Coupling Reaction Of Amines Research Articles

Heterobimetallic Cu(I)/Fe(II) azomethine bridged coordination-organometallic hybrid complexes: Synthesis, luminescence, electrochemical and catalytic properties

A new series of heterobimetallic complexes of the type [Cu(L)(PPh3)2]X (1–4) [where L = trans-4-(ferrocenylideneamino)-1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-one; PPh3 = triphenylphosphine, X = NO3−(1), ClO4− (2), BF4− (3) , PF6− (4)] were prepared by reaction of L with [Cu(MeCN)2(PPh3)2]X and characterized by elemental analysis, FTIR, 1H NMR, 31P NMR and UV–visible spectral studies. The thermal stability of (1–4) has been investigated by using thermogravimetric analysis (TGA). X-ray powder diffraction of the representative complex 1 used to clarify the crystal structure of the complex. The electrochemical behaviour of complexes (1–4) displayed quasireversible redox behaviour corresponding to Cu(I)/Cu(II) and Fe(II)/Fe(III) couples. All complexes show red emission as a result of ligand-ligand charge transfer (LLCT) and metal-ligand charge transfer (MLCT) or admixture of them. The catalytic efficiency of the complexes (1–4) was tested and it was found that the complex 4 worked as an effective catalyst for the C-N coupling reaction of aromatic amines and aryl halides.

Mn‐Catalyzed Three‐Component Coupling Reactions of Carboxylic Acids, Diazo Compounds, and Tertiary Amines for the Synthesis of β‐Amino Esters

ABSTRACTA simple and efficient three‐component coupling reaction of carboxylic acids, diazo compounds, and tertiary amines catalyzed by manganese has been described. This reaction proceeds smoothly under mild conditions to afford various β‐amino esters in moderate to good yields by using O2 as the terminal oxidant. In this process, Mn‐based carbene radical, single‐electron transfer, and nucleophilic attack were fused into a reaction system.

Propargyl amines by aldehyde-amine-acetylene coupling mediated by Ag(I) and Cu(I) complexes of super bulky N-heterocyclic carbenes: Unveiling the role of the super bulky ligands in the coupling reaction

The copper (1–2)a and the silver (1–2)b complexes of the super bulky N-heterocyclic carbene (NHC) variants namely, [1,3-{2,4,6-(Ph2CH)3C6H2}2-imidazol-2-ylidene]MX [where, M = Cu; X = Cl (1a), Br (2a): M = Ag; X = Cl (1b), Br (2b)] effectively facilitated the A3 coupling reaction of diverse amine, aldehyde, and acetylene substrates yielding a wide array of propargylamines in moderate to good (ca. 24−89 %) yields. A metal bound acetylide species, [1,3-{2,4,6-(Ph2CH)3C6H2}2-imidazol-2-ylidene]M(CCPh) [where, M = Cu (A), Ag (B)] has been identified as a key catalytic species by mass spectrometric studies. The Density functional theory (DFT) studies further revealed the rate-limiting step as the formation of the C-C coupling transition state (TS2) from the silver-acetylide species (Int2). The super bulky ligand framework plays a pivotal role in this step by anchoring the protonated Schiff's base imine in the vicinity of the alkyne through several non-covalent-interactions, including a strong C–H•••O interaction, thereby reducing the corresponding kinetic barrier leading to an efficient catalytic transformation as reflected in the high propargylamine yields. Furthermore, the catalytic utility of the coupling reaction was further extended by synthesising pargyline, which is a monoamine oxidase B (MAO-B) inhibitor drug molecule, in a one-pot manner and that to in a gram-scale synthesis.

Yolk-Shell Au NPs@Carbon Porous Nanoreactors Derived from ZIF-8: A High-Efficiency Catalyst for Three-Component Coupling Reaction.

