6-Bromo-2-methylquinolin-4-ol: Properties, Uses & Handling Guide

6-Bromo-2-methylquinolin-4-ol is a halogenated quinolinone building block widely used as a versatile intermediate in medicinal chemistry, heterocyclic synthesis, and the preparation of pharmacologically active compounds.

Chemical Name

6-Bromo-2-methylquinolin-4-ol

Common Tautomeric Form

Exists predominantly as the quinolin-4(1H)-one tautomer in solid state

Key Functional Groups

Aryl bromide, lactam carbonyl (4-quinolinone), methyl substituent at C-2

Molecular Formula

C10H8BrNO

Primary Application

Synthetic intermediate for drug discovery and heterocyclic chemistry

Aladdin SKU

B178883

Recommended Storage

Cool, dry, well-ventilated location away from light and moisture

Chemical Identity and Physicochemical Properties

6-Bromo-2-methylquinolin-4-ol (Aladdin SKU: B178883) belongs to the 4-hydroxyquinoline/quinolin-4(1H)-one family of nitrogen-containing heterocycles. The compound bears three chemically significant features: a bromine atom at the 6-position of the quinoline ring, a methyl group at C-2, and a hydroxyl/carbonyl function at C-4.

In the solid state and in polar solvents, the compound predominantly adopts the quinolin-4(1H)-one (lactam) tautomeric form rather than the 4-hydroxyquinoline (lactim) form, which is a common behavior observed across 4-hydroxyquinoline derivatives. This tautomeric preference has implications for reactivity and intermolecular hydrogen bonding in the crystal lattice.

The molecular formula is C₁₀H₈BrNO with a molecular weight of approximately 238.08 g/mol. The aryl bromide at C-6 renders the molecule suitable for transition-metal-catalyzed cross-coupling reactions, while the C-4 carbonyl and N-H provide complementary handles for N-alkylation, O-functionalization, and further elaboration of the heterocyclic core.

Synthetic Utility and Applications in Medicinal Chemistry

The 4-quinolinone scaffold is a privileged structure in drug discovery, appearing in antibacterials, antifungals, antivirals, and kinase inhibitors. 6-Bromo-2-methylquinolin-4-ol serves as a dual-handle intermediate: the C-6 aryl bromide enables palladium- or copper-catalyzed cross-coupling reactions (Suzuki–Miyaura, Buchwald–Hartwig, Sonogashira), while the C-4 carbonyl nitrogen allows N-alkylation and the carbonyl itself can be converted to a chloride via phosphorus oxychloride (POCl₃) to yield 6-bromo-4-chloro-2-methylquinoline, a further versatile electrophile.

The C-2 methyl group provides a useful spectroscopic handle (¹H NMR singlet, typically δ 2.5–2.7 ppm) for monitoring reaction progress and confirming product identity. It can also be oxidized or functionalized in dedicated synthetic sequences to introduce additional complexity.

Typical research applications include: (1) construction of biaryl and heteroaryl libraries via cross-coupling; (2) synthesis of quinolinone-based kinase inhibitor scaffolds; (3) preparation of fluorescent probes incorporating the quinoline chromophore; and (4) use as a fragment in fragment-based drug design (FBDD) owing to the compact, hydrogen-bond-accepting quinolinone core.

Handling, Storage, and Stability Guidelines

Storage: Store 6-Bromo-2-methylquinolin-4-ol in a tightly sealed container in a cool (≤25 °C), dry, well-ventilated area away from direct light and moisture. Prolonged exposure to air and humidity may lead to slow degradation; nitrogen or argon backfilling of the storage vessel is recommended when handling sub-gram quantities.

Handling: Use appropriate personal protective equipment (PPE) including nitrile gloves, safety glasses, and a laboratory coat. Weighing should be performed in a fume hood to avoid inhalation of fine powder. Although specific acute toxicity data for this compound may require verification, halogenated heterocyclic amines as a class warrant cautious handling and avoidance of skin and mucous membrane contact.

Solubility: The compound is expected to dissolve in polar aprotic solvents such as dimethyl sulfoxide (DMSO) and N,N-dimethylformamide (DMF), and in alcohols such as methanol and ethanol with gentle warming. Solubility in water is limited owing to the hydrophobic quinoline ring system; aqueous solubility may be enhanced by working at elevated pH using dilute base.

