Acids trifluoroacetic

The advantages of trifluoroacetic acid as a very strong organic acid have, of course, been appreciated for a long time they include its unusual properties as a solvent for kinetic 

The field of fluorinated amino acids and peptides is already established and recent developments are important to both chemistry and biology. The reader is directed to an excellent entry volume [52] and reviews [53]. 

LABORATORY CHEMICAL SAFETY SUMMARY TRIFLUOROACETIC ACID  

Physical Properties Colorless liquid bp 72 °C, mp -15 °C Miscible with water 

Toxicity Data LD50 oral (rat) 200 mg/kg LC50 inhal (rat) 2000 ppm (4 h) 

Major Hazards Corrosive to the skin and eyes vapor or mist is very irritating and can be destructive to the eyes and respiratory system ingestion causes internal irritation and severe 

Flammability and Explosibility 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. 

Alkenes do not polymerise in the presence of trifluoroacetic acid, but only give the correspondii esters. Isobutene can be bubbled throu the pure acid without any noticeable pol5mierisation  

No studies have been reported on the action of this acid on dienes, but in view of the effectiveness of trichloroacetic acid on cyclopentadiene one would expect an even easier catalysis by the stronger trifluoro derivative. Furan polymerises in the presence of fairly hi concentration of trifluoacetic acid giving rise to poly-conjugated products. The stmcture of these prdymers has been analysed in det but the mechanian of initiation and the nature of the chain carriers vdiich produce them remain unexplored, particularly in the early stages of the reaction. 

Aromatic and heteroaromatic olefins can be polymerised by this acid, but regrettably the number of studies of these systems is still very limited. In fact, only styrene 

Before describing the preparation and properties of trifluoroacetate compounds in general, particular consideration will be given to the parent acid. The normal commercial preparation of trifluoroacetic acid is the electrolytic fluorination of acetyl fluoride or chloride 210). Other preparative methods include the oxidation of trifluorotoluidine or other trifluoromethyl aryl derivatives 247) and the hydrolysis of trifluoro-acetylchloride (6). 

The physical properties of liquid trifluoroacetic acid are given in Table I. At normal temperatures it is a colorless liquid which fumes readily in moist air and has a powerful odor. 

Trifluoroacetic acid is known to form cyclic dimers in the vapor phase which appear to be analogous to those formed by acetic acid. An electron diffraction study of gaseous trifluoroacetic acid identified monomeric and dimeric species, the O—H---0 bond in the latter being 

The nature of the association of trifluoroacetic acid in inert and slightly basic solvents is still disputed. Murty and Pitzer (IT S) have suggested that infrared spectra indicate that a linear association of trifluoroacetic acid molecules occurs in such media however, further such measurements obtained by Kirszenbaum et al. (141) appear to conflict with this interpretation. 

The and F NMR line parameters obtained for a powdered sample of trifluoroacetic acid have been interpreted (72) on the basis of dimeric molecules in this phase. However, the arrangement of these dimers in the crystal lattice appears to differ from that in trichloroacetic acid. 

Viscosity at 25 C Dielectric Constant at 25 C Conductivity at 25°C Surface Tension at 26°C 

Compound Formula Boiling Point °C Melting Point C 

SOLUBILITY OF SALTS IN 100 GRAMS OF TRIFLUOROACETIC ACID AT ABOUT 25 C 

It is interesting to note that Si(OjCCFj)., TiOCOjCCF.,)., Zr(OjCCF,)4 and Th(0 CCF,)4 have been prepared (77). The silicon compound exhibits covalent character. 

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CF3CO2H. Colourless liquid, b.p. 72-5 C, fumes in air. Trifluoroacetic acid is the most important halogen-substituted acetic acid. It is a very strong acid (pK = o y) and used extensively for acid catalysed reactions, especially ester cleavage in peptide synthesis. 

Cations like that present in (iv) exist in solutions of aromatic hydrocarbons in trifluoroacetic acid containing boron trifluoride, and in liquid hydrogen fluoride containing boron trifluoride. Sulphuric acid is able to protonate anthracene at a mero-position to give a similar cation. ... 