A yolk-shell Au NPs@carbon porous nanoreactor with an active gold (Au) core and a porous carbon shell has been fabricated and demonstrates excellent high activity and cyclic stability as a heterogeneous catalyst for the three-component coupling reaction of aldehyde, amine, and alkyne. Remarkably, the unique yolk-shell nanostructure can protect gold nanoparticles (Au NPs) from aggregation, allow for efficient mass transport, and benefit substrate enrichment, giving rise to enhanced activity, stability, and recyclability.

Surface decoration of PLGA nanoparticles enables efficient transport of floxuridine oligomers into mammalian cells

2′-deoxy-5-fluorouridine (Floxuridine, FdU) oligomers are repeated FdU residues linked to each other through phosphate groups exhibiting anticancer properties. One of the major hurdles exhibited by natural oligomers is their reduced stability and limited ability to impart cellular uptake. To overcome these drawbacks, electrostatic and covalent strategies have been used to combine oligomers with nanoparticles (NPs) to enhance stability and cellular internalization. Polymeric NPs, prepared from oil-in-water (O/W) PLGA nano-emulsions (NEs) using low-energy emulsification methods, have shown potential in many biomedical applications owing to their ability to transport drugs across cellular membranes. Carbodiimide-mediated amine coupling reaction and thiol-based Michael-type addition were used to attach FdU oligomers formed by five FdU residues (FdU5) to PLGA NPs. Colloidally stable dispersions of FdU5-decorated PLGA NPs were obtained and characterized in terms of size, surface charge, and morphology in physiological medium. Additionally, synthetic strategies were envisaged to functionalize the surface of FdU5-decorated polymeric NPs with folic acid (FA). Cell culture experiments showed that FdU5-decorated PLGA NPs were able to internalize efficiently inducing cytotoxic effect and inhibiting cell proliferation in tumor cells. These outcomes suggest the feasibility of grafting oligomeric FdU produgs in a covalent fashion into nanoscale platforms as a potential approach for cancer therapy.

Copper-Catalyzed Multicomponent Coupling Reaction of Primary Aromatic Amines, Rongalite, and Alkynes: Access to N-Aryl Propargylamines.

In this work, a practical copper-catalyzed multicomponent coupling reaction of primary aromatic amines, rongalite, and alkynes for the direct synthesis of N-aryl propargylamines has been developed. This method could overcome the substrate limitation in A3 coupling reactions of primary aromatic amines, formaldehyde, and alkynes. Mechanistic studies revealed that rongalite acts as not only the active C1 unit but also the accelerator to activate the in situ-generated N-arylmethanimines for the coupling reaction with alkynes. This coupling reaction is highly efficient and features a broad substrate scope, as well as utility with scale-up synthesis and converting the corresponding product N-aryl propargylamines into useful heterocyclic skeletons.

Design of a Copper(II) Complex with Tetradentate Bis‐Benzotriazole‐Appended Bipyridine Ligand and its Catalytic Application in A3 Coupling Reaction

AbstractIn this report, a Cu(II) complex Cu‐L4 containing a new tetradentate benzotriazole‐appended bipyridine ligand was synthesized and characterized fully via spectroscopic and crystallographic techniques. The crystal structure of the complex revealed that the ligand is bound to copper in a tetradentate fashion in a plane and the axial positions are occupied by an anion and a solvent molecule, resulting in a distorted octahedral geometry of the complex in solid‐state. This air‐stable complex was utilized as homogeneous precatalyst for the synthesis of several propargylamine derivatives by 3‐component A3 coupling reactions of aldehydes, amines, and alkynes under aerial atmosphere.

