Trifluoroacetic acid compounds

The following acid-catalyzed cyclizations leading to steroid hormone precursors exemplify some important facts an acetylenic bond is less nucleophilic than an olelinic bond acetylenic bonds tend to form cyclopentane rather than cyclohexane derivatives, if there is a choice in proton-catalyzed olefin cyclizations the thermodynamically most stable Irons connection of cyclohexane rings is obtained selectively electroneutral nucleophilic agents such as ethylene carbonate can be used to terminate the cationic cyclization process forming stable enol derivatives which can be hydrolyzed to carbonyl compounds without this nucleophile and with trifluoroacetic acid the corresponding enol ester may be obtained (M.B. Gravestock, 1978, A,B P.E. Peterson, 1969). 

Fluorinated Acids. This class of compounds is characterized by the strength of the fluorocarbon acids, eg, CF COOH, approaching that of mineral acids. This property results from the strong inductive effect of fluorine and is markedly less when the fluorocarbon group is moved away from the carbonyl group. Generally, their reactions are similar to organic acids and they find apphcations, particularly trifluoroacetic acid [76-05-1] and its anhydride [407-25-0] as promotors in the preparation of esters and ketones and in nitration reactions. 

Many carbamates have been used as protective groups. They are arranged in this chapter in order of increasing complexity of stmcture. The most useful compounds do not necessarily have the simplest stmctures, but are /-butyl (BOC), readily cleaved by acidic hydrolysis benzyl (Cbz or Z), cleaved by catalytic hy-drogenolysis 2,4-dichlorobenzyl, stable to the acid-catalyzed hydrolysis of benzyl and /-butyl carbamates 2-(biphenylyl)isopropyl, cleaved more easily than /-butyl carbamate by dilute acetic acid 9-fluorenylmethyl, cleaved by /3-elimination with base isonicotinyl, cleaved by reduction with zinc in acetic acid 1-adamantyl, readily cleaved by trifluoroacetic acid and ally], readily cleaved by Pd-catalyzed isomerisation. 

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 ... 

Although fluonnation of peroxoanions [S2] has been examined, the major emphasis in the fluonnation of oxygenated material is the preparation offhioroxy compounds The simplest, trifluoromethyl hypofluorite, can be prepared almost quantitatively by the action of fluorine on carbonyl fluoride (fluorophosgene) in the presence of various catalysts [Si, 84] Addition of fluorine to trifluoroacetic acid [S5] or its sodium salt [S6] gives rise to FjCF(OF)2 Long-chain fluoroxy compounds can also... 

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)... 

The methacrylic backbone structure makes the spherical Toyopearl particles rigid, which in turn allows linear pressure flow curves up to nearly 120 psi (<10 bar), as seen in Fig. 4.45. Toyopearl HW resins are highly resistant to chemical and microbial attack and are stable over a wide pH range (pH 2-12 for operation, and from pH 1 to 13 for routine cleaning and sanitization). Toyopearl HW resins are compatible with solvents such as methanol, ethanol, acetone, isopropanol, -propanol, and chloroform. Toyopearl HW media have been used with harsh denaturants such as guanidine chloride, sodium dodecyl sulfate, and urea with no loss of efficiency or resolution (40). Studies in which Toyopearl HW media were exposed to 50% trifluoroacetic acid at 40°C for 4 weeks revealed no change in the retention of various proteins. Similarly, the repeated exposure of Toyopearl HW-55S to 0.1 N NaOH did not change retention times or efficiencies for marker compounds (41). 

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. 

Stereoselectivity in the condensation reaction of 2-arylethylamines with carbonyl compounds to give 1,2,3,4-tetrahydroisoquinoline derivatives was somewhat dependent on whether acid catalysis or superacid catalysis was invoked. Particularly in the cases of 2-alkyl-N-benzylidene-2-phenethylamines, an enhanced stereoselectivity was observed with trifluorosulfonic acid (TFSA) as compared with the weaker acid, trifluoroacetic acid (TFA). Compound 43 was cyclized in the presence of TFA to give modest to good transicis product ratios. The analogous compound 44 was cyclized in the presence of TFSA to give slightly improved transicis product ratios. 

Ebumamonine was assembled utilizing a Pictet-Spengler cyclization of hydroxy-lactam 52 in the presence of trifluoroacetic acid at low temperature to give a mixture of diastereomers 53 in 95% yield. These compounds were readily separated by chromatography and the a-epimer was further elaborated to give the natural product. 

