A3 Coupling Reaction Research Articles

A green approach for A3-coupling reactions: an experimental and theoretical study on NHC silver and gold catalysts

N-heterocyclic carbene silver and gold complexes active in A3-coupling (aldehyde–alkyne–amine) reactions in green conditions.

Gold nanoparticle stabilized dithiocarbamate functionalized magnetite carbon as promise clean nanocatalyst for A3-coupling organic transformation

A novel, efficient, and core/shell nanosphere catalyst (Fe3O4@C-NHCS-Au0) was successfully synthesized with a movable magnetite core encapsulated in a carbon shell. It was modified using APTES (3-aminopropyltriethoxysilane) to convert dithiocarbamate (DTC) functional group in the carbon surface though post-modification with CS2 (carbon disulfide). Au0-nanoparticles were decorated via DTC binder to improve the catalytic activity. It was applied as a high-efficiency nanocatalyst in promoting three-component A3 coupling reaction of alkynes, aldehydes, and amines for the synthesis of propargyl amines under the optimized condition.

Dihydroquinazolinones via A3 -Type Reactions of N-Carbamoyliminium Ions.

A variant of the A3 coupling reaction was developed utilizing in situ generated N-carbamoyliminium ions. The tandem INCIC/A3 -coupling sequence provided a facile one-pot synthesis of dihydroquinazolinone derivatives. The scope of the reaction was demonstrated in solution as well as on solid support. The reaction was further combined with peptide synthesis, SN Ar reactions, CuAAC triazole formation or bromination, providing additional opportunities for further diversification of the dihydroquinazolinone scaffolds.

REACTION OF SOME SALICYL ALDEHYDE DERIVATIVES WITH AMINES ANDPHENYL ACETYLENE

Salicylic aldehydes, amine, and phenyl acetylene could react under the solvent-free, metal-free conditions to form propargylamines 1-4 via A3 coupling reaction. The yield of the reaction was up to 83% for 5h. In acetonitrile, the amine became a catalyst to form 6-bromo-3-(5-bromo-2-hydroxybenzyl)-2-phenyl-4Hchromen-4-one (5). Under microwave conditions, it took about 20 min to complete the reaction and gave the same yields as theconventional method. Structures of these compounds were firm with NMR, MS spectra.

Solvent‐free synthesis of propargylamines via A3 coupling reaction and organic pollutant degradation in aqueous condition using Cu/C catalyst

The present report focuses on the efficient and operationally simple synthesis of biomass‐derived carbon as support to immobilize copper particles as a catalyst for the one‐pot synthesis of propargylamines from furfural via the A3 coupling reaction. This new catalyst showed remarkable catalytic performance leading to a 97% yield within 5 h at 80 °C using 5 mg (0.0022 mmol Cu) of Cu/C catalyst under solvent‐free condition. Moreover, nitro‐substituted compounds such as 4‐nitrophenol (4‐NP) are highly toxic and not easily degradable. Hence, a quick and effective method is required to neutralize these toxic compounds. The synthesized active support Cu/C catalyst having various electron‐donating groups containing small amounts of Cu plays an essential role in the catalytic reduction of 4‐NP (0.1 g). Using only 3 mg (0.0013 mmol Cu) of Cu/C catalyst and NaBH4 (10 mmol), a 99% yield (100% selectivity) in the aqueous condition at 25 °C was achieved. The catalytic reduction follows the pseudo‐first‐order kinetics with reaction rate constant of 0.028 s−1. Moreover, results demonstrate that the Cu/C catalyst has superior catalytic activity due to the presence of electron‐donating molecules such as O, S, and N atoms, which enable synergistic effect in enhancing the overall catalytic performance. Notably, the recoverability and recyclability of the synthesized catalyst were evaluated for up to four cycles, which confirmed its stability in these cycles.

Silver-catalyzed multicomponent reactions for the construction of γ-carbonyl-α-amino acid derivatives

Silver-catalyzed multicomponent strategy for the construction of highly functionalized γ-carbonyl-α-amino acid derivatives has been developed under mild conditions, in which various γ-carbonyl-α-amino acid derivatives were obtained in moderate to excellent yields. Preliminary mechanistic studies suggested that silver-catalyzed A3-coupling reaction and alkyne hydration process were accomplished in a simple operation.

