456-24-6

Basic information

• Product Name: 2-Fluoro-5-nitropyridine
• Synonyms: 2-FLUORO-5-NITROPYRIDINE;6-FLUORO-3-NITROPYRIDINE
• CAS NO: 456-24-6
• Molecular Formula: C₅H₃FN₂O₂
• Molecular Weight: 142.09
• EINECS: 207-260-6
• Product Categories: Fluorin-contained pyridine series;blocks;FluoroCompounds;NitroCompounds;Pyridines;Pyridine;Pyridine series;Boronic Acid;Fluorine series
• Mol File: 456-24-6.mol

Chemical Properties

• Melting Point: 142-144 C
• Boiling Point: 86-87℃/7mm lit.
• Flash Point: 97.5 °C
• Appearance: Colorless to pale yellow/Liquid
• Density: 4,64g/cm
• Vapor Pressure: 0.0686mmHg at 25°C
• Refractive Index: 1.5250
• Storage Temp.: Inert atmosphere,Room Temperature
• PKA: -4.47±0.10(Predicted)
• Water Solubility: Slightly soluble in water.
• Sensitive: Moisture Sensitive
• CAS DataBase Reference: 2-Fluoro-5-nitropyridine(CAS DataBase Reference)
• NIST Chemistry Reference: 2-Fluoro-5-nitropyridine(456-24-6)
• EPA Substance Registry System: 2-Fluoro-5-nitropyridine(456-24-6)

Safety Data

• Hazard Codes: Xn
• Statements: 20/21/22-22
• Safety Statements: 36
• RIDADR: UN 1549
• Hazardous Substances Data: 456-24-6(Hazardous Substances Data)

Usage

Uses

Used in Organic Synthesis:
2-Fluoro-5-nitropyridine is used as an organic synthesis intermediate for the preparation of various nitropyridine derivatives. Its unique structure allows for further functionalization and modification, making it a valuable building block in the synthesis of complex organic molecules.
Used in Pharmaceutical Industry:
2-Fluoro-5-nitropyridine can be used as a pharmaceutical intermediate, playing a crucial role in the development of new drugs and therapeutic agents. Its presence in the molecular structure can impart specific biological activities and properties, contributing to the effectiveness of the final drug product.
Used in Laboratory Research and Development:
2-Fluoro-5-nitropyridine is utilized in laboratory research and development processes, where it serves as a key component in the synthesis and study of novel compounds. Its reactivity and structural features make it an attractive candidate for exploring new chemical reactions and mechanisms.
Used in Chemical Production Process:
In the chemical production process, 2-Fluoro-5-nitropyridine is employed as a key intermediate for the large-scale synthesis of various chemical products. Its versatility and reactivity enable the efficient production of a wide range of compounds, contributing to the advancement of the chemical industry.

Synthesis

Synthesis of 5-amino-2-fluoropyridine. A mixture of 5-nitro-2-chloropyridine (2.0 g, 12.6 mmol) and anhydrous potassium fluoride (2.2 g, 38 mmol) in a combination of sulfalone ( 6 mL) and benzene (4 mL) was stirred at RT for 20 min. The benzene was then removed by distillation. The resulting mixture was heated at 150 °C for 12h. The mixture was cooled to RT whereupon water (60 mL) was added. The desired product was separated from the solution via steam distillation. Extraction of the distillate with diethyl ether (2 × 1 0 mL) followed by drying (Na2SO4) and concentration gave the compound. 5-nitro-2-fluoropyridine, water white oil (1.3 g, 73%).

InChI:InChI=1/C5H3FN2O2/c6-5-2-1-4(3-7-5)8(9)10/h1-3H

Upstream product

• 4214-76-0 5-nitro-pyridin-2-ylamine 
• 4548-45-2 2-chloro-5-nitropyridine 
• 372-48-5 2-fluoropyridine 
• 2127-10-8 5,5'-dinitro-2,2'-disulfanediyl-bis-pyridine 

