2942-03-2

Usage

Uses

2,3-dimethyl-6-nitroquinoxaline is a useful reactant for the synthesis of organic products.

Upstream product

• 431-03-8 dimethylglyoxal 
• 99-56-9 4-Nitrophenylene-1,2-diamine 
• 513-86-0 3-hydroxy-2-butanon 
• 2028-63-9 but-3-yn-2-ol 

Downstream Products

• 19031-45-9 6-Acetylamino-2,3-dimethyl-chinoxalin 
• 1290058-76-2 N-(2,3-dimethylquinoxalin-6-yl)-1-(4-benzyl-piperidine)-carboxamide 
• 1290058-68-2 N-(2,3-dithienylquinoxalin-6-yl)-N-tosyl-(4-methyl-benzene)sulfonamide 
• 177264-57-2 1-(2,3-dimethylquinoxalin-6-yl)-3-phenylurea 
• 170948-50-2 2-[(2,3-dimethylquinoxalin-6-ylamino)methylene]malonic acid diethyl ester 
• 7576-88-7 2,3-dimethyl-6-quinoxalinamine 

Relevant academic research and scientific papers

In water organic synthesis: Introducing itaconic acid as a recyclable acidic promoter for efficient and scalable synthesis of quinoxaline derivatives at room temperature

Substituted quinoxaline derivatives are traditionally synthesized by co-condensation of various starting materials. Herein, we describe a novel environmentally benign in water synthetic route for the synthesis of structurally and electronically diverse ninety quinoxalines with readily available substituted o-phenylenediamine and 1,2-diketones using cheap and biodegradable itaconic acid as a mild acid promotor in 1 hours. The reaction is performed at room temperature, which proceeds through cyclo-condensation reaction followed by obtaining the aforesaid nitrogen-containing heterocyclic adducts without performing the column chromatography up to 96% total yields. The simplicity, high efficiency, and reusable of the catalyst merits this reaction condition as “green synthesis” which enables it to be useful in synthetic transformations upto gram scale level.

Synthesis, biological evaluation, and in silico studies of new acetylcholinesterase inhibitors based on quinoxaline scaffold

A quinoxaline scaffold exhibits various bioactivities in pharmacotherapeutic interests. In this research, twelve quinoxaline derivatives were synthesized and evaluated as new acetyl-cholinesterase inhibitors. We found all compounds showed potent inhibitory activity against acetyl-cholinesterase (AChE) with IC50 values of 0.077 to 50.080 μM, along with promising predicted drug-likeness and blood–brain barrier (BBB) permeation. In addition, potent butyrylcholinesterase (BChE) inhibitory activity with IC50 values of 14.91 to 60.95 μM was observed in some compounds. Enzyme kinetic study revealed the most potent compound (6c) as a mixed-type AChE inhibitor. No cytotoxicity from the quinoxaline derivatives was noticed in the human neuroblastoma cell line (SHSY5Y). In silico study suggested the compounds preferred the peripheral anionic site (PAS) to the catalytic anionic site (CAS), which was different from AChE inhibitors (tacrine and galanthamine). We had proposed the molecular design guided for quinoxaline derivatives targeting the PAS site. Therefore, the quinoxaline derivatives could offer the lead for the newly developed candidate as potential acetylcholinesterase inhibitors.

Organocatalytic Green Approach Towards the Fabrication of Fused Benzo N,N-containing Heterocycles Facilitated by Ultrasonic Irradiation

The development of a metal-free protocol for transformations in organic synthesis offers a significant potential environmental benefit. This article reports the exploration of meglumine, a nontoxic and biodegradable amino sugar, as an organocatalyst for the synthesis of biologically active 1H-dibenzo[b,e][1,4]diazepin-1-ones, highly regioselective benzimidazole derivatives and derivatives of quinoxalines. Operational simplicity, mild reaction conditions, shorter reaction times, and use of green solvents are the highlights of this protocol. The advantage of ultrasonic irradiation has been significantly explored for the synthesis of the aforesaid compounds. Furthermore, the multifaceted use of o-phenylenediamine has also been accentuated in the study.

Ionic liquid functionalized cellulose as an efficient heterogeneous catalyst for the facile and green synthesis of benzoxazine, pyrazine and quinoxaline derivatives in aqueous media

Immobilization of acidic ionic liquid, 1-methyl-3-(3-trimethoxysilylpropyl) imidazolium hydrogen sulfate on cellulose (Cell-[pmim]HSO4) as an efficient heterogenous catalyst for the simple and environmentally benign synthesis of benzoxazine, pyrazine and quinoxaline derivatives in aqueous media at room temperature is described. The catalyst was characterized by FTIR spectroscopy and X-ray diffraction pattern. This method provides several advantages such as mild reaction conditions, environmentally friendly catalyst, good to excellent yields and simple work-up procedure.

