3-Chloro-2-methylquinoline: Properties, Handling & Lab Use Guide

3-Chloro-2-methylquinoline is a halogenated quinoline heterocycle widely employed as a versatile synthetic intermediate in medicinal chemistry, agrochemical research, and the preparation of biologically active nitrogen-containing compounds.

CAS Number

4964-71-0

Molecular Formula

C₁₀H₈ClN

Molecular Weight

177.63 g/mol

Appearance

Off-white to pale yellow crystalline solid

Key Functional Groups

Chloro substituent at C-3; methyl substituent at C-2 of the quinoline ring

Primary Application

Synthetic intermediate for pharmaceuticals and agrochemicals

Chemical Properties and Structure

3-Chloro-2-methylquinoline (CAS 4964-71-0) is a bicyclic aromatic heterocycle belonging to the quinoline family. Its structure consists of a benzene ring fused to a pyridine ring, with a chlorine atom at position 3 and a methyl group at position 2. The molecular formula is C₁₀H₈ClN with a molecular weight of approximately 177.63 g/mol.

The electron-withdrawing chlorine at C-3 and the electron-donating methyl at C-2 create a distinct electronic environment on the quinoline ring, making this compound highly reactive toward nucleophilic aromatic substitution (SNAr) and transition-metal-catalyzed cross-coupling reactions such as Suzuki, Buchwald-Hartwig, and Negishi couplings. These reactivity patterns underpin its broad utility as a building block in organic synthesis.

The compound is typically isolated as an off-white to pale yellow crystalline solid and is sparingly soluble in water but readily soluble in common organic solvents including dichloromethane, chloroform, ethyl acetate, and dimethyl sulfoxide (DMSO).

Synthetic Applications and Research Use

3-Chloro-2-methylquinoline serves as a key building block in multiple synthetic strategies. The C-3 chloro group is susceptible to displacement by nitrogen, oxygen, sulfur, and carbon nucleophiles, enabling efficient access to 3-substituted quinoline libraries. This reactivity makes it indispensable in the preparation of pharmacologically relevant scaffolds including antimalarial, antibacterial, anticancer, and anti-inflammatory quinoline derivatives.

In transition-metal-catalyzed reactions, the C–Cl bond participates in palladium-catalyzed cross-coupling (e.g., Suzuki-Miyaura, Negishi, and Sonogashira couplings) to introduce aryl, vinyl, alkyl, or alkynyl groups at C-3, greatly expanding structural diversity. The C-2 methyl group can also be functionalized through benzylic bromination or oxidation to introduce additional handles for further elaboration.

Beyond medicinal chemistry, the compound finds use in materials science research, particularly in the synthesis of quinoline-based fluorescent probes, ligands for metal complexes, and pi-conjugated materials relevant to organic electronics.

Safe Handling, Storage, and Disposal

Personal Protective Equipment (PPE): When handling 3-Chloro-2-methylquinoline, wear appropriate PPE including nitrile gloves, a laboratory coat, and safety goggles. Where dust or aerosols may be generated, use a NIOSH-approved respirator or work inside a fume hood to minimise inhalation exposure.

Storage: Store the compound in a tightly sealed container in a cool, dry, well-ventilated area, away from strong oxidising agents, strong bases, and ignition sources. A storage temperature of 2–8 °C is recommended to preserve purity and prevent decomposition over extended periods. Always confirm specific storage recommendations on the product Certificate of Analysis (CoA).

Spill Management: In the event of a spill, contain the material with inert absorbent (e.g., vermiculite or dry sand), collect into a labelled waste container, and clean the affected area with water. Avoid generating dust.

Disposal: Dispose of this compound and contaminated materials in accordance with applicable local, regional, and national regulations for chemical waste. Do not pour down the drain. Consult your institution's Environmental Health and Safety (EHS) office for guidance.

Quality, Purity, and Analytical Verification

For research applications, the purity of 3-Chloro-2-methylquinoline is critical to ensuring reproducible experimental outcomes. Aladdin Scientific supplies this compound with a Certificate of Analysis (CoA) that documents lot-specific purity data typically determined by high-performance liquid chromatography (HPLC) or gas chromatography (GC).

Researchers should verify identity and purity upon receipt using standard analytical techniques: ¹H NMR and ¹³C NMR spectroscopy confirm structural integrity; GC-MS or LC-MS provides molecular weight confirmation and detects trace impurities; melting point determination offers a rapid purity check against literature reference values.

When using this compound as a synthetic starting material, high purity (≥97%) is recommended to avoid interference from structurally similar quinoline by-products that may co-elute or co-react under standard conditions. Always consult the CoA provided with each lot and contact Aladdin Scientific's technical support team if purity specifications do not meet application requirements.

Frequently asked questions

What reactions is 3-Chloro-2-methylquinoline commonly used for in organic synthesis?

3-Chloro-2-methylquinoline is primarily used in nucleophilic aromatic substitution (SNAr) reactions and palladium-catalyzed cross-coupling reactions, including Suzuki-Miyaura, Negishi, Buchwald-Hartwig, and Sonogashira couplings, to install diverse substituents at the C-3 position. The C-2 methyl group can also be functionalized via benzylic bromination or oxidation.

What are the recommended storage conditions for 3-Chloro-2-methylquinoline?

Store 3-Chloro-2-methylquinoline in a tightly sealed container at 2–8 °C in a cool, dry, well-ventilated area, away from strong oxidising agents, strong bases, and ignition sources. Always refer to the lot-specific Certificate of Analysis for confirmed storage instructions.

What purity grade should I select for use as a synthetic starting material?

For synthetic applications, a purity of ≥97% (as determined by GC or HPLC) is generally recommended to minimise the impact of structurally similar quinoline impurities on reaction outcomes and product isolation. Contact Aladdin Scientific technical support if your application demands higher purity specifications.

Is 3-Chloro-2-methylquinoline soluble in common laboratory solvents?

Yes. 3-Chloro-2-methylquinoline is sparingly soluble in water but dissolves readily in common organic solvents such as dichloromethane, chloroform, ethyl acetate, and DMSO. For reactions requiring aqueous conditions, co-solvent systems or phase-transfer conditions may be employed.

How should I verify the identity and purity of the compound upon receipt?

Upon receipt, confirm identity using ¹H NMR and ¹³C NMR spectroscopy and verify the molecular weight by GC-MS or LC-MS. A melting point determination can provide a rapid orthogonal purity check. Compare all data against the lot Certificate of Analysis supplied by Aladdin Scientific.

References

1. March, J. Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 4th ed.; Wiley-Interscience: New York, 1992.
2. Clayden, J.; Greeves, N.; Warren, S. Organic Chemistry, 2nd ed.; Oxford University Press: Oxford, 2012.
3. Eicher, T.; Hauptmann, S.; Speicher, A. The Chemistry of Heterocycles: Structures, Reactions, Synthesis, and Applications, 3rd ed.; Wiley-VCH: Weinheim, 2012.
4. Aladdin Scientific. Product Certificate of Analysis for 3-Chloro-2-methylquinoline, SKU C697794. Aladdin Scientific Corp.

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