A3 Coupling Reaction Research Articles

One-pot multicomponent polymerization towards heterocyclic polymers: a mini review.

Multicomponent polymerization (MCP) is an innovative field related to polymer-based chemistry that offers numerous advantages derived from multicomponent reactions (MCRs). One of the key advantages of MCP is its ability to achieve high efficiency. Additionally, MCP offers other advantages, including operational simplicity, mild reaction conditions, and atom economy. MCP is a versatile technique that is used for synthesizing a wide range of analogs from several classes of heterocyclic compounds. The ring structures of heterocyclic polymers give them different mechanical, photophysical, and electrical properties to other types of polymers. Because of their unique properties, heterocyclic polymers have been widely utilized in various significant applications. MCRs are a type of chemical reaction that can be used to synthesize a wide variety of compounds in a single pot, which allows researchers to quickly assemble libraries of compounds. The development of MCPs from MCRs has made it easier to access a library of polymers with tunable structures. However, MCPs related to alkynes or acetylene triple bonds have more potential. In this review study, we provide an overview of the synthesis of heteroatom-functional polymers and alkyne-based development or other reactions such as Cu-catalyzed, catalyst-free, MCCP, MCTPs, green monomers, A3 coupling reactions, Passerini reactions, and sequence- and controlled-multicomponent polymerization. The up-to-date progress provides a convenient and efficient kind of approach related to heteroatoms and MCP synthesis, and perspectives in terms of future directions are also discussed in the study.

Mechanochemical Cu(ii) complexes and propargylamine synthetic adventures

We synthesized and characterized known and new Cu(ii)–salen complexes and investigated their efficacy in yielding propargylamines (PAs) via an A3 coupling reaction mechanochemically.

CuS Morphology Control for Enhanced Catalytic Performance in A3 Coupling Reaction

AbstractA3 coupling reaction can be used to efficiently synthesize propargylamine, which is an important bioactive molecule intermediate, and copper sulfide (CuS) as its catalyst is rarely reported. Herein, CuS with different morphologies including nanoflowers (NFS), nanorods (NR), nanoparticles (NP) were synthesized and applied to the A3 coupling reaction. The results show that CuS NP has the highest catalytic activity (99 % conversion) compared to other CuS, and also has good group compatibility and recyclability. Combining the activity with the CuS surface structure checked by XPS, BET and HRTEM etc., the excellent catalytic performance of CuS NP can be attributed to its higher specific surface area ((SBET=26.9 m2/g, SLangmuir=144.2 m2/g), and higher Cu+/Cu0 (58.9 %), Sn2− (16.7 %). The large specific surface area can provide more active sites, and higher Cu+/Cu0, Sn2− content are conducive to promoting the activation of alkyne terminal C−H, which is an important step in the A3 coupling reaction.

Effect of counterion on the catalytic activity of NHC-gold(I) in A3 coupling reactions

Synthetic A3-coupling represents an efficient and environmentally convenient procedure for the production of propargylamines, relevant intermediates for the preparation of pharmacologically active substances. Gold(I) complexes of general formula NHC-Au-X have been synthesized, characterized, and tested in the A3-coupling reaction of benzaldehyde, piperidine and phenylacetylene on varying the anionic fragment X as halogenide (Cl, Br, I), acetate (OAc), hexafluorophosphate (PF6) or phenylacetylide (-C≡CPh), with 5-dichloro[N-methyl, N’(2-hydroxy-2-phenyl)ethyl imidazole-2-ylidene as NHC ligand. The kinetic profiles were interpreted with DFT (Density Functional Theory) studies on bond dissociation energies (BDE) of the counterion as well as on the relative stability of the neutral NHC-Au-X complexes with respect to their ionic forms [Au(NHC)2]+[AuX2]−.

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.

Recyclable bispyridine functionalized polyacrylonitrile fibers as ligand of Cu(II) for A3 coupling reaction

Developing an effective and economical technology to achieve the recovery of catalysts in the process of organometallic synthesis has attracted significant attention. Herein, a novel functional fiber catalyst with bispyridine structure was successfully constructed by modifying the commercial polyacrylonitrile fiber. Modified bidentate ligand fiber-based can be used to efficiently complexe Cu(II). The functional fibers were fully characterized by FTIR, ICP, XPS, XRD, SEM, and TGA. To verify the catalytic activity of PANbis(Py)-Cu(II)F, A3 coupling reaction was applied in this work. The results showed that only 0.1 mol% catalyst dosage was needed and the maximum isolated yield was up to 99%. Recycle experiments showed that PANbis(Py)-Cu(II)F has fine recycling performance, and there is no decrease in catalytic efficiency during the first six cycles. Consequently, as a recyclable functional fiber catalyst based on commercial polyacrylonitrile fiber, it provided a new insight for green synthesis and industrial production.

