Trifluoroacetic acid anhydride, formation

A suspension of potassiumperoxodisulfate in a mixture of trifluoroacetic acid and trifluoroacetic acid anhydride at a methane pressure of 20-30 atmospheres methane and 80-100 °C in the presence of catalytic amounts of 18 and 20 leads to the formation of the trifluoroacetic acid methylester. Scheme 23 shows the oxidative character of the reaction which formally can be described as CH4 [CH3]" -1- H -l- 2e". 

There is an interesting difference in properties between fluoro compounds and the corresponding hydrogen compounds that can be explained by the assumption of the formation of C—H---X bonds. For example, trifluoroacetyl chloride, F CC0C1, has a boiling point below 0°C, whereas that of acetyl chloride is 51°C similarly, trifluoroacetic acid anhydride, (FjCCO O, boils at 20°C and acetic acid anhydride at 137°C. 

The addition of alcohols to nitrilium salts gives rise to formation of alkoxymethyleneiminium salts, which react with bases to yield imido esters (231 Scheme 33). - By deprotonation of carboxylic acid amides ambident anions are formed, which can be alkylated in the presence of silver ions to give imido esters, e.g. (232). " Secondary amides react with trifluoroacetic acid anhydride or trifluorosulfonic acid anhydride to give mixed anhydrides of imidic acids (233). ... 

When the number of the bridge increases, a conventional process gradually does not tend to proceed. For example, trifluoroacetic acid anhydride, which is used in the first bridge formation reaction, is changed to polyphosphoric acid or poly-... 

More recent work indicated that this reaction proceeds thru the intermediate formation of the mixed anhydride of nitrous and trifluoroacetic acids (F3CCONO) (Ref 11). 

Studies on Trifluoroacetic Acid. Part I. Trifluoroacetic Anhydride as a Promotor of Ester Formation between Hydroxy-Compounds and Carboxylic Acids, E. J. Bourne, M. Stacey, J. C. Tatlow, and J. M. Tedder, J. Chem. Soc., (1949) 2976-2979. 

One study of the Et3SiH/TFA reduction of acid anhydrides reports the formation of one equivalent each of the alcohol and the trifluoroacetate ester of the acid (Eq. 139).287... 

Reaction of the imidazole (7-4) with the benzofuran derivative (6-7) leads to the displacement of the benzylic halogen and the formation of the alkylation product (8-1). Treatment of that intermediate with trifluoroacetic acid breaks open the urethane to afford the corresponding free amine. This is allowed to react with ttiflic anhydride to afford the trifluoromethyl sulfonamide (8-2). The ester group on the imdidazole is then saponified, and the newly formed acid is reacted with carbonyl diimidazole. Reaction with ammonia converts the activated carboxyl group to the amide. There is thus obtained the angiotensin antagonist saprisartan (8-3) [6]. 

The norbelladine derivative 408, which served as the starting material for the synthesis of ( )-oxocrinine (415) (Scheme 35), may be readily prepared from the reductive animation of piperonal with tyramine followed by acylation with trifluoroacetic anhydride (191,192). When the N-acylated monophenol 408 was treated with excess thallium tris(trifluoroacetate) in methylene chloride, the di-enone 412 was obtained in 19% yield (191), whereas use of the oxidant vanadium oxyfluoride in trifluoroacetic acid/trifluoroacetic anhydride afforded 412 in 88% yield (192). Base-induced N-deacylation of 412 was accompanied by spontaneous cyclization to furnish racemic oxocrinine (415). Attempts to oxidize the free amine derived from 408 led to the formation of a number of products, some of which resulted from oxidation at nitrogen. 

Irradiation of mixtures of benzene and maleic anhydride in the presence of trifluoroacetic acid has shed more light on the mechanism of the photoaddition [36], Under these circumstances, formation of the 1 2 adduct is completely suppressed and a new 1 1 adduct, phenylsuccinic anhydride, is obtained. It was concluded from these experiments that excitation of the ground-state complex between benzene and maleic anhydride leads to a zwitterionic intermediate that can be intercepted by protonation (Scheme 5). 

Scheme 5 Formation of phenylsuccinic anhydride by irradiation of benzene and maleic anhydride in the presence of trifluoroacetic acid.

Azotomycin is anticancer antibiotic produced by Streptomyces ambofaciens. Total sythesis of it from y-benzyl-N-tert-butyloxycarbonyl-L-glutamic acid (y-OBzi-N-Boc-L-Glu) has been accomplished in nine steps. The mixed carbonic anhydride method was chosen for peptide bond formation. Commerically available y-OBzi-N-Boc-L-Glu was esterified with ethereal diazomethane, deprotected with trifluoroacetic acid-methylene chloride (1 1), and converted to hydrochloride y-benzyl-L-glutamic acid a-methyl ester (y-OBzi-L-Glu-a-OMe HCI) by treatment with dry hydrogen chloride in ethyl ether, MP 129°-135°C (dec.) [a]D25= + 13.3° (CHCI3). 

The inability of C-terminal proline to be derivatized to a thiohydantoin has been a major impediment to the development of a routine method for the C-terminal sequence analysis of proteins and peptides. Since the method was first described in 1926 (2), the derivatization of C-terminal proline has been problematic. While over the years a few investigators have reported the derivatization of proline, either with the free amino acid or on a peptide, to a thiohydantoin (6-8), others have been unable to obtain any experimental evidence for the formation of a thiohydantoin derivative of proline (9-12). Recently, utilizing a procedure similar to that described by Kubo et al. (6), Inglis et al. (13) have described the successful synthesis of thiohydantoin proline from N-acetylproline. This was done by the one-step reaction of acetic anhydride, acetic acid, trifluoroacetic acid, and ammonium thiocyanate with N-acetyl proline. We have reproduced this synthesis and further developed it to a large scale synthesis of TH-Proline. 

The role of trifluoroacetic anhydride in these acylations was indicated by the diminished yield of acylation product obtained when the ratio of trifluoroacetic anhydride to hydroxy compound lay below unity, optimum conditions requiring a slight excess of this reagent. A catalytic function was, therefore, excluded, and the view was advanced that trifluoroacetic anhydride serves the purpose of converting the added carboxylic acid into the corresponding acyl trifluoroacetate. Later work on the nature of the equilibria between acyl anhydrides and acids in the presence of trifluoroacetic anhydride showed that the acylating capacity of a mixture of a carboxylic acid and trifluoroacetic anhydride is enhanced by the trifluoroacetic acid liberated when the unsymmetrical anhydride is formed. Further, cryo-scopic studies on solutions in acetic acid of the pure, unsymmetrical anhydride, acetyl trifluoroacetate, have shown that, contrary to an earlier conclusion that acetic anhydride is not formed to any appreciable extent, acetyl trifluoroacetate is, in fact, almost completely converted into acetic anhydride in excess acetic acid. In carrying out an acylation with trifluoroacetic anhydride and a carboxylic acid, it is, therefore, important to avoid an excess of the acid, so that the maximum concentration of the unsymmetrical anhydride is present in the equilibrium system. Extensive studies made on the action of acyl trifluoroacetates on hydroxy compounds under different conditions, with the simultaneous formation of the acyl and trifluoroacetyl derivatives, will be discussed later. 

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