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• Trifluoroacetic acid (TFA) is the simplest stable perfluorinated carboxylic acid chemical compound, with the formula CF3CO2H. It is a strong carboxylic acid due to the influence of the electronegative trifluoromethyl group. TFA is almost 100,000-fold more acidic than acetic acid. TFA is widely used in organic chemistry.

• TFA occurs naturally in sea water, but only in small concentrations (<200 ng/L). Therefore, TFA is prepared industrially by the electrofluorination of acetyl chloride and acetic anhydride, followed by hydrolysis of the resulting trifluoroacetyl fluoride.

• TFA is the precursor to many other fluorinated compounds such as trifluoroacetic anhydride and 2,2,2-trifluoroethanol. It is a reagent used in organic synthesis because of a combination of convenient properties: volatility, solubility in organic solvents, and its strength as an acid. TFA is also less oxidizing than sulfuric acid but more readily available in anhydrous form than many other acids.

• TFA is popularly used as a strong acid in peptide synthesis and other organic synthesis to remove the t-butoxycarbonyl protecting group. An older route to TFA proceeds via the oxidation of 1,1,1-trifluoro-2,3,3-trichloropropene with potassium permanganate. The trifluorotrichloropropene can be prepared by Swarts fluorination of hexachloropropene.

• Trifluoroacetic acid (TFA) is a strong carboxylic acid, with pKa of 0.3. TFA is widely used in chemistry as reagent and as counter-ion for basic drugs and other compounds. TFA is very polar in nature, and has low UV activity. It is often required to quantitate trifluoracetic acid in various formulations. HPLC method for determination of trifluoroacetic acid on Obelisc N column provides a viable alternative for quantitation of TFA. TFA is retained by ion-exchange mechanism on mixed-mode HILIC column.

• Trifluoroacetic acid is widely used in the chemical industry in processes where it is either consumed or becomes part of a chemical waste stream.To assess the potential for a halocarbon to produce trifluoroacetic acid, it is necessary to quantify the yield of trifluoroacetyl halide in its gas phase oxidation mechanism.

• TFA is used in ion pairing agent in liquid chromatography (HPLC) of organic compounds, particularly peptides and small proteins. TFA is a versatile solvent for NMR spectroscopy (for materials stable in acid). It is also used as a calibrant in mass spectrometry.

• Typical concentrations of TFA (0.1% v/v) have high surface tension and prevent efficient spray formation (nebulization). TFA ions in the gas phase ion-pair with the peptide’s basic groups suppressing their ionization and reducing sensitivity.

• Both Acetic acid and Trifluoroacetic acid, similarly to formic acid, adsorb dissociatively on the TiO2(110) surface. Trifluoroacetic acid (or its deuterated analogue CF3COOD) is condensed by exposing the substrate to a volumetrically calibrated effusive outflow from a capillary located 7mm from the crystal.

• Trifluoroethanoic acid or trifluoroacetic acid (TFA) is one of the strongest known organic acids and plays a significant role in several branches of chemistry owing to its strong acidity [1]. It is of particular interest as a solvent as, in addition to its strong acidity, it possesses a range of useful additional properties including small nucleophilicity, high anodic discharge potential and satisfactory affinity with other organic solvents.

• Trifluoroacetic acid (TFA) is commonly used in the manufacturing process to release synthesized peptides from solid-phase resins. TFA or acetate is also used during reversed-phase HPLC purification of peptides. TFA is manufactured using acetate and fluoride as precursors, and residual levels of these compounds may be present whenever TFA is used.

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