76-05-1 Usage
description
Trifluoroacetic acid (TFA, molecular formula: CF3COOH) is a kind of colorless, volatile and fuming liquid with a similar odor as acetic acid. It is hygroscopic and has irritating odor. It has strong acidic property due to being affected by the electron-attracting trifluoromethyl group with its acidicity being 100000 higher than acetic acid. It has a melting point being-15.2 ℃, boiling point being 72.4 ℃, and the density being 1.5351g/cm3 (1℃). It is miscible with water, fluorinated hydrocarbons, methanol, ethanol, ethyl ether, acetone, benzene, carbon tetrachloride, and hexane; it is partially soluble in carbon disulfide and alkane containing more than six carbons. It is an excellent solvent of protein and polyester.
Trifluoroacetic acid is also a good solvent for the organic reaction which allows obtaining certain results which are difficult in the cases of application of common solvents. For example, when quinolone is being catalyzed for hydrogenation in a common solvent, the pyridine ring is preferentially hydrogenated; in contrast, the benzene ring will be preferentially hydrogenated in the presence of trifluoroacetic acid as the solvent. Trifluoroacetic acid is decomposed into carbon dioxide and fluorine in the presence of aniline. It can be reduced by sodium borohydride or lithium aluminum hydride into trifluoroacetic acetaldehyde and trifluoro-ethanol. It is stable at temperature higher than 205 ℃ stable. But its ester and amides derivatives are easily subject to hydrolysis which allows them to prepare carbohydrate, amino acids, and peptide derivative in the form of acid or anhydride. It is easily to be dehydrated under action of phosphorus pentoxide and be converted to trifluoroacetic anhydride.
Trifluoroacetic acid is a kind of important intermediates of fat fluorine. Owing to the special structure of trifluoromethyl, it has a different property from other alcohols and can participate in a variety of organic reactions, especially being used in the field of the synthesis of fluorine-containing pharmaceutical, pesticides and dyes. Its domestic and foreign demand is increasing and has become one of the important intermediates for fluorine-containing fine chemicals.
chemical properties
It is colorless, volatile fuming liquid with a similar odor as acetic acid. It is hygroscopic and has stimulating smell. It is miscible with water, fluorinated alkanes, methanol, benzene, ether, carbon tetrachloride and hexane. It can partially dissolve alkane with over six carbons as well as carbon disulfide.
pKa
Trifluoroacetic acid (TFA) is a kind of strong acid with its pKa being 0.23. It can stimulate the body tissue and skin. However, it is only slightly toxic. However, its enrichment in immobilizing surface water will affect agriculture and aquatic systems. Moreover, TFA can generate greenhouse gases CHF3 after undergoing the microbial degradation.
The above information is edited by the lookchem of Dai Xiongfeng.
uses
Trifluoroacetic acid is mainly for the production of new pesticide, medicine and dyes, and also has great potential of application and development in the fields of materials and solvents. Trifluoroacetic acid is mainly used for the synthesis of various kinds of trifluoromethyl group or heterocyclic containing herbicides. It is currently available for synthesizing various kinds of novel herbicide containing pyridyl and qunoilyl; acting as a strong proton acid, it is widely applied as the catalyst for alkylation, acylation, and olefin polymerization of aromatic compound; as a solvent, trifluoroacetic acid is a kind of excellent solvent for fluorination, nitration and halogenations. In particular, the excellent protective effect of its trifluoroacetyl derivatives on hydroxy and amino group has very important application in the synthesis of amino acid and poly-peptide synthesis, for example, the compound can be used as the protection agent of tert-butoxycarbonyl (t-boc) which is used for removing amino acids during the synthesis of poly-peptide. Trifluoroacetic acid, as the raw material and modifier for the preparation of the ion membrane, can largely improve the current efficiency of soda industry and significantly extend the working life of the membrane; trifluoroacetic acid can also be used for synthesizing trifluoro-ethanol, trifluoroacetic acetaldehyde and trifluoroacetic anhydride. At room temperature, the mercury trifluoroacetic acid can have mercury-fluorophenyl be able to have mercuration reaction (electrophilic substitution), and can also convert hydrazone to diazo compound. The lead salt of this acid can convert arene to phenol. In the experiment of reverse phase chromatography for isolation of peptides and proteins, using trifluoroacetic acid (TFA) as the ion-pairing reagents is a common approach. Trifluoroacetic acid in the mobile phase can improve the peak shape and overcome the problem of the peak broadening and trailing issue through interaction with hydrophobic bonded phase and residual polar surface in a variety of models. Trifluoroacetic acid has an advantage over other ion modifier due to that it is volatile and can be easily removed from the sample preparation. On the other hand, the maximum UV absorption peak of trifluoroacetic acid is less than 200 nm, and thus having very small interference on the detection of polypeptides at low wavelengths.
