Dimethyl Acetylenedicarboxylate Research Articles

Green synthesis of functionalized graphene-based material with dimethyl but-2-ynedioate for electrochemical energy storage devices

Functionalization of graphene with dimethyl acetylenedicarboxylate is achieved through a microwave-assisted Diels-Alder reaction. The physical, chemical, and electrochemical properties of the modified sheets are thoroughly investigated by complementary characterization techniques. Density Functional Theory calculations are employed to examine the functionalization mechanism and to highlight the role of defects such as epoxide bridges introduced in graphene during exfoliation. Our findings provide valuable insights into the development of efficient and cost-effective methods for large-scale production of high-quality graphene-based materials. Specifically, the electrochemical properties of anode materials containing functionalized graphene are evaluated for Li-ion electrochemical energy storage devices, demonstrating excellent electrochemical reversibility and rate capability. The cyclic voltammetry analysis reveals material stabilization after a few cycles, resulting in a coulombic efficiency of up to 95 % and a discharge capacity of 162.3 mA·h·g−1. The galvanostatic cycling test indicates that the material electrode retains 57 % of its initial capacity at a C-rate of 10C, indicating high-power capability. These promising results position organic modified graphene as a potential material for Li-ion capacitors, with a specific capacity that aligns with the last intercalation stage capacity at a lower potential. Overall, the study's findings offer significant contributions to the advancement of graphene-based materials in energy storage applications.

Isolation and characterization of a bis(dithiolene)-supported tungsten-acetylenic complex as a model for acetylene hydratase

Acetylene hydratase is currently the only known mononuclear tungstoenzyme that does not catalyze a net redox reaction. The conversion of acetylene to acetaldehyde is proposed to occur at a W(IV) active site through first-sphere coordination of the acetylene substrate. To date, a handful of tungsten complexes have been shown to bind acetylene, but many lack the bis(dithiolene) motif of the native enzyme. The model compound, [W(O)(mnt)2]2−, where mnt2− is 1,2-dicyano-1,2-dithiolate, was previously reported to bind an electrophilic acetylene substrate, dimethyl acetylenedicarboxylate, and characterized by FT-IR, UV–vis, potentiometry, and mass spectrometry (Yadav, J; Das, S. K.; Sarkar, S., J. Am. Chem. Soc., 1997, 119, 4316–4317). By slightly changing the electrophilic acetylene substrate, an acetylenic-bis(dithiolene)‑tungsten(IV) complex has been isolated and characterized by FT-IR, UV–vis, NMR, X-ray diffraction, and X-ray absorption spectroscopy. Activation parameters for complex formation were also determined and suggest coordination-sphere reorganization is a limiting factor in the model complex reactivity.

Copper (II)‐azo sulfathiazole complex immobilized on UiO‐66‐NH2 (MOF) as a catalyst for the one‐pot synthesis of spiroindole‐pyranopyrazoles

In this work, a new metal–organic framework nanocatalyst (Cu@UIO‐66‐AST) has been prepared from UiO‐66‐NH2 through a post‐synthesis modification process. The Cu (II)@UIO‐66‐AST nanocatalyst formation was confirmed from TGA, FT‐IR, TEM, XRD, BET, CHN, ICP, SEM, EDS, and elemental analyses. The catalytic efficiency of the synthesized MOF (Cu@UIO‐66‐AST), as an acid Lewis, was investigated in the four‐component reaction of isatin, malononitrile, hydrazine, and dimethyl acetylene dicarboxylate and compared to UiO‐66‐NH2 (as a basic catalyst) and Cu (OAc)2 (as an acidic heterogeneous catalyst). The obtained results clearly show that Cu@UIO‐66‐AST has a higher catalytic activity (93%) than UiO‐66‐NH2 (13%) and Cu (OAc)2 (43%). It could be due to the increase of dispersibility of Cu2+ by the formation of several stable complexes between Cu2+ ions and functional groups of ligand AST (OH, C=N, NH, and C‐S) on the surface of the nanocatalyst. Also, the catalyst can be recycled and reused for up to eight subsequent runs without significant loss of activity.

