Pyridine Backbone Research Articles

Chemical and photophysical properties of amine functionalized bis‐NHC‐pyridine‐RuII complexes

AbstractThe effects of backbone amine functionalization in three new homoleptic C^N^C type ruthenium(II) complexes bearing a tridentate bis‐imidazole‐2‐ylidene pyridine ligand framework are characterized and studied by single crystal diffraction, electrochemistry, optical spectroscopy and transient absorption spectroscopy in combination with ab initio DFT calculations. Functionalization by dimethylamine groups in 4‐position of the pyridine backbone significantly influences the properties of the complexes as revealed by comparison with the unfunctionalized references. As a result of the amine functionalization, a higher molar absorption coefficient of the MLCT bands, a decreased photoluminescence quantum yield at room temperature together with a shortened excited state lifetime but an improved photostability is observed. Introduction of electron donating and withdrawing groups at the NHC unit modifies the electronic and optical properties, such as the oxidation potential, absorption and emission properties, and the lifetimes of the excited states.

Manganese-catalyzed Efficient Synthesis of N-heterocycles and Aminoketones Using Glycerol as a C3 Synthon.

Glycerol is one of the important biomass-derived feedstocks and the high-value utilizations of glycerol have attracted much attentions in recent years. Herein, we report a manganese catalyzed dehydrogenative coupling of glycerol with amines for the synthesis of substituted 2-methylquinoxalines, 2-ethylbenzimidazoles, and α-aminoketones without any external oxidant. In these reactions, NHC-based pincer manganese complex featuring a pyridine backbone displayed high catalytic activity and selectivity, in which hydrogen and water were produced as the only by-products using glycerol as a C3 synthon.

An Update on the Recent Green Synthetic Approaches for Imidazo[1,2-a] Pyridine: A Privileged Scaffold

Abstract: Imidazo[1,2-a]pyridine is a fused bicyclic heterocycle that is known as a "drug prejudice" scaffold because of its numerous uses in organic and medicinal chemistry for the development of new drugs. As an outcome, numerous techniques for synthesizing this important class of compounds have been established. Some methods, however, are associated with toxic and corrosive catalysts, longer reaction times, poor yields, lower purity, and by-products in addition to the desired product. Green synthetic methods, which include microwave-assisted synthesis, catalyst-free, solvent-free, green solvent-based synthesis, mechanochemistry, and many others, are used to reduce the usage and production of harmful organic substances. These techniques improve reaction efficiency compared to conventional ones and also reduce the utilization and production of hazardous chemicals. Due to the implication of the imidazo[1,2-a]pyridine backbone as a biologically active ubiquitous fragment and the current demands of reducing toxic solvents, catalysts, and energy consumption, this review focuses on providing comprehensive highlights of the recent green synthetic pathways for imidazo[1,2-a]pyridine.

Nitrogen Reduction to Ammonia by a Phosphorus-Nitrogen PN 3 P-Mo(V) Nitride Complex: Significant Enhancement via Ligand Postmodification

Nitrogen Reduction to Ammonia by a Phosphorus-Nitrogen PN ³ P-Mo(V) Nitride Complex: Significant Enhancement via Ligand Postmodification

Discovery, optimization and evaluation of isothiazolo[5,4-b]pyridine derivatives as RIPK1 inhibitors with potent in vivo anti-SIRS activity

Receptor-interacting protein kinase-1 (RIPK1) is involved in the necroptosis pathway, which regulates inflammatory signaling and cell death in a variety of diseases, including inflammatory and neurodegenerative disorders. We identified a novel hit compound 36 by a cell-based screening assay (anti-necroptosis EC50 = 58 nM). Starting from compound 36, we designed a series of scaffolds to improve anti-necroptosis activity, physicochemical properties and metabolic stability. The isothiazolo[5,4-b]pyridine backbone proved to be a promising scaffold which provided a number of potent necroptosis inhibitors. Compound 56, for example, effectively blocked necroptosis in both human and mouse cells (EC50 = 1–5 nM). A binding assay showed that compound 56 potently binds to RIPK1 (Kd = 13 nM), but not RIPK3 (Kd > 10,000 nM). Kinase functional assay (ADP-Glo) confirmed that compound 56 inhibits RIPK1 phosphorylation with an IC50 at 5.8 nM. Importantly, compound 56 displayed excellent cross-species liver microsomal metabolic stability (t1/2 > 90 min). Furthermore, compound 56 exhibited favorable in vitro safety profiles in hERG and CYP assays. Finally, pre-treatment with 56 significantly reduced hypothermia and lethal shock in the systemic inflammatory response syndrome mice model. Taken together, compound 56 represented a promising prototype for the development of therapeutic agent to treat inflammation-related diseases.

