Sonogashira Cross-coupling Reaction Research Articles

Sizable iodine uptake of porous copolymer networks bearing Tröger's base units

Copolymer networks containing Tröger's base units TBP1-3 were synthesized in very good yields from a Sonogashira cross-coupling reaction of a specially designed diethynyl Tröger's base synthon TB with various tetrabrominated aryl derivatives. Thermogravimetric analysis (TGA) of TBP1-3 discloses high 10% weight loss temperature values reaching up to 443 °C. Nitrogen adsorption measurements of the target copolymers TBP1-3 reveal a strong correlation between porosity and the geometry of the aryl spacer whose inflexible rigid structure (biphenyl, TBP1), contorted configuration (spirobifluorene, TBP2), or fused aromatic structure (pyrene, TBP3) affords Brunauer-Emmett-Teller (BET) surface areas ranging from ~586 m2 g−1 to ~620 m2 g−1. Inspection of the iodine adsorption properties of TBP1-3 reveals their significant uptake of iodine vapors reaching a maximum of 440 wt% for TBP1 whereas TBP2 exhibits a very good removal efficiency of iodine solution in hexane attaining 77% (qe = 192 mg g−1). Furthermore, reusability tests disclose the possibility to regenerate the polymers even after several iodine adsorptions-desorption cycles.

Modifications of Isoalantolactone Leading to Effective Anti-bacterial and Anti-viral Compounds

Background: Natural sesquiterpene lactones are an important class of heterocyclic compounds in drug discovery since they possess a wide range of biological properties, including antibacterial activity. Objective: The objective of this study was to synthesize isoalantolactone derivatives with a furo[2,3-d] pyrimidin-2-оne moiety, and to evaluate their antibacterial and antiviral activity. Methods: The Sonogashira cross-coupling and subsequent Ag-catalyzed cyclization reactions were used forthe synthesis. The antibacterial activity and the ability to inhibit biofilms formation on E. coli, S. aureus, A. viscosus, P. aeruginosa, and E. faecalis bacterial strains were evaluated in this study. A study of the molecular interactions of new compounds with the multiple virulence factor regulators was performed using docking simulations. The anti-viral activity against influenza A virus and human orthopneumovirus H-2А was also studied. Results: The in vitro anti-bacterial activity for compound 4 (MIC = 58.33 ± 4.41 μg/mL) concerning E. coli and compound 5 (MIC = 96.5 ± 3.25 μg/mL) against A. viscosus and the inhibition of biofilm formation for compounds 2, 4, and 5 on E. coli, S. aureus, P. aeruginosa, and E. faecalis bacterial strains, have been of interest for the search of improved anti-microbial agents. Compound 3 possessed antiviral activity against human orthopneumovirus H-2А with SI >33. The activity of the new type of hybrid compounds is dependent on the substituent in the 6th position of the furo[2,3-d] pyrimidin-2-one fragment. Conclusion: The decoration of isoalantolactone with a furo[2,3-d]pyrimidin-2-one fragment led to perspective antiviral and antimicrobial agents. Due to antimicrobial activity, pyridine-4-yl substituted isoalantolactone-furopyrimidinone hybrid is considered as a candidate compound to participate in further research.

Sonogashira cross-coupling of (Z)-2‑bromo-2-CF3-vinyl benzyl sulfide and access to 4-CF3-3-iodo-2-substituted thiophenes

The Sonogashira cross-coupling reaction of (Z)-2‑bromo-2-CF3-vinyl benzyl sulfide with various terminal acetylenes afforded the corresponding (E)-2-CF3-1-buten-3-ynyl benzyl sulfides in good to high yields. Subsequent iodocyclization afforded the corresponding 4-CF3-3-iodo-2-substituted thiophenes in good to high yields.

Tuning the Fluorescence and the Intramolecular Charge Transfer of Phenothiazine Dipolar and Quadrupolar Derivatives by Oxygen Functionalization.

