Dialkyl Acetylenedicarboxylates Research Articles

Three-component reaction of triphenylphosphine, dialkyl acetylenedicarboxylates, and 2-nitrocyclohexanone

Three-component reaction of triphenylphosphine, dialkyl acetylenedicarboxylates, and 2-nitrocyclohexanone

An efficient synthesis of phosphonated cyclopentenones by NaN3-catalyzed three-component reaction between trialkyl phosphites, ethyl arylmethylidenecyanoacetates and dialkyl acetylenedicarboxylates.

NaN3-catalysed three-component reaction between trialkyl phosphites, dialkyl acetylenedicarboxylates and ethyl arylmethylidenecyanoacetates afforded phosphonated cyclopentenone derivatives. The process involves one C-P and two C-C bond formations in one synthetic step. All reactions were conducted in acetone as solvent at room temperature and the products were obtained in high yields as stable solids. The products were isolated and purified by simple washing with water and diethyl ether without need to tedious chromatography methods. The structures of products were proved by 1H, 13C and 31P NMR and IR spectral and elemental analysis data.

An Efficient One-Pot, Three-Component Synthesis of Tetrasubstituted Pyrroles under Catalyst- and Solvent-Free Conditions

AbstractAn environmentally benign, catalyst- and solvent-free, three-component synthesis of tetrasubstituted pyrroles was established. The reaction proceeds via a nucleophilic attack of primary amine on dialkyl acetylenedicarboxylate followed by Michael addition with β-nitrostyrene and successive intramolecular cyclization and aromatization to yield 1,2,3,4-tetrasubstituted pyrroles in good to excellent yields. A wide range of primary amines including aromatic amines and benzylamines were coupled with differently substituted β-nitrostyrenes and dialkyl acetylenedicarboxylate. Furthermore, compared to previous reported methods, the present study is highly atom economical and environmentally benign and can be scaled up.

Straightforward synthesis of quinoxaline-furan bis-heterocyclic structures via a multicomponent reaction

An efficient and straightforward synthetic strategy based on the higher-order multicomponent reactions (MCRs) is established for the synthesis of quinoxaline-furan bis-heterocyclic structures. The process includes a one-pot, pseudo-five component reaction of 3,4-diaminobenzoic acid, a 1,2-dicarbonyl compound, a dialkyl acetylenedicarboxylate, and two equivalents of an isocyanide as the readily available precursors. The noticeable features of the method are pot and atom economy, seven new bond formations, operational simplicity, high yields, and applicability on the gram-scale. Indolo[2,3-b]quinoxaline-furan tris-heterocycles were also synthesized using isatin derivatives via consecutive reactions.

The unique reactivity of 5,6-unsubstituted 1,4-dihydropyridine in the Huisgen 1,4-diploar cycloaddition and formal [2 + 2] cycloaddition.

The three-component reaction of isoquinolines, dialkyl acetylenedicarboxylates, and 5,6-unsubstituted 1,4-dihydropyridines in acetonitrile at room temperature afforded functionalized isoquinolino[1,2-f][1,6]naphthyridines in good yields and with high diastereoselectivity. More importantly, the formal [2 + 2] cycloaddition reaction of dialkyl acetylenedicarboxylates and 5,6-unsubstituted 1,4-dihydropyridines in refluxing acetonitrile gave unique 2-azabicyclo[4.2.0]octa-3,7-dienes as major products and 1,3a,4,6a-tetrahydrocyclopenta[b]pyrroles as minor products via further rearrangement.

Enantioselective Synthesis of Axially Chiral Figure-Eight Spirocycloparaphenylenes via Rh-Catalyzed Intermolecular [2 + 2 + 2] Cycloaddition.

We have achieved the enantioselective synthesis of axially chiral figure-eight spiro[9.9]cycloparaphenylene (CPP) tetracarboxylates with up to 75:25 er via the cationic Rh(I)/(R)-H8-BINAP complex-catalyzed chemo-, regio-, and enantioselective intermolecular double [2 + 2 + 2] cycloaddition of an achiral symmetric tetrayne with dialkyl acetylenedicarboxylates followed by reductive aromatization. The spiro[9.9]CPP tetracarboxylates are highly distorted at the phthalate moieties with large dihedral and boat angles and exhibit weak aggregation-induced emission enhancement behavior.