Polymer Beads Decorated with Dendritic Systems as Supports for A3 Coupling Catalysts

The gel type microscopic polymer beads bearing epoxy functionalities were modified using the two-stage procedures in order to decorate their surface with the moieties of the zeroth order PAMAM type dendrimer and different heterocyclic aldehydes (2-pyridinecarboxaldehyde, 2-pyrrolidinecarboxaldehyde, furfural or 2-thiophenecarboxaldehyde). The polymeric supports provided in this manner were then used for the immobilization of copper(II) ions. The resulting materials were characterized using different instrumental techniques (optical microscopy, SEM, FTIR microscopy, DR UV–Vis, ICP-OES, and thermal analysis). They were also used as catalysts in the model A3 coupling reaction of benzaldehyde, morpholine and phenylacetylene. The best catalytic activity was found for the polymeric catalyst bearing 2-pyridinecarboxaldehyde moieties. It turned out to be effective in the A3 coupling reactions included different benzaldehyde, alkyne, and secondary amine derivatives, as well. It could also be recycled several times without a significant decrease in its activity in the model A3 coupling reaction.Graphic

Core-shell iron oxide@cathecol-polymer@palladium/copper nanocomposites as efficient and sustainable catalysts in cross-coupling reactions

Magnetic core-shell Fe2O3@polymer-Pd/Cu nanocomposites (NCs) were developed as efficient and sustainable nanocatalysts for cross-coupling reactions. The designed NCs consisted of three components: i) a magnetic core (Fe2O3 nanoparticle), which allowed the recovery and reuse of the NCs, enhancing thus their attractiveness as green catalysts; ii) a catechol-based polymer coating, chosen because of its strong chelating ability towards metal ions, and its potential to be obtained from biomass (lignin depolymerization); and iii) catalytically active metal nanoparticles (Pd and Cu NPs) immobilized via in situ formation onto the polymeric shell. As-prepared Pd-based NCs successfully catalyzed Suzuki-Miyaura cross-coupling reactions, achieving yields between 87% and 97% in only 20–40 min depending on the aryl halides and boronic acid derivatives. Similarly, Cu-based NCs exhibited a quite good catalytic efficiency (> 80%) in the synthesis of propargylamines via A3 coupling reaction of phenylacetylene with various aldehydes and amines. Importantly, these NCs presented a good reusability, without significant decrease in efficiency after several cycles. However, the major advantage of the designed NCs is the lower Pd or Cu content (1.5 wt% and 2.6 wt%, respectively) as compared to most of the reported similar catalysts (between 3 – 6 wt% for Pd and > 5 wt% for Cu), which is a key challenge in view of developing cost-effective and environment-friendly catalysts while maintaining a high efficiency.

Copper mediated A3-coupling reaction for the preparation of enantioselective deoxy sugar based chiral propargylamines using bifunctional ligand l-proline

An efficient three component coupling of aromatic aldehyde, deoxy sugar based alkyne (α-2-deoxy propargyl glycoside) and heterocyclic amine have been refluxed to synthesize stereoselective chiral propargylamines with good to excellent yield using only CuI catalyst along with bifunctional ligand l-proline. This method has proved to be applicable in wide range of substrates and found highly enantioselective with respect to earlier reported methods. In addition, l-proline was found as a chiral source which demonstrated that it could be developed as a highly enantioselective method for the construction of deoxy sugar based chiral propargylamines. The ligand l-proline was used for the first time in enantioselective A3-coupling reaction of α-2-deoxy propargyl glycosides involving substituted aromatic aldehyde and heterocyclic amines. Herein, we have synthesized 15 novel compounds based on A3-coupling reaction and structures of all the enantioselective compounds were characterised by TLC and NMR spectroscopy.

Biosynthesis of Copper Oxide Nanoparticles with Potential Biomedical Applications.