Downstream Products

• 5446-92-4 2-methoxy-5-nitropyridine 
• 1827-27-6 2-fluoro-5-aminopyridine 
• 36977-08-9 N-(5-nitro-[2]pyridyl)-phenylalanine 
• 438226-87-0 {(5,5-bis-dodecyloxymethyl-[1,3]dithian-2-yl)-[4-(tetrahydro-pyran-2-yloxy)-phenyl]-methyl}-(5-nitro-pyridin-2-yl)-amine 
• 171178-41-9 (6-fluoro-pyridin-3-yl)-carbamic acid, tert-butyl ester 
• 171178-42-0 5-[N-(tert-Butoxycarbonyl)-amino]-2-fluoropyridine-4-carboxylic acid 
• 305371-18-0 4-chloro-6-fluoro-[1,7]naphthyridine-3-carbonitrile 
• 305371-17-9 6-fluoro-4-hydroxy-[1.7]naphthyridine-3-carbonitrile 
• 305371-15-7 5-tert-butoxycarbonylamino-2-fluoro-isonicotinic acid, methyl ester 
• 305371-16-8 [6-fluoro-4-(3-nitrilo-propionyl)-pyridin-3-yl]-carbamic acid, tert-butyl ester 
• 305371-21-5 6-amino-4-(3-bromo-phenylamino)-[1.7]naphthyridine-3-carbonitrile 
• 305371-19-1 4-(3-bromo-phenylamino)-6-fluoro-[1.7]naphthyridine-3-carbonitrile 
• 305371-33-9 4-(3-chloro-4-fluorophenylamino)-6-fluoro-[1,7]naphthyridine-3-carbonitrile 
• 305371-20-4 4-(3-bromo-phenylamino)-6-(4-methoxy-benzylamino)-[1.7]naphthyridine-3-carbonitrile 

Relevant articles and documents

Method for pipeline continuous fluorination with fluorine salt as fluorine source

The method comprises the following steps: dissolving a fluorine salt in an aqueous polar aprotic solvent as reaction liquid A, dissolving an aryl (heterocyclic) chloride in a polar aprotic solvent as reaction liquid B, and reacting a polar aprotic solvent in the reaction liquid A with a polar aprotic solvent of the reaction liquid B. The reaction medium consisting of the preheated reaction liquid A and the preheated reaction liquid B enters the reaction coil for a fluorination reaction, and the resulting product from the reaction coil is subjected to post-treatment to obtain the product. The method has the characteristics of no need of adding a phase transfer catalyst, continuous production, low production cost and the like.

Nucleophilic Fluorination of Heteroaryl Chlorides and Aryl Triflates Enabled by Cooperative Catalysis

Aryl and heteroaryl fluorides are growing to be dominant motifs in pharmaceuticals and agrochemicals, yet they are rare in both nature and commodity chemicals. As a consequence, there is an increasingly urgent need to develop mild, cost-effective, and scalable methods for fluorination. The most straightforward route to synthesize aryl fluorides is through the halide exchange "halex"reaction, but conditions, cost, and atom economy preclude most available methods from large-scale manufacturing processes. We report a new approach that leverages the cooperative action of 18-crown-6 ether and tetramethylammonium chloride to catalytically access the reactivity of tetramethylammonium fluoride and achieve halex fluorinations under mild conditions with operational ease. The described methodology readily converts both heteroaryl chlorides and aryl triflates to their corresponding (hetero)aryl fluorides in high yields and purities.

Tetramethylammonium Fluoride Alcohol Adducts for SNAr Fluorination

Nucleophilic aromatic fluorination (SNAr) is among the most common methods for the formation of C(sp2)-F bonds. Despite many recent advances, a long-standing limitation of these transformations is the requirement for rigorously dry, aprotic conditions to maintain the nucleophilicity of fluoride and suppress the generation of side products. This report addresses this challenge by leveraging tetramethylammonium fluoride alcohol adducts (Me4NF·ROH) as fluoride sources for SNAr fluorination. Through systematic tuning of the alcohol substituent (R), tetramethylammonium fluoride tert-amyl alcohol (Me4NF·t-AmylOH) was identified as an inexpensive, practical, and bench-stable reagent for SNAr fluorination under mild and convenient conditions (80 °C in DMSO, without the requirement for drying of reagents or solvent). A substrate scope of more than 50 (hetero) aryl halides and nitroarene electrophiles is demonstrated.

