to Thermodynamically Less Favoured (Z)-α,β-Unsaturated Ketones.

Mono α-acylation of acetone has been achieved for the first time by reacting with bench-stable acyl azolium salts under violet-LED light at room temperature. The intermolecular hydrogen atom transfer (HAT) from acetone to triplet state of azolium salts under violet LED irradiation resulted in thermodynamically less favourable (Z)-α,β-unsaturated ketones with up to 99 : 1 selectivity via C-C bond formation. This compelling protocol access the desired α-C(sp3 )-H acylation product under metal-, ligand- and oxidant-free conditions on a wide range of substrates.

Investigation of the intermolecular origins of high and low heats of fusion in azolium salt phase change materials for thermal energy storage

Azolium salts are potential intermediate-temperature phase change materials. Crystallographic analysis shows that H-bonding along with other intermolecular interactions strongly influence the melting enthalpy of azolium salts.

Synthesis and characterization of Markó-type (NHC)Pt(dvtms) complexes and their evaluation in the hydrosilylation reaction of alkenes

A series of Markó-type complexes of the structure (NHC)Pt(dvtms) were prepared (dvtms = 1,1,3,3-tetramethyl-1,3-divinyldisiloxane, NHC = N-heterocyclic carbene, Im = imidazole, Trz = triazole; NHC = iPrIm (1), PhIm (2), 2-PyIm (3), MesTrzMeIm (4) Mes(Me)Trz (5) MeIm (6), MesIm(7)), with 5 being the first reported abnormal 1,2,3-triazole-5-ylidene Pt(0) complex. All these compounds are easily accessible using Karstedt's catalyst [Pt2(dvtms)3], the respective azolium salts (L1-7) and potassium tert-butoxide. Comprehensive characterization by NMR spectroscopy (1H, 13C, 29Si, 195Pt), SC-XRD and CHNS analysis is presented. The hydrosilylation reactions of oct-1-ene or MMVi with MDHM, respectively, where the latter mimics the cross linking of silicones, are efficiently catalyzed at remarkable low Pt-loadings of 50–100 ppm.

Synthesis, characterization and molecular docking of benz-imidazolium Se-adducts: Antimicrobial and anticancer studies

N-heterocyclic carbene (NHC) based compounds are remarkably known for astonishing biological potentials. Coordination of metal center with these compounds could substantially improve the biological potential for better efficacy. In this context, three binuclear azolium salts (S1–S3) and their selenium adducts (C1–C3) were synthesized and assured through various analytical tools. Compounds C1–C3 were confirmed through ESI-MS and mass spectra were found consistent with theoretical values and structural pattern. Synthesized compounds were simulated through computational approach and results were compared with experimental findings which confirm successful synthesis of designed compounds. Synthesized compounds were screened against bacterial strains and interestingly, the studied compounds showed good antimicrobial having IC50 8.41–21.55 and 11.85–20.84 µM against S.aureus and E.coli respectively. The studied compounds showed good antioxidant activity to scavenge DPPH free radicals among which azolium salts were found better in antioxidant potential (IC50 5.75–6.55 µg/mL) than their respective selenium compounds (IC50 12.55–6.12 µg/mL). Interestingly, selenium compounds showed better cytotoxicity against HEK-293 and HepG2 cell lines than that of azolium salts which confirmed the contributing role of selenium for biological potential of compounds. The haemolytic assay against red blood cells showed that selenium compounds are least toxic and can be further trailed for in vivo studies.

Heterobimetallic Complexes Bridged by an Unsymmetrical Bis(NHC) Ligand: Study of Enhanced Catalytic Activity in Tandem Transformations and Understanding of Cooperativity between the Metal Centers.

