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Nickel/Photoredox-Catalyzed Methylation of (Hetero)aryl Chlorides Using Trimethyl Orthoformate as a Methyl Radical Source

Methylation of organohalides represents a valuable transformation, but typically requires harsh reaction conditions or reagents. We report a radical approach for the methylation of (hetero)aryl chlorides using nickel/photoredox catalysis wherein trimethyl orthoformate, a common laboratory solvent, serves as a methyl source. This method permits methylation of (hetero)aryl chlorides and acyl chlorides at an early and late stage with broad functional group compatibility. Mechanistic investigations indicate that trimethyl orthoformate serves as a source of methyl radical via beta-scission from a tertiary radical generated upon chlorine-mediated hydrogen atom transfer.

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Pyridazine – Wikipedia,
Pyridazine | C4H4N2046 – PubChem

 

Brief introduction of 6-Chloropyridazine-3-carboxylic acid

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Synthesis of 2-fluoro-6-O-propargyl-11,12-carbamate ketolides. A novel class of antibiotics.

A novel class of 2-fluoro-6-O-propargyl-11,12-carbamate ketolide derivatives of erythromycin has been synthesized for antibacterial SAR studies. Replacement of the C2-hydrogen by a fluorine atom allows the synthesis of 6-O-propargylic ketones and electron-deficient 6-O-propargylic aromatic derivatives by preventing intramolecular C2-enolate Michael cyclization.

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Pyridazine – Wikipedia,
Pyridazine | C4H4N2061 – PubChem

 

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Visible-Light-Induced, Base-Promoted Transition-Metal-Free Dehalogenation of Aryl Fluorides, Chlorides, Bromides, and Iodides

We report a simple and efficient visible-light-induced transition-metal-free hydrogenation of aryl halides. The combined visible light and base system is used to initiate the desired radical-mediated hydrogenation. A variety of aryl fluorides, chlorides, bromides, and iodides could be reduced to the corresponding (hetero)arenes with excellent yields under mild conditions. Various functional groups and other heterocyclic compounds are tolerated.

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Pyridazine – Wikipedia,
Pyridazine | C4H4N2045 – PubChem

 

Some scientific research about 6-Chloropyridazine-3-carboxylic acid

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Quinoline derivatives with indoleamine -2,3- dioxygenase inhibitory activity (by machine translation)

The application provides a preparation method of a compound of formula, or a pharmaceutically acceptable salt, thereof (I), a pharmaceutical composition, of the compound, and application, of the quinoline derivative and/inhibitor in preparation of immunomodulatory and prevention and IDO or treatment of diseases related to/expression of abnormal and, or tryptophan metabodystrophy, and application HDAC thereof in preparation of antitumor drugs. (by machine translation)

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Pyridazine – Wikipedia,
Pyridazine | C4H4N2042 – PubChem

 

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A visible-light-photocatalytic water-splitting strategy for sustainable hydrogenation/deuteration of aryl chlorides

Hydrogenation/deuteration of carbon chloride (C?Cl) bonds is of high significance but remains a remarkable challenge in synthetic chemistry, especially using safe and inexpensive hydrogen donors. In this article, a visible-light-photocatalytic watersplitting hydrogenation technology (WSHT) is proposed to in-situ generate active H-species (i.e., Had) for controllable hydrogenation of aryl chlorides instead of using flammable H2. When applying heavy water-splitting systems, we could selectively install deuterium at the C?Cl position of aryl chlorides under mild conditions for the sustainable synthesis of high-valued added deuterated chemicals. Sub-micrometer Pd nanosheets (Pd NSs) decorated crystallined polymeric carbon nitrides (CPCN) is developed as the bifunctional photocatalyst, whereas Pd NSs not only serve as a cocatalyst of CPCN to generate and stabilize H (D)-species but also play a significant role in the sequential activation and hydrogenation/deuteration of C?Cl bonds. This article highlights a photocatalytic-WSHT for controllable hydrogenation/deuteration of low-cost aryl chlorides, providing a promising way for the photosynthesis of high-valued added chemicals instead of the hydrogen evolution.

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Pyridazine – Wikipedia,
Pyridazine | C4H4N2056 – PubChem

 

Extracurricular laboratory:new discovery of 6-Chloropyridazine-3-carboxylic acid

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Intramolecular Desulfitative Coupling: Nickel-Catalyzed Transformation of Diaryl Sulfones into Biaryls via Extrusion of SO2

As a new transformation of organosulfur compounds, intramolecular desulfitative coupling of diaryl sulfones to the corresponding biaryls has been developed with the aid of nickel-NHC catalysts. This catalytic elimination of SO2 was also applicable to alkenyl aryl sulfone to furnish the corresponding alkenyl arene.

