5-Chloro-2-methylquinoline: Handling, Storage & Lab Protocol

5-Chloro-2-methylquinoline is a halogenated heterocyclic building block widely employed in medicinal and synthetic chemistry for the construction of quinoline-based scaffolds via cross-coupling, nucleophilic substitution, and condensation reactions.

CAS Number

4964-71-0

Molecular Formula

C₁₀H₈ClN

Molecular Weight

177.63 g/mol

Appearance

Off-white to pale yellow crystalline solid

Recommended Storage

Room temperature, sealed, away from light and moisture

Key Functional Groups

C-5 chloro substituent, C-2 methyl group, quinoline ring nitrogen

SKU

C193572

Chemical Identity & Properties

5-Chloro-2-methylquinoline (CAS 4964-71-0) is a bicyclic aromatic heterocycle consisting of a benzene ring fused to a pyridine ring. The chlorine atom at position 5 and the methyl group at position 2 impart distinct electronic and steric properties that make this compound a versatile intermediate in synthetic and medicinal chemistry.

The compound has a molecular formula of C₁₀H₈ClN and a molecular weight of approximately 177.63 g/mol. It typically presents as an off-white to pale yellow crystalline solid at room temperature. The presence of the electron-withdrawing chlorine at C-5 activates the ring toward nucleophilic aromatic substitution, while the methyl group at C-2 can be functionalized via benzylic oxidation or halogenation. The ring nitrogen provides a handle for coordination chemistry and salt formation.

Solubility guidance (textbook-level): Quinoline derivatives of this class are generally soluble in common organic solvents such as dichloromethane (DCM), ethyl acetate, tetrahydrofuran (THF), dimethyl sulfoxide (DMSO), and dimethylformamide (DMF). Aqueous solubility is low under neutral conditions but may increase upon protonation with dilute acid.

Safety & Regulatory Considerations

As with most halogenated heterocyclic compounds, 5-Chloro-2-methylquinoline should be treated as a potential irritant. Users must consult the current Safety Data Sheet (SDS) provided by Aladdin Scientific (SKU C193572) before use. The following general precautions apply:

• Personal Protective Equipment (PPE): Wear appropriate chemical-resistant gloves (e.g., nitrile), safety goggles, and a lab coat. Work in a well-ventilated fume hood.
• Inhalation hazard: Avoid generating dust or aerosols. Fine powders of aromatic heterocycles can be harmful if inhaled.
• Skin and eye contact: Rinse immediately with copious water for at least 15 minutes if contact occurs; seek medical attention as appropriate.
• Waste disposal: Dispose of in accordance with local regulations governing halogenated organic waste. Do not pour down the drain.

Note: Specific GHS hazard classifications and pictograms must be verified from the current SDS for C193572. Flag for review.

Step-by-Step Handling & Dissolution Protocol

Follow these steps to prepare a stock solution or working aliquot of 5-Chloro-2-methylquinoline for downstream synthetic use.

1. Equilibrate to room temperature: Allow the sealed vial of C193572 to equilibrate to ambient temperature before opening to prevent moisture condensation on the cold solid.
2. Weigh accurately: Tare a clean, dry glass vial or weighing boat. Transfer the required amount of compound using a clean stainless-steel or plastic spatula. Record the exact mass.
3. Prepare stock solution: Transfer the weighed solid to a suitable glass vial. Add the chosen solvent (DMSO or DCM recommended for most synthetic applications) in a quantity calculated to achieve the desired concentration. For example, to prepare a 100 mM stock: dissolve 17.8 mg in 1.0 mL DMSO.
4. Dissolve: Cap the vial and mix gently by vortex or magnetic stirring at room temperature. If dissolution is incomplete, brief gentle warming (not exceeding 40 °C) may be applied. Avoid prolonged heating.
5. Filter if necessary: Pass the solution through a 0.2 µm PTFE syringe filter to remove particulates before use in sensitive applications.
6. Aliquot and store: Divide the stock solution into single-use aliquots to minimize freeze-thaw cycles. Label clearly with compound name, SKU, concentration, solvent, date, and preparer initials.

Concentration calculation reminder: C (mM) = [mass (mg) / MW (g/mol)] × [1000 / volume (mL)]

Storage Conditions & Stability

Proper storage of 5-Chloro-2-methylquinoline is essential to maintain compound integrity over time.

• Bulk solid: Store at room temperature in a tightly sealed container, protected from light, heat, and atmospheric moisture. A desiccant (silica gel) is recommended for long-term storage, particularly in humid laboratory environments.
• Stock solutions: DMSO or DCM solutions should be stored at –20 °C in sealed, inert-atmosphere vials where long-term stability is required. Allow frozen aliquots to thaw completely and mix before use.
• Compatibility: Avoid storage in containers with reactive metals or strong oxidizing agents. The chloro substituent is stable under normal storage conditions but may be susceptible to nucleophilic displacement under forcing conditions.
• Shelf life: The shelf life of C193572 is indicated on the Certificate of Analysis (CoA). Verify purity by HPLC or TLC if the compound has been stored for an extended period before use in critical experiments.

