5-Chloro-3-fluoropyridin-2-ol: Properties & Applications
5-Chloro-3-fluoropyridin-2-ol: Properties & Applications
5-Chloro-3-fluoropyridin-2-ol is a halogen-substituted hydroxypyridine that serves as a versatile heterocyclic building block in pharmaceutical synthesis, agrochemical research, and materials science.
- IUPAC Name
- 5-Chloro-3-fluoropyridin-2-ol
- Molecular Formula
- C₅H₃ClFNO
- Molecular Weight
- 147.54 g/mol
- Compound Class
- Halogenated hydroxypyridine (fluorochloropyridinol)
- Primary Use
- Synthetic intermediate and building block in medicinal and agrochemical chemistry
- Aladdin SKU
- C193684
Chemical Structure and Key Properties
5-Chloro-3-fluoropyridin-2-ol belongs to the class of halogenated hydroxypyridines, featuring a pyridine ring bearing a hydroxyl group at position 2, a fluorine atom at position 3, and a chlorine atom at position 5. This specific substitution pattern creates a molecule that can exist in tautomeric equilibrium between its pyridinol (hydroxy) and pyridinone (keto) forms, a common characteristic of 2-hydroxypyridines.
The presence of both fluorine and chlorine substituents profoundly influences the electronic distribution of the aromatic ring. Fluorine, being the most electronegative element, exerts a strong inductive withdrawal effect while simultaneously donating electron density through resonance, whereas chlorine acts primarily as an electron-withdrawing substituent by induction. Together, these halogens modulate ring reactivity, acidity of the hydroxyl group, and intermolecular interactions such as hydrogen bonding, making the compound an electronically tunable scaffold for downstream functionalization.
The molecular formula is C₅H₃ClFNO with a molecular weight of approximately 147.54 g/mol. Researchers should handle this compound following appropriate laboratory safety protocols, consulting the relevant Safety Data Sheet (SDS) before use.
Role as a Synthetic Building Block
Halogenated pyridinols such as 5-Chloro-3-fluoropyridin-2-ol are highly valued in synthetic chemistry because their multiple reactive sites allow selective and sequential functionalization. The hydroxyl (or carbonyl in the pyridinone tautomer) group can participate in O-alkylation, O-acylation, or conversion to triflates, providing handles for further elaboration. Meanwhile, the ring-bound chlorine at position 5 is amenable to nucleophilic aromatic substitution (SNAr) or palladium-catalyzed cross-coupling reactions such as Suzuki-Miyaura, Buchwald-Hartwig, and Negishi couplings, given the activation provided by adjacent electron-withdrawing groups.
The fluorine substituent at position 3, while generally less reactive toward substitution than chlorine under typical SNAr conditions, serves as a bioisosteric element that modulates physicochemical properties of derived target molecules, including lipophilicity (logP), metabolic stability, and membrane permeability — all critical parameters in drug discovery and optimization workflows.
This combination of features makes 5-Chloro-3-fluoropyridin-2-ol a practical and versatile intermediate for constructing more complex heterocyclic frameworks used in active pharmaceutical ingredient (API) synthesis and crop-protection compound development.
Applications in Medicinal and Agrochemical Research
In medicinal chemistry, fluorinated and chlorinated pyridine scaffolds are ubiquitous in approved drugs and clinical candidates targeting a wide range of biological pathways. The pyridinol/pyridinone core can mimic amide bond geometry, engage in hydrogen bonding with biological targets, and improve aqueous solubility compared to purely carbocyclic analogs. Researchers exploit 5-Chloro-3-fluoropyridin-2-ol to introduce a pre-functionalized, biologically compatible nitrogen-containing ring into lead compounds during hit-to-lead and lead optimization phases.
In agrochemical research, halogenated pyridines have a strong track record as core structures in fungicides, herbicides, and insecticides. The electron-withdrawing character of the combined halogens enhances binding affinity to agricultural target proteins, and the inherent metabolic stability of the C–F bond can be advantageous for field performance and residue profiles.
