N-heterocyclic Carbene Salt Research Articles

Synthesis of bis(indolyl)methanes using N-heterocyclic carbene salt as a C1 precursor.

We herein describe an alkylation reaction of indoles with NHC salts to access bis(indolyl)methanes as product. The NHC salt (or free NHC) serves as a C1 precursor due to decomposition of its N-heterocyclic ring. Although the exact roles of zinc powder and acetic/formic acid remain elusive, both of them are indispensable for this reaction. Two possible reaction pathways are proposed based on the results of mechanistic experiments.

On the Role of N-Heterocyclic Carbene Salts in Alkyl Radical Generation from Alkyl Alcohols: A Computational Study.

Formation of carbon-carbon bonds through cross-coupling reactions using readily available substrates, like alcohols, is crucial for modern organic chemistry. Recently, direct alkyl alcohol functionalization has been achieved by the use of N-Heterocyclic Carbene (NHC) salts via in situ formation of an alcohol-NHC adduct and its activation by a photoredox catalyst to generate carbon-centered alkyl radicals. Experimentally, only electron deficient NHC activators work but the reasons of this behavior remain underexplored. Herein, a DFT computational study of the mechanism of alcohol activation using up to seven NHC salts is performed to shed light into the influence of their electronic properties in the alkyl radical formation. This study demonstrates that four reaction steps are involved in the transformation and characterizes how the electronic properties of the NHC salt affect each step. A fine balance of the NHC electron-richness is proved to be determinant for this transformation.

Theoretical and experimental investigation of N-alkyl substituted bis-imidazolium salts and their binuclear N-heterocyclic carbene silver acetate complexes

Our research centers on structural, biological, and electronic properties of N-heterocyclic carbene salts and their silver acetate-based complexes. After theoretical calculations, compounds were synthesized. In the DFT studies, functional of B3LYP was used with the basis set of 6-31++G and LanL2DZ for salts and complexes, respectively. The most stable structures were calculated and non-covalent interactions evaluated. Electronic parameters were checked while calculating their HOMO and LUMO energies so that their biological potential can be evaluated. Density of states were studied to check the electronic densities. Among all compounds, 3 was considered the best with energy gap of 0.121 eV. As all eight compounds have very reasonable HOMO-LUMO energy gaps they were considered feasible to synthesize and have strong biological potentials. Compounds were characterized by FT-IR and NMR spectroscopy.

Bioactivities of Triazolium-Based N-Heterocyclic Carbene Salts.

1,2,4-Triazolium salts are precursors of N-heterocyclic carbenes (NHCs), which have been extensively used as effective catalysts and ligands for both asymmetric and non-enantioselective reactions. Nevertheless, they are also a kind of quaternary ammonium compounds (QACs) that possess amphipathic properties. The unique chemical and physical properties of 1,2,4-triazolium salts have received significant attention from scientists focusing on the development of novel bioactive molecules as pesticides and medicines. It is timely and meaningful to summarize the bioactivities of 1,2,4-triazolium salt derivatives against various bacteria, fungi, cancer cells, and other pathogens in the past 30 years. Meanwhile, the structure-activity relationship (SAR) of 1,2,4-triazolium salts was also summarized. Finally, our perspective on the future development and applications of triazolium salts as agrichemicals or human drugs is presented.

Molecular Docking and DFT Analysis of Methallyl Substituted N-Heterocyclic Carbene Salts for Potential Anticancer Activity

The research recorded that growth hormones are effective in malignant cell formation and metastasis in many types of cancer. The release of vascular endothelial growth hormone has regulated by vascular endothelial growth hormone receptors. Therefore, inhibition of the vascular endothelial growth hormone receptor is important in hindering the formation of cancerous cells and metastasis. Many new molecules have been synthesized for fighting against cancer and their anticancer activity has been investigated. Since the first synthesis of N-heterocyclic carbene molecules, much bioactivities research has been performed and some of them have become drugs that are used in treatment procedures. Due to the difficulty and cost of the methods used to examine the bioactivities of molecules, foresight regarding the activities of possible active molecules is valuable. It is useful to make these preliminary evaluations in-silico methods. Comparing the results of the experimental analysis with the in-silico results is important in terms of having information about the validity of computational methods. In this study, N-heterocyclic carbene type benzimidazolium cations were analyzed with DFT/TDDFT computational methods and molecular docking for vascular endothelial growth factor receptor-2.