IntroductionIn recent years, the use of cost-effective, multifunctional, environmentally friendly and simple prepared nanomaterials/nanoparticles have been emerged considerably. In this manner, different synthesizing methods were reported and optimized, but there is still lack of a comprehensive method with multifunctional properties.Materials and MethodsIn this study, we aim to synthesis the copper oxide nanoparticles using Achillea millefolium leaf extracts for the first time. Catalytic activity was investigated by in situ azide alkyne cycloaddition click and also A3 coupling reaction, and optimized in terms of temperature, solvent, and time of the reaction. Furthermore, the photocatalytic activity of the synthesized nanoparticles was screened in terms of degradation methylene blue dye. Biological activity of the synthesized nanoparticles was evaluated in terms of antibacterial and anti-fungal assessments against Staphylococcus aureus, M. tuberculosis, E. coli, K. pneumoniae, P. mirabili, C. diphtheriae and S. pyogenes bacteria’s and G. albicans, A. flavus, M. canis and G. glabrata fungus. In the next step, the biosynthesized CuO-NPs were screened by MTT and NTU assays.ResultsBased on our knowledge, this is a comprehensive study on the catalytic and biological activity of copper oxide nanoparticles synthesizing from Achillea millefolium, which presents great and significant results (in both catalytic and biological activities) based on a simple and green procedure.ConclusionComprehensive biomedical and catalytic investigation of the biosynthesized CuO-NPs showed the mentioned method leads to synthesis of more eco-friendly nanoparticles. The in vitro studies showed promising and considerable results, and due to the great stability of these nanoparticles in a green media, effective biological activity considered as an advantageous.

Synthesis, characterization, and application of zinc supported on ionic liquid‐based periodic mesoporous organosilica (Zn@PMO-IL) in A3-coupling reaction for the synthesis of propargylamines

The present paper shows the preparation of a highly porous periodic mesoporous organosilica (PMO) including the ionic liquid pore walls that supported with zinc ions onto PMO-IL (Zn@PMO-IL). Moreover, the material was characterized using field emission‐scanning electron microscopy, transmission electron microscopy, inductively coupled plasma, and N2 adsorption–desorption. Likewise, the catalytic activity of the Zn@PMO-IL, illustrating a highly efficient nanocatalyst for the synthesis of propargylamines through three-component A3-coupling reaction of various aldehydes, amines, and arylacetylene. The results demonstrate an eco-friendly and appealing method with high efficiency and facile work-up procedure. Furthermore, the nanocatalyst can be revived by a simple filtration process and reuse at least five successive runs without considerable reducing in its activity.

Silica Encapsulated-Gold Nanoparticles as a Nano-reactor for Aerobic Oxidation of Benzyl alcohols and Tandem Oxidative A3 coupling Reactions in Water

In this work, the encapsulated-Au nanoparticles (NPs) into the silica hollow NPs were synthesized by microwave-assisted preparation of PEG-coated Au NPs, coating them with a layer of organically modified silica and removing the PEG around the Au NPs. The structure of these encapsulated NPs was characterized by TEM, SEM, XRD, FTIR, EDX, TGA, and ICP-OES. These NPs have shown excellent activities in the aerobic oxidation of benzyl alcohol derivatives and tandem oxidative A3 coupling reactions as a catalyst and reactor in the water at room temperature. Synthesis of a new silica/gold nanoparticles as catalytic nano-reactor for carrying out A3-coupling reaction in the water at ambient temperature

Green synthesis of quinolines via A3-coupling by using graphene oxide-supported Brønsted acidic ionic liquid

Graphene oxide-supported Bronsted acidic ionic liquid ([GrBenzImi]SO3H) has been prepared by covalent grafting of benzimidazole unit in the matrix of graphene oxide followed by reaction with 1,4-butane sultone and hydrochloric acid. [GrBenzImi]SO3H has been characterized by various techniques including Fourier transform infrared spectroscopy (FTIR), FT-Raman (FT-Raman spectroscopy), CP-MAS 13C NMR spectroscopy, thermogravimetric analysis, energy-dispersive X-ray analysis, Brunauer–Emmett–Teller surface area, X-ray diffraction, and transmission electron microscopy. [GrBenzImi]SO3H was successfully employed as heterogeneous catalyst in A3-coupling reaction of aryl aldehydes, anilines and phenylacetylene for the synthesis of 2,4-disubstituted quinolines using water/ethanol system (1:1) as green medium. [GrBenzImi]SO3H could be recycled six times without significant loss in the yield of product.