Applications in HPLC
In the experiment of reverse phase chromatography for isolation of peptides and proteins, using trifluoroacetic acid (TFA) as the ion-pairing reagents is a common approach. Trifluoroacetic acid in the mobile phase can improve the peak shape and overcome the problem of the peak broadening and trailing issue through interaction with hydrophobic bonded phase and residual polar surface in a variety of models. Trifluoroacetic acid can bind to the positive charge and polar groups on the polypeptide in order to reduce the polar retention, and bring the polypeptide back to the hydrophobic inverting surface. With the same way, trifluoroacetate shield the residual polar surface in fixed phase. The behavior of TFA can be understood as it stuck in the phase surface of the reverse phase fixed phase, while having interaction with the polypeptide and column bed.
Trifluoroacetic acid has an advantage over other ion modifier due to that it is volatile and can be easily removed from the sample preparation. On the other hand, the maximum UV absorption peak of trifluoroacetic acid is less than 200 nm, and thus having very small interference on the detection of polypeptides at low wavelengths.
Varying the concentration of trifluoroacetic acid can slightly adjust the selectivity of polypeptide on reverse phase chromatography. The impact is very useful for optimizing separation conditions, increasing the amount of information contained in complex chromatography assay (such as the fingerprint of polypeptide).
Trifluoroacetic acid was added to the mobile phase in a general concentration of 0.1%. At this concentration, most of the reversed-phase column can produce good peak shape. In contrast, if the concentration of trifluoroacetic acid is significantly below this level, the peak broadening and tailing would become very obvious.
Trifluoroacetic acid has a good efficacy in the separation of proteins and other macromolecules. However, during the actual usage, we have a difficult time in controlling TFA concentrations because it is a volatile substance. If you configure it for a long time, it will be volatile causing change in the concentration. After completion of preparing it, it must be sealed for prevention of its evaporation.
preparation
Trifluoroacetic acid is an important reagent in organic synthesis. Preparation of trifluoroacetic acid has a variety of routes:1. Obtain it through the oxidation of 1, 3, 3, 3-trifluoropropene by potassium permanganate.2. acetic acid (alternatively; acetyl chloride or acetic anhydride) can have electrochemical fluorination with hydrofluoric acid and sodium fluoride and then be hydrolyzed.3. Trifluoroacetic acid can be obtained by the oxidation of 1, 1, 1-trifluoro-2, 3, 3-trichloropropene through potassium permanganate. This raw material can be made through the Swarts fluorination of hexachloropropylene.4. Prepared from the oxidation of 2,3-dichloro-hexafluoro-2-butene.5. Trifluoroacetic acid can be generated by the reaction between trichloro-acetonitrile and hydrogen fluoride, which generates trifluoromethyl acetonitrile, which further undergoes hydrolysis to obtain the product.6. obtained through the oxidation of benzotrifluoride.
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.
Uses
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.
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.
Check Digit Verification of cas no
The CAS Registry Mumber 76-05-1 includes 5 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 2 digits, 7 and 6 respectively; the second part has 2 digits, 0 and 5 respectively.
Calculate Digit Verification of CAS Registry Number 76-05:
(4*7)+(3*6)+(2*0)+(1*5)=51
51 % 10 = 1
So 76-05-1 is a valid CAS Registry Number.
InChI:InChI=1/C2HF3O2/c3-2(4,5)1(6)7/h(H,6,7)
76-05-1Relevant articles and documents
Enthalpies of Hydration of Alkenes. 1. The n-Hexenes
Wiberg, Kenneth B.,Wasserman, David J.
, p. 6563 - 6566 (1981)
Alkenes undergo a rapid reaction with trifluoroacetic acid containing 0.25 M trifluoroacetic anhydride in the presence of a strong acid catalyst.The enthalpies of trifluoroacetolysis of the five n-hexenes were determined and were corrected to the enthalpies corresponding to the formation of the equilibrium mixture of 2-hexyl trifluoroacetate and 3-hexyl trifluoroacetate.The enthalpy difference between the latter was determined by measuring the equilibrium constant as a function of temperature.The trifluoroacetolysis data may be combined with the measured enthalpies of formation of the alkenes to derive more precise values for the latter.The enthalpies of reaction of water, 2-hexanol, and 3-hexanol with the reaction solvent were determined, and when combined with the other data lead to enthalpies of hydration of the alkenes and the enthalpies of formation of the alcohols.
