Trifluoroacetic acid oxidations

Thallium (ITT) salts of formic, acetic, and trifluoroacetic acids are prepared from the corresponding acid and thaUium(III) oxide (11). Other thaUium(III) carboxylates can be obtained from the metathesis of thaUium(III) acetate and the carboxyUc acid (12). They are colorless, hygroscopic soUds. 

Esters derived from the primary alcohols are the most stable and those derived from the tertiary alcohols are the least stable. The decomposition temperature is lower in polar solvents, eg, dimethyl sulfoxide (DMSO), with decomposition occurring at 20°C for esters derived from the tertiary alcohols (38). Esters of benzyl xanthic acid yield stilbenes on heating, and those from neopentyl alcohols thermally rearrange to the corresponding dithiol esters (39,40). The dialkyl xanthate esters catalytically rearrange to the dithiol esters with conventional Lewis acids or trifluoroacetic acid (41,42). The esters are also catalytically rearranged to the dithiolesters by pyridine Ai-oxide catalysts (43) ... 

Aqueous salt solutions such as saturated 2inc chloride [7646-85-7] or calcium thiocyanate [2092-16-2] can dissolve limited amounts of cellulose (87). Two non-aqueous salt solutions are ammonium thiocyanate [1762-95-4]— uoamonia. and lithium chloride /744Z-4/A/—dimethyl acetamide [127-19-5]. Solutions up to about 15% can be made with these solvents. Trifluoroacetic acid [76-05-17—methylene chloride [75-09-2] and /V-methy1morpho1ine N-oxide [7529-22-8]—(92—94) are two other solvent systems that have been studied (95). 

Surprisingly, there are very few examples of successful fV-oxidation of pyrazoles. Simple fV-alkylpyrazoles generally do not react with peracids (B-76MI40402,77JCS(P1)672). The only two positive results are the peracetic acid (hydrogen peroxide in acetic acid) transformation of 1-methylpyrazoIe into 1-methylpyrazole 2-oxide (268) in moderate yield and the peroxy-trifluoroacetic acid (90% hydrogen peroxide in trifluoroacetic acid) transformation of 5-amino-l-methylpyrazoIe into l-methyl-5-nitropyrazoIe 2-oxide (269). 

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). 

This thiourea, prepared from an amino acid and phenyl isothiocyanate, is cleaved by anhydrous trifluoroacetic acid (an N-COCF3 group is stable), and by oxidation (/72-CIC6H4CO3H, 0°, 1.5 h, 73% yield H2O2/ACOH, 80°, 80 min, 44% yield). ... 

Bis(3,4-diethyl-2-pyrrolylmethyl)-3,4-dietliyl-l//-pyrrole (2), prepared in situ from the di-t-butylester of the 5,5 -dicarboxylic acid (/), reacts with 4//-1,2,4-triazole-3,5-dialdehyde (3) in di-chloromethane in the presence of trifluoroacetic acid and 2,3-dichloro-5,6-dicyano-/)-benzoquino-ne as an oxidation reagent. Dark blue crystals are obtained after chromatographic purification. The dark violet chloroform solution fluoresces purple at 360 nm and gives the NMR experiments 39. Which compound and which tautomer of it has been formed ... 

A. Silver trifluoroacetate. To a suspension of 187 g. (0.81 mole) of silver oxide (Note 1) in 200 ml. of water is added 177 g. (1.55 moles) of trifluoroacetic acid (Note 2). The resulting solution is filtered, and the filtrate is evaporated to dryness under reduced pressure. The dry silver trifluoroacetate thus obtained is purified by placing it in a Soxhlet thimble and extracting with ether, or by dissolving the salt in 1.2 1. of ether, filtering through a thin layer of activated carbon, and evaporating the filtered ether solution to dryness. The yield of colorless crystalline salt obtained after removal of the ether is 300 g. (88%). 

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. 

Because of Us high polarity and low nucleophilicity, a trifluoroacetic acid medium is usually used for the investigation of such carbocationic processes as solvolysis, protonation of alkenes, skeletal rearrangements, and hydride shifts [22-24] It also has been used for several synthetically useful reachons, such as electrophilic aromatic substitution [25], reductions [26, 27], and oxidations [28] Trifluoroacetic acid is a good medium for the nitration of aromatic compounds Nitration of benzene or toluene with sodium nitrate in trifluoroacetic acid is almost quantitative after 4 h at room temperature [25] Under these conditions, toluene gives the usual mixture of mononitrotoluenes in an o m p ratio of 61 6 2 6 35 8 A trifluoroacetic acid medium can be used for the reduction of acids, ketones, and alcohols with sodium borohydnde [26] or triethylsilane [27] Diary Iketones are smoothly reduced by sodium borohydnde in trifluoroacetic acid to diarylmethanes (equation 13)... 

Trifluoroacetic acid is a useful medium for a number of oxidation reactions It IS highly resistant to strong oxidants, even to permanganates and chromates For instance, various alkanes, cycloalkanes, and arenes can be oxidized degradatively by potassium permanganate in trifluoroacetic acid under mild conditions [28]... 

