5-Bromo-2-pyridinecarboxylic Acid: Properties & Applications

5-Bromo-2-pyridinecarboxylic Acid is a halogenated pyridine carboxylic acid widely used as a versatile building block in heterocyclic synthesis, medicinal chemistry, and the preparation of pharmaceutically relevant intermediates.

Chemical Name

5-Bromo-2-pyridinecarboxylic Acid

CAS Number

30766-11-1

Molecular Formula

C₆H₄BrNO₂

Molecular Weight

202.01 g/mol

Appearance

White to off-white crystalline powder

Key Functional Groups

Carboxylic acid, aromatic C–Br bond, pyridine nitrogen

SKU

B151859

Chemical Structure and Properties

5-Bromo-2-pyridinecarboxylic Acid (CAS 30766-11-1) is a pyridine derivative bearing a bromine substituent at the 5-position and a carboxylic acid group at the 2-position of the aromatic ring. The molecular formula is C₆H₄BrNO₂, with a molecular weight of approximately 202.01 g/mol.

The compound typically appears as a white to off-white crystalline solid. The combination of an electron-deficient pyridine ring, a reactive aryl bromide, and an ionizable carboxylic acid group makes this molecule a multifunctional scaffold. The pyridine nitrogen and the carboxylic acid can participate in hydrogen bonding and metal coordination, while the C–Br bond is a handle for transition-metal-catalyzed cross-coupling reactions.

Solubility characteristics follow those of other halopyridine carboxylic acids: moderate solubility in polar organic solvents such as dimethyl sulfoxide (DMSO), methanol, and ethanol, with limited solubility in non-polar solvents and water at neutral pH. Aqueous solubility improves markedly under basic conditions due to carboxylate formation.

Synthesis and Reactivity

5-Bromo-2-pyridinecarboxylic Acid serves as both a synthetic target and a key intermediate in multi-step organic synthesis. The aryl bromide at the 5-position is well-suited for palladium-catalyzed cross-coupling reactions, including Suzuki–Miyaura, Negishi, Stille, and Sonogashira couplings, enabling efficient introduction of diverse carbon substituents onto the pyridine ring.

The carboxylic acid functionality at the 2-position provides additional synthetic handles: it can be converted to acid chlorides, esters, amides, and reduced to the corresponding alcohol or aldehyde. When combined with the adjacent pyridine nitrogen, the 2-carboxylic acid moiety can also participate in chelation-directed metalation and cyclization reactions, facilitating the construction of fused heterocyclic systems.

Researchers have employed such halopyridine carboxylic acids in the preparation of bidentate ligands for coordination chemistry, as well as in the synthesis of biologically active small molecules where the pyridine ring is a pharmacophoric element. Care should be taken during reactions involving strong bases or reductants, as these may affect both the aryl halide and the acidic proton simultaneously.

Research and Pharmaceutical Applications

The dual functionality of 5-Bromo-2-pyridinecarboxylic Acid makes it particularly valuable in medicinal chemistry and drug discovery. Pyridine-containing scaffolds are among the most prevalent heterocyclic motifs found in approved pharmaceuticals, and the 2-carboxypyridine unit is a recognized pharmacophore in enzyme inhibitors, receptor ligands, and metal-chelating agents.

In drug discovery workflows, the compound is commonly used as a fragment or building block that introduces a nitrogen-containing aromatic ring while retaining the ability to diversify the molecule through the reactive bromide and the carboxylic acid. This makes it suitable for fragment-based drug design and library synthesis.

Beyond medicinal chemistry, 5-Bromo-2-pyridinecarboxylic Acid finds use in the development of functional materials, coordination polymers, and metal-organic frameworks (MOFs), where pyridyl carboxylates serve as bridging ligands. It is also employed in agrochemical research and as a reference standard in analytical chemistry applications.

Handling, Storage, and Safety

5-Bromo-2-pyridinecarboxylic Acid should be handled using standard laboratory safety practices appropriate for organic acids and organobromine compounds. Personal protective equipment including gloves, safety glasses, and a laboratory coat is recommended. Work should be performed in a well-ventilated fume hood, particularly when handling fine powders to minimize inhalation exposure.

The compound should be stored in a cool, dry, and well-ventilated area, protected from moisture and direct light. Sealed containers help prevent absorption of atmospheric moisture and maintain product quality. It is advisable to store the material at room temperature or as specified on the product certificate of analysis.

Disposal must comply with local regulations governing halogenated organic waste. Users should consult the Safety Data Sheet (SDS) provided by Aladdin Scientific for detailed hazard classifications, first-aid measures, and waste disposal guidance before use.

Frequently asked questions

What reactions is 5-Bromo-2-pyridinecarboxylic Acid commonly used for?

5-Bromo-2-pyridinecarboxylic Acid is most commonly employed in palladium-catalyzed cross-coupling reactions such as Suzuki–Miyaura, Negishi, and Sonogashira couplings via its aryl bromide. The carboxylic acid group can be further functionalized to esters, amides, or acid chlorides, enabling diverse synthetic transformations.

How should 5-Bromo-2-pyridinecarboxylic Acid be stored to maintain its integrity?

The compound should be stored in a tightly sealed container in a cool, dry, and well-ventilated location, away from moisture and direct light. These conditions prevent hydrolysis and degradation, maintaining purity over the product's shelf life.

Is 5-Bromo-2-pyridinecarboxylic Acid suitable for use in medicinal chemistry libraries?

Yes, 5-Bromo-2-pyridinecarboxylic Acid is well-suited for medicinal chemistry library synthesis because it combines a biologically relevant pyridine pharmacophore with two orthogonal reactive handles—the aryl bromide and carboxylic acid—allowing rapid structural diversification. It is widely used in fragment-based drug design and lead optimization programs.

What solvents are recommended for dissolving 5-Bromo-2-pyridinecarboxylic Acid?

5-Bromo-2-pyridinecarboxylic Acid dissolves well in polar aprotic solvents such as DMSO, and in polar protic solvents like methanol and ethanol. Aqueous solubility is low at neutral pH but increases significantly under basic conditions due to formation of the carboxylate salt.

References

1. General reference: Joule, J. A.; Mills, K. Heterocyclic Chemistry, 5th ed.; Wiley-Blackwell, 2010. (Background on pyridine reactivity and cross-coupling applications)
2. Miyaura, N.; Suzuki, A. Palladium-Catalyzed Cross-Coupling Reactions of Organoboron Compounds. Chem. Rev. 1995, 95, 2457–2483. doi:10.1021/cr00039a007
3. Aladdin Scientific product page for 5-Bromo-2-pyridinecarboxylic Acid, SKU B151859.

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