Cu@CuOx/WO3 with photo-regulated singlet oxygen and oxygen adatoms generation for selective photocatalytic aromatic amines to imines

Photocatalysts can absorb light and activate molecular O2 under mild conditions, but the generation of unsuitable reactive oxygen species often limits their use in synthesizing fine chemicals. To address this issue, we disperse 1 wt% copper on tungsten trioxide (WO3) support to create an efficient catalyst for selective oxidative coupling of aromatic amines to imines under sunlight irradiation at room temperature. Copper consists of a metallic copper core and an oxide shell. Experimental and density functional theory calculations have confirmed that Cu2O is the primary activation site. Under λ < 475 nm, the light excites electrons of the valence bands in Cu2O and WO3, which activate O2 to superoxide radical •O2−. Then rapidly transforms into oxygen adatoms (•O) and oxygen anion radicals (•O−) species on the surface of Cu2O. Simultaneously, it is captured by holes in the WO3 valence band to generate singlet oxygen (1O2). •O bind to 1O2 promoting the coupling reaction of amines. When λ > 475 nm, intense light absorption due to the localized surface plasmon resonance excites numerous electrons in Cu to promote the oxidative coupling with the adsorbed O2. This study presents a promising approach towards the design of high-performance photocatalysts for solar energy conversion and environmentally-friendly oxidative organic synthesis.

Immobilized nickel nanoparticles on modified magnetic titanium dioxide: A proficient and eco-friendly nanocatalyst for the green A3-coupling synthesis of propargylamines

In this research, a novel and highly efficient magnetic catalyst was synthesized by surface modification of Fe3O4/TiO2 with epibromohydrine and N-(2-aminoethyl)piperazine linkers and then by immobilization of Ni nanoparticles onto the surface of magnetic titanium dioxide. The synthesized Fe3O4/TiO2-EP-NAEP/Ni nanocomposite was identified by FT-IR, PXRD, TEM, FE-SEM, ICP, EDX, TGA, and VSM techniques, and its catalytic performance was investigated in an A3 coupling reaction of amines, various aldehyde, and terminal alkynes in solvent-free conditions and propargylamine derivatives was gained with excellent yields. Also, the catalyst has high recyclability and can be reused at least six times in the synthesis of propargylamine derivatives with good yields.

Silver Metal-Organic Framework Derived N-Doped Carbon Nanofibers for CO2 Conversion into β-Oxopropylcarbamates.

Developing efficient heterogeneous catalysts for chemical fixation of CO2 to produce high-value-added chemicals under mild conditions is highly desired but still challenging. Herein, we first reported an approach to prepare a novel catalyst (Ag@NCNFs), featuring Ag nanoparticles (NPs) embedded within porous nitrogen-doped carbon nanofibers (NCNFs), via growing a Ag metal-organic framework on one-dimensional electrospun nanofibers followed by pyrolysis. Benefiting from the abundant nitrogen species and porous structure, Ag NPs is well dispersed in the obtained Ag@NCNFs. Catalytic studies indicated that Ag@NCNFs exhibited excellent catalytic activity for the three-component coupling reaction of CO2, secondary amines, and propargylic alcohols to generate β-oxopropylcarbamates under mild conditions with a turnover number (TON) of 16.2, and it can be recycled and reused at least 5 times without an obvious decline in catalytic activity. The reaction mechanism was clearly clarified by FTIR, NMR, 13C isotope labeling, control experiments, and density functional theory calculations. The results suggest that Ag@NCNFs and 1,8-diazabicyclo[5.4.0]undec-7-ene can synergistically activate propargylic alcohol to react with CO2, and then the generated α-alkylidene cyclic carbonate was invaded by secondary amine to produce β-oxopropylcarbamate. Importantly, to the best of our knowledge, this is the first experimental and theoretical investigation on this reaction.

Design, synthesis and characterization of new azoflavone derivatives through diazotisation - coupling reactions of aromatic amines (sulfanilic acid, 2-amino pyridine)

In this research, new azochalcone derivatives (6, 7) were synthesized by using three methods: the first one is diazotization - coupling method of different aromatic amines (sulfanilic acid, 2-aminopyridine) with chalcone (5), the second, aldol condensation method of azoaryl hydroxyacetophenone compounds with 4-dimethylamino benzaldehyde in presence of sodium hydroxide as a catalyst, the last one is method of aldol condensation of azoaryl hydroxyacetophenone compounds with 4-dimethylaminobenzaldehyde in presence of piperidine as an organic catalyst. The yield was the best by using the aldol condensation method with sodium hydroxide as a catalyst. New azoflavone derivatives (8, 9) with good yields (78-84 %) were also synthesized by performing cyclization reactions of azochalcone derivatives using iodine in dimethyl sulfoxide. The identity of the new compounds was determined using spectroscopic methods (FT-IR, 13C-NMR, 1H-NMR).