A very common oxidizing reagent is peroxytrifluoroacetic acid, which is usually generated in situ from trifluoroacetic acid [29, 30, 31] or trifluoroacetic anhydride [32, 33, 34] and hydrogen peroxide Peroxytrifluoroacetic acid is one of the most efficient epoxidizing reagents [35] It can be used to prepare epoxides... 

The salts of some enamines crystallize as hydrates. In such cases it is possible that they are derived from either the tautomeric carbinolamine or the amino ketone forms. Amino ketone salts (93) ( = 5, 11) can serve as examples. The proton resonance spectra of 93 show that these salts exist in the open-chain forms in trifluoroacetic acid solution, rather than in the ring-closed forms (94, n = 5, 11). The spectrum of the 6-methylamino-l-phenylhexanone cation shows a multiplet at about 2.15 ppm for phenyl, a triplet for the N-methyl centered at 7.0 ppm and overlapped by signals for the methylene protons at about 8.2 ppm. The spectrum of 93 ( = 11) was similar. These assignments were confirmed by determination of the spectrum in deuterium oxide. Here the N-methyl group of 93 showed a sharp singlet at about 7.4 ppm since the splitting in —NDjMe was much reduced from that of the undeuterated compound. 

The 5-isobutoxymethyl monothioacetal is stable io2N hydrochloric acid and to 50% acetic acid some decomposition occurs in 2 A sodium hydroxide. The monothioacetal is also stable to 12 A hydrochloric acid in acetone (used to remove an A -triphenylmethyl group) and to hydrazine hydrate in refluxing ethanol (used to cleave an A-phthaloyl group). It is cleaved by boron trifluoride etherate in acetic acid, by silver nitrate in ethanol, and by trifluoroacetic acid. The monothioacetal is oxidized to a disulfide by thiocyanogen, (SCN)2. ... 

Phenotellurazine bis(trifluoroacetates) can be obtained by the oxidation of A-methylphenotellurazines with lead dioxide in trifluoroacetic acid solution. The... 

Tiiazine 4-oxides 55 react with indoles in the presence of trifluoroacetic acid, giving more or less stable cr -adducts, 5-indolyl-4-hydroxy-4,5-dihydro-1,2,4-tiiazines 57, which were isolated from the reaction mixture (98ZOR429). In this case the acid activates the substrate, and the protonated 1,2,4-triazinium cation is more active toward nucleophilic attack. 

Triazine 4-oxides 55 react with phenols (phenol, 2,6-dimethylphenol, resorcinol, 4-hexyh esorcinol) in trifluoroacetic acid in a similar way, yielding intermediate (T -adducts 5-hydroxyphenyl-4-hydroxy-4,5-dihydro-l,2,4-triazines 61. Subsequent oxidation leads to the corresponding 5-hydroxyphenyl-l,2,4-triazine 4-oxides 62 (97MC116). 

The reaction of 1,2,4-triazine 4-oxides 55 with CH-active 1,3-diketones (dime-done, indanedione, iV.iV -dimethylbarbituric acid) in the presence of trifluoroacetic acid (substrate activation by protonation) or KOH (activation of the nucleophile) leads to stable cr -adducts 63, whose oxidative aromatization by the action of KMn04 results in 5-substituted 1,2,4-triazine 4-oxides 64 (98MI). 

Accordingly, cyclic nitronates can be a useful synthetic equivalent of functionalized nitrile oxides, while reaction examples are quite limited. Thus, 2-isoxazoline N-oxide and 5,6-dihydro-4H-l,2-oxazine N-oxide, as five- and six-membered cyclic nitronates, were generated in-situ by dehydroiodination of 3-iodo-l-nitropropane and 4-iodo-l-nitrobutane with triethylamine and trapped with monosubstituted alkenes to give 5-substituted 3-(2-hydroxyethyl)isoxazolines and 2-phenylperhydro-l,2-oxazino[2,3-fe]isoxazole, respectively (Scheme 7.26) [72b]. Upon treatment with a catalytic amount of trifluoroacetic acid, the perhydro-l,2-oxazino[2,3-fe]isoxazole was quantitatively converted into the corresponding 2-isoxazoline. Since a method for catalyzed enantioselective nitrone cycloadditions was established and cyclic nitronates should behave like cyclic nitrones in reactivity, there would be a good chance to attain catalyzed enantioselective formation of 2-isoxazolines via nitronate cycloadditions. 

A completely different concept13 makes use of a highly reduced bilane 5 which is oxidatively cyclized to an isobacteriochlorin 6 with copper(II) acetate. The ring closure is initiated by ester cleavage with trifluoroacetic acid and decarboxylative formylation with trimethyl orthoformate to yield a dialdehyde. One of the aldehyde functions forms the desired methine bridge whereas the other is lost during cyclization. 

Triethylamine, 61,83,87,88,94,99,100,112 Triethylamine N-oxide, 84 Triethylbenzylammonium chloride, 49 Triethylsilane, 104,127.128 Trifluoroacetic acid, 59 Trimethyi-m-dimethylaminophenylsilane, 40 Trimethyl orthoformate, 109... 

Both the submitters and the checkers used thallium(III) tri-fluoroacetate prepared from thallium(III) oxide and trifluoroacetic acid.3 Although this material may be purchased from Aldrich Chemical Company, Inc. and Eastman Organic Chemicals, the submitters recommend that the reagent be freshly prepared prior to use. 

---