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Pyridazine – Wikipedia,
Pyridazine | C4H4N2068 – PubChem

 

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Synthesis and structure-activity relationships of 8-substituted-2-aryl-5- alkylaminoquinolines: Potent, orally active corticotropin-releasing factor-1 receptor antagonists

We previously reported a series of 8-methyl-2-aryl-5-alkylaminoquinolines as a novel class of corticotropin-releasing factor-1 (CRF1) receptor antagonists. A critical issue encountered for this series of compounds was low aqueous solubility at physiological pH (pH 7.4). To address this issue, derivatization at key sites (R2, R3, R5, R 5?, and R8) was performed and the relationships between structure and solubility were examined. As a result, it was revealed that introduction of a methoxy substituent at the C8 position had a positive impact on the solubility of the derivatives. Consequently, through in vivo and in vitro biological studies, compound 21d was identified as a potent, orally active CRF1 receptor antagonist with improved physicochemical properties.

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Pyridazine – Wikipedia,
Pyridazine | C4H4N2069 – PubChem

 

Discovery of 6-Chloropyridazine-3-carboxylic acid

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Coordination Assisted Distal C?H Alkylation of Fused Heterocycles

Distal C?H bond functionalization of heterocycles remained extremely challenging with covalently attached directing groups (DG). Lack of proper site for DG attachment and inherent catalyst poisoning by heterocycles demand alternate routes for site selective functionalization of their distal C?H bonds. Utilizing non-productive coordinating property to hold the heterocycle into the cavity of a template system in a host?guest manner, we report distal C?H alkylation (C-5 of quinoline and thiazole, C-7 of benzothiazole and benzoxazole) of heterocycles. Upon complexation with heterocyclic substrate, nitrile DG in template directs the metal catalyst towards close vicinity of the specific distal C?H bond of the heterocycles. Our hypothesized pathway has been supported by various X-ray crystallographically characterized intermediates.

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Pyridazine – Wikipedia,
Pyridazine | C4H4N2062 – PubChem

 

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Prediction of corrosion inhibition efficiency of pyridines and quinolines on an iron surface using machine learning-powered quantitative structure-property relationships

Linear and non-linear quantitative structure?property relationship (QSPR) models were developed to predict corrosion inhibition efficiency for a series of 41 pyridine and quinoline N-heterocycles. Out of 20 physicochemical and quantum chemical variables related to the surface adsorption behaviour of the inhibitors, consensus models were constructed using the genetic algorithm-partial least squares (GA-PLS) and genetic algorithm-artificial neural network (GA-ANN) methods. The consensus GA-PLS model comprised of eight variables (exponential of the calculated adsorption energy, LUMO, van der Waals surface area and volume, polarizability, electron affinity, electrophilicity, electron donor capacity) exhibited an %RMSECV of 16.5% and mean %RMSE of 14.9%. Such a model moderately captured the complex relationships between inhibition efficiency and the quantum chemical variables. The consensus GA-ANN model comprised of nine input variables (exponential of the calculated adsorption energy, HOMO, LUMO, HOMO-LUMO Gap, electronegativity, softness, electrophilicity, electron donor capacity and N atomic charge) exhibited an %RMSECV of 16.7 ¡À 2.3% and mean %RMSE (training/testing/validation) of 8.8%, performing better than its linear counterpart in terms of predictive ability. Both models revealed the importance of adsorption to the metal surface, and electronic parameters quantifying electron acceptance/donation to/from the iron surface, suggesting key corrosion inhibition design principles.

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Reference£º
Pyridazine – Wikipedia,
Pyridazine | C4H4N2066 – PubChem

 

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Synthesis of N-(Hetero)aryl Carbamates via CuI/MNAO Catalyzed Cross-Coupling of (Hetero)aryl Halides with Potassium Cyanate in Alcohols

An efficient route to N-(hetero)aryl carbamates was developed through CuI/MNAO [2-((2-methylnaphthalen-1-yl)amino)-2-oxoacetic acid] catalyzed cross-coupling of (hetero)aryl chlorides with potassium cyanate in alcohols at 120-130 C. This method utilizes broadly available substrates to afford various N-(hetero)aryl carbamates in good to excellent yields. Moreover, (hetero)aryl bromides and (hetero)aryl iodides were also reacted at low catalyst loadings and relatively low temperatures to provide N-(hetero)aryl carbamates.

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Reference£º
Pyridazine – Wikipedia,
Pyridazine | C4H4N2054 – PubChem