Isocyanide-based synthesis of spirorhodanine-cyclopentadiene and spirorhodanine-iminobutenolide conjugates from Winterfeldt's zwitterions and 5-ylidene rhodanines.

An ultrasonic-assisted isocyanide-based protocol to access a series of functionalized spirorhodanine-cyclopentadiene and spirorhodanine-iminobutenolide conjugates from alkyl isocyanides and dialkyl acetylenedicarboxylates in the presence of 5-ylidene rhodanines in MeCN, is described. The reaction proceeds via interception of the reactive Winterfeldt's zwitterions by 5-ylidene rhodanine derivatives. The structures of the target compounds were confirmed by X-ray diffraction studies.

One-pot three-component synthesis of novel pyrano[3,2-e]pyrazolo[1,5-a]pyrimidines and investigation of their biological activities

In this study, pyrano[3,2-e]pyrazaolo[1,5-a]pyrimidine derivatives were produced in high yields (80–89%), at room temperature, by three-component reactions involving alkyl isocyanides, dialkyl acetylenedicarboxylates, and 7‑hydroxy pyrazolo[1,5-a]pyrimidines. Using FT-IR, 1H and 13C NMR, and mass spectral data, the structure of the synthesized compounds was identified. The created molecules were tested against cancer, bacteria, and free radicals to evaluate how effective they could be. It was determined whether or not the tested substances had any cytotoxic effects on the MCF-7 (breast cancer) and the MCF-10 (breast epithelial) cell lines. Compound 4l, in comparison to other compounds, has shown the most potent anti-cancer activity (IC50=19.70±0.89 µM), which is roughly as excellent as the standard medicine etoposide (IC50= 18.71±1.09 µM). Also, the antioxidant properties of the products were investigated using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. The results demonstrated that compound 4 h had the highest free radical scavenging effect (IC50= 12.12±0.40 µM), which was very close to the value for ascorbic acid (IC50= 11.85±0.30 µM), as the antioxidant standard. The Kirby-Bauer disk diffusion technique was applied to examine the bactericidal impact of the synthesized compounds. According to the findings, virtually all the compounds had a modest level of action against Gram-positive bacteria (Bacillus subtilis and Staphylococcus aureus).

An efficient synthesis of functionalized β-amino- and β-hydrazinoalkylphosphonates by three-component reaction between trialkyl phosphites, dialkyl acetylenedicarboxylates and aromatic amines or hydrazines.

Three-component reaction between trialkyl phosphites, dialkyl acetylenedicarboxylates and aromatic amines afforded β-aminoalkylphosphonate derivatives. Similar reaction between trialkyl phosphites, dialkyl acetylenedicarboxylates and dinitrophenylhydrazine afforded β-hydrazinooalkylphosphonate derivatives. This method includes both the C-N and C-P bond formation in a one pot and single synthetic step in neutral and simple reaction conditions. All reactions were conducted in CH2Cl2 as solvent at room temperature without using any catalyst, and the stable products were obtained in high yields. The structures of all products were proved by 1H, 13C and 31P NMR and IR spectral and elemental analysis data.

Progress in Isocyanide‐Based Step‐Growth Polymerization

AbstractIsocyanide is an important class of active synthon with a special electronic structure and abundant chemical properties, which can participate in various organic reactions and has a wide range of applications in the efficient synthesis of pharmaceutical molecules, heterocyclic compounds, and natural products, etc. With the development of chemical science, isocyanide‐based reactions have been gradually applied from the synthesis of low mass molecules to functional polymers. This review focuses on the recent progress in isocyanide‐based step‐growth polymerization, as well as the properties and applications of the resultant functional polymers. These polymerizations are divided into six main parts including Passerini polymerization, Ugi polymerization, multicomponent polymerization (MCP) of isocyanide and dialkylacetylenedicarboxylates (DAADs), MCP of isocyanide and green monomer, MCP of isocyanide and industrial waste, as well as the polymerization based on isocyanoacetate. The existing challenges and the promising opportunities are concisely discussed.

