1. Product Overview
6-Bromo-2,4-dichloroquinoline (CAS: 406204-90-8) is a polyhalogenated quinoline derivative with the molecular formula C₉H₄BrCl₂N and a molecular weight of 276.95 g/mol. This compound features a quinoline bicyclic core substituted with bromine at the 6-position and chlorine atoms at the 2- and 4-positions. As a fully halogenated quinoline, it contains no hydrogen-bond donor groups (zero H-bond donors, one H-bond acceptor from the ring nitrogen), conferring high lipophilicity and making it an excellent electrophile for nucleophilic aromatic substitution (SNAr) and transition-metal-catalyzed cross-coupling reactions.
The orthogonal halogen reactivity—where the 2- and 4-chlorines are typically more labile toward nucleophiles, while the 6-bromine is preferentially active in Pd-catalyzed couplings—enables sequential and regioselective functionalization. This makes 6-bromo-2,4-dichloroquinoline a strategically important building block in medicinal chemistry for assembling quinoline-based bioactive molecules, particularly kinase inhibitors, antiparasitic agents, and antimicrobial compounds.
2. Key Features and Advantages
• Orthogonal Halogen Reactivity: The 2-Cl and 4-Cl are susceptible to nucleophilic displacement (amines, alkoxides, thiols), while the 6-Br is ideal for Suzuki, Sonogashira, and Buchwald–Hartwig cross-couplings, supporting stepwise scaffold elaboration.
• Quinoline Privileged Scaffold: The quinoline core is a cornerstone in drug discovery, appearing in approved drugs (chloroquine, mefloquine, quinine analogues) and numerous clinical candidates targeting cancer, malaria, and bacterial infections.
• High Lipophilicity & Membrane Permeability: Zero H-bond donors and high calculated Log P (~3.9) make derived compounds suitable for CNS penetration and oral bioavailability optimization.
• High Purity Grade: Typically supplied at ≥98% purity (HPLC), meeting rigorous standards for pharmaceutical R&D and SAR studies.
• Stable Solid Form: White to off-white solid with good stability under recommended cool, dry, inert-atmosphere storage.
• Scalable Supply: Available from 100 mg screening quantities up to kilogram scale for process development and pilot campaigns.
3. Main Applications
3.1 Pharmaceutical Intermediate & Drug Discovery
This compound is a key intermediate for constructing quinoline-based drug candidates:
• Antimalarial & Antiparasitic Agents: The 2,4-dichloroquinoline motif is central to 4-aminoquinoline antimalarials; sequential substitution at C4 (with amines) and C2, plus cross-coupling at C6, enables next-generation antimalarial and antitrypanosomal libraries.
• Kinase Inhibitors: Quinolines are widely used in ATP-competitive kinase inhibitors (e.g., VEGFR, EGFR, CDK programmes); the 6-bromo handle introduces aryl/heteroaryl groups to tune potency and selectivity.
• Antimicrobial & Antifungal Agents: Employed in synthesizing 4-aminoquinoline and 2-chloroquinoline derivatives with activity against resistant bacteria and fungi.
3.2 Medicinal Chemistry & Library Synthesis
• The C4-chlorine is most electrophilic and is typically displaced first by primary/secondary amines to install the canonical 4-aminoquinoline pharmacophore.
• The C2-chlorine can then be substituted by alkoxides, thiols, or a second amine to generate 2,4-disubstituted patterns.
• The C6-bromine remains intact through these steps and is used in a final Pd-catalyzed cross-coupling to append diverse aryl/alkynyl fragments for SAR exploration.
• Ideal for parallel synthesis of focused quinoline libraries targeting HTS follow-up and lead optimization.
3.3 Organic Synthesis & Material Science
• Serves as a model substrate for studying regioselective SNAr on dichloroquinolines and for developing new Pd-catalyzed C–Br functionalization methods.
• Quinoline derivatives are also explored in organic electronics (fluorescent probes, OLED materials) where halogenated precursors enable controlled functionalization.
4. Technical Specifications
5. Storage and Handling
Storage Conditions
• Store in a cool, dry place at 2–8 °C.
• Keep container tightly sealed under inert atmosphere (argon or nitrogen) to prevent slow hydrolysis of the chloro groups under humid conditions and to avoid oxidative discoloration.
• Protect from light; use amber vials or foil wrapping.
• Store away from strong bases (risk of SNAr hydrolysis), strong nucleophiles, and moisture.
• For long-term storage (>6 months), maintain under inert gas with desiccant (silica gel or molecular sieves).
Handling Precautions
• Handle in a well-ventilated area or fume hood to avoid inhalation of fine dust.
• Avoid contact with skin, eyes, and clothing. Polyhalogenated aromatics should be handled with care to prevent thermal decomposition releasing HBr/HCl.
• Use appropriate PPE as detailed in Section 6.
6. Safety Overview
Hazard Identification
• GHS Classification (typical supplier SDS): GHS07, Signal Word: Warning.
• Hazard Statements: H302 (Harmful if swallowed), H315 (Causes skin irritation), H319 (Causes serious eye irritation), H332 (Harmful if inhaled), H335 (May cause respiratory irritation).
• Intended strictly for industrial and scientific research use; not for human or veterinary therapeutic use, not for food, feed, or cosmetic application.
• Polyhalogenated quinolines should be handled as potentially hazardous organic halides; avoid generating dust or aerosols.
First Aid Measures
• Inhalation: Move to fresh air. Seek medical attention if coughing, wheezing, or irritation persists.
• Skin Contact: Remove contaminated clothing. Rinse affected area thoroughly with soap and water.
• Eye Contact: Rinse immediately with plenty of running water for at least 15 minutes, holding eyelids open. Consult an ophthalmologist if irritation continues.
• Ingestion: Rinse mouth. Do NOT induce vomiting. Seek immediate medical attention.
Personal Protective Equipment (PPE)
• Eye/Face Protection: Safety goggles or face shield.
• Hand Protection: Nitrile chemical-resistant gloves.
• Body Protection: Lab coat, long sleeves, closed-toe shoes.
• Respiratory Protection: NIOSH-approved dust mask or particulate respirator if handling generates airborne particles.
Disposal Considerations
• Dispose of as hazardous chemical waste per local, regional, and national regulations.
• Do not discard in drains or release into the environment.
• Incinerate in a licensed chemical waste facility.
