5021-45-4

A transition metal free mechanically induced C(sp2)-H arylation of quinoxalin(on)es is described. In this study, diaryliodonium salts generate aryl radical by planetary ball milling, with the assist of piezoelectric material BaTiO3. A broad range of functional groups are tolerated to give products in moderate to good yields via radical mechanism.

The invention discloses a method for synthesizing 2-aryl quinoxaline and 3-aryl quinoxaline-2 (1H)-one based on mechanical grinding of aryl diazonium salt. According to the method, an active free radical precursor is generated through mechanical induction, 2-aryl quinoxaline and 3-aryl quinoxaline-2 (1H)-one are synthesized under the condition of mechanical grinding, and 2-aryl quinoxaline and 3-aryl quinoxaline-2 (1H)-one are prepared from aryl diazonium salt through a single electron transfer process without a solvent or even a catalyst in the reaction. The method is simple in synthesis step and green, does not need to consume the solvent, can be used for large-scale production, and provides a new and green synthesis strategy for synthesizing quinoxaline compounds.

A green synthesis strategy of 2-arylquinoxalines and 3-arylquinoxalin-2(1H)-ones via ball milling, which could avoid copious solvent waste, was accomplished in this work. Aryl radicals were produced from aryldiazonium salts by using a solvent-free or catalyst-free single electron transfer process induced by mechanical force, affording a series of 2-arylquinoxalines and 3-arylquinoxalin-2(1H)-ones with 28%–85 yield. (Figure presented.).

A facile protocol to access a novel series of spirocyclodiazepines from cyclocondensation of 1-(2-oxo-2-arylethylidene)-5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-2(1H)-ones (derived from 5,6-dihydro-1H-pyrrolo[3,2,1-ij]quinolone-1,2(4H)?dione) with ethane-1,2-diamines and benzene-1,2-diamines, generates polycyclic spirooxindoles and unexpectedly produces 2-arylquinoxalines instead of spiro[indole-1,5-benzodiazepines], respectively, in the presence of p-TSA as an efficient catalyst in a green solvent.

Quinoxaline derivatives have been synthesized in good to excellent yields by the cyclocondensation reaction of o-pheneylenediamine with substituted phenacyl bromides/benzil in the presence of SO42?/ZrO2-TiO2 as an efficient and heterogeneous catalyst. The catalyst can be recovered up to five catalytic cycles without significant loss in catalytic activity. The reported SO42?/ZrO2-TiO2 catalyst has been thoroughly characterized by using infrared spectroscopy, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and powder X-ray diffraction (XRD). Here, we have used ethanol as a green solvent in this cyclocondensation. This new method has several advantages, such as excellent yields, short reaction time, nontoxic, and easily recoverable catalyst.

A NaOH-mediated sustainable synthesis of functionalized quinoxalines is disclosed via redox condensation of o-nitroamines with diols and α-hydroxy ketones. Under optimized conditions, various o-nitroamines and alcohols are well tolerated to generate the desired products in 44-99% yields without transition metals and external redox additives.

Ferroptosis is a recently characterized form of regulated necrosis with the iron-dependent accumulation of (phospho)lipid hydroperoxides (LOOH). It has attracted considerable attention for its putative involvement in diverse pathophysiological processes, such as cardiovascular disease and neurodegeneration. Here we describe the discovery of tetrahydroquinoxaline, a novel scaffold of ferroptosis inhibitors based on quantum chemistry methods. Tetrahydroquinoxaline deviates showed very good inhibition of ferroptosis, while being non cytotoxic for human cancer cells. And, the advantage of them is their small molecular weight (MW. = 148 Da) that can be coupled with other drugs to form multi-target drugs to better meet the treatment of complicated diseases.

Visible light promoted domino synthesis of 2-aryl benzimidazoles is reported through the reaction ofortho-phenylenediamines and arylmethyl amines under aerobic conditions. The methodology has wide substrate scope and tolerates a wide range of functional groups affording the products in high yields. The use of arylethyl amines instead of arylmethyl amines gives 2-aryl quinoxalines.

A facile synthesis of quinoxalines by the cyclocondensation of substituted phenacyl bromides with o-pheneylenediamines using silica-supported dodecatungstophosphoric acid (DTP/SiO2) as a recyclable heterogeneous catalyst is unveiled in this res

Transition metals mediated cross coupling methodologies provide an extremely powerful versatile pathway in organic syntheses undoubtedly, a facile route for syntheses and derivatization of biologically important heterocycles from easily available precurso

A synthetic method for quinoxaline derivatives from the [4+2] annulation of β-keto sulfoxonium ylides and o-phenylenediamine by using (Cp*IrCl2)2 catalyst is described. This novel protocol features mild reaction conditions, moderate to excellent yields, wide substrate scope, and high functional-group compatibility. Moreover, this cyclization strategy was successfully applied in late-stage modification for structurally complex bioactive compounds.

