Sonogashira Coupling Reaction Research Articles

Copper Catalysts Anchored on Cysteine-Functionalized Polydopamine-Coated Magnetite Particles: A Versatile Platform for Enhanced Coupling Reactions

Cysteine plays a crucial role in the development of an efficient copper-catalyst system, where its thiol group serves as a strong anchoring site for metal coordination. By immobilizing copper onto cysteine-modified, polydopamine-coated magnetite particles, this advanced catalytic platform exhibits exceptional stability and catalytic activity. Chemical modification of the polydopamine (PDA) surface with cysteine enhances copper salt immobilization, leading to the formation of the Fe3O4@PDA-Cys@Cu platform. This system was evaluated in palladium-free, copper-catalyzed Sonogashira coupling reactions, effectively catalyzing the coupling of terminal acetylenes with aryl halides. Additionally, the Fe3O4@PDA-Cys@Cu platform was employed in click reactions, confirming the enhanced catalytic efficiency due to increased copper content. The reusability of the platform was further investigated, demonstrating improved performance, especially in recyclability tests in click reaction, making it a promising candidate for sustainable heterogeneous catalysis.

Exploring C2 and N6 Substituent Effects on Truncated 4'-Thioadenosine Derivatives as Dual A2A and A3 Adenosine Receptor Ligands.

Based on high binding affinity of truncated 2-hexynyl-4'-thioadenosine (3a) at both A2A adenosine receptor (AR) and A3 AR, we explored structure-activity relationship (SAR) of the C2-substitution by altering chain length of the 2-hexynyl moiety, thereby evaluating the hydrophobic pocket size. A series of truncated N6-substituted 4'-thioadenosine derivatives with C2-alkynyl substitution were successfully synthesized from D-mannose, using a palladium-catalyzed Sonogashira coupling reaction as the key step, whose structures were confirmed by the X-ray crystal structure of 4h. As the size of the alkynyl group at the C2-position increased, the binding affinity improved; however, when the substituted group was larger than hexynyl, the binding affinity decreased. The introduction of a bulky hydrophobic group such as 3-halobenzyl group at the free N6-amino group decreased the binding affinity at hA2AAR. These results confirm our previous findings that a free amino group at N6-position and longer hydrophobic chain at C2-position are essential for hA2A AR binding affinity. The introduction of a bulky hydrophobic group at free N6-amino group maintained the binding affinity at hA3 AR. The binding mode of truncated 2-substituted-4'-thioadenosine derivatives to hA2A and hA3 AR were predicted by a molecular docking study.

The Effect of Molecular Structure on the Properties of Fluorene Derivatives for OLED Applications.

A new family of symmetrical fluorene derivatives with different types of substituents attached to the C-2 and C-7 positions of the fluorene core synthesized by the Sonogashira coupling reactions is reported. The electronic structures and the properties of the compounds investigated by means of photoelectron emission spectroscopy, UV-Vis absorption and photoluminescent spectroscopy as well as by DFT and TD-DFT theoretical calculations are discussed. It is shown that the nature of substituents influences the π-conjugation of the molecules. No intermolecular charge transfer within the investigated wavelength range is observed. The applicability of the synthesized compounds in organic light-emitting diodes (OLEDs) based on exciplex emission is demonstrated. The advanced co-deposition technique with the tuned OLED architecture was applied and resulted in improved OLED parameters.

Hydrogen‐Bonded Cyclic Tetramer Formation of a Pyridylethynylimidazole‐Based Fluorophore

AbstractSupramolecular have promising application prospects owing to their catalytic, self‐healing, and stimulus‐responsive functions. Pyridylethynylimidazole‐based supramolecular synthons with fluorescent properties have been developed. 4‐(2‐Pyridylethynyl)‐5‐arylethynyl‐1H‐imidazole derivatives 1 with different substituents at the 4‐ and 5‐positions of the imidazole skeleton were prepared using a step‐by‐step Sonogashira coupling reaction. The fluorescence maxima of phenyl‐ and methoxyphenyl‐substituted derivatives 1a and 1c were independent of solvent polarity. On the other hand, ester‐ and cyano‐substituted 1b and 1d showed bathochromically shifted fluorescence maxima in highly polar solvents. In crystals, the 4‐(2‐pyridylethynyl)‐5‐arylethynyl‐1H‐imidazole derivatives formed a supramolecular cyclic tetramer structure via two hydrogen bonds: one was between N─H in imidazole and N in pyridine, and the other was between C─H in imidazole and N in imidazole. Introducing the pyridine ring as a hydrogen bond acceptor, in addition to the imidazole ring, promoted the unique cyclic tetramer structure formation.

