5-Bromo-3-chloro-2-hydroxypyridine: Properties & Lab FAQ

5-Bromo-3-chloro-2-hydroxypyridine is a halogenated pyridine derivative widely used as a versatile building block in pharmaceutical synthesis, agrochemical research, and heterocyclic chemistry due to its reactive halogen substituents and tautomeric hydroxyl/carbonyl functionality.

CAS Number

7368-77-6

Molecular Formula

C₅H₃BrClNO

Molecular Weight

208.44 g/mol

Appearance

White to off-white solid

Key Functional Groups

Bromine (C5), Chlorine (C3), Hydroxypyridine/Pyridinone (C2)

Aladdin SKU

B185358

What Is 5-Bromo-3-chloro-2-hydroxypyridine?

5-Bromo-3-chloro-2-hydroxypyridine (CAS 7368-77-6) is a dihalogenated pyridine bearing a hydroxyl group at the 2-position, bromine at the 5-position, and chlorine at the 3-position. In the solid state and in polar solvents it predominantly exists in the pyridinone tautomeric form (2-pyridinone), which significantly influences its reactivity and hydrogen-bonding capacity.

This compound serves as a key building block in medicinal chemistry and materials science. Its two distinct halogens — bromine and chlorine — offer orthogonal handles for selective cross-coupling reactions (e.g., Suzuki, Negishi, Buchwald–Hartwig), enabling the stepwise construction of complex heterocyclic scaffolds. The carbonyl/hydroxyl moiety further provides opportunities for O-alkylation, N-alkylation, and condensation reactions.

How Should 5-Bromo-3-chloro-2-hydroxypyridine Be Stored and Handled?

Store 5-Bromo-3-chloro-2-hydroxypyridine in a tightly sealed container in a cool, dry, and well-ventilated area, away from heat sources, moisture, and incompatible materials such as strong oxidizers and strong bases. Recommended storage temperature is typically 2–8 °C or room temperature under inert atmosphere; consult the specific lot Certificate of Analysis for confirmed storage conditions.

When handling this compound, wear appropriate personal protective equipment (PPE) including chemical-resistant gloves, safety glasses, and a lab coat. Work in a fume hood to avoid inhalation of dust or vapors. As with all organohalogen compounds, wash hands thoroughly after handling and dispose of waste in accordance with local regulations for halogenated organic waste.

What Are the Primary Synthetic Applications?

5-Bromo-3-chloro-2-hydroxypyridine is principally employed as an advanced intermediate in the synthesis of bioactive molecules. The orthogonal reactivity of its C–Br and C–Cl bonds allows chemists to perform sequential, chemoselective palladium- or nickel-catalyzed cross-coupling reactions. The C–Br bond is typically more reactive toward oxidative addition, allowing selective functionalization at C5 first, followed by transformation at C3.

Common transformations include: (1) Suzuki–Miyaura coupling to introduce aryl or heteroaryl groups; (2) Buchwald–Hartwig amination for C–N bond formation; (3) O-alkylation or O-arylation of the hydroxyl/pyridinone nitrogen to tune pharmacokinetic properties; and (4) use as a ligand precursor or coordination chemistry substrate. These features make it valuable in the discovery of kinase inhibitors, antimicrobials, and other pharmacologically relevant compound classes.

Purity, Grade, and Quality Specifications

Aladdin Scientific supplies 5-Bromo-3-chloro-2-hydroxypyridine (SKU: B185358) for research use. Each production lot is accompanied by a Certificate of Analysis (CoA) specifying purity (typically assessed by HPLC or GC), appearance, and identity confirmation by NMR or MS. Researchers requiring high purity for sensitive applications — such as asymmetric catalysis or biological assays — should review the CoA prior to use and contact Aladdin Scientific if custom purity grades are needed.

For procurement and specification inquiries, including bulk quantities and custom packaging, please contact the Aladdin Scientific sales team. Purity and specification data listed on the product page are representative; always refer to the lot-specific CoA for definitive values.