The bis(azolium) salt [L1-H2 ]Br2 was found to serve as a suitable platform for accessing the heterobimetallic IrIII -M (M=PdII /AuI ) and PdII -IrIII complexes. Initially, selective mono-metalation of [L1-H2 ]Br2 yielded an orthometalated IrIII - or non-orthometalated PdII -complex. Sequential metalation of the mono-IrIII complex resulted in the formation of heterobimetallic IrIII -PdII /AuI complexes. Similarly, a distinct heterobimetallic PdII -IrIII complex was synthesized starting from the mono-PdII complex. Further, the corresponding homobimetallic IrIII -IrIII and PdII -PdII complexes were directly obtained from [L1-H2 ]Br2 . Additionally, monometallic PdII and IrIII analogues were synthesized from [L2-H]Br and [L3-H]Br, respectively. The heterobimetallic IrIII -PdII and PdII -IrIII complexes were then evaluated as catalysts in various one-pot tandem catalytic reactions in which they demonstrated superior activity than the mixtures of both their corresponding homobimetallic IrIII -IrIII /PdII -PdII and monometallic IrIII /PdII counterparts, under the constant concentrations of metal centers. Moreover, while comparing complexes IrIII -PdII and PdII -IrIII , the former exhibits higher activity in all the studied reactions. All these findings suggest the presence of some form of cooperativity between the two metal centers (Ir and Pd) connected by a single ligand framework in IrIII -PdII and PdII -IrIII complex, with IrIII -PdII displaying better cooperativity that has been validated by electrochemical, NMR, and DFT studies.

N-heterocyclic carbene based Bi-nuclear organoselenium compounds impart a mild biocidal potential compared to their ligands: Synthesis, characterization, computational studies

N-heterocyclic carbene (NHC) based compounds are remarkably known for astonishing biological potentials. Coordination of metal center with these compounds can substantially improve the biological potential for better efficacy. In this context, three binuclear azolium salts (L1-L3) and subsequent selenium adducts L1Se-L3Se were synthesized and assured through analytical techniques. Synthesized compounds were also simulated through computational approach and results were compared with experimental observations that also relatable with biological potentials. Synthesized compounds were screened against bacterial strains and interestingly, the studied compounds showed good antimicrobial potential with MIC values of 7.01, 10.7 and 10.5 µM for S. Aureus (gram positive bacteria) while 12.5, 11.75 and 14.5 µM against E. Coli (gram negative bacteria). The studied compounds showed good antioxidant activity to scavenge DPPH free radicals among which azolium salts were found better in antioxidant potential (IC50 5.75–6.55 µg/mL) than their respective selenium compounds (IC50 9.50–12.75 µg/mL). The hemolytic assay against red blood cells showed that ligands are least toxic comparative to their Se-adducts and can be further trialed for In Vivo studies.

Inhibition of cell proliferation by azolium salts and silver(I)-N-heterocyclic carbene complexes: Synthesis, spectral and X-ray crystallographic characterizations

The study focuses on the synthesis, characterization, and evaluation of silver (I)-N-heterocyclic carbene complexes for their inhibitory effect on cell proliferation. The benzimidazolium salts (3–5) and their respective silver complexes (6–8) were synthesized and characterized by various techniques including FTIR, NMR and X-ray crystallography. The salts and complexes were then evaluated for their ability to inhibit the proliferation of four different cancer cell lines (EA.hy926, HeLa, MDA-MB-231 and A549). MTT assay demonstrated that the salts and complexes exhibited potent cytotoxicity towards all cancer lines. The study highlights the importance of N-heterocyclic carbene ligands in the development of silver-based drugs with anticancer properties.