Synthesis and Identification of New N,N-Disubstituted Thiourea, and Thiazolidinone Scaffolds Based on Quinolone Moiety as Urease Inhibitor.

Synthesis of thiazolidinone based on quinolone moiety was established starting from 4-hydroxyquinol-2-ones. The strategy started with the reaction of ethyl bromoacetate with 4-hydroxyquinoline to give the corresponding ethyl oxoquinolinyl acetates, which reacted with hydrazine hydrate to afford the hydrazide derivatives. Subsequently, hydrazides reacted with isothiocyanate derivatives to give the corresponding N,N-disubstituted thioureas. Finally, on subjecting the N,N-disubstituted thioureas with dialkyl acetylenedicarboxylates, cyclization occurred, and thiazolidinone derivatives were obtained in good yields. The two series based on quinolone moiety, one containing N,N-disubstituted thioureas and the other containing thiazolidinone functionalities, were screened for their in vitro urease inhibition properties using thiourea and acetohydroxamic acid as standard inhibitors. The inhibition values of the synthesized thioureas and thiazolidinones exhibited moderate to good inhibitory effects. The structure−activity relationship revealed that N-methyl quinolonyl moiety exhibited a superior effect, since it was proved to be the most potent inhibitor in the present series achieving (IC50 = 1.83 ± 0.79 µM). The previous compound exhibited relatively much greater activity, being approximately 12-fold more potent than thiourea and acetohydroxamic acid as references. Molecular docking analysis showed a good protein−ligand interaction profile against the urease target (PDBID: 4UBP), emphasizing the electronic and geometric effect of N,N-disubstituted thiourea.

Magnetically recoverable Fe3O4 nanocatalyst for the synthesis of biodynamically significant 1H-pyrazolo[1,2-b]phthalazine-5,10-diones derivatives and its DFT study.

An environmentally sustainable and proficient method is reported for the synthesis of medicinally important pyrazolo[1,2-b] phthalazine dione derivatives by aqueous micellar medium catalysed by Fe3O4 NPs. Dialkyl acetylenedicarboxylate with isocyanides in the presence of phthalhydrazide is used as starting material. The main advantages of this protocol are the availability of starting materials, short reaction times, green solvents and practical simplicity.

Synthesis of polyfunctionalized dihydro-2-oxypyrroles catalyzed by 1,2,3,5-tetrakis(carbazol-9-yl)-4,6-dicyanobenzene (4CzIPN) as a novel donor-acceptor fluorophore

We developed a green radical synthesis method for polyfunctionalized dihydro-2-oxypyrroles based on the Michael–Mannich cyclocondensation of amines, dialkyl acetylenedicarboxylates, and formaldehyde. To generate a renewable energy sources from visible light, a PCET (proton-coupled electron transfer) photocatalyst was used in an ethanol solution in an air environment and at room temperature. In this study, we aim to develop an inexpensive and easily accessible novel donor–acceptor (D–A) fluorophore. Besides its speed-saving features and ease of use, the carbazole-based photocatalyst (4CzIPN) also shows high yields, energy-efficient, and is environmentally friendly. In this way, it is possible to monitor changes in chemical and environmental variables over time. The variety of yields is pretty uniform (84–97%, average 92.3%), and the kind of response times be very speedy (15–25 min, average 17.6 min), and the element noted within the dialogue is that the system tolerates a variety of donating and withdrawing functional groups, at the same time as nevertheless giving very fast rate and tremendous yields. A study of polyfunctionalized dihydro-2-oxypyrroles was conducted to calculate the turnover number (TON) and turnover frequency (TOF). Gram-scale cyclization proves that it can be applied to industry in a practical manner.

Use of Dialkyl Acetylenedicarboxylates in the Multicomponent Synthesis of Heterocyclic Structures

AbstractDialkyl acetylenedicarboxylates (DAAD) are the class of acetylenic compounds that are broadly used in organic synthesis in a noticeable quantity. Their wide application has made them an important moiety in heterocyclic compounds and drug discovery programs. Dialkyl acetylenedicarboxylate is a di‐ester in which the ester groups are conjugated with a carbon‐carbon triple bond. As such, the molecule is very electrophilic, and is broadly used as a dienophile in various cycloaddition reactions, for example the Diels‐Alder reaction. In addition, it is a strong Michael acceptor. Due the importance of dialkyl acetylenedicarboxylate in organic synthesis, we are trying to show the applications of this compound in the synthesis of different heterocycles using multicomponent reactions. In this review, we show recent advances (2016–2022) for the synthesis of various heterocycles that have different ring sizes (five, six and seven membered, Spiro and fused heterocycles), using DAAD via multicomponent reactions.

