Anhydride, trifluoroacetic

Primary alkanols and 2-alkenols are converted into the corresponding halides in high yield by a one-pot, two-step reaction via transformation into intermediate trifluoroacetates, followed by nucleophilic substitution with lithium halides (eq 5).  

Form Supplied in colorless liquid commercially available. Analysis of Reagent Purity by standard analytical techniques. Preparative Methods by distilling Trifluoroacetic Acid from Phosphorus(V) Oxide  

Handling, Storage, and Precautions corrosive and moisture sensitive toxic by inhalation should be freshly distilled prior to reaction. Use in a fume hood. 

Activated Esters. Mixed anhydrides may be prepared by reaction of carboxylic acids with trifluoroacetic anhydride. The method has been used widely as a means of activating carboxyl groups to nucleophilic attack. The method has also been highly useful in Friedel-Crafts acylation of arenes (eqs 1 and 2). Sulfonic acids are also activated to nucleophilic attack substituted sulfones result. Intramolecular Friedel-Crafts reactions are also facilitated, but only for formation of six-membered rings.  

Anhydrides of diacids are prepared in (about) 90% yield by reaction with TFAA in ether. The method involves formation of the monotrifluoroacetyl mixed anhydride, which may be converted to the cyclic anhydride by heating under vacuum (eq 3)7 

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Formation - with trifluoroacetic anhydride or trifluoroacetyl chloride Cleavage - K2CO3, MeOH... 

Trifluoroacetamides are more stable toward nucleophiles than the corresponding esters and are easily formed from trifluoroacetic anhydride and the amine. The trifluoroacetyl group (Tfac) is slowly cleaved by aqueous or methanolic HQ, NH, or Ba(OH)2 solutions as well as by NaBHj in methanol (M.L. Wolfrom, 1967). 

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... 

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... 

Several electrophiles, such as acetic anhydride, nitric acid or alternative nitrating agents, such as ammonium nitrate in trifluoroacetic anhydride (41), or sodium hypochlorite, react at N-1, which is followed by reaction at N-3 under suitable conditions. In the case of acetic anhydride, the reaction can take place exclusively at N-3 if N-1 is hindered this fact has served as a criterion for studying the stereochemistry of 5-spirohydantoin derivatives (42,43). 

AijAT-dicyclohexylcarhodiimide (DCC) also leads to essentially quantitative conversion of amic acids to isoimides, rather than imides (30,31). Combinations of trifluoroacetic anhydride—triethjlarnine and ethyl chi oroform a te—triethyl amine also result in high yields of isoimides (30). A kinetic study on model compounds has revealed that isoimides and imides are formed via a mixed anhydride intermediate (12) that is formed by the acylation of the carboxylic group of amic acid (8). 

The need for pyrazoles substituted with the trifluoroacetyl group led to the reaction of ethoxyvinyl ether with trifluoroacetic anhydride, yielding 4-ethoxy-l,l,l-trifluoro-3-buten-2-one (38) this further reacted with aldehyde / fZ-butyUiydrazones, and after cyclization at room temperature under mildly acidic conditions the pyrazoles were obtained in satisfactory yields (eq. 7). Further treatment with H2SO4 removed the tert-huty group, thus providing an opportunity for further derivatization at N. ... 

SAMs of OH-terrninated alkanethiols have been used in many surface modification reactions (Fig. 14). These reacted with OTS to yield a weU-ordered bdayer (322), with octadecyldimethylchlorosilane (323,324), with POCI3 (325—327), with trifluoroacetic anhydride (328), epichlorohydrin (329), with alkyhsothiocyanate (330), with glutaric anhydride (331), and with chlorosulfonic acid (327). 

The reactivity of five-membered rings with one heteroatom to electrophilic reagents has been quantitatively compared in a variety of substitution reactions. Table 2 shows the rates of substitution compared to thiophene for formylation by phosgene and iV,AT-dimethylfor-mamide, acetylation by acetic anhydride and tin(IV) chloride, and trifluoroacetylation with trifluoroacetic anhydride (71AHC(13)235). 

Alkyl substituents. The steric effect of 1-alkyl substituents in the pyrrole series has been demonstrated in, for example, Vilsmeier formylation reactions. Thus as the bulk of the alkyl substituent on nitrogen is increased e.g. from Me to Bu ) so does the proportion of /3 substitution (70JCS(C)2573). A similar trend has been observed in a series of experiments on the trifiuoroacetylation of A-alkylpyrroles with trifluoroacetic anhydride (80JCR(S)42). 