Direct Access to meta‐Alkylated N‐Arylazolium Salts via Ruthenium Catalyzed Electronically Controlled Site Selective Functionalization: Scope and Mechanistic Aspect

AbstractEffective access to azolium salts with varying stereoelectronic properties has always fascinated the organometallic chemists. Herein, we described a Ru(II)‐catalyzed one‐step access to diverse meta‐alkylated N‐aryl (benz)imidazolium salts (>40 examples) via σ‐bond activation strategy starting from the readily available azolium salts using alkyl bromide. Notably, the present method is compatible with a wide range of azolium salts and secondary/tertiary alkyl bromides, including the biologically relevant motifs. Various control experiments along with the DFT calculation established the reaction pathway of orthometalated Ru(II)‐NHC complex (6) formation followed by the generation of a Ru(III)‐intermediate, which controls the observed meta‐selectivity, via single electron transfer. Crucially, detailed insight of the reaction mechanism helped to comprehend why some substrates are challenging for this methodology.

Insights into the effect of contact ion-pairs on C[sbnd]H bond activation for the synthesis of Ru(III)-NHC complexes: A combined experimental and computational study

The effect of contact ion pairs and comparison of the three halide ions on the electrophilic CH activation during the base-free synthesis of Ru(III)-NHC complexes [RuIII(PyNHCR)(Cl)3(H2O)] (1a; R = Me, and 1b; R = iPr) have been investigated. DFT modelling of two pathways for the formation of Ru(III)-NHC complexes, viz. halide coordination pathway and ion-pair pathway, reveals the effect of halide ions during electrophilic CH activation for the generation of carbene. The ion-pair path is preferred for azolium salts with Cl− and I−, whereas with Br−, the reaction follows the halide coordination route leading to the mixed halide complex. The synthetic route follows concerted-metalation-deprotonation (CMD) mechanism for ion pair pathway. The higher activation barrier for the reaction with Cl− ions can be explained in terms of greater stabilization of the intermediates, compared to the transition states, due to halide coordination or hydrogen bonding with Cl− ions. Furthermore, the successful synthesis of 1b from the reaction of RuCl3·3H2O and the corresponding imidazolium salt precursor with Cl− in dioxane at 100 °C validates the conclusions of the DFT studies.

Palladium(II) complexes with a chelating, monoanionic sulfur ylide

The insoluble, yellow dimeric palladium compound [PdI{κ2C-(CH2)2SO(Me)}]2 reacts with ammonia solutions to form the colourless ammine complex cis-[Pd(NH3)I{κ2C-(CH2)2SO(Me)}]. Although this material readily reconverts to the parent dimer, crystals for a structure determination could be obtained. The ammonia ligand in this compound can be displaced by Ph3P or it can function as a “built-in” base to deprotonate species with acidic protons. The latter reactivity has been observed with acylchalcogenoureas. Imidazolium salts however did not react with the ammine complex directly. They were accessible from the reaction of the parent dimer with the azolium salts in the presence of base. X-rax structures of several examples are reported and DFT calculations were used to elucidate the electronic structure of the ylide ligand and the bonding interactions with the palladium atom.

A pyridine promoted ‘weak base route’ to (NHC)2NiCl2 complexes with bulky N,N'-diaryl carbene ligands

A simple one-step synthesis of (NHC)2NiCl2 complexes containing bulky N-heterocyclic carbene (NHC) ligands relies on the C–H metallation of N,N'-diaryl-substituted azolium salts, NHC-precursors, with NiCl2Py2 in the presence of Cs2CO3 and pyridine. This procedure allows one to implement all synthetic manipulations in air.

Base-catalyzed Effective C2-Amidation of Azolium Salts Using Isocyanates under Mild Conditions.

An unprecedented base-catalyzed hydroarylation of isocyanates with azolium salts was developed, which follows a simple reaction pathway and provided facile access to diverse C2-amidated azolium salts under mild conditions. Importantly, this methodology can also be applied for the successive C2-amidation of a bisimidazolium salt with two different isocyanates to provide the corresponding unsymmetrically substituted bisamide derivatives. Notably, the obtained amidated salts can also serve as a prominent carbene surrogate for the synthesis of metal-NHC complexes.

Photoinduced Acylations Via Azolium-Promoted Intermolecular Hydrogen Atom Transfer.

