KA2 Coupling Research Articles

Silver Complex Bearing N-Heterocyclic Carbene Bidentate Chelating Ligand as an Efficient Catalyst in Solvent-Free KA2 Coupling.

We report a synthesis of silver complexes bearing chelating bidentate N-heterocyclic carbene, with various substitutions at the terminal positions of the imidazole moiety of the NHC units. The long aliphatic substituents proved to be beneficial in terms of the synthetic efficiency of the complexes, compared to previously reported methyl substitution. The complexes demonstrated excellent suitability for the KA2 coupling reaction, providing quaternary carbon-containing propargylic amines in yields up to 95 %, under solvent-free conditions. The method showed high tolerance for a wide range of substrates, including naturally occurring ketones, underscoring its practicality. To our knowledge, this represents the first use of a well-defined silver species in KA2 coupling, marking an advancement in the field.

Synthesis of propargylamine: pioneering a green path with non-conventional KA2 coupling approach.

The KA2 coupling reaction is a well-explored and versatile method for forming C-C bonds in synthetic chemistry. It is composed of ketone, amine, and alkyne, which play a major role in the synthesis of propargylamines, known for their diverse biological activities and are used in treating neurogenetical disorders. The KA2 coupling is highly challenging due to the low reactivity of ketimines toward nucleophilic attacks with metal acetylide intermediates formed by activating the C-H bond of the alkyne. Despite predominant studies conducted on thermal conditions for KA2 coupling reactions, green and sustainable approaches like non-conventional methods still have a lot to achieve. This review article provides a comprehensive introduction to the non-conventional approach in the KA2 coupling reaction, outlining its mechanisms and exploring future aspects.

Zinc-aluminum mixed oxide nanocomposites catalyzed KA2 coupling of ketone, amine, and an alkyne: An environmentally benign approach

Heterogeneous catalysis is of prime importance especially to produce essential fine chemicals and organic molecules. Herein, we presented the simplest synthesis and application of zinc-aluminum mixed oxide nanocomposites (ZnAl-MO NCs) as an efficient catalyst for three component one-pot KA2 coupling reactions to prepare tetrasubstituted propargylamines. The as synthesized ZnAl-MO NCs were well characterized using spectroscopic tools viz. PXRD, BET, XPS, HRTEM, ICP techniques. ZnAl-MO NCs selectively catalyze the KA2 coupling reactions between ketone, amine and an alkyne affording wide range of functional substrates with higher conversion rates and yield. The sustainability of the catalyst was also studied systematically by evaluating the green chemistry metrics such as E factor, atom economy and turn over numbers. Notably, the architectures proposed methodology not only highlights the versatility of environmentally benign novel catalyst but also displays lower leaching levels for zinc and aluminum respectively.

Clay based heterogeneous catalysts for carbon-nitrogen bond formation: a review.

Clay and modified clay-based catalysts are widely used in organic transformation. Owing to the interlayer ions and good ion exchange capacity of clay, replacement with another ion and incorporation of different nanomaterials can be done. Due to these significant properties of clay, it can be utilized in the synthesis of various organic compounds. Carbon-nitrogen bonded compounds possess diverse applications in different fields. These compounds are prepared using different solid acid heterogeneous catalysts. This review presents a detailed discussion on clay used for the carbon-nitrogen bond formation reaction, such as the Biginelli reaction and A3 and KA2 coupling reactions. Additionally, other C-N bond formation reactions using various clay-based catalysts such as bentonite, montmorillonite, hydrotalcite and halloysite clay with various metals, metal oxides, Kegging type heteropoly acid and various nanomaterial incorporated clay heterogeneous catalysts are discussed.