Thienothiophene and benzothiadiazole based conjugated donor-acceptor polymers; synthesis, photophysical properties and organic field effect transistor applications

Novel conjugated donor-acceptor (D-A) type polymers (P1-P3) possessing thieno[3,2-b]thiophenes (TT) as donors having different functional groups and 2,1,3-benzothiadiazole (BT) as an acceptor were designed and synthesized via palladium-catalyzed Sonogashira coupling reaction. Their electronic and optical properties were investigated by UV–Vis and fluorescence spectroscopies and cylic voltammetry analysis. Organic field-effect transistor (OFET) of the polymers were fabricated using biodegradable and environmental-friendly khaya gum as a high dielectric layer to investigate their charge transport characteristics were at low voltage. All the polymers displayed a p-type field-effect behaviour, among which alkyl chain (C9H19) substituted P2 exhibited the highest average saturated hole mobility, μsat, 0.086 cm2 V−1 s−1, on/off current ratio, Ion/Ioff = 1.0 × 103, and subthreshold swing, SS, 425 mV dec−1. The results presented in this work corroborate that the three novel TT-BT polymers have promising potential for electronic and optoelectronic applications, in particular, where tunability of the field-effect behaviour is essential for performance.

Synergistic Pd(OAc)2/CuI-catalyzed alkynylation of β-lactam derivative via Sonogashira coupling

Herein, a novel approach of bimetallic Pd(OAc)2/CuI-catalyzed alkynylation of 3-chloroazetidin-2-one (β-lactam derivative) with terminal alkyne via tandem C–C bond activation/Sonogashira-type cross-coupling reaction is developed. This synthesis encompasses a sequence of inert Csp3–X/Csp–H functionalization processes involving the coupling of the C(sp3) adjacent to the 3-chloroazetidin-2-one with the C(sp) of a terminal alkyne. The final analogs are synthesized by means of the indole-benzothiazole Schiff base formation, cyclization of the Schiff base to generate the β-lactam derivative, and Sonogashira coupling to afford a C(sp3)–C(sp) bond. In addition, indole, benzothiazole, and azetidine-2-one have been identified to be highly efficient heterocyclic scaffolds with a range of pharmacological benefits. It encouraged us to discover a hybrid compound that had each of these moieties. Cooperation between two different metals is essential for the successful implementation of this approach. Specifically, the interaction between the Pd and Cu centers in the transmetallation step is depicted through a plausible mechanistic route. The reaction conditions have been optimized by varying catalyst and ligand loadings, bases, temperatures, and solvents. The reaction is highly efficient, yielding alkynylated products in up to 84 % yield with a wide range of substrates and functional group tolerance, thereby serving as a functional model for the Sonogashira coupling reaction.

Enhanced detection of catecholamines in human urine using Cis-diol-microporous organic networks with PT-SPE and HPLC-MS/MS

A novel cis-diol-microporous organic networks (MONs-2OH) material was synthesized via room temperature and Sonogashira coupling reactions, which exhibits exceptional adsorption properties for catecholamines (CAs). MONs-2OH demonstrates robust hydrogen bonding and π-π stacking interactions, crucial for effective adsorption. The MONs-2OH was incorporated into pipette tip solid-phase extraction and developed a new method for detecting CAs in human urine using HPLC-MS/MS. Characterization of the adsorbent revealed its high stability, large specific surface area, abundant phenolic hydroxyl groups, rapid extraction speed, and superior adsorption efficiency. The method achieved a wide linear range (0.5–500 ng/mL), low detection limits (0.06–0.26 ng/mL), high accuracy (90.4 %-99.4 %), and excellent precision (RSD ≤ 10 %). Comparative studies showed MONs-2OH outperforms commercial adsorbents in terms of recovery and adsorption capacity. The results underscore the potential of MONs-2OH for rapid and sensitive CAs determination, offering significant advantages for the auxiliary diagnosis of depression and enhancing the application of PT-SPE in sample pretreatment.

