4'-Bromo-2'-chloroacetanilide: Properties, Uses & FAQs

4'-Bromo-2'-chloroacetanilide is a halogenated acetanilide derivative serving as a versatile electrophilic building block in pharmaceutical and fine-chemical synthesis.

Chemical Name

4'-Bromo-2'-chloroacetanilide

SKU

B152338

Molecular Formula

C₈H₇BrClNO

Functional Class

Halogenated acetanilide; aryl halide intermediate

Primary Application

Electrophilic building block in organic and medicinal chemistry synthesis

Key Structural Features

Bromine at para position and chlorine at ortho position on the acetanilide ring

Chemical Identity and Structure

4'-Bromo-2'-chloroacetanilide (SKU B152338) is an acetanilide derivative in which the aniline ring bears a bromine substituent at the 4'-position (para) and a chlorine substituent at the 2'-position (ortho), while the amino nitrogen carries an acetyl group. Its molecular formula is C₈H₇BrClNO. The presence of two distinct halogen atoms on the aromatic ring provides complementary reactivity: the C–Br bond is particularly amenable to transition-metal-catalyzed cross-coupling reactions (e.g., Suzuki, Buchwald–Hartwig), while the C–Cl bond can participate in nucleophilic aromatic substitution under appropriate conditions. The acetamido group acts as a directing and activating moiety and can be hydrolyzed to reveal the free aniline when required in downstream transformations.

Synthesis and Preparation

4'-Bromo-2'-chloroacetanilide is typically prepared by acetylation of the corresponding 4-bromo-2-chloroaniline using acetic anhydride or acetyl chloride in the presence of a suitable base (e.g., pyridine or sodium acetate) under mild conditions. The reaction proceeds via nucleophilic acyl substitution at the aniline nitrogen. This straightforward route affords the product in good yield after workup and recrystallization. Researchers should verify that starting aniline precursors are of adequate purity, as regioisomeric impurities can be difficult to separate from the final acetanilide product.

Alternatively, directed electrophilic halogenation of pre-formed acetanilide scaffolds can introduce halogens regioselectively, though the two-step route from the dihalogenated aniline is generally preferred for its predictability and scalability.

Applications in Organic and Medicinal Chemistry

The dual halogen substitution pattern of 4'-Bromo-2'-chloroacetanilide makes it a valuable intermediate in medicinal chemistry and materials science. Key applications include:

• Cross-coupling chemistry: The aryl bromide undergoes Suzuki–Miyaura, Negishi, and Buchwald–Hartwig couplings to install aryl, alkenyl, or amino groups at the 4'-position, enabling construction of biaryl and aminobiaryl pharmacophores.
• Nucleophilic aromatic substitution (SNAr): The ortho-chloro group, activated by the electron-withdrawing acetamido moiety, can be displaced by amines, thiols, or alkoxides to generate structurally diverse analogs.
• Scaffold diversification: Hydrolysis of the acetyl group liberates the free dihalogenated aniline, which can be further functionalized or coupled into heterocyclic frameworks relevant to drug discovery programs.

These properties position the compound as a flexible building block in library synthesis and lead optimization campaigns.

Handling, Storage, and Safety

As with all halogenated acetanilide derivatives, appropriate laboratory safety precautions should be observed when handling 4'-Bromo-2'-chloroacetanilide:

• Personal protective equipment (PPE): Wear nitrile gloves, a laboratory coat, and safety goggles. Use a fume hood to avoid inhalation of dust or aerosols.
• Storage: Store in a tightly sealed container in a cool, dry, well-ventilated area, away from incompatible materials such as strong oxidizers and strong bases. Typical storage temperature is room temperature unless otherwise indicated on the product label.
• Disposal: Dispose of waste material in accordance with local, regional, and national regulations for halogenated organic compounds.
• First aid: In case of skin or eye contact, flush immediately with copious water and seek medical attention if irritation persists.

Consult the Safety Data Sheet (SDS) provided by Aladdin Scientific for complete hazard classification, GHS pictograms, and emergency response information specific to lot B152338.

