Catalyst-free Reaction Research Articles

Synthesis of tetracyclic pyrido-fused dibenzodiazepines via a catalyst-free cascade reaction.

An efficient, eco-friendly protocol has been described for the chemoselective synthesis of tetracyclic pyrido-fused dibenzodiazepines derivatives via catalyst-free, three-component reaction of dimedone, 1,2-diamines, 3-formylchromones, and malononitrile. The significant advantages of this cascade approach are to create two new rings and four new σ bonds containing three C-N and one C-C bond, as well as the breakdown of a C-O bond.

Ultrasound-promoted Green Synthesis of pyrido[2,1-a]isoquinoline Derivatives and Studies on their Antioxidant Activity.

To a stirred mixture of phthalaldehyde 1 (2 mmol) and methylamine 2 (2 mmol) in water (3 mL) under ultrasonic irradiation was added to activated acetylenic compounds 4 after 20 min. Alkyl bromide 3 and triphenylphosphine 5 react in another pot in water (3 mL) under ultrasonic irradiation for 15 min. After this time, this mixture was added to the first pot. After completion of the reaction, the solid residue was separated by filtration and washed with Et2O to afforded pure title compound 6. In this work, generation of pyrido[2,1-a]isoquinoline derivatives 6 are performed using phthalaldehyde 1, methylamine 2, α-halo substituted carbonyls 3, activated acetylenic compounds 4 and triphenylphosphine 5 in water under ultrasonic irradiation condition at room temperature in excellent yield at short time. In summary, multicomponent reaction of phthaladehyde, methylamine, activated acetylenic compounds, alkyl bromides and triphenylphosphine in water under ultrasonic irradiation at room temperature produced pyrido[2,1-a]isoquinoline derivatives in excellent yields. Also, Diels-Alder reaction of pyrido[2,1-a]isoquinoline derivatives with activated acetylenic compounds and triphenylphosphine under ultrasonic irradiation is investigated in two procedures. Also, the antioxidant activities of 6a, 6c, 6g and 6i were evaluated by DPPH radical scavenging and ferric reducing power analyzes. The compounds 6a exhibit excellent DPPH radical scavenging activity and FRAP compared to synthetic antioxidants BHT and TBHQ. The chief benefits of our method are high atom economy, green reaction conditions, higher yield, shorter reaction times, and easy work-up, which agree with some principles of green chemistry.

Cross-Dehydrogenative Coupling of Azoarenes with Dialkyl Disulfides.

A catalyst-free cross-dehydrogenative coupling reaction of purines and some azoarenes with dialkyl disulfides has been developed. This procedure provided a novel strategy to construct unsymmetrical disulfides through the α-heterocyclic functionalization of symmetrical dialkyl disulfides. The S-S bond was successfully tolerated in this transformation. The mild conditions and the broad scope of azoarenes indicated the potential application of this procedure.

Nitrile N-oxide-terminated poly(γ-benzyl l-glutamate) (PBLG): synthesis and catalyst-free grafting onto polybutadiene (PBD) and natural rubber (NR)

A nitrile N-oxide-functionalized polypeptide was synthesized by a two-step method involving the combination of ring-opening polymerization of an α-amino acid N-carboxyanhydride monomer using a primary amine initiator containing a nitroalkane group and a subsequent terminal conversion. The catalyst-free grafting reaction of the formed functionalized peptide with rubbers containing double bonds was achieved with high efficiency. A nitrile N-oxide-functionalized polypeptide was synthesized by a two-step method involving the combination of ring-opening polymerization of an amino acid N-carboxyanhydride (NCA) monomer using a primary amine initiator containing a nitroalkane group and a subsequent terminal conversion. The formed peptide was fully characterized by NMR, FT-IR, and MALDI-TOF MS measurements. The catalyst-free grafting reaction of the formed functionalized peptide with rubbers containing double bonds was achieved with high efficiency via an environmentally benign process. These results surely contributed to the development of novel peptide-grafted polymers.

Triazene-Activated Donor–Acceptor Cyclopropanes: Ring-Opening and (3 + 2) Annulation Reactions

Donor-acceptor cyclopropanes substituted with 3,3-dialkyltriazenyl groups are described herein. The strong electron-donating character of the triazene renders the cyclopropanes highly reactive, allowing for catalyst-free ring-opening reactions with methanol and tetracyanoethylene under mild conditions. The triazene-substituted cyclopropanes could also be used as substrates in Lewis acid catalyzed (3 + 2) annulations with silyl enol ethers.

