5-Bromo-4-fluoro-2-methylaniline is an aromatic amine in which a benzene ring is substituted with a bromine atom at position 5, a fluorine atom at position 4, and a methyl group at position 2, along with an amino group at position 1. Its molecular formula is C7H7BrFN, with a molecular weight of approximately 189.04 g/mol. The presence of electron-withdrawing halogens and an electron-donating methyl group influences the electronic distribution on the aromatic ring, affecting both the reactivity of the amino group and the overall chemical behavior.
The compound can be synthesized by selective halogenation and methylation of aniline derivatives or by functional group transformations starting from suitably substituted benzene precursors. One approach involves controlled bromination and fluorination of 2-methylaniline under conditions that ensure regioselective substitution while minimizing polyhalogenation. Alternative methods may involve nucleophilic aromatic substitution or directed ortho-metalation to install the halogen and methyl groups at the desired positions. Reaction conditions are carefully optimized to preserve the amino functionality, which is reactive toward acylation or oxidation.
Chemically, 5-bromo-4-fluoro-2-methylaniline exhibits reactivity primarily at the amino group and at the halogenated positions. The amino group can undergo acylation, sulfonylation, or diazotization, providing access to a wide range of derivatives. The bromine atom is a reactive site for cross-coupling reactions, including Suzuki, Sonogashira, and Buchwald–Hartwig reactions, allowing the introduction of various aryl, alkenyl, or alkyl substituents. The fluorine atom, due to its strong electron-withdrawing nature, stabilizes the ring and influences regioselectivity in further reactions.
Physically, the compound is typically a solid at room temperature and is soluble in organic solvents such as ethanol, acetone, and dichloromethane. It is stable under neutral conditions but may undergo oxidation, especially at the amino group, or substitution at the bromine atom under harsh conditions. Its combination of polar and halogenated substituents influences solubility, melting point, and intermolecular interactions, which are relevant for handling and purification.
In practical applications, 5-bromo-4-fluoro-2-methylaniline is used as an intermediate in organic synthesis, particularly for the preparation of substituted anilines, heterocycles, and pharmaceuticals. The combination of an amino group and reactive halogens enables modular synthesis of bioactive molecules, agrochemical agents, and functional materials. Its substitution pattern allows systematic exploration of electronic and steric effects in chemical reactions and molecular design.
Overall, 5-bromo-4-fluoro-2-methylaniline is a multifunctional aromatic amine with reactive halogen and methyl substituents. Its defined electronic and steric properties, combined with the nucleophilicity of the amino group, make it a versatile intermediate for selective functionalization and the synthesis of diverse organic compounds in research and applied chemistry.
References
2023. Multigram-scale synthesis of GS-4997, an inhibitor of apoptosis signal-regulating kinase 1. Chemical Papers.
DOI: 10.1007/s11696-023-02835-y
|
GHS07 Warning Details
Discovory and Applicatios