A3 polycondensation: A multicomponent step-growth polymerization reaction for the synthesis of polymeric propargylamines

Multicomponent reactions lead to the straightforward synthesis of organic compounds in a one-pot manner. The three-component coupling of aldehydes or ketones with amines and alkynes, commonly known as A3 or KA2 coupling, respectively, is a convenient, highly efficient strategy for the synthesis of propargylamines, a family of compounds with multifaceted chemical behavior. Transferring this multicomponent strategy into the polymer synthesis field can lead to polymers bearing a variety of properties and possible applications. Herein, we report the efficient, straightforward, air tolerant, and sustainable synthesis of various new polymeric propargylamines, in very high to excellent yields. A highly-reactive, earth-abundant, inexpensive, well-defined copper catalyst is employed. An extensive thermal degradation study of the new polymers is also carried out.

Catalysts For Propargylamines Synthesis Via A3, AHA, and KA2 Coupling - A Review

Abstract: Different intermediates are key molecules to synthesize high-added value bioactive and pharmacology molecules such as propargylamines may be synthesized in several ways using catalysts in homogeneous and heterogeneous conditions. This review presents the catalysts which are used in the A3, AHA, and KA2 coupling reactions to afford propargylamines. It also provides a classification of all the propargylamines known up to date in the literature and their reported synthesis conditions.

Gold nanoparticles immobilized on N‐doped ordered mesoporous carbon: An efficient catalyst for A3 and KA2 coupling reactions

Gold nanoparticles immobilized on egg yolk biomass derived N‐doped ordered mesoporous carbon (Au@OMC) were prepared by nano‐casting process using SBA‐15 template and carbonization, followed by removing silica moiety of SBA‐15, and then immobilization of Au nanoparticles. Synthesized Au@OMC was characterized using XRD, SEM, TEM, EDS, XPS, DLS, and BET analysis, revealing the successful immobilization of Au nanoparticles on the surface of OMC material. Au@OMC exhibited high catalytic activity for three‐component A3 coupling reaction between aldehydes, amines, and phenylacetylene to furnish propargyl amines. Also, KA2 coupling reaction between ketones, amines, and phenylacetylene was efficiently performed using Au@OMC catalytic system. Recyclability studies indicated that the recovered catalyst can be reused for five runs without considerable changes in the catalytic activity. The leaching experiment revealed that there is no Au catalyst leaching into the reaction solution.

Silver incorporated into g-C3N4/Alginate as an efficient and heterogeneous catalyst for promoting click and A3 and KA2 coupling reaction

Fe3O4/g-C3N4/Alginate-Ag nanocomposite as a novel and effective nanocatalyst was successfully prepared. This nanocomposite was fully characterized using several techniques such as X‐ray diffraction (XRD), field emission scanning electron microscopy with energy dispersive spectroscopy (FESEM-EDS), transmission electron microscopy (TEM), and Fourier transform infrared spectroscopy (FTIR). In addition, the catalytic activity of this novel and characterized nanocatalyst was investigated in the regioselective synthesis of 1,4-disubstituted 1,2,3-triazoles via click reaction and A3 and KA2 coupling reaction in aqueous media. The prepared nanocatalyst was simply recovered by using an external magnet and reused for several times with a slight loss of catalytic activity.

KA2 and A3 coupling reactions promoted by Fe3O4@T-CS@Cys@Ag+ nanocomposite

Chitosan biopolymer was functionalized with cysteine amino acid via trichloro-1,3,5-triazine-bridged agent. The magnetization process was done due to the treatment of functionalized chitosan with iron oxide nanoparticles. In the final nanocomposite (Fe3O4@T-CS@Cys@Ag+), thiol and carboxylate groups of cysteine were surrounded by silver ions. The catalytic activity of the prepared nanocomposite was studied in KA2 and A3 coupling reactions for the synthesis of propargylamines.

