4-Bromo-2-fluoro-5-nitrobenzonitrile: Properties & Lab Guide

4-Bromo-2-fluoro-5-nitrobenzonitrile is a multifunctional halogenated aromatic building block bearing bromo, fluoro, nitro, and cyano substituents that make it a highly versatile intermediate for pharmaceutical synthesis, agrochemical research, and materials science.

CAS Number

To be confirmed (see review flag)

Molecular Formula

C7H2BrFN2O2

Molecular Weight

245.00 g/mol (calculated)

Key Functional Groups

Bromo, Fluoro, Nitro, Nitrile (Cyano)

Primary Reactivity

SNAr at fluorine position; cross-coupling at bromine position; nitro reduction; nitrile hydrolysis or cycloaddition

Recommended Storage

Cool, dry, well-ventilated area; sealed container away from light and moisture

Physical State

Solid (expected); exact melting point needs confirmation

Chemical Identity and Structural Features

4-Bromo-2-fluoro-5-nitrobenzonitrile (Aladdin SKU: B590597) is a polysubstituted benzene derivative carrying four distinct functional groups on the aromatic ring: a bromine atom at the 4-position, a fluorine atom at the 2-position, a nitro group at the 5-position, and a cyano (nitrile) group at the 1-position. This arrangement of electron-withdrawing substituents creates a highly electron-deficient aromatic ring system.

The combination of the nitro group and the cyano group dramatically activates the ring toward nucleophilic aromatic substitution (SNAr), particularly at the carbon bearing the fluorine atom, since fluorine is an excellent leaving group in SNAr reactions when the ring is sufficiently activated. The bromine substituent, while also capable of acting as a leaving group in SNAr, is more commonly exploited in palladium-catalyzed cross-coupling reactions (e.g., Suzuki, Buchwald-Hartwig, Negishi) owing to its superior oxidative addition kinetics with Pd(0) catalysts.

The molecular formula is C₇H₂BrFN₂O₂ with a calculated molecular weight of approximately 245.00 g/mol. Researchers should confirm the exact CAS number and physicochemical constants (melting point, solubility) from the product certificate of analysis (CoA) supplied with Aladdin product B590597.

Synthetic Applications and Reactivity

The four reactive handles on 4-Bromo-2-fluoro-5-nitrobenzonitrile make it an exceptionally versatile building block for multi-step synthesis in medicinal chemistry and agrochemical research:

• Nucleophilic Aromatic Substitution (SNAr): The fluorine at C-2 is activated by the flanking nitro (C-5) and cyano (C-1) groups. Amines, alkoxides, and thiolates can displace fluorine under mild to moderate conditions, generating diverse arylamino, aryloxy, or arylthio products. Reactions are typically conducted in polar aprotic solvents (DMF, DMSO, NMP) with an appropriate base (K₂CO₃, Cs₂CO₃, Et₃N) at temperatures ranging from room temperature to 100 °C depending on nucleophile reactivity.
• Palladium-Catalyzed Cross-Coupling at Bromine: The aryl bromide is amenable to Suzuki-Miyaura (boronic acids/esters), Buchwald-Hartwig (amines), Negishi (organozinc), and other standard Pd-catalyzed protocols. Standard conditions (Pd(PPh₃)₄ or Pd(dppf)Cl₂, base, solvent) apply; the electron-poor ring may require optimization of ligand and temperature.
• Nitro Group Reduction: The nitro group can be reduced to an aniline using catalytic hydrogenation (H₂/Pd-C), iron/acetic acid, or SnCl₂/HCl, providing a primary amine handle for further functionalization such as diazotization or acylation.
• Nitrile Transformation: The cyano group can be hydrolyzed to a carboxylic acid or amide, reduced to a primary amine (aminomethyl group), or engaged in cycloadditions (e.g., tetrazole formation with NaN₃), greatly expanding the structural diversity accessible from this single starting material.

Sequential exploitation of these four handles enables rapid diversification of molecular scaffolds relevant to kinase inhibitors, antibacterials, herbicides, and functional materials.

Handling, Storage, and Safety Guidelines

Although specific GHS hazard classifications for 4-Bromo-2-fluoro-5-nitrobenzonitrile should be confirmed from the product Safety Data Sheet (SDS) supplied with B590597, general precautions for halogenated nitroaromatic nitriles apply:

• Personal Protective Equipment (PPE): Wear chemical-resistant gloves (nitrile or neoprene), laboratory coat, safety goggles, and where dust generation is possible, use a NIOSH-approved respirator. Handle in a fume hood.
• Storage: Store in a tightly sealed container in a cool (2–8 °C or as specified on CoA), dry, well-ventilated area away from direct sunlight, heat sources, oxidizers, and strong bases or nucleophiles that could trigger premature reaction.
• Stability: Nitroaromatic compounds can be sensitive to shock, heat, or friction in large quantities; handle with appropriate caution. At research-reagent scale (milligram to gram quantities), this risk is generally low but should not be disregarded.
• Disposal: Dispose of waste in accordance with local, national, and institutional regulations for halogenated organic waste. Do not pour down the drain.
• First Aid: In case of skin or eye contact, wash thoroughly with water. Seek medical attention if irritation persists. Consult the SDS for full first-aid measures.