Efficient Synthesis of Novel Quinolinone Derivatives via Catalyst-free Multicomponent Reaction

The synthesis of 3-(aryl(piperidin-1-yl)methyl)-4-hydroxyquinolin-2(1H)-one derivatives via catalyst-free multicomponent reaction is described. The reaction of 4-hydroxyquinolin-2(1H)-one, piperidine, and 4-chlorobenzaldehyde was carried out in different solvents and under solvent-free conditions at room temperature. The best solvent in terms of the yield and reaction time was found to be dichloromethane. Most substituted benzaldehydes reacted with 4-hydroxyquinolin-2(1H)-one and piperidine to afford corresponding products in good-to-excellent yields. Aldehydes with electronwithdrawing groups were more reactive to exhibit higher reaction rates. However, 2-substituted benzaldehydes did not react with 4-hydroxyquinolin-2(1H)-one and piperidine under the reaction condition. Aldehydes bearing a hydroxyl group failed to produce the corresponding products.

Catalyst-Free Three-Component Synthesis, Antibacterial, Antifungal, and Docking Studies of Spiroindoline Derivatives

A sequence of functionalized 1′H-spiro-[indoline-3,5′-pyrimido[4,5-b]quinoline] − 2,2′,4′ (3′H,10′H)-trione derivatives have been synthesized by a catalyst-free three-component reaction of barbituric acid with arylamines and isatin under aqueous conditions. Neutral reaction conditions, high yields, and operational simplicity are the important features of the present protocol. The molecular docking studies of all the synthesized compounds were performed with jackbean urease (PDB ID: 3LA4). The results suggest that the compounds 4a-4j showed good binding affinities with the active site of jackbean urease having an inhibition constant Ki = 76.26 nm. This study offers the first example of the exhibition of urease inhibitory potential by spiro indoline derivatives paying route to develop more potent anti-urease compounds of medicinal and agricultural interest. The selected compounds 4a and 4j were evaluated for antimicrobial studies.

Green Method for the Synthetic Ugi Reaction by Twin Screw Extrusion without a Solvent and Catalyst.

This study describes the solvent and catalyst-free Ugi reaction by way of twin screw extrusion (TSE). Multicomponent chemical synthesis can be converted into a single process without repeated use of solvents through TSE. High synthetic yields are achieved in short reaction times and produced in solvent-free conditions, which lead to a more environmentally friendly process.

HFIP-promoted catalyst-free cascade reactions for the synthesis of biologically relevant 3,3-di(indolyl)indolin-2-ones from indoles and isatins

The first HFIP-promoted catalyst-free cascade reactions for the synthesis of biologically relevant 3,3-di(indolyl)indolin-2-ones (27 examples, up to 98% yield) from readily available indoles and isatin derivatives are described. This protocol shows well tolerance of different functional groups and features mild reaction conditions such as short reaction time (∼ 1 h), no usage of catalyst, easy operation and product isolation. Of particular interest is the formation of two CC bonds and one all-carbon quaternary center. This protocol could serve as an alternative strategy to synthesize biologically important 3,3-di(indolyl)indolin-2-ones for biological testing.

Catalyst-Free Decarboxylation of Carboxylic Acids and Deoxygenation of Alcohols by Electro-Induced Radical Formation.

Electro-induced reduction of redox active esters and N-phthalimidoyl oxalates derived from naturally abundant carboxylic acids and alcohols provides a sustainable and inexpensive approach to radical formation via undivided electrochemical cells. The resulting radicals are trapped by an electron-poor olefin or hydrogen atom source to furnish the Giese reaction or reductive decarboxylation products, respectively. A broad range of carboxylic acid (1°, 2°, and 3°) and alcohol (2° and 3°) derivatives are applicable in this catalyst-free reaction, which tolerated a diverse range of functional groups. This method features simple operation, is a sustainable platform, and has broad application.

Green catalyst-free one-pot synthesis of novel tetrahydropyridine-3-carboxamides by microwave-assisted approach

A clean, facile and catalyst-free four-component domino reaction of aromatic aldehyde, ethyl cyanoacetate, acetoacetanilide and ammonium acetate in ethanol under microwave irradiation (MWI) conditions is described. Eleven novel and diverse tetrahydropyridine-3-carboxamide derivatives were synthesized in excellent yields (91–97%) using this green protocol. The significant benefits of this method are simple handling, ethanol as solvent, catalyst-free reaction under mild conditions, short reaction times (<10 min) and excellent product yields. Easy workup procedure and simple purification technique of the target molecules evade column chromatography. Novel tetrahydropyridine-3-carboxamide derivatives were synthesized under the microwave irradiation (MWI) method in short reaction time (<10 min). All the synthesized compounds confirmed by various spectroscopic techniques such as 1H NMR, 13C NMR, 15N NMR and HRMS. Ethanol as a solvent, easy workup procedure and simple handling are the benefit of green protocol.

