5-Bromo-2-ethoxy-4-methyl-3-nitropyridine: Properties & Uses

5-Bromo-2-ethoxy-4-methyl-3-nitropyridine is a multifunctionally substituted pyridine building block bearing bromo, ethoxy, methyl, and nitro substituents that make it a versatile intermediate for heterocyclic and pharmaceutical synthesis.

IUPAC Name

5-Bromo-2-ethoxy-4-methyl-3-nitropyridine

SKU

B180230

Molecular Formula

C8H9BrN2O3

Molecular Weight

261.07 g/mol

Key Functional Groups

Bromo, Ethoxy, Methyl, Nitro on pyridine ring

Primary Use

Heterocyclic synthesis intermediate and pharmaceutical building block

Chemical Structure and Properties

5-Bromo-2-ethoxy-4-methyl-3-nitropyridine (SKU B180230) is a pyridine derivative carrying four distinct substituents: a bromine atom at the 5-position, an ethoxy group at the 2-position, a methyl group at the 4-position, and a nitro group at the 3-position. This combination of electron-withdrawing (nitro, bromo) and electron-donating (ethoxy, methyl) groups creates a polarized aromatic ring with differentiated reactivity at each position.

The molecular formula is C₈H₉BrN₂O₃ with a molecular weight of approximately 261.07 g/mol. The nitro group at C-3, flanked by the electron-donating methyl at C-4 and the ring nitrogen, confers electrophilic character to adjacent positions, while the bromine at C-5 serves as a handle for metal-catalyzed cross-coupling reactions. The ethoxy group at C-2 can be hydrolyzed or displaced under appropriate conditions, providing additional synthetic flexibility.

Synthesis Relevance and Reactivity

The bromine substituent in 5-Bromo-2-ethoxy-4-methyl-3-nitropyridine is well-suited for palladium-catalyzed cross-coupling reactions, including Suzuki-Miyaura, Negishi, and Buchwald-Hartwig couplings, enabling the introduction of aryl, vinyl, or amino groups at C-5. Such transformations are foundational in the construction of complex heterocyclic scaffolds used in medicinal chemistry programs.

The nitro group at C-3 can be reduced to a primary amine using standard reducing agents (e.g., iron/acetic acid, catalytic hydrogenation, or SnCl₂), generating an aminopyridine intermediate that is highly reactive toward further cyclization or acylation. This two-step sequence—coupling followed by nitro reduction—is a common strategy for accessing fused bicyclic systems such as imidazopyridines or pyrrolopyridines, which are privileged scaffolds in drug discovery.

The ethoxy group at C-2 may also be displaced by nucleophiles such as amines under forcing conditions, enabling the preparation of 2-aminopyridine analogs without requiring separate protection-deprotection steps.

Research and Pharmaceutical Applications

Multifunctionalized nitropyridines such as 5-Bromo-2-ethoxy-4-methyl-3-nitropyridine are valued in medicinal chemistry as starting materials or key intermediates for active pharmaceutical ingredients (APIs) and drug candidates. The pyridine ring is one of the most prevalent heterocycles in approved drugs, owing to its favorable pharmacokinetic profile and capacity to form hydrogen bonds with biological targets.

The combination of a reducible nitro group, a cross-coupling-ready bromo substituent, and a displaceable ethoxy group in a single molecule allows chemists to execute divergent synthetic routes from a single building block, reducing the number of synthetic steps and improving overall efficiency. This compound is therefore particularly useful in fragment-based drug discovery and lead optimization campaigns where rapid analog synthesis is required.

Beyond pharmaceutical applications, halogenated nitropyridines are also used in materials science research, including as precursors to nitrogen-rich heterocyclic ligands for coordination chemistry and organic electronics.

Handling, Storage, and Safety Considerations

As with all aromatic nitro compounds and organobromine reagents, 5-Bromo-2-ethoxy-4-methyl-3-nitropyridine should be handled with appropriate 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 cool, dry place away from direct sunlight, strong oxidizers, and reducing agents. Sealed containers under inert atmosphere (nitrogen or argon) are recommended to maintain purity and prevent moisture uptake. Consult the current Safety Data Sheet (SDS) available from Aladdin Scientific for specific hazard classifications, first-aid measures, and disposal guidance before use.

Researchers should verify local regulations regarding the handling and disposal of brominated and nitro-containing organic compounds, as these may be subject to environmental reporting requirements.

Frequently asked questions

What cross-coupling reactions are compatible with 5-Bromo-2-ethoxy-4-methyl-3-nitropyridine?

The C–Br bond at the 5-position is compatible with a broad range of palladium-catalyzed cross-coupling reactions, including Suzuki-Miyaura (arylboronic acids), Negishi (organozinc reagents), and Buchwald-Hartwig amination. Standard Pd(0) or Pd(II) pre-catalysts with appropriate phosphine ligands and base are typically employed. Reaction conditions should be optimized to avoid competing reduction of the nitro group under strongly reducing conditions.

How can the nitro group in this compound be reduced, and what intermediate does it yield?

The nitro group can be reduced to a primary amine using several methods, including catalytic hydrogenation (H2/Pd-C), iron powder in acetic acid, or stannous chloride (SnCl2) in ethanol under reflux. The resulting product is the corresponding 3-amino-5-bromo-2-ethoxy-4-methylpyridine, a reactive amine intermediate suitable for further functionalization such as acylation, cyclization, or additional coupling reactions.

What are the recommended storage conditions for B180230?

5-Bromo-2-ethoxy-4-methyl-3-nitropyridine (B180230) should be stored in a tightly sealed container under an inert atmosphere in a cool, dry, dark location. These conditions minimize potential decomposition from moisture, light, or reactive atmospheric components and help maintain reagent purity over time. Always refer to the current SDS from Aladdin Scientific for authoritative storage guidance.

Can the ethoxy group at C-2 be replaced by an amine?

Yes, the ethoxy group at C-2 can act as a leaving group and be displaced by primary or secondary amines under forcing conditions, such as heating in a polar aprotic solvent or neat amine at elevated temperature. This transformation offers a route to 2-aminopyridine analogs without the need for prior protection of other functional groups, though selectivity and competing reactions should be evaluated empirically for each specific amine nucleophile.

References

1. March, J. Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 4th ed.; Wiley-Interscience: New York, 1992.
2. Joule, J. A.; Mills, K. Heterocyclic Chemistry, 5th ed.; Wiley-Blackwell: Oxford, 2010.
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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