A series of new naphthalimide and phenothiazine-based push–pull systems (NPI-PTZ1–5), in which we structurally modulate the oxidation state of the sulfur atom in the thiazine ring, i.e., S(II), S(IV), and S(VI), was designed and synthesized by the Pd-catalyzed Sonogashira cross-coupling reaction. The effect of the sulfur oxidation state on the spectral, photophysical, and electrochemical properties was investigated. The steady-state absorption and emission results show that oxygen functionalization greatly improves the optical (absorption coefficient and fluorescence efficiency) and nonlinear optical (hyperpolarizability) features. The cyclic voltammetry experiments and the quantum mechanical calculations suggest that phenothiazine is a stronger electron donor unit relative to phenothiazine-5-oxide and phenothiazine-5,5-dioxide, while the naphthalimide is a strong electron acceptor in all cases. The advanced ultrafast spectroscopic measurements, transient absorption, and broadband fluorescence up conversion give insight into the mechanism of photoinduced intramolecular charge transfer. A planar intramolecular charge transfer (PICT) and highly fluorescent excited state are populated for the oxygen-functionalized molecules NPI-PTZ2,3 and NPI-PTZ5; on the other hand, a twisted intramolecular charge transfer (TICT) state is produced upon photoexcitation of the oxygen-free derivatives NPI-PTZ1 and NPI-PTZ4, with the fluorescence being thus significantly quenched. These results prove oxygen functionalization as a new effective synthetic strategy to tailor the photophysics of phenothiazine-based organic materials for different optoelectronic applications. While oxygen-functionalized compounds are highly fluorescent and promising active materials for current-to-light conversion in organic light-emitting diode devices, oxygen-free systems show very efficient photoinduced ICT and may be employed for light-to-current conversion in organic photovoltaics.

Synthesis, characterization and anticancer evaluation of nitrogen-substituted 1-(3-aminoprop-1-ynyl)-4-hydroxyanthraquinone derivatives

Anthraquinones are of significant interest due to their biological activity, coloring properties, and synthetic applications. Here, we describe a mild and convenient method for modification of 1-ethynyl-4-hydroxyanthraquinone that was obtained from the Sonogashira cross-coupling reaction of 1-hydroxy-4-iodoanthraquinone with alkynes. The copper(I) catalyzed one-pot three-component reaction (A3-coupling) of the new 1-ethynyl-4-hydroxyanthraquinone with secondary amines and formaldehyde was the main approach for the synthesis of nitrogen-substituted 1-[3-(amino)prop-1-ynyl]-4-hydroxyanthraquinones. The influence of different substituents in the amine on reaction rate and yield has been evaluated. The cytotoxicity of 1-ethynyl-4-hydroxyanthraquinones was assessed using the conventional MTT assay. Among all compounds synthesized, anthraquinone-propargylamine derivatives 28, 29, 30, and 34 possess the most promising cytotoxic potential towards glioblastoma cancer cells; compounds 14 and 19 shown selectivity towards the prostate cancer cells DU-145, and 18, 24 — on breast cancer cell line MCF-7. The grown inhibition on these cancer cells by compounds 18 and 24 was comparable to those of standard drug Doxorubicin. Molecular modeling of new anthraquinone derivatives in DNA G-quadruplex binding sites was performed to help understand the observed SAR trends.

Large screening of DNA-compatible reaction conditions for Suzuki and Sonogashira cross-coupling reactions and for reverse amide bond formation

Progress in DNA-encoded chemical library synthesis and screening crucially relies on the availability of DNA-compatible reactions, which proceed with high yields and excellent purity for a large number of possible building blocks. In the past, experimental conditions have been presented for the execution of Suzuki and Sonogashira cross-coupling reactions on-DNA. In this article, our aim was to optimize Suzuki and Sonogashira reactions, comparing our results to previously published procedures. We have tested the performance of improved conditions using 606 building blocks (including boronic acids, pinacol boranes and terminal alkynes), achieving >70% conversion for 84% of the tested molecules. Moreover, we describe efficient experimental conditions for the on-DNA synthesis of amide bonds, starting from DNA derivatives carrying a carboxylic acid moiety and 300 primary, secondary and aromatic amines, as amide bonds are frequently found in DNA-encoded chemical libraries thanks to their excellent DNA compatibility.