An efficient synthesis of phosphonate derivatives and stable phosphorus ylids by three-component reaction between phosphines or phosphites, benzil hydrazone and dialkyl acetylenedicarboxylates

An efficient synthesis of phosphonate derivatives and stable phosphorus ylids by three-component reaction between phosphines or phosphites, benzil hydrazone and dialkyl acetylenedicarboxylates

A facile one-pot synthesis of new functionalized pyrazolone-1,4-dithiafulvene hybrids.

In this study, a one-pot reaction between β-keto esters or dialkyl acetylenedicarboxylates with hydrazines, carbon disulfide, and dialkyl acetylenedicarboxylates in the presence of triethylamine is reported. This reaction proceeded at room temperature and was completed within 6h to produce functionalized pyrazolone-1,4-dithiafulvene hybrids in good yields.

Visible Light Mediated, Catalyst Free, One-Pot Convenient Synthesis of Dihydropyridines

: A simple, efficient and green protocol has been developed for the synthesis of polysubstituted dihydropyridines via one-pot, four-component reaction of aldehydes, arylamines, dialkyl acetylenedicarboxylate, and malononitrile. The reaction was proceeded at room temperature in the absence of catalyst in aqueous ethyl lactate under visible light irradiation. The main advantages of the present approach are mild reaction condition, high yield, no column chromatography, clean reaction profile, environmentally friendly and sustainable from the economic point of view

Synthesis of arylphosphinoyl-functionalized dihydroisoquinolines by Reissert-type reaction and their biological evaluation

An efficient synthetic method for potentially biologically active new arylphosphinoyl-functionalized dihydroisoquinoline derivatives was developed by the Reissert-type reaction of isoquinoline, dialkyl acetylenedicarboxylates and secondary phosphine oxides or ethyl phenyl-H-phosphinate. The model reaction of isoquinoline, diethyl acetylenedicarboxylate and diphenylphosphine oxide was optimized in respect of the solvent, the temperature and the reaction time, as well as the dosing order of the starting materials. The protocol developed enabled the preparation of the target derivatives under mild conditions for a short reaction time. The in vitro cytotoxicity on different cell lines and the antibacterial effect of the phosphorylated dihydroisoquinolines synthesized were also investigated. Based on the IC50 values determined, the derivatives, which contain 3,5-dimethylphenyl or 2-naphtyl groups on the phosphorus atom, showed a promising activity against human promyelocytic leukemia (HL-60) cells and against Bacillus Subtilis Gram-positive bacteria.

A one-pot synthesis 3-alkoxycarbonyl-3,4-dihydro-2H-pyran-2-ones from vinylidene melderum's acids, dialkyl acetylenedicarboxylates, and simple alcohols.

A one-pot synthesis of 3-alkoxycarbonyl-3,4-dihydro-2H-pyran-2-ones from intermolecular hetero-Diels-Alder reaction between vinylidene Melderum's acids and dialkyl acetylenedicarboxylates, in the presence of simple alcohols at room temperature, is described. The advantages of this procedure are good yields, short reaction time, and easy workup. Antioxidant properties of four derivatives of these 3,4-dihydro-2H-pyran-2-ones, together with their antimicrobial activities, are investigated.

Diastereoselective Synthesis of Spirocyclopentene-Indanediones from Isocyanides, Acetylenic Esters, and NH-Acidic Compounds

AbstractA diastereoselective synthesis of spirocyclopentene-1H-indene-1,3(2H)-diones through a three-component reaction of alkyl isocyanides, dialkyl acetylenedicarboxylates, and 2-(alkylamino)-2-(1,3-dioxo-1H-inden-2(3H)-ylidene)acetonitriles is described. This reaction forms two stereogenic centers with remarkable diastereoselectivity. The crystal structure of a typical product has been determined by X-ray diffraction.