Azo functionalized polystyrene supported Copper nanoparticles: An economical and highly efficient catalyst for A[formula omitted] and KA[formula omitted] coupling reaction under microwave irradiation

The combination of polymeric support and metal nanoparticles were always leading towards better catalytic systems. Herein, we report Cu supported on azo functionalized polystyrene. The synthesized catalyst was characterized by (SEM, HR-TEM, EDX, RAMAN, XPS, and IR). Active Cu species stabilized by azo linkages present in the polymer matrices is responsible for the catalytic activity. We enrolled in the catalyst in A3 (aldehyde, amine, and acetylene) and KA2 (cyclic ketone, amine, acetylene) coupling reaction. Synthesized catalyst performs much better under microwave irradiation as compared to the conventional method. The better activity of the catalyst may be due to the presence of azo linkages which stabilized the copper nanoparticles in polymer matrices. We achieved 98% yield in both the coupling reactions and time ranges between 15–20 min. We synthesized six derivatives of tetra substituted propargylamine and twenty two derivatives of propargylamines by utilizing optimized conditions. Furthermore, the synthesized catalyst and the reaction conditions were environmentally friendly. In the reusability scan, we found that catalyst was reuse more than seven times with a slight loss in its activity.

Zn-Catalyzed Multicomponent KA2 Coupling: One-Pot Assembly of Propargylamines Bearing Tetrasubstituted Carbon Centers

Tetrasubstituted propargylamines comprise a unique class of highly useful compounds, which can be accessed through the multicomponent coupling between ketones, amines, and alkynes (KA2 coupling), an underexplored transformation. Herein, the development of a novel, highly efficient, and user-friendly catalytic system for the KA2 coupling, based on the environmentally benign, inexpensive, and readily available zinc acetate, is described. This system is employed in the multicomponent assembly of unprecedented, tetrasubstituted propargylamines derived from structurally diverse, challenging, and even biorelevant substrates. Notable features of this protocol include the demonstration of the enhancing effect that neat conditions can have on catalytic activity, as well as the expedient functionalization of hindered, prochiral cyclohexanones, linear ketones, and interesting molecular scaffolds such as norcamphor and nornicotine.

Solvent-Free A3 and KA2 Coupling Reactions with mol ppm Level Loadings of a Polymer-Supported Copper(II)–Bipyridine Complex for Green Synthesis of Propargylamines

A copper(II)–bipyridine complex immobilized on amphiphilic polystyrene–poly(ethylene glycol) (PS–PEG) resin (PS–PEG-BPy–CuBr2) has been developed. The immobilized copper(II)–bipyridine complex at a mol ppm level of loading efficiently catalyzed the three-component coupling of aldehydes or ketones, amines, and alkynes (A3 or KA2 coupling) under solvent-free conditions to give the corresponding propargylamines in good-to-excellent yields. Moreover, 10 g-scale green syntheses of propargylamines proceeded with excellent atom economy (E factor ≥ 0.38) through a solvent-free A3 coupling using 5 mol ppm of PS–PEG-BPy–CuBr2. The total turnover number and turnover frequency of the catalyst reached as high as 178 800 and 7450 h–1, respectively.

Covalently Copper(II) Porphyrin Cross-Linked Graphene Oxide: Preparation and Catalytic Activity

In this study, copper(II)-coordinated 5,10,15,20-tetrakis(aminophenyl)porphyrin (CuPPh) as a macrocyclic copper complex was covalently linked to the surface of graphene oxide (GO–CuPPh). This covalently cross-linked catalyst was characterized with various analysis such as FT-IR, SEM, TEM, EDS, ICP, TGA and UV–Vis. All analysis confirm the successful covalently immobilization of CuPPh on the GO. Then, the activity of catalyst has been tested for the preparation of propargylamine derivatives by the reaction of different aldehydes/ketones various amines and phenylacetylene via A3 and KA2 coupling reactions. The catalytic system indicated great catalytic activity in this reaction and the yields of the products were good to marvelous. The results of this work are hoped to aid the establishment of new class of heterogeneous catalysts as the high performance and low-cost candidates for industrial applications.

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.