New Membrane Active Antibacterial and Antiviral Amphiphiles Derived from Heterocyclic Backbone of Pyridinium-4-Aldoxime

Quaternary ammonium salts (QAS) are irreplaceable membrane-active antimicrobial agents that have been widely used for nearly a century. Cetylpyridinium chloride (CPC) is one of the most potent QAS. However, recent data from the literature indicate that CPC activity against resistant bacterial strains is decreasing. The major QAS resistance pathway involves the QacR dimer, which regulates efflux pump expression. A plausible approach to address this issue is to structurally modify the CPC structure by adding other biologically active functional groups. Here, a series of QAS based on pyridine-4-aldoxime were synthesized, characterized, and tested for antimicrobial activity in vitro. Although we obtained several potent antiviral candidates, these candidates had lower antibacterial activity than CPC and were not toxic to human cell lines. We found that the addition of an oxime group to the pyridine backbone resulted in derivatives with large topological polar surfaces and with unfavorable cLog P values. Investigation of the antibacterial mode of action, involving the cell membrane, revealed altered cell morphologies in terms of corrugated and/or disrupted surface, while 87% of the cells studied exhibited a permeabilized membrane after 3 h of treatment at 4 × minimum inhibitory concentration (MIC). Molecular dynamic (MD) simulations of the interaction of QacR with a representative candidate showed rapid dimer disruption, whereas this was not observed for QacR and QacR bound to the structural analog CPC. This might explain the lower bioactivity of our compounds, as they are likely to cause premature expression of efflux pumps and thus activation of resistance.

Pyrrolo-imidazo[1,2-a]pyridine Scaffolds through a Sequential Coupling of N-Tosylhydrazones with Imidazopyridines and Reductive Cadogan Annulation, Synthetic Scope, and Application

A new strategy for the construction of 3-phenyl-1H-pyrrolo-imidazo[1,2-a]pyridine backbone is described. The reaction starts from the coupling between N-tosylhydrazones and 2-chloro-3-nitroimidazo[1,2-a]pyridines leading to the formation of 3-nitro-2-(arylvinyl)imidazo[1,2-a]pyridine derivatives. Optimization of Cadogan-reductive conditions allowed the conversion of the obtained nitro derivative to a new scaffold of the type 3-aryl-1H-pyrrolo-imidazo[1,2-a]pyridine. This method provides rapid access to new libraries in the context of diversity-oriented synthesis, which intends to generate small molecules with a large structure diversity in an efficient manner. Screening of the biological activity of the newly generated compounds leads to the identification of a new promising compound 5cc, which exhibits good antiproliferative activity in the submicromolar range against a human colon cancer cell line.

Synthesis and antitumor evaluation of some new derivatives and fused heterocyclic compounds derived from thieno[2,3‐b]pyridine

On the basis of the proven activity of thieno[2,3‐b]pyridines as anticancer, we have designed to synthesize a novel several heterocyclic compounds utilizing thieno[2,3‐b]pyridine as a skeleton through various chemical reactions. The synthesized compounds bear rings that are either directly attached to the thieno[2,3‐b]pyridine as in compounds 4 to 6 and 9 or connected through an amide bridge as compounds 2, 3a‐b, 7, and 8. As well as, compounds 10, 12 to 28, 30, 31, and 33 to 36 bear fused rings to the thieno[2,3‐b]pyridine backbone. The newly synthesized compounds were screened for their antiproliferative activity in vitro against hepatocellular carcinoma (HepG‐2) and breast cancer (MCF‐7) compared with the standard drug (doxorubicin). Compounds 3b, 4, 6, 22, and 28 exhibited promising growth inhibitory effect toward both HepG‐2 and MCF‐7 cell lines with IC50 values ranging from 5.88 to 11.70 μg/mL and 9.64 to 15.10 μg/mL, respectively.

Hydration of nitriles using a metal-ligand cooperative ruthenium pincer catalyst.

Nitrile hydration provides access to amides that are important structural elements in organic chemistry. Here we report catalytic nitrile hydration using ruthenium catalysts based on a pincer scaffold with a dearomatized pyridine backbone. These complexes catalyze the nucleophilic addition of H2O to a wide variety of aliphatic and (hetero)aromatic nitriles in t BuOH as solvent. Reactions occur under mild conditions (room temperature) in the absence of additives. A mechanism for nitrile hydration is proposed that is initiated by metal-ligand cooperative binding of the nitrile.