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.

Post-synthetic modification of UIO-66-NH2 as a highly efficient and recyclable nanocatalyst in the three-component coupling (A3) reaction for the synthesis of propargylamine derivatives

In this work, modified metal-organic frameworks (MOFs) of UIO-66-NH2-Glyoxal@Pd nanoparticles (UIO-66-NH2-Gl@Pd NPs) and UIO-66-NH2-Furfural@Ni (UIO-66-NH2-Fu@Ni) NPs were prepared to investigate their performance as nanocatalysts in synthesis of propargylamine derivatives using three-component coupling reaction. A number of analyzes were used to confirm the synthesis of the modified frameworks. ICP-OES analysis showed the presence of 2.98 wt.% of Pd in the UIO-66-NH2-Gl@Pd NPs framework structure and 2.98 wt.% of Ni in the UIO-66-NH2-Fu@Ni. The catalytic activities of the modified frameworks were considered in the A3-coupling reaction by benzaldehyde derivatives, amine, and phenylacetylene for the preparation of propargylamine derivatives. High surface area and porosity of UIO-66-NH2 cause to high catalytic activity of nanocatalysts in the A3-coupling reaction. The nanocatalysts can be recycle and reuse several times. The proposed method for the synthesis of propargylamine derivatives is feasible to wide range of substrates and cause to some benefits such as short time of reaction and fruitful results.

Tandem CuI – Zinc dust as a sustainable catalyst for the preparation of propargylamine derivatives via an A3 coupling reaction, under neat conditions

The cooperative activity of two proximal metal ions is well-known to exhibit highly efficient and synergistic catalytic activities in living organisms. Owing to this knowledge, tandem Cu–Zn systems have been widely used to catalyze a diversity of chemical transformations. This report describes the use of CuI and zinc dust as a sustainable tandem catalyst for the preparation of propargylamines via a three-component coupling reaction under neat conditions. This reaction proceeds at low temperature, and produces good yields with a number of aliphatic and aromatic aldehydes. The reactivity of a number of amines and alkynes has also been explored under these reaction conditions, resulting in 33 fully characterized compounds prepared in the process. Among the ketones tested during this study, only cyclohexanone was able to produce the expected product in a decent yield. The catalytic system reported here represents one of the sustainable approaches to the preparation of propargylamines, as it involves the use of naturally abundant metals as a tandem catalyst, at a low temperature and under neat conditions.

A sustainable avenue for the synthesis of propargylamines and benzofurans using a Cu-functionalized MIL-101(Cr) as a reusable heterogeneous catalyst

A heterogeneous copper-catalyzed A3 coupling reaction of aldehydes, amines, and alkynes for the synthesis of propargylamines and benzofurans has been developed. Here, the modified metal–organic framework MIL-101(Cr)-SB-Cu complex was chosen as the heterogeneous copper catalyst and prepared via post-synthetic modification of amino-functionalized MIL-101(Cr). The structure, morphology, thermal stability, and copper content of the catalyst were determined by FT-IR, PXRD, SEM, TEM, EDX, TGA, XPS, and ICP-OES. The catalyst shows high catalytic activity for the aforementioned reactions under solvent-free reaction conditions. High yields, low catalyst loading, easy catalyst recovery and reusability with not much shrink in catalytic activity, and a good yield of 82% in gram-scale synthesis are some of the benefits of this protocol that drove it towards sustainability.

HAuCl4 Catalyzed and Dibenzyl amine Centered A3 coupling reaction: Synthesis, Spectroscopic Proofing and Anti‐microbial Efficacy

AbstractThis research suggests an ideal method for synthesizing propargyl amine adducts by a three‐component condensation of dibenzyl amine (DBA), aldehyde, and phenylacetylene (known as A3 coupling reactions). The aimed synthesis was carried out using a gold catalyst, chlouro auric acid (HAuCl4) and compared with Cu(I) systems to check the involvement of metals to generate enantiomerically pure compounds (4 a–4 j). No major deactivation of the catalyst was observed after repeated use in a similar reaction system (>10 times). The derived motifs′ spectroscopic profiling (1H NMR, 13C NMR, APT, IR and MS) has confirmed the structural fragments in a single core. Moreover, the applications of the derived motifs confirmed the comparable antimicrobial activity in some selected Gram‐positive and Gram‐negative bacterial; and fungi strains. Our consequences show that the scaffolds 4 d and 4 i having 4‐F and 4‐NMe2 substitution in the araldehyde system exhibited potent antimicrobial activity in most used bacterial and fungi strains.