Troubleshooting Common Issues in Laboratory Use

Low coupling yield: Ensure the compound is fully dissolved before addition to the reaction mixture. Use dry, degassed solvents (e.g., anhydrous DMF, THF, or dioxane) for palladium-catalyzed reactions. Moisture and oxygen are common causes of catalyst poisoning and reduced yield.

Discoloration or degradation: If the solid appears darker than described in the CoA, it may have absorbed moisture or undergone partial decomposition. Re-dry under vacuum over P₂O₅ or molecular sieves if possible, and verify identity by TLC or NMR before use in critical experiments.

Solubility issues: The compound is generally soluble in polar aprotic solvents (DMSO, DMF) and moderately soluble in ethanol and acetone. Aqueous solubility is limited due to the hydrophobic aromatic ring. Sonication or gentle warming may improve dissolution; avoid prolonged heating above 60 °C.

Frequently asked questions

What is the difference between the hydroxypyridine and pyridinone tautomers, and which form predominates?

5-Bromo-3-chloro-2-hydroxypyridine can exist as either the 2-hydroxypyridine (enol) or the 2-pyridinone (keto) tautomer. In polar solvents and the solid state, the pyridinone (lactam) form generally predominates due to its greater thermodynamic stability and favorable intermolecular hydrogen bonding. This tautomeric equilibrium can influence reactivity, particularly in N- versus O-alkylation reactions, and should be considered when designing synthetic routes.

Can I perform selective cross-coupling at C5 (bromo) without reacting the C3 (chloro) position?

Yes. The C–Br bond at C5 is intrinsically more reactive toward oxidative addition with palladium(0) catalysts compared to the C–Cl bond at C3. By carefully selecting catalyst systems and reaction conditions (e.g., Pd(PPh₃)₄ or Pd(dppf)Cl₂ at mild temperatures), it is generally possible to achieve selective monosubstitution at C5. Subsequent functionalization of C3 can then be accomplished using more reactive nickel catalysts or more forcing palladium conditions. Optimization of temperature, ligand, and base is recommended for each specific substrate.

What solvents are recommended for dissolving 5-Bromo-3-chloro-2-hydroxypyridine?

This compound dissolves well in polar aprotic solvents such as DMSO and DMF, and shows moderate solubility in ethanol, acetone, and ethyl acetate. Aqueous solubility is low. For NMR characterization, DMSO-d₆ is commonly used. Always prepare fresh solutions for sensitive reactions and store stock solutions under inert atmosphere to minimize decomposition.

Is 5-Bromo-3-chloro-2-hydroxypyridine available in bulk quantities from Aladdin Scientific?

Yes. Aladdin Scientific (SKU: B185358) offers this compound for research use and can accommodate inquiries for larger quantities. Contact the Aladdin Scientific sales or customer service team directly to discuss bulk pricing, custom packaging, and lead times.

What safety precautions are required when working with this compound?

As an organohalogen compound, 5-Bromo-3-chloro-2-hydroxypyridine should be handled with standard laboratory precautions: use chemical-resistant gloves, safety glasses, and a lab coat; work in a well-ventilated fume hood to avoid inhalation of dust or aerosols. Avoid contact with eyes, skin, and clothing. Consult the Safety Data Sheet (SDS) for full hazard classification, first-aid measures, and disposal requirements before use.

References

1. Clayden, J.; Greeves, N.; Warren, S. Organic Chemistry, 2nd ed.; Oxford University Press: Oxford, 2012. (General reference for tautomerism and cross-coupling reactions)
2. Joule, J. A.; Mills, K. Heterocyclic Chemistry, 5th ed.; Wiley-Blackwell: Oxford, 2010. (Reference for hydroxypyridine/pyridinone tautomerism and reactivity)
3. Miyaura, N.; Suzuki, A. Palladium-Catalyzed Cross-Coupling Reactions of Organoboron Compounds. Chem. Rev. 1995, 95, 2457–2483. doi:10.1021/cr00039a007

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