Synthesis Of Propargylamines Research Articles

Glucoconjugated Dinuclear Copper(II) Complex: An Efficient Catalyst for Stereoselective Synthesis of Trisubstituted Propargylamines via Solvent-free A3 Coupling Reaction.

Development of catalytic systems using nontoxic natural precursors is the need of the era, and along this line, we have synthesized a new D-glucose derived ligand (4,6-O-ethylidene-N-(2-hydroxy-4-(octyloxy)benzylidene)-β-D-glucopyranosylamine) and its dinuclear copper(II) complex. The molecular structure of the complex has been established by single-crystal X-ray diffraction studies and detailed noncovalent intermolecular interactions present in it have been explored by Hirshfeld surface analysis. Further, the complex has been used as a catalyst in the enantioselective (87-99 % ee) synthesis of propargylamines in good to excellent yield (82-95 %) via aldehyde-amines-alkynes (A3) coupling reaction under solvent-free condition. The formation of aminal intermediate during the reaction has been confirmed by 1H-NMR and single-crystal X-ray diffraction studies. The catalytic system is reusable without any appreciable loss in the enantioselectivity or product yield.

One–pot A3–coupling solvent–free synthesis of propargylamines by Pd–impregnated Al–based LDHs synthesized from aluminum salt slag

Several Al3+–based LDHs with different divalent cations have been synthesized by coprecipitation from aluminum salt slag and have been impregnated with Pd. After their characterization by PXRD, FT–IR, thermal analysis, N2 adsorption–desorption isotherms at –196 °C and electron microscopy (SEM and TEM), they were used as heterogeneous catalysts in the A3–coupling reaction (benzaldehyde + morpholine + phenylacetylene) to produce propargylamines. The catalyst that showed the best results was NiAl–Pd and the optimal reaction conditions were: catalyst dose 30 mg, temperature 80 °C and reaction time 6 h. In addition, this catalyst showed a good cyclic behavior, retaining a catalytic activity higher than 80 % after 4 cycles.

Synthesis of Au/Ce2S3@CeO2/CuS nanocomposites for promoted catalytic performance in propargylamine conversion

A newly developed nanocomposite catalyst, Au/Ce2S3@CeO2/CuS, has been engineered for effective propargylamine synthesis through the A3 coupling reaction. The catalyst’s synthesis involved the targeted addition of 15 wt% CeO2 to the CuS sulfur precursor, leading to the formation of a Ce2S3 layer due to its lower solubility product constant (Ksp). This layer, along with 0.5 wt% Au nanoparticles, significantly increased the Ce3+ concentration (16.9 % to 33 %∼52 %), which can accelerate the Cu+/Cu2+ valence state changes, thereby promoting the activation of the alkynyl hydrogen to enhance propargylamine formation. After 2 h reaction, the Au/Ce2S3@CeO2/CuS catalyst achieved over 99 % conversion, nearly 55 % more than pure CuS (45.5 %). The Au/Ce2S3@CeO2/CuS nanocomposite also showed excellent recyclability (80 % retention after 5 cycles) and a high conversion rate of 222.5 mmol·g−1·h−1.

Egg shell powder mediated Cu catalyst: A biowaste based catalytic approach for the synthesis of quinazolin-4(3H)-ones and propargyl amines

A novel and efficient approach for a tandem oxidative synthesis of quinazolin-4(3H)-one from 2-aminobenzonitrile and benzyl alcohol has been unveiled via Cu2(CO3)(OH)2. Herein CuSO4.5H2O accompanied by egg shell powder is used for the easy preparation of Cu2(CO3)(OH)2. The reported method portrays a wide range of substrate scope with good to excellent yield and the given reaction proceed at room temperature within 12 h. Single crystal of one of the synthesized quinazolin-4(3H)-ones was analysed through single crystal X-ray diffraction (SC-XRD). Some of the compounds reported here are also known to possess various pharmaceutical activities. Eventually the newly prepared catalyst was applied for propargylamine synthesis via a multi component reaction. Perceiving all the advantages, present protocol is conceivably considered as clean, cost-effective and sustainable over reported procedures used for synthesis of quinazolin-4(3H)-ones and propargyl amines.

Α Metal‐Free Photochemical Atom Transfer Radical Addition of CBr4 onto Alkenes as a Key Step for Their Conversion to Propargylamines

Α green and sustainable metal‐free photochemical protocol for the atom transfer radical addition (ATRA) of carbon tetrabromide onto alkenes was developed. Phenylglyoxylic acid was employed as the photoinitiator to promote the water‐mediated anti‐Markovnikov photochemical addition. A vast variety of alkenes was employed successfully, providing the corresponding products in good to high yields with excellent regioselectivity. The photochemical protocol found an application towards the three‐step synthesis of secondary or tertiary propargylamines starting from alkenes.