Investigations of Donor–Acceptor Interactions in 1,3,5-Tris-(3-Methoxy & 3-Methyl Carboxy) Phenyl Ethynyl Benzene Derivatives Using Experimental and DFT Study

Two new 1,3,5-tris-(3-methoxy (6a) & 3-methyl carboxy (6b)) phenyl ethynyl benzene derivatives were synthesized from 1,3,5-triethynylbenze and 3-bromo anisole/methyl-3-bromo benzoate, respectively, under Sonogashira cross-coupling reaction conditions. The molecular structures of these two compounds were confirmed by spectral, CHN, and single-crystal XRD analysis. The compound 6a, crystallized in triclinic system (Space group = Pî, Z = 2, a (Å) = 8.4849(1); b (Å) = 12.0292(2); c (Å) = 12.9601(2); α(°) = 95.580(1); β(°) = 93.170(1); γ (°) = 99.942(1)) and 6b, crystallized in monoclinic system (Space group = P21/n, Z = 4, a (Å) = 3.9282(6); b (Å) = 32.274(1); c (Å) = 27.440(2); β(°) = 92.29(1)). Furthermore, the optimized molecular geometries were compared with experimental counter parts employing DFT approach. The complete spectroscopic studies of the titled compounds were carried out using analytical techniques, such as FT-IR, NMR, CV, and UV–VIS analysis and compared with the theoretical results. The first order hyper-polarizability, natural bond orbital analysis, frontier molecular orbitals, and molecular electrostatic potentials were performed on 6a&b, by employing the DFT method and compared with their ortho- and para-substituent compounds. These results indicated that the two compounds 6a&b, showed different donor–acceptor (D–A) interactions based on donor (−OCH3) or acceptor (–COOCH3) moieties attached to the benzene ring.

Magnetic chitosan-functionalized cobalt-NHC: Synthesis, characterization and catalytic activity toward Suzuki and Sonogashira cross-coupling reactions of aryl chlorides

• Co-NHC@MC is the first example of Cobalt-NHC catalyst catalyzed the reaction of substituted phenylboronic acid and phenlacethylene with derivatives of aryl chlorides. • Co-NHC@MC showed outstanding catalytic activity toward Suzuki and Sonogashira cross coupling reaction. • Co-NHC@MC catalyzed Suzuki and Sonogashira cross coupling reaction without any toxic reducing agent in PEG as green solvent. • Chitosan was used as an accessible, easily and non-toxic modification-support for cobalt catalyst. • Co-NHC@MC is easily recovered and reused for 7 runs for Suzuki and Sonogashira cross coupling reaction. Aryl chlorides are one of the most stable and available electrophiles, however, their coupling with nucleophiles remains a challenge in organic synthesis. Herein, we prepared a Cobalt-NHC (N-Heterocyclic carbene) complex anchored on magnetic chitosan nanoparticles and assayed its catalytic activity for the reactions of substituted phenylboronic acid and also phenlacetylene with derivatives of aryl chlorides. These reactions are of great importance since they are employed for the synthesis of unsymmetrical diarylethynes and biphenyls, which belong to a prime class of building blocks. The synthesized nanocatalyst was found to be highly efficient in Suzuki and Sonogashira coupling in terms of their activity and recyclability in polyethylene glycol (PEG) as a green reaction media under conditions of temperatures (70 and 100 °C) and Co loading (3 and 6 mol%). To the best of our knowledge, this is the first attempt of using cobalt-NHC complex for catalyzing the abovementioned reactions. Moreover, replacing the earth-abundant Cobalt-based catalyst as an alternative to high cost palladium make this approach promising from sustainable chemistry view.