A simple, efficient, and environmentally friendly ionic liquid mediated protocol for the synthesis of quinoxaline derivatives using carbonyl substrate and phenylenediamines has been described. A range of ionic liquids were synthesized, characterized via IR, 1H and 13C NMR and used as a solvent as well as catalyst for above protocol. The catalytic activities of ILs were evaluated and the relationship between the catalytic activity and acidity was discussed. It was also found that among the all ILs, [Bmim]CF3SO3 was the most effective, eco-friendly and less expensive solvent and catalyst for the above etiquette. This method is of significant value due to the eco-friendly nature of ionic liquid and non usage of separate catalyst to drive the reaction forward. The protocol proves to be efficient and environmentally benign in terms of good to excellent yields, low reaction times, simple work-up, ease of recovery, and reusability of ionic liquid for six times.

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N-bromosuccinimide (NBS)-mediated one-pot, green, efficient and practical synthesis of substituted imidazoles and quinoxalines has been achieved by the reaction of styrenes with N-arylbenzamidines and o-phenylenediamines, respectively, in a water:1,4-dioxane mixture. The reaction involves formation of an α-bromo ketone as an intermediate in the presence of NBS and water, followed by condensation with the N-arylbenzamidine and o-phenylenediamine. Use of an inexpensive NBS as a bromine source as well as an oxidant, water as a solvent and readily available starting materials makes this protocol environmentally benign and economically viable. Substituted imidazoles and quinoxalines were obtained in good to excellent yields with wide functional group compatibility. (Figure presented.).

Valuable and direct aerobic oxidation reactions of 2-hydroxyacetophenones were explored. The concept was based on the in situ treatment of small quantities of aerobically formed α-keto aldehydes that drove the reactions to the corresponding products. This new strategy was applied for a variety of oxidative reactions of 2-hydroxyacetophenones, and valuable products such as phthalides, quinoxalines, and α-keto amides were obtained in good to high yields.

Substituted 2-arylquinoxalines have been synthesized by an unprecedented CuI-catalyzed ring-opening/cyclization reaction followed by detosylation/aromatization of activated aziridines with 2-bromoanilines. The transformation efficiently accommo

A copper-catalyzed oxidative coupling reaction of o-phenylenediamines with 2-aryl/heteroarylethylamines using molecular oxygen as an oxidant has been developed. This approach provides a practical and direct access to construct quinoxalines in excellent yields at room temperature. The reaction has a broad substrate scope and exhibits excellent functional-group tolerance. This method could be easily scaled up and applied to the synthesis of biologically active molecules bearing a quinoxaline structural scaffold.

The bioinspired ortho-quinone catalysts have been applied to heterocycles synthesis. Without any metal cocatalysts, a sole ortho-quinone catalyst enables the oxidative synthesis of benzimidazoles, quinoxalines and benzoxazoles from primary amines in high yields under mild conditions with oxygen as the terminal oxidant.

A metal free protocol for the synthesis of quinoxalines from alkynes has been developed. The reaction was carried out by treating alkynes with TsNBr2in presence of O-phenylenediamines in a mixture of acetonitrile and water (9:1). This one-pot reaction proceeds via an oxidative transformation of alkynes to α,α-dibromoketones in presence of TsNBr2and eventually to quinoxalines in presence of 1,2-diamines in a cascade process.

Substituted phenacyl chlorides (1a–f) were cyclocondensed with nucleophiles thiourea (2a) and thiobenzamide (2b) in presence of baker’s yeast (Saccharomyces cerevisiae) as whole-cell enzyme source in acetonitrile at room temperature to obtain 4-(4-substituted phenyl)thiazol-2-amines (3a–f) and 4-(substituted phenyl)-2-phenylthiazoles (4a–f), respectively. Moreover, substituted phenacyl chlorides also reacted with nucleophiles 2-amino-1,3,4-thiadiazole (2c), o-phenylenediamine (2d), 1-amino-2-mercapto-5-phenyl triazole (2e), and pyridin-2-amine (2f) at room temperature in presence of baker’s yeast to give fused heterocycles 6-(4-substituted phenyl)-2-phenylimidazo[2,1-b][1,3,4]thiadiazoles (5a–f), 2-(4-substituted phenyl)quinoxalines (6a–f), 6-(4-substituted phenyl)-3-phenyl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazines (7a–f), and 2-(4-substituted phenyl)H-imidazo[1,2-a]pyridines (8a–f), respectively. The experimental conditions for these cyclocondensations were optimized to obtain the biodynamic heterocycles in high yield. The unique features of this work are use of baker’s yeast as a cheap and readily available natural source of biocatalyst, noticeable rate acceleration, convenient route to products, cost effectiveness, and scalability.

