6-Chloro-2-hydroxyquinoline: Handling & Lab Protocol Guide

6-Chloro-2-hydroxyquinoline is a chlorine-substituted quinolinol building block widely employed in medicinal chemistry and organic synthesis as a versatile intermediate for constructing biologically active heterocyclic scaffolds.

CAS Number

4965-33-7

Molecular Formula

C₉H₆ClNO

Molecular Weight

179.60 g/mol

Appearance

White to off-white crystalline solid

Recommended Storage

Store at room temperature in a cool, dry, well-ventilated area away from light

SKU

C132925

Overview and Chemical Properties

6-Chloro-2-hydroxyquinoline (also named 6-chloroquinolin-2(1H)-one in its tautomeric lactam form; CAS 4965-33-7) is a halogenated bicyclic heteroaromatic compound. Its molecular formula is C₉H₆ClNO with a molecular weight of approximately 179.60 g/mol. The compound exists predominantly in the 2-quinolinone (lactam) tautomeric form in the solid state, which influences its reactivity in nucleophilic and electrophilic reactions.

The 6-chloro substituent provides a handle for transition-metal-catalyzed cross-coupling reactions (e.g., Suzuki, Buchwald–Hartwig), while the C-2 carbonyl/hydroxyl functionality can participate in O- or N-alkylation, enabling diverse library synthesis. These dual reactive sites make it a highly valued scaffold in drug discovery programs targeting kinase inhibitors, antimicrobial agents, and fluorescent probes.

Storage, Handling and Safety

Storage: Store 6-Chloro-2-hydroxyquinoline at room temperature (15–25 °C) in a tightly sealed container, away from moisture, direct light, and incompatible materials such as strong oxidizers and strong bases. Shelf life is typically adequate for at least 24 months under proper conditions; verify lot-specific expiry on the Certificate of Analysis (CoA).

Personal Protective Equipment (PPE): Handle in a chemical fume hood. Wear appropriate gloves (nitrile recommended), a lab coat, and safety goggles. Avoid inhalation of dust or aerosols.

Disposal: Dispose of waste material in accordance with local, regional, and national regulations for halogenated organic compounds. Do not discharge into drains or waterways.

Note: Always consult the Safety Data Sheet (SDS) for this product before use. Specific GHS classifications and hazard statements should be verified against the current SDS supplied with SKU C132925.

Dissolution and Solution Preparation Protocol

Recommended solvents: 6-Chloro-2-hydroxyquinoline shows limited solubility in water but dissolves in polar aprotic solvents such as dimethyl sulfoxide (DMSO) and N,N-dimethylformamide (DMF), as well as in ethanol and methanol with gentle warming.

1. Weigh the required amount of compound using an analytical balance in a tared vessel. Work in a fume hood.
2. Add the appropriate solvent (e.g., DMSO for biological assays) in small increments with stirring or brief ultrasonication (30–60 s) until fully dissolved.
3. For stock solutions intended for biological use, prepare at a concentration ≤100 mM in DMSO; dilute into aqueous buffer immediately before use to minimize precipitation. Final DMSO concentration in assay should not exceed 0.1–1% v/v.
4. Filter the solution through a 0.22 µm PTFE syringe filter if particulates are observed.
5. Aliquot the stock solution into amber vials, seal under inert gas (N₂ or Ar) if long-term storage is required, and store at –20 °C.

Flag: Exact solubility values (mg/mL) for this specific compound require experimental verification or literature sourcing; values above are general guidance for quinolinone-class compounds.