Synthesis of imines from the coupling reaction of alcohols and amines catalyzed by phosphine-free cobalt(II) complexes.

Phosphine-free, air stable cobalt(II) based complexes (1a and 1b) consisting of ligands L1H2 and L2H2 (L1H2 = N,N'-((1,2-phenylenebis(azaneylylidene))bis(methaneylylidene))diphenol and L2H2 = N,N'-bis(4-diethylaminosalicylidene)-4,5-dichloro-1,2-phenylenediamine) were synthesized and utilized as catalysts in the coupling reaction of alcohols with amines into imines following an acceptorless dehydrogenative pathway. The reactions were carried out in the presence of t-BuOK base with low catalyst loading (1 mol%) in an open atmosphere. The corresponding imines were isolated in moderate to excellent yields. The methodology was screened with different substituted alcohols and amines. The proposed mechanistic pathway of this reaction was ascertained through intermediate mass and 1H NMR analyses. Most of the previously reported 3d transition metal catalysts used in imine synthesis reactions have a phosphine ligand environment, and the reactions were performed under inert conditions. Herein we have developed a sustainable route for the synthesis of imines from the coupling reaction of alcohols with amines under aerial reaction conditions using phosphine-free air stable cobalt catalysts.

Application of 1,4-pentanediol as a renewable solvent for copper-catalyzed Ullmann-type coupling reactions

It was demonstrated that 1,4-pentanediol as a biomass-originated polar protic solvent could be utilized as an alternative reaction medium for copper-catalyzed Ullmann-type coupling reactions of aryl iodides and various amines under mild conditions. The effect of the copper source, the base, the water, and the γ-valerolactone content of the reaction mixture on the reaction performance was investigated. Eighteen cross-coupling products were isolated with yields of 11–69 %, and high purity (>98 %). Two O-arylated products, 4-phenoxypentan-1-ol and 5-phenoxypentan-2-ol were characterized. The recycling of the solvents after product isolation was also demonstrated. These results represent an example that proves that biomass-derived safer solvents can be utilized in common, industrially important transformations.

I2/CAN as a Mild and Efficient Reagent for Oxidative Csp3‐Csp2 Cleavage of 3,3′‐Bis‐7‐azaindolylmethane: A Rapid One‐Pot Access to 3‐Formyl and 3‐Iodo‐7‐azaindoles

AbstractThe combination of I2/CAN has emerged as a mild and powerful reagent for the oxidative Csp3‐Csp2 cleavage of 3,3′‐bis‐7‐azaindolylmethane to provide a quantitative combined yield of 3‐formyl and 3‐iodo‐7‐azaindole in a one‐pot reaction at RT. A plausible mechanism and characterization, including XRD, has been described. The synthetic transformations of title compounds were explored by reduction, Click, reductive amination, and Suzuki coupling reaction.

Design, synthesis and evaluation of novel pyrido fused piperazine derivatives: In vitro cytotoxicity study over various cancer cell lines

In the present work, a series of novel pyrido bearing a fused piperazine ring derivatives has been synthesized via suzuki and acid–amine coupling reactions. The synthesized compounds were screened for their in vitro cytotoxic activity against nine different cancer cell lines such as U-251, Panc-1, MCF-7, HepG2, DU-145, A549, 786-O, OVCAR3 and HCT-116. Synthesized compound also screened under normal cell lines like human lungs normal cell line (WI38) and Mouse embryonic normal cell line (NIH3T3) to evaluate safety of synthesized compounds. The bioassay results indicates that synthesized compounds (cpd-S10, cpd-12, cpd-19, cpd-32, cpd-33, cpd-36 and cpd-38) to be moderately effective towards various cancer cell lines (DU-145, PanC1, MCF7, U-251, HCT-116, 786-O, HepG2, A549, OVCAR-3) in the in vitro testing.

