3-Chloro-4-nitropyridine: Properties, Synthesis & Applications

3-Chloro-4-nitropyridine is a halogenated, electron-deficient pyridine derivative widely employed as a reactive building block in medicinal chemistry, heterocyclic synthesis, and the preparation of biologically active compounds.

CAS Number

13100-13-5

Molecular Formula

C₅H₃ClN₂O₂

Molecular Weight

158.54 g/mol

Appearance

Pale yellow to yellow crystalline solid

Key Functional Groups

Chloro (C-3), Nitro (C-4), Pyridine nitrogen (N-1)

Primary Reactivity

Nucleophilic aromatic substitution (SNAr) at C-4 chloro position

Storage

Cool, dry place; away from light and moisture

Aladdin SKU

C190557

Chemical Structure and Properties

3-Chloro-4-nitropyridine (CAS 13100-13-5) is a disubstituted pyridine bearing a chlorine atom at the 3-position and a nitro group at the 4-position of the aromatic ring. The combination of the electron-withdrawing nitro group and the ring nitrogen renders the aromatic system strongly electron-deficient, significantly activating the C–Cl bond toward nucleophilic attack.

The molecule has a molecular formula of C₅H₃ClN₂O₂ and a molecular weight of approximately 158.54 g/mol. It typically presents as a pale yellow to yellow crystalline solid at room temperature. The mutually ortho-disposed chloro and nitro substituents create a highly polarized environment at C-4, making that position the preferred site for nucleophilic aromatic substitution (SNAr).

Reactivity and Synthetic Utility

The principal chemical transformation of 3-Chloro-4-nitropyridine is nucleophilic aromatic substitution (SNAr) at the C-4 chloro position. The adjacent nitro group stabilizes the Meisenheimer complex intermediate, facilitating displacement of chloride by a wide range of nucleophiles including primary and secondary amines, alkoxides, and thiolates. This allows efficient construction of 4-amino-, 4-alkoxy-, and 4-thioether-substituted nitropyridines.

The nitro group itself is a versatile handle: it can be reduced to the corresponding amine using catalytic hydrogenation or chemical reductants (e.g., iron/acetic acid, SnCl₂), generating 3-chloropyridin-4-amine intermediates that are valuable for further coupling reactions. Additionally, the remaining C-3 chloro group can participate in transition-metal-catalyzed cross-coupling reactions (e.g., Suzuki–Miyaura, Buchwald–Hartwig amination), providing rapid access to polysubstituted pyridine scaffolds.

This orthogonal dual-handle reactivity — SNAr at C-4 and cross-coupling at C-3 — makes 3-Chloro-4-nitropyridine an especially efficient building block for library synthesis and medicinal chemistry campaigns.

Applications in Medicinal Chemistry and Drug Discovery

Pyridine is one of the most prevalent heterocyclic ring systems in approved pharmaceuticals, and electron-deficient variants such as 3-Chloro-4-nitropyridine are routinely exploited to introduce this scaffold into drug candidates. The compound serves as a direct precursor to aminopyridine and diaminopyridine motifs that appear in kinase inhibitors, antimicrobials, and other therapeutic classes.

In kinase inhibitor programs, 4-aminopyridine and related fragments are frequently incorporated as hinge-binding elements. 3-Chloro-4-nitropyridine enables rapid parallel synthesis of amine-diversified analogues via SNAr, supporting structure–activity relationship (SAR) studies. After SNAr diversification, nitro reduction and subsequent acylation or sulfonylation yield urea or sulfonamide analogues commonly found in drug candidates targeting oncology and inflammation.

Beyond pharmaceuticals, the compound is used in agrochemical research and in the preparation of ligands for coordination chemistry and materials science.

Handling, Safety, and Storage

3-Chloro-4-nitropyridine should be handled with standard laboratory precautions appropriate for reactive halogenated nitroaromatics. Personal protective equipment including chemical-resistant gloves, safety goggles, and a laboratory coat should be worn at all times. Operations generating dust or aerosols should be performed in a well-ventilated fume hood.

