609783-45-1 | Benzamide, 4-amino-2-fluoro- (9CI)

CAS:609783-45-1 | Benzamide, 4-amino-2-fluoro- (9CI),Description

4-Amino-2-fluorobenzamide is a chemical compound that has been synthesized through various methods for use in different chemical reactions and applications. The compound is characterized by the presence of an amino group and a fluorine atom attached to a benzamide moiety. The specific placement of the fluorine atom at the 2-position and the amino group at the 4-position on the benzene ring is crucial for its chemical properties and reactivity.

Synthesis Analysis

The synthesis of 4-amino-2-fluoro-N-methyl-benzamide, a derivative of 4-amino-2-fluorobenzamide, has been reported to start with the oxidation of 2-fluoro-4-nitrotoluene using potassium permanganate in the presence of a phase transfer catalyst, yielding 2-fluoro-4-nitrobenzoic acid with a 74% yield. Subsequent chlorination and amination steps produce N-methyl-2-fluoro-4-nitrobenzamide in a 95% yield. The final step involves hydrogenation over Pd/C to afford 4-amino-2-fluoro-N-methyl-benzamide with an impressive 98% yield.

Molecular Structure Analysis

The molecular structure of 4-amino-2-fluorobenzamide derivatives can be quite flexible, as indicated by the synthesis and crystal structures of various (N-pyridylmethylene)aminobenzamides. These structures are dominated by hydrogen bonding interactions, such as amide-py N–H…N and amide–carbonyl N–H…O bonds. The differences in hydrogen bonding patterns among similar compounds suggest a structural flexibility that could be advantageous for co-crystallization reactions.

Chemical Reactions Analysis

4-Amino-2-fluorobenzamide derivatives have been utilized in a variety of chemical reactions. For instance, N-fluorobenzamides have been used in a formal [4+2] cycloaddition reaction with maleic anhydride, facilitated by CuI and LiOH, to produce fluorescent 1-amino-2,3-naphthalic anhydrides. This multistep process involves radical generation, hydrogen atom transfer, and benzylic radical addition, leading to the formation of diverse naphthalimides with fluorescent properties.

Physical and Chemical Properties Analysis

The physical and chemical properties of 4-amino-2-fluorobenzamide derivatives are influenced by their molecular structure. For example, the photophysical properties of certain derivatives, such as 2-amino-3-carboxamide-1,1′-biaryls and 4-(arylamino)-[1,1′-biphenyl]-3-carboxamides, have been studied. These compounds exhibit luminescence in the blue region with large Stokes shifts, and some show high fluorescence quantum yields, indicating their potential use in optical applications.

Scientific Research Applications

PET Imaging Ligand for σ Receptors

4-Amino-2-fluorobenzamide derivatives, particularly N-(N-Benzylpiperidin-4-yl)-2-fluorobenzamide, have shown promise in positron emission tomography (PET) imaging. This compound binds to σ receptors with high affinity and selectivity. It was labeled with 18F and evaluated as a σ receptor radioligand, showing potential as a ligand for PET imaging of σ receptors in humans. This could be significant for neuroimaging and the study of neurological disorders (Shiue et al., 1997).

Fluorescent Detection of Zn2+/Cd2+ Ions

Carbazolone substituted 2-aminobenzamides, including derivatives of 4-Amino-2-fluorobenzamide, have been used as fluorescent probes for the detection of Zn2+ and Cd2+ ions. These compounds exhibit a transformation from “off–on” to “on–off” molecular switch, showcasing their potential in analytical chemistry for metal ion detection (Xu et al., 2014) .

Fluorescent Aminonaphthalic Anhydrides Synthesis

N-Fluorobenzamide-directed formal [4+2] cycloaddition reaction with maleic anhydride has been developed, producing fluorescent 1-amino-2,3-naphthalic anhydrides. This reaction, involving N-fluorobenzamides, represents a method for synthesizing compounds with potential applications in fluorescent imaging and molecular probes (Lu et al., 2022).

Radiochemical Synthesis for Protein Labeling

4-Amino-2-fluorobenzamide derivatives, like N-[2-(4-[18F]fluorobenzamido)ethyl]maleimide, are used in radiochemical synthesis for labeling proteins and peptides. This synthesis is important for developing radiotracers and imaging agents in nuclear medicine (Kiesewetter et al., 2011).

19F NMR Spectroscopy in Helical Peptides

In the field of spectroscopy, 4-fluorobenzamide labeled peptides have been utilized to study solvent-dependent chemical shifts in 19F NMR spectroscopy. This research aids in understanding protein folding and structure (Kubasik et al., 2006).

Anticancer and Antibacterial Activities

Derivatives of 4-Amino-2-fluorobenzamide have been evaluated for their anticancer and antibacterial activities. Compounds like N-(3-(2-acetamidothiazol-4-yl)phenyl)-3-fluorobenzamide have shown remarkable antitumor effects and modulation of cellular pathways, indicating their potential as therapeutic agents (Zhang et al., 2017).

Charge Density Analysis in Molecular Crystals

Experimental charge density distribution studies of 4-fluorobenzamide have contributed to understanding intermolecular interactions in molecular crystals. This research is vital for crystal engineering and material science (Hathwar & Row, 2011) .

A2B Adenosine Receptor Antagonists

4-Amino-2-fluorobenzamide derivatives have been explored in the synthesis of A2B adenosine receptor antagonists, which have potential pharmaceutical applications, especially in the treatment of inflammatory diseases (Cheung et al., 2010).

Safety And Hazards

The compound is classified as potentially harmful if swallowed or inhaled, and it may cause skin and eye irritation, as well as respiratory irritation. Safety precautions include avoiding dust formation, avoiding contact with skin and eyes, and using personal protective equipment.

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