Microwave-Accelerated N-Acylation of Sulfoximines with Aldehydes under Catalyst-Free Conditions

An efficient catalyst-free radical cross-coupling reaction between aromatic aldehydes and sulfoximines was developed. The reaction took place in the presence of N-bromosuccinimide as the radical initiator under microwave irradiation to afford the corresponding acylated sulfoximines in moderate to excellent yields (27 examples). This protocol proved to be rapid, easy to handle, and applicable to a broad scope of substrates.

Photoinduced direct hydration of dipyridylacetylenes in acidic aqueous solution.

Photoinduced direct hydration of dipyridylacetylenes (DPAs) in acidic aqueous solution was achieved upon UV irradiation at room temperature. This is a catalyst-free reaction with moderate-to-good yields, and asymmetric dipyridylacetylenes afford the corresponding Markovnikov addition products.

Polyester nitrile N-oxides for click reactions synthesized with nitroalkane precursors as the initiator

Polyesters that have a nitrile N-oxide function at the initiation end were prepared and applied to a catalyst-free click reaction for star polymer synthesis.

Divergent synthesis of oxindole derivatives via controllable reactions of isatin-derived para-quinone methides with sulfur ylides.

A catalyst-free and controllable reaction of isatin-derived para-quinone methides with sulfur ylides was developed. This protocol enables the divergent synthesis of two different valuable oxindole derivatives with a broad substrate scope and high stereoselectivities (up to >20 : 1 dr and only the (Z)-configuration).

Halogen bonding matters: visible light-induced photoredox catalyst-free aryl radical formation and its applications.

Photo-involving aryl halide activation plays a pivotal role in organic synthesis and materials science. Revealing the mechanism and understanding the photophysical and photochemical processes in the activation is of great importance. Here, we found that aryl halides could be directly activated to form aryl radicals via halogen bonding under visible light irradiation without using photocatalysts or high power light. The interaction between the aryl halide and Lewis base (Et3N), as well as the triplet state formation, play crucial roles. Halogen bonding between aryl halide and Et3N facilitates intersystem crossing (ISC) and leads to an abundance of the triplet aryl halide/Et3N complex, where the carbon-halogen bond is much lengthened and prone to fracture. Therefore, visible light-driven photoredox catalyst-free C-C coupling reaction and radical-initiated polymerization were achieved. Avoiding the use of a catalyst not only brings convenience for low-cost operation, but also facilitates further purification. Meanwhile, the wide scope of aryl halide tolerance provides opportunities for chemical synthesis and polymerization.

A solvent- and catalyst-free tandem reaction: synthesis, and photophysical and biological applications of isoindoloquinazolinones

An easy green synthetic approach for fused isoindoloquinazolinones has been developed under neat reaction (yields up to 91%) conditions.

Catalyst-and organic solvent-free synthesis, structural, and theoretical studies of 1-arylidenamino-2,4-disubstituted-2-imidazoline-5-ones

We have developed a solvent- and catalyst-free cyclization reaction for the synthesis of 1-arylidenamino-2,4-disubstituted-2-imidazoline-5-ones under neat conditions. The new synthetic procedure is efficient and green in nature. All synthesized compounds were obtained in good yields (70–78%) and have been characterized by 1H and 13C NMR spectroscopy. The structure of compound 2d was characterized crystallographically using a single crystal X-Ray diffractometer. Compound 2d was found to crystallize in the triclinic space group P-1 with Z = 2. Moreover, the Frontier Molecular Orbitals (FMOs), the global chemical reactivity descriptors, and the molecular Electrostatic Potential (MEP) of 2d have been calculated at B3LYP/6-31G(d,p) level of theory.

A catalyst-free aqueous mediated multicomponent reaction of isocyanide: expeditious synthesis of polyfunctionalized cyclo[b]fused mono-, di- and tricarbazoles

A new multi-component reaction is developed for the synthesis of cyclo[b]fused mono-, di- and tricarbazoles from o-alkenyl arylisocyanides, aldehydes, and cyclic diketones in ethanol/water (1 : 1) as the solvent system.

A highly green approach towards aromatic nitro group substitutions: catalyst free reactions of nitroimidazoles with carbon nucleophiles in water.

We have successfully developed a flexible green aqueous approach for the formation of a carbon–carbon bond by the reaction of highly-enolizable carbanions (mostly derived from 1,3-dicarbonyl compounds) with an aromatic carbon bearing a nitro group. The key step involves a nucleophilic displacement reaction. All newly synthesized compounds were unambiguously characterized via various spectroscopic techniques including NMR, mass spectrometry and single-crystal X-ray diffraction as applicable. We believe that our study will be useful in providing new insights into catalyst-free water-mediated nucleophilic substitution reactions.