Bioactive Pyrrolo[2,1-f][1,2,4]triazines: Synthesis, Molecular Docking, In Vitro Cytotoxicity Assay and Antiviral Studies

A series of 2,4-disubstituted pyrrolo[2,1-f][1,2,4]triazines containing both aryl and thienyl substituents were synthesized by exploiting the 1,3-cycloaddition reaction of N(1)-ethyl-1,2,4-triazinium tetrafluoroborates with dimethyl acetylenedicarboxylate. The antiviral activity of the synthesized compounds against influenza virus strain A/Puerto Rico/8/34 (H1N1) was studied in experiments on Madin-Darby canine kidney (MDCK) cell culture. Among the pyrrolo[2,1-f][1,2,4]triazine derivatives, compounds with low toxicity and high antiviral activity were identified. Dimethyl 4-(4-methoxyphenyl)-7-methyl-2-p-tolylpyrrolo[2,1-f][1,2,4]triazine-5,6-dicarboxylate was found to demonstrate the best antiviral activity (IC50 4 µg/mL and selectivity index 188). Based on the results of in vitro tests and molecular docking studies performed, a plausible mechanism of action for these compounds was suggested to involve inhibition of neuraminidase.

Modeling stages of domino reaction of thiopyrano[4,3-b]indole-3(5H)-thiones and dimethyl acetylenedicarboxylate: a new synthetic route to γ-carbolines with thione group

Modeling stages of the cascade reaction of thiopyrano[4,3-b]indole-3(5H)-thiones and dimethyl acetylenedicarboxylate were studied. Alkylation of thiones with alkyl halides or dimethyl sulfate affording to thiopyrano[4,3-b]indole-2-ium salts models the first stage of the process. The attack at the 3-position of the obtained salts by secondary amines can serve as a model for the second stage of the cascade transformation; it gives 3-benzoylindoles with thioamide-group. Reactions of thiopyrano[4,3-b]indole-2-ium salts with primary amines lead to a series of γ-carbolines with thione group. The action of ammonia on these salts causes dealkylation and gives thiopyrano[4,3-b]indole-3(5H)-thiones.

Synthesis of Highly Functionalized Spirocycles and Pentafulvene-Containing Dyes Involving 2-(2'-ketoalkyl)-1,3-indandiones.

Synthesis of highly functionalized spiro[4.4]nonane and spiro[4.5]decane motifs by the reaction of dimethylacetylenedicarboxylate (DMAD) with 2-(2'-ketoalkyl)-1,3-indandiones and 2-(3'-ketoalkyl)-1,3-indandiones, respectively, has been developed by utilizing a catalytic amount of DABCO. The tertiary hydroxy-containing spiro[4.4]nonane products were converted into fully conjugated pentafulvene π-systems in an acidic medium through dehydration and unprecedented C-C bond rearrangement.

Convenient Synthesis of Functionalized Tetracyclic Dihydrochromeno[2,3-b]pyrrolo[3,4-e]pyridine-triones via Four-Component Reactions

AbstractIn this research, a simple and efficient strategy for the straightforward synthesis of tetracyclic dihydrochromeno[2,3-b]pyrrolo[3,4-e]pyridine-trione derivatives is presented by a sequential four-component reaction of arylamines, dimethyl acetylenedicarboxylate, alkylamines, and 3-formylchromones as readily available starting materials in MeOH at room temperature. The merit of this sequential enamine formation/1,2-nucleophilic addition/intramolecular aza-Michael addition is highlighted by its high energy conserving (short reaction times at room temperature), excellent yields, metal-free catalyst, easy purification (the products can be purified by simple filtration and washing with EtOH), and green and mild conditions in a one-pot reaction. Presumably, there are no previous reports for the synthesis of these classes of heterocyclic dihydrochromeno[2,3-b]pyrrolo[3,4-e]pyridine-trione derivatives.

Anti-Alzheimer’s and Anti-Fungal Activities of Pyrrolo[1,2-a] Quinoline Derivatives

Psychiatrists have described the protein deposits in the brain that causes various diseases such as cerebral, functional,physiological dysfunction, and neurodegenerative diseases. Although Alzheimer's disease is detectable, its treatment remainsunattainable. More than 4.6 million new patients are recorded yearly, who are affected by Alzheimer's disease and only a fewdrugs are currently in use for treatment with side effects. Hence, there is a clinical need for new drugs, design, and development.On the other hand, despite the development of antifungal therapeutics over the last three decades, antifungal resistance is still amajor cause. Regularly using inappropriate antimicrobials has become a major healthcare problem globally in the 21st century andhas been titled a "silent tsunami facing modern medicine." It has been estimated that over 8,000,000 die yearly, which providesscope for developing novel antifungal drugs. In this research paper, we describe the synthesized dimethyl-1-(4-substitutedbenzoyl)-5-methylpyrrolo[1,2-a] quinoline-2,3-dicarboxylate 1a-c and ethyl-1-(4-substituted benzoyl) 5-methylpyrrolo[1,2-a]quinoline-3-carboxylate 1d-f were evaluated for in vitro antifungal and anti-Alzheimer’s activities. The derivatives1a-f wereobtained by 1,3-dipolar cycloaddition reaction by treating quaternary salt with dimethyl acetylene dicarboxylate and ethylpropiolate respectively, in the presence of K2CO3 and DMF as a solvent. Among all compounds, 1a, 1d, and 1e showed thehighest inhibitory capacity with IC50 values of 0.28, 0.32, and 0.30 μM, respectively. On the other hand, derivatives were alsoscreened for antifungal activity that displayed moderate activity, whereas 1a and 1f derivatives showed good activity.

