3-Bromo-2-nitropyridine: Properties, Synthesis & Applications

3-Bromo-2-nitropyridine is a halogenated nitropyridine building block widely employed in pharmaceutical, agrochemical, and materials research owing to its dual electrophilic handles—a bromine atom and an ortho-nitro group—that enable diverse synthetic transformations.

CAS Number

58530-53-3

Molecular Formula

C₅H₃BrN₂O₂

Molecular Weight

203.00 g/mol

Appearance

Pale yellow to yellow crystalline solid

Key Functional Groups

C–Br (C-3), nitro (C-2), pyridine ring nitrogen

Primary Use

Synthetic intermediate in medicinal and heterocyclic chemistry

Chemical Structure and Key Properties

3-Bromo-2-nitropyridine (CAS 58530-53-3) is a six-membered nitrogen-containing heterocycle bearing a bromine substituent at the 3-position and a nitro group at the 2-position of the pyridine ring. The molecular formula is C₅H₃BrN₂O₂ and the molecular weight is approximately 203.00 g/mol. The compound typically presents as a pale yellow crystalline solid at room temperature.

The electron-withdrawing nitro group at C-2 strongly activates the C-3 carbon toward nucleophilic aromatic substitution (SNAr) while simultaneously activating the ring nitrogen toward coordination and further functionalization. The C–Br bond at C-3 is a versatile handle for transition-metal-catalyzed cross-coupling reactions. Together, these two ortho-positioned reactive sites make the molecule an unusually rich bifunctional synthon in modern synthetic chemistry.

Synthetic Utility and Reaction Chemistry

The bromine atom at C-3 participates readily in palladium-catalyzed cross-coupling reactions, including Suzuki–Miyaura, Negishi, Stille, and Buchwald–Hartwig amination reactions. These transformations allow researchers to install aryl, heteroaryl, vinyl, alkyl, and amino groups at C-3 in a single step, building molecular complexity efficiently.

The ortho-nitro group at C-2 can be exploited in two complementary ways. First, it can be reduced to an amine—using catalytic hydrogenation or chemical reductants such as iron/acetic acid or SnCl₂—to furnish 3-substituted-2-aminopyridines, which are key scaffolds in kinase-inhibitor and anti-infective drug discovery. Second, the activated nitro group undergoes SNAr displacement with amines, thiolates, and alkoxides, providing rapid access to 2-amino-, 2-thio-, and 2-alkoxypyridine derivatives without requiring a metal catalyst.

Combinations of these strategies—sequential cross-coupling followed by nitro reduction, or SNAr followed by coupling—enable the construction of polyfunctionalized pyridine cores used in fragment-based drug discovery and natural-product synthesis.

Applications in Pharmaceutical and Agrochemical Research

In medicinal chemistry, 3-Bromo-2-nitropyridine serves as a privileged intermediate for the preparation of aminopyridine-based pharmacophores. The 2-aminopyridine motif obtained after nitro reduction is prevalent in marketed kinase inhibitors, antibacterials, and antiviral agents, making this compound a high-value entry point for lead-optimization campaigns.

In agrochemical research, halonitropyridines are established precursors to fungicidal and herbicidal active ingredients. The ability to diversify both positions orthogonally allows rapid generation of compound libraries for structure–activity relationship (SAR) studies.

Beyond small-molecule therapeutics, the compound has been applied in the synthesis of fluorescent probes, ligands for metal-organic frameworks (MOFs), and photoredox-active heterocyclic dyes, reflecting the broad utility of its reactive handles in materials science.

Handling, Storage, and Safety Considerations

3-Bromo-2-nitropyridine should be handled in a well-ventilated fume hood using appropriate personal protective equipment (PPE), including nitrile gloves, safety glasses, and a lab coat. The nitro group confers potential oxidizing character; avoid contact with strong reducing agents, flammable materials, or heat sources that could trigger decomposition.

The compound should be stored in a cool, dry place away from direct sunlight and moisture, preferably in a tightly sealed amber glass vial at room temperature or under mild refrigeration (2–8 °C) to maintain long-term stability. Consult the Safety Data Sheet (SDS) supplied with the product for complete hazard classifications, first-aid measures, and disposal guidance in accordance with local regulations.

Waste containing this compound must be disposed of as chemical waste according to institutional and governmental environmental regulations. Do not pour down the drain without verifying local permissibility.

Frequently asked questions

What cross-coupling reactions can be performed with 3-Bromo-2-nitropyridine?

The C–Br bond at C-3 is compatible with a broad range of palladium-catalyzed cross-coupling protocols, including Suzuki–Miyaura (boronic acids), Negishi (organozinc), Stille (organostannane), and Buchwald–Hartwig amination reactions. These reactions can typically be performed before or after manipulation of the C-2 nitro group, allowing flexible synthetic planning.

How can the nitro group of 3-Bromo-2-nitropyridine be converted to an amine?

The nitro group can be reduced to an amine using catalytic hydrogenation (H₂, Pd/C) under mild conditions, or via chemical reduction with reagents such as iron powder in acetic acid or tin(II) chloride in ethanol. Care must be taken to select conditions that do not simultaneously cleave the C–Br bond if it is still needed for subsequent steps.

Is nucleophilic aromatic substitution (SNAr) possible at the C-2 position without a metal catalyst?

Yes. The combination of the ring nitrogen and the ortho-nitro group makes the C-2 position highly electron-deficient, enabling SNAr reactions with nitrogen, oxygen, and sulfur nucleophiles under relatively mild, metal-free conditions. This provides a straightforward route to 2-amino-, 2-alkoxy-, and 2-thio-substituted pyridines.

What storage conditions are recommended for 3-Bromo-2-nitropyridine?

Store the compound in a tightly sealed container in a cool, dry location away from light and moisture. Room temperature storage is generally acceptable; mild refrigeration at 2–8 °C may extend shelf life. Always consult the product SDS for specific guidance.

What safety precautions should be observed when working with this compound?

Work in a fume hood and wear nitrile gloves, safety glasses, and a lab coat. Avoid exposure to strong reducing agents and heat. Dispose of all waste according to institutional and local chemical-waste regulations, and refer to the SDS for complete hazard information.

References

1. Joule, J. A.; Mills, K. Heterocyclic Chemistry, 5th ed.; Wiley-Blackwell: Oxford, 2010. (General reference for pyridine reactivity and SNAr chemistry.)
2. Clayden, J.; Greeves, N.; Warren, S. Organic Chemistry, 2nd ed.; Oxford University Press: Oxford, 2012. (Textbook-level coverage of nucleophilic aromatic substitution and cross-coupling reactions.)
3. Miyaura, N.; Suzuki, A. Palladium-Catalyzed Cross-Coupling Reactions of Organoboron Compounds. Chem. Rev. 1995, 95, 2457–2483. doi:10.1021/cr00039a007

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