3-Chloro-4-fluoropyridine: Properties, Uses & FAQs
3-Chloro-4-fluoropyridine: Properties, Uses & FAQs
3-Chloro-4-fluoropyridine is a halogenated pyridine building block widely used as a versatile intermediate in the synthesis of pharmaceuticals, agrochemicals, and specialty fine chemicals.
- Chemical Name
- 3-Chloro-4-fluoropyridine
- SKU / Catalog Number
- C1369404
- Molecular Formula
- C₅H₃ClFN
- Molecular Weight
- 131.54 g/mol
- CAS Number
- 101491-93-4
- Compound Class
- Halogenated heterocyclic aromatic compound
- Primary Application
- Pharmaceutical and agrochemical intermediate
Chemical Identity and Structure
3-Chloro-4-fluoropyridine (CAS 101491-93-4, SKU C1369404) is a dihalogenated pyridine derivative bearing a chlorine substituent at the 3-position and a fluorine substituent at the 4-position of the pyridine ring. Its molecular formula is C₅H₃ClFN, with a molecular weight of approximately 131.54 g/mol. The compound is an electron-deficient heteroaromatic system owing to both the ring nitrogen and the two halogen substituents, making it highly reactive toward nucleophilic aromatic substitution (SNAr) reactions. The differential reactivity of the C–Cl and C–F bonds allows selective functionalization, a property that is especially valuable in medicinal chemistry and materials science.
The compound is typically encountered as a colorless to pale-yellow liquid or low-melting solid at room temperature. Its physicochemical properties—including boiling point, melting point, and solubility—should be confirmed against the Certificate of Analysis (CoA) supplied with each lot from Aladdin Scientific.
Synthesis and Reactivity
3-Chloro-4-fluoropyridine can be prepared through several routes, including the Balz–Schiemann reaction starting from the corresponding aminopyridine, halogen-exchange (halex) fluorination of 3,4-dichloropyridine under forcing conditions, or directed metalation strategies followed by electrophilic halogenation. In industrial and laboratory settings, the halex approach—treating a chloropyridine precursor with a fluoride source such as KF in a polar aprotic solvent—is commonly employed, though reaction conditions vary.
In downstream synthesis, 3-Chloro-4-fluoropyridine participates readily in palladium-catalyzed cross-coupling reactions (e.g., Suzuki, Buchwald–Hartwig, and Negishi couplings) via the C–Cl bond, while the C–F bond is amenable to SNAr displacement with amines, alkoxides, and thiolates. This dual-handle reactivity makes it a privileged scaffold for library synthesis and lead optimization in drug discovery programs.
Applications in Research and Industry
The principal applications of 3-Chloro-4-fluoropyridine span pharmaceutical intermediate synthesis, agrochemical development, and materials chemistry. In medicinal chemistry, fluorinated and chlorinated pyridines are frequently incorporated into drug candidates to improve metabolic stability, membrane permeability, and binding affinity. The fluorine atom at the 4-position can modulate the pKa of adjacent functional groups and enhance lipophilicity in a controlled manner.
In the agrochemical sector, halopyridines serve as key building blocks for herbicides, fungicides, and insecticides. 3-Chloro-4-fluoropyridine is used to introduce the pyridine core into active ingredient structures, contributing to the selectivity and potency of crop-protection molecules. Additionally, researchers working on coordination chemistry and functional materials use electron-deficient pyridines as ligand components or precursors to more complex heterocyclic systems.
Handling, Storage, and Safety
As with all halogenated aromatic compounds, 3-Chloro-4-fluoropyridine should be handled with appropriate personal protective equipment (PPE), including chemical-resistant gloves, safety glasses, and a lab coat. Operations generating vapors or aerosols should be performed in a well-ventilated fume hood. The compound should be kept away from strong oxidizers, strong bases, and moisture unless the reaction specifically requires these conditions.
For storage, the material should be kept in a tightly sealed container in a cool, dry, and well-ventilated area, away from direct sunlight and incompatible materials. Recommended storage temperature and specific hazard classifications should be confirmed from the Safety Data Sheet (SDS) and the CoA provided by Aladdin Scientific for lot C1369404. Users should consult local regulations for disposal of halogenated organic waste.
Ordering and Quality Information
3-Chloro-4-fluoropyridine is available from Aladdin Scientific under SKU C1369404. Researchers and procurement teams can place orders directly through the Aladdin Scientific website or by contacting customer service. Purity specifications and analytical data (including NMR, GC, or HPLC traces as applicable) are detailed on the product page and the accompanying CoA for each production lot.
For bulk inquiries, custom packaging, or questions regarding regulatory documentation (e.g., export compliance, REACH), please contact Aladdin Scientific's sales team. Lot-specific CoAs and SDS documents can be downloaded from the product page using the lot number printed on the label. If a specific purity grade or packaging format is required for your application, Aladdin Scientific's technical support team can advise on available options.
Frequently asked questions
What is the CAS number of 3-Chloro-4-fluoropyridine?
The CAS registry number for 3-Chloro-4-fluoropyridine is 101491-93-4. Aladdin Scientific supplies this compound under catalog number C1369404. Always verify the CAS number against the product label and CoA upon receipt.
What purity grade is available for 3-Chloro-4-fluoropyridine (C1369404)?
Purity specifications for SKU C1369404 are detailed on the Aladdin Scientific product page and the lot-specific Certificate of Analysis. We recommend downloading the current CoA from the website or contacting customer service to confirm the purity grade that meets your application requirements.
What solvents are compatible with 3-Chloro-4-fluoropyridine?
3-Chloro-4-fluoropyridine is generally soluble in common organic solvents such as dichloromethane, THF, acetonitrile, DMF, and DMSO. It has limited solubility in water due to its lipophilic character. Solubility should be verified experimentally under your specific conditions, as lot-to-lot and concentration-dependent variations may occur.
How should 3-Chloro-4-fluoropyridine be stored?
The compound should be stored in a tightly sealed container in a cool, dry, and well-ventilated location, protected from light and moisture. Refer to the Aladdin Scientific SDS for C1369404 for the exact recommended storage temperature and hazard classification applicable to your jurisdiction.
Can 3-Chloro-4-fluoropyridine undergo selective cross-coupling at the C–Cl bond?
Yes. The C–Cl bond in 3-Chloro-4-fluoropyridine is generally more reactive than the C–F bond toward palladium-catalyzed cross-coupling reactions (e.g., Suzuki–Miyaura, Negishi, Buchwald–Hartwig). This selectivity allows the fluorine substituent to be retained for subsequent SNAr functionalization or as a pharmacophoric element in the final compound. Reaction conditions should be optimized for each specific coupling partner.
How do I request a Safety Data Sheet (SDS) or Certificate of Analysis (CoA) for C1369404?
SDS and lot-specific CoA documents for 3-Chloro-4-fluoropyridine (C1369404) can be downloaded directly from the product page on the Aladdin Scientific website using your batch/lot number. If you require additional documentation or cannot locate the document online, please contact Aladdin Scientific customer service for assistance.
References
- March, J.; Smith, M. B. March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 7th ed.; Wiley: Hoboken, NJ, 2013. (General reference for SNAr and cross-coupling reactions of halogenated heterocycles.)
- Chambers, R. D. Fluorine in Organic Chemistry; Blackwell: Oxford, 2004. (Reference for halex fluorination and properties of fluorinated pyridines.)
- Aladdin Scientific. Product page: 3-Chloro-4-fluoropyridine, SKU C1369404. https://www.aladdin-e.com (accessed 2024).
Products are supplied for research and development use only. Not for use in humans, animals, diagnosis, or therapy.
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