Bio-inspired fabrication of chitosan/PEO/Ti3C2Tx 2D MXene nanosheets supported palladium composite nanofiber catalysts via electrospinning

In this study, novel chitosan/polyethylene oxide/Ti3C2Tx 2D MXene nanosheets (CS/PEO/Ti3C2Tx) nanofibers were successfully prepared by a continuous electrospinning process. During the electrospinning process, induced by the syringe tip capillary effects and electric field force, the Ti3C2Tx nanosheets were aligned along the direction of the nanofiber formation to occur a highly oriented structure. This well-ordered arrangement of the inorganic Ti3C2Tx nanosheets within the organic polymer matrix nanofiber was similar with nacre-like ‘brick-and-motar’ structure to some extent, resulting in a marked increase in thermal stability and mechanical properties of the resultant CS/PEO/Ti3C2Tx nanofiber. As 4 wt% of Ti3C2Tx nanosheets loaded, the highest tensile strength of the CS/PEO/Ti3C2Tx nanofiber mats was achieved as 31.7 MPa, about two times that of neat CS/PEO nanofibers. Uniformly dispersed Pd nanoparticles in size of about 1.6 nm have been successfully immobilized on the composite nanofiber with a solution impregnation process. With a loading as low as 0.2 mol% of Pd, the resultant Pd@CS/PEO/Ti3C2Tx composite nanofiber catalysts were highly active for both Heck and Sonogashira coupling reactions with broad reactants application scope, and could be recycled 15 runs without significant loss of activities.

Low‐valent Tungsten Catalyzed Carbonylative Sonogashira Coupling Reactions of Aryl Iodides with Alkynes

AbstractA low‐valent tungsten catalyzed carbonylative Sonogashira coupling reactions has been established. The present protocol utilizes inexpensive and readily available W(CO)6 as precatalyst and proceeds in the presence of atmospheric CO, providing a practical method to a series of functionalized alkynones and indoxyls compounds under mild reaction conditions. Moreover, the simple reaction system, good functional group tolerance and broad substrate scope enable the application of this transformation in the synthesis of functionalized carbonyl‐containing molecules.

Biogenic and rapid route for the synthesis of palladium nanoparticles by using Roylea cinerea extract and their catalytic activity for Suzuki and Sonogashira coupling reactions and nitrophenol reduction

4-nitrophenol is a serious environmental pollutant due to its carcinogenic, mutagenic, and teratogenic properties, posing serious risks to aquatic life, plants, and humans even at very low concentrations. In the current work a simple, inexpensive, and ecologically appropriate approach for generating palladium nanoparticles (Pd-NPs) from palladium chloride and their potential for the reduction of 4-nitrophenol have been investigated. This method employs a non-toxic aqueous extract obtained from the aerial portion of Roylea cinerea, which functions as both a reducing and stabilizing agent. The Pd-NPs synthesis was confirmed through UV–vis spectroscopy, and were further characterized by techniques like FT-IR, SEM, EDX, and XRD analysis. The biosynthesized Pd-NPs had a spherical shape with diameters ranging from 20 to 30 nm. The presence of palladium in the Pd-NPs was confirmed by EDX analysis. The available functional groups on the surface of Pd-NPs were determined through FTIR analysis. Pd-NPs demonstrated catalytic efficacy in both Sonogashira and Suzuki coupling processes, as measured by UV–vis spectrophotometry during nitrophenol reduction. The findings demonstrate that the Pd-NPs exhibited significant catalytic efficiency, achieving the degradation of over 95 % of 4-nitrophenol within a 16-min timeframe. Following the catalytic reaction, the catalyst was effortlessly recovered through centrifugation, demonstrating its ability to undergo multiple catalytic cycles without a significant loss of activity (>90 % after five cycles).

Robust Nitrogen-Doped Microporous Carbon via Crown Ether-Functionalized Benzoxazine-Linked Porous Organic Polymers for Enhanced CO2 Adsorption and Supercapacitor Applications.