Design and Synthesis of Ketenimine Sulfonamide Conjugates through Multicomponent Reactions; A Combined Cytotoxic Analysis and Computational Exploration.

Multicomponent reactions involving zwitterion generated from dimethyl acetylenedicarboxylate, aryl sulfonamide, and isocyanide to generate sulfonamide-conjugated ketenimines is reported. The synthetic strategy adopted is highly atom economical and stereoselective. Ketenimine sulfonamide analogues are key intermediates for further synthetic conversions to generate a combinatorial library of compounds. Furthermore, sulfonamide compounds are known to possess a broad spectrum of biological applications. All the novel molecules synthesized exhibit the potential to target the nonhomologous DNA end-joining (NHEJ) pathway with cytotoxic ability. Computational studies compliment the in vitro biological assays of the 8 small-molecule inhibitors. DNA double-strand breaks (DSBs) are considered as the most lethal among different DNA damages. NHEJ repairs about 70% of the DSBs generated in cells within mammals. The DNA-dependent protein kinase catalytic subunit is one of the PI3 kinases associated with NHEJ. Compounds DK01-DK08 were investigated for their ability to induce cancer cell death by treating with two leukemic cell lines where NHEJ is high. Results showed that bromoaryl (DK04)- and nitroaryl (DK05)-conjugated molecules showed excellent biological activity, having IC50 values of ∼2 μM in Nalm6 cell lines.

Green synthesis of new quinolinoquinazoline derivatives via one‐pot multicomponent reactions using ZnO/TiO2@MWCNTs as a new nanocatalyst

AbstractA ZnO/TiO2@MWCNTs nanocomposite as an effective catalyst was employed for generating quinolinoquinazoline derivatives in high yields. These new compounds were synthesized by using multicomponent reaction of quinoline, isothiocyanate, 6‐amino‐2‐(prop‐1‐en‐2‐yl)‐1H‐indole‐5‐carbaldehyde, primary amines, and dimethyl acetylenedicarboxylate in aqueous media. It should be mentioned that the high performance of nanocatalyst was synthesized by using water extract of Aloe vera, which was utilized in these reactions for many times to confirm the reusability of nanocatalyst. The antioxidant property of new synthesized quinolinoquinazoline was evaluated by two procedures. Also, the antimicrobial activity of newly generated quinolinoquinazoline was evaluated by disk distribution process utilizing two kinds of Gram‐negative bacteria and Gram‐positive bacteria, proving bacterial growth was stopped by using of these compounds. Applied to the preparation of quinolinoquinazoline derivatives, this method has short reaction times, high product yields, and the ability to separate catalyst and product using simple procedures.

Three-Component Synthesis of New C3-Substituted 5,6-Dihydropyrrolo[2,1-a]isoquinolines

New C3-substituted 5,6-dihydropyrrolo[2,1-a]isoquinolines have been synthesized via three-com­ponent domino reaction of 1-aroyl-3,4-dihydroisoquinolines, dimethyl acetylenedicarboxylate, and CH acids in anhydrous acetonitrile under microwave irradiation at 130°C.

Isocyanide Cu(I) complexes with unexpected μ2‐bridging pseudohalides: Synthesis, characterization and catalytic activity towards CuAAC

Three neutral Cu(I) complexes bearing 2,6‐dimethylphenyl isocyanide (CNXyl) and different triatomic pseudohalogens (SCN−, OCN− and N3−) as ligands were efficiently synthesized and characterized. The solid‐state structures were unambiguously determined through single‐crystal X‐ray diffraction, revealing unexpected bridging coordination modes in the case of OCN− and N3−. All the complexes were tested for azide‐alkyne cycloaddition (CuAAC), showing interesting catalytic activity towards the formation of 1,4‐disubstituted‐1,2,3‐triazoles for the cyanato and the azido Cu(I) complexes. Both species afforded yields above 90% with 0.5 mol% of catalyst at 50°C for 24 h. Several alkynes and azides were tested using the more active azido Cu(I) complex, affording the corresponding triazoles in high yields. The azido Cu(I) complex also induced the intramolecular CuAAC in the presence of dimethyl acetylenedicarboxylate and benzyl bromide/phenylacetylene.

