2-Chloro-4-methoxy-5-nitropyridine: Properties & Applications

2-Chloro-4-methoxy-5-nitropyridine is a halogenated, methoxy- and nitro-substituted pyridine building block widely employed as a versatile electrophilic intermediate in the synthesis of pharmaceuticals, agrochemicals, and other nitrogen-containing heterocyclic compounds.

CAS Number

Not specified in source material — see product datasheet

Molecular Formula

C6H5ClN2O3

Molecular Weight

188.57 g/mol

Key Functional Groups

Chloro (C-2), methoxy (C-4), nitro (C-5) substituents on a pyridine ring

Primary Application

Electrophilic building block in nucleophilic aromatic substitution and cross-coupling reactions

SKU

C638313

Chemical Identity and Structure

2-Chloro-4-methoxy-5-nitropyridine is a pyridine derivative bearing three distinct substituents: a chlorine atom at the 2-position, a methoxy group at the 4-position, and a nitro group at the 5-position. Its molecular formula is C₆H₅ClN₂O₃ with a molecular weight of approximately 188.57 g/mol. The combination of the electron-withdrawing nitro group and the ring nitrogen renders the carbon bearing the chloro substituent highly susceptible to nucleophilic attack, making this compound an attractive electrophilic partner in nucleophilic aromatic substitution (SNAr) chemistry. The methoxy group at C-4 provides an additional handle for further functionalization or serves to modulate electronic density across the ring system.

Synthetic Utility and Reactivity

The electron-poor pyridine ring of 2-Chloro-4-methoxy-5-nitropyridine supports several important reaction classes. In nucleophilic aromatic substitution, the C–Cl bond at the activated 2-position can be displaced by a range of nucleophiles including amines, alkoxides, and thiols, enabling rapid construction of diverse N-, O-, and S-linked pyridine derivatives. This reactivity pattern is particularly valuable in medicinal chemistry fragment coupling and lead optimization workflows.

The compound is also compatible with transition-metal-catalyzed cross-coupling reactions, such as Suzuki–Miyaura, Buchwald–Hartwig, and Negishi couplings, where the aryl chloride serves as the electrophilic coupling partner. Following installation of desired substituents, the nitro group can be selectively reduced to the corresponding amine under standard catalytic hydrogenation or chemical reduction conditions, unmasking a primary amine for further elaboration into amides, ureas, sulfonamides, or heterocycles.

Applications in Drug Discovery and Agrochemical Research

Substituted nitropyridines and their reduced amino analogs are privileged scaffolds in medicinal chemistry. 2-Chloro-4-methoxy-5-nitropyridine serves as a key building block for the preparation of kinase inhibitors, antiviral agents, and antimicrobial compounds, where the pyridine nitrogen and peripheral substituents contribute to target binding through hydrogen bonding and hydrophobic interactions. The methoxy group can improve membrane permeability and metabolic stability of the resulting drug candidates.

In agrochemical research, pyridine-based heterocycles are common pharmacophores in herbicides, fungicides, and insecticides. The activated chloro and nitro functionalities of this compound facilitate the introduction of biologically relevant groups required for selective crop-protection activity. Researchers in both sectors value the compound's commercial availability, defined purity, and predictable reactivity as a reliable intermediate in multi-step synthesis campaigns.

Handling, Storage, and Safety Considerations

As with all halogenated nitroaromatic compounds, 2-Chloro-4-methoxy-5-nitropyridine should be handled with appropriate precautions. Laboratory personnel should wear suitable personal protective equipment including chemical-resistant gloves, safety glasses, and a laboratory coat. Operations generating dust or aerosols should be conducted in a well-ventilated fume hood.

The compound should be stored in a tightly sealed container in a cool, dry environment away from incompatible materials such as strong reducing agents and strong bases. Always consult the current Safety Data Sheet (SDS) provided by Aladdin Scientific before use, as it contains up-to-date hazard classification, first-aid measures, and disposal guidance compliant with applicable regulations. Waste containing this compound must be disposed of in accordance with local environmental and chemical-waste regulations.

Product Specifications and Ordering Information

Aladdin Scientific offers 2-Chloro-4-methoxy-5-nitropyridine under SKU C638313. The compound is supplied to research-grade purity standards suitable for synthetic chemistry applications. Researchers requiring specific purity certificates, analytical data (such as NMR, HPLC, or mass spectrometry confirmation), or custom pack sizes are encouraged to contact Aladdin Scientific's technical support or consult the product datasheet available on the product page.

For bulk quantities, custom synthesis inquiries, or institutional pricing, please reach out to the Aladdin Scientific sales team. All orders are subject to Aladdin Scientific's standard terms regarding shipping, payment, and returns as detailed on the company website.

Frequently asked questions

What reactions is 2-Chloro-4-methoxy-5-nitropyridine commonly used for?

It is primarily used in nucleophilic aromatic substitution (SNAr) reactions, where the C-2 chloro group is displaced by nitrogen, oxygen, or sulfur nucleophiles. It is also employed in transition-metal-catalyzed cross-coupling reactions (e.g., Suzuki, Buchwald–Hartwig) and as a precursor to 5-aminopyridine derivatives following nitro-group reduction.

How should 2-Chloro-4-methoxy-5-nitropyridine be stored to maintain stability?

The compound should be stored in a tightly sealed container under cool, dry conditions, away from light, moisture, strong reducing agents, and strong bases. Always refer to the current SDS and product datasheet for the most accurate storage recommendations specific to this lot.

Can the nitro group in this compound be selectively reduced without affecting the methoxy substituent?

In general, nitro groups on electron-poor heterocycles can be selectively reduced to the corresponding amine using catalytic hydrogenation (e.g., Pd/C under H2) or chemical reductants such as iron in acetic acid or tin(II) chloride, without cleaving the C–O bond of the methoxy group. However, specific conditions should be optimized empirically for this substrate, and researchers should monitor reaction progress by TLC or HPLC.

What is the SKU for 2-Chloro-4-methoxy-5-nitropyridine at Aladdin Scientific?

The product is listed under SKU C638313. Please visit the Aladdin Scientific website or contact the sales team for current availability, pricing, and pack-size options.

References

1. 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.)
2. Joule, J. A.; Mills, K. Heterocyclic Chemistry, 5th ed.; Wiley-Blackwell: Oxford, 2010. (General reference for pyridine reactivity and functionalization.)
3. Aladdin Scientific product datasheet: 2-Chloro-4-methoxy-5-nitropyridine, SKU C638313. (Consult for lot-specific analytical data, purity, and storage conditions.)

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