Trifluoroacetic acid

Description

Trifluoroacetic acid (TFA) is a strong organic acid typically used as a solvent or acid catalyst. TFA is the CF3 analogue of acetic acid (AcOH) which due to the electron withdrawing effect of the fluorine atoms is much more acidic than AcOH. The pKa of TFA is 0.23, compared to a pKa of 4.76 for AcOH. The low boiling point (bp = 72 C) of TFA facilitates simpler product isolation due to the fact that it can be removed via concentration on rotovap.

Chemical properties

Trifluoroacetic acid (TFA) is an analogue of acetic acid with the three hydrogen atoms replaced by three fluorine atoms. It has a vinegar-like odor and is a strong acid, a good solvent and has excellent reactive properties. The specific gravity of liquid TFA is 1.48 and it boils at 72 °C. Trifluoroacetic Acid is a solvent that is used in the production of pharmaceutical and agricultural chemicals as well as in many other specialized applications. Some of the more popular uses for TFA are as a silyl catalyst when derivatizing carbohydrates, as a reagent for purifying large peptides, as an ion pair reagent, and as an LC mobile phase additive.

The Uses of Trifluoroacetic acid

Trifluoroacetic acid is an important building block in the synthesis of pharmaceuticals, agrochemicals and performance products. It is a precursor to many fluorinated compounds, and widely used in peptide synthesis and other organic transformations involving deprotection of t-BOC group. The combination of properties like solubility in most of the solvents, volatility, catalytic property, and strong acidity with non-oxidizing nature makes it a widely used reagent in organic synthesis. Trifluoroacetic acid can use as an ion pairing agent in liquid chromatography, as a solvent in NMR spectroscopy and as a calibrant in mass spectrometry. It is used as a catalyst in esterification reaction and condensation reaction and a protective agent for hydroxyl and amino.

What are the applications of Application

Trifluoroacetic acid is a strong non-oxidizing acid

Definition

ChEBI: Trifluoroacetic acid is a monocarboxylic acid that is the trifluoro derivative of acetic acid. It has a role as a reagent and a human xenobiotic metabolite. It derives from an acetic acid. It is a conjugate acid of a trifluoroacetate.

Synthesis Reference(s)

The Journal of Organic Chemistry, 26, p. 923, 1961 DOI: 10.1021/jo01062a068

General Description

Trifluoroacetic acid appears as a colorless fuming liquid with a pungent odor. Soluble in water and denser than water. Corrosive to skin, eyes and mucous membranes. Used to make other chemicals and as a solvent.

Air & Water Reactions

Fumes in air. Soluble in water.

Reactivity Profile

Trifluoroacetic acid is a strong acid; attacks many metals [Handling Chemicals Safely 1980. p. 935]. A 30% solution of hydrogen peroxide in Trifluoroacetic acid is often used to destructively oxidize aromatic rings in preference to the side chains. Explosions have occurred, if the excess peroxide is not catalytically destroyed, prior to removal of solvent, [Tetrahedron Lett., 1977, 1703-1704]. The reduction of amides of Trifluoroacetic acid with lithium aluminum hydride are dangerous at all phases of the process, explosions have occurred, [Chem. Eng. News, 1955, 33, 1368].

Health Hazard

Trifluoroacetic acid is a highly corrosive substance. Contact of the liquid with the skin, eyes, and mucous membranes can cause severe burns, and ingestion can result in serious damage to the digestive tract. TFA vapor is highly irritating of the eyes and respiratory tract, and inhalation of high concentrations can lead to severe destruction of the upper respiratory tract and may be fatal as a result of pulmonary edema. Symptoms of overexposure to TFA vapor include a burning feeling, coughing, headache, nausea, and vomiting.
Trifluoroacetic acid has not been found to be carcinogenic or to show reproductive or developmental toxicity in humans.

Fire Hazard

Trifluoroacetic acid is not combustible. Nevertheless, the presence of trifluoroacetic acid at the site of a fire would be of great concern because of its high vapor pressure and extreme corrosiveness. Some are oxidizers and may ignite combustibles (wood, paper, oil, clothing, etc.). Contact with metals may evolve flammable hydrogen gas. Containers may explode when heated.

Biochem/physiol Actions

Trifluoroacetic acid?(TFA) is mainly preferred as an internal chemical shift referencing agent in?19F NMR.

Safety Profile

Poison by ingestion and intraperitoneal routes. Moderately toxic by intravenous route. Mildly toxic by inhalation. A corrosive irritant to skin, eyes, and mucous membranes. When heated to decomposition it emits toxic fumes of F-. Used as a strong organic acid catalyst.

storage

trifluoroacetic acid should be stored in an acid cabinet away from other classes of compounds. Because of its high vapor pressure, fumes of trifluoroacetic acid can destroy labels on other bottles if the container is not tightly sealed.

Purification Methods

The purification of trifluoroacetic acid, reported in earlier editions of this work, by refluxing over KMnO4 for 24hours and slowly distilling has resulted in very SERIOUS EXPLOSIONS on various occasions, but not always. This apparently depends on the source and/or age of the acid. The method is NOT RECOMMENDED. Water can be removed by adding trifluoroacetic anhydride (0.05%, to diminish water content) and distilling. [Conway & Novak J Phys Chem 81 1459 1977]. It can be refluxed and distilled from P2O5. It is further purified by fractional crystallisation by partial freezing and again distilled. Highly TOXIC vapour. Work in an efficient fume hood. [Beilstein 2 IV 458.]

Incompatibilities

Mixing trifluoroacetic acid and water evolves considerable heat.

Waste Disposal

Trifluoroacetic acid and waste material containing this substance should be placed in an appropriate container, clearly labeled, and handled according to your institution's waste disposal guidelines.