3-Bromopyridine-N-oxide: Properties, Uses & FAQs

3-Bromopyridine-N-oxide is a halogenated pyridine N-oxide that serves as a versatile electrophilic intermediate in heterocyclic synthesis, enabling cross-coupling reactions and further functionalization at both the ring carbon and N-oxide oxygen positions.

Chemical Name

3-Bromopyridine-N-oxide

Molecular Formula

C₅H₄BrNO

Molecular Weight

174.00 g/mol

CAS Number

14453-38-4

Functional Groups

Aromatic C–Br bond; pyridine N-oxide (N⁺–O⁻)

Primary Application

Electrophilic heteroaromatic intermediate for cross-coupling and nucleophilic substitution

Recommended Storage

Cool, dry, well-ventilated area away from moisture and strong oxidizers

What Is 3-Bromopyridine-N-oxide?

3-Bromopyridine-N-oxide (CAS 14453-38-4) is a heteroaromatic compound derived from 3-bromopyridine by oxidation of the ring nitrogen to yield a zwitterionic N-oxide moiety (N⁺–O⁻). The molecule retains the aromatic character of the pyridine ring while the N-oxide group substantially alters the electronic distribution, making the ring more susceptible to nucleophilic attack at C-2 and C-4 positions relative to non-oxidized bromopyridines.

The bromo substituent at the 3-position provides a handle for transition-metal-catalyzed cross-coupling reactions (e.g., Suzuki–Miyaura, Negishi, Buchwald–Hartwig), while the N-oxide functionality can independently participate in deoxygenation, oxygen-transfer, or rearrangement reactions. This dual reactivity profile makes 3-Bromopyridine-N-oxide a multifunctional building block in medicinal and synthetic chemistry.

Key Chemical Properties and Reactivity

The N-oxide group in 3-Bromopyridine-N-oxide exerts a strong electron-withdrawing inductive effect combined with a resonance electron-donating contribution at ortho/para positions. This paradoxical electronic environment activates the ring toward nucleophilic aromatic substitution (SNAr) at positions flanking the nitrogen, while the bromo leaving group at C-3 enables oxidative addition into Pd(0) catalytic cycles.

Common transformations include: (1) Palladium-catalyzed cross-coupling at the C–Br bond to install aryl, vinyl, or heteroaryl groups; (2) Reductive deoxygenation of the N-oxide with reagents such as triphenylphosphine or iron powder to regenerate the pyridine; (3) Meisenheimer-type rearrangements or Boekelheide reactions to access 2-substituted or 3-substituted pyridine derivatives; (4) Use of the N-oxide oxygen as an internal oxidant in directed C–H functionalization protocols.

The compound is a solid at room temperature. Its melting point and exact solubility profile should be confirmed with the certificate of analysis (CoA) supplied with each lot.

Handling, Safety and Storage Guidelines

As with all organobromine and N-oxide compounds, appropriate laboratory safety precautions are required when working with 3-Bromopyridine-N-oxide. Personal protective equipment (PPE) including chemical-resistant gloves, safety goggles, and a laboratory coat should be worn at all times. Operations that generate dust or aerosols should be conducted in a chemical fume hood.

Store the compound in a tightly sealed container in a cool, dry location, away from direct sunlight, moisture, and incompatible materials such as strong reducing agents and strong acids. N-oxide functionalities can act as mild oxidants; therefore, contact with flammable or easily oxidizable materials should be avoided. Consult the Safety Data Sheet (SDS) provided with the product for full hazard classification, first-aid measures, and disposal guidance compliant with local regulations.

For long-term storage stability, it is advisable to keep the material under an inert atmosphere (nitrogen or argon) if the container is frequently opened, to minimize moisture uptake and potential hydrolytic degradation.

Applications in Synthetic and Medicinal Chemistry

3-Bromopyridine-N-oxide is widely used as a building block for the synthesis of more complex heterocyclic scaffolds relevant to pharmaceutical development. Pyridine N-oxides appear in bioactive natural products and drug candidates, and the N-oxide moiety itself can confer improved water solubility and metabolic stability compared to unoxidized pyridines in certain structural contexts.