Reaction of the cyclopentadienyl rhodium and iridium tris(acetone) complexes with indole leads to the species 118 (M = Rh, Ir) [77JCS(D)1654 79JCS(D)1531]. None of these compounds deprotonates easily in acetone, but the iridium complex loses a proton in reaction with bases (Na2C03 in water, r-BuOK in acetone) to form the ri -indolyl complex 119. This reaction is easily reversed in the presence of small amounts of trifluoroacetic acid. 

Also. 77/-pyrrolo[l,2-fl]azepin-7-ones, e.g. 22, available by the thermal rearrangement of 1-azaspiro[4.5]dcca-l,3,6,9-tetraen-8-ones 21, in trifluoroacetic acid form the deep-blue 7-hy-droxypyrrolo[l,2-tf]azepinium cations, e.g. 23.219 In hot 48 % hydrobromic acid, however, the spiro compound 21 is re-formed. 

In addition to the reactions of luciferin shown in Fig. 7.2.3, Trainor (1979) made an interesting discovery that arylsulfatase from Pattela vulgata (Sigma) converts luciferin into a violet compound (treatment conditions pH 5.05, 37°C, 4 hr). The compound showed absorption peaks at 344 nm and 560 nm (Fig. 7.2.7), and the peaks shifted reversibly to 347 nm and 547 nm in acid, and to 364 nm and 720 nm in an alkaline solution. The violet compound was also obtained from the pink compound by treatment with arylsulfatase, or from luciferin by heating in 50% trifluoroacetic acid at 100°C for 1 hr, followed by an addition of oxygenated water. These results, together with the... 

The original procedure for the trifluoroacetylation of amino acids used trifluoroacetic anhydride [Acetic acid, trifluoro-, anhydride].4 This reagent, although inexpensive and readily available, has certain disadvantages it is a highly reactive compound and thus has caused undesired reactions such as the cleavage of amide or peptide bonds,5 unsymmetrical anhydrides are formed between the newly formed A-trifluoroacetylamino acids and the by-product trifluoroacetic acid, and excess trifluoroacetic anhydride has caused racemization of asymmetric centers. 

Hanstein and Traylor544 used a 4.3 M solution of trifluoroacetic acid in chloroform to measure the rates of deuteration of (PhCH2)2Hg at 35 °C, for which kx = 2,100 x 10"7. Comparison with other deuteration rates (which, however, were neither quoted nor referred to) was said to give a (CH2HgCH2Ph) = — 1.14 and the ortho para ratio was 0.84. For the compound PhCH2B(OH)j, the rate of deuteration by 3 M tartaric acid at 100 °C was found to be 5 x 10 7 (ortho para ratio = 1.1) and from this a value of ff4 (CH2B(OH)J) of —1.11 was claimed, but without the relevant data used to obtain these c+ values cautious use of them seems appropriate. 

Nesmeyanov et a/.545 used a mixture of ferrocene, deuterated trifluoroacetic acid and benzene in the molar ratios 1 2 20 in a preliminary investigation of the reactivity of ferrocene and its derivatives. At 25 °C, rate coefficients were 1,620 x 10-7 (ferrocene) and 19.3 xlO-7 (acetylferrocene). In a subsequent publication by Alikhanov and Shatenshtein543 these values were altered to 1,600 x 10-7 and 1.5 x 10 7, respectively, and a value of 0.77 x 10"7 added for 1,1-diacetylferrocene. Under the same conditions, toluene gave a value of 0.3 x 10-7 so that the activating effects of these compounds relative to benzene can be approximately determined. 

Blackley548 measured the rates of deuteration of biphenylene, fluorene, tri-phenylene, and phenanthrene relative to o-xylene as 6.15 5.85 1.08 1.32, which is in very good agreement with the values of 8.80 7.00 - 1.14 which may be deduced from the detritiation data in Table 159, obtained using anhydrous trifluoroacetic acid. Aqueous trifluoroacetic acid (with the addition in some cases of benzene to assist solubility) was used by Rice550, who found that triptycene was 0.1 times as reactive per aromatic ring as o-xylene (cf. 0.13 derivable from Table 159) whereas the compound (XXXI) was 0.9 times as reactive as o-xylene. An exactly comparable measure is not available from Table 158, but dihydroanthracene (XXXII), which is similar, was 0.51 times as reactive as o-xylene and... 

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. 

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