Total Synthesis of Racemic Thieno[3,2-f]thiochromene Tricarboxylate, a Luciferin from Marine Polychaeta Odontosyllis undecimdonta.

We report the first total synthesis of racemic Odontosyllis undecimdonta luciferin, a thieno[3,2-f]thiochromene tricarboxylate comprising a 6-6-5-fused tricyclic skeleton with three sulfur atoms in different electronic states. The key transformation is based on tandem condensation of bifunctional thiol-phosphonate, obtained from dimethyl acetylene dicarboxylate, with benzothiophene-6,7-quinone. The presented convergent approach provides the synthesis of the target compound with a previously unreported fused heterocyclic core in 11 steps, thus allowing for unambiguous confirmation of the chemical structure of Odontosyllis luciferin by 2D-NMR spectroscopy.

Reaction of 1-(Methylpyridin-2-yl)-3-phenyl-thioureas with Dimethyl Acetylenedicarboxylate: Formation of Isomeric Substituted 2-imino-thiazolidin-4-one Derivatives

Reaction of 1-(Methylpyridin-2-yl)-3-phenyl-thioureas with Dimethyl Acetylenedicarboxylate: Formation of Isomeric Substituted 2-imino-thiazolidin-4-one Derivatives

The Diels–Alder Reaction between Euparin and Dimethyl Acetylenedicarboxylate; a Joint Experimental and Density Functional Theory Study

In this project, we have investigated the Diels–Alder (DA) reaction between euparin (as a natural furan derivative) and dimethyl acetylenedicarboxylate (DMAD) as an electrophilic acetylene. The experimental observations during the reaction in different conditions showed that the yield and the rate of the process would increase with increasing the polarity of the solvent. Such observation suspected us that like several recent reports, the mechanism of this DA reaction takes place through a stepwise route containing a zwitterionic intermediate or at least through a relatively polar transition state (TS). Next, during the density functional theory (DFT) studies and the potential energy surface (PES) investigations, we have detected a stepwise reaction pathway in parallel with the one-step route. The results of this work are in agreement with the recent reports about the competition between the one-step and multisteps routes in the DA reactions.

Exploring the peri- and stereo- selectivities of the cycloaddition reaction of 2-(2- dimethylaminovinyl)-1-benzopyran-4-one with N-phenylmaleimide (NPM) and dimethylacetylenedicarboxylate (DMAD) - A DFT study

The [4 + 2] cycloaddition reactions of 2-styrylchromones have been predominantly described as one of the efficient methods for the synthesis of xanthones-a prominent class of tricyclic molecules that occur widely in nature. These xanthones are well known for their pharmacological activities especially their role as anti-cancer agents in the medicinal world. In this study, the mechanistic insight into the unusual (peri- and stereo-) selectivities of the reaction of 2-(2-dimethylaminovinyl)-1-benzopyran-4-one (A1) with N-phenylmaleimide (NPM) and dimethylacetylenedicarboxylate (DMAD) has been studied using density functional theory (DFT) at the M06-2X/6-311G (d, p) level of theory. The reaction of A1 and NPM in dimethylformamide (DMF) is periselective towards the initial formation of a [4 + 2] cycloadduct and stereoselectively in an exo fashion with an activation energy of 6.8kcalmol−1 and a rate constant of 6.43×107s−1 which occurs about 878 million times faster than the closest competing pathway for the initial [2 + 2] cycloaddition fashion with an activation energy of 19.0kcalmol−1 and a rate constant of 7.32×10−2s−1. For the substituent effect on the reaction, the reaction selectivity is still maintained where the exo intermediate remains the most kinetically favored cycloadduct. However, the magnitude of the barriers increases slightly with a margin of about 0.1−4.8kcalmol for the electron-donating groups (EDGs) in the order; strong EDGs (OH < NH2 < OCH3) < weak EDGs (<Ph) and 5.3−6.4kcalmol for electron-withdrawing groups in the order; strong EWGs (CF3) < weak EWGs (Cl < Br). On the other hand, DMAD periselectively adds across the amino substituted olefinic bond of A1 via an initial [2 + 2] stepwise cycloaddition fashion followed by an intramolecular rearrangement to form the xanthone product. The rate constant of the rate-determining step in the pathway for the formation of the kinetically favored [4 + 2] cycloadduct with an activation barrier of 17.3kcalmol−1 is 1.29s−1 which occurs about 373,000 times slower than the most preferred pathway affording a [2 + 2] cycloadduct with an activation barrier of 9.7kcalmol−1 and a rate constant of 4.81×105s−1. Both reactions are normal electron-demand cycloaddition reactions and are kinetically controlled.