Beyond pharmaceuticals and agrochemicals, this compound finds utility in materials science and specialty chemical synthesis, where its reactive sites enable incorporation into functional polymers, ligands for transition-metal catalysis, and optoelectronic materials requiring nitrogen-heterocycle motifs.
Handling, Storage, and Quality Considerations
As with all halogenated heterocyclic reagents, 5-Chloro-3-fluoropyridin-2-ol should be handled with standard laboratory precautions. Personnel should wear appropriate personal protective equipment (PPE) including gloves, safety glasses, and a lab coat. Operations generating dust or aerosol should be performed in a well-ventilated fume hood. The full Safety Data Sheet (SDS) for SKU C193684 should be consulted prior to first use and kept accessible in the laboratory.
For storage, the compound should be kept in a tightly sealed container away from moisture, heat, and incompatible materials (strong oxidizers, strong bases). Storage under cool, dry conditions, as specified on the product label, helps maintain compound integrity over time. Aladdin Scientific provides purity specifications and analytical data (such as NMR and HPLC) with each lot to support reproducibility in research applications.
Researchers performing sensitive coupling reactions or those requiring high-purity material for biological assays should verify lot-specific purity certificates available from Aladdin Scientific upon request. Proper documentation of reagent lot numbers supports GLP-compliant experimental records.
Frequently asked questions
What tautomeric forms does 5-Chloro-3-fluoropyridin-2-ol exist in?
5-Chloro-3-fluoropyridin-2-ol can exist in equilibrium between a pyridinol (2-hydroxypyridine) tautomer and a pyridinone (2-pyridinone) tautomer, where a proton shifts between the ring nitrogen and the oxygen. The dominant form in solution or the solid state depends on solvent polarity, concentration, and temperature. This tautomerism can influence reactivity and should be considered when designing synthetic routes.
Which cross-coupling reactions are compatible with 5-Chloro-3-fluoropyridin-2-ol?
The C–Cl bond at position 5 of the pyridine ring is well-suited for palladium-catalyzed cross-coupling reactions, including Suzuki-Miyaura (with boronic acids/esters), Negishi (with organozinc reagents), and Buchwald-Hartwig amination (with amines), owing to activation by the adjacent electron-withdrawing nitrogen and halogen substituents. The hydroxyl group may require protection as an ether or triflate depending on reaction conditions. The C–F bond at position 3 is generally more resistant to substitution under standard palladium catalysis but can participate in selective SNAr with reactive nucleophiles under appropriate conditions.
How should I store 5-Chloro-3-fluoropyridin-2-ol to maintain its stability?
Store 5-Chloro-3-fluoropyridin-2-ol in a tightly sealed container under cool, dry conditions, away from moisture, direct light, strong oxidizing agents, and strong bases. Always refer to the product label and the SDS for SKU C193684 for the specific recommended storage temperature and any additional precautions. Checking the certificate of analysis for each lot ensures the compound meets purity specifications before use.
Is 5-Chloro-3-fluoropyridin-2-ol used in pharmaceutical research?
Yes, 5-Chloro-3-fluoropyridin-2-ol is employed as a building block in pharmaceutical research, where its halogenated pyridinol scaffold provides multiple sites for selective functionalization. The fluorine substituent acts as a bioisostere that can improve metabolic stability, membrane permeability, and binding interactions of derived drug candidates. It is particularly useful in hit-to-lead and lead optimization programs targeting a variety of biological pathways.
References
- Clayden, J.; Greeves, N.; Warren, S. Organic Chemistry, 2nd ed.; Oxford University Press: Oxford, 2012. (General reference for nucleophilic aromatic substitution and heterocyclic chemistry.)
- Müller, K.; Faeh, C.; Diederich, F. Fluorine in pharmaceuticals: looking beyond intuition. Science 2007, 317, 1881–1886. doi:10.1126/science.1145820
- Aladdin Scientific product page for 5-Chloro-3-fluoropyridin-2-ol, SKU C193684. (Accessed via Aladdin Scientific internal catalog.)
Products are supplied for research and development use only. Not for use in humans, animals, diagnosis, or therapy.
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