Electron-modulating effects of intercalating molecules in functionalized graphene oxide: Optimizing the coordination microenvironment of Ag nanoparticles for efficient catalytic A3 coupling reactions

In this paper, functionalized graphene oxide (GO) nanosheets were modified by forming benzamide (BzA) bonds using aniline with different substituents (4-tertbutylaniline, 4-nitroaniline, aniline) as intercalating molecules. Then the Ag@R-BzA/GO composite catalysts were prepared by loading Ag nanoparticles to reveal the electronic modulation of functionalized graphene oxide interfaces by aniline molecules effects with different substituents. The experimental results showed that the layer spacing of the composites obtained after intercalation with aniline whose substituent is an electron-giving group increased by about 40%. Moreover, the electron donating role of tert‑butyl regulates the charge distribution on the graphene oxide material and provides a good coordination environment for the loading of Ag nanoparticles. AgNPs are stably present in the interlayer of graphene oxide nanosheets by ligating with amide bonds and oxygen-containing functional groups to produce strong metal-carrier interactions. Ag@4‑tert-BzA/GO composites showed high catalytic activity in the A3 coupling reaction of aldehydes, alkynes and amines for the synthesis of alkynylamines(TON=19225.82). The electronic effect of the substituent groups on the intercalated molecules reported in this paper is a modulation on the molecular and atomic scale, which provides a new idea for the modulation of the microenvironment in metal-loaded catalysts.

Gold nanoparticle decorated post-synthesis modified UiO-66-NH2 for A3-coupling preparation of propargyl amines

In this report, the novel UiO‑66‑NH2 based-MOF(Zr) catalytic system which further modified with nitrogen-rich organic ligand (5-aminotetrazole) using post synthetic modification (PSM) approach has been prepared here as an efficient catalyst to promote the A3-coupling preparation of propargyl amines in green aquatic media. This newly highly efficient catalyst was synthesized upon Zr-based MOF (UiO‑66‑NH2) which successfully functionalized with 2,4,6‑trichloro‑1,3,5‑triazine (TCT) and 5‑aminotetrazole, following through stabilization of gold metal (Au) nanopartilces. The addition of N-rich organic ligand through post-synthesis modification which can be assisted to stabilize the bister and stable gold nanoparticles caused to unique structure of the final composite in favor of the progress of the A3 coupling reaction. Also several strategies comprising XRD, FT-IR, SEM, BET, TEM, TGA, ICP, EDS and elemental mapping analyzes, were used to indicate the successful preparation of the UiO-66-NH2@ Cyanuric Chloride@ 5-amino tetrazole/Au-NPs. The results of productivity catalyst are accomplished in good to excellent yields for all sort of reactions under mild conditions which is a proof of superior activity heterogeneous catalyst containing Au-nanoparticles. In addition, the suggested catalyst represented excellent reusability with no remarkable loss in activity up 9 sequential runs.

A novel nanomagnetic palladium (II) complex of bisimidazolium-based N[sbnd]heterocyclic carbene; An efficient heterogeneous catalyst for A3 coupling reactions

Herein, a novel nanomagnetic NHC-Palladium complex was successfully prepared applying post-synthetic modification (PSM) condensation between Fe3O4-support imidazole and a synthetic bisamide moiety, carrying the alkyl halide functionalities at the end of its chain, followed by chelation of Pd ions to generate the corresponding complex. The [Fe3O4@bisimidazolium-Pd]2Cl− complex gave the best catalytic performance in synthesizing propargylamines through A3 coupling of various substituted aromatic and cycloaliphatic aldehydes and secondary amines with aromatic and liner alkynes in PEG-400. Primary amines are inefficient to produce unknown byproducts; whereas, secondary amines react quickly. Significantly, alkynes having a high electron density reduce the conversion rate. Moreover, aromatic and aliphatic aldehydes are active, but the electron-drawing substituent on benzaldehyde decreases the rate of conversion. Furthermore, the [Fe3O4@bisimidazolium-Pd]2Cl− catalyst can be reused seven times without metal leaching or losing its ability, which shows how stable it is when used in a reaction.

Synthesis of Ag-Cu-Ni Nanoparticles Stabilized on Functionalized g-C3N4 and Investigation of Its Catalytic Activity in the A3-Coupling Reaction.