Studies on photophysical and electrochemical properties of triphenylamine α, β-unsaturated ketone side-arm PAE CPs

A series of polyaryleneethynylene (PAE) conjugated polymers (CPs) have been synthesized using 1-(4-((2,5-diethynylphenyl)ethynyl)phenyl)-3-(4-(diphenylamino)phenyl)prop-2-en-1-one, 1,4-diiodo-2,5-bis(octyloxy)benzene, 1,4-bis(dodecyloxy)-2,5-diiodobenzene and 2,7-diiodo-9,9′-dioctyl-9H-fluorene with terminal hydrogen presented diethynylene and diiodo–substituted precursor as acceptor and donor monomers. The donor and acceptor (D-A) unit network of CPs developed through the Heck–Sonogashira cross-coupling reaction mechanism. The triphenylamine attached α,β unsaturated ketone of phenylethynylene side-arm PAE CPs was studied for their photophysical and electrochemical behaviors based on the molecular-level electronic properties. From the solution-phase UV–visible (UV–Vis) and Fluorescence (FL) measurements explained the π–π* electronic transition and intramolecular charge transfer (ICT) behavior of the CPs. The shift between UV–Vis maxima and FL maxima are well accounted for calculating the Stokes shift, which supports the evidence for the red shift of PAE CPs, namely NPAEC8-127 nm, NPAEC12-131 nm, and NPAEF8-25 nm. The thin-film UV–Vis absorption spectra and electrochemical measurements ascertain the existence of the optical low band gap (Eg) (NPAEC8-2.57 nm, NPAEC12-2.62 nm, and NPAEF8-2.70 nm) and HOMO–LUMO energy levels of the PAE CPs. Based on data obtained from different studies, it is suggested that the synthesized PAE CPs are suitable for the photovoltaic and sensor applications.

Acetophenyl-thienyl-aniline-Linked Nucleotide for Construction of Solvatochromic Fluorescence Light-Up DNA Probes Sensing Protein-DNA Interactions.

The synthesis of 2'-deoxycytidine and its 5'-O-triphosphate bearing solvatochromic acetophenyl-thienyl-aniline fluorophore was developed using the Sonogashira cross-coupling reaction as the key step. The triphosphate was used for polymerase synthesis of labelled DNA. The labelled nucleotide or DNA exerted weak red fluorescence when excited at 405 nm, but a significant colour change (to yellow or green) and light-up (up to 20 times) was observed when the DNA probes interacted with proteins or lipids.

Cross-Coupled Phenyl- and Alkynyl-Based Phenanthrolines and Their Effect on the Photophysical and Electrochemical Properties of Heteroleptic Cu(I) Photosensitizers.

With the aims of increasing the antenna system and improving the photophysical properties of Cu(I)-based photosensitizers, the backbone of 2,9-dimethyl-1,10-phenanthroline was selectively extended in the 5,6-position. Applying specifically tailored Suzuki-Miyaura and "chemistry-on-the-complex" Sonogashira cross-coupling reactions enabled the development of two sets of structurally related diimine ligands with a broad variety of different phenyl- and alkynyl-based substituents. The resulting 11 novel heteroleptic Cu(I) complexes, including five solid-state structures, were studied with respect to their structure-property relationships. Both sets of substituents are able to red-shift the absorption maxima and to increase the absorptivity. For the alkynyl-based complexes, this is accompanied by a significant anodic shift of the reduction potentials. The phenyl-based substituents strongly influence the emission wavelength and quantum yield of the resulting Cu(I) complexes and lead to an increase in the emission lifetime of up to 504 ns, which clearly indicates competition with the benchmark system [(xantphos)Cu(bathocuproine)]PF6.

