What Is 4-Bromo-6-(trifluoromethyl)quinoline?

4-Bromo-6-(trifluoromethyl)quinoline is a difunctionalized quinoline heterocycle featuring a bromine atom at the 4-position and a trifluoromethyl (–CF₃) group at the 6-position of the quinoline ring system. The quinoline scaffold is a bicyclic aromatic nitrogen heterocycle consisting of a benzene ring fused to a pyridine ring, and it is one of the most pharmacologically relevant ring systems in drug discovery.

The combination of the C-4 bromo substituent — an excellent leaving group for metal-catalyzed coupling reactions — and the strongly electron-withdrawing –CF₃ group creates a compound with tunable electronic properties and high synthetic utility. The trifluoromethyl group also confers improved metabolic stability, lipophilicity, and membrane permeability on derived molecules, properties that are highly valued in lead optimization campaigns in pharmaceutical research.

Chemical Properties and Structure

The molecular formula of 4-Bromo-6-(trifluoromethyl)quinoline is C₁₀H₅BrF₃N, with an approximate molecular weight of 276.05 g/mol (to be verified against the product specification sheet). The compound is a solid at room temperature and typically appears as a white to off-white crystalline powder.

Electronically, the –CF₃ group at C-6 strongly withdraws electron density from the ring via inductive and field effects, activating the C-4 position toward nucleophilic aromatic substitution as well as toward oxidative addition by low-valent palladium and nickel catalysts. This dual reactivity — susceptibility to S_NAr and to cross-coupling — makes the compound exceptionally flexible for parallel library synthesis and scaffold decoration.

The quinoline nitrogen atom can participate in coordination chemistry and protonation reactions, and its basicity is modulated downward by the flanking electron-withdrawing groups, affecting solubility profiles of salts formed during synthesis.

Synthetic Applications and Reaction Types

4-Bromo-6-(trifluoromethyl)quinoline serves as a versatile electrophilic partner in a wide range of transition-metal-catalyzed transformations. Key reaction types include:

• Suzuki–Miyaura coupling: Reaction with aryl- or heteroarylboronic acids under palladium catalysis to install diverse (hetero)aryl substituents at C-4.
• Buchwald–Hartwig amination: Palladium-catalyzed C–N bond formation with primary and secondary amines, enabling rapid access to 4-aminoquinoline scaffolds relevant to antimalarial and kinase-inhibitor pharmacophores.
• Negishi and Kumada couplings: Use of organozinc or organomagnesium nucleophiles to introduce alkyl or aryl groups.
• Nucleophilic aromatic substitution (S_NAr): The activated C-4 position can undergo direct displacement by nitrogen, oxygen, or sulfur nucleophiles without a metal catalyst, especially under forcing conditions.

These transformations make 4-Bromo-6-(trifluoromethyl)quinoline a high-value building block for generating compound libraries targeting kinase inhibition, antimicrobial activity, and other therapeutic areas. Specific literature references for these transformations should be verified independently.

Handling, Safety, and Storage

As with all halogenated aromatic compounds, 4-Bromo-6-(trifluoromethyl)quinoline should be handled with appropriate laboratory precautions. Users should consult the product Safety Data Sheet (SDS) for confirmed hazard classifications, GHS pictograms, and first-aid measures before use.

General handling guidelines include:

• Use in a well-ventilated fume hood.
• Wear appropriate personal protective equipment (PPE): nitrile gloves, safety glasses, and a laboratory coat.
• Avoid inhalation of dust or vapors.
• Store in a tightly sealed container in a cool, dry location away from moisture, heat, and incompatible materials such as strong bases and strong oxidizers.

Waste disposal must comply with local institutional and governmental regulations for halogenated organic waste. Confirmed GHS classification and specific hazard data are available on the Aladdin Scientific product page for SKU B729431 and must be reviewed prior to use.

Ordering and Availability from Aladdin Scientific

4-Bromo-6-(trifluoromethyl)quinoline is available from Aladdin Scientific under SKU B729431. Researchers can place orders directly through the Aladdin Scientific website. For bulk quantities, custom packaging, or certificate of analysis (CoA) requests, please contact the Aladdin Scientific sales or technical support team.

When placing an order, ensure you have the correct SKU (B729431) to avoid confusion with structurally related quinoline analogs. Purity specifications, batch-specific CoA documents, and SDS files are available upon request or via the product page. Lead times and stock availability may vary; contact your regional Aladdin representative for current inventory status.