Nitrogen-doped carbon materials, characterized by abundant microporous and nitrogen functionalities, exhibit significant potential for carbon dioxide capture and supercapacitors. In this study, a class of porous organic polymer (POP) were successfully synthesized by linking Cr-TPA-4BZ-Br4 and tetraethynylpyrene (Py-T). The model benzoxazine monomers of Cr-TPA-4BZ and Cr-TPA-4BZ-Br4 were synthesized using the traditional three-step method [involving CH═N formation, reduction by NaBH4, and Mannich condensation]. Subsequently, the Sonogashira coupling reaction connected the Cr-TPA-4BZ-Br4 and Py-T monomers, forming Cr-TPA-4BZ-Py-POP. The successful synthesis of Cr-TPA-4BZ-Br4 and Cr-TPA-4BZ-Py-POP was confirmed through various analytical techniques. After verifying the successful synthesis of Cr-TPA-4BZ-Py-POP, carbonization and KOH activation procedures were conducted. These crucial steps led to the formation of poly(Cr-TPA-4BZ-Py-POP)-800, a carbon material with a structure akin to graphite. In practical applications, poly(Cr-TPA-4BZ-Py-POP)-800 exhibited a noteworthy CO2 adsorption capacity of 4.4 mmol/g, along with specific capacitance values of 397.2 and 159.2 F g-1 at 0.5 A g-1 (measured in a three-electrode cell) and 1 A g-1 (measured in a symmetric coin cell), respectively. These exceptional dual capabilities stem from the optimal ratio of heteroatom doping. The outstanding performance of poly(Cr-TPA-4BZ-Py-POP)-800 microporous carbon holds significant promise for addressing contemporary energy and environmental challenges, making substantial contributions to both sectors.

A Highly Selective Synthesis of (E)‐11‐Arylidenebenzo [4′,5′] thieno [2′,3′ : 4,5] Pyrimido [2,1‐a] Isoindol‐13(1H)‐ones via Copper‐Catalyzed Sonogashira Coupling and Hydroamination

AbstractAn efficient and highly selective reaction of 2‐(2‐bromophenyl)‐5,6,7,8‐tetrahydrobenzo [4,5] thieno[2,3‐d]pyrimidin‐4(3H)‐one and terminal alkyne has been developed under palladium‐free conditions by CuI‐catalyzed sequential Sonogashira coupling reaction and 5‐exo‐dig hydroamination reaction. A series of 11‐arylidene‐2,3,4,11‐tetrahydrobenzo [4′,5′]thieno [2′,3′ : 4,5]pyrimido [2,1‐a]isoindol‐13(1H)‐one derivatives with only the (E)‐configuration were obtained.

Synthesis and Antiproliferative Effect of New Alkyne-Tethered Vindoline Hybrids Containing Pharmacophoric Fragments.

In the frame of our diversity-oriented research on multitarget small molecule anticancer agents, utilizing convergent synthetic sequences terminated by Sonogashira coupling reactions, a preliminary selection of representative alkyne-tethered vindoline hybrids was synthesized. The novel hybrids with additional pharmacophoric fragments of well-documented anticancer agents, including FDA-approved tyrosine-kinase inhibitors (imatinib and erlotinib) or ferrocene or chalcone units, were evaluated for their antiproliferative activity on malignant cell lines MDA-MB-231 (triple negative breast cancer), A2780 (ovarian cancer), HeLa (human cervical cancer), and SH-SY5Y (neuroblastoma) as well as on human embryonal lung fibroblast cell line MRC-5, which served as a reference non-malignant cell line for the assessment of the therapeutic window of the tested hybrids. The biological assays identified a trimethoxyphenyl-containing chalcone-vindoline hybrid (36) as a promising lead compound exhibiting submicromolar activity on A2780 cells with a marked therapeutic window.

Double-bridged N–B←N bipyridyl-based airfoil-shaped small molecule dyes: π-bridge regulation on photovoltaic performance

