A3 Coupling Research Articles

Copper incorporated into 1H-1,2,3-triazole-5-methanol functionalized halloysite nano clay as an efficient and heterogeneous catalyst for promoting green A3 and KA2 coupling reaction: Optimization of reaction variables using response surface methodology

Abstract Design and synthesis of a novel heterogeneous catalyst based on functionalization of halloysite nanoclay with 1H-1,2,3-triazole-5-methanol and subsequent incorporation of copper is disclosed. The obtained catalyst was fully characterized by employing ICP-AES, SEM/EDX, TGA, XRD, BET and FTIR and successfully used for promoting the A3 and KA2 coupling reactions of phenylacetylene, amines and aldehydes or ketone in aqueous media. The reaction variables including reaction temperature and amount of the catalyst were optimized using Response Surface Methodology (RSM). The catalyst exhibited excellent catalytic activity under optimum reaction condition. Notably, the investigation of the reusability of the catalyst confirmed that the catalyst could be recovered and reused up to four reaction runs with only slight loss of the catalytic activity. The hot filtration experiment also demonstrated low leaching of copper species, indicating the heterogeneous nature of the catalysis. Easy work-up procedures, performing the reaction in aqueous media, broad range of substrate scope and low reaction times are other merits of this protocol.

MIL-101 supported highly active single-site metal catalysts for tricomponent coupling

Metal-organic frameworks with regular pore structures provide powerful platforms for the design of single-site metal catalysts for chemical transformation. In this paper, we develop a facile, stable and recyclable MOF-supported Cu(II) catalyst, MIL-101-SO3Cu. It shows extremely high activity for the A3 coupling of alkynes, aldehydes and amines. The turnover frequency can reach 6.8 × 105 h−1 under neat conditions, which is the highest so far reported for the reaction. The high activity is because the specific structure of the MIL-101-SO3 support enables a single-site dispersion and an unhindered open environment for the metal ion. MIL-101-SO3Cu also exhibits high activity for the one-pot cascade reactions combining A3 coupling and 5-endo-dig cyclization.

Fiber-polyquaterniums@Cu(I) as recyclable polymer-supported copper complex catalysts for alkyne coupling and cycloaddition reactions

Herein, a newly designed and synthesized fiber-supported polyquaterniums@Cu(I) served as efficient and recyclable polymer-supported copper complex catalysts for alkyne coupling and cycloaddition reactions, is reported. The fiber-supported copper complex catalyst was prepared systematically from commercially available polyacrylonitrile fiber, and characterized detailedly by elemental analysis, FTIR spectroscopy, mechanical properties, and SEM during both of the preparation and utilization processes. Moreover, the fiber-supported polyquaterniums@Cu(I) has been verified to possess high catalytic activities for the homocoupling of terminal alkyne in ethyl acetate (10 samples yields 83–99%, 10 cycles from 98% to 95%), A3 coupling of alkyne, aldehyde and amine in toluene (10 samples yields 81–94%, 10 cycles from 94% to 90%), and click chemistry of CuAAC reactions in water (10 samples yields 82–99%, 21 cycles from 97% to 96%). Furthermore, the newly developed fiber catalyst in spinning basket reactor displayed excellent stability and recyclability, and the concise and effective gram-scalable operation has extensive application prospect on chemical productions.

Oxidation or Reduction State of Au Stabilized by an MOF: Active Site Identification for the Three‐Component Coupling Reaction

AbstractAs one of the most efficient catalysts for the three‐component coupling reaction of aldehyde, amine, and alkyne (A3 coupling), Au has attracted extensive attention, but there is a debating issue on whether Auδ+ (δ > 0, representing the oxidation state of Au species) or Au0 is the better active site. According to previous reports, both Auδ+ and Au0 can catalyze the A3 coupling reaction. Therefore, the establishment of a suitable comparison model to identify the better active site is highly desired. In this work, an ideal model to identify the efficient active sites for the A3 coupling reaction based on a metal–organic framework (MOF) platform is rationally fabricated. The Auδ+ in oxidation state can be well bound to the MOF, MIL‐101‐NH2, via postsynthetic modification, and the Au0 catalyst with retained MOF skeleton can be formed via a subsequent one‐step reduction, which provide ideal comparison models with the only difference in the Au oxidation state. Strikingly, the two catalysts exhibit significant activity difference in the A3 coupling reaction. The activity of Auδ+ catalyst is 11‐fold higher than that of Au0, which reveals that Auδ+ serves as a much more effective active site in the A3 coupling reaction.

