5-Bromo-4-fluoropyridin-2-ol: Properties & Lab FAQs
5-Bromo-4-fluoropyridin-2-ol: Properties & Lab FAQs
5-Bromo-4-fluoropyridin-2-ol is a halogenated heteroaromatic building block bearing both bromo and fluoro substituents on the pyridine ring, making it a versatile intermediate for medicinal chemistry and pharmaceutical synthesis.
- IUPAC Name
- 5-Bromo-4-fluoropyridin-2-ol
- Molecular Formula
- C₅H₃BrFNO
- Functional Groups
- Hydroxypyridine (lactam tautomer), aryl bromide, aryl fluoride
- Primary Application
- Intermediate in pharmaceutical and agrochemical synthesis via cross-coupling and nucleophilic aromatic substitution
- SKU
- B587741
- Tautomeric Form
- Exists predominantly as the 2-pyridinone tautomer in solid state and polar solvents
Chemical Identity and Structure
5-Bromo-4-fluoropyridin-2-ol belongs to the hydroxypyridine family of heteroaromatic compounds. Its pyridine ring carries a hydroxyl group at the 2-position, a fluorine at the 4-position, and a bromine at the 5-position. In solution and solid state, hydroxypyridines typically exist predominantly in the 2-pyridinone (lactam) tautomeric form rather than the enol (hydroxypyridine) form, a consideration relevant to reactivity predictions.
The simultaneous presence of two distinct halogens—bromine and fluorine—on the same ring provides orthogonal handles for sequential functionalization: the C–Br bond is amenable to palladium-catalyzed cross-coupling reactions (Suzuki, Negishi, Buchwald–Hartwig), while the C–F bond can participate in nucleophilic aromatic substitution (SNAr) under appropriate nucleophile and base conditions. The electron-withdrawing fluorine also modulates the ring's electron density, influencing both acidity and reactivity.
Handling, Storage, and Safety
As with most halogenated heteroaromatic compounds, 5-Bromo-4-fluoropyridin-2-ol should be handled using standard laboratory precautions: nitrile or latex gloves, safety glasses, and a lab coat. Operations that generate dust or aerosols should be performed in a fume hood. Consult the product Safety Data Sheet (SDS) for full hazard classification before use.
For storage, the compound should be kept in a tightly sealed container, away from moisture and strong oxidising agents. Storage at room temperature under inert atmosphere (argon or nitrogen) or at 2–8 °C in a desiccated environment is generally recommended for long-term stability of halogenated pyridine building blocks. Specific confirmed storage conditions for this lot should be verified against the Aladdin product certificate of analysis.
Solubility and Reaction Setup
Halogenated hydroxypyridines of this structural type typically show moderate solubility in polar aprotic solvents such as dimethyl sulfoxide (DMSO), N,N-dimethylformamide (DMF), and N-methylpyrrolidinone (NMP), and limited solubility in non-polar solvents such as hexane or diethyl ether. Solubility in water may be low due to the hydrophobic halogen substituents, though the ionisable hydroxyl group can confer some aqueous solubility at elevated pH. Researchers should conduct preliminary solubility tests in their intended solvent system before designing large-scale reaction setups.
For cross-coupling reactions employing the C–Br bond, standard palladium catalyst systems (e.g., Pd(PPh₃)₄, Pd(dppf)Cl₂) in dioxane, toluene, or THF with an appropriate base are typical starting points. For SNAr at the C–F position, strong nucleophiles in polar aprotic solvents at elevated temperature are generally required.
Applications in Medicinal and Synthetic Chemistry
5-Bromo-4-fluoropyridin-2-ol is valued as a multi-functional building block in the synthesis of pharmaceutical candidates and agrochemical compounds. The 2-pyridinone/hydroxypyridine core is a privileged scaffold found in numerous bioactive molecules and approved drugs, conferring hydrogen-bond donor/acceptor capacity and metabolic stability advantages over simple phenol analogues.
The bromo substituent enables Pd-catalysed coupling to introduce aryl, heteroaryl, vinyl, or amino groups, while the fluorine at the 4-position can be displaced by amines, alkoxides, or thiols under SNAr conditions, or retained to provide beneficial pharmacokinetic effects such as improved lipophilicity and metabolic resistance. This dual-handle strategy allows efficient library synthesis in fragment-based drug discovery and lead optimisation campaigns.