Recognizing the Mechanism of Sulfurized Polyacrylonitrile Cathode Materials for Li–S Batteries and beyond in Al–S Batteries

Sulfurized polyacrylonitrile (SPAN) is the most promising cathode for next-generation lithium–sulfur (Li–S) batteries due to the much improved stability. However, the molecular structure and reaction mechanism have not yet been fully understood. Herein, we present a new take on the structure and mechanism to interpret the electrochemical behaviors. We find that the thiyl radical is generated after the cleavage of the S–S bond in molecules in the first cycle, and then a conjugative structure can be formed due to electron delocalization of the thiyl radical on the pyridine backbone. The conjugative structure can react with lithium ions through a lithium coupled electron transfer process and form an ion-coordination bond reversibly. This could be the real reason for the superior lithium storage capability, in which the lithium polysulfide may not be formed. This study refreshes current knowledge of SPAN in Li–S batteries. In addition, the structural analysis is applicable to analyze the current organic catho...

Mn2+ complexes of open-chain ligands with a pyridine backbone: less donor atoms lead to higher kinetic inertness

The loss of a coordinating donor atom in the ligand leads to lower thermodynamic stability, but higher kinetic inertness of Mn2+ complexes.

Formal oxidative addition of a C-H bond by a 16e iridium(i) complex involves metal-ligand cooperation.

The first example of oxidative addition of a C-H bond to a square planar d8-Iridium complex, without any external additive, such as an acid, is described. Our mechanistic investigations show that metal-ligand cooperation through aromatization-dearomatization of the lutidine backbone is involved in this process, and that the actual C-H activation step occurs through an Ir(iii) intermediate.

Mononuclear, dinuclear and polymeric cobalt(II) complexes built on 4-aryl-2,6-bis(2′-pyrazinyl)pyridines

Two new multidentate nitrogen ligands containing a 2,6-bis(2′-pyrazinyl)pyridine (bpp) backbone were synthesized and characterized. The facile Kröhnke condensation procedure allows for efficient synthesis and modification of this class of N-rich ligands. The metal-mediated self-assembly of these ligands along with a previously known derivative with Co(NCS)2 was studied. X-ray structural analysis of the metal assemblies reveals that mononuclear, dinuclear and polymeric structures could be obtained based on the ligands used. Although in most cases including the previously reported results the coordination chemistry of bpp-based ligands involves only inner N3 cavity, with the outer-N donors remaining uncoordinated, the introduction of a 3-pyridyl group to the 4-position of central pyridine of bpp is found to be critical for the synthesis of new coordination polymers. The thermal properties of these metal complexes have been studied.

Hemilabile N-heterocyclic carbene (NHC)-nitrogen-phosphine mediated Ru (II)-catalyzed N-alkylation of aromatic amine with alcohol efficiently

Based on the hemilability, a novel N-heterocyclic carbene (NHC)-nitrogen-phosphine ligand (1) was synthesized, and the combination of it with [Ru(COD)Cl2]n showed the high activity and selectivity with a low Ru loading of 0.1% for the N-alkylation of amine with alcohol. Especially, for these substrates with pyridine backbone, even if the catalyst loading was as low as 0.01%, good yields (81–95%) of the desired products were achieved.

Air Stable Iron(II) PNP Pincer Complexes as Efficient Catalysts for the Selective Alkylation of Amines with Alcohols

AbstractA series of well‐defined iron(II) complexes of the types [Fe(PNP)Br2] and [Fe(PNP)(CO)Br2] with PNP pincer ligands based on triazine and pyridine backbones were prepared and fully characterized. These complexes were tested as catalysts for the alkylation of amines by alcohols. The high‐spin complexes [Fe(PNP)Br2] are catalytically inactive. The low‐spin complexes [Fe(PNP)(CO)Br2] bearing a carbonyl co‐ligand efficiently and selectively convert primary alcohols and aromatic and benzylic amines selectively into mono‐N‐alkylated amines in good to excellent isolated yields. A mechanistic proposal is given.magnified image

Syntheses and non-covalent interactions of naphthalene-bearing Schiff base complexes of Zn(II), Co(III), Cu(II) and V(IV): Selective detection of Zn(II)

A new Schiff base ligand, 1-[(2-pyridin-2-yl-ethylimino)-methyl]-naphthalen-2-ol, (HPEMN) has been synthesized equipped with naphthalene and pyridine backbone, to study the interplay of various non-covalent interactions. Experiments have been carried out to investigate the outcome of combinations of HPEMN and ZnCl2 (1), ZnBr2 (2), ZnI2 (3), Zn(NO3)2·6H2O (4), Co(ClO4)2·6H2O (5), Cu(ClO4)2·6H2O (6) and VO(acac)2 (7). The prevalent non-covalent interactions described here include naphthalene–naphthalene (for 1, 2, 3 and 5) and pyridine–pyridine π–π stacking (for 4) interactions, nitrate anion⋯π interaction (for 4) and hydrogen bonding (for 6). HPEMN is able to sense Zn(II) selectively and this phenomenon was further demonstrated by the results of fluorescence studies in H2O/acetonitrile (8:2, v/v) HEPES buffer (pH=7.4) solution and human lung cancer cell lines.