Furan can also be acylated by the Vilsmeier-Haack method. Acylation of furans can also be carried out with acid anhydrides and acyl halides in the presence of Friedel-Crafts catalysts (BF3-Et20, SnCU or H3PO4). Reactive anhydrides such as trifluoroacetic anhydride, however, require no catalyst. Acetylation with acetyl p-toluenesulfonate gives high yields. 

The nucleophilic attack of hydroxylamine at the 5-position of 4-trifluoroacetyloxazoles (414) led to a mixture of stereoisomeric isoxazolines (415). Dehydration of these isomeric isoxazolines (415) in the presence of trifluoroacetic anhydride gave isoxazoles (416) in good yields (76JHC825). 

The o-nitrobenzyl and p-nitrobenzyl ethers can b prepared and cleaved by many of the methods described for benzyl ethers. The p-nitrobenzyl ether is also prepared from an alcohol and p-nitrobenzyl alcohol (trifluoroacetic anhydride, 2,6-lutidine, CH2CI2, 67% yield). In addition, the o-nitrobenzyl ether can be cleaved by irradiation (320 nm, 10 min, quant, yield of carbohydrate " 280 nm, 95% yield of nucleotide ). The p-nitrobenzyl ether has been cleaved by electrolytic reduction (—1.1 V, DMF, R4N X, 60% yield) and by reduction with Na2S204 (pH 8-9, 80-95% yield). These ethers can also be cleaved oxidatively (DDQ or electrolysis) after reduction to the aniline derivative. ... 

Bistrifluoroacetamide [407-24-9] M 209.1, m 85 , b 135-136 /744mm, 141 /760mm. Major impurity is trifluoroacetamide. Add trifluoroacetic anhydride, reflux for 2h and fractionate using a Vigreux column at atmospheric pressure. [J Chromatogr 7S 273 1973.]... 

Mercury(II) trifluoroacetate [13257-51-7] M 426.6. Recrystd from trifluoroacetic anhydride/trifluoroacetic acid [Lan and Kochi J Am Chem Soc 108 6720 7986]. Very TOXIC and hygroscopic. 

Potassium trifluoroacetate [2923-16-2] M 152.1, m 140-142°, pK 0.52 (for CFjCOjH). To purify dissolve the salt in trifluoroacetic acid with ca 2% of trifluoroacetic anhydride, filter and evaporate carefully to dryness (avoid over heating), and finally dry in a vacuum at 100°. It can be recrystallised from trifluoroacetic acid (solubility in the acid is ca 50.1%). [J Am Chem Soc 74 4746 1952, 76 4285 1954-, J Inorg Nucl Chem 9 166 1959.]... 

The checkers purchased trifluoroacetic acid from Aldrich Chemical Company, Inc., and distilled it from phosphorous pentoxide. The submitters point out that some trifluoroacetic anhydride, whose effects have not been fully investigated, is obtained under these conditions. The submitters prefer to use trifluoroacetic acid which has been distilled through a glass packed column without the use of a drying agent. 

Carboxylic acids react with trifluoroacetic anhydride to give mixed anhydrides that are especially useful for the acylation of hindered alcohols and phenols ... 

A very convenient synthetic procedure for nitration involves the mixing of a nitrate salt with trifluoroacetic anhydride. This presumably generates trifluoroacetyl nitrate. 

Note 1. When the trifluoroacetic anhydride treatment is omitted, the product is isolated in 15-26% yield. 

Acylation of various oxygen functions by use of common and commercially available fluonnated carboxylic acid denvatives such as trifluoroacetic anhydride or the corresponding acyl halides have already been discussed sufficiently in the first edition [10] Therefore only exceptional observations will be described in this section In the past 15 years, many denvatizations of various nonfluonnated oxygen compounds by fluoroacylation were made for analytical purposes. Thus Mosher s acid chlorides for example became ready-to-use reagents for the determination of the enantiomeric purity of alcohols and amines by NMR or gas-liquid chromatographic (GLC) techniques [//] (equation 1)... 

A rather interesting trifluoroacetylated acetal is formed in good yield when cyclohexanone is allowed to react with trifluoroacetic anhydride at room temperature [23] (equation 12). 

Epoxides are easily attacked by trifluoroacetic anhydride. The reactions lead to diesters of vicinal diols and monoesters of unsaturated allylic alcohols in ratios depending on the reaction conditions [24] (equation 13). 

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