Raman spectroscopic characterization of selenium N-heterocyclic carbene compounds

In this study, Raman spectroscopy is employed to analyze and characterize two salts (N-heterocyclic carbene) and their respective selenium N-heterocyclic carbene compounds. The features observed as differences among Raman spectral data of two different N-heterocyclic carbene salts are called Salt-I and Salt-II and their respective Se compounds, called Compound-I & Compound-II, are used to confirm the formation covalent bond between Se atom carbon atom of carbene. Enhancement in peak intensities and shifting of peak positions is directly related with compound formation. Raman spectral data provide a detail information about bond formation, chemical and structural differences between salts and compounds. The observed Raman spectral features of both salts and compounds are in consistent with computationally calculated Raman spectral features. Raman spectral features of each salt and its respective compound was further analyzed with principal component analysis, which was found helpful for differentiating each salt from its respective compound.

Metallaphotoredox-enabled deoxygenative arylation of alcohols.

Metal-catalysed cross-couplings are a mainstay of organic synthesis and are widely used for the formation of C-C bonds, particularly in the production of unsaturated scaffolds1. However, alkyl cross-couplings using native sp3-hybridized functional groups such as alcoholsremain relatively underdeveloped2. In particular, a robust and general method for the direct deoxygenative coupling of alcohols would have major implications for the field of organic synthesis. A general method for the direct deoxygenative cross-coupling of free alcohols must overcome several challenges, most notably the in situ cleavage of strong C-O bonds3, but would allow access to the vast collection of commercially available, structurally diverse alcohols as coupling partners4. We report herein a metallaphotoredox-based cross-coupling platform in which free alcohols are activated in situ by N-heterocyclic carbene salts for carbon-carbon bond formation with aryl halide coupling partners. This method is mild, robust, selective and most importantly, capable of accommodating a wide range of primary, secondary and tertiary alcohols as well as pharmaceutically relevant aryl and heteroaryl bromides and chlorides. The power of the transformation has been demonstrated in a number of complex settings, including the late-stage functionalization of Taxol and a modular synthesis of Januvia, an antidiabetic medication. This technology represents a general strategy for the merger of in situ alcohol activation with transition metal catalysis.

Synthesis, characterization, crystal structure, Hirshfeld surface analysis, and theoretical study on a N-heterocyclic carbene salt and two NHC–palladium complexes

An N-ethylphthalimide functionalized 1,3-dialkylbenzimidazolium salt has been synthesized and characterized by elemental analysis, FTIR, 1H NMR, and 13C NMR spectroscopy. Crystal structures of the salt and two palladium complexes were determined by single-crystal X-ray diffraction studies. Theoretical calculations were obtained by density functional theory (DFT) methods at the HSEh1PBE/SDD level of theory. Structural parameters of the compounds are well represented by DFT calculations. Noncovalent interactions in the compounds have also been studied through two-dimensional fingerprint plots based on Hirshfeld surface analysis. Frontier molecular orbitals (HOMO-LUMO) and their energy gap were determined to explore the stability of the molecules. The large HOMO-LUMO energy gaps point out a high kinetic stability of the compounds in their electron transfer.

