Difluoroacetic acid sodium salt
[CAS# 2218-52-2]

Identification

• Classification: Organic raw materials >> Carboxylic compounds and derivatives >> Halogenation, sulfonation, nitration or nitrosation of carboxylic acids
• Name: Difluoroacetic acid sodium salt
• Molecular Formula: C₂HF₂NaO₂
• Molecular Weight: 118.01
• CAS Registry Number: 2218-52-2
• EC Number: 218-720-0
• SMILES: C(C(=O)[O-])(F)F.[Na+]

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H302-H315-H319-H335
• Safety Statements: P261-P280-P301+P312-P302+P352-P305+P351+P338

Discovery and Applications

Difluoroacetic acid sodium salt is an organofluorine compound with the chemical formula NaO₂CCHDF₂. It is the sodium salt of difluoroacetic acid, in which the acidic proton of the carboxyl group is replaced by a sodium cation (Na⁺). This compound combines the high reactivity of a carboxylate with the strong electron-withdrawing effect of two fluorine atoms on the α-carbon, giving it unique chemical and biochemical properties.

The origins of difluoroacetic acid and its salts lie in the mid-20th century, when fluorinated carboxylic acids were systematically studied as part of the broader exploration of organofluorine chemistry. Fluorine substitution was known to significantly alter acidity, stability, and reactivity, and difluoroacetic acid quickly gained attention for its higher acidity compared to acetic acid. Conversion to its sodium salt provided a more manageable, stable, and water-soluble form for laboratory and industrial use.

Difluoroacetic acid sodium salt has found application as an intermediate in organic synthesis. The strongly electron-withdrawing difluoromethyl group stabilizes carbanionic intermediates, making the compound useful in the preparation of fluorinated molecules, particularly pharmaceuticals and agrochemicals where the CF₂ group enhances metabolic stability and modulates biological activity. It is often employed in nucleophilic substitution and condensation reactions, where it introduces difluoromethyl functionality into target molecules.

In biochemistry and medicinal research, salts of difluoroacetic acid have been explored for their effects on metabolic pathways. Structural similarity to pyruvate allows difluoroacetate derivatives to interact with enzymes in cellular energy cycles, influencing processes such as oxidative phosphorylation. While sodium difluoroacetate itself is not widely used as a drug, it has been studied as a biochemical tool for investigating mitochondrial function and enzyme inhibition.

The compound is also relevant in materials chemistry, serving as a building block in the design of fluorinated polymers and specialty chemicals. Its carboxylate functionality allows it to participate in condensation and coordination reactions, while the difluoro group imparts hydrophobicity and chemical resistance.

Synthesis of difluoroacetic acid sodium salt is typically achieved by neutralizing difluoroacetic acid with sodium hydroxide, producing the salt in aqueous solution. Isolation as a solid is possible by careful evaporation and drying, though the material must be handled with care due to its hygroscopic nature and potential for decomposition under harsh conditions.

Overall, difluoroacetic acid sodium salt is a valuable reagent in organofluorine chemistry. Its combination of carboxylate reactivity and difluoromethyl electronic effects has made it an important tool in synthesis, biochemical research, and the development of fluorine-containing compounds with specialized industrial and pharmaceutical applications.

References

2023. Structural insights into hydrolytic defluorination of difluoroacetate by microbial fluoroacetate dehalogenases. The FEBS Journal, 290(14).
DOI: 10.1111/febs.16903

2021. Residue analytical method for the determination of trifluoroacetic acid and difluoroacetic acid in plant matrices by capillary electrophoresis tandem mass spectrometry (CE-MS/MS). Journal of Chromatography A, 1646.
DOI: 10.1016/j.chroma.2021.462096

2019. Evidence for the Formation of Difluoroacetic Acid in Chlorofluorocarbon-Contaminated Ground Water. Molecules, 24(6).
DOI: 10.3390/molecules24061039