4-Oxo-1,4-dihydroquinoline-3-carboxylic acid
[CAS# 13721-01-2]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Quinoline compound
• Name: 4-Oxo-1,4-dihydroquinoline-3-carboxylic acid
• Synonyms: 1,4-Dihydro-4-oxo-3-quinolinecarboxylic acid; 1,4-Dihydro-4-oxo-3-quinolinecarboxylic acid; 4-Quinolone-3-carboxylic acid
• Molecular Formula: C₁₀H₇NO₃
• Molecular Weight: 189.17
• CAS Registry Number: 13721-01-2
• EC Number: 604-008-0
• SMILES: C1=CC=C2C(=C1)C(=O)C(=CN2)C(=O)O

Properties

• Density: 1.5±0.1 g/cm³ Calc.^*
• Melting point: 269 - 270 °C (Expl.)
• Boiling point: 384.7±32.0 °C 760 mmHg (Calc.)^*
• Flash point: 186.5±25.1 °C (Calc.)^*
• Index of refraction: 1.73 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H302-H315-H319-H335
• Safety Statements: P261-P264-P264+P265-P270-P271-P280-P301+P317-P302+P352-P304+P340-P305+P351+P338-P319-P321-P330-P332+P317-P337+P317-P362+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Skin irritation	Skin Irrit.	2	H315
Eye irritation	Eye Irrit.	2	H319
Specific target organ toxicity - single exposure	STOT SE	3	H335
Eye irritation	Eye Irrit.	2A	H319
Acute toxicity	Acute Tox.	4	H302

Discovery and Applications

4-Oxo-1,4-dihydroquinoline-3-carboxylic acid is an aromatic heterocyclic compound that belongs to the quinoline family. It contains a fused benzene and pyridine ring system with a ketone group at position 4, a carboxylic acid group at position 3, and a hydrogen at the nitrogen in position 1, indicating the "1,4-dihydro" tautomeric form. The molecular formula is C₁₀H₇NO₃.

This compound serves as a key structural intermediate in the synthesis of many biologically active molecules, particularly in the development of quinolone antibiotics. The core structure—4-oxo-1,4-dihydroquinoline—is crucial for the activity of a wide range of synthetic antibacterial agents. The carboxylic acid group at position 3 plays a vital role in metal chelation and binding to bacterial DNA gyrase and topoisomerase IV enzymes, which are essential for bacterial DNA replication and repair.

4-Oxo-1,4-dihydroquinoline-3-carboxylic acid can be synthesized through cyclization reactions involving aniline derivatives and β-ketoesters or through condensation of appropriate anthranilic acid derivatives followed by intramolecular ring closure. These methods allow for variation in substituents and functional groups, providing a platform for structural diversification in medicinal chemistry.

In pharmaceutical research, this compound and its derivatives are widely investigated for antibacterial, antiviral, and anticancer activities. It is the core scaffold of numerous fluoroquinolones, including drugs such as ciprofloxacin and norfloxacin. Structural modifications at positions 1, 6, 7, and 8 of the quinoline ring can lead to significant changes in antimicrobial potency, spectrum of activity, and pharmacokinetic behavior.

Physically, 4-oxo-1,4-dihydroquinoline-3-carboxylic acid is typically a crystalline solid with limited solubility in water but moderate solubility in polar organic solvents such as dimethyl sulfoxide and ethanol. It exhibits characteristic UV absorbance due to its conjugated aromatic system and can be analyzed by NMR, IR, and mass spectrometry. The IR spectrum shows strong absorption bands for the ketone (around 1700 cm^-1) and carboxylic acid groups.

Chemically, the compound is stable under normal laboratory conditions but may undergo decarboxylation at elevated temperatures. The 4-oxo group can participate in tautomerism with its enol form, especially in polar protic solvents, although the keto form is typically predominant under neutral and acidic conditions.

In addition to pharmaceutical applications, derivatives of 4-oxo-1,4-dihydroquinoline-3-carboxylic acid are explored in agrochemical and material science fields, including uses as herbicides, corrosion inhibitors, and ligands in coordination chemistry.

In summary, 4-oxo-1,4-dihydroquinoline-3-carboxylic acid is a quinoline-based heterocycle featuring essential functional groups for biological and synthetic applications. Its structural core serves as a foundation for the design of a wide range of therapeutically important molecules, particularly antibiotics.

References

2016. Novel quinolone-3-carboxylic acid derivatives as anti-HIV-1 agents: design, synthesis, and biological activities. Medicinal Chemistry Research, 25(7).
DOI: 10.1007/s00044-016-1631-x

2014. 4-Quinolone-3-carboxylic acids as cell-permeable inhibitors of protein tyrosine phosphatase 1B. Bioorganic & Medicinal Chemistry, 22(14).
DOI: 10.1016/j.bmc.2014.05.028

2011. Investigations on the 4-Quinolone-3-carboxylic Acid Motif. 4. Identification of New Potent and Selective Ligands for the Cannabinoid Type 2 Receptor with Diverse Substitution Patterns and Antihyperalgesic Effects in Mice. Journal of Medicinal Chemistry, 54(13).
DOI: 10.1021/jm200476p