Ordering and Quality Information
5-Bromo-4-fluoropyridin-2-ol is available from Aladdin Scientific under SKU B587741. Researchers should request the certificate of analysis (CoA) for the specific lot to verify purity (typically assessed by HPLC or GC), identity (confirmed by NMR or MS), and any additional quality parameters relevant to their application.
For bulk quantities, custom synthesis inquiries, or questions regarding regulatory documentation (e.g., SDS, export compliance), please contact Aladdin Scientific customer service. Volume pricing and institutional procurement options may be available. Ensure that ordering, shipping, and import requirements for brominated and fluorinated organic compounds comply with applicable local regulations.
Frequently asked questions
What tautomeric form does 5-Bromo-4-fluoropyridin-2-ol adopt in solution?
Hydroxypyridines like 5-Bromo-4-fluoropyridin-2-ol predominantly exist in the 2-pyridinone (lactam) tautomeric form in polar solvents and in the solid state, rather than as the enol (hydroxypyridine) tautomer. This tautomeric preference affects hydrogen-bonding behaviour and should be considered when designing reactions or interpreting spectral data. If the specific tautomeric ratio in your solvent system is critical, confirmation by NMR is recommended.
Can I selectively react the C–Br bond without disturbing the C–F bond in 5-Bromo-4-fluoropyridin-2-ol?
Yes, selective functionalization of the C–Br bond is generally achievable using palladium-catalysed cross-coupling reactions (e.g., Suzuki–Miyaura, Negishi, or Buchwald–Hartwig amination) under mild conditions, as C–Br bonds are significantly more reactive toward oxidative addition to Pd(0) than C–F bonds. The C–F bond is largely inert under typical Pd-coupling conditions and can subsequently be engaged in SNAr reactions with appropriate nucleophiles. Careful optimisation of catalyst, base, temperature, and solvent is recommended to maximise selectivity and yield.
What solvents are recommended for dissolving 5-Bromo-4-fluoropyridin-2-ol in the lab?
Based on the structural class, polar aprotic solvents such as DMSO, DMF, and NMP are generally good choices for dissolving 5-Bromo-4-fluoropyridin-2-ol. Solubility in water is expected to be limited, though it may improve under basic aqueous conditions due to deprotonation of the hydroxyl group. Non-polar solvents such as hexane are likely to be poor choices. Researchers should perform a small-scale solubility test in their intended solvent before proceeding with the full reaction setup, and consult the CoA or SDS for any supplier-confirmed solubility data.
How should I store 5-Bromo-4-fluoropyridin-2-ol to maintain its stability?
Store 5-Bromo-4-fluoropyridin-2-ol in a tightly sealed container under dry, inert conditions (argon or nitrogen atmosphere) at room temperature or at 2–8 °C for extended periods. Protect from light, moisture, and strong oxidising agents. Always verify the specific recommended storage conditions on the Aladdin product label or certificate of analysis, as lot-specific recommendations take precedence.
Is 5-Bromo-4-fluoropyridin-2-ol suitable for fragment-based drug discovery (FBDD)?
Yes, 5-Bromo-4-fluoropyridin-2-ol is well-suited as a fragment or building block in FBDD campaigns. Its low molecular weight, the privileged 2-pyridinone scaffold, and the two orthogonal reactive sites (C–Br for coupling, C–F for SNAr) allow rapid elaboration into more complex structures. The fluorine atom also contributes favourably to binding affinity and metabolic stability in lead optimisation. Its dual-handle reactivity makes it particularly useful for parallel synthesis of compound libraries.
References
- Clayden, J.; Greeves, N.; Warren, S. Organic Chemistry, 2nd ed.; Oxford University Press: Oxford, 2012. General principles of halogenated heterocycles and tautomerism.
- 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
- Fier, P. S.; Hartwig, J. F. Selective C-F Reductive Elimination from a Nickel(II) Complex. Science 2013, 342, 956–960. (General reference on C-F bond reactivity in SNAr context.) doi:10.1126/science.1243759
- Aladdin Scientific Product Page: 5-Bromo-4-fluoropyridin-2-ol, SKU B587741. Internal reference BD01193596.
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