Effect of conjugation on the optoelectronic properties of pyrazine-based push-pull chromophores: Aggregation-induced emission, solvatochromism, and acidochromism

A series of pyrazine-based bipodal D-π-A-π-D and D-π-A-π-A molecules with multi-stimuli response have been synthesized via Suzuki and Sonogashira cross-coupling reactions. We present a joint theoretical and experimental study to elucidate structure-property relationship of these push-pull chromophores. The modification of the end-capped donor-acceptor units and the extension of π-conjugation are key factors in tuning their optical, thermal and electrochemical properties. Depending on the different electron-donating substituents, the chromophores emit blue to orange fluorescence. The solvent dependent emission was observed and their Dimroth-Reichardt plots show a linear correlation. The aggregation-induced study shows enhanced emission in aggregates. Our work has elucidated that these small structural isomers can be utilized to develop a promising multi-stimuli responsive fluorescent materials.

Process Development of a Sonogashira Cross-Coupling Reaction as the Key Step of Tirasemtiv Synthesis Using Design of Experiments

Palladium-catalyzed coupling reactions represent an important tool for modern organic synthesis and have been extensively used in the pharmaceutical industry for the past 30 years to produce active...

A Novel Conjugated Pyrene-BODIPY Dyad: Synthesis, Characterization and Properties

In the present work, a novel highly conjugated pyrene-BODIPY (BODPhPy) with a D-A (donor-acceptor) skeleton small molecule was synthesized by Sonogashira cross-coupling reaction between 1-ethynylpyrene as a donor group (EthyPy) and BODIPY as an acceptor group (BrPh-BOD). The new compound was characterized by fourier transform-infrared (FT-IR), nuclear magnetic resonance spectroscopy (NMR), mass spectrometry (MALDI-TOF) and elemental analysis. The photophysical and electrochemical properties of the compound (BODPhPy) were investigated by UV-vis absorption, fluorescence emission spectroscopy, and cyclic voltammetry (CV) in dichloromethane. It was found from the optical and electrocemical measurements that the target compound has highest occupied molecular orbital energy level (EHOMO) of -5.70 eV, lowest unoccupied molecular orbital energy level (ELUMO) of -3.27 eV, and the band gap was calculated as 2.43 eV. In addition, theoretic computational studies was also carried out via density functional techniques (DFT) for investigation of molecular structure and energy levels of the compound. According to this results, the novel compound could be potential candidate for optoelectronic devices.

Prospects and Applications of Palladium Nanoparticles in the Cross-coupling of (hetero)aryl Halides and Related Analogues.

Discovering efficient methods for the formation of carbon‐carbon bonds is a central ongoing theme in organic synthesis. Cross‐coupling reactions catalysed by metal nanoparticles are attractive alternatives to the traditional use of metal counterparts due to the catalytic tunability, selectivity, recyclability and reusability of the nanoparticles. The ongoing search for sustainable processes demands that reusable and environmentally benign catalysts are used. While the advantages of nanoparticles catalysts over bulk catalysts cannot be overemphasised, the problem of sintering, agglomeration and leaching are drawbacks to their full industrial applications. Hence, efforts are being made towards advancing the efficiency of the catalytic nanoparticle systems over the years. This review presents the progress, the challenges and the prospects of palladium nanoparticle with focus on Heck, Suzuki, Hiyama and Sonogashira cross‐coupling reactions involving (hetero) aryl halides and the analogues.

Introduction of a Recyclable Basic Ionic Solvent with Bis-(NHC) Ligand Property and The Possibility of Immobilization on Magnetite for Ligand- and Base-Free Pd-Catalyzed Heck, Suzuki and Sonogashira Cross-Coupling Reactions in Water

A new versatile and recyclable NHC ligand precursor has been developed with ligand, base, and solvent functionalities for the efficient Pd-catalyzed Heck, Suzuki and Sonogashira cross-coupling reactions under mild conditions. Furthermore, NHC ligand precursor was immobilized on magnetite and its catalytic activity was also evaluated towards the coupling reactions as a heterogeneous catalyst. The NHC ligand precursor was prepared with imidazolium functionalization of TCT followed by a simple ion exchange by hydroxide ions. However, the results revealed an excellent catalytic activity for the both homogeneous and heterogeneous catalytic systems. 1.52 g.cm−3 and 1194 cP was obtained for the density and viscosity of the NHC ligand precursor respectively. On the other hand, the heterogeneous type could be readily recovered from the reaction mixture and reused for several times while preserving its properties. Heterogeneous nature of the magnetic catalyst was studied by hot filtration, mercury poisoning, and three-phase tests. High to excellent yields were obtained for all entries for the both homogeneous and heterogeneous catalysts, which reflects the high consistency of the catalyst.