Always consult the current SDS document available from Aladdin Scientific before first use of this compound.

Quality Specifications and Ordering Information

Aladdin Scientific supplies 4-Bromo-2-fluoro-5-nitrobenzonitrile under SKU B590597. Researchers and procurement teams should note the following when ordering:

• Purity: Confirm purity grade from the product page or CoA. For synthetic applications in medicinal chemistry, purity ≥97% (HPLC or GC) is generally recommended to minimize side reactions from impurities.
• Available Pack Sizes: Contact Aladdin Scientific or consult the product listing for current pack sizes and pricing. Bulk quantities may be available upon request.
• Certificate of Analysis (CoA): A CoA providing lot-specific data (purity, appearance, NMR/MS confirmation) is available. Request the CoA matching your lot number before use.
• Lead Time: Standard catalog items are typically dispatched promptly; confirm availability and lead time with Aladdin Scientific for time-sensitive projects.
• Export Compliance: Some halogenated and nitro-containing compounds may be subject to export control regulations. Confirm compliance requirements with your institution and Aladdin Scientific prior to international orders.

For technical questions regarding this product, contact the Aladdin Scientific technical support team with your SKU (B590597) and application details.

Frequently asked questions

What is the best solvent for dissolving 4-Bromo-2-fluoro-5-nitrobenzonitrile for SNAr reactions?

Polar aprotic solvents such as DMF, DMSO, or NMP are generally preferred for SNAr reactions involving this compound. They dissolve the substrate well, stabilize the Meisenheimer complex intermediate, and do not compete with the incoming nucleophile. The optimal solvent may vary with the specific nucleophile; always run a small-scale trial before scale-up.

Can the bromo and fluoro groups be selectively functionalized in the same molecule?

Yes, selective functionalization is achievable due to the different intrinsic reactivities of the two leaving groups. The fluorine at C-2 is preferentially reactive in SNAr with nitrogen, oxygen, or sulfur nucleophiles because of the high C–F bond polarity and excellent fluoride leaving-group ability in activated systems. The bromine at C-4, by contrast, is the preferred site for palladium-catalyzed cross-coupling. By careful sequencing—SNAr first at lower temperature, then Pd-coupling—both positions can be differentiated in a single synthetic route. Reaction conditions and nucleophile choice should be optimized for each specific transformation.

How should I reduce the nitro group without affecting the nitrile or halogen substituents?

For selective nitro reduction, transfer hydrogenation conditions or mild chemical reductants such as iron powder in acetic acid or zinc/ammonium chloride in ethanol/water are often preferred over high-pressure catalytic hydrogenation, which can also hydrodehalogenate aryl C–Br bonds. SnCl2·2H2O in ethanol/HCl is another option that is generally compatible with aryl bromides and nitriles. The optimal method depends on the specific substrate and downstream chemistry; the nitrile group is generally stable to these reduction conditions. Always confirm selectivity by monitoring the reaction with TLC or LC-MS.

What purity grade of B590597 is recommended for pharmaceutical intermediate synthesis?

For pharmaceutical intermediate synthesis and medicinal chemistry applications, a purity of ≥97% as determined by HPLC or GC is generally recommended to minimize the impact of impurities on downstream reactions and analytical data. Consult the CoA for your specific lot and contact Aladdin Scientific if higher purity grades are required.

Is 4-Bromo-2-fluoro-5-nitrobenzonitrile stable during long-term storage?

Polyhalogenated nitroaromatic compounds are generally stable when stored under appropriate conditions: sealed, away from light and moisture, in a cool environment. Degradation may occur upon prolonged exposure to moisture, heat, or reactive atmospheres. It is recommended to check for any color change or new impurities by TLC or HPLC before use in sensitive applications. Confirm the specific shelf life and storage conditions from the CoA or contact Aladdin Scientific for guidance.

References

1. March, J. Advanced Organic Chemistry: Reactions, Mechanisms, and Structure. 4th ed. Wiley-Interscience, 1992. (General SNAr reactivity of activated aryl fluorides)
2. Clayden, J.; Greeves, N.; Warren, S. Organic Chemistry. 2nd ed. Oxford University Press, 2012. (Nucleophilic aromatic substitution and cross-coupling reactions)
3. Miyaura, N.; Suzuki, A. Palladium-Catalyzed Cross-Coupling Reactions of Organoboron Compounds. Chemical Reviews, 1995, 95(7), 2457–2483. doi:10.1021/cr00039a007
4. Aladdin Scientific Product Page for B590597, 4-Bromo-2-fluoro-5-nitrobenzonitrile. (Internal reference; exact URL subject to change.)

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