An experimental and theoretical study of intramolecular regioselective oxidations of 6-substituted 2,3-dimethylquinoxaline derivatives

An experimental and theoretical study of the regioselective Riley oxidation was conducted on a series of 2,3-dimethyl-6-substituted-quinoxalines bearing EWG (NO2, CN, CF3, Cl, Br, F, COOH, COOMe, COPh) and EDG (2,3-dimethylquinoxaline, OMe, OH, NH2) substituents. The nitrogen lone pair of electrons of the symmetric benzopyrazine moiety initiates the oxidation and promotes nucleophilic competition between the two active sites to give carbaldehyde regioisomers a and b. The mesomeric effect provides the dominant contribution to the regioselectivity. The compounds were characterized by NMR, measuring the 1H, 13C, pfg-HSQC, pfg-HMBC, and 15N, 1H correlation signals established by pfg-HMQC. The nucleophilic reactivity of nitrogen was evaluated by 1H NMR titration and analyzed using Perrin linearization to determine the reactivity ratio, ΔK, of the N4 and N1 nitrogen atoms. The structures were optimized using density functional theory at the ωB97XD/6-311G++(d,p) level of theory. The highest occupied molecular orbitals modeled using the HF/6-311G++(d,p) functionals revealed an asymmetric electron density that confirmed the asymmetric nucleophilicity of the nitrogen centers. These values agreed with the experimentally measured ΔK ratios. The PM6 theoretical calculations of the heats of formation of the mesomeric forms and intermediates of (2,3-dimethyl-6-substituted-quinoxalines)-SeO2 allowed us to identify the reaction routes that minimized energy expenditures. The regioselectivities were explained in terms of the energetic diagrams of the regioisomers. All compounds evaluated indicated a preference toward forming regioisomer b, except for the derivative bearing the EDG substituent (2,3-dimethylquinoxaline) which displayed a preference for regioisomer a.

A zirconium Schiff base complex immobilized on starch-coated maghemite nanoparticles catalyzes heterogeneous condensation of 1,2-diamines with 1,2-dicarbonyl compounds

A magnetically separable zirconium Schiff base nanocatalyst was synthesized under ultrasonic agitation. TEM images revealed a uniform spherical particle shape with average size of 10-14 nm for the as-prepared catalyst. The catalytic performance of ZrOL2@SMNP in the heterogeneous condensation of various 1,2-diamines and 1,2-dicarbonyls for the synthesis of heterocyclic compounds in ethanol has been explored.

New 6-Aminoquinoxaline Derivatives with Neuroprotective Effect on Dopaminergic Neurons in Cellular and Animal Parkinson Disease Models

Parkinson's disease (PD) is a neurodegenerative disorder of aging characterized by motor symptoms that result from the loss of midbrain dopamine neurons and the disruption of dopamine-mediated neurotransmission. There is currently no curative treatment for this disorder. To discover druggable neuroprotective compounds for dopamine neurons, we have designed and synthesized a second-generation of quinoxaline-derived molecules based on structure-activity relationship studies, which led previously to the discovery of our first neuroprotective brain penetrant hit compound MPAQ (5c). Neuroprotection assessment in PD cellular models of our newly synthesized quinoxaline-derived compounds has led to the selection of a better hit compound, PAQ (4c). Extensive in vitro characterization of 4c showed that its neuroprotective action is partially attributable to the activation of reticulum endoplasmic ryanodine receptor channels. Most interestingly, 4c was able to attenuate neurodegeneration in a mouse model of PD, making this compound an interesting drug candidate for the treatment of this disorder.

Ferrocene-quinoxaline Y-shaped chromophores as fascinating second-order NLO building blocks for long lasting highly active SHG polymeric films

The first example of a Y-shaped ferrocene quinoxaline derivative with a surprisingly high and stable second harmonic generation (SHG) response in composite polymeric films is reported. The interesting quadratic hyperpolarizability values of different substituted Y-shaped chromophores are also investigated in solution by the EFISH technique.

Efficient solvent-free synthesis of pyridopyrazine and quinoxaline derivatives using copper-DiAmSar complex anchored on SBA-15 as a reusable catalyst

A catalytic system comprising mesoporous silica functionalized with Cu(II)-DiAmSar was synthesized. This was demonstrated as an efficient heterogeneous catalyst for the synthesis of biologically useful pyridopyrazine and quinoxaline heterocycles under solvent-free conditions. X-ray diffraction, transmission electron microscopy, N2 adsorption-desorption, Fourtier transformation infrared spectroscopy, and thermogravimetric analysis were used to characterize the catalyst and investigate the texture of SBA-15 during the grafting process.

Aqueous hydrofluoric acid catalyzed facile synthesis of 2,3,6-substituted quinoxalines

A versatile synthetic route for the preparation of 2,3,6-trisubstituted quinoxalines in excellent yield is developed from θ-diamines and 1,2-dicarbonyl compounds in which aqueous hydrofluoric acid was employed as the medium and catalyst. Other salient features of this protocol include milder conditions, absence of coupling agents, and easy workup procedures.