Gold Catalyzed Multicomponent Reactions beyond A³ Coupling.

The preparation of complex architectures has inspired the search for new methods and new processes in organic synthesis. Multicomponent reactions have become an interesting approach to achieve such molecular diversity and complexity. This review intends to illustrate important gold-catalyzed examples for the past ten years leading to interesting skeletons involved in biologically active compounds.

Altering Copper‐Catalyzed A3 Couplings by Mechanochemistry: One‐Pot Synthesis of 1,4‐Diamino‐2‐butynes from Aldehydes, Amines, and Calcium Carbide

AbstractThe ability of mechanochemistry to alter established chemical selectivity is demonstrated. A copper(I)‐catalyzed mechanochemical aldehyde/alkyne/amine coupling using calcium carbide as the acetylene source provides selective access to 1,4‐diamino‐2‐butynes, which contrasts classical approaches that provide propargylamine‐type products. Solventless milling conditions were found to be essential to unmask A3 coupling products with new compositions.

Altering Copper-Catalyzed A3 Couplings by Mechanochemistry: One-Pot Synthesis of 1,4-Diamino-2-butynes from Aldehydes, Amines, and Calcium Carbide.

The ability of mechanochemistry to alter established chemical selectivity is demonstrated. A copper(I)-catalyzed mechanochemical aldehyde/alkyne/amine coupling using calcium carbide as the acetylene source provides selective access to 1,4-diamino-2-butynes, which contrasts classical approaches that provide propargylamine-type products. Solventless milling conditions were found to be essential to unmask A3 coupling products with new compositions.

Iron oxide modified with pyridyl‐triazole ligand for stabilization of gold nanoparticles: An efficient heterogeneous catalyst for A3 coupling reaction in water

Fe3O4 nanoparticles were modified with pyridyl‐triazole ligand and the new magnetic solid was applied for the stabilization of very small and uniform gold nanoparticles. The resulting magnetic material, Fe3O4@PT@Au, was characterized using various methods. These gold nanoparticles on a magnetic support were applied as an efficient heterogeneous catalyst for the three‐component reaction of amines, aldehydes and alkynes (A3 coupling) in neat water with 0.01 mol% Au loading. Using magnetic separation, this catalyst could be recycled for seven consecutive runs with very small decrease in activity. Characterization of the reused catalyst did not show appreciable structural modification.

N-Heterocyclic carbene–copper complex supported on ionic liquid-modified graphene oxide: versatile catalyst for synthesis of (i) 1,2,3-triazole and (ii) propargylamine derivatives

A N-heterocyclic carbene–copper complex grafted on graphene oxide with an ionic liquid framework was prepared. The synthesis of (i) 1,2,3-triazole derivatives by ‘Click reaction’ and (ii) propargylamine derivatives by ‘A3 coupling reaction’ in aqueous media by this new catalyst were all successfully accomplished. The catalyst is characterized using infrared spectroscopy, Raman spectroscopy, scanning electron microscopy, thermogravimetric analysis and energy dispersive X-ray spectroscopy, X-ray photoelectron spectroscopy, transmission electron microscopy, and elemental analysis. The catalyst is reused in the ten reaction cycles without considerable loss of catalytic activity.