PROCESS FOR FLUORINATING COMPOUNDS

Disclosed are mild temperature (e.g., from 0 to 80°C) SNAr fluorinations of a variety of halide and sulfonate substituted aryl and heteroaryl substrates using NMe4F.

Anhydrous Tetramethylammonium Fluoride for Room-Temperature SNAr Fluorination

This paper describes the room-temperature SNAr fluorination of aryl halides and nitroarenes using anhydrous tetramethylammonium fluoride (NMe4F). This reagent effectively converts aryl-X (X = Cl, Br, I, NO2, OTf) to aryl-F under mild conditions (often room temperature). Substrates for this reaction include electron-deficient heteroaromatics (22 examples) and arenes (5 examples). The relative rates of the reactions vary with X as well as with the structure of the substrate. However, in general, substrates bearing X = NO2 or Br react fastest. In all cases examined, the yields of these reactions are comparable to or better than those obtained with CsF at elevated temperatures (i.e., more traditional halex fluorination conditions). The reactions also afford comparable yields on scales ranging from 100 mg to 10 g. A cost analysis is presented, which shows that fluorination with NMe4F is generally more cost-effective than fluorination with CsF.

Synthesis and characterization of 2-pyridylsulfur pentafluorides

Current approaches to prepare SF5-substituted heterocycles during the synthesis of targeted heterocyclic compounds require the use of SF5-functionalized aryl or alkyne reagents or SF5Cl as a source of the SF5 functional group. Herein we report that excess oxidative fluorination of 2,2' -dipyridyl disulfide with a KF/Cl2 /MeCN system leads to the formation of thirteen new 2-pyridylsulfur chlorotetrafluorides (2-SF4Cl-pyridines). These molecules are found to undergo further chlorine-fluorine exchange reactions by treatment with silver(I) fluoride enabling ready access to a series of ten new substituted 2-pyridylsulfur pentafluorides (2-SF5-pyridines). This is the first preparatively simple and readily scalable example of the transformation of an existing heterocyclic sulfur functionality to prepare SF5-substituted heterocycles.

Dihydrolevoglucosenone (Cyrene) as a bio-based alternative for dipolar aprotic solvents

Dihydrolevoglucosenone (Cyrene) is a bio-based molecule, derived in two simple steps from cellulose, which demonstrates significant promise as a dipolar aprotic solvent. The dipolarity of dihydrolevoglucosenone is similar to NMP, DMF and sulpholane. Dihydrolevoglucosenone demonstrates similar performance to NMP in a fluorination reaction and the Menschutkin reaction. This journal is the Partner Organisations 2014.

Preparation of nitropyridines by nitration of pyridines with nitric acid

Preparation of nitropyridines by nitration of pyridines with nitric acid was discussed. Trifluoroacetic anhydride was chilled in an ice bath and the pyridine or substituted pyridines were slowly added and stirred at chilled conditions for 2 h. Relative amounts of the reactants were required for the nitration of pyridine were characterized by 1H and Nuclear magnetic resonance (NMR) spectroscopy and elemental analysis. It was observed that the yields of β-nitropyridines obtained using the standard protocol were generally higher than those obtained using N2O3.

Syntheses and EGFR kinase inhibitory activity of 6-substituted-4-anilino [1,7] and [1,8] naphthyridine-3-carbonitriles

The syntheses and EGFR kinase inhibitory activity of a series of 6-substituted-4-anilino [1,7] and [1,8] naphthyridine-3-carbonitriles are described. Both reversible and irreversible binding inhibitors were prepared. These series were compared with each other and with the corresponding 4-anilinoquinoline-3-carbonitriles. Compounds having a 1,7-naphthyridine core structure can retain high potency while those with a 1,8-naphthyridine core are significantly less active. These results are consistent with molecular modeling observations.

SUBSTITUTED-3-CYANO-[1.7],[1.5], AND [1.8]-NAPHTHYRIDINE INHIBITORS OF TYROSINE KINASES

This invention provides compounds of formula (I) having structure (a) wherein A'' is a diavalent moiety selected from the group (a, b, c) which are useful as inhibitors of protein tyrosine kinase.