2,5-Difluoro-4-chlorobenzoic acid
[CAS# 132794-07-1]

Identification

• Classification: Organic raw materials >> Organic fluorine compound >> Fluorobenzoic acid series
• Name: 2,5-Difluoro-4-chlorobenzoic acid
• Synonyms: 4-chloro-2,5-difluorobenzoic acid
• Molecular Formula: C₇H₃ClF₂O₂
• Molecular Weight: 192.55
• CAS Registry Number: 132794-07-1
• EC Number: 626-140-8
• SMILES: C1=C(C(=CC(=C1F)Cl)F)C(=O)O

Properties

• Density: 1.6±0.1 g/cm³ Calc.^*
• Melting point: 154 - 157 °C (Expl.)
• Boiling point: 277.5±35.0 °C 760 mmHg (Calc.)^*
• Flash point: 121.6±25.9 °C (Calc.)^*
• Index of refraction: 1.535 (Calc.)^*

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

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H302-H312-H315-H319-H332-H335
• Safety Statements: P261-P264-P264+P265-P270-P271-P280-P301+P317-P302+P352-P304+P340-P305+P351+P338-P317-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
Specific target organ toxicity - single exposure	STOT SE	3	H335
Eye irritation	Eye Irrit.	2	H319
Acute toxicity	Acute Tox.	4	H302
Acute toxicity	Acute Tox.	4	H312
Acute toxicity	Acute Tox.	4	H332
Eye irritation	Eye Irrit.	2A	H319

Discovery and Applications

2,5-Difluoro-4-chlorobenzoic acid is a halogenated aromatic compound derived from benzoic acid and is characterized by the presence of two fluorine atoms at the 2 and 5 positions and a chlorine atom at the 4 position of the benzene ring. Its molecular formula is C7H3ClF2O2, and it exists as a crystalline solid under standard conditions. The compound exhibits notable thermal and chemical stability, owing to the electron-withdrawing nature of its halogen substituents, which significantly influence its reactivity and solubility profile.

This compound has gained relevance in synthetic organic chemistry, where it is employed as a valuable intermediate for the development of complex molecules, particularly in pharmaceutical and agrochemical research. Its structural framework allows for facile derivatization through classical aromatic substitution reactions. The electron-deficient aromatic ring created by the fluorine and chlorine substituents enhances the compound’s reactivity toward nucleophilic aromatic substitution (SNAr), a mechanism commonly exploited in the modification of halogenated benzenes.

In medicinal chemistry, 2,5-difluoro-4-chlorobenzoic acid serves as a precursor in the synthesis of bioactive molecules, including enzyme inhibitors, antimicrobial agents, and anti-inflammatory compounds. The introduction of fluorine atoms into a molecule is a well-established strategy for enhancing pharmacokinetic properties such as metabolic stability and membrane permeability. Fluorine's small size and high electronegativity can influence a compound’s binding affinity to biological targets by modulating dipole moments and altering hydrogen-bonding patterns. Similarly, chlorine contributes to lipophilicity and can assist in fine-tuning a drug candidate’s ability to interact with hydrophobic pockets in target proteins.

In agrochemical applications, derivatives of 2,5-difluoro-4-chlorobenzoic acid are investigated for their potential as herbicides, fungicides, and insecticides. The electron-withdrawing effects of the fluorine and chlorine atoms make the molecule more resistant to oxidative degradation, enhancing the environmental stability of formulations derived from it. Additionally, such halogenated benzoic acid derivatives have been used as starting materials in the design of systemic crop protection agents that can be absorbed and transported within plant tissues.

From a materials chemistry standpoint, this compound can be incorporated into polymers and resins that benefit from halogen-substituted aromatic monomers. These materials often exhibit enhanced thermal resistance, chemical inertness, and altered optical properties, all of which are advantageous in the development of coatings, adhesives, and electronic components. Furthermore, the compound’s acidic nature allows for salt formation with basic moieties, which can be exploited to improve solubility or generate ionically conductive materials.

The synthesis of 2,5-difluoro-4-chlorobenzoic acid typically begins with a fluorinated or chlorinated benzene precursor. It may be synthesized via selective halogenation of difluorobenzoic acid derivatives or through directed ortho-lithiation followed by electrophilic chlorination. These synthetic routes are compatible with standard laboratory procedures and enable the compound’s preparation in high yield and purity.

Handling of the compound generally requires standard precautions for halogenated aromatic acids, including the use of gloves and eye protection. It is moderately soluble in organic solvents such as dimethylformamide, methanol, and acetone, while its solubility in water is limited. The carboxylic acid functional group allows for further derivatization into esters, amides, and other functionalized analogs, which broadens the scope of chemical transformations that can be performed using this substrate.

Overall, 2,5-difluoro-4-chlorobenzoic acid represents a versatile intermediate in chemical synthesis, with applications spanning medicinal chemistry, agrochemical design, and materials science. Its halogen-substituted aromatic framework imparts unique chemical and physical properties that make it a desirable scaffold for the development of advanced functional molecules.

References

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