Key Synthetic Applications

6-Chloro-2-hydroxyquinoline serves as a multifunctional intermediate in organic synthesis:

• Cross-coupling reactions: The C-6 chloro group undergoes palladium-catalyzed Suzuki–Miyaura coupling with aryl/heteroarylboronic acids, Negishi coupling with organozinc reagents, and Buchwald–Hartwig amination with primary or secondary amines, enabling rapid diversification of the quinoline core.
• O-Alkylation: Treatment with alkyl halides under basic conditions (e.g., K₂CO₃ in DMF) affords 2-alkoxyquinoline derivatives, useful as pharmacophores in medicinal chemistry.
• N-Alkylation: Under appropriate conditions, the lactam nitrogen can be alkylated to yield N-substituted quinolinone products.
• Condensation and cyclization: The compound has been employed in multi-step syntheses of fused polycyclic systems relevant to kinase inhibitor scaffolds and fluorescent dye precursors.

Flag: Specific literature references and reaction yields for these transformations should be cited from primary literature; no specific papers are named in the source material provided.

Quality Control and Verification

Aladdin Scientific supplies 6-Chloro-2-hydroxyquinoline (SKU C132925) with a Certificate of Analysis (CoA) that documents purity, appearance, and analytical data. Researchers are advised to:

• Verify purity by HPLC (≥98% recommended for synthetic applications) and confirm identity by ¹H NMR and/or mass spectrometry against literature or CoA reference spectra.
• Check melting point as a rapid identity confirmation (literature values for this class of compound should be verified against the CoA).
• Inspect the compound visually for color changes or caking before use, which may indicate degradation due to moisture uptake or improper storage.
• For GMP-adjacent or regulated research, retain CoA records and lot numbers for traceability.

Flag: The specific purity grade and exact analytical specifications for SKU C132925 should be confirmed against the current Aladdin CoA. Melting point value not confirmed in source material — needs review.

Frequently asked questions

What is the preferred solvent for dissolving 6-Chloro-2-hydroxyquinoline for biological assays?

DMSO is the most widely used solvent for dissolving quinolinone derivatives for biological assays due to its high solvating power and compatibility with aqueous buffers upon dilution. Prepare a concentrated stock (≤100 mM) in DMSO and dilute into buffer immediately before use, keeping the final DMSO concentration at ≤1% v/v to avoid cytotoxic effects.

Can 6-Chloro-2-hydroxyquinoline be used directly in Suzuki cross-coupling reactions?

Yes, the C-6 chloro substituent on 6-Chloro-2-hydroxyquinoline is reactive toward palladium-catalyzed Suzuki–Miyaura cross-coupling with arylboronic acids under standard conditions (Pd catalyst, base, aqueous co-solvent). However, the C-2 hydroxyl/lactam group may require protection or careful condition optimization to avoid side reactions. Reaction yields and exact conditions should be optimized empirically.

How should I store 6-Chloro-2-hydroxyquinoline to maximize shelf life?

Store the compound in a tightly closed container at room temperature (15–25 °C) in a cool, dry, and well-ventilated area, protected from light and moisture. For long-term archival storage of dissolved stock solutions, seal aliquots in amber vials under inert gas and store at –20 °C. Always check the lot-specific expiry date on the Aladdin Certificate of Analysis.

What is the tautomeric form of 6-Chloro-2-hydroxyquinoline and why does it matter?

6-Chloro-2-hydroxyquinoline exists predominantly in the 2-quinolinone (lactam) tautomeric form in the solid state, meaning the C-2 position bears a carbonyl rather than a hydroxyl group. This tautomerism is important because it affects the compound's reactivity: the lactam form influences whether O- or N-alkylation predominates under given reaction conditions, and researchers must account for this when designing synthetic routes.

References

1. Aladdin Scientific. Certificate of Analysis, 6-Chloro-2-hydroxyquinoline, SKU C132925. Aladdin Scientific Inc.
2. March, J. Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 4th ed. Wiley-Interscience, 1992. (General reference for quinolinone tautomerism and reactivity)
3. Miyaura, N.; Suzuki, A. Palladium-Catalyzed Cross-Coupling Reactions of Organoboron Compounds. Chemical Reviews, 1995, 95(7), 2457–2483. doi:10.1021/cr00039a007

Products are supplied for research and development use only. Not for use in humans, animals, diagnosis, or therapy.