2-Bromo-4-fluoro-N-methylaniline: Properties & Applications

2-Bromo-4-fluoro-N-methylaniline is a halogenated aromatic amine building block widely valued in medicinal chemistry and agrochemical research for its dual electrophilic and nucleophilic reactivity derived from the combination of a bromo substituent, a para-fluoro group, and a secondary amine functionality on the aniline scaffold.

Chemical Name

2-Bromo-4-fluoro-N-methylaniline

SKU / Catalog Number

B733256

Molecular Formula

C7H7BrFN

Molecular Weight

204.04 g/mol

Key Functional Groups

Aryl bromide, aryl fluoride, secondary amine (N-methyl)

Primary Application Area

Pharmaceutical and agrochemical intermediate synthesis

Supplier

Aladdin Scientific

Chemical Identity and Physical Properties

2-Bromo-4-fluoro-N-methylaniline (CAS requires verification; SKU B733256) is a secondary arylamine bearing three distinct substituents on the aniline scaffold: a bromine atom at the ortho position (C-2), a fluorine atom at the para position (C-4), and an N-methyl group on the nitrogen. Its molecular formula is C₇H₇BrFN with a molecular weight of approximately 204.04 g/mol.

The compound is typically a pale yellow to amber liquid or low-melting solid at ambient temperature. The presence of the electronegative fluorine atom at the para position reduces the electron density of the ring and modulates the basicity of the amine relative to unsubstituted N-methylaniline. The ortho-bromo substituent introduces steric effects near the nitrogen, influencing both reactivity and conformational preferences. Researchers should confirm exact physical constants—such as boiling point, melting point, density, and refractive index—against the certificate of analysis supplied with each lot.

Synthetic Utility and Reactivity

The synthetic value of 2-bromo-4-fluoro-N-methylaniline lies in the orthogonal reactivity of its functional groups. The aryl C–Br bond is an excellent handle for transition-metal-catalyzed cross-coupling reactions, including Suzuki–Miyaura, Buchwald–Hartwig, and Sonogashira couplings, enabling rapid diversification of the aryl scaffold.

The aryl C–F bond, while generally less reactive toward nucleophilic aromatic substitution than aryl chlorides under mild conditions, can participate in SNAr reactions when activated by strong electron-withdrawing groups or harsh conditions, or it can be retained as a metabolically stable fluorine substituent in drug candidates. The secondary amine (N–H) can be acylated, alkylated, or engaged in further C–N bond-forming reactions, providing an additional vector for structural elaboration. This multi-functional reactivity makes the compound a versatile intermediate for constructing complex heterocyclic and carbocyclic frameworks.

Applications in Pharmaceutical and Agrochemical Research

Halogenated N-methylanilines occupy an important niche in drug discovery as pharmacophore precursors and building blocks for bioactive molecules. The combination of fluorine and bromine substituents on the aniline ring is particularly attractive because fluorine can improve metabolic stability, membrane permeability, and binding selectivity, while the bromine serves as a synthetic handle for further functionalization late in the synthetic sequence.

In agrochemical research, fluorinated and brominated aniline derivatives are commonly employed in the synthesis of herbicides, fungicides, and insecticides. The electron-withdrawing character of both halogens can influence the biological activity profile of the final active ingredient. Researchers in both sectors use 2-bromo-4-fluoro-N-methylaniline as a starting material or intermediate when constructing libraries of candidate compounds for structure–activity relationship (SAR) studies.

Safe Handling, Storage, and Regulatory Considerations

As an aromatic amine, 2-bromo-4-fluoro-N-methylaniline should be treated as a potentially harmful substance. Aromatic amines as a class carry concerns regarding mutagenicity and skin/eye irritation; users must consult the Safety Data Sheet (SDS) provided by Aladdin Scientific before use. Personal protective equipment (PPE) including chemical-resistant gloves, laboratory coat, and eye protection is recommended. Work in a well-ventilated fume hood to minimize inhalation exposure.

The compound should be stored in a tightly sealed container, away from heat, oxidizing agents, and strong acids or bases. Recommended storage is typically at 2–8 °C or room temperature under inert atmosphere (nitrogen or argon) to prevent oxidative degradation of the amine. Disposal must comply with local regulations for halogenated organic waste. Users outside the United States should verify import and export regulatory requirements for organobromine and organofluorine compounds in their jurisdiction.

Frequently asked questions

What cross-coupling reactions is 2-Bromo-4-fluoro-N-methylaniline suitable for?

The aryl C–Br bond makes this compound a suitable substrate for palladium-catalyzed cross-coupling reactions, including Suzuki–Miyaura (with boronic acids), Buchwald–Hartwig (C–N bond formation), and Sonogashira (with terminal alkynes) couplings. Reaction conditions should be optimized based on the desired coupling partner and catalyst system.

How should 2-Bromo-4-fluoro-N-methylaniline be stored to maintain purity?

Store the compound in a tightly sealed container under an inert atmosphere (nitrogen or argon) at 2–8 °C or at room temperature away from light, moisture, heat, and oxidizing agents. Always re-seal the container promptly after use and verify purity against the certificate of analysis before use in sensitive applications.

Is 2-Bromo-4-fluoro-N-methylaniline available from Aladdin Scientific, and what is the catalog number?

Yes, 2-Bromo-4-fluoro-N-methylaniline is available from Aladdin Scientific under catalog number B733256. Contact Aladdin Scientific or visit the product page for current stock levels, pack sizes, pricing, and purity specifications.

What safety precautions are required when handling this compound?

Users should wear chemical-resistant gloves, a laboratory coat, and safety goggles, and handle the compound in a well-ventilated fume hood. The full Safety Data Sheet (SDS) must be consulted before use, as aromatic amines may pose irritation and potential mutagenicity hazards.

Can the aryl fluoride in 2-Bromo-4-fluoro-N-methylaniline be selectively functionalized?

The aryl C–F bond is generally more resistant to nucleophilic aromatic substitution than the C–Br bond under standard transition-metal catalysis conditions, allowing selective manipulation of the bromide. However, under forcing SNAr conditions with suitable nucleophiles, the fluoride can be displaced. The orthogonal reactivity of C–Br versus C–F provides synthetic flexibility in multi-step sequences.

References

1. Clayden, J.; Greeves, N.; Warren, S. Organic Chemistry, 2nd ed.; Oxford University Press: Oxford, 2012. (General reference for aryl halide reactivity and cross-coupling reactions.)
2. Roughley, S. D.; Jordan, A. M. The Medicinal Chemist's Toolbox: An Analysis of Reactions Used in the Pursuit of Drug Candidates. J. Med. Chem. 2011, 54, 3451–3479. doi:10.1021/jm200187y
3. Hagmann, W. K. The Many Roles for Fluorine in Medicinal Chemistry. J. Med. Chem. 2008, 51, 4359–4369. doi:10.1021/jm800219f
4. Aladdin Scientific. Product Page: 2-Bromo-4-fluoro-N-methylaniline, SKU B733256. (Accessed via Aladdin Scientific catalog.)

Products are supplied for research and development use only. Not for use in humans, animals, diagnosis, or therapy.