Efficient Sonogashira and A3 coupling reactions catalyzed by biosynthesized magnetic Fe3O4@Ni nanoparticles from Euphorbia maculata extract

In this work, biosynthesized Fe3O4@Ni nanoparticles using Euphorbia maculata aqueous have been used as effective catalysts in the synthesis of 2,3‐disubstituted benzo[b]furan derivatives using three component coupling of aldehydes, secondary amines and alkynes (A3 coupling reaction). Using novel nanoscale materials, the current green, practical and economical method leads to short reaction times and high yields. The biosynthesized catalyst was also successfully employed in the Sonogashira cross‐coupling reactions of various aryl halides with phenylacetylene. The best performance was observed using just 20 mg of the catalyst and ethanol as a green solvent. The developed protocol provides easy workup, short reaction times and good to excellent product yields. Furthermore, since the composite is highly stable, an external permanent magnet can be easily used for separating the catalyst. Thus, the catalyst can be recycled several times without considerable loss of catalytic activity.

Modern Catalysts in A3- Coupling Reactions

:Propargylamines are an important constituent of diverse, biologically active and industrially valuable compounds. These useful, convenient and effective compounds can be synthesized via the A3-coupling reactions between an aldehyde, amine, and alkyne in the presence of a catalyst. In the past years, most of the catalysts containing transition metals were applied in these reactions, but today, various heterogeneous catalysts, especially nanocatalysts are used. The purpose of this review was to introduce some modern catalysts for the A3-coupling reaction.

Copper-based catalysts derived from salen-type ligands: synthesis of 5-substituted-1H-tetrazoles via [3+2] cycloaddition and propargylamines via A3-coupling reactions

Base-metal copper(ii) complexes derived from unsymmetrical salen-type ligands were designed and synthesized using ligands L1H to L4H. These complexes were employed as catalysts for [3+2] cycloaddition and A3-coupling reactions.

A multifunctional use of bis(methylene)bis(5-bromo-2-hydroxyl salicyloylhydrazone): from metal sensing to ambient catalysis of A3 coupling reactions.

The potential use of bis(methylene)bis(5-bromo-2-hydroxylsalicyloylhydrazone) as a multifunctional fluorescence sensor for Cu2+, Ni2+, Co2+ and Fe2+ ions was investigated. The optical behaviour shows an increase in an absorption band at 408 nm which can be ascribed to the d–d transition (UV-vis) of the metal ions and a concomitant decrease in fluorescence intensity at 507 nm. The crystallographic analysis shows the binding site of the sensor to two Cu2+ ions and confirms the stoichiometry of 1 : 2 (ligand to metal) which is in good agreement with a Job plot analysis. Furthermore the Cu2+-complex catalyses A3 coupling reactions at 1 mol% catalytic loading; chiral propargylamine derivatives were obtained in high yield after 24 h reaction time under ambient conditions.

DFT study on theE-stereoselective reductive A3-coupling reaction of terminal alkynes with aldehydes and 3-pyrroline

The mechanism of the Cu(i)-catalyzed reductive A3-coupling reaction of terminal alkynes with aldehydes and 3-pyrroline for the synthesis ofE-allylic amines has been studied by DFT calculations.

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.

Fibroin‐functionalized magnetic carbon nanotube as a green support for anchoring silver nanoparticles as a biocatalyst for A3 coupling reaction

Novel and powerful fibroin‐functionalized magnetic carbon nanotube–supported silver nanoparticles (CNT–Fe3O4–fibroin–Ag) were successfully synthesized as a nontoxic and inexpensive biocatalyst. The structure of the organic–inorganic hybrid bionanocomposite was characterized by various techniques such as Fourier transform infrared spectroscopy, thermogravimetric analysis, energy‐dispersive X‐ray, field emission‐scanning electron microscopy, transmission electron microscopy, X‐ray diffraction, vibrating sample magnetometry, atomic absorption spectroscopy, and inductively coupled plasma‐optical emission spectrometry. Then, the catalytic activity of synthesized bionanocomposite was evaluated in the three‐component A3 coupling reaction under solvent‐free conditions with good to excellent yields. Several propargylamine derivatives were synthesized by the reaction of different aldehydes with amines and phenylacetylene. Biodegradability, biocompatibility, availability, easy synthesis, high stability, high‐throughput, cost‐effectiveness, and efficient magnetic separation are some advantages of this catalyst that make it economically justified and sustainable. Moreover, the catalyst can be recycled for several runs without appreciable loss in its catalytic activity.