4-Chloropyridine-2-Carboxylic Acid: Properties & Applications

4-Chloropyridine-2-Carboxylic Acid is a halogenated pyridinecarboxylic acid widely employed as a versatile building block in medicinal chemistry, agrochemical research, and the synthesis of biologically active heterocyclic compounds.

Chemical Name

4-Chloropyridine-2-Carboxylic Acid

SKU

C107903

Molecular Formula

C6H4ClNO2

Molecular Weight

157.55 g/mol

CAS Number

5470-96-2

Functional Groups

Carboxylic acid, chloro substituent, pyridine ring

Primary Use

Pharmaceutical and agrochemical intermediate, heterocyclic synthesis

Chemical Identity and Physical Properties

4-Chloropyridine-2-Carboxylic Acid (CAS 5470-96-2) is a chlorine-substituted pyridine derivative bearing a carboxylic acid group at the 2-position and a chloro substituent at the 4-position of the aromatic ring. Its molecular formula is C₆H₄ClNO₂ with a molecular weight of approximately 157.55 g/mol.

The compound typically appears as a white to off-white crystalline solid. The electron-withdrawing nature of both the ring nitrogen and the 4-chloro substituent renders the pyridine ring electrophilic, facilitating nucleophilic aromatic substitution reactions at the halogenated position. The carboxylic acid group further enhances the reactivity profile, enabling amide bond formation, esterification, and metal-catalyzed coupling reactions.

Proper storage under cool, dry conditions away from moisture is recommended to maintain purity and stability.

Synthesis and Reactivity

4-Chloropyridine-2-Carboxylic Acid serves as a multifunctional synthetic intermediate owing to the dual reactivity of its carboxylic acid and aryl chloride functionalities. Key reaction pathways include:

• Nucleophilic Aromatic Substitution (SNAr): The 4-chloro group is susceptible to displacement by amines, alkoxides, and other nucleophiles under appropriate conditions, enabling the rapid diversification of the pyridine scaffold.
• Amide Coupling: The carboxylic acid moiety can be activated using standard coupling reagents (e.g., HATU, EDC) to produce bioactive amide derivatives of interest in drug discovery programs.
• Esterification: Reaction with alcohols under acidic or coupling conditions affords pyridine ester intermediates.
• Transition-Metal Catalysis: The C–Cl bond participates in palladium-catalyzed cross-coupling reactions such as Suzuki–Miyaura and Buchwald–Hartwig couplings, expanding access to biaryl and aminopyridine motifs.

This broad reactivity makes the compound a valuable linchpin in multi-step synthesis.

Applications in Medicinal and Agrochemical Research

Halogenated pyridinecarboxylic acids such as 4-Chloropyridine-2-Carboxylic Acid are indispensable building blocks in both pharmaceutical and agrochemical industries due to the privileged status of the pyridine ring in bioactive molecules.

Medicinal Chemistry: The compound is frequently employed in the construction of kinase inhibitors, antiviral agents, and other small-molecule therapeutics. The chloro group enables late-stage diversification via SNAr or cross-coupling, while the carboxylic acid supports the introduction of amide bioisosteres. Pyridine-2-carboxylic acid derivatives are also known metal chelators, which has implications in the design of metalloenzyme inhibitors.

Agrochemical Research: Chloropyridine scaffolds appear in several commercial herbicides and fungicides. 4-Chloropyridine-2-Carboxylic Acid can serve as a precursor in the preparation of novel pyridine-based agrochemicals.

Materials and Coordination Chemistry: The compound's ability to act as a bidentate ligand (via the ring nitrogen and carboxylate oxygen) makes it useful in the preparation of metal–organic frameworks (MOFs) and coordination complexes for catalysis and sensing applications.

Handling, Safety, and Storage Recommendations

As with all laboratory reagents, appropriate safety precautions should be observed when handling 4-Chloropyridine-2-Carboxylic Acid. Researchers should consult the current Safety Data Sheet (SDS) prior to use for comprehensive hazard information, first-aid measures, and disposal guidance.

Personal Protective Equipment (PPE): Chemical-resistant gloves, safety goggles, and a laboratory coat are recommended. Avoid inhalation of dust; work in a fume hood when handling larger quantities.

Storage: Store in a tightly sealed container in a cool (2–25 °C), dry, well-ventilated location, away from incompatible materials such as strong bases and oxidizing agents. Keep away from moisture to prevent hydrolytic degradation of the compound.

Disposal: Dispose of waste material in accordance with applicable local, regional, and national regulations.

Always verify the latest SDS and regulatory status before use, as guidelines may be updated.

Frequently asked questions

What is the CAS number for 4-Chloropyridine-2-Carboxylic Acid?

The CAS registry number for 4-Chloropyridine-2-Carboxylic Acid is 5470-96-2. Aladdin Scientific supplies this compound under SKU C107903.

What reactions can be performed with 4-Chloropyridine-2-Carboxylic Acid?

The compound participates in nucleophilic aromatic substitution at the 4-chloro position, amide coupling and esterification via the carboxylic acid group, and palladium-catalyzed cross-coupling reactions (e.g., Suzuki–Miyaura, Buchwald–Hartwig) at the C–Cl bond. This dual functionality makes it highly versatile in multi-step organic synthesis.

How should 4-Chloropyridine-2-Carboxylic Acid be stored?

Store the compound in a tightly sealed container under cool (2–25 °C), dry, and well-ventilated conditions. Protect from moisture and incompatible materials such as strong bases and oxidizing agents. Always refer to the current SDS for detailed storage requirements.

Is 4-Chloropyridine-2-Carboxylic Acid suitable for use as a metal chelator?

Yes, pyridine-2-carboxylic acid derivatives are established metal chelators, coordinating through the ring nitrogen and carboxylate oxygen to form stable chelate rings. This property is exploited in coordination chemistry, metalloenzyme inhibitor design, and the synthesis of metal–organic frameworks.

What is the molecular weight of 4-Chloropyridine-2-Carboxylic Acid?

The molecular weight of 4-Chloropyridine-2-Carboxylic Acid (C6H4ClNO2) is approximately 157.55 g/mol.

References

1. Clayden, J.; Greeves, N.; Warren, S. Organic Chemistry, 2nd ed.; Oxford University Press: Oxford, 2012. (General reference for nucleophilic aromatic substitution and carboxylic acid reactivity.)
2. Joule, J. A.; Mills, K. Heterocyclic Chemistry, 5th ed.; Wiley-Blackwell: Chichester, 2010. (Reference for pyridine chemistry and reactivity.)
3. Aladdin Scientific product page for 4-Chloropyridine-2-Carboxylic Acid, SKU C107903. (Source for SKU and product identity.)

Products are supplied for research and development use only. Not for use in humans, animals, diagnosis, or therapy.