Aerobic Cu and amine free Sonogashira and Stille couplings of aryl bromides/chlorides with a magnetically recoverable Fe3O4@SiO2 immobilized Pd(II)-thioether containing NHC

Two value added CC cross coupling reactions; Sonogashira and Stille couplings were achieved at milder conditions in the catalytic presence of a magnetically recoverable heterogeneous catalyst Fe3O4@SiO2@NHC^SPh-Pd(II). The catalyst was earlier reported for Suzuki-Miyaura reaction, and as an extension of its catalytic efficiency, the Stille and Sonogashira cross coupling reactions under aerobic condition has been explored in present report. The Sonogashira coupling of aryl bromides and terminal alkynes produced an excellent yield (~96% at 0.25 mol% Pd) of the desired coupling product under copper and amines free conditions. Moreover, an excellent Stille coupling of readily available and more latent aryl chlorides and trialkylstannane was obtained (yields up to 95% at 0.25 mol% Pd) in absence of toxic fluorides additives. The broad substrate scope of the catalyst for both the coupling reactions and the magnetically recoverable feature of catalyst make this reaction highly desirable for industrial applications of present heterogeneous catalysis.

II- from ecological recycling of Pd to greener sonogashira cross-coupling reactions

Based on a new process derived from biosorption technology that uses roots from aquatic and wetland plants (Mentha aquatica, Eichhornia crassipes, Pistia stratiotes, Ludwigia peploides, Fallopia japonica), materials rich in lignin (pinecone, bark pine) and wastes rich in tannins (coffee grounds), we were able to prepare a new class of ecocatalyst, called Eco-Pd. The formed Eco-Pd are characterized via MP-AES and XRDP in the order to elucidate the chemical composition and the structure of the new formed materials. Interestingly, the presence of higher-oxidation-state palladium species, namely K2PdCl6, is observed. We describe the use of this new generation of Eco-Pd for a green and sustainable Sonogashira reaction. The absence of copper, ligands, additives, a lower Pd loading (0.05 mol% - 0.1 mol%), the use of green solvents (glycerol/n-BuOH), and the use of biosourced Pd and base (Eco-Ca), are significant advantages of this approach. The combination TON/TOF (103/250 h−1) can be advantageously compared with literature and demonstrates the remarkable practical utility of these new catalysts. Most importantly, the Eco-Pd can be easily recycled by biosorption and reused, that is another asset in terms of sustainable Chemistry.

Bimetallic Ni/Cu mesoporous silica nanoparticles as an efficient and reusable catalyst for the Sonogashira cross-coupling reactions

A bimetallic mesoporous system (Ni/Cu-MCM-41) has been developed and evaluated as an efficient catalyst for the Sonogashira cross-coupling reaction, under palladium-free conditions. In this new methodology, a wide range of aryl halides react with phenylacetylene to give the corresponding disubstituted alkynes in good yields. Moreover, the present catalytic system is desired because of its high efficiency, easy preparation, low cost, high activity, and good recyclability.

Layered double hydroxides as heterogeneous catalyst systems in the cross-coupling reactions: an overview.

Layered double hydroxides (LDHs) are recognized as two-dimensional (2D) clay materials, which comprise the interlayer anions and host layers with a positive charge (brucite-like M(OH)6 octahedral). They have been used as effective and eco-friendly heterogeneous catalytic systems in cross-coupling reactions. In this review, we try to underscore the applications of (LDHs) as an efficient and green catalyst in some important name reactions, namely Suzuki, Heck, Sonogashira, and Ullmann cross-coupling reactions leading to carbon-carbon bond formations.