Application of trifluoroacetic anhydride

Applications of trifluoroacetic anhydride in carbohydrate chemistry, T. G. Bonner, Adv. Carbohydr. Chem., 16 (1961). 

From the synthetic viewpoint, a particularly interesting trifluoroacetylation reaction of simple vinyl ethers was reported first by Hojo et al in 1976 [73] The scope and limitation of this particular reaction were elaborated intensively, the reaction proved to be of general applicability with practically no restrictions on substituents of the vinyl ether moiety 9] (equation 34) This general validity is particularly beneficial because a trifluoroacetylated vinyl ether is the synthetic equivalent of a specifically protected tnfluoromethyl-substituted 1,3-dicarbonyl compound 19], thus the reaction provides access to a broad spectrum of variously substituted synthetic building blocks with selective reactivities on each carbon acceptor (a) and donor (d) center (equation 35) Obviously, such building blocks can react as heterodiene systems m cycloaddition reactions [< 74] or can be treated with a wide variety ot 1,2 or 1 3-dinucleophihc species to give any desired tnfluoromethyl-substituted carbocychc or heterocyclic system [8 75] Treatment of simple vinyl ethers with an excess of trifluoroacetic anhydride at elevated temperature leads to doubly acylated products [76] Comparable acylation reactions occur with vinyl thioethers [73], and the mesoiomc l,3-oxathiol-4-ones show, at least in a formal sense, similar behavior [77] (equation 36)... 

Summary TNTC is prepared by treating NIHT.HC1 with nitromethane and ammonium nitrate in the presence of trifluoroacetic anhydride. After the reaction, the TNTC is contaminated with a by-product and hence needs to be purified. To do this, the contaminated TNTC is treated with ethyl acetate, and reciystallized. Commercial Industrial note For related, or similar information, see Application No. 471,906, January 29, 1990, by Gencorp Aerojet, to Der-Shing Hunag, Folsom, CA. Part or parts of this laboratory process may be protected by international, and/or commercial/industrial processes. Before using this process to legally manufacture the mentioned explosive, with intent to sell, consult any protected commercial or industrial processes related to, similar to, or additional to, the process discussed in this procedure. This process may be used to legally prepare the mentioned explosive for laboratory, educational, or research purposes. 

Cyanotrialkylborates (11), which can Iw readily prej red and are stable, are of interest due to their synthetic applicability in organic synthesis. Although no detail introduction of the reactions is n here, a brief account is presented. Cyanotrialkylborates react smoothly with 1 equivalent of trifluoroacetic anhydride (TFAA) at —78 °C and then at room temperature. Oxidation of the intermediates with hydrogen peroxide under basic conditions gives the corresponding symmetrical ketones in excellent yields The reaction is considered to proceed via the reaction path, as indicated in Eq. 23. Unsymmetrical ketones can also be obtained... 

The reaction of trifluoroacetic anhydride on the A(-oxides of 3)5-dimethytamino-steroids (51) (e.g., iV-methyl-5a-dihydroparavallarine) leads to the immonium salts (52) and (53), which can be hydrolysed to the 3-keto- or the 3-methylamino-steroid, respectively. " This reaction is generally applicable to other amines trimethylamine oxide is converted into iViV-dimethylformaldimmonium tri-fluoroacetate (54), which is an excellent Mannich reagent. ... 

A recent study has further proven the applicability of gas-phase reactions to functional groups at the monolayer surface. Alcohol terminal groups were quantitatively converted to trifluoroacetates by exposure to the vapours of trifluoroacetic anhydride (equation 7). Reaction with perfluoropropionic and perfluorobutyric anhydrides proceeded similarly, but with ca 80% yield (XPS). Very high contact angles (>120°) of perfluoro-terminated layers proved the formation of esters333. 

Several alternative procedures have been developed in which other reagents replace carbon monoxide as the migration terminus.11 The most generally applicable of these methods involves the use of cyanide ion and trifluoroacetic anhydride (TFAA). In this reaction the borane initially forms an adduct with cyanide ion. The migration is induced by N-acylation of the cyano group by TFAA. Oxidation and hydrolysis then give a ketone. 

Another example is provided by the application of the modified Polonovski reaction to A3-piperideines. Treatment of amine oxides (141) with trifluoroacetic anhydride results in the formation of iminium ion (142). These compounds can behave as useful synthetic intermediates, reacting with a number of nucleophiles such as cyanide ion (80JA1064). 

Thus, in line with earlier observation, the use of dimethylsulfoxide and trifluoroacetic anhydride led, by preferential oxidation of the secondary alcohol, to the hemiketal ( )-tazettine (400). On the other hand, application of the Dess-Martin method furnished, by selective oxidation of the primary alcohol group, ( )-11-epipretazettine (412) (also known as ( )-6a-epipretazettine), in 73% yield, previously converted into ( )-tazettine [100]. 

The molecular specificity of Fourier transform infrared (FTIR) lends itself quite well to applications in pharmaceutical development labs, as pointed out in a review article with some historical perspective.10 One of the more common applications of mid-IR in development is a real-time assessment of reaction completion when used in conjunction with standard multivariate statistical tools, such as partial least squares (PLS) and principal component analysis (PCA).18,19 Another clever use of FTIR is illustrated in Figure 9.1, where the real-time response of a probe-based spectroscopic analyzer afforded critical control in the charge of an activating agent (trifluoroacetic anhydride) to activate lactol. Due to stability and reactivity concerns, the in situ spectroscopic approach was... 

Ube Industries LtdinYamaguchi, Japan, and Kyoto University investigated the Swern oxidation for pharmaceutical intermediates [57,58]. In this reaction, alcohols are oxidized to carbonyl compounds using dimethyl sulfoxide. The reaction variant using dimethyl sulfoxide activated by trifluoroacetic anhydride (shown below) has found industrial application, but is limited to low-temperature operation (—50 °C or below) to avoid decomposition of an intermediate. 

Chemistry for the Automated C-Terminal Sequence Analysis of Proline Containing Polypeptides. Application of the acetic anhydride/TMS-ITC/TFA procedure, used for the synthesis of TH-proline, to the tripeptide, N-acetyl-Ala-Phe-Pro, in our laboratory, found that thiohydantoin proline was formed in low yield (approx. 1-2% of theoretical). Recovery of the peptide products after the reaction revealed that approximately half of the starting peptide was unchanged and the remaining hdf had been decarboxylated at the C-terminus, thereby blocking it to C-terminal sequence analysis. This was most likely caused by the high concentration of trifluoroacetic acid, the excess of acetic anhydride present, and the high temperature (80°C) at which the reaction was performed. 

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