An eco-friendly, expeditious one-pot multicomponent synthesis of substituted 2-phenyl quinoxaline and 7-bromo-3-(4-ethylphenyl) pyrido[2,3-b]pyrazine 4a–k in water–ethanol from easily available starting materials as acetophenone 1, succinamide 2, aromatic

A facile and efficient method was investigated for the synthesis of different quinoxalines by the reaction of o-phenylene diamine and 2-bromoacetophenones. This procedure was carried out in ethanol under catalyst-free conditions. Several sulfonamides were synthesized from 2-(4-methoxyphenyl)-quinoxaline in two steps. At first chlorosulfonation of 2-(4-methoxyphenyl) quinoxaline was done using chlorosulfonic acid and led to 2-methoxy-5-quinoxalin-2-yl-benzenesulfonyl chloride. Then quinoxaline sulfonamides were synthesized by the reaction of quinoxaline sulfonyl chloride with different aromatic amines under solvent-free conditions. All the products were obtained in excellent yields after an easy work-up and were evaluated for antibacterial activities against Staphylococcus spp. and Escherichiacoli bacteria.

Abstract: Herein, fabrication of spherical SiO2 nanoparticles (5?±?0.2?nm) with uniform size is followed by their homogeneous distribution on graphene oxide (SiO2–GO) by using a simple in situ one-step method. These as synthesized ca

The reaction of α-hydroxy ketones with 1,2-diamines in the presence of triphenylstibane (10 mol%) as catalyst led to the formation of 2-arylquinoxalines in moderate to good yield under aerobic conditions. This reaction is the first example of oxidative cy

An efficient synthesis of 2-arylquinoxaline derivatives (3a-f) has been developed from the reaction of α,α-dibromoacetophenones (1a-f) and o-phenylenediamine (2) under mild reaction conditions.

α-Chloroketones-obtained by the atom-economical chlorination of ketones with trichloroisocyanuric acid (TCCA) in the presence of p-TSA under ball-milling conditions-were set up for a sequential base-mediated condensation reaction with thiourea/thiosemicarbazides, o-phenylenediamine and salicylaldehyde to afford 2-aminothiazoles, 2-hydrazinylthiazoles, quinoxalines and benzoylbenzofurans, respectively, in respectable yields. The viability of one-pot sequential acid- and base-mediated reactions in the solid state under ball-milling conditions is thus demonstrated.

A copper-catalyzed cycloamination of α-Csp3-H bond of N-aryl ketimines with sodium azide has been developed. This methodology provides an efficient access to quinoxalines and features mild reaction conditions and readily available ketimines with diverse functional group tolerance.

An easy and efficient propylphosphonic anhydride (T3P)-DMSO or T3P mediated oxidation-condensation or condensation reaction for the synthesis of quinoxalines derived from the interaction of different arrays of condensing partners with ortho-phenylene diamines (o-PDs) under simple and mild reaction conditions in one step has been reported for the first time.

A new series of novel quinazolinones with allylphenyl quinoxaline hybrids 9a-n were efficiently synthesized in good yields by the reaction of 3-allyl-2-methylquinazolin-4(3H)-one (5a-n) with bromophenyl)quinoxaline (8) utilizing Pd catalyzed Heck-cross coupling and evaluated for anti-proliferative activity against four cancer cell lines such as HeLa (cervical), MIAPACA (pancreatic), MDA-MB-231 (breast) and IMR32 (neuroblastoma). Compounds 9a, 9e, 9g and 9h exhibited promising anti-proliferative activity with GI50 values ranging from 0.06 to 0.2 μM against four cell lines, while compounds 9e and 9k showed significant activity against HeLa and MIAPACA cell lines and compounds 9b, 9d, 9h and 9j showed selective potency against IMR32 and MDA-MB-231 cell lines. This is the first report on the synthesis and in vitro anti-proliferative evaluation of E-2-(4-substituted)-3-(3-(4-(quinoxalin-2-yl)phenyl)allyl)quinazolin-4(3H)-ones (9a-n). Docking results indicate a sign of good correlation between experimental activity and calculated binding affinity (dock score), suggesting that these compounds could act as promising DNA intercalates.

