Trifluoroacetic acid as solvent

With trifluoroacetic acid as solvent, toluene and o-xylene gave second-order kinetics and for the activation energy for toluene was 12.7 (from data at 1.6 and 25.2 °C), i.e. considerably less than for the zinc chloride-catalysed reaction in acetic acid330. 

Direct C-H activation of hydrocarbon by means of transition metals has also been explored. Cyclohexane reacted with Pd(OAc)2 in the presence of potassium persulfate-trifluoroacetic acid under CO pressure and produced the desired cyclo-hexanecarboxylic acid in low yields and TON (eq. (13)). The electrophilic carbox-ylation is explained by the change of Pd(OAc)2 to Pd(OCOCp3)2 in trifluoroacetic acid as solvent. Electrophilic attack on a C-H bond should give an alkyl Pd complex. CO insertion followed by reductive elimination affords a reactive mixed anhydride which was detected before workup. 

FIGURE 14.4. Nitration of an aromatic ketone using trifluoroacetic acid as solvent... 

Salin B.N., Cemeris M., Mironov D.P., Zatsepin A.G., Trifluoroacetic acid as solvent for the synthesis of cellulose esters. 1. Synthesis of triesters of cellulose and aliphatic carboxylic acids, Koksnes Kimija, 3, 1991,65-69. 

Azides that are a- to a pyridine-like nitrogen usually exist predominantly in the tetrazole form and so difficulties are often encountered in their photolysis. Photolysis of tetrazoles has been found to be facilitated by the use of trifluoroacetic acid as solvent which converts the tetrazole to azide before nitrogen is lost ... 

In acidic media (e.g., in trifluoroacetic acid as solvent), the exchange of the ammonium protons is slowed down to such an extent that the vicinal coupling H-N -C-H generally becomes observable. In other media, signals are usually broad owing to intermediate exchange rates. 

Preparation by reaction of m-chloroperoxyben-zoic acid with 2,6-diacetyl-4-methylphenol using chloroform and trifluoroacetic acid as solvent at r.t. (39%) [3188],... 

Benzene and monosubstituted benzene derivatives could be radiolabeled with iodide-131 by reaction of the substrate with iodine-131 in presence of cerium(IV) triflate (Mennicke et al., 2000). The reaction was carried out in trifluoroacetic acid as solvent. Cerium(IV) is however not soluble in this solvent. 

Specific solvation is the effective factor which controls conformer stability. The correlation between equilibrium constants of the investigated processes [8.1.60] and [8.1.61] and polarity of solvation-inert solvents is very indefinite. For instance, diaxial conformer of 4-methoxycyclohexanone in acetone (as solvent) (s = 20.7) is sufficiently more stable than in methanol (s = 32.6). But the maximum stability of that isomer is reached in low-polar trifluoroacetic acid as solvent (s = 8.3). 

Nitrenium ions have also been generated through the decomposition of azides under acidic conditions (e.g., trifluoroacetic acid-arene solvent mixtures). There are two potential pathways for the formation of the nitrenium ion from the precursors (Fig. 13.24). The first involves initial dissociation of the azide 41 to give a singlet nitrene 42, followed by proton transfer to the latter to yield the primary nitrenium ion 43. The second involves acid-induced decompostion of the azide, whereby preprotonation of the azide (44) forms the primary nitrenium ion in a direct manner. As with the hydroxylamine route, this method is limited to acidic or protic media. 

Katz, J. J. Trifluoroacetic Acid as Protein Solvent Chem. Eng. News... 

Addition of halogen fluorosulfates XOS02F (X=C1, Br, I) to fluoroolefins is considered an electrophilic reaction [8]. However, the question of whether this process is concerted or the reaction proceeds via an independent carbocationic intermediate (Eqs. 2 and 3) is still open. Formation of carboxylic acid esters as byproducts in the reaction of HFP with C10S02F, which was carried out in trifluoroacetic or heptafluorobutyric acids as solvents, could not be a solid proof of conjugate addition, since formation of esters may be a result of addition of C10C(0)Rf to olefin. These materials are known to be formed in the reaction of ClOS02F with fluorinated carboxylic acids, even at low temperature [99]. 

Use of trifluoroacetic acid as a co-solvent usually increases the rate of the reaction, but often reduces the yield of products. Acetate anion may accelerate enolization... 

The use of trifluoroacetic acid as both a protonat-ing agent and a solvent frequently allows classification of amines as primary, secondary, or tertiary. This is illustrated in Table 3.4 in which the number of protons on nitrogen determines the multiplicity of the methylene... 

Similarly, unactivated arenes readily react with thallium(III) trifluoroacetate in TFA to give the corresponding arylthallium trifluoroacetates, ArTl(02CCF3)2, which are stable and do not readily decompose to aryl trifluoroacetates and T1(I) 282-286 The rate of aromatic mercuration is increased by a factor of 7 X 10s in TFA relative to acetic acid as solvent.292... 

Katz, J. J. Anhydrous hydrogen fluoride as a solvent for proteins and other biologically important substances. Arch. Biochem. Biophys. 51, 293 (1954) Anhydrous trifluoroacetic acid as a solvent for proteins. Nature 174, 509 (1954) A. L. Koch, W. A. Lamont and J. J. Katz The effect of anhydrous strong acids on ribonuclease and lysozyme. Arch. Biochem. Biophys. 63, 106 (1956). 

Solvent-induced H chemical shifts of hydrogen-bonded H-atoms are not only found for hydrogen-bonded solutejsolvent complexes but also for hydrogen-bonded soluteffolute complexes. A well-studied example is the intermolecularly hydrogen-bonded 1 1 complex between trifluoroacetic acid (as HBD) and 2,4,6-trimethylpyridine (as HBA), as shown in Eq. (6-23) [408] cf. also Eq. (4-29) in Section 4.4.1. 

Mohammadizadeh MR, Hasaninejad A, Bahramzadeh M (2009) Trifluoroacetic acid as an efficient catalyst for one-pot, four-component synthesis of 1, 2, 4, 5-tetrasubstituted imidazoles under microwave-assisted, solvent-free conditions. Synth Commun 39 3232-3242... 

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... 

Rosbash, D.O. and Leavitt, D., Decalcification of bone with trifluoroacetic acid, Am. J. Clin. Pathol. 22, 914-915, 1952 Katz, J.J., Anhydrous trifluoroacetic acid as a solvent for proteins, Nature 174, 509, 1954 Uphaus, R.A., Grossweiner, L.I., Katz, J.J., and Kopple, K.D., Fluorescence of tryptophan derivatives in trifluoroacetic acid, Science 129, 641-643, 1959 Acharya, A.S., di Donato, A., Manjula, B.N. et al., Influence of trifluoroacetic acid on retention times of histidine-containing tryptic... 

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