Synthesis of Novel Palladium Complexes Containing β‐Diketonate and NHC Ligands and their Catalytic Ability for Addition Polymerizations of the Functional Norbornenes

Palladium complexes containing various N‐heterocyclic carbene (NHC) ligands have been successfully synthesized by the reaction with various β‐diketonate complexes. Treatments of Pd(acac)2 with NHC salts such as 1,3‐di(2,6‐diisopropylphenyl)imidazolium chloride (IPr·HCl) or 1,3‐di(mesityl)imidazolium chloride (IMes·HCl) resulted in [Pd(acac)(NHC)Cl] complexes and these complexes were characterized by NMR. Moreover, these palladium complexes showed moderate to good catalytic activities towards addition polymerization of various functional norbornenes. The effects of various reaction parameters onto the catalytic activity towards polymerization of functional norbornenes have been thoroughly investigated.

Synthesis, characterization and anticancer activity of allyl substituted N-Heterocyclic carbene silver(I) complexes

Metal N-heterocyclic carbene (NHC) complexes have attracted considerable attention in biological fields for their potential applications in cancer and antimicrobial therapies. In this study, four new benzimidazole-based N-heterocyclic carbene salts (1a-d) and their silver (I) complexes (2a-d) were synthesized. All new compounds were characterized by elemental analysis, FT-IR, 1H NMR and, 13C NMR spectroscopy. Additionally, single crystal structural studies for complex 2d show that the benzene rings (C9C14) and the central benzimidazole ring system make dihedral angles of 83.58(13)°. The AgCl and AgC single bond lengths are 2.3267(8) and 2.087(3) Å, respectively. The CAgCl bond angle is 175.20(7)°. The prop-1-ene moiety attached at the second N-atom of benzimidazole is disordered at two set of sites with an occupancy ratio of 0.592(6): 0.408(6). There is one intramolecular hydrogen bond interaction between C22A-H22A … N2. The salts and Ag-complexes were further evaluated for their in vitro anticancer activities against DU-145 human prostate cancer cells, MCF-7, MDA-MB-231 human breast cancer cells and L-929 non-cancer cell for 24 h, 48 h and 72 h using the MTT assay. The Ag(I)NHC complexes (2a-d) showed a dose and time-dependent cytotoxic activity against all cell lines. The IC50s for all Ag(I)NHC complexes lower than 1 μM for 72 h time points on cancer cells. The results showed that complex 2d exhibited the highest activity against all cancer cell lines studied. Further, the complexes had relatively higher cytotoxicity to cancer cells than to non-cancer cell lines.

The synthesis and characterization of 1-(Allyl)-3-(2-methylbenzyl)benzimidazolium chloride: FT-IR, NMR, and DFT computational investigation

A new N-heterocyclic carbene (NHC) salt was synthesized by the reaction of 1-allyl benzimidazole with 2-methyl benzyl chloride. The structure of N-heterocyclic carbene salt was determined by elemental analysis, FT-IR, 1H NMR and 13C NMR spectroscopy and supported by the computational spectral analyses. For this purpose, the stable conformational structures obtained by Potential Energy Surface (PES) scan at B3LYP/6-31G (d,p) level of the theory have been used to elucidate the spectroscopic studies of the NHC salt as well as to search the electronic properties being important to predict the chemical reactivity behavior and nonlinearity properties of the NHC salt. FMO amplitudes and MEP diagrams have been used to show the chemically active sites of each stable conformer.

Synthesis, characterisation and cytotoxic properties of N -heterocyclic carbene silver(I) complexes

Abstract A benzimidazolium salt bearing hydroxyethyl group, 1a and a new series of zwitterionic sulphonated benzimidazolium salts, 1b–e were reacted with Ag2O to produce Ag(I)-N-heterocyclic carbene (NHC) complexes, 2a–e respectively. Synthesised silver(I)-N-heterocyclic carbene complexes were fully characterised by 1H and 13C NMR, elemental analysis and HRMS spectroscopic methods. Anti-cancer potential of both NHC salts and complexes were tested and the IC50 values of these NHC salts and complexes were determined by a proliferation BrdU enzyme-linked immunosorbent assay (ELISA) against HeLa (Human cervix carcinoma), HT29 (human adenocarcinoma) and L929 (mouse fibroblast) cell lines. The IC50 values are in the range of 11 ± 1–126 ± 3 μM show that all new Ag(I)-NHC complexes especially complex 2b demonstrated remarkable cytotoxic activity against HeLa, HT29 and L929 while 1a–e NHC salts are found to be inactive against HeLa, HT29 and L929. Also, the high IC50 value of complex 2b against L929 cells can be interpreted high selectivity against healthy cells. This complex has been highlighted as new types of metalodrug.

