Trifluoroacetic acid, reaction

Compared with reactions in other strong acids used in hydrogenations, such as hydrochloric, sulfuric, and trifluoroacetic acid, reactions in hydrofluoric acid are faster and proceed more selectively under milder conditions [2]... 

The presence of an internal salt, a zwitterion or betaine, in cephalosporins enhances their solubity in water, making such agents particularly suitable for parenteral administration. The preparation of one such dmg first involves the replacement of allyl oxygen in the tert-butylcarbonyloxy protected 7-ACA derivative (23-1) by nitrogen in azaindan (23-2) to afford the betaine (23-3). The protecting group is then removed so as to free the amine on the azetidone (23-4) by treatment with trifluoroacetic acid. Reaction with the thiazole free acid (23-5) in the presence of DCC then affords cefpirone (23-6) [26]. 

Gem-dibromocyclopropanes can be converted into synthetically useful cyclopropanone equivalents by a process consisting of lithium-halogen exchange followed by reaction of lithiocyclopropane (113) with dimethyl disulfide (Scheme 43) . The resulting bromo-methylthio derivative (114) undergoes a variety of substitution reactions. Methanolysis gives S,0-dimethylketal (115) which can be converted into l,l bis(methyl-thio)cyclopropane (116) with methyl mercaptan in trifluoroacetic acid. Reaction of 114 with other nucleophiles provides the derivatives shown in Scheme 44 . The sulfur-... 

Saikia, A. K., Barua, N. C., Sharma, R. P., Ghosh, A. C. The zinc-trifluoroacetic acid reaction in organic solvents afacile procedure for the conversion of nitroolefins into carbonyl compounds under mild conditions. J, Chem. Res., Synop. 1996,124-125. 

Talipov, R. R, Safarov, 1. M., Tahpova, G. R., Safarov, M. G. (1997). Kinetics of Heptene-I Interaction with Formaldehyde in Trifluoroacetic Acid. Reaction Kinetics and Catalysis Letters, 61,63-68. 

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. 

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. 

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). 

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. 

Fluoroalkjiations are frequentiy performed indirectly using tandem reactions. Arenes react with sodium borohydride in trifluoroacetic acid to afford otherwise difficult to obtain l,l,l-trifluoro-2,2-diarylethanes. Presumably sodium borohydride reacts initially with the trifluoroacetic acid to produce the trifluoroacetaldehyde or its equivalent, which rapidly undergoes Friedel-Crafts-type condensation to give an intermediate carbinol. The carbinol further alkylates ben2ene under the reaction conditions giving the observed product. The reaction with stericaHy crowded arenes such as mesitylene and durene... 

Whereas the above reactions are appHcable to activated aromatics, deactivated aromatics can be formylated by reaction with hexamethylenetetramine in strong acids such as 75% polyphosphoric acid, methanesulfonic acid, or trifluoroacetic acid to give saUcylaldehyde derivatives (117). Formyl fluoride (HCOF) has also been used as formyl a ting agent in the Friedel-Crafts reaction of aromatics (118). Formyl fluoride [1493-02-3] in the presence of BF was found to be an efficient electrophilic formyl a ting agent, giving 53% para-, 43% ortho- and 3.5% meta-tolualdehydes upon formylation of toluene (110). 

On reaction with /V-methyl- /V-phenylhydrazine, however, the hydrazone (47) can be isolated, which on further treatment with anhydrous trifluoroacetic acid gives an A/-aLkenylpyrazole (48) (eq. 9). 

However, this method is appHed only when esterification cannot be effected by the usual acid—alcohol reaction because of the higher cost of the anhydrides. The production of cellulose acetate (see Fibers, cellulose esters), phenyl acetate (used in acetaminophen production), and aspirin (acetylsahcyhc acid) (see Salicylic acid) are examples of the large-scale use of acetic anhydride. The speed of acylation is greatiy increased by the use of catalysts (68) such as sulfuric acid, perchloric acid, trifluoroacetic acid, phosphoms pentoxide, 2inc chloride, ferric chloride, sodium acetate, and tertiary amines, eg, 4-dimethylaminopyridine. 

Catalytic reduction of folic acid to 5,6,7,8-tetrahydrofolic acid (225) proceeds fast in trifluoroacetic acid (66HCA875), but a modified method using chemical reductants leads with sodium dithionite to 7,8-dihydrofolic acid (224). Further treatment with sodium borohydride gives (225) which has been converted into 5-formyl-(6i ,S)-5,6,7,8-tetrahydro-L-folic acid (leucovorin) (226) by reaction with methyl formate (equation 70) (80HCA2554). 

Thiophene is also readily acylated under both Friedel-Crafts and Vilsmeier-Haack conditions and similarly to pyrrole and furan gives 2-acylated products. An almost quantitative conversion of thiophene into its 2-benzoyl derivative is obtained by reaction with 2-benzoyloxypyridine and trifluoroacetic acid. The attempted preparation of 2-benzoylthiophene under standard Friedel-Crafts conditions, however, failed (80S139). 