Photoinduced hydrogen atom transfer (HAT) has been developed as a powerful tool to generate synthetically valuable radical species. The direct photoexcitation of ketones has been known to promote HAT or to generate acyl radicals through Norrish-type pathways, but these modalities remain severely limited by radical side reactions. We report herein a catalyst- and transition metal-free method for the acylation of C-H bonds that leverages the unique properties of stable, isolable acyl azolium species. Specifically, acyl azolium salts are shown to undergo an intermolecular and regioselective HAT upon LED irradiation with a range of substrates bearing active C-H bonds followed by C-C bond formation to afford ketones. Experimental and computational studies support photoexcitation of the acyl azolium followed by facile intersystem crossing to access triplet diradical species that promote selective HAT and radical-radical cross-coupling.

Cytotoxic, Thrombolytic and Antibacterial Evaluation of Synthesized Substituted and Un-Substituted Selenium-N-Heterocyclic Carbene Adducts

Alkyl-substituted azolium salts (1-8) and their Se-N-heterocyclic carbene (Se-N-Het-C) adducts (9-12) were obtained in very reasonable yields. All synthesized azolium salts and their Se-N-Het-C adducts were characterized by different spectroscopic techniques such as FT-IR, 1HNMR, 13CNMR, and elemental analysis. It was found that all synthesized Se-N-Het-C adducts were stable at room temperature in both air and moisture. In-vitro these compounds (5-12) were assessed for their antimicrobial potential against Bacillus subtilis (B. subtilis), Macrococcus brunensis (M. brunensis), and Bacillus cereus (B. cereus) in vitro. Results of MIC and inhibition zone values revealed that the majority of the Selenium N-Heterocyclic carbene adducts were active against Bacillus subtilis (B. subtilis) than Macrococcus brunensis (M. brunensis) and Bacillus cereus (B. cereus) whereas opposite in the azolium salts (5-8). Compounds 5-8 have an inhibition zone of 16and#177;0.1-26and#177;0.3mm against all tested bacterial strains while selenium-NHC adducts 9-12 have a zone of inhibition (16and#177;0.2 to 25 and#177; 0.4mm). Adduct 12 showed good activity against all tested strains with ZI values 25 and#177; 0.1, 22and#177; 0.5, 17 and#177; 0.3 mm and MIC values 17 and#177; 0.2, 16 and#177; 0.4 and 18 and#177; 0.3 and#181;g/mL against Bacillus subtilis (B. subtilis), Macrococcus brunensis (M. brunensis) and Bacillus cereus (B. cereus) respectively. Adduct 10 showed the highest thrombolysis i-e 86.9% and adduct 12 showed good hemolysis i-e 0.51%. Overall results of thrombolysis and cytotoxicity studies revealed that the compounds are safe for preclinical studies of mouse blood in vitro.

Base-free synthesis of benchtop stable Ru(III)-NHC complexes from RuCl3·3H2O and their use as precursors for Ru(II)-NHC complexes.

A series of Ru(III)-NHC complexes, identified as [RuIII(PyNHCR)(Cl)3(H2O)] (1a-c), have been prepared, starting from RuCl3·3H2O following a base-free route. The Lewis acidic Ru(III) centre operates via a halide-assisted, electrophilic C-H activation for carbene generation. The best results were obtained with azolium salts having the I- anion, while ligand precursors with Cl-, BF4-, and PF6- gave no complex formation and those with Br- gave a product with mixed halides. The structurally simple, air and moisture-stable complexes represent rare examples of paramagnetic Ru(III)-NHC complexes. Furthermore, these benchtop stable Ru(III)-NHC complexes were shown to be excellent metal precursors for the synthesis of new [RuII(PyNHCR)(Cl)2(PPh3)2] (2a-c) and [RuII(PyNHCR)(CNCMe)I]PF6 (3a-c) complexes. All the complexes have been characterised using spectroscopic methods, and the structures of 1a, 1b, 2c, and 3a have been determined using the single-crystal X-ray diffraction technique. This work allows easy access to new Ru-NHC complexes for the study of new properties and novel applications.