KA2‐Coupling Reaction Catalyzed by Semi‐Heterogeneous Magnetically Graphene Oxide Supported Copper Catalyst under Microwave Condition

AbstractFunctional Schiff base chelating groups (PCA) were covalently grafted onto the surface of magnetic graphene oxide (GO‐Fe3O4) via a facile silanization reaction under mild condition. The obtained GO‐Fe3O4‐PCA was further chelated with CuCl2 as an efficient, robust, and recyclable semi‐heterogeneous catalyst (GO‐Fe3O4‐CuCl2) for one‐pot three‐component KA2 coupling of ketones, amines, and alkynes. It exhibited environmentally benign, excellent magnetic separation performance, and higher catalytic activity than other commercially available copper sources. A series of propargylamines are prepared from cycloketones, cycloamines, and phenylacetylene in moderate to excellent yields under microwave (MW) irradiation (70–93%). Interestingly, the catalyst can be separated conveniently by a simple magnetic separation and reused at least four consecutive runs with a slight drop in the product yields. The semi‐heterogeneous property and excellent accessibility of GO‐Fe3O4‐CuCl2 might cause high catalytic activity.

Preparation of Ag‐doped g‐C3N4 Nano Sheet Decorated Magnetic γ‐Fe2O3@SiO2 Core–Shell Hollow Spheres through a Novel Hydrothermal Procedure: Investigation of the Catalytic activity for A3, KA2 Coupling Reactions and [3 + 2] Cycloaddition

Taking advantageous of both g‐C3N4 and magnetic core‐shell hollow spheres, for the first time a heterogeneous and magnetically separable hybrid system was prepared through a novel and simple hydrothermal procedure and used for immobilization of bio‐synthesized Ag(0) nanoparticles. The hybrid system was fully characterized by using SEM/EDS, FTIR, VSM, TEM, XRD, TGA, DTGA, ICP‐AES, BET and elemental mapping analysis. The catalytic utility of the obtained system, h‐Fe2O3@SiO2/g‐C3N4/Ag, for promoting ultrasonic‐assisted A3, KA2 coupling reactions and [3 + 2] cycloaddition has been confirmed. The results established that the catalyst could efficiently catalyze the reaction to afford the corresponding products in high yields in short reaction times. The reusability study confirmed that the catalyst could be recovered and reused for at least five reaction runs with only slight loss of the catalytic activity. The hot filtration test also proved low silver leaching, indicating the heterogeneous nature of the catalysis.

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.

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.

Microwave assisted one pot three component synthesis of propargylamine, tetra substituted propargylamine and pyrrolo[1,2-a]quinolines using CuNPs@ZnO–PTh as a heterogeneous catalyst

A Cu@ZnO–PTh nanocomposite was synthesized and used as a heterogeneous catalyst for KA2 and A3 coupling, which is a highly efficient and green technique.

Green bio‐based synthesis of Fe2O3@SiO2‐IL/Ag hollow spheres and their catalytic utility for ultrasonic‐assisted synthesis of propargylamines and benzo[b]furans

A novel magnetic hybrid system containing nano‐magnetic Fe2O3 hollow spheres, silica shell, [pmim]Cl ionic liquid and silver nanoparticles was synthesized and characterized. The silver nanoparticles were prepared via biosynthesis using Achillea millefolium flower as reducing and stabilizing agent. The hybrid system was successfully used as an efficient and reusable catalyst for promoting green ultrasonic‐assisted A3 and KA2 coupling reactions as well as benzo[b]furan synthesis. It was found that decoration of the magnetic core with non‐magnetic moieties decreased the maximum saturation magnetization. However, the catalyst was still superparamagnetic and could be simply separated from the reaction mixture using an external magnet. The heterogeneous nature of the catalyst was also confirmed by studying its reusability and stability and the leaching of silver. Use of aqueous media, high yields, short reaction times, broad substrate tolerance and low required amount of catalyst are the merits of this protocol.