2-Chloro-3-methylpyridine: Properties, Synthesis & Applications

2-Chloro-3-methylpyridine is a halogenated pyridine building block widely employed in organic synthesis, serving as a key intermediate in the preparation of pharmaceuticals, agrochemicals, and other fine chemicals.

CAS Number

18368-76-8

Molecular Formula

C₆H₆ClN

Molecular Weight

127.57 g/mol

Appearance

Colorless to pale yellow liquid

Boiling Point

Approximately 196–198 °C (literature; verify with CoA)

Key Functional Groups

Aryl chloride, pyridine ring, methyl substituent

Primary Use

Synthetic intermediate in pharmaceutical and agrochemical research

Chemical Identity and Physical Properties

2-Chloro-3-methylpyridine (CAS 18368-76-8) is a six-membered nitrogen-containing heterocycle bearing a chlorine atom at the 2-position and a methyl group at the 3-position of the pyridine ring. Its molecular formula is C₆H₆ClN, giving a molecular weight of approximately 127.57 g/mol. The compound typically presents as a colorless to pale yellow liquid at room temperature.

The electronic structure of the pyridine ring makes the nitrogen atom electron-withdrawing by induction, rendering the ring electron-deficient. This characteristic, combined with the electron-withdrawing chloro substituent at the 2-position adjacent to nitrogen, significantly activates the C–Cl bond toward nucleophilic aromatic substitution (SNAr). The 3-methyl group provides a modest steric and electronic directing influence for further functionalization. Storage under cool, dry conditions away from light is recommended to maintain product integrity.

Note: Precise physical constants such as boiling point, density, and refractive index should be confirmed against the certificate of analysis (CoA) supplied with each lot.

Synthesis and Key Reactions

2-Chloro-3-methylpyridine can be obtained via several established routes in heterocyclic chemistry:

• Direct chlorination of 3-methylpyridine: Electrophilic or directed metalation strategies can introduce chlorine at the 2-position, although selectivity control requires careful choice of reagents and conditions.
• Sandmeyer-type reactions: Starting from the corresponding 2-amino-3-methylpyridine, diazotization followed by treatment with CuCl provides the 2-chloro product with good regioselectivity.
• Cyclization approaches: Appropriately substituted open-chain precursors can be cyclized using classical Hantzsch or Chichibabin-type condensation methods to afford the desired substitution pattern directly.

As a substrate, 2-Chloro-3-methylpyridine participates in a broad range of transformations:

• Nucleophilic Aromatic Substitution (SNAr): Amines, alkoxides, and thiolates readily displace chloride under mild to moderate conditions, enabling direct access to 2-amino-, 2-alkoxy-, and 2-thio-3-methylpyridines.
• Transition-metal-catalyzed cross-coupling: The aryl C–Cl bond undergoes Suzuki–Miyaura, Negishi, Buchwald–Hartwig, and related couplings with appropriate catalyst systems, enabling attachment of aryl, alkenyl, alkyl, and amino groups.
• Directed C–H functionalization: The methyl group at C-3 and the directing ability of the pyridine nitrogen can be leveraged for benzylic or ring C–H activation under suitable catalytic conditions.

Review flag: Specific reaction conditions, yields, and catalyst loadings cited in literature should be verified against primary sources before use in experimental protocols.

Applications in Pharmaceutical and Agrochemical Research

The combination of the reactive aryl chloride and the methyl handle makes 2-Chloro-3-methylpyridine a high-value building block in both pharmaceutical and agrochemical discovery programs.

Pharmaceutical research: Pyridine-containing scaffolds are among the most prevalent heterocycles in approved drugs and drug candidates. The 2-chloro-3-methylpyridine motif serves as a starting point for constructing kinase inhibitors, GPCR modulators, and other bioactive molecules. The 2-position chlorine is easily replaced by nitrogen nucleophiles to install amine pharmacophores, while cross-coupling reactions allow elaboration of the ring with diverse carbon fragments needed for structure–activity relationship (SAR) studies.

Agrochemical research: Chloropyridines are key structural components in a range of herbicides, fungicides, and insecticides. 2-Chloro-3-methylpyridine and its derivatives have been employed as intermediates in the synthesis of pyridyloxy- and pyridylamino-based active ingredients targeting plant and pest biology.

Materials and dye chemistry: Substituted pyridines also find use as ligands in coordination chemistry and as chromophoric units in functional materials, though these represent secondary application areas relative to pharma and agro uses.

Review flag: Specific named drug or agrochemical products derived from this building block should be cited with primary literature or patent references before inclusion in promotional materials.