Design of efficient benzimidazole-derived N-heterocyclic carbene Ag(I) catalysts for aldehyde–amine–alkyne coupling

A mild catalytic protocol for aldehyde, amine, and alkyne coupling (A3-coupling) allows for the selective synthesis of propargyl amines using 5,6-dimethylbenzimidazole-derived N-heterocyclic carbene (BNHC) silver(I) catalysts. A series of BNHC Ag(Ⅰ) halide complexes were synthesized and their structures have been elucidated through the use of multinuclear NMR and FT-IR spectroscopy. Furthermore, the pseudo-linear geometry of two different compounds was substantiated by single-crystal X-ray diffraction. Silver-based A3-coupling was achieved for both acyclic and cyclic secondary amines using a diverse set of alkynes to afford propargyl amines with yields of up to 95 %. The present approach is environmentally benign and water is generated as the sole byproduct.

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.

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.

Catalytic Enantioselective Alkyne Addition to Nitrones Enabled by Tunable Axially Chiral Imidazole-Based P,N-Ligands.

Although catalytic enantioselective alkyne addition is an established method for the synthesis of chiral propargylic alcohols and amines, addition to nitrones presents unique challenges, and no general chiral catalyst system has been developed. In this manuscript, we report the first Cu-catalyzed enantioselective alkyne addition to nitrones utilizing tunable axially chiral imidazole-based P,N-ligands. Our approach effectively overcomes difficulties in both reactivity and selectivity, resulting in a simple Cu-catalyzed protocol. The reaction accommodates a wide range of nitrones and alkynes, enabling the streamlined synthesis of chiral propargyl N-hydroxylamines via the enantioselective C-C bond formation. A diverse array of optically active nitrogen-containing compounds, including chiral hydroxylamines, can be accessed directly through facile transformations of the reaction products.

Enantioselective Synthesis of C2-Quaternary Indolin-3-ones by Pt-Catalyzed Alkynylation of 2-Aryl-3H-indol-3-one with Alkynylsilanes.

An efficient method for the synthesis of five-membered chiral propargylic amines from 2-aryl-3H-indol-3-one and alkynylsilanes has been developed. The reaction proceeded under the catalytic system of PtCl4, oxazoline-based ligand L11, Zn(CF3COO)2, and AcOH in DCE at 95 °C via in situ desilylation of TMS-alkynes. This methodology also highlights a new protocol for the in situ desilylation of alkynylsilanes. The reaction showed a broad substrate scope with good yields and enantioselectivity.

Catalytic Insights of Copper(I) Complexes with phosphole Ligands in three-component reactions to produce propargylamines and 1,4-substituted 1,2,3-triazoles.

The catalytic activity of two complexes, 2a ([CuCl{k1(P)-1a}{k2(P,N)-1a}]; 1a = 2,5-bis(2-pyridyl)-1-phenylphosphole) and 2b ([CuCl{k1(P)-1b}2]; 1b = 2,5-bis(2-thienyl)-1-phenylphosphole), was investigated in three-component reactions for the synthesis of propargylamines and 1,4-substituted 1,2,3-triazoles. This article introduces the first-time synthesis and characterization of complex 2a, while complex 2b has been previously reported by us. An X-ray crystallographic analysis revealed that the copper(I) complex 2a exhibits a pseudo-tetrahedral geometry with two phosphole ligands demonstrating k1(P)- and k2(P,N)-coordination, in contrast to complex 2b, which adopts a trigonal planar geometry. In a solution environment, 1a exhibits hemilability, leading to a dynamic equilibrium between the tetra-coordinated complex (2a) and its tri-coordinated counterpart (2a’). This behavior is substantiated by theoretical calculations, which confirm a preference for the tetra-coordinated geometry. Regarding catalytic activity, 2a and 2b exhibited effective catalytic activity in A3-coupling reactions and the direct synthesis of 1,4-disubstituted 1,2,3-triazoles. However, 2b demonstrated superior catalytic performance in both reactions compared to 2a. Theoretical calculations suggest that the stronger N–Cu σ-bond in 2a hinders the interaction of the alkyne with the copper center, whereas the trigonal planar geometry of 2b facilitates better copper-alkyne π-interactions.

Recent advances in the application of alkynes in multicomponent reactions.

Alkynes have two active positions to carry out chemical reactions: C[triple bond, length as m-dash]C and C-H. These two positions are involved and activated in different reactions using different reagents. In this study, we investigated the reactions of alkynes that are involved in multi-component reactions through the C-C and C-H positions and examined the progress and gaps of each reaction by carefully studying the mechanism of the reactions. Firstly, we investigated and analyzed the reactions involving the C[triple bond, length as m-dash]C position of alkynes, including the reactions between derivatives of alkynes with RN3, sulfur compounds (RSO2R', DMSO, S8, DABCO(SO2)2 and DABSO), barbituric acids, aldehydes and amines, COOH, α-diazoesters or ketones, and isocyanides. Then, we examined and analyzed the important reactions involving the C-H position of alkynes and the progress and gaps in these reactions, including the reaction between alkyne derivatives with amines and aldehydes for the synthesis of propargylamines, the reaction between alkynes with CO2 and the reaction between alkynes with CO.

