944401-77-8 | 2-AMINO-4-FLUOROPYRIDINE

CAS:944401-77-8 | 2-AMINO-4-FLUOROPYRIDINE,Description

2-Amino-4-fluoropyridine is a fluorinated pyridine derivative that is of significant interest in the field of medicinal chemistry and as an intermediate in organic synthesis. The presence of both amino and fluorine substituents on the pyridine ring makes it a valuable compound for the development of pharmaceuticals and other biologically active molecules.

Synthesis Analysis

The synthesis of 2-aminopyridine derivatives, including 2-amino-4-fluoropyridine, can be achieved through various methods. One approach involves the nucleophilic substitution and hydrolysis of 2-fluoropyridine and acetamidine hydrochloride under catalyst-free conditions, which has been shown to yield high chemoselectivity and wide substrate adaptability. Another method for synthesizing 2-amino-5-fluoropyridine, which is closely related to 2-amino-4-fluoropyridine, uses a diazotization process followed by solventless thermolysis and hydrolysis, resulting in a 66% overall yield. Additionally, a novel synthesis route has been proposed that simplifies experimental operations and improves the yield and purity of the final product.

Molecular Structure Analysis

The molecular structure of 2-amino-4-fluoropyridine derivatives can be influenced by the presence of substituents on the pyridine ring. For instance, the reaction of 4-amino-2-fluoropyridine with copper halides has led to the formation of neutral coordination complexes with distinct crystal structures and magnetic properties. These structural variations can significantly affect the physical and chemical properties of the compounds.

Chemical Reactions Analysis

2-Amino-4-fluoropyridine can undergo various chemical reactions due to its reactive amino and fluorine groups. The fluorine atom can participate in selective fluorination reactions, which have been demonstrated with high regioselectivity in aqueous solutions. Moreover, the amino group can be involved in palladium-catalyzed amination reactions, as shown in the synthesis of 2-amino-5-[18F]fluoropyridines.

Physical and Chemical Properties Analysis

The physical and chemical properties of 2-amino-4-fluoropyridine are influenced by its molecular structure. The electron-deficient pyridine system, activated by the amino group at C2, allows for selective fluorination reactions. The compound's melting point and structure have been confirmed through various analytical techniques, including 1H-NMR and IR spectroscopy, ensuring the consistency and purity of the synthesized material. The coordination complexes formed with copper halides exhibit specific magnetic properties, which are determined by their crystal packing and geometry.

Scientific Research Applications

Synthesis and Chemical Applications

• Novel Synthesis Methods : 2-Amino-4-fluoropyridine has been utilized in various novel synthesis pathways. For instance, a new method using 2-fluoroallylic alcohols led to 4-fluoropyridines with potential aryl and alkyl substituents (Wittmann et al., 2006). Another study explored an efficient synthesis method of 2-Amino-5-fluoropyridine via diazotization and thermolysis, demonstrating the chemical versatility of similar compounds (Huang Gang, 2006).

Medical and Biological Applications

• Positron Emission Tomography (PET) Imaging : A significant application of 2-Amino-4-fluoropyridine derivatives is in PET imaging. For example, 3-[18 F]fluoro-4-aminopyridine, a derivative, is being investigated for PET imaging of demyelination in multiple sclerosis, showcasing its potential in medical diagnostics (Basuli et al., 2018).

Material Science and Coordination Chemistry

• Magnetic Properties in Coordination Complexes : Research involving 2-Amino-4-fluoropyridine has also delved into the field of coordination chemistry. Studies have explored its role in the formation of coordination complexes with copper halides, which have distinct magnetic properties (Krasinski et al., 2017).

Organic Chemistry and Catalysis

• Catalyst-Free Amination Reactions : In organic chemistry, 2-Amino-4-fluoropyridine derivatives have been synthesized via catalyst-free amination, reflecting their potential in more sustainable and efficient chemical processes (Abel et al., 2015).

Safety And Hazards

2-Amino-4-fluoropyridine is harmful if swallowed, in contact with skin, or if inhaled. It causes skin irritation and serious eye irritation. It may also cause respiratory irritation. It is advised to avoid breathing dust/fume/gas/mist/vapours/spray, and to wear protective gloves/protective clothing/eye protection/face protection.

Future Directions

2-Amino-4-fluoropyridine is widely applied to the synthesis of medicines, pesticides, and fine chemicals. It is used as a novel medical intermediate, and is an important intermediate of a plurality of inhibitors such as tyrosine kinase inhibitors, PI3K inhibitors, aldosterone synthase inhibitors, and more. Therefore, it is expected to continue to play a significant role in the synthesis of these and potentially new compounds in the future.

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