The invention discloses a pyrazine derivative and application thereof in an organic electroluminescence device. The structure of the material is as shown in formula I in the specification. By adopting the material, the start voltage of the organic electro

Reaction of α-halo ketone (a-bromo ketone) under microwave, irradiation gives the pyrazine and quinoxaline derivative in good yields. This reaction affords a clean and convenient synthetic method for pyrazine and quinoxaline derivatives.

Radical addition to vinyltriazole was developed as a new approach to achieve 1,2,3-triazole ring opening under mild conditions. Through reagent control, excellent chemoselectivity was achieved, giving either nitrile under basic conditions or quinoxaline under neutral conditions. Reactivities made this method an attractive new reaction mode.

One-pot, atom-economic synthesis of quinoxalines has been achieved through generation of arylglyoxal from easily available ethylarenes, ethylenearenes and ethynearenes, and subsequent condensation with o-phenylenediamines. Catalytic I2 with TBHP as an oxidant in DMSO is the system of choice for this domino reaction involving C-H functionalization/oxidative cyclization. This metal-free, mechanistically distinct and functional group tolerant tandem approach could be a powerful complement to traditional approaches for the synthesis of quinoxalines. This journal is

A new synthetic strategy of tandem N-aroylmethylation-nitro reduction-cyclocondensation has been developed for the first and generalized regioselective synthesis of 2-aryl quinoxalines adopting "all water chemistry." Water plays the critical role through

An equivalent amount of N-heteroaryl and aryl Grignard or lithium reagents, after mediation by an equivalent of titanate, was facilely coupled to furnish N-heteroaryl-aryl compounds under the catalysis of FeCl3/TMEDA at ambient temperature using oxygen as an oxidant. Most of the common N-heteroaryls were all good candidates, and thus provided a general, green and pratical protocol for the flexible construction of various N-heteroaryl-aryl structures. This journal is

Abstract An efficient and facile method for the synthesis of 2-arylindoles, 2-arylimidazo[1,2-a]pyridines and 2-arylquinoxalines by the reaction of various α-bromo ketones with anilines, 2-aminopyridine and 1,2-phenylenediamine, respectively, in the presence of N-methylimidazolium trifluoromethanesulfonate ionic liquid supported on nano-silica ([Hmim]OTf@nano-SiO2) as a reusable catalyst under solvent-free conditions has been developed. The bis-derivatives of these compounds were also prepared efficiently, for the first time, using this catalytic system. All products were obtained in high yields and in short reaction times.

In this work, the natural nanozeolite clinoptilolite (Nano CP) was successfully functionalized by propylsulfonic acid and applied as efficient heterogeneous catalyst for the synthesis of quinoxaline derivatives in aqueous media. The nanocatalyst was chara

Quinoxalines are a class of important heterocycles, so to explore a facile and practical new synthetic method is always demanded. We have developed a new catalyst-free domino synthesis of quinoxalines from phenacyl halides and 1,2-diaminoarenes. Phenacyl

A simple, efficient and eco-friendly method has been developed for quinoxaline synthesis from inexpensive and readily available diamines and phenacyl bromides by catalyst- and additive-free protocol.

Alzheimer's disease (AD) is a progressive brain disorder which occurs due to lower levels of acetylcholine (ACh) neurotransmitters, and results in a gradual decline in memory and other cognitive processes. Acetycholinesterase (AChE) and butyrylcholinesterase (BChE) are considered to be primary regulators of the ACh levels in the brain. Evidence shows that AChE activity decreases in AD, while activity of BChE does not change or even elevate in advanced AD, which suggests a key involvement of BChE in ACh hydrolysis during AD symptoms. Therefore, inhibiting the activity of BChE may be an effective way to control AD associated disorders. In this regard, a series of quinoxaline derivatives 1-17 was synthesized and biologically evaluated against cholinesterases (AChE and BChE) and as well as against achymotrypsin and urease. The compounds 1-17 were found to be selective inhibitors for BChE, as no activity was found against other enzymes. Among the series, compounds 6 (IC50 = 7.7 ± 1.0μM) and 7 (IC50 = 9.7 ± 0.9 μM) were found to be the most active inhibitors against BChE. Their IC50 values are comparable to the standard, galantamine (IC50 = 6.6 ± 0.38 μM). Their considerable BChE inhibitory activity makes them selective candidates for the development of BChE inhibitors. Structure-activity relationship (SAR) of this new class of selective BChE inhibitors has been discussed.