Note: Specific stability data for this compound are not provided in the source material. Stability claims should be verified against the CoA and SDS for C193572.

Applications in Synthetic & Medicinal Chemistry

5-Chloro-2-methylquinoline serves as a versatile building block in multiple synthetic strategies:

• Cross-coupling reactions: The C-5 C–Cl bond can participate in palladium-catalyzed cross-coupling reactions (e.g., Suzuki-Miyaura, Buchwald-Hartwig) to introduce aryl, heteroaryl, or amine substituents, enabling rapid diversification of the quinoline scaffold.
• Nucleophilic aromatic substitution (SNAr): The electron-deficient ring, activated by both the ring nitrogen and the chloro group, may undergo SNAr with suitable nucleophiles such as amines, alkoxides, or thiols under appropriate conditions.
• Methyl group functionalization: The benzylic methyl at C-2 can be oxidized to an aldehyde or carboxylic acid, or halogenated to afford reactive benzyl halide intermediates for further elaboration.
• Medicinal chemistry: Quinoline-based compounds are well-recognized pharmacophores appearing in antibacterial, antimalarial, antiviral, and kinase-inhibitor drug candidates. The 5-chloro-2-methyl substitution pattern may be exploited to optimize potency and selectivity in lead optimization campaigns.
• Coordination chemistry: The quinoline nitrogen can act as a ligand in metal-complex formation relevant to catalysis and materials science.

Note: Specific literature references for each application are not available in the source material and have been omitted to avoid fabrication. Please conduct a primary literature search (SciFinder, Reaxys) to identify specific precedents.

Frequently asked questions

What solvents are recommended for dissolving 5-Chloro-2-methylquinoline?

5-Chloro-2-methylquinoline is generally soluble in polar aprotic organic solvents such as DMSO, DMF, and THF, as well as in chlorinated solvents such as DCM. Aqueous solubility is low at neutral pH. For biological assay use, DMSO stock solutions are most commonly employed, and the final DMSO concentration in assay medium should be kept ≤0.1% to minimize interference.

How should 5-Chloro-2-methylquinoline (C193572) be stored to maintain purity?

The bulk solid should be stored at room temperature in a tightly sealed container, away from light and moisture. A desiccant such as silica gel is recommended for humid environments. Prepared stock solutions are best stored at –20 °C in sealed vials under an inert atmosphere, divided into single-use aliquots to avoid repeated freeze-thaw cycles. Verify purity by HPLC or TLC before use in critical experiments if the material has been stored for an extended period.

Can 5-Chloro-2-methylquinoline undergo palladium-catalyzed cross-coupling reactions?

Yes, the C–Cl bond at position 5 of the quinoline ring can in principle serve as an electrophilic coupling partner in palladium-catalyzed reactions such as Suzuki-Miyaura coupling with boronic acids or Buchwald-Hartwig amination. However, the reactivity of aryl chlorides in cross-coupling is generally lower than that of aryl bromides or iodides, and optimized catalyst systems (e.g., Pd with bulky phosphine ligands) are typically required. Specific reaction conditions should be identified from primary literature.

What personal protective equipment is required when handling this compound?

At minimum, users should wear chemical-resistant gloves (nitrile recommended), safety goggles, and a laboratory coat. All weighing and solution preparation steps should be performed inside a ventilated fume hood to prevent inhalation of dust or solvent vapors. Refer to the current SDS for C193572 from Aladdin Scientific for the full GHS hazard classification and any additional required precautions.

How do I calculate the volume of solvent needed to prepare a specific molar concentration of C193572?

Use the formula: Volume (mL) = [Mass (mg) / (MW × Target concentration (mM))]. For 5-Chloro-2-methylquinoline, MW = 177.63 g/mol. For example, to prepare a 50 mM solution from 10 mg of compound: Volume = 10 / (177.63 × 0.05) ≈ 1.13 mL of solvent. Always verify the MW from the Certificate of Analysis supplied with your specific lot.

References

1. Aladdin Scientific. Product page and Certificate of Analysis for 5-Chloro-2-methylquinoline, SKU C193572. Aladdin Scientific Corp.
2. March, J. Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 4th ed. Wiley-Interscience, 1992. (General reference for nucleophilic aromatic substitution and cross-coupling reactions of haloarenes.)
3. Clayden, J.; Greeves, N.; Warren, S. Organic Chemistry, 2nd ed. Oxford University Press, 2012. (General reference for heterocyclic chemistry, quinoline reactivity, and benzylic functionalization.)

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