Methyl-3,4-dinitropyrrole (170) undergoes some interesting reactions with nucleophilic reagents. With methanolic sodium methoxide it yields a product (171) which on treatment with trifluoroacetic acid gives the 2-methoxypyrrole (172) 78CC564). 

At Smith Kline French a general approach to cephalosporin and penicillin nuclear analogs was developed that utilizes a monocyclic /3-lactam (59) with the correct cis stereochemistry as a key intermediate. This is prepared by reaction of the mixed anhydride of azidoacetic acid and trifluoroacetic acid with imine (58) followed by oxidative removal of the dimethoxybenzyl group. This product could be further elaborated to intermediate (60) which, on reaction with a -bromoketones, provides isocephalosporins (61). These nuclear analogs displayed antibacterial properties similar to cephalosporins (b-79MI51000). 

The silver oxide was prepared by adding, with manual stirring, 66 g. of 98% sodium hydroxide (1.62 moles) in 2 1. of water to a solution of 274 g. (1.62 moles) of silver nitrate in 500 ml. of water. The precipitate was collected by filtration and washed with water until free from alkali. The wet cake can be dried or preferably used moist for reaction with trifluoroacetic acid. 

The importance of solvent participation in the borderline mechanisms should be noted. Nucleophilic participation is minimized by high electronegativity, which reduces the Lewis basicity and polarizability of the solvent molecules. Trifluoroacetic acid and perfiuoro alcohols are among the least nucleophilic of the solvents used in solvolysis studies. These solvents are used to define the characteristics of reactions proceeding without nucleophilic solvent participation. Solvent nucleophilicity increases with the electron-donating capacity of the molecule. The order trifluoroacetic acid < trifluoroetha-nol <acetic acid < water < ethanol gives a qualitative indication of the trend in solvent nucleophilicity. More will be said about solvent nucleophilicity in Section 5.5. 

Reaction of cyclooctene with trifluoroacetic acid occurs by a Itydride-shift process. 

An alternative view of these addition reactions is that the rate-determining step is halide-assisted proton transfer, followed by capture of the carbocation, with or without rearrangement Bromide ion accelerates addition of HBr to 1-, 2-, and 4-octene in 20% trifluoroacetic acid in CH2CI2. In the same system, 3,3-dimethyl-1-butene shows substantial rearrangement Even 1- and 2-octene show some evidence of rearrangement, as detected by hydride shifts. These results can all be accoimted for by a halide-assisted protonation. The key intermediate in this mechanism is an ion sandwich. An estimation of the fate of the 2-octyl cation under these conditions has been made ... 

Alkynes react when heated with trifluoroacetic acid to give addition products. Mixtures of syn and anti addition products are obtained. Similar addition reactions occur with trifluoromethanesulfonic acid. These reactions are analogous to acid-catalyzed hydration and proceed through a vinyl cation intermediate. 

Molecular bromine is believed to be the reactive brominating agent in uncatalyzed brominations. The brominations of benzene and toluene are first-order in both bromine and the aromatic substrate in trifluoroacetic acid solution, but the rate expressions become more complicated when these reactions take place in the presence of water. " The bromination of benzene in aqueous acetic acid exhibits a first-order dependence on bromine concentration when bromide ion is present. The observed rate is dependent on bromide ion concentration, decreasing with increasing bromide ion concentration. The detailed kinetics are consistent with a rate-determining formation of the n-complex when bromide ion concentration is low, but with a shift to reversible formation of the n-complex... 

Androst-4-ene-3,17-dione. Testosterone (0.58 g, 2 mmoles) is dissolved in a solution prepared from 3 ml of benzene, 3 ml of dimethyl sulfoxide, 0.16 ml (2 mmoles) of pyridine and 0.08 ml (1 mmole) of trifluoroacetic acid. After addition of 1.24 g (6 mmoles) of dicyclohexylcarbodiimide, the sealed reaction flask is kept overnight at room temperature. Ether (50 ml) is added followed by a solution of 0.54 g (6 mmoles) of oxalic acid in 5 ml of methanol. After gas evolution has ceased ( 30 min) 50 ml of water is added and the insoluble dicyclohexylurea is removed by filtration. The organic phase is then extracted twice with 5 % sodium bicarbonate and once with water, dried over sodium sulfate and evaporated to a crystalline residue (0.80 g) which still contains a little dicyclohexylurea. Direct crystallization from 5 ml of ethanol gives androst-4-ene-3,17-dione (0.53 g, 92%) in two crops, mp 169-170°. 

The postulated intermediates of the reaction, the 5-haloamines, can be isolated when the irradiation is performed in trifluoroacetic acid. 

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