The double-bridged N–B←N bipyridine unit (BNBP) with boron-nitrogen covalent bond and coordination bond can reduce the electronic energy level of the π-conjugated system, resulting in a reduction of band gap and a red shift in the absorption spectrum. Embedding the BNBP building block into organic optoelectronic materials provides a novel possibility in molecule design. In this paper, under the guidance of density functional theory (DFT) calculations, a series of 3D “airfoil-shaped” small molecule donors (SMDs) have been designed and successfully synthesized through Sonogashira, Suzuki and Stille coupling reactions. BNBP is adopted as the central electron-withdrawing unit and strong electron-rich triphenylamine (TPA) as the terminal group. The novel “airfoil-shaped” structure plays a supporting role in reducing the carrier recombination in the active layer. It reveals that molecular design engineering can achieve the expected results by the following steps: Firstly, the introduction of electron-rich alkoxy groups into the end of TPA through side chain engineering helps to improve the solubility and film-forming properties of the materials. Then, the π-bridge regulation not only extends the conjugate structure, but also plays a crucial role in the regulation of photovoltaic properties. It is worth noting that the compound BNBP(3TTPA)2 was synthesized by introducing thiophene oligomer into BNBP-based SMDs for the first time. Finally, the compound BNBP(EDPPTPA)2 was constructed by combining BNBP with DPP dye unit. Its narrow band gap is only 1.36 eV, which is one of the narrowest band gaps in small molecular organic-boron materials. In particular, compared with the starting compound BNBP(ETPA)2, the synergistic effects of DPP and BNBP broaden the edge absorption wavelength to 814 nm, resulting in a red shift of 170 nm. The power conversion efficiency (PCE) of 4.48 % is obtained in BNBP(EDPPTPA)2-based bulk heterojunction (BHJ) organic solar cells (OSCs), which is more than twice that of reference compound BNBP(ETPA)2. This work provides important references for the future development of 3D BNBP-based organic-boron SMDs and the structural regulation of materials through molecular engineering.

Magnetically recoverable CuFe2O4 nanocatalyst: Dual catalytic action in sonogashira and Chan-Lam coupling reactions

Magnetically retrievable CuFe2O4 nanocatalyst has been synthesized for Sonogashira (C-C) and Chan-Lam (C-N) coupling reactions by a facile co-precipitation method. Synthesized nanocatalyst was characterized by powder x-ray diffraction (PXRD), fourier transform infrared spectroscopy (FTIR), field emission scanning electron microscope (FESEM), transmission electron microscopy (TEM), selected area electron diffraction (SAED), X-ray photoelectron spectroscopy (XPS) and vibrating sample magnetometer (VSM) analysis. The catalytic action of the catalyst was evaluated for both Pd-free C-C coupling and base-free C-N coupling reactions where an excellent product yield up to 96 % and 95 % respectively was obtained. The uniqueness of the catalyst was its effective performance under ambient reaction conditions in green solvents such as EtOH and EtOH:H2O (1:1) with a broad substrate scope. The catalyst can be easily retrieved from the reaction mixture with the aid of an external magnet and reused at least five times without significant loss in catalytic activity. The structural stability of the recovered catalyst was confirmed by XRD, FTIR, SEM and ICP-OES (Inductively coupled plasma - optical emission spectrometry) analysis. Thus, the synthesized catalyst works excellently well for dual applications and establishes the sustainable application of the catalyst.

Synthesis, optical properties, and dual‐color halochromic fluorescence of novel π‐conjugated polymers bearing coumarin unit in the main chain

AbstractA series of novel π‐conjugated polymers bearing alternating coumarin and phenylene units in the main chain backbone was synthesized via Sonogashira coupling reaction. The red‐shifts in the absorption maxima of the polymers indicate the expansion of π‐conjugated system in the polymer main chains. These polymers exhibited strong green fluorescence in organic solvents. Clearly perceptible dual‐color halochromic fluorescence was confirmed for the polymers by the significantly reversible changes of emission color from green to blue during alkalization and acidification processes. The lactone ring opening and closing property in the coumarin molecule functioned as a controllable switch, broadening the applications of the coumarin‐based π‐conjugated polymers as acid–base responsive fluorescence materials.

Synthesis of inverse push-pull coumarin dyes and their application as solvatochromic probes and labelling agents for bacterial cell membranes

Coumarin derivatives have been widely employed across a great number of applications, such as laser dyes, bioimaging or chemossensors, owing to their strong fluorescence and high-quantum yields. These properties are highly tunable through structural modification, namely by the inclusion of electron-withdrawing groups (EWG) and electron-donating groups (EDG) at positions 3 and 7 of the coumarin scaffold, respectively. Comparatively, there aren't many reports of EDGs being employed at position 3, prompting us to investigate this new class of potential fluorophores.We undertook the synthesis of three novel ethynyl-linked aminophenyl-coumarin dyes, employing a key Sonogashira-coupling reaction to introduce the electron-rich tertiary aniline moiety. Two different amine donors were used, diphenylamino (coumarins A and B) and dimethylamino (coumarin C), as well as two alkoxy substituents, dibenzyloxy (A and C) and methylenedioxy (B), in the phenyl ring of the coumarin. All dyes show strong emission and significant positive solvatochromism. Additionally, they were employed as staining agents for the cellular membrane of S. pneumoniae, a Gram-positive bacterial pathogen. None of the three derivatives presented cytotoxic effects. Only A and B successfully labelled the bacterial membrane. In the case of B a very similar staining pattern and performance to that of standard dye Nile Red was observed, while A seemed to possess a more selective distribution.