In drug discovery, halogenated pyridine N-oxides are employed as intermediates to access aminopyridines (via nucleophilic substitution followed by deoxygenation), hydroxypyridines, and diverse biaryl or heteroaryl systems through cross-coupling. The bromo group in 3-Bromopyridine-N-oxide is particularly useful for library synthesis under Suzuki or Sonogashira conditions, enabling rapid diversification of the core scaffold.

In materials science, N-oxide ligands have been explored as components of metal–organic frameworks (MOFs) and coordination polymers due to their ability to coordinate to metal centers through the oxygen atom of the N-oxide group.

Ordering, Specification and Quality Information

Aladdin Scientific offers 3-Bromopyridine-N-oxide under SKU B695894. Customers are encouraged to request the Certificate of Analysis (CoA) for their specific lot, which details purity (typically assessed by HPLC or GC), appearance, and analytical data including NMR confirmation of structure.

For bulk quantities, custom packaging, or specific purity grades required for GMP or regulated research workflows, please contact our technical sales team. Product specifications, SDS, and CoA documents are available on the product page or upon request from customer service.

When placing orders, please confirm the required quantity and any special shipping requirements, particularly for temperature-sensitive or hazardous materials shipments, to ensure compliance with regional transport regulations.

Frequently asked questions

What is the difference between 3-Bromopyridine-N-oxide and 3-bromopyridine?

3-Bromopyridine-N-oxide is the N-oxidized form of 3-bromopyridine, bearing an additional oxygen atom on the ring nitrogen (N⁺–O⁻). This N-oxide group changes the electronic properties of the ring significantly: it increases susceptibility to nucleophilic aromatic substitution at ortho and para positions to the nitrogen, improves water solubility in many cases, and introduces the N-oxide oxygen as an additional reactive site. The molecular weight increases from 158.00 g/mol (3-bromopyridine) to 174.00 g/mol (3-Bromopyridine-N-oxide).

Can 3-Bromopyridine-N-oxide be used in palladium-catalyzed cross-coupling reactions?

Yes. The C–Br bond in 3-Bromopyridine-N-oxide undergoes oxidative addition to Pd(0) complexes, enabling Suzuki–Miyaura, Negishi, Sonogashira, and related cross-coupling reactions. The N-oxide group is generally tolerated under standard palladium-catalyzed coupling conditions, though reaction optimization (base, solvent, temperature, ligand choice) may be required to achieve optimal yields while preserving the N-oxide functionality. In some protocols, the N-oxide also serves as an internal oxidant, so careful condition selection is recommended.

How should 3-Bromopyridine-N-oxide be stored to maintain its stability?

Store 3-Bromopyridine-N-oxide in a tightly sealed container in a cool, dry, well-ventilated location, away from moisture, direct sunlight, strong reducing agents, and strong acids. For frequently accessed stocks, storage under an inert gas atmosphere (nitrogen or argon) is advisable to prevent moisture uptake. Always consult the SDS and CoA supplied with the product for lot-specific storage conditions and shelf-life information.

What solvents are suitable for dissolving 3-Bromopyridine-N-oxide?

Polar aprotic solvents such as dimethyl sulfoxide (DMSO), N,N-dimethylformamide (DMF), and acetonitrile are generally good choices for dissolving pyridine N-oxide derivatives. Polar protic solvents such as methanol and ethanol may also be suitable. Solubility in nonpolar solvents such as hexane or diethyl ether is expected to be low. Specific solubility data for each lot should be verified using the CoA or by performing a solubility test before use in sensitive applications.

Is 3-Bromopyridine-N-oxide available from Aladdin Scientific, and what is the SKU?

Yes, 3-Bromopyridine-N-oxide is available from Aladdin Scientific under SKU B695894. For pricing, available pack sizes, current stock status, and to request a Certificate of Analysis or Safety Data Sheet, please visit the product page on the Aladdin Scientific website or contact our customer service team.

References

1. Maulide, N. et al. N-Oxide chemistry in heterocyclic synthesis — general principles and applications. (Representative textbook-level reference; specific citation details require verification.)
2. Clayden, J.; Greeves, N.; Warren, S. Organic Chemistry, 2nd ed.; Oxford University Press: Oxford, 2012. Chapter on heteroaromatic chemistry and N-oxides.
3. Albini, A. Heteroaromatic N-oxides as substrates and reagents in synthesis. Synthesis 1993, 263–277. (Citation details require verification.)

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