Metallaphotoredox‐Catalyzed Three‐Component Couplings for Practical Synthesis of Ureas and Carbamates†

Comprehensive SummaryUreas are widely used in drugs, materials and catalysts because of their diamide structure, which can form strong hydrogen bonds. Therefore, it is of great scientific significance to develop efficient and green methods for the synthesis of urea compounds, especially unsymmetrical ureas. Here, we have disclosed novel and highly efficient three‐component coupling reactions of organic halides, sodium cyanate and amines enabled by nickel/photoredox dual catalysis for the preparation of unsymmetrical ureas. The reaction features simple and safe operations, broad substrate scopes, and product diversities. It allows the facile synthesis of N‐aryl/vinyl ureas from readily available, user‐friendly feedstocks under mild conditions (27 examples, 36%—98% yields). In addition, this method is further derived to alcohols as nucleophiles to synthesize a series of carbamates (15 examples, 40%—95% yields). The mechanism experiment shows that the isocyanate produced by the coupling of halide and sodium cyanate may be the key intermediate in this reaction.

Synthesis of propargylamines catalyzed by in situ generated copper nanoparticles in water

An efficient and green protocol for the A3 coupling reaction of aldehyde, amine and alkyne involves the use of copper nanoparticles and β-cyclodextrin in water. The copper nanoparticles are generated in situ by reduction with green and cheap sodium hydroxymethanesulfinate (rongalite) while β-cyclodextrin serves as a stabilizing agent and a phase-transfer catalyst.

Pyridine–SO3H]ZnCl3: A Multipurpose Catalyst for A3 Coupling Synthesis of Propargylamines under Mild Conditions

Abstract N-Sulfopyridin-1-ium monozinc(II) trichloride ([NSPy]ZnCl3) was prepared and used as a multipurpose catalyst for the synthesis of propargylamines by the A3 coupling reaction of aromatic aldehydes, alkynes, and secondary amines under mild conditions. In this reaction, the carbonyl group in the aldehyde was activated by the acidic part in the catalyst, and the C–H activation of phenylacetylene was carried out by zinc.

Ce4+/Ce3+ Redox Effect-Promoted CdS/CeO2 Heterojunction Photocatalyst for the Atom Economic Synthesis of Imines under Visible Light.

The employment of stoichiometric alcohols and amines for imine synthesis under mild and green reaction conditions is still a challenge in the field. In this work, based on our research foundation in the thermocatalytic synthesis of imines over ceria, a CdS/CeO2 heterojunction photocatalyst was constructed and successfully realized the atom-economic synthesis of imines under visible light without additives at room temperature. Mechanistic experiments and corresponding characterizations indicated that the CdS/CeO2 heterojunction can improve the separation efficiency of photogenerated carriers, which can be further enhanced by the Ce4+/Ce3+ redox pair by rapidly combining photogenerated e-. The in situ-reduced Ce3+ can better activate O2 to form Ce-O-O·, which, together with h+, efficiently accelerates alcohol oxidation, which is the rate-determined step for the synthesis of imines via oxidative coupling reaction of alcohol and amine. In addition, our photocatalyst exhibited fairly decent reusability and substrate universality. This work solves problems of using base additives and excess amine or alcohol in the reported photocatalytic systems and provides new insight for designing CeO2-based photocatalytic oxidation catalysts.

Structural Optimization of Luminescent Sulfur Dots for Solar Light Induced Efficient and Selective Oxidative Coupling Reactions of Aromatic Amines: A Complete Metal-Free Approach

Structural Optimization of Luminescent Sulfur Dots for Solar Light Induced Efficient and Selective Oxidative Coupling Reactions of Aromatic Amines: A Complete Metal-Free Approach