Handling, Safety, and Storage

As with most halogenated pyridine derivatives, 2-Chloro-3-methylpyridine should be handled with appropriate laboratory precautions:

• Personal Protective Equipment (PPE): Wear chemical-resistant gloves, safety glasses or goggles, and a laboratory coat. Work in a well-ventilated fume hood to avoid inhalation of vapors.
• Storage: Store in a tightly sealed container in a cool, dry, well-ventilated area away from incompatible materials such as strong oxidizers and strong bases. Recommended storage temperature is typically room temperature or as specified on the product label and CoA.
• Disposal: Dispose of waste in accordance with local, regional, and national regulations governing halogenated organic solvents and intermediates.
• First Aid: In case of skin or eye contact, rinse thoroughly with water. Seek medical attention if irritation persists. Refer to the current Safety Data Sheet (SDS) for complete hazard information.

Review flag: GHS hazard classification, specific H-statements, P-statements, and flash point values must be taken directly from the current lot SDS and verified before publication.

Ordering Information and Specifications

Aladdin Scientific offers 2-Chloro-3-methylpyridine under product SKU C124347. Researchers and procurement teams should note the following when ordering:

• Purity: Confirm purity grade and analytical method (e.g., GC, HPLC) on the current CoA prior to use in sensitive applications.
• Available pack sizes: Contact Aladdin Scientific or visit the product page for current stock quantities, pack sizes, and pricing.
• Documentation: A Certificate of Analysis (CoA), Safety Data Sheet (SDS), and, where available, NMR or GC trace can be requested at the time of order or downloaded from the product page.
• Custom quantities: For bulk or custom orders, please contact our sales team directly.

When specifying this compound for regulated research or GMP-adjacent workflows, confirm that the supplied lot meets your internal specification requirements by reviewing the full CoA.

Frequently asked questions

What is the CAS number for 2-Chloro-3-methylpyridine?

The CAS registry number for 2-Chloro-3-methylpyridine is 18368-76-8. This number uniquely identifies the compound and can be used when searching supplier catalogs, safety databases, and literature.

Why is the C–Cl bond in 2-Chloro-3-methylpyridine particularly reactive toward nucleophilic substitution?

The electron-deficient pyridine ring, due to the electronegative ring nitrogen, activates the carbon bearing the chlorine atom toward nucleophilic aromatic substitution (SNAr). The placement of chlorine at the 2-position, ortho to the ring nitrogen, further increases electrophilicity at that carbon, lowering the activation energy for nucleophilic attack relative to simple chlorobenzenes.

Can 2-Chloro-3-methylpyridine be used in palladium-catalyzed cross-coupling reactions?

Yes. Aryl chlorides are well-established partners in palladium-catalyzed cross-coupling reactions, including Suzuki–Miyaura boronic acid couplings, Negishi organozinc couplings, and Buchwald–Hartwig amination, provided that sufficiently active catalyst systems (e.g., bulky phosphine ligands) are employed to facilitate oxidative addition of the less reactive C–Cl bond. The pyridine nitrogen may require ligand selection considerations to avoid catalyst inhibition.

How should I store 2-Chloro-3-methylpyridine to maintain its stability?

Store 2-Chloro-3-methylpyridine in a tightly sealed container in a cool, dry, well-ventilated location, away from strong oxidizing agents, strong acids, and strong bases. Refer to the product label and current SDS for lot-specific storage temperature recommendations and shelf-life guidance.

What documentation is available with Aladdin Scientific's C124347?

Aladdin Scientific provides a Certificate of Analysis (CoA) confirming identity, purity, and lot-specific test results, as well as a Safety Data Sheet (SDS) covering GHS hazard classification, handling, and disposal information. Additional analytical data such as NMR or GC traces may be available upon request; contact our customer service team or check the product page for current documentation.

References

1. Clayden, J.; Greeves, N.; Warren, S. Organic Chemistry, 2nd ed.; Oxford University Press: Oxford, 2012. (General reference for nucleophilic aromatic substitution and heterocyclic chemistry.)
2. Joule, J. A.; Mills, K. Heterocyclic Chemistry, 5th ed.; Wiley-Blackwell: Oxford, 2010. (Reference for pyridine reactivity and synthesis.)
3. Schlummer, B.; Scholz, U. Palladium-Catalyzed C–N and C–O Coupling – A Practical Guide from an Industrial Vantage Point. Adv. Synth. Catal. 2004, 346, 1599–1626. doi:10.1002/adsc.200404216
4. CAS Registry entry for 2-Chloro-3-methylpyridine, CAS RN 18368-76-8. SciFinder (accessed via institutional subscription).

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