Trifluoroselenoacetic acid, CF3C(O)SeH: Preparation and properties
Gomez Castano, Jovanny A.,Romano, Rosana M.,Beckers, Helmut,Willner, Helge,Della Vedova, Carlos O.
, p. 9972 - 9977 (2010)
The hitherto unknown trifluoroselenoacetic acid was prepared through the reaction of trifluoroacetic acid with Woollins' reagent. The compound was fully characterized by mass spectrometry, 1H, 19F, 77Se, and 13C NMR, UV-visible, IR and Raman spectroscopy, and the boiling point at 46 °C was estimated from the vapor pressure curve. An IR matrix isolation study revealed the presence of two different syn-anti and anti-syn conformers. The IR spectra of the two stereoisomers have been assigned, aided by DFT, and ab initio calculations. The UV photolysis of Ar matrix isolated CF3C(O)SeH yielded CO, OCSe, CF3SeH, and CHF3. Apart from CF3SeH, these products were also obtained by vacuum flash-pyrolysis (310 °C) of gaseous CF3C(O)SeH. Instead of CF3SeH, CF2Se, and HF were detected among the pyrolysis products. The different decomposition pathways of CF 3C(O)SeH are discussed.
-
Cook,Taft
, p. 6103 (1952)
-
-
Shreidev et al.
, (1977)
-
Degradation of phenyltrifluoromethylketone in water by separate or simultaneous use of TiO2 photocatalysis and 30 or 515 kHz ultrasound
Theron, Philippe,Pichat, Pierre,Guillard, Chantal,Petrier, Christian,Chopin, Thierry
, p. 4663 - 4668 (1999)
TiO2 photocatalysis and ultrasound are emerging technologies for the mineralization of pollutants in water. To further investigate these technologies and to assess whether advantages and synergy can be expected from their differences, phenyltrifluoromethylketone (PTMK) was selected as a test compound for pollutants generating CF3COOH, an undesirable final product. The PTMK first-order removal rate constant k was ca. 14 times higher when the ultrasound frequency was 515 kHz instead of 30 kHz for the same energy, and ca. 2.5 times higher when a TiO2 sample we synthesized was used instead of TiO2 Degussa P25. On simultaneous photocatalytic and ultrasonic treatment an increase in k by a factor between 1.4 and 1.9, depending on the TiO2 sample, was observed at 30 kHz but not at 515 kHz. On the basis of catalase enzymatic effect upon k, these observations are tentatively explained by a photocatalytic OH radical production from sonochemically formed H2O2, provided that the H2O2 residence time on TiO2 is sufficient. PTMK ultrasonic pyrolysis was demonstrated by product analysis. The amount of CF3COOH was ca. 8 times lower in sonicated solutions than in UV-irradiated TiO2 suspensions, for both frequencies and both TiO2 samples. Therefore, because of a higher k value, a high frequency ultrasonic (pre)treatment is preferable to minimize CF3COOH formation.
Oxidation of fluoroalkyl alcohols using sodium hypochlorite pentahydrate [1]
Kirihara, Masayuki,Suzuki, Katsuya,Nakakura, Kana,Saito, Katsuya,Nakamura, Riho,Tujimoto, Kazuki,Sakamoto, Yugo,Kikkawa, You,Shimazu, Hideo,Kimura, Yoshikazu
, (2021/02/05)
Fluoroalkyl alcohols are effectivity oxidized to the corresponding fluoroalkyl carbonyl compounds by reaction with sodium hypochlorite pentahydrate in acetonitrile in the presence of acid and nitroxyl radical catalysts. Although the reaction proceeded slower under a nitroxyl radical catalyst- free condition, the desired carbonyl compounds were obtained in high yields. For the reaction with fluoroalkyl allylic alcohols, the corresponding α,β-epoxyketone hydrates were obtained in high yields.
The aliphatic ring-opening and SNAr substitution in the reactions of perfluorobenzocycloalkenones with K2CO3 in water and methanol
Zonov, Yaroslav V.,Wang, Siqi,Karpov, Victor M.,Mezhenkova, Tatyana V.
, (2021/07/28)
In the reactions with aqueous K2CO3, perfluorinated benzocyclobuten-1-one, 3-R-indan-1-ones and 4-R-tetralin-1-ones (R = F, C2F5) undergo selective cleavage of the СO–С(Ar) bond to yield (2,3,4,5-tetrafluorophen