The facile alkylation and iodination of imidazol(in)ium salts in the presence of cesium carbonate.

The alkylation or iodination of imidazol(in)ium salts takes place readily in the presence of Cs2CO3. The procedure is very easy to implement and provides facile and straightforward access to a wealth of C2-substituted azolium salts. Furthermore, a C2α alkylation is also feasible, which extends the chemistry of NHCs and weak bases to their NHO analogues.

Reactivity and Structure of a Bis-phenolate Niobium NHC Complex.

We report the facile synthesis of a rare niobium(V) imido NHC complex with a dianionic OCO-pincer benzimidazolylidene ligand (L 1 ) with the general formula [NbL 1 (N t Bu)PyCl] 1-Py. We achieved this by in situ deprotonation of the corresponding azolium salt [H 3 L 1 ][Cl] and subsequent reaction with [Nb(N t Bu)Py 2 Cl 3 ]. The pyridine ligand in 1-Py can be removed by the addition of B(C6F5)3 as a strong Lewis acid leading to the formation of the pyridine-free complex 1. In contrast to similar vanadium(V) complexes, complex 1-Py was found to be a good precursor for various salt metathesis reactions, yielding a series of chalcogenido and pnictogenido complexes with the general formula [ NbL 1 (N t Bu)Py(EMes)] (E = O (2), S (3), NH (4), and PH (5)). Furthermore, complex 1-Py can be converted to alkyl complex (6) with 1equiv of neosilyl lithium as a transmetallation agent. Addition of a second equivalent yields a new trianionic supporting ligand on the niobium center (7) in which the benzimidazolylidene ligand is alkylated at the former carbene carbon atom. The latter is an interesting chemically "noninnocent" feature of the benzimidazolylidene ligand potentially useful in catalysis and atom transfer reactions. Addition of mesityl lithium to 1-Py gives the pyridine-free aryl complex 8, which is stable toward "overarylation" by an additional equivalent of mesityl lithium. Electrochemical investigation revealed that complexes 1-Py and 1 are inert toward reduction in dichloromethane but show two irreversible reduction processes in tetrahydrofuran as a solvent. However, using standard reduction agents, e.g., KC8, K-mirror, and Na/Napht, no reduced products could be isolated. All complexes have been thoroughly studied by various techniques, including 1H-, 13C{1H}-, and 1H-15N HMBC NMR spectroscopy, IR spectroscopy, and X-ray diffraction analysis.

Preparation of Mixed Bis-N-Heterocyclic Carbene Rhodium(I) Complexes.

A series of mixed bis-NHC rhodium(I) complexes of type RhCl(η2-olefin)(NHC)(NHC’) have been synthesized by a stepwise reaction of [Rh(μ-Cl)(η2-olefin)2]2 with two different NHCs (NHC = N-heterocyclic carbene), in which the steric hindrance of both NHC ligands and the η2-olefin is critical. Similarly, new mixed coumarin-functionalized bis-NHC rhodium complexes have been prepared by a reaction of mono NHC complexes of type RhCl(NHC-coumarin)(η2,η2-cod) with the corresponding azolium salt in the presence of an external base. Both synthetic procedures proceed selectively and allow the preparation of mixed bis-NHC rhodium complexes in good yields.

An Alternative Method for the Synthesis of N-Pentafluorophenyl Triazolium Salts.

A route for the synthesis of 1,2,4-triazolium salts via oxidation of a thione precursor is demonstrated. N-Pentafluorophenyl-substituted salts are produced in 20-63% overall yields. Isolation and purification of the azolium salts are simplified compared to the traditional synthetic route. Late-stage selection of the counterion allows the synthesis of a variety of salts from a parent thione. The salts have been compared in Stetter and cross-benzoin reactions with an appreciable counterion effect in both reactions.