A DFT Investigation of the Reactivity of Guanidinium Salts in Tandem aza-Michael Addition/Intramolecular Cyclization

A proposed mechanism of the reaction of guanidinium chlorides with dimethyl acetylenedicarboxylate in a tandem aza-Michael addition reaction/intramolecular cyclization was investigated by DFT M06-2X and B3LYP computational approaches. The energies of the products were compared against the G3, M08-HX, M11, and wB97xD data or experimentally obtained product ratios. The structural diversity of the products was interpreted by the concurrent formation of different tautomers formed in situ upon deprotonation with a 2-chlorofumarate anion. A comparison of relative energies of the characteristic stationary points along the examined reaction paths indicated that the initial nucleophilic addition is energetically the most demanding process. The overall reaction is strongly exergonic, as predicted by both methods, which is primarily due to methanol elimination during the intramolecular cyclization step producing cyclic amide structures. Formation of a five-membered ring upon intramolecular cyclization is highly favored for the acyclic guanidine, while optimal product structure for the cyclic guanidines is based on a 1,5,7-triaza [4.3.0]-bicyclononane skeleton. Relative stabilities of the possible products calculated by the employed DFT methods were compared against the experimental product ratio. The best agreement was obtained for the M08-HX approach while the B3LYP approach provided somewhat better results than the M06-2X and M11 methods.

Oxidopyridinium Cycloadditions Revisited: A Combined Computational and Experimental Study on the Reactivity of 1-(2-Pyrimidyl)-3-oxidopyridinium Betaine.

To investigate the effect of N-substituents on their reactivity and selectivity of oxidopyridinium betaines, we performed density functional theory (DFT) calculations of model cycloadditions with N-methylmaleimide and acenaphthylene. The theoretically expected results were compared with the experimental results. Subsequently, we demonstrated that 1-(2-pyrimidyl)-3-oxidopyridinium can be used for (5 + 2) cycloadditions with various electron-deficient alkenes, dimethyl acetylenedicarboxylate, acenaphthylene, and styrene. In addition, a DFT analysis of the cycloaddition of 1-(2-pyrimidyl)-3-oxidopyridinium with 6,6-dimethylpentafulvene suggested the possibility of pathway bifurcations involving a (5 + 4)/(5 + 6) ambimodal transition state, although only (5 + 6) cycloadducts were experimentally observed. A related (5 + 4) cycloaddition was observed in the reaction of 1-(2-pyrimidyl)-3-oxidopyridinium with 2,3-dimethylbut-1,3-diene.

Thermodynamic control synthesis of spiro[oxindole-3,3'-pyrrolines] via 1,4-dipolar cycloaddition utilizing imidazo[1,5-a]quinoline.

A series of novel 2-(quinolin-2-yl)-spiro[oxindole-3,3'-pyrrolines] were synthesized by one-pot three-component reaction involving dimethyl acetylenedicarboxylate, 1-phenylimidazo[1,5-a]quinoline and N-alkylisatins in chloroform at ∼60°C for 24h. Structures of these new spiro derivatives were deduced from HRMS and NMR spectral data. A plausible mechanism for the observed thermodynamic control pathway is presented herewith. Interestingly, the spiro adduct, derived from 5-chloro-1-methylisatin, exhibited excellent antiproliferative activity on MCF7, A549 and Hela human cell lines (IC50≃7μM).

Nucleophilicities of Cyclic α‐Diazo Carbonyl Compounds

AbstractThe one‐bond nucleophilic reactivities of seven cyclic α‐diazo carbonyl compounds in dichloromethane were determined by analyzing the kinetics of their reactions with benzhydrylium ions (one‐bond reference electrophiles) at 20 °C according to the Mayr‐Patz equation. Though not calibrated for pericyclic reactions, the identified nucleophilicities also reflect relative reactivities of the α‐diazo carbonyl compounds in 1,3‐dipolar cycloadditions with dimethyl acetylenedicarboxylate. These (3+2)‐cycloadditions primarily gave spirocyclic 3H‐pyrazoles, which underwent thermal [1,5]‐sigmatropic (van Alphen‐Hüttel) rearrangements to furnish 1H‐pyrazole‐fused tricyclic products.