Carboxylic acid esters trifluoroacetic anhydride

Treatment of a carboxylic acid with trifluoroacetic anhydride leads to an unsym-metiical anhydride that rapidly reacts with alcohol to give an ester ... 

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. ... 

E. J. Bourne, M. Stacey, J. C. Tatlow, and J. M. Tedder, Studies on the trifluoroacetic acid 1. Trifluoroacetic anhydride as a promoter of ester formation between hydroxy-compounds and carboxylic acids, J. Chem. Soc. (1949) 2976-2979. 

In mixed trifluoroacetic anhydrides, the strong electron-withdrawing tri-fluoroacetyl group polarizes the bonds to the anhydride oxygen in such a way that it tends to split to acylium cation and trifluoroacetate anion [/0/. Generally, the products of the reaction of hydroxy compounds with acyl trifluoroacetates are esters of carboxylic acids and trifluoroacetic acid, because the acyl carbonyl is better fit for a nucleophilic attack than the carbonyl next to the trifluoromethyl group [707]. 

Other than those of the carboxylic type for example, a mixture of p-toluene-sulfonic acid and triduoroacetic anhydride forms sulfones by reaction with suitably activated aromatic compounds. By the same technique, the hexa-nitrate esters of o-mannitol and D-glucitol were obtained by use of solutions of fuming nitric acid in trifluoroacetic anhydride at 0°. The probable reaction mechanisms of these and other examples of the conversion of oxy acids into reactive entities have been briefly considered. ... 

Besides acetates and benzoates many other types of carboxylic acid esters can be formed, such as chloroacetates, trifluoroacetates, pivalates, carbonates, and thiocarbonates, by reaction with chloroacetic anhydride, trifluoroacetic anhydride, pivaloyl chloride (2,2-dimethyl propanoyl chloride), phosgene or methylchloro-formate, and carbon disulfide or carbonyl sulfide, respectively. Each of the ester derivatives imparts specific chemical properties to the carbohydrates so they can be used selectively in synthetic schemes. It was found that the sulfonic acid esters... 

So do anhydrides and many compounds that enolize easily (e.g., malonic ester and aliphatic nitro compounds). The mechanism is usually regarded as proceeding through the enol as in 12-4. If chlorosulfuric acid (CISO2OH) is used as a catalyst, carboxylic acids can be ot-iodinated, as well as chlorinated or brominated. N-Bromosuccinimide in a mixture of sulfuric acid-trifluoroacetic acid can mono-brominate simple carboxylic acids. ... 

Carboxylic acids on the outer surface of SAMs may also be activated as symmetric anhydrides by action of trifluoroacetic anhydride as dehydrating agent57 The most common active esters are A-hydroxysuccinimidyl esters (NHS esters). They are usually prepared by reacting the carboxyl-terminated SAMs with... 

Allyl-7-amino-4-oxo-4H-chromene-2-carboxylic acid ethyl ester (32 mmol) dissolved in 400 ml of CH2C12 was treated first with A.IV-diisopropylethylamine (50 mmol), then trifluoroacetic anhydride (50 mmol) while cooling the mixture in an ice bath. The mixture was stirred 1 hour at ambient temperature, then washed with 200 ml apiece 2M HC1, saturated NaHC03 solution, and brine, dried with Na2S04, and filtered. The material was concentrated and 12.2 g product isolated as a pale yellow solid, mp = 136-137°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). ... 

Cyclodehydration Aluminum chloride see also Methyl fluorene-9-carboxylate). Dowtherm. Fluorosulfonic acid. Hydrogen fluoride. Perchloric add. Phosphorus pentoxide. Phosphoryl chloride. Polyphosphate ester. Polyphosphoric add. Potassium bisulfate. Sodium aluminum chloride. Sulfur trioxide-Dimelhylformamide. />-Toluenesulfonic acid. Trifluoroacetic acid. Trifluoroacetic anhydride. 

NHS trifluoroacetate is an amazing reagent. Not only does is activate the carboxylic acid through a mixed anhydride to form an ester under mild conditions, but the NHS leaving group is also the nucleophile that forms an ester that is both stable enough to work with, yet easily reactive when it needs to be. Perfect ... 

Fairly high yields of coumarins are obtainable by irradiation for 4-6 h of methoxycinnamic acids in acetonitrile-water saturated with oxygen and containing naphthalene-1,4-dinitrile. Further routes to the flavone ring system continue to appear. Flavone-3-carboxylic acids are ao ssible from fi-phenoxybenzylidenemalonic acids and either sulphuric acid or trifluoroacetic acid-trifluoroacetic anhydride. Attempts to cyclize the malonic esters were less... 

Deblocking with HCl in acetic acid or with trifluoroacetic acid can leave, even after thorough washing, small amounts of acetic acid or trifluoroacetic acid attached to the peptidyl-resin. The carboxyl groups of these acids are activated in the next coupling step, certainly by carbodiimides, but potentially also by symmetrical anhydrides or active esters... 

---