4-Bromo-3,5-Difluorobenzonitrile: Properties, Uses & Handling
4-Bromo-3,5-Difluorobenzonitrile: Properties, Uses & Handling
4-Bromo-3,5-difluorobenzonitrile is a halogenated, fluorinated aromatic nitrile that serves as a versatile electrophilic building block for pharmaceutical synthesis, agrochemical research, and transition-metal-catalyzed cross-coupling chemistry.
- Chemical Name
- 4-Bromo-3,5-difluorobenzonitrile
- CAS Number
- Needs review — not confirmed in source material
- Molecular Formula
- C7H2BrF2N
- Molecular Weight
- Needs review — not confirmed in source material
- SKU / Product Code
- B586730
- Key Functional Groups
- Nitrile (–CN), bromo (–Br), two fluoro (–F) substituents on a benzene ring
- Primary Application
- Electrophilic building block in palladium- and copper-catalyzed cross-coupling reactions and nucleophilic aromatic substitution
Chemical Identity and Physical Properties
4-Bromo-3,5-difluorobenzonitrile (Aladdin SKU B586730) is an aromatic compound bearing three electronegative substituents on the benzene ring: a cyano group at the 4-position and fluorine atoms at the 3- and 5-positions, with bromine also at the 4-position relative to each fluorine. The molecular formula is C7H2BrF2N. The combined electron-withdrawing effects of the nitrile and two ortho-fluorine atoms create a highly electron-deficient aromatic ring, which profoundly influences both its reactivity and its utility as a synthetic intermediate.
The compound is typically presented as a white to off-white crystalline solid at room temperature. Specific melting point, boiling point, density, and exact CAS number should be confirmed against the Certificate of Analysis (CoA) supplied with each lot and are subject to review (see review flags).
Synthetic Applications and Reactivity
The three-pronged electronic activation of 4-Bromo-3,5-difluorobenzonitrile makes it an exceptionally reactive electrophile in several key reaction classes:
- Palladium-catalyzed cross-coupling: The C–Br bond is well-suited for Suzuki–Miyaura, Negishi, Stille, and Buchwald–Hartwig coupling reactions, enabling the introduction of aryl, vinyl, amino, and alkyl groups at the 4-position while retaining the fluorine and nitrile handles for further functionalization.
- Nucleophilic Aromatic Substitution (SNAr): The flanking fluorine atoms at the 3- and 5-positions are activated toward SNAr by the combined electron-withdrawing power of the neighboring bromo group and the para-nitrile. Amines, alkoxides, and thiolates can displace fluorine under mild conditions, providing rapid access to diversely substituted aniline and ether scaffolds.
- Nitrile transformations: The –CN group can be hydrolyzed to a carboxylic acid, reduced to an amine, or converted to heterocycles such as tetrazoles and imidazoles, expanding the scaffold diversity accessible from a single starting material.
These orthogonal reactive handles make 4-Bromo-3,5-difluorobenzonitrile a privileged fragment in medicinal chemistry programs targeting kinase inhibitors, GPCR modulators, and other small-molecule therapeutics.
Safe Handling, Storage, and Waste Disposal
Personal Protective Equipment (PPE): Handle 4-Bromo-3,5-difluorobenzonitrile in a well-ventilated fume hood. Wear chemical-resistant gloves (nitrile recommended), a laboratory coat, and safety goggles. Avoid inhalation of dust or vapors.
Storage: Store in a tightly sealed container in a cool, dry, well-ventilated area away from moisture, heat sources, and incompatible oxidizing agents. Refer to the supplier Safety Data Sheet (SDS) for specific temperature recommendations. Confirm storage temperature requirements from the product-specific SDS (subject to review).
Stability: The compound is expected to be stable under recommended storage conditions; however, prolonged exposure to moisture may lead to slow hydrolysis of the nitrile group. Keep the container sealed when not in use.
Waste Disposal: Dispose of this compound and contaminated materials in accordance with local, regional, and national regulations governing halogenated organic waste. Do not pour down the drain. Consult your institution's 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 and seek medical attention. If inhaled, move to fresh air. Consult the SDS for complete first-aid measures.
Quality, Purity, and Ordering Information
Aladdin Scientific supplies 4-Bromo-3,5-difluorobenzonitrile under SKU B586730. Each lot is accompanied by a Certificate of Analysis (CoA) documenting purity (typically assessed by GC or HPLC), appearance, and other specification data. Researchers are encouraged to verify purity by NMR or HPLC upon receipt for critical synthetic applications.
Purity grade, exact specifications, available pack sizes, and pricing are confirmed at the time of purchase. Contact Aladdin Scientific's technical support team for bulk quantities, custom purity grades, or additional characterization data. For procurement, updated pricing and availability information can be found on the Aladdin Scientific product page or by contacting your regional account manager.
Frequently asked questions
What makes 4-Bromo-3,5-difluorobenzonitrile useful in medicinal chemistry?
The compound carries three orthogonal reactive sites — a C–Br bond for palladium-catalyzed cross-coupling, two activated C–F bonds for SNAr reactions, and a nitrile group amenable to further transformation — on a single electron-deficient aromatic ring. This versatility allows chemists to build complex, drug-like molecules efficiently from a single starting material.
Can the fluorine atoms in 4-Bromo-3,5-difluorobenzonitrile be selectively displaced?
Yes. The fluorine atoms at the 3- and 5-positions are activated toward nucleophilic aromatic substitution by the combined electron-withdrawing effect of the cyano group and the bromine substituent. With appropriate nucleophiles (e.g., amines, alkoxides) and reaction conditions, selective mono- or bis-substitution can often be achieved, though selectivity will depend on stoichiometry, temperature, and the nucleophile used. Specific selectivity data should be verified in primary literature.
How should I store 4-Bromo-3,5-difluorobenzonitrile to maintain its quality?
Store the compound in a tightly sealed container in a cool, dry location away from moisture and oxidizing agents. Refer to the Safety Data Sheet and Certificate of Analysis supplied with your lot for specific temperature and humidity recommendations. Minimize repeated freeze-thaw cycles and exposure to ambient air to prevent potential hydrolysis of the nitrile group.
Is 4-Bromo-3,5-difluorobenzonitrile suitable for Suzuki–Miyaura coupling?
Yes, the aryl bromide functionality in 4-Bromo-3,5-difluorobenzonitrile is well-suited for Suzuki–Miyaura coupling with aryl- and alkenylboronic acids under standard palladium catalysis conditions. The electron-deficient ring can facilitate oxidative addition. Optimum catalyst, base, solvent, and temperature conditions should be determined empirically or by reference to published protocols for analogous substrates.
References
- Aladdin Scientific Product Page: 4-Bromo-3,5-difluorobenzonitrile, SKU B586730.
- General reference: Clayden, J.; Greeves, N.; Warren, S. Organic Chemistry, 2nd ed.; Oxford University Press: Oxford, 2012. (Nucleophilic aromatic substitution and cross-coupling chapters.)
- General reference: Johansson Seechurn, C. C. C.; Kitching, M. O.; Colacot, T. J.; Snieckus, V. Palladium-catalyzed cross-coupling: a historical contextual perspective to the 2010 Nobel Prize. Angew. Chem. Int. Ed. 2012, 51, 5062–5085. doi:10.1002/anie.201107017
Products are supplied for research and development use only. Not for use in humans, animals, diagnosis, or therapy.
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