Metal-ligand cooperative activation of nitriles by a ruthenium complex with a de-aromatized PNN pincer ligand.

The pincer complex (PNN)RuH(CO), with a de-aromatized pyridine in the ligand backbone, is shown to react with nitriles in a metal-ligand cooperative manner. This leads to the formation of a series of complexes with new Ru-N(nitrile) and C(ligand)-C(nitrile) bonds. The initial nitrile cycloaddition products, the ketimido complexes 3, have a Brønsted basic (nitrile-derived) Ru-N fragment. This is able to deprotonate a CH2 side-arm of the pincer ligand to give ketimine complexes (4) with a de-aromatized pyridine backbone. Alternatively, the presence of a CH2 group adjacent to the nitrile functionality can lead to tautomerization to an enamido complex (5). Variable-temperature NMR studies and DFT calculations provide insight in the relative stability of these compounds and highlight the importance of their facile interconversion in the context of subsequent nitrile transformations.

Switching of “Rollover Pathway” in Rhodium(III)-Catalyzed C–H Activation of Chelating Molecules

Organic molecules containing imidazolium and pyridine backbone are of special interest in many branches of chemistry, and therefore, overcoming the scarcity of their catalytic functionalization protocol leading to structurally important derivatives is strongly desired. This study demonstrates an unprecedented bimodal C–H activation–functionalization catalysis on such organic molecules which contain imidazolium motif (potential N-heterocyclic carbene donor) and pyridine in chelating fashion and difficult to functionalize by trivial C–H activation strategy. The unique feature of this protocol is a flip-flop NHC-directed pyridine rollover and pyridine-directed NHC-rollover C–H activation within a stable “NHC–RhIII–pyridine” chelate platform followed by functionalization with internal alkynes to furnish structurally important annulated products. Electronic and steric factors play a key role in achieving such novel chemistry.

ChemInform Abstract: Non‐Symmetric Pincer Ligands: Complexes and Applications in Catalysis

AbstractReview: 108 refs.

ChemInform Abstract: A Metal—Ligand Cooperative Pathway for Intermolecular Oxa‐Michael Additions to Unsaturated Nitriles.

ChemInformVolume 46, Issue 31 Preparative Organic Chemistry ChemInform Abstract: A Metal—Ligand Cooperative Pathway for Intermolecular Oxa-Michael Additions to Unsaturated Nitriles. Sebastien Perdriau, Sebastien Perdriau Stratingh Inst. Chem., Univ. Groningen, NL-9747 AG Groningen, Neth.Search for more papers by this authorDouwe S. Zijlstra, Douwe S. Zijlstra Stratingh Inst. Chem., Univ. Groningen, NL-9747 AG Groningen, Neth.Search for more papers by this authorHero J. Heeres, Hero J. Heeres Stratingh Inst. Chem., Univ. Groningen, NL-9747 AG Groningen, Neth.Search for more papers by this authorJohannes G. de Vries, Johannes G. de Vries Stratingh Inst. Chem., Univ. Groningen, NL-9747 AG Groningen, Neth.Search for more papers by this authorEdwin Otten, Edwin Otten Stratingh Inst. Chem., Univ. Groningen, NL-9747 AG Groningen, Neth.Search for more papers by this author Sebastien Perdriau, Sebastien Perdriau Stratingh Inst. Chem., Univ. Groningen, NL-9747 AG Groningen, Neth.Search for more papers by this authorDouwe S. Zijlstra, Douwe S. Zijlstra Stratingh Inst. Chem., Univ. Groningen, NL-9747 AG Groningen, Neth.Search for more papers by this authorHero J. Heeres, Hero J. Heeres Stratingh Inst. Chem., Univ. Groningen, NL-9747 AG Groningen, Neth.Search for more papers by this authorJohannes G. de Vries, Johannes G. de Vries Stratingh Inst. Chem., Univ. Groningen, NL-9747 AG Groningen, Neth.Search for more papers by this authorEdwin Otten, Edwin Otten Stratingh Inst. Chem., Univ. Groningen, NL-9747 AG Groningen, Neth.Search for more papers by this author First published: 16 July 2015 https://doi.org/10.1002/chin.201531033Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume46, Issue31August, 2015 RelatedInformation