Trifluoroacetic acid is a corrosive organofluorine compound that is structurally analogous to, but stronger than, acetic acid. Available in various quantities and reagent grades, it is used in NMR spectroscopy, mass spectrometry, organic synthesis, etc.

Almost 100,000-fold more acidic than acetic acid, TFA is widely used in organic chemistry. TFA is used as a reagent in organic synthesis because of its properties: volatility, organic solvent solubility, and acidic strength. It is less oxidizing than sulfuric acid and is more readily available in its anhydrous form than some other acids . Other features include:

• Used in acid-catalyzed reactions, especially peptide synthesis (to cleave esters)
• Dissolves protein when mixed with liquid SO₂
• Removes t-butyl derived side-chain protecting groups in Fmoc peptide synthesis
• Can remove the t-butoxycarbonyl protecting group in organic synthesis
• At low concentrations, acts as an ion-pairing agent for peptides and small proteins in organic compound liquid chromatography
• For acid-stable materials, can be a solvent for NMR spectroscopy
• Acts as a calibrant in mass spectrometry
• Used to produce trifluoroacetate salts
• An ingredient in adhesives, sealants, paints, and coatings

When TFA combines with bases and metals, especially light metals, a strong exothermic reaction occurs. When mixed with lithium aluminum hydride (LAH), the reaction is explosive.

Although nonflammable, TFA is corrosive to skin, eyes, and mucous membranes and requires careful use and handling. It is harmful when inhaled, causes severe skin burns and eye damage, and is toxic to aquatic organisms at even low concentrations.

TFA is also a product of the metabolic breakdown of the anesthetic agent halothane. It is the suspected cause of halothane-induced hepatitis.