4-Chloroquinoline-7-carboxylic Acid: Properties & Applications
4-Chloroquinoline-7-carboxylic Acid: Properties & Applications
4-Chloroquinoline-7-carboxylic acid is a halogenated quinoline carboxylic acid building block widely used as a versatile intermediate in medicinal chemistry, heterocyclic synthesis, and the development of biologically active small molecules.
- Chemical Name
- 4-Chloroquinoline-7-carboxylic acid
- Molecular Formula
- C₁₀H₆ClNO₂
- Molecular Weight
- 207.61 g/mol
- Key Functional Groups
- Chloro substituent at C-4, carboxylic acid at C-7 of the quinoline ring
- Aladdin SKU
- C193584
- Typical Applications
- Pharmaceutical intermediate, heterocyclic building block, medicinal chemistry research
Chemical Structure and Properties
4-Chloroquinoline-7-carboxylic acid belongs to the quinoline family of bicyclic heteroaromatic compounds, consisting of a benzene ring fused to a pyridine ring. The compound features two key substituents: a chlorine atom at the 4-position of the quinoline scaffold and a carboxylic acid group at the 7-position. These functional groups confer distinct reactivity profiles that make this molecule particularly attractive in synthetic chemistry.
The chlorine atom at the electron-deficient 4-position is highly susceptible to nucleophilic aromatic substitution (SNAr) reactions, enabling straightforward displacement by amines, thiols, and other nucleophiles under mild conditions. This reactivity is a direct consequence of the electron-withdrawing influence of the ring nitrogen, which activates the C-4 position toward nucleophilic attack.
The carboxylic acid group at the 7-position provides a versatile handle for further functionalization, including amide bond formation, esterification, and decarboxylation reactions. The combination of these two reactive sites within a single, compact aromatic scaffold makes 4-Chloroquinoline-7-carboxylic acid a bifunctional building block of considerable synthetic value.
Synthesis and Functionalization Strategies
4-Chloroquinoline-7-carboxylic acid serves as a pivotal starting material in multi-step synthetic sequences. Its primary utility lies in nucleophilic aromatic substitution at the C-4 chloro position. Researchers can readily introduce diverse amine nucleophiles to generate 4-aminoquinoline-7-carboxylic acid derivatives, a transformation widely exploited in the preparation of drug candidates and biological probes.
The carboxylic acid moiety can be independently activated using standard coupling reagents such as HATU, EDC, or HBTU to form amide bonds with primary or secondary amines, yielding quinoline-7-carboxamide products. Alternatively, the acid can be converted to the corresponding acid chloride, ester, or reduced to the alcohol, each providing access to distinct downstream scaffolds.
Orthogonal functionalization — sequential modification of the chloro and carboxylic acid groups in a controlled order — enables the efficient construction of structurally complex, diversely substituted quinoline derivatives from a single, readily available precursor. This versatility makes C193584 a cost-effective choice for library synthesis and structure–activity relationship (SAR) studies.
Research and Medicinal Chemistry Applications
Quinoline scaffolds have a long history in medicinal chemistry, underpinning the development of antimalarial agents, antibacterial compounds, antiviral molecules, and kinase inhibitors. The specific substitution pattern of 4-Chloroquinoline-7-carboxylic acid — chloro at C-4 and carboxylic acid at C-7 — makes it relevant to the synthesis of analogues targeting a range of biological pathways.
The 4-chloroquinoline motif is structurally related to well-known antimalarial pharmacophores, and derivatives prepared from this building block may be evaluated for antiparasitic activity. Additionally, 4-aminoquinoline derivatives accessed via SNAr reactions have been investigated as inhibitors of various kinases and other enzyme targets relevant to oncology and infectious disease research.
Beyond target-based drug discovery, this compound is also employed in the synthesis of fluorescent probes, coordination chemistry ligands, and functionalized materials, reflecting the broad utility of the quinoline carboxylic acid scaffold across multiple scientific disciplines.
Handling, Storage, and Safety Considerations
As with all laboratory reagents, appropriate handling procedures should be followed when working with 4-Chloroquinoline-7-carboxylic acid. Researchers should consult the Safety Data Sheet (SDS) provided by Aladdin Scientific (SKU: C193584) for complete hazard classification, first-aid measures, and disposal guidance prior to use.
The compound should be stored in a cool, dry, well-ventilated area, away from moisture, heat, and incompatible materials. Standard personal protective equipment — including laboratory coat, nitrile gloves, and safety glasses — should be worn during weighing and handling operations. Work in a fume hood is recommended when handling powdered or dissolved forms to minimize inhalation exposure.
Waste disposal must comply with applicable local, national, and institutional regulations for chemical waste. Users are advised to verify the current SDS for the most up-to-date safety information specific to this compound.
Frequently asked questions
What makes the C-4 chloro group of 4-Chloroquinoline-7-carboxylic acid reactive?
The C-4 position of the quinoline ring is activated toward nucleophilic aromatic substitution (SNAr) because the ring nitrogen acts as a strong electron-withdrawing group, stabilizing the Meisenheimer complex intermediate. This makes displacement of the chloride by amine, thiol, or alkoxide nucleophiles facile under mild to moderate reaction conditions.
How can the carboxylic acid group of C193584 be functionalized?
The carboxylic acid at the 7-position can be functionalized using standard methods: amide coupling with reagents such as HATU or EDC/NHS, conversion to an acid chloride with thionyl chloride or oxalyl chloride, esterification under Fischer conditions or with diazomethane, or reduction to the primary alcohol using reducing agents such as LiAlH4 or borane. Each approach provides access to a distinct class of quinoline derivatives.
Is 4-Chloroquinoline-7-carboxylic acid suitable for library synthesis?
Yes. The bifunctional nature of 4-Chloroquinoline-7-carboxylic acid — with orthogonally reactive chloro and carboxylic acid groups — makes it well suited for parallel synthesis and combinatorial library construction. By independently varying the nucleophile at C-4 and the amine partner for amide coupling at C-7, researchers can rapidly generate structurally diverse quinoline analogue libraries for SAR studies.
What are recommended storage conditions for SKU C193584?
4-Chloroquinoline-7-carboxylic acid should be stored in a cool, dry, and well-ventilated location away from moisture and incompatible substances. Users should refer to the current Aladdin Scientific SDS for C193584 for precise storage temperature requirements and any additional precautionary guidance.
References
- Eicher, T.; Hauptmann, S.; Speicher, A. The Chemistry of Heterocycles: Structure, Reactions, Synthesis, and Applications, 3rd ed.; Wiley-VCH: Weinheim, 2012.
- Manske, R. H. F. (Ed.) The Chemistry of Heterocyclic Compounds: Quinolines; Wiley-Interscience: New York, 1977.
- Clayden, J.; Greeves, N.; Warren, S. Organic Chemistry, 2nd ed.; Oxford University Press: Oxford, 2012. Chapter on aromatic nucleophilic substitution.
- Aladdin Scientific. Product Data Sheet: 4-Chloroquinoline-7-carboxylic acid, SKU C193584. Aladdin Scientific Corp.
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