In the present research, using ethylenediamine and hydrazine hydrate as the capping and reducing agents in this investigation, respectively, Ag-Cu-Ni NPs were immobilized on the functionalized g-C3N4 surface. This nanocatalyst was studied in terms of its catalytic activities for the A3-coupling reaction to synthesize propargylamine derivatives. According to the results, in the presence of 1 mL of toluene as the solvent and 20 mg of the g-C3N4-TCT-2AEDSEA-Ag-Cu-Ni nanocatalyst, the maximum efficiency of the nanocatalyst occurred at a temperature of 80 °C. Products were purified using thin-layer chromatography plates (silica gel) by employing n-hexane/ethyl acetate with a 90:10 ratio. In addition, the prominent benefits of the synthesized nanocatalyst include its high yields of the product, cost-effectiveness, recyclability, and easy separation. The novelty of the catalyst is due to the presence of Ag-Cu-Ni nanoparticles at the same time in the structure of the functionalized g-C3N4 substrate. So, Ag-Cu-Ni can be strongly connected to the substrate. The structure of the synthesized nanocatalyst was characterized using Fourier transformed infrared spectroscopy, X-ray powder diffraction, field emission scanning electron microscopy, energy-dispersive X-ray spectroscopy, vibrating-sample magnetometry, and transmission electron microscopy.

Recent Advances in N-Heterocyclic Carbene Coinage Metal Complexes in A3-Coupling and Carboxylation Reaction

Owing of their accessibility and wide range of reactivities, alkynes make for fascinating building blocks. Either a selective alkyne carbon-carbon triple bond reaction or activation of the terminal alkyne C-H bond may be employed to functionalize them. Monocationic coinage metal complexes with a d10 electronic configuration are effective catalysts for alkyne activation. Silver(I) and gold(I) N-heterocyclic (NHC) systems are emerging as promising catalysts in multicomponent alkyne activation reactions; this review paper focuses on A3 (aldehyde-amine-alkyne)-coupling reaction and carbon dioxide fixation, furnishing a systematic overview of the scientific advances achieved during the last two decades. This study will carefully compare the corresponding silver and gold complexes employed in the two processes. The differences in reaction routes brought about by the catalyst ligand structure will be investigated with an emphasis on evaluating the benefits provided by the easily tuneable NHC backbone, in terms of chemo- and stereo-selectivity.

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.

Insights into the Three-Component Coupling Reactions of Aldehydes, Alkynes, and Amines Catalyzed by N-heterocyclic Carbene Silver: A DFT Study

Density functional theory (DFT) was used to investigate the three-component coupling reactions of aldehydes, alkynes, and amines (A3 coupling) using N-heterocyclic carbene silver as the catalyst. This study reveals that the addition reaction between the catalyst N-heterocyclic carbene silver and phenylacetylene (PAE) forms Ag_PAE. Subsequently, one hydrogen atom of the Ag_PAE migrates to the nitrogen atom of the Amine. Thereafter, the amine aldehyde condensation reaction generates a molecule of water and an imine ion with (Path one) or without (Path two) another amine catalyst. Path one has a lower reaction barrier than Path two. Subsequently, the imine ion reacts with silver phenylacetylide to generate the A3 coupling reaction product propargylamine (PPA). Furthermore, the triple bond and −N3 group in PPA undergo a cycloaddition reaction and generate the final product (PR). The entire reaction is strongly exothermic, and, therefore, the reaction is easy to conduct. Moreover, conceptual density functional theory calculations confirm the reaction mechanism. Investigating the mechanism of these reactions will be helpful for understanding and developing new synthesis strategies for similar functional compounds.

Coupling of Amino Acid Terminal Alkyne with in situ Iminium Ion to Access Nε‑Substituted Lysine Mimetics

Key words copper catalysis - lysine mimetics - A3 coupling reaction - terminal alkynes - amino acids

Synchronous Metal Rearrangement on Two-Dimensional Equatorial Surfaces of Au-Cu Alloy Nanoclusters.

Understanding the growth of nanoclusters and the relationship between structure-activity depends on the precise arrangement of metals on their surface. In this work, we realized the synchronous rearrangement of metal atoms on the equatorial plane of Au-Cu alloy nanoclusters. Upon adsorption of the phosphine ligand, the Cu atoms on the equatorial plane of the Au52Cu72(SPh)55 nanocluster are irreversibly rearranged. The whole metal rearrangement process can be understood from a synchronous metal rearrangement mechanism initiated by the adsorption of the phosphine ligand. Furthermore, this metal rearrangement can effectively improve the efficiency of A3 coupling reactions without increasing the amount of catalyst.