852062-17-0 | 2-Amino-3-fluoro-5-(trifluoromethyl)pyridine

CAS:852062-17-0 | 2-Amino-3-fluoro-5-(trifluoromethyl)pyridine,Description

The compound "3-Fluoro-5-(trifluoromethyl)pyridin-2-amine" is a fluorinated pyridine derivative, which is a class of compounds known for their diverse applications in pharmaceuticals, agrochemicals, and materials science. The presence of fluorine atoms in the molecule can significantly alter its physical and chemical properties, making it a valuable target for synthesis and application in various chemical reactions.

Synthesis Analysis

The synthesis of fluorinated pyridines, such as "3-Fluoro-5-(trifluoromethyl)pyridin-2-amine," can be achieved through several methods. One approach involves the C-F bond cleavage of anionically activated fluoroalkyl groups, as described in a new strategy for synthesizing poly-substituted pyridines. This method allows for the formation of 2,6-disubstituted 4-amino pyridines under metal-free conditions, which is a significant advantage in terms of cost and environmental impact.

Molecular Structure Analysis

The molecular structure of fluorinated pyridines is characterized by the presence of fluorine atoms, which can influence the electronic distribution and steric hindrance within the molecule. For instance, the tris(2-fluoro-6-pyridylmethyl)amine ligand (F3TPA) exhibits a trigonal bipyramidal iron center due to the steric hindrance provided by the three fluorine substituents. This structural feature is crucial for the ligand's coordination properties and reactivity.

Chemical Reactions Analysis

Fluorinated pyridines participate in various chemical reactions, leveraging the unique reactivity of the fluorine atoms. For example, the F3TPA ligand reacts instantaneously with molecular dioxygen to afford dinuclear species, demonstrating the ligand's potential in oxidation reactions. Additionally, the selective fluorination of 2-aminopyridines in aqueous solution has been achieved with high regioselectivity, indicating the possibility of further functionalizing the pyridine ring at specific positions.

Physical and Chemical Properties Analysis

The introduction of fluorine atoms into the pyridine ring can significantly affect the compound's physical and chemical properties. Fluorinated pyridines often exhibit increased thermal stability, low moisture absorption, and high hygrothermal stability, as seen in the synthesis of soluble fluoro-polyimides derived from fluorinated aromatic diamines. These properties make fluorinated pyridines particularly attractive for the development of advanced materials with enhanced performance characteristics.

Scientific Research Applications

• Agrochemical Industry

  • TFMP and its derivatives are key structural motifs in active agrochemical ingredients. They are used in the protection of crops from pests.
  • The major use of TFMP derivatives is in the protection of crops from pests. Fluazifop-butyl was the first TFMP derivative introduced to the agrochemical market, and since then, more than 20 new TFMP-containing agrochemicals have acquired ISO common names.

• Pharmaceutical Industry

  • TFMP derivatives are also used in the pharmaceutical and veterinary industries. Five pharmaceutical and two veterinary products containing the TFMP moiety have been granted market approval, and many candidates are currently undergoing clinical trials.
  • 2-Amino-3-chloro-5-trifluoromethylpyridine, a derivative of TFMP, acts as a reactant in the synthesis of novel imidazo [1,2-a]pyridine-coumarin hybrid molecules as inhibitors of NS5B in potential treatment of Hepatitis C.

• Synthesis of Metal-Organic Frameworks (MOFs)

  • TFMP is used in the preparation of (trifluoromethyl)pyridyllithiums, via metalation reaction.
  • It is also used in the synthesis of metal-organic frameworks (MOFs).

• Synthesis of Crop-Protection Products

  • Among TFMP derivatives, 2,3-dichloro-5-(trifluoromethyl)pyridine (2,3,5-DCTF), which is used as a chemical intermediate for the synthesis of several crop-protection products, is in the highest demand.
  • It can be obtained by direct chlorination and fluorination of 3-picoline and followed by aromatic nuclear chlorination of the pyridine ring.

• Inhibitors of NS5B in Potential Treatment of Hepatitis C

  • 2-Amino-3-chloro-5-trifluoromethylpyridine, a derivative of TFMP, acts as a reactant in the synthesis of novel imidazo [1,2-a]pyridine-coumarin hybrid molecules as inhibitors of NS5B in potential treatment of Hepatitis C.

• Synthesis of Selective Inhibitors of Urokinase Plasminogen Activator

  • 2-Amino-5-(trifluoromethyl)pyridine, another derivative of TFMP, is a reagent used in the synthesis of selective inhibitors of urokinase plasminogen activator in a non-cytotoxic form of cancer therapy.

• Synthesis of Fluorinated Organic Chemicals

  • Trifluoromethylpyridine (TFMP) and its intermediates are important ingredients for the development of fluorinated organic chemicals.
  • The presence of a fluorine atom and a carbon-containing pyridine are thought to bestow many of the distinctive physical–chemical properties observed with this class of compounds.

• Development of Pesticides

  • With the global population rapidly expanding, agrochemicals are in increasing demand to maintain crop production.
  • In addition, the agricultural research community faces the challenge of producing pesticides that not only prevent crop losses caused by parasites, but also protect human populations from the spread of diseases such as malaria, dengue fever, or the Zika virus, all of which are carried by mosquitoes.

• Manufacturing of TFMP Derivatives

  • The demand for TFMP derivatives has been increasing steadily in the last 30 years.
  • Tsukamoto and Nakamura guide the readers through the different synthetic methods for introducing TFMP groups within the structures of other molecules.

Safety And Hazards

The compound is classified as hazardous according to the 2012 OSHA Hazard Communication Standard. It has hazard statements H302, H315, H319, and H335, indicating that it is harmful if swallowed, causes skin and eye irritation, and may cause respiratory irritation.

Future Directions

Trifluoromethylpyridine derivatives, such as “3-Fluoro-5-(trifluoromethyl)pyridin-2-amine”, have gained significant interest in the field of agrochemical and pharmaceutical compounds. They are key structural ingredients for the development of many such compounds. Therefore, the demand for these derivatives is expected to increase in the future.

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