CuI@Sulfur-functionalized halloysite nanoclay: a novel recyclable catalyst for the ultrasonic-assisted synthesis of propargylamines: a combination of experimental and DFT simulation

A novel heterogeneous catalyst, CuI supported on sulfur functionalized halloysite (CuI@HNTs-S), was designed and synthesized through functionalization of the halloysite nanoclay surface with 3-mercaptopropyl trimethoxysilane and subsequent immobilization of CuI. The catalyst was characterized by using various characterization techniques such as FTIR, SEM/EDS, XRD, ICP and TGA. The catalytic activity of CuI@HNTs-S for the synthesis of propargylamines through ultrasonic-assisted multi-component A3 coupling reaction of aldehydes, phenyl acetylene and amines was also studied. The results established that CuI@HNTs-S could efficiently catalyze the reaction to furnish the desired products in excellent yield and in short reaction time. Notably the catalyst was recyclable and could be recycled with slight loss of the catalytic activity for five reaction runs. Then, the ability of pristine HNTs and sulfur functionalized HNTs toward CuI grabbing was compared quantitatively using molecular simulation. Calculated energies confirmed better performance of HNTs-S toward CuI physisorption, which decreases its leaching during catalytic reaction. This result was experimentally confirmed by observing the superior recyclability and low copper leaching of CuI@HNTs-S compared to CuI@HNTs.

Copper oxide nanoparticle catalysed synthesis of imidazo[1,2-a]pyrimidine derivatives, their optical properties and selective fluorescent sensor towards zinc ion

Synthesis of biologically active fused imidazo[1,2-a]pyrimidines were achieved via A3 coupling involving 2-aminobenzimidazole, aldehyde and terminal alkyne, followed by 6-endo-dig cyclization using copper oxide nanoparticles under solvent free condition. Further optical properties of imidazo[1,2-a]pyrimidines were studied which showed the effect of electron-donating and electron-withdrawing substitution on the fluorescence intensities of these compounds. Out of 20 compounds, 2,4-bis(4-methoxyphenyl)benzo[4,5]imidazo[1,2-a]pyrimidine can act as a fluorescent sensor for zinc ion with detection limit 4.74 μM, which is much lower than the maximum allowable zinc concentration in drinking water by WHO.

Gold Nanoparticles Supported on Imidazole‐Modified Bentonite: Environmentally Benign Heterogeneous Catalyst for the Three‐Component Synthesis of Propargylamines in Water

Gold nanoparticles supported on imidazole-modified bentonite, Bent@Im@Au NPs, has been developed for the first time as an effective heterogeneous catalyst for the synthesis of propargylamines under mild reaction conditions in water at a loading of 0.07 mol % of Au. Various techniques such as X-ray diffraction, high-resolution transmission electron microscopy, Fourier transform infrared spectroscopy, and element mapping by scanning electron microscopy were used to determine the physicochemical properties of the catalysts. The new gold catalyst was found to be highly active providing high to excellent yields of A3 coupling products via the reactions of various aldehydes, having electron-withdrawing as well as electron-donating substituents, with different amines and alkynes. The catalysts can be easily recovered and reused without significant loss of activity and the recycled catalyst was characterized.

Preparation, Characterization, and Catalytic Property of a Cu(II) Complex with 2-Carboxybenzaldehyde-p-Toluenesulfonyl Hydrazone Ligand

Metal-organic complex hybrid materials constructed from carboxylate ligands and hydrazone ligands have exhibited potential application in many fields. In order to enrich the applications of the metai-organic complex materials, a new hydrazone ligand contains carboxylate group, 2-carboxybenzaldehyde-p-toluenesulfonyl hydrazone (L1), and its Cu(II) complex (C2), have been prepared. The structure of L1 was determined by elemental analysis, IR spectra and single crystal X-ray diffraction, and the composition of Cu(II) complex (C2) has also been determined by elemental analysis, IR and UV spectra. The catalytic activity for A3 coupling reaction of benzaldehyde, piperidine, and phenylacetylene has been investigated. The results show that Cu(II) complex displays a 100 % selectivity to the product of propargylamine during A3 coupling reaction and benzaldehyde conversions were 95.3, 94.2, and 93.4 % at 120 °C for 12 h in the first, second, and third reaction cycles, respectively.

