2-Chloro-6-methylpyridine: Properties, Uses & FAQs

2-Chloro-6-methylpyridine is a halogenated pyridine building block widely employed in pharmaceutical, agrochemical, and fine-chemical synthesis owing to its dual reactive sites—the electrophilic C-2 chloro substituent and the nucleophilically activatable methyl group at C-6.

CAS Number

18368-64-4

Molecular Formula

C₆H₆ClN

Molecular Weight

127.57 g/mol

Appearance

Colorless to pale yellow liquid

Boiling Point

approximately 175–177 °C (reported; verify against CoA)

Primary Application

Pharmaceutical and agrochemical intermediate; cross-coupling partner

Aladdin SKU

C124344

Chemical Identity and Physical Properties

2-Chloro-6-methylpyridine (also called 2-chloro-6-picoline) is a six-membered nitrogen-containing heteroaromatic compound bearing a chlorine atom at the 2-position and a methyl group at the 6-position of the pyridine ring. Its molecular formula is C₆H₆ClN with a molecular weight of 127.57 g/mol and CAS registry number 18368-64-4.

At room temperature the compound is typically a colorless to pale yellow liquid or low-melting solid. It is sparingly soluble in water but miscible with common organic solvents such as dichloromethane, ethyl acetate, tetrahydrofuran, and toluene. The electron-withdrawing pyridine nitrogen activates the ring toward nucleophilic aromatic substitution (S_NAr), particularly at C-2 bearing the chloro leaving group.

Note: Exact boiling point, density, refractive index, and purity specifications should be confirmed against the current Aladdin Certificate of Analysis (CoA) for lot C124344.

Reactivity and Synthetic Applications

The compound offers two orthogonal handles for chemical elaboration, making it a versatile building block in medicinal and process chemistry:

• Nucleophilic Aromatic Substitution (S_NAr): The C-2 chloride is readily displaced by amines, alkoxides, thiolates, and other nucleophiles under mild conditions, yielding 2-amino-, 2-alkoxy-, or 2-thio-6-methylpyridine derivatives.
• Transition-Metal-Catalyzed Cross-Coupling: The C–Cl bond participates in palladium- or nickel-catalyzed Suzuki–Miyaura, Buchwald–Hartwig, and Negishi coupling reactions to install aryl, heteroaryl, or amino groups.
• Benzylic Functionalization: The methyl group at C-6 is activated toward radical bromination (e.g., NBS/AIBN), oxidation to an aldehyde or carboxylic acid, or deprotonation with strong bases to generate a stabilized benzylic carbanion for further alkylation.
• Directed Metalation: The nitrogen atom can direct ortho-lithiation sequences for further functionalization of the ring.

These attributes underpin the use of 2-chloro-6-methylpyridine as a key intermediate in the preparation of active pharmaceutical ingredients (APIs), crop-protection compounds, and ligands for catalysis.

Storage, Handling, and Safety

Storage: Store in a tightly sealed container in a cool, dry, well-ventilated area away from heat sources, oxidizers, and incompatible materials. Refrigerated storage (2–8 °C) is commonly recommended for prolonged shelf life; confirm with the Aladdin product page or CoA.

Handling Precautions: 2-Chloro-6-methylpyridine should be handled with appropriate personal protective equipment (PPE), including nitrile gloves, safety glasses, and a lab coat. Work in a fume hood to avoid inhalation of vapors. The compound may be irritating to skin, eyes, and the respiratory tract.

Regulatory and Safety Data: Consult the current Safety Data Sheet (SDS) provided by Aladdin Scientific for GHS hazard classification, first-aid measures, fire-fighting information, and disposal guidance. Specific GHS pictograms, H-statements, and P-statements should be verified against the SDS for lot C124344, as classifications can vary by supplier and jurisdiction.

Waste Disposal: Dispose of waste material in accordance with local, regional, and national regulations governing halogenated organic solvents and intermediates.

Quality Specifications and Ordering Information

Aladdin Scientific offers 2-Chloro-6-methylpyridine under SKU C124344. Each lot is accompanied by a Certificate of Analysis (CoA) detailing purity (typically assessed by GC or HPLC), appearance, and key physical constants.

Researchers requiring high-purity material for sensitive catalysis or API synthesis should request the CoA before use and may wish to perform additional quality checks such as NMR spectroscopy or Karl Fischer titration (for moisture content).

For bulk quantities, custom packaging, or regulatory documentation (e.g., country-of-origin certificates), please contact Aladdin Scientific customer service. Volume pricing may be available; consult the promotions and pricing section of the Aladdin website or speak with a technical sales representative.

Frequently asked questions

What is 2-Chloro-6-methylpyridine used for in synthesis?

2-Chloro-6-methylpyridine is primarily used as a versatile heterocyclic building block in pharmaceutical and agrochemical synthesis. The C-2 chloro group undergoes nucleophilic aromatic substitution and transition-metal-catalyzed cross-coupling reactions, while the C-6 methyl group can be functionalized via benzylic bromination, oxidation, or deprotonation. Together, these reactive sites allow rapid construction of complex pyridine-containing scaffolds.

How should 2-Chloro-6-methylpyridine be stored to maintain its stability?

The compound should be stored in a tightly sealed container in a cool, dry, and well-ventilated location, away from heat, light, and incompatible reagents such as strong oxidizers. Refrigerated storage at 2–8 °C is typically recommended to maximize shelf life. Always consult the current Aladdin CoA and SDS for lot-specific storage conditions.

Is 2-Chloro-6-methylpyridine suitable for palladium-catalyzed cross-coupling reactions?

Yes, aryl and heteroaryl chlorides bearing electron-withdrawing groups—such as the ring nitrogen in pyridines—are generally competent partners in palladium-catalyzed Suzuki–Miyaura, Negishi, and Buchwald–Hartwig reactions, often requiring slightly more active catalyst systems (e.g., bulky phosphine ligands) compared with aryl bromides or iodides. Reaction conditions should be optimized empirically, and the specific catalyst, ligand, base, and solvent system should be selected based on the desired transformation.

What purity grade of 2-Chloro-6-methylpyridine does Aladdin Scientific supply?

Aladdin Scientific supplies 2-Chloro-6-methylpyridine under SKU C124344; purity and grade specifications are detailed in the lot-specific Certificate of Analysis (CoA) available on the product page. Customers with stringent purity requirements are encouraged to review the CoA or contact Aladdin customer service for further analytical data.

Can the methyl group of 2-Chloro-6-methylpyridine be selectively oxidized without affecting the C-Cl bond?

Selective benzylic oxidation of the methyl group to an aldehyde or carboxylic acid is feasible using appropriate oxidants (e.g., SeO₂ for aldehyde, KMnO₄ or CrO₃-based reagents for carboxylic acid formation) under controlled conditions. However, selectivity and yield are highly dependent on reagent choice and reaction conditions; preliminary optimization and literature precedent should be consulted before scale-up.

References

1. Clayden, J.; Greeves, N.; Warren, S. Organic Chemistry, 2nd ed.; Oxford University Press: Oxford, 2012. (General reference for nucleophilic aromatic substitution and cross-coupling reactions.)
2. Negishi, E. Handbook of Organopalladium Chemistry for Organic Synthesis; Wiley-Interscience: New York, 2002. (Reference for palladium-catalyzed cross-coupling of heteroaryl chlorides.)
3. Aladdin Scientific. Product page and Certificate of Analysis for 2-Chloro-6-methylpyridine, SKU C124344. https://www.aladdin-e.com (accessed 2024).

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