Although 2-imino-1H-imidazol-5(2H)-ones have important biological activities in metabolism, their synthesis has rarely been investigated. Quinoxalines as privileged scaffolds in medicinal chemistry have been extensively investigated, but the development of novel and efficient synthetic methods remains very attractive. Herein, we have developed two copper-catalyzed domino reactions for the synthesis of 2-imino-1H-imidazol-5(2H) -ones and quinoxalines involving C-C bond-cleavage with a 1,3-dicarbonyl unit as a leaving group. The domino sequence for the synthesis of 2-imino-1H-imidazol- 5(2H)-ones includes aza-Michael addition, intramolecular cyclization, C-C bond-cleavage, 1,2-rearrangement, and aerobic dehydrogenation reaction, whereas the domino sequence for the synthesis of quinoxalines includes aza-Michael addition, intramolecular cyclization, elimination reaction, and C-C bond-cleavage reaction. The two domino reactions have significant advantages including high efficiency, mild reaction conditions, and high tolerance of various functional groups.

In situ generated iron sulfide from elemental sulfur and ferric chloride was found to be a highly efficient catalyst for the redox condensation cascade reaction between o-nitroanilines and 2-arylethylamines. This method constitutes a new atom-, step-, and redox-economical route to 2-arylquinoxalines.

An iodobenzene-catalysed domino route to quinoxalines from ketones and o-phenylenediamines in one pot has been developed. This transformation consisted of the generation of Koser's generation, α-tosyloxylation of ketones, nucleophilic substitution and intramolecular dehydration with o-phenylenediamines, and dehydrogenation. Website

The arylation of C-H bonds to generate heteroaryl-aryl (Het-Ar) and arylated quinone (Quin-Ar) compounds has received great attention to achieve sustainable goals in synthetic chemistry. Despite significant advances, arylation of a broad range of Het-Ar and Quin-Ar derivatives remains a challenging task. Herein, a variety of heterocycles are arylated by using arylboronic acids in the presence of catalytic amounts of inexpensive Fe(NO 3)3. The C-arylated quinone compounds can be prepared by reacting arylboronic acids with either quinone or hydroquinone. The present method is operationally simple, scalable, does not require prefunctionalization of the heterocycle or quinone, and can tolerate a wide variety of functional groups in the coupling partners. These qualities are expected to render this method attractive for academic and industrial use. Direct C-H arylation of a variety of heterocycles and quinones with arylboronic acids has been developed. An inexpensive iron catalyst, Fe(NO3)3, and a co-oxidant, persulfate, were used in air. The protocol is applicable for large-scale synthesis and is expected to find application as a result of its operational simplicity. Copyright

Various 2-aryl quanoxalines were synthesized with good yields from o-phenylene diamines and phenacyl bromides in one pot using novel nanocrystalline 5 % Fe/ZnO catalyst, at room temperature. The salient feature of this method includes mild reaction condit

A simple and efficient sodium dodecylsulfate (SDS) induced method for the synthesis of quinoxalines in excellent yields in water at room temperature by the reaction of phenacyl bromide and o-phenylene diamines has been developed. Simple reaction conditions, wide compatibility and high yields are the advantages of this protocol.

γ-Maghemite-silica nanocomposite has been applied as a green catalyst to synthesize variety of aromatic N-heterocycles under solvent free conditions. Characterization was done by modern analytical tools (UV, IR, AAS, DSC, EDXRF, powdered XRD, EPR, Mo?ssbauer and TEM). Mild reaction conditions and recyclability have made the present protocol both environmentally and economically viable.

A new approach for the synthesis of 2-substituted quinoxalines by Ga(ClO4)3-catalyzed cycloaddition of α- hydroxyketones and o-phenylenediamines is introduced. The reaction is catalyzed by 10 mol % of Ga(ClO4)3 in EtOH at room temperature. It is performed under simple and mild conditions to afford the product in good yield.

A novel protocol for the synthesis of quinoxalines has been developed from simple ketones and 1,2-diamines. This process underwent a logic approach to bis-substituted quinoxalines via a consecutive iodination/Kornblum oxidation/cyclization in the presence of I2/CuO/DMSO and to mono-substituted quinoxalines via an iodination/cyclization/aromatization in the presence of I2/CuO/K3PO4·3H 2O.

A novel Et3N-catalyzed oxidative dehydrogenative coupling of α-unsubstituted carbonyl compounds with aryl diamines leading to quinoxaline derivatives using molecular oxygen as oxidant has been developed. Six hydrogen dissociations involving 2 sp3 C-H bonds activation are realized under mild conditions in this approach. Plausible mechanism is proposed for this novel Et3N-catalyzed transformation on the basis of the aboratively designed mechanistic studies including the radical detection by EPR. 2012 Elsevier Science. All rights reserved.