Facile synthesis of propargylamines by metal-free doubly decarboxylative coupling

Doubly decarboxylative coupling between two different carboxylic acids to form a new C–C bond is a powerful tool for the rapid assembly of complex compounds. Herein, we report a metal-free...

Eco-friendly and sustainable basil seed hydrogel-loaded copper hydroxide-based catalyst for the synthesis of propargylamines and tetrazoles.

The broad use of propargyl amines and tetrazoles in pharmaceutical applications presents a well-established challenge. Their synthesis relies heavily on catalysis, which, in turn, has been hindered by the scarcity of stable and practical catalysts. In response to this issue, we have developed an environmentally friendly and sustainable catalyst by infusing copper hydroxide into basil seed hydrogel (Cu(OH)2-BSH), creating a 3D nanoreactor support structure. To verify the structural, physical, chemical, and morphological properties of the prepared samples, a comprehensive analysis using various techniques, including FT-IR, EDX, FE-SEM, TEM, XRD, BET, TGA, and XPS, were conducted. The results not only confirmed the presence of Cu(OH)2 but also revealed a porous structure, facilitating faster diffusion and providing a substantial number of active sites. This catalyst boasts a high surface area and can be easily recovered, making it a cost-effective, safe, and readily available option. This catalyst was applied to the synthesis of propargyl amines and tetrazoles through multi-component reactions (MCRs), achieving excellent results under mild conditions and in a remarkably short timeframe. Consequently, this work offers a straightforward and practical approach for designing and synthesizing metal hydroxides and 3D hydrogels for use in heterogeneous catalysis during organic syntheses. This can be achieved using basic and affordable starting materials at the molecular level.

Natural Halloysite@Si(CH2)3NH2@Cu(acac)2 as an efficient nanocatalyst for the one-pot and three-component synthesis of propargylamines under solvent-free conditions

Natural Halloysite@Si(CH2)3NH2@Cu(acac)2 as an efficient nanocatalyst for the one-pot and three-component synthesis of propargylamines under solvent-free conditions

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.

Synthesis of Propargylamine and Indolazine Derivatives via Three‐Component Reaction Catalyzed by CuOx/CeO2 Materials

AbstractIn this paper, nanorod CeO2 supports were prepared by hydrothermal method using Ce(NO3)3 ⋅ 6H2O as raw material. CuOx/CeO2‐r materials were prepared by calcination using Cu salt‐loaded CeO2‐r supports as raw materials. The three‐component coupling reaction of phenylacetylene, amine and aldehyde was successfully catalyzed by CuOx/CeO2‐r material as a non‐homogeneous catalyst, which showed good catalytic activity. Furthermore, a series of indolizine derivatives can be obtained in higher isolated yields by replacing benzaldehyde with pyridinecarbaldehyde and catalyzing the three‐component synthesis with the same CuOx/CeO2‐r material. The synthesis mechanisms of propargylamine and indolizine were discussed. It is worth noting that the CuOx/CeO2‐r material system is provided for two three‐component reactions, and has the advantages of less catalyst dosage, short reaction time, simple post‐treatment, and a wide range of substrates.

Deciphering the Primary Role of Au⋅⋅⋅H-X Hydrogen Bonding in Gold Catalysis.

Au⋅⋅⋅H-X (X=N or C) hydrogen bonding is gaining increasing interest, both in the study of its intrinsic nature and in their operability in different fields. While the role of these interactions has been studied in the stabilization of gold(I) complexes, their role during the minimum free energy reaction pathway of a given catalytic process remains unexplored. We report herein that complex [Au(C≡CPh)(pip)] (pip=piperidine) catalyses the A3 -coupling reaction for the synthesis of propargylamines, thanks to the ability of Au(I) to promote weak hydrogen bonding interactions with the reactants along the free energy profile. Density Functional Theory (DFT) calculations show that these Au⋅⋅⋅H-X interactions play a directing role in the catalysed A3 -coupling. Topological non-covalent interactions (NCI), interaction region indicator (IRI) and quantum theory of atoms in molecules (QTAIM) analysis in real space of the electron density provide a description of these interactions accurately.

Deciphering the Primary Role of Au⋅⋅⋅H−X Hydrogen Bonding in Gold Catalysis

AbstractAu⋅⋅⋅H−X (X=N or C) hydrogen bonding is gaining increasing interest, both in the study of its intrinsic nature and in their operability in different fields. While the role of these interactions has been studied in the stabilization of gold(I) complexes, their role during the minimum free energy reaction pathway of a given catalytic process remains unexplored. We report herein that complex [Au(C≡CPh)(pip)] (pip=piperidine) catalyses the A3‐coupling reaction for the synthesis of propargylamines, thanks to the ability of Au(I) to promote weak hydrogen bonding interactions with the reactants along the free energy profile. Density Functional Theory (DFT) calculations show that these Au⋅⋅⋅H−X interactions play a directing role in the catalysed A3‐coupling. Topological non‐covalent interactions (NCI), interaction region indicator (IRI) and quantum theory of atoms in molecules (QTAIM) analysis in real space of the electron density provide a description of these interactions accurately.