The compound should be stored in a tightly sealed container in a cool, dry location away from direct light, heat, and moisture. It should be kept away from strong reducing agents, bases, and reactive metals, which may trigger uncontrolled reactions with the nitro group or C–Cl bond. Users should consult the current Safety Data Sheet (SDS) provided by Aladdin Scientific for comprehensive hazard information, first-aid measures, and disposal guidelines before use.

Waste containing this compound must be disposed of in accordance with applicable local, national, and institutional regulations governing halogenated and nitroaromatic chemical waste.

Ordering Information

3-Chloro-4-nitropyridine is available from Aladdin Scientific under SKU C190557. The compound is offered to support research and development workflows in synthetic organic chemistry, medicinal chemistry, and related disciplines. For quantity pricing, bulk availability, certificate of analysis (CoA), and safety data sheets, please contact Aladdin Scientific sales or visit the product page directly.

Research scientists and procurement teams requiring custom quantities or specific purity grades are encouraged to reach out to our technical support team for tailored solutions.

Frequently asked questions

What is 3-Chloro-4-nitropyridine used for in synthesis?

3-Chloro-4-nitropyridine is primarily used as a building block in nucleophilic aromatic substitution (SNAr) reactions, where the C-4 chloro group is displaced by amines, alkoxides, or thiolates. It is also used as a precursor to aminopyridines via nitro-group reduction and in cross-coupling reactions at the C-3 position, making it highly versatile in drug discovery and heterocyclic chemistry.

Why is the C-4 chloro position more reactive than C-3 in SNAr reactions?

The nitro group at C-4 is an extremely strong electron-withdrawing group that stabilizes the anionic Meisenheimer complex formed during SNAr when nucleophiles attack the ipso carbon bearing the chloro substituent. Because the nitro group is directly attached at C-4, it most effectively stabilizes negative charge build-up at that carbon during the addition step, making displacement of the C-4 chloride energetically favorable compared to the C-3 position.

How should 3-Chloro-4-nitropyridine be stored to maintain stability?

The compound should be stored in a tightly sealed container in a cool, dry place, protected from light and moisture. It should be kept away from strong reducing agents and reactive metals. Always consult the current Aladdin Scientific Safety Data Sheet (SDS) for specific storage temperature recommendations and shelf-life information.

Can 3-Chloro-4-nitropyridine undergo transition-metal-catalyzed cross-coupling?

Yes. The C-3 chloro substituent can participate in palladium-catalyzed cross-coupling reactions such as Suzuki–Miyaura (with boronic acids) and Buchwald–Hartwig amination, among others. This reactivity, orthogonal to the SNAr reactivity at C-4, allows sequential functionalization of both positions to rapidly build molecular complexity.

What are the key safety considerations when working with 3-Chloro-4-nitropyridine?

Users should wear appropriate personal protective equipment including gloves, goggles, and a lab coat. The compound should be handled in a fume hood to avoid inhalation of dust or vapors. As a halogenated nitroaromatic, it may be irritating to skin, eyes, and respiratory tract. Dispose of waste according to local hazardous waste regulations and review the SDS from Aladdin Scientific before first use.

References

1. March, J. Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 4th ed.; Wiley-Interscience: New York, 1992. (General reference for SNAr mechanism and nitroaromatic reactivity.)
2. Clayden, J.; Greeves, N.; Warren, S. Organic Chemistry, 2nd ed.; Oxford University Press: Oxford, 2012. (Textbook reference for nucleophilic aromatic substitution and pyridine chemistry.)
3. Joule, J. A.; Mills, K. Heterocyclic Chemistry, 5th ed.; Wiley-Blackwell: Oxford, 2010. (Reference for pyridine reactivity and substitution patterns.)

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