The blocking and deblocking of carboxyl groups occurs by reactions similar to those described for hydroxyl and amino groups. The most important protected derivatives are /-butyl, benzyl, and methyl esters. These may be cleaved in this order by trifluoroacetic acid, hydrogenolysis, and strong acid or base (J.F.W. McOmie, 1973). 2,2,2-Trihaloethyl esters are cleaved electro-lytically (M.F. Semmelhack, 1972) or by zinc in acetic acid like the Tbeoc- and Tceoc-protected hydroxyl and amino groups. 

In each step of the usual C-to-N peptide synthesis the N-protecting group of the newly coupled amino acid must be selectively removed under conditions that leave all side-chain pro-teaing groups of the peptide intact. The most common protecting groups of side-chains (p. 229) are all stable towards 50% trifluoroacetic acid in dichloromethane, and this reagent is most commonly used for N -deprotection. Only /ert-butyl esters and carbamates ( = Boc) are solvolyzed in this mixture. 

The following acid-catalyzed cyclizations leading to steroid hormone precursors exemplify some important facts an acetylenic bond is less nucleophilic than an olelinic bond acetylenic bonds tend to form cyclopentane rather than cyclohexane derivatives, if there is a choice in proton-catalyzed olefin cyclizations the thermodynamically most stable Irons connection of cyclohexane rings is obtained selectively electroneutral nucleophilic agents such as ethylene carbonate can be used to terminate the cationic cyclization process forming stable enol derivatives which can be hydrolyzed to carbonyl compounds without this nucleophile and with trifluoroacetic acid the corresponding enol ester may be obtained (M.B. Gravestock, 1978, A,B P.E. Peterson, 1969). 

The l,5-hexadien-3-ol derivatives 792 and 794 are cycli2ed to form the cyclo-pentadiene derivatives 793 and 795 by insertion of an alkene into -allylpalla-dium formed from allylic alcohols in the presence of trifluoroacetic acid (lO mol%) in AcOH[490],... 

A -(2 2-Diethoxyethyl)anilines are potential precursors of 2,3-unsubstituted indoles. A fair yield of 1-methylindole was obtained by cyclization of N-inethyl-M-(2,2-diethoxyethyl)aniline with BFj, but the procedure failed for indole itself[2], Nordlander and co-workers alkylated anilines with bromo-acetaldehyde diethyl acetal and then converted the products to N-trifliioro-acetyl derivatives[3]. These could be cyclized to l-(trifluoroacetyl)indoles in a mixture of trifluoroacetic acid and trifluoroacetic anhydride. Sundberg and... 

A solution of trifluoroacetic acid in toluene was found to be advantageous for cydization of pyruvate hydrazoncs having nitro substituents[4]. p-Toluene-sulfonic acid or Amberlyst-15 in toluene has also been found to give excellent results in preparation of indole-2-carboxylale esters from pyruvate hydra-zoiies[5,6J. Acidic zeolite catalysts have been used with xylene as a solvent to convert phenylhydraziiies and ketones to indoles both in one-flask procedures and in a flow-through reactor[7]. 

The most suitable synthetic method for these products is the heterocyc-lization reaction of N-thioacyl derivatives of amino acids (202) with phosphorus tribromide (378, 442-450, 559, 560) or anhydrous trifluoroacetic acid (448, 449, 451, 452) (Scheme 103). Treatment of N-thioacyl amino acids with acetic anhydride leads directly to the thiazolylacetate without isolation of an intermediate thiazolinone (365. 452). 2-Alkoxy-derivatives of A-2-thiazoline-5-one, however, can be obtained without acetylation by this method (453, 454). 

The NMR determination in strongly acidic medium (trifluoroacetic acid) of the chemical shifts of the protons in the 4- or 5-position can be used to establish a reactivity scale. If the proton appears at low field, this indicates that this substitution site wiE be poorly or not at all nitrated (111). 