A Review on Recent Advances in the Application of Nanocatalysts in A3 Coupling Reactions.

A3 coupling is one of the few transition-metal catalyzed carbon-carbon bond forming reactions that have been established as a most direct, efficient and atom-economical synthetic approach to afford propargylamine derivatives using various catalysts. A large number of nanosized heterogeneous catalysts for three-component coupling reactions between an aldehyde, an amine, and a terminal alkyne have been popularly introduced as an A3 coupling in the last decade. The coupling product has found a broad application as a key intermediate for a variety of heterocyclic useful compounds and numerous biologically active molecules such as β-lactams, conformationally restricted peptides, isosteres, herbicides, fungicides, indolizines, pyrroles, quinolines and therapeutic drug molecules. This review aims to give an overview of the current progress made towards the preparation and application of various nanocatalysts-catalyzed A3 coupling transformations for the synthesis of propargylamines from 2007 to 2017. Several nanocatalysts based on metal and metal oxide nanoparticles (NPs) such as copper, gold, silver, iron, nickel, cobalt and zinc have successfully been employed in A3 coupling reactions. Besides, core-shells NPs, polymers, complexes, graphenes, metal-organic frameworks and ionic liquids have also been used in these reactions. Abundant examples have been given in this area. Different aspects of the reactions, disparate methods of preparation of nanocatalysts, characterization and their reusability have been perused.

Eco‐friendly magnetic clinoptilolite containing Cu(0) nanoparticles (CuNPs/MZN): as a new efficient catalyst for the synthesis of propargylamines via A3 and KA2 coupling reactions

In this reaserch a new and eco‐friendly magnetic catalyst for the synthesis of propargylamines is reported. Initial incorporation of Fe3O4 magnetic nanoparticles (MNPs) into the pores of the natural clinoptilolite zeolite followed by modification with epichlorohydrine and ethylenediamine and then immobilization of CuNPs on the surface of functionalized zeolite gave the desired catalyst (CuNPs/MZN). The CuNPs/MZN was fully characterized by various techniques such as FT‐IR, CHN, TGA, ICP, XRD, SEM, TEM and BET. A host of propargylamines were readily synthesized through using the catalyst in high yields and short reaction times via A3 and KA2 coupling reactions of aldehydes/ketones, amines, and phenylacetylene. The CuNPs/MZN was easily separated from the reaction mixture by an external magnet and reused several times successfully. The catalyst has the potential for catalysis of various organic transformations.

Efficient Synthesis of Propargylamines in Aqueous Media Catalyzed by Au Nanoparticles under Ambient Temperature

AbstractAn eco‐friendly gold‐based catalyst supported on proline decorated montmorillonite was synthesized. The catalyst was characterized by combination of Fourier‐transform infrared spectroscopy (FT‐IR), Field Emission Scanning Electron Microscopy (FE‐SEM), transmission electron microscopy (TEM), X‐ray diffraction (XRD), Brunauer–Emmett Teller (BET) surface area analysis, Ultraviolet–visible spectroscopy (UV‐Vis), Energy‐dispersive X‐ray spectroscopy (EDX), thermo gravimetric analysis (TGA) and atomic absorption spectroscopy (AAS) techniques. The synthesized catalyst was found to be a highly efficient heterogeneous nanocatalyst for multi component A3 coupling reaction of aldehyde, amine and alkyne in water as a green solvent at room temperature. This novel catalyst promotes multicomponent reaction of a large library of functional substrates under mild and sustainable conditions (water as a green solvent at ambient temperature). In addition, the catalyst could be easily recovered by simple filtration and reused for at least 6 cycles without losing its activity.

