2,4,5-Trifluorobenzoic acid
[CAS# 446-17-3]

Identification

• Classification: Organic raw materials >> Organic fluorine compound >> Fluorobenzoic acid series
• Name: 2,4,5-Trifluorobenzoic acid
• Molecular Formula: C₇H₃F₃O₂
• Molecular Weight: 176.09
• CAS Registry Number: 446-17-3
• EC Number: 610-198-6
• SMILES: C1=C(C(=CC(=C1F)F)F)C(=O)O

Properties

• Melting point: 98-101 °C

Safety Data

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

Hazard Classification

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

Discovery and Applications

2,4,5-Trifluorobenzoic acid is an aromatic carboxylic acid characterized by the presence of three fluorine atoms at the 2, 4, and 5 positions on the benzene ring. The discovery of trifluorinated benzoic acids can be traced to early fluorine chemistry, where researchers aimed to introduce fluorine atoms into organic molecules to alter their physical and chemical properties. Fluorine’s electronegativity and small size make it highly influential in modifying the behavior of organic compounds, often enhancing their stability, lipophilicity, and bioactivity.

The synthesis of 2,4,5-trifluorobenzoic acid typically involves selective fluorination reactions starting from substituted benzoic acid derivatives or through catalytic methods using fluorinating agents. One approach uses halogen exchange reactions, where chlorine atoms on a precursor molecule are replaced by fluorine through nucleophilic substitution. This fluorinated benzoic acid offers interesting reactivity due to the electron-withdrawing nature of the fluorine atoms, which influences both the acidity of the carboxylic group and the overall reactivity of the aromatic ring.

The applications of 2,4,5-trifluorobenzoic acid span various fields, particularly in pharmaceuticals, agrochemicals, and materials science. In pharmaceutical research, the introduction of fluorine atoms into drug molecules has become a common strategy to improve drug properties, including metabolic stability and binding affinity. Trifluorinated benzoic acids, including 2,4,5-trifluorobenzoic acid, serve as intermediates in the synthesis of a variety of drug candidates. Their ability to modulate the pharmacokinetics of biologically active compounds makes them valuable building blocks in medicinal chemistry. For instance, trifluorobenzoic acid derivatives have been investigated for their potential as anti-inflammatory, antimicrobial, and anticancer agents.

In the agrochemical industry, 2,4,5-trifluorobenzoic acid plays a role in the development of herbicides, insecticides, and fungicides. The fluorinated benzene ring enhances the biological activity and environmental persistence of these compounds, making them more effective at lower concentrations and reducing the frequency of application. Fluorinated agrochemicals are known for their ability to resist metabolic degradation in plants and pests, contributing to their efficacy in controlling crop diseases and pests.

Furthermore, 2,4,5-trifluorobenzoic acid is used in the field of materials science, particularly in the development of specialty polymers and coatings. The presence of fluorine atoms improves the thermal stability, chemical resistance, and hydrophobic properties of polymeric materials. These properties are especially valuable in coatings, adhesives, and sealants used in harsh environments or applications requiring high durability.

Overall, 2,4,5-trifluorobenzoic acid is a versatile chemical intermediate that finds application in diverse industries. Its discovery and development have been driven by the unique effects of fluorine substitution on the reactivity and properties of aromatic compounds. Whether in drug development, agrochemicals, or materials, this trifluorinated benzoic acid plays an important role in advancing chemical innovation.

References

1998. Ultra trace determination of fluorinated aromatic carboxylic acids in aqueous reservoir fluids by solid phase extraction in combination with negative ion chemical ionisation mass spectrometry after derivatisation with pentafluorobenzyl bromide. Fresenius' Journal of Analytical Chemistry, 362(2).
DOI: 10.1007/s002160051018

2016. Rapid ion-exchange matrix removal for a decrease of detection limits in the analysis of salt-rich reservoir waters for fluorobenzoic acids by liquid chromatography coupled with tandem mass spectrometry. Analytical and Bioanalytical Chemistry, 408(5).
DOI: 10.1007/s00216-016-0060-5

2018. Synergistic coupling of in-line single-drop microextraction and on-line large-volume sample stacking for capillary electrophoresis/mass spectrometry. Analytical and Bioanalytical Chemistry, 411(2).
DOI: 10.1007/s00216-018-1535-3