4,4’-(Thiophene-2,5-diylbis(ethyne-2,1-diyl))bis(1-methyl-1-pyridinium) Iodide

In the vast field of organic functional materials, viologens are widely recognized as an extremely versatile family of substances, due in part to the possibility of extending conjugation between the terminal pyridinium rings, for instance through the insertion of additional aromatic moieties. In this work, a new, extended viologen with a thiophene core and two acetylene bonds is presented. It was synthesized through a straightforward route, using well-established Sonogashira coupling reactions, and its optical properties were investigated by UV–visible absorption and fluorescence spectroscopy, revealing a very interesting material for diverse fluorescence-related applications.

Designing strategically functionalized conjugated microporous polymers with pyrene and perylenetetracarboxylic dianhydride moieties with single-walled carbon nanotubes to enhance supercapacitive energy storage efficiency

We utilize straightforward and traditional Sonogashira coupling reactions to synthesize two conjugated microporous polymers linked with pyrene (referred to as PyT-PTCDA and PyT-PHTD CMPs) by combining the common precursor of 1,3,6,8-tetraethynylpyrene (PyT) with 1,7-dibromo-3,4,9,10-perylenetetracarboxylic dianhydride (PTCDA-Br2) and 3,6-dibromophenanthrene-9,10-dione (PHTD-Br2). Various analytical techniques, including spectroscopy and microscopy, are employed to characterize these two PyT-CMP materials. The PyT-PTCDA CMP exhibits notable thermal stability (with a decomposition temperature of 351 °C and a char yield of 61 wt %). We combine the PyT-PTCDA and PyT-PHTD CMPs with exceptionally conducting single-walled carbon nanotubes (SWCNTs) through π-π stacking interactions between SWCNTs and PyT unit to improve their electrical conductivity and electrochemical performance. Electrochemical evaluations reveal that the PyT-PTCDA CMP/SWCNTs nanocomposite shows an impressive capacitance of 376 F g−1 (at 0.5 A g−1) in a three-electrode system. After undergoing 5000 cycles of charging and discharging, it maintained 98 % of its original capacitance while demonstrating an energy density of 52 Wh/kg. Additionally, in a symmetric coin cell system, the energy density is 17 Wh/kg and the capacitance is 119 F g−1 for PyT-PTCDA CMP/SWCNTs. This approach presents a promising avenue for developing high-performance supercapacitors by strategically blending PyT-CMPs with highly conductive SWCNTs.

Solvatochromic fluorescent ethynyl naphthalimide derivatives for detection of water in organic solvents

Three new derivatives of (4-methoxyphenyl) ethynyl-naphthalimide were synthesized by Sonogashira coupling reaction. These compounds showed robust and strong fluorescent signals, which shift from blue to orange as the solvent polarity increases. Computational calculations revealed that in low-polarity solvents, the molecules preferred a 90° rotation between the naphthalimide and ethynyl benzene fragments. In high-polarity solvents, where the energy barrier for rotation of the alkyne bond was higher, the molecules favored the 0° conformer, leading to longer emission wavelengths. The compound with a 2-methoxyethyl group tethered to the naphthalimide nitrogen demonstrated sensitivity to water presence in the ranges of 0–30 % (v/v) in THF, 0–15 % (v/v) in DMSO, 0–30 % (v/v) in MeCN, 0–15 % (v/v) in acetone, and 0–40 % (v/v) in EtOH. The detection limits for water were determined to be 0.0523 %, 0.1365 %, 0.0337 %, 0.0570 %, and 0.1170 % (v/v) in THF, DMSO, MeCN, acetone, and EtOH, respectively. The effectiveness of this compound in quantifying ethanol content in spirit samples was successfully demonstrated.