Ultrasonic and bio‐assisted synthesis of Ag@HNTs‐T as a novel heterogeneous catalyst for the green synthesis of propargylamines: A combination of experimental and computational study

A novel heterogeneous catalyst is prepared through functionalization of halloysite nanotube with 1H‐1,2,3‐triazole‐5‐methanol and subsequent immobilization of silver nanoparticles through bio‐assisted approach using Arctiumplatylepis extract. The resulting catalyst, Ag@HNTs‐T, was characterized by using SEM/EDX, BET, XRD, FTIR, ICP‐AES, TGA, DTGA and elemental mapping analysis. Moreover, we computationally assessed metal‐ligand interactions in Ag@HNTs‐T complex model to interpret the immobilization behavior of silver nanoparticles on HNTs surface via quantum chemistry computations. The catalytic activity of the catalyst was studied for the synthesis of propargylamines via A3 and KA2 coupling reactions under ultrasonic irradiation. The results demonstrated that Ag@HNTs‐T could efficiently promote these reactions to furnish the corresponding products in high yields and short reaction times. The study of the recyclability of the catalyst and Ag(0) leaching confirmed that the catalyst was recyclability up to four reaction runs with slight Ag(0) leaching.

A 12-Fold ThSi2 Interpenetrated Network Utilizing a Glycine-Based Pseudopeptidic Ligand

We report the synthesis and characterization of a 3D Cu(II) coordination polymer, [Cu3(L1)2(H2O)8]·8H2O (1), with the use of a glycine-based tripodal pseudopeptidic ligand (H3L1 = N,N′,N″-tris(carboxymethyl)-1,3,5-benzenetricarboxamide or trimesoyl-tris-glycine). This compound presents the first example of a 12-fold interpenetrated ThSi2 (ths) net. We attempt to justify the unique topology of 1 through a systematic comparison of the synthetic parameters in all reported structures with H3L1 and similar tripodal pseudopeptidic ligands. We additionally explore the catalytic potential of 1 in the A3 coupling reaction for the synthesis of propargylamines. The compound acts as a very good heterogeneous catalyst with yields up to 99% and loadings as low as 3 mol %.

Copper(I)‐catalyzed multicomponent reactions in sustainable media

Multicomponent reactions including Biginelli reaction and A3 coupling are useful synthetic methodologies as they can provide valuable intermediates and building blocks for the synthesis of bioactive natural compounds. The heterocyclic products of these transformations represent antibacterial, antitumor or anti‐inflammatory properties. In presented study, copper‐mediated protocols for Biginelli reaction and A3 coupling in sustainable solvents were reported. At first, charged NHC copper complexes were synthesized in few steps and characterized using spectroscopic methods followed by preliminary activity tests in sustainable media. Later in this study, Biginelli reaction and A3 coupling were proceeded using prepared copper catalytic systems under mild conditions. Desired nitrogen‐bearing products were obtained with moderate to very high yields. Some attempts to recycle one of the received NHC copper initiators were also investigated.

Progress in Synthesis of Propargylamine and Its Derivatives by Nanoparticle Catalysis via A3 coupling: A Decade Update

AbstractPropargylamine and its derivatives are important skeletal structure for synthesis of many nitrogen containing active biological and pharmaceutical compounds. They are classically prepared from aldehyde, amine and alkyne (A3 coupling) which proved to be an exciting method since water is the only by‐product with the desired compound. Three component coupling strategies are very attractive research domain in organic chemistry during the past two decades for the synthesis of highly functionalized organic molecules. Molecular diversity in three component reactions ends up with several methods for drug discovery process towards the synthesis of structurally tailored heterocyclic compounds. These one pot transformation processes do involve simultaneous addition of reactants, reagents and catalyst. The reactions are generally carried out by employing several transition metal catalysts. Nanoparticles have shown their potential as catalysts in several fields of chemical research in modern era. Now, they have taken entry in multicomponent reaction system for playing the role of a catalyst. This review highlights a library of metal nanoparticles which have been used in recent years for synthesis of propargylamine and its derivatives via A3 coupling reactions.