Synthesis, Structural Analysis and Antimicrobial Activities of Novel Water Soluble Ionic Liquids Derived from N-Heterocyclic Carbene Salts

Synthesis, Structural Analysis and Antimicrobial Activities of Novel Water Soluble Ionic Liquids Derived from N-Heterocyclic Carbene Salts

Well-Defined Silica-Supported Olefin Metathesis Catalysts

Silica-supported N-heterocyclic carbene (NHC) ruthenium complexes were developed as immobilized metathesis catalysts. Thus, for example, allylation of bisimine 1 and subsequent reduction with NaBH4 gave diamine 2 which was treated with HCl and HC(OEt)3 to afford the imidazolium chloride 3. Pt(0)-catalyzed hydrosilylation of 3 using HSiCl3 followed by EtOH/Et3N treatment gave the NHC salt 4. Ruthenium complex 5 was prepared by deprotonation of 4 with KHMDS and treatment of the resulting free carbene with ruthenium complex 7. Ruthenium complex 5 was anchored to silica gel to afford the ­silica-supported ruthenium complex 6.

Expanded ring and functionalised expanded ring N-heterocyclic carbenes as ligands in catalysis

The synthesis of new functionalised 6- and 7-membered NHC (N-heterocyclic carbene) precursors bearing anisidyl or pyridine N-substituents, both symmetrically and non-symmetrically substituted is reported. Their corresponding rhodium(i) and iridium(i) complexes, M(COD)(NHC)Cl, were also prepared and characterised. The unusual Rh(iii)/Rh(i) salt, [Rh(eta(2)-NHC-py)(2)Cl(2)][Rh(COD)Cl(2)], was obtained with one of the pyridyl-functionalised NHC ligands. Single-crystal X-ray analyses have been obtained for the majority of the complexes and NHC salts. The activity of these complexes was tested in the hydrogenation of a range of substrates with molecular hydrogen, including 1-cyclooctadiene and 2-methyl styrene, where they show enhanced activity and stability in comparison to non-functionalised NHC analogues, operating under exceptionally mild conditions (ambient temperature and atmospheric pressure).

Intramolecular Cycloisomerization of Aryl-Substituted Alkylidenecyclo­propanes via NHC Palladium-Catalyzed Cascade C-C Bond Cleavage/C-H Activation/C-C Bond Formation

A well-defined N-heterocyclic carbene (NHC) palladium-catalyzed intramolecular cyclization reaction of aryl-substituted alkylidenecyclopropanes (ACP) to 1 -aryl dihydronaphthalenes is described. The NHC salts were found to suppress β-hydride elimination from the homoallylpalladium intermediate, which may lead to unwanted alkene formation. A plausible mechanism for the cycloisomerization was proposed.

Synthesis and Characterization of a Novel Cobalt Carbonyl N-Heterocyclic Carbene Salt. Crystal Structure of [Co(CO)3(IMes)2]+[Co(CO)4]-

The disproportionation of dicobalt octacarbonyl induced by the free carbene 1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene (IMes) and the X-ray characterization of the cyclohexane solvate of the resulting cobalt carbonyl N-heterocyclic carbene salt, [Co(CO)3(IMes)2]+[Co(CO)4]-.1/4C6H12, is reported. The crystal structure represents the first example of a [Co(CO)3(L)2][Co(CO)4] disproportionate salt reported to date.