Quality, Purity, and Regulatory Considerations

Aladdin Scientific supplies 4'-Bromo-2'-chloroacetanilide (SKU B152338) as a research-grade reagent. Researchers should review the Certificate of Analysis (CoA) supplied with each lot for purity data determined by techniques such as HPLC or GC, as well as NMR confirmation of structure. Key quality attributes to verify include:

• Assay purity (typically reported as ≥95% or higher for research-grade material; confirm on CoA)
• Absence of regioisomeric contaminants (e.g., 2-bromo-4-chloro isomer)
• Residual solvent content within acceptable limits
• Appearance and melting point consistent with literature values

For regulated research environments (e.g., GMP-adjacent or IND-enabling studies), additional testing and documentation may be required. Contact Aladdin Scientific's technical support team for custom purity specifications or analytical data requirements.

Frequently asked questions

What is the molecular formula and molecular weight of 4'-Bromo-2'-chloroacetanilide?

The molecular formula of 4'-Bromo-2'-chloroacetanilide is C₈H₇BrClNO. The molecular weight is approximately 248.50 g/mol, calculated from the atomic weights of carbon, hydrogen, bromine, chlorine, nitrogen, and oxygen. Please verify the exact value against the Certificate of Analysis provided with SKU B152338.

Which cross-coupling reactions are compatible with 4'-Bromo-2'-chloroacetanilide?

The aryl bromide (C–Br) at the 4'-position is the preferred site for palladium-catalyzed cross-coupling reactions, including Suzuki–Miyaura (with arylboronic acids), Negishi (with organozinc reagents), and Buchwald–Hartwig amination. Under standard conditions, the C–Cl bond exhibits lower reactivity toward oxidative addition than the C–Br bond, enabling selective functionalization at the bromo position. Highly active palladium catalyst systems may also activate the C–Cl bond if dual functionalization is desired.

How should 4'-Bromo-2'-chloroacetanilide be stored to maintain stability?

Store 4'-Bromo-2'-chloroacetanilide in a tightly sealed container in a cool, dry, and well-ventilated area at room temperature, away from strong oxidizing agents, strong bases, and moisture. Always refer to the Aladdin Scientific Safety Data Sheet and the product label for lot-specific storage recommendations. Proper storage conditions help preserve reagent purity and ensure reliable experimental results.

Can the acetyl group of 4'-Bromo-2'-chloroacetanilide be removed to give the free amine?

Yes, the acetamido group can be hydrolyzed under acidic conditions (e.g., concentrated HCl or H₂SO₄ in aqueous solution with heating) or basic conditions (e.g., aqueous NaOH) to afford the corresponding 4-bromo-2-chloroaniline. This deprotection step is commonly employed in multistep syntheses where the acetyl group serves as a temporary protecting group for the aniline nitrogen during earlier functionalization steps.

What purity grade is SKU B152338, and how can I obtain a Certificate of Analysis?

SKU B152338 is supplied as a research-grade reagent. The purity specification is lot-dependent and is confirmed by analytical methods such as HPLC or GC. A Certificate of Analysis (CoA) for your specific lot can be obtained directly from the Aladdin Scientific website by searching the lot number, or by contacting Aladdin Scientific customer service. Reviewing the CoA before use is strongly recommended to confirm purity, identity, and any special storage requirements.

References

1. March, J. Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 4th ed.; Wiley: New York, 1992. (General reference for acetanilide chemistry and halogenated arene reactivity.)
2. Miyaura, N.; Suzuki, A. Palladium-Catalyzed Cross-Coupling Reactions of Organoboron Compounds. Chem. Rev. 1995, 95, 2457–2483. doi:10.1021/cr00039a007
3. Hartwig, J. F. Palladium-Catalyzed Amination of Aryl Halides: Mechanism and Rational Catalyst Design. Acc. Chem. Res. 1998, 31, 852–860. doi:10.1021/ar970109z
4. Aladdin Scientific Certificate of Analysis, SKU B152338, 4'-Bromo-2'-chloroacetanilide. (Lot-specific document; available on request from Aladdin Scientific.)

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