Ammonium trifluoroacetate
[CAS# 3336-58-1]

Identification

• Classification: Inorganic chemical industry >> Inorganic salt >> Inorganic ammonium salt
• Name: Ammonium trifluoroacetate
• Synonyms: azanium 2,2,2-trifluoroacetate
• Molecular Formula: C₂H₄F₃NO₂
• Molecular Weight: 131.05
• CAS Registry Number: 3336-58-1
• EC Number: 222-072-4
• SMILES: C(=O)(C(F)(F)F)[O-].[NH4+]

Properties

• Melting point: 123 - 125 °C (Expl.)

Safety Data

• Hazard Symbols: GHS06;GHS07;GHS09 Danger
• Risk Statements: H300-H315-H319-H335-H400
• Safety Statements: P261-P264-P264+P265-P270-P271-P273-P280-P301+P316-P302+P352-P304+P340-P305+P351+P338-P319-P321-P330-P332+P317-P337+P317-P362+P364-P391-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	2	H300
Acute hazardous to the aquatic environment	Aquatic Acute	1	H400
Eye irritation	Eye Irrit.	2	H319
Specific target organ toxicity - single exposure	STOT SE	3	H335
Skin irritation	Skin Irrit.	2	H315

Discovery and Applications

Ammonium trifluoroacetate is a fluorinated salt composed of ammonium cations (NH₄⁺) and trifluoroacetate anions (CF₃COO^-). The compound was developed as part of the mid-20th century expansion of organofluorine chemistry, when chemists explored trifluoroacetic acid and its derivatives for their unique electronic and chemical properties. The trifluoromethyl group strongly withdraws electrons, increasing the acidity of the conjugate acid and stabilizing the anion, while the ammonium cation provides a stable, water-soluble counterion. Ammonium trifluoroacetate is a white crystalline solid that is highly soluble in polar solvents and is generally stable under standard laboratory conditions.

The primary applications of ammonium trifluoroacetate are in chemical synthesis and analytical chemistry. In organic synthesis, it serves as a source of the trifluoroacetate anion, which can participate in nucleophilic substitution reactions and other transformations requiring a mild base or counterion. Its role as a trifluoroacetate source allows chemists to introduce the trifluoroacetyl or trifluoromethyl group into organic molecules, which is important in the design of pharmaceuticals, agrochemicals, and specialty materials. The electron-withdrawing properties of the trifluoromethyl group enhance the reactivity of adjacent functional groups, making the compound a versatile intermediate in fluorine chemistry.

In analytical chemistry, ammonium trifluoroacetate is often used in mass spectrometry and high-performance liquid chromatography (HPLC) as a volatile buffer or additive. Its decomposition during ionization produces minimal non-volatile residues, which improves signal clarity and reproducibility. This property makes it particularly useful in peptide and protein analysis, where trifluoroacetate salts can improve solubility and ionization efficiency.

The compound has also found indirect applications in pharmaceutical research. Fluorinated intermediates are highly valued in drug development because they can enhance metabolic stability, lipophilicity, and receptor binding. As a trifluoroacetate source, ammonium trifluoroacetate contributes to the synthesis of such fluorinated molecules, even though it is not itself used as a therapeutic agent.

In materials science, ammonium trifluoroacetate has been used in the preparation of fluorinated polymers and coatings. The trifluoromethyl group imparts chemical resistance, hydrophobicity, and thermal stability to materials, and the ammonium salt provides a convenient and soluble precursor for introducing these features. Its use in specialty chemical syntheses allows for controlled incorporation of fluorine into complex molecular architectures.

The development and continued use of ammonium trifluoroacetate reflect the broader importance of trifluoroacetate salts in modern chemistry. Its stability, solubility, and versatility make it a practical tool for the introduction of trifluoromethyl and trifluoroacetyl groups, supporting research and applications in organic synthesis, analytical chemistry, pharmaceuticals, and materials science.

References

2025. Demonstrating Bioequivalence for a Lumacaftor Monosubstance Formulation Versus Orkambi® (Lumacaftor/Ivacaftor) in Healthy Subjects. Drugs in R&D, 25(6).
DOI: 10.1007/s40268-025-00514-9

2024. Crystallization of Aminium Salts and Amides of Trifluoroacetic Acid. Molecular Structure of Ethylenediamine N,N'-Bis(trifluoroacetyl). Crystallography Reports, 69(12).
DOI: 10.1134/s1063774524601692

2024. Preparation, Physicochemical Properties, and Crystal Structures of Trifluoroacetic Acid Aminium Salts. Crystallography Reports, 69(12).
DOI: 10.1134/s1063774524600534