2-Chloro-5-methoxy-3-methylpyridine: Properties & Lab FAQ

2-Chloro-5-methoxy-3-methylpyridine is a halogenated methoxypyridine building block widely used as a versatile intermediate in medicinal chemistry and the synthesis of biologically active heterocyclic compounds.

Chemical Name

2-Chloro-5-methoxy-3-methylpyridine

SKU / Catalog Number

C194869

Molecular Formula

C7H8ClNO

Molecular Weight

157.60 g/mol

CAS Number

886372-07-2

Functional Class

Halogenated pyridine intermediate

Key Functional Groups

Aryl chloride, methoxy, methyl on pyridine ring

Overview and Chemical Identity

2-Chloro-5-methoxy-3-methylpyridine (Aladdin SKU C194869) is a substituted pyridine carrying three distinct substituents on the six-membered nitrogen-containing ring: a chloro group at the 2-position, a methyl group at the 3-position, and a methoxy group at the 5-position. Its molecular formula is C₇H₈ClNO with a molecular weight of approximately 157.60 g/mol.

The combination of an electron-withdrawing chloro group adjacent to the ring nitrogen and an electron-donating methoxy group at the 5-position creates a polarised aromatic system that is particularly amenable to nucleophilic aromatic substitution (S_NAr) at C-2 as well as transition-metal-catalysed cross-coupling reactions. The methyl substituent at C-3 offers additional steric and electronic modulation, making this compound a useful and differentiated building block compared with simpler chloropyridines.

Synthetic Applications and Reactivity

The C–Cl bond at the 2-position is activated toward nucleophilic aromatic substitution due to the ring nitrogen acting as an electron-withdrawing group in the ortho/para relationship. This allows displacement with amines, alkoxides, and thiolates under mild-to-moderate conditions to furnish 2-amino-, 2-alkoxy-, or 2-thioether-substituted pyridines.

Additionally, the aryl chloride is a competent electrophilic partner in palladium-catalysed cross-coupling reactions including Suzuki–Miyaura (boronic acids), Buchwald–Hartwig (amination), and Negishi (organozinc) couplings. These transformations enable rapid elaboration of the pyridine scaffold for medicinal chemistry programmes targeting kinase inhibitors, GPCRs, and other druggable targets where methoxy- and methyl-substituted pyridine motifs are prevalent.

The methoxy group at C-5 can also be demethylated under Lewis-acidic or hydrobromic acid conditions to unmask a phenol-equivalent hydroxypyridine for further derivatisation.

Handling, Storage, and Safety Guidance

As with most halogenated aromatic compounds, 2-Chloro-5-methoxy-3-methylpyridine should be handled with standard laboratory precautions. Work in a well-ventilated fume hood, wear appropriate personal protective equipment including nitrile gloves, safety glasses, and a lab coat. Avoid inhalation of dust or vapours.

Storage recommendations for halogenated pyridine building blocks of this class typically include a cool, dry, well-ventilated area away from incompatible materials such as strong oxidisers and strong bases. Sealing the container under an inert atmosphere (nitrogen or argon) after each use helps prevent moisture absorption and oxidative degradation, extending shelf life. Refrigerated storage (2–8 °C) is generally advisable for long-term stability.

Consult the Safety Data Sheet (SDS) provided by Aladdin Scientific before first use. Dispose of waste in accordance with local institutional and regulatory guidelines for halogenated organic waste streams.

Purity, Specification, and Quality Assurance

Aladdin Scientific supplies 2-Chloro-5-methoxy-3-methylpyridine (SKU C194869) as a research-grade reagent. Typical analytical characterisation for compounds in this class includes ¹H NMR, ¹³C NMR, GC or HPLC purity assessment, and high-resolution mass spectrometry (HRMS). Customers requiring lot-specific certificates of analysis (CoA) should contact Aladdin's technical support or access them through the product page on the Aladdin Scientific website.

When incorporating this building block into multi-step synthesis, it is advisable to verify purity by an independent analytical method prior to use, particularly in reactions sensitive to moisture or trace metal contamination. If a higher purity grade is required for a specific application, please contact Aladdin Scientific's sales team to discuss custom specifications.

Ordering and Customer Support

2-Chloro-5-methoxy-3-methylpyridine is available from Aladdin Scientific under catalog number C194869. To place an order, visit the Aladdin Scientific website, search by name or SKU, and proceed through the standard online checkout. Bulk quantities and custom pack sizes may be available upon request — contact our sales or procurement team for pricing and lead-time information.

For technical inquiries regarding synthesis protocols, compatibility, or application-specific recommendations, Aladdin's scientific support team is available via email and telephone. Certificates of Analysis, Safety Data Sheets, and additional product documentation can be downloaded directly from the product page.

Frequently asked questions

What reactions can 2-Chloro-5-methoxy-3-methylpyridine undergo at the C-2 chloro position?

The C-2 aryl chloride is activated by the adjacent ring nitrogen and is reactive toward nucleophilic aromatic substitution (SᵊAr) with amines, alkoxides, and thiolates. It is also an effective electrophilic coupling partner in palladium-catalysed reactions such as Suzuki–Miyaura, Buchwald–Hartwig, and Negishi cross-couplings, enabling broad structural diversification of the pyridine scaffold.

How should 2-Chloro-5-methoxy-3-methylpyridine (C194869) be stored to maintain stability?

The compound should be stored in a cool, dry, well-ventilated location, ideally at 2–8 °C for long-term preservation. After opening, reseal the container under an inert atmosphere of nitrogen or argon to minimise moisture uptake and prevent oxidative degradation. Always consult the Aladdin Scientific SDS for full storage and safety guidance.

What is the CAS number for 2-Chloro-5-methoxy-3-methylpyridine, and how does it help when ordering?

The CAS number for 2-Chloro-5-methoxy-3-methylpyridine is 886372-07-2. CAS numbers serve as universal identifiers for chemical substances, allowing researchers and procurement teams to unambiguously confirm they are ordering the correct compound regardless of the trade name or catalog number used by different suppliers. When ordering from Aladdin Scientific, you can search by CAS number, compound name, or SKU C194869.

Is a Certificate of Analysis available for lot C194869?

Yes. Lot-specific Certificates of Analysis (CoA) for 2-Chloro-5-methoxy-3-methylpyridine (C194869) are available from Aladdin Scientific. You can download the CoA directly from the product page on the Aladdin Scientific website using your lot number, or contact our customer support team for assistance.

Can the methoxy group of 2-Chloro-5-methoxy-3-methylpyridine be removed synthetically?

Yes. The methoxy group at C-5 can be demethylated using Lewis acid reagents (e.g., BBr₃ or AlCl₃) or by treatment with concentrated hydrobromic acid, revealing the corresponding hydroxypyridine. This approach is commonly employed in medicinal chemistry when a free hydroxyl handle is required for further synthetic elaboration or bioisosteric exploration.

References

1. Aladdin Scientific product page for 2-Chloro-5-methoxy-3-methylpyridine, SKU C194869. Aladdin Scientific, Shanghai.
2. March, J. Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 4th ed.; Wiley-Interscience: New York, 1992. (General reference for nucleophilic aromatic substitution and cross-coupling reactions.)
3. Johansson Seechurn, C. C. C.; Kitching, M. O.; Colacot, T. J.; Snieckus, V. Palladium-Catalyzed Cross-Coupling: A Historical Contextual Perspective to the 2010 Nobel Prize. Angew. Chem. Int. Ed. 2012, 51, 5062–5085. doi:10.1002/anie.201107017

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