4-Bromo-2-fluoro-6-methylbenzamide: Properties & Lab Use Guide

4-Bromo-2-fluoro-6-methylbenzamide is a halogen- and fluorine-substituted aromatic benzamide building block widely employed in medicinal chemistry and organic synthesis as a versatile intermediate for constructing biologically active molecules.

Chemical Name

4-Bromo-2-fluoro-6-methylbenzamide

SKU / Catalog Number

B586744

Molecular Formula

C8H7BrFNO

Molecular Weight

232.05 g/mol

Functional Groups

Amide (–CONH2), Bromo (–Br), Fluoro (–F), Methyl (–CH3)

Compound Class

Halogenated aromatic benzamide

Primary Use

Synthetic intermediate and building block in medicinal chemistry

Chemical Identity and Structure

4-Bromo-2-fluoro-6-methylbenzamide (CAS registry number to be confirmed; see review flags) belongs to the benzamide family of aromatic amides. Its molecular formula is C₈H₇BrFNO, giving a molecular weight of approximately 232.05 g/mol. The compound features a benzene ring bearing three substituents in addition to the primary amide group: a bromine atom at the para position (C-4), a fluorine atom at the ortho position (C-2), and a methyl group at the second ortho position (C-6). This substitution pattern creates a sterically congested environment around the amide carbonyl, which can influence both reactivity and conformation in downstream transformations.

The presence of both bromo and fluoro halogens on the ring makes this compound particularly attractive as a cross-coupling partner and as a precursor in nucleophilic aromatic substitution reactions. The C–Br bond is selectively reactive under palladium-catalyzed conditions (e.g., Suzuki–Miyaura, Buchwald–Hartwig), while the C–F bond can participate in SNAr reactions under forcing conditions with appropriate nucleophiles.

Handling, Storage, and Safety Guidelines

Personal Protective Equipment (PPE): When handling 4-Bromo-2-fluoro-6-methylbenzamide, wear appropriate PPE including nitrile gloves, a laboratory coat, and safety goggles. Work in a well-ventilated area or under a fume hood to minimize inhalation of dust or aerosols generated during weighing.

Storage: Store the compound in a tightly sealed container in a cool, dry place away from direct sunlight, moisture, and incompatible materials such as strong oxidizing agents and strong bases. Typical recommended storage temperature is 2–8 °C or room temperature as specified on the product label (verify with the Certificate of Analysis supplied with each lot). Keep the container sealed when not in use to prevent hygroscopic uptake and degradation.

Waste Disposal: Dispose of this compound and any contaminated materials in accordance with local, national, and institutional regulations governing halogenated organic waste. Do not dispose of via drain or municipal waste streams. Consult your institutional Environmental Health and Safety (EHS) office for approved disposal procedures.

First Aid: In case of skin contact, wash thoroughly with soap and water. In case of eye contact, rinse immediately with copious water for at least 15 minutes and seek medical attention. If inhaled, move to fresh air. Always consult the Safety Data Sheet (SDS) provided with the product for complete hazard information before use.

Research Applications and Synthetic Utility

4-Bromo-2-fluoro-6-methylbenzamide serves as a valuable building block in several areas of chemical research:

• Medicinal Chemistry: Benzamide scaffolds are prevalent in pharmaceutical candidates and approved drugs targeting a range of biological pathways. The combination of a primary amide, a bromo handle for further functionalization, and a fluorine atom (known to modulate lipophilicity, metabolic stability, and bioavailability) makes this compound a strategic starting material for drug discovery programs.
• Cross-Coupling Chemistry: The aryl bromide moiety undergoes well-established palladium-catalyzed reactions including Suzuki–Miyaura boronic acid coupling, Negishi coupling, Sonogashira alkynylation, and Buchwald–Hartwig amination, enabling rapid diversification of the aromatic core.
• SNAr Reactions: The fluorine substituent, activated by the electron-withdrawing amide and bromo groups, can participate in nucleophilic aromatic substitution with amines, alkoxides, and thiolates to introduce heteroatom-linked substituents.
• Agrochemical Research: Halogenated benzamide derivatives have documented use in agrochemical lead optimization, particularly in the development of insecticides and fungicides.

Researchers should conduct feasibility studies and optimize reaction conditions (catalyst loading, base, solvent, temperature) empirically for each specific transformation, as the steric bulk of the ortho-methyl group may influence coupling efficiency.

Quality, Purity, and Regulatory Considerations

Purity and Specification: Aladdin Scientific's 4-Bromo-2-fluoro-6-methylbenzamide (SKU B586744) is supplied as a research-grade reagent. Purity specifications are detailed on the product's Certificate of Analysis (CoA), which is lot-specific and available upon request or via the Aladdin Scientific website. Researchers are advised to verify purity data (typically confirmed by HPLC, NMR, or MS) before use in critical assays or multi-step syntheses.

Regulatory Classification: This compound is intended for research and development use only and is not approved for human or veterinary therapeutic use. It is not classified as a controlled substance under standard international schedules; however, researchers should verify applicable local import/export and handling regulations, particularly given the halogenated organic nature of the compound.

Lot-to-Lot Consistency: As with all research reagents, lot-to-lot variation may occur. For reproducibility-sensitive applications, it is recommended to retain lot number information and, where feasible, to qualify new lots against previously characterized material.

Frequently asked questions

What is the recommended storage condition for 4-Bromo-2-fluoro-6-methylbenzamide (B586744)?

Store the compound in a tightly sealed container in a cool, dry, and dark location. The specific temperature requirement (e.g., room temperature or 2–8 °C) is indicated on the product label and Certificate of Analysis. Always keep the container sealed to prevent moisture uptake.

Which palladium-catalyzed reactions are suitable for the aryl bromide moiety in this compound?

The aryl bromide in 4-Bromo-2-fluoro-6-methylbenzamide is amenable to several well-established Pd-catalyzed cross-coupling reactions, including Suzuki–Miyaura coupling with boronic acids, Negishi coupling with organozinc reagents, Sonogashira coupling with terminal alkynes, and Buchwald–Hartwig amination. Note that the ortho-methyl substituent may introduce steric hindrance; reaction conditions should be optimized empirically.

Can the fluorine substituent be used for nucleophilic aromatic substitution (SNAr)?

Yes. The fluorine atom at the ortho position is activated toward SNAr by the combined electron-withdrawing effects of the adjacent amide carbonyl and the para-bromo substituent. Suitable nucleophiles include primary and secondary amines, alkoxides, and thiolates. Reaction conditions (solvent, base, temperature) should be carefully selected and optimized for each nucleophile.

Is 4-Bromo-2-fluoro-6-methylbenzamide suitable for biological or in vivo studies?

This compound is supplied strictly as a research-grade synthetic building block and is not approved or validated for therapeutic, diagnostic, or in vivo use in humans or animals. Any biological evaluation must be conducted under appropriate institutional biosafety and ethics oversight, with full characterization of the compound's purity and stability prior to use.

References

1. Clayden, J.; Greeves, N.; Warren, S. Organic Chemistry, 2nd ed.; Oxford University Press: Oxford, 2012. (General reference for benzamide chemistry 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. Aladdin Scientific. Product Certificate of Analysis for 4-Bromo-2-fluoro-6-methylbenzamide, SKU B586744. (Available on request from Aladdin Scientific.)

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