The greater positive character hence the increased acidity of the O—H proton of 2 2 2 tnfluoroethanol can be seen m the electrostatic potential maps displayed m Figure 1 8 Structural effects such as this that are transmitted through bonds are called indue tive effects A substituent induces a polarization m the bonds between it and some remote site A similar inductive effect is evident when comparing acetic acid and its trifluoro derivative Trifluoroacetic acid is more than 4 units stronger than acetic acid... 

The tert butyl group is cleaved as the corresponding carbocation Loss of a proton from tert butyl cation converts it to 2 methylpropene Because of the ease with which a tert butyl group is cleaved as a carbocation other acidic reagents such as trifluoroacetic acid may also be used... 

Step n When the peptide is completely assembled it is removed from the resin by treatment with hydrogen bromide m trifluoroacetic acid... 

Nonvolatile analytes must be chemically converted to a volatile derivative before analysis. For example, amino acids are not sufficiently volatile to analyze directly by gas chromatography. Reacting an amino acid with 1-butanol and acetyl chloride produces an esterfied amino acid. Subsequent treatment with trifluoroacetic acid gives the amino acid s volatile N-trifluoroacetyl- -butyl ester derivative. 

Many ceUulosic derivatives form anisotropic, ie, Hquid crystalline, solutions, and cellulose acetate and triacetate are no exception. Various cellulose acetate anisotropic solutions have been made using a variety of solvents (56,57). The nature of the polymer—solvent interaction determines the concentration at which hquid crystalline behavior is initiated. The better the interaction, the lower the concentration needed to form the anisotropic, birefringent polymer solution. Strong organic acids, eg, trifluoroacetic acid are most effective and can produce an anisotropic phase with concentrations as low as 28% (58). Trifluoroacetic acid has been studied with cellulose triacetate alone or in combination with other solvents (59—64) concentrations of 30—42% (wt vol) triacetate were common. 

Fluorinated Acids. This class of compounds is characterized by the strength of the fluorocarbon acids, eg, CF COOH, approaching that of mineral acids. This property results from the strong inductive effect of fluorine and is markedly less when the fluorocarbon group is moved away from the carbonyl group. Generally, their reactions are similar to organic acids and they find apphcations, particularly trifluoroacetic acid [76-05-1] and its anhydride [407-25-0] as promotors in the preparation of esters and ketones and in nitration reactions. 

Chemically, 2,2,2-trifluoroethanol behaves as a typical alcohol. It can be converted to trifluoroacetaldehyde [75-90-1] or trifluoroacetic acid [76-05-1] by various oxidi2iag agents such as aqueous chlorine solutions (51) or oxygen ia the preseace of a vanadium pentoxide catalyst (52). Under basic conditions, it adds to tetrafluoroethylene and acetylene to give, respectively, 1,1,2,2-tetrafluoroethyl 2/2/2 -trifluoroethyl ether [406-78-0] (53) and... 

Trifluoroethanol was first prepared by the catalytic reduction of trifluoroacetic anhydride [407-25-0] (58). Other methods iaclude the catalytic hydrogeaatioa of trifluoroacetamide [354-38-1] (59), the lithium aluminum hydride reductioa of trifluoroacetyl chloride [354-32-5] (60) or of trifluoroacetic acid or its esters (61,62), and the acetolysis of 2-chloro-l,l,l-trifluoroethane [75-88-7] followed by hydrolysis (60). More recently, the hydrogenation of... 

Physical Properties. Trifluoroacetic acid [76-05-1], CF COOH, is a colorless Hquid with a sharp odor resembling that of acetic acid. Its... 

Health and Safety Factors. Unlike fluoroacetic acid, trifluoroacetic acid presents no unusual toxicity problems. However, owing to its strong acidity, its vapors can be irritating to tissue, and the Hquid acid can cause deep bums if allowed to contact the skin. The acid can be safely stored in containers made of glass or common corrosion-resistant alloys and metals such as stainless steel or alurninum. 

Economic Aspects. Halocarbon Products Corp. is the largest producer of trifluoroacetic acid. The commercial grade is of very high purity with the main impurity being ca 0.2% water. A grade, which has a low residue specification, intended for use in protein synthesis (Biograde) is available. Other producers include Rhc ne-Poulenc and Solvay. The 1992 price was ca 15/kg. 

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