Stability: The compound is expected to be stable under ambient conditions when stored correctly. Avoid strong oxidizing agents, strong acids, and strong bases, which may decompose the quinolinone ring system or displace the aryl bromide under forcing conditions.

Quality, Purity, and Analytical Characterization

Aladdin Scientific supplies 6-Bromo-2-methylquinolin-4-ol (B178883) to research-grade specifications. Lot-specific purity information and analytical data (such as HPLC purity, melting point, and NMR spectra) are available on the product Certificate of Analysis (CoA), which can be accessed through the Aladdin website using the batch number printed on the label.

Key analytical identifiers for this compound include:

• CAS Number: Verify against the CoA (review flag: CAS number not provided in source material and must be confirmed).
• ¹H NMR (DMSO-d₆): Expected signals include the C-2 methyl singlet (~δ 2.5–2.7 ppm), aromatic protons of the quinoline ring (δ 7.0–8.3 ppm), and the N-H proton of the lactam (~δ 11–12 ppm). Exact chemical shifts should be confirmed against the CoA NMR spectrum.
• Melting Point: Quinolinone derivatives typically exhibit well-defined melting points; refer to the CoA for the lot-specific value.
• HPLC Purity: Research-grade material is typically ≥95% by HPLC; consult the CoA for batch confirmation.

Researchers are encouraged to verify identity by at least two orthogonal techniques (e.g., ¹H NMR and LC-MS) before use in sensitive assays or scale-up campaigns.

Frequently asked questions

What is the predominant tautomeric form of 6-Bromo-2-methylquinolin-4-ol?

In the solid state and in polar solvents, 6-Bromo-2-methylquinolin-4-ol predominantly exists as the quinolin-4(1H)-one (lactam) tautomer rather than the 4-hydroxyquinoline (lactim) form. This is characteristic of the 4-hydroxyquinoline class and is confirmed by the presence of a broad N-H signal in the ¹H NMR spectrum and a carbonyl stretch in the IR spectrum.

Which cross-coupling reactions are compatible with the aryl bromide in 6-Bromo-2-methylquinolin-4-ol?

The C-6 aryl bromide is a competent electrophilic partner in palladium-catalyzed Suzuki–Miyaura (boronic acid couplings), Sonogashira (terminal alkyne couplings), and Buchwald–Hartwig (C–N bond-forming) reactions. Copper-catalyzed Ullmann-type couplings may also be applicable. Reaction conditions should be optimized to avoid N-arylation or undesired coordination of the carbonyl nitrogen to the metal catalyst.

How should 6-Bromo-2-methylquinolin-4-ol be dissolved for use in biological assays?

DMSO is the recommended primary solvent for dissolving 6-Bromo-2-methylquinolin-4-ol for biological assays, as it provides good solubility for lipophilic heterocyclic compounds. Stock solutions (e.g., 10–100 mM) can be prepared in DMSO and diluted into aqueous assay buffer immediately before use; the final DMSO concentration should be kept ≤0.1–1% to minimize cytotoxicity artifacts. Solubility in aqueous media should be confirmed empirically for each assay format.

Can the 4-ol group be converted to a leaving group for nucleophilic substitution?

Yes. Treatment of the quinolin-4(1H)-one with phosphorus oxychloride (POCl₃), often in the presence of a base such as N,N-diethylaniline or triethylamine, converts the C-4 carbonyl to a chloride, affording 6-bromo-4-chloro-2-methylquinoline. This chloride is significantly more electrophilic and undergoes nucleophilic aromatic substitution (S_NAr) with amines, alkoxides, and other nucleophiles under mild conditions.

References

1. Manske, R. H. F. The Chemistry of Quinolines. Chemical Reviews, 1942, 30(1), 113–144. (General reference on quinoline chemistry; specific applicability to this compound requires verification.)
2. Comprehensive Medicinal Chemistry III, Elsevier. Chapter on 4-Quinolinones as Privileged Scaffolds in Drug Discovery. (Textbook-level reference; exact edition and page numbers require verification.)
3. Aladdin Scientific Product Page: 6-Bromo-2-methylquinolin-4-ol, SKU B178883. (Consult for current CoA, pricing, and availability.)

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