Trifluoroacetyl removal

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. ... 

The hydrogeh atom bound to the amide nitrogen in 15 is rather acidic and it can be easily removed as a proton in the presence of some competent base. Naturally, such an event would afford a delocalized anion, a nucleophilic species, which could attack the proximal epoxide at position 16 in an intramolecular fashion to give the desired azabicyclo[3.2.1]octanol framework. In the event, when a solution of 15 in benzene is treated with sodium hydride at 100 °C, the processes just outlined do in fact take place and intermediate 14 is obtained after hydrolytic cleavage of the trifluoroacetyl group with potassium hydroxide. The formation of azabi-cyclo[3.2.1]octanol 14 in an overall yield of 43% from enone 16 underscores the efficiency of Overman s route to this heavily functionalized bicycle. 

These reactions involve a diazonium ion (see 12-47) and are much faster than ordinary hydrolysis for benzamide the nitrous acid reaction took place 2.5 x lo times faster than ordinary hydrolysis. Another procedure for difficult cases involves treatment with aqueous sodium peroxide. In still another method, the amide is treated with water and f-BuOK at room temperature. " The strong base removes the proton from 107, thus preventing the reaction marked k j. A kinetic study has been done on the alkaline hydrolyses of A-trifluoroacetyl aniline derivatives. Amide hydrolysis can also be catalyzed by nucleophiles (see p. 427). 

Niki and Kuwatsuka reported a method involving trifluoroacetylation of the amino derivatives of chlornitrofen, nitrofen and chlomethoxyfen. A 1-mL volume of 10 M NaOH solution was added to 50 g of soil and the mixture was extracted with 100 mL of benzene. After separation and drying over anhydrous Na2S04, the benzene solution was trifluoroacetylated by adding successively 1 mL of 0.1% trifluoroacetic anhydride in benzene and 1 mL of 0.1% triethylamine in benzene. The mixture was shaken for 30 s and diluted to 10 mL with benzene. To remove the excess of trifluoroacetic anhydride, about 2 mL of water were added to the mixture and shaken for 30 s. The benzene layer was dried over anhydrous Na2S04 and injected for gas chromatography/flame ionization detection (GC/FID). 

The trifluoroacetyl group, which is extremely labile towards hydrolysis, may be readily removed under mild conditions from carbohydrate mixed-esters. Thus, treatment of an acetone solution of methyl... 

Oxidative dehalogenation. Halogen atoms may be removed from xenobiotics in an oxidative reaction catalyzed by cytochromes P-450. For example, the anesthetic halothane is metabolized to trifluoroacetic acid via several steps, which involves the insertion of an oxygen atom and the loss of chlorine and bromine (Fig. 4.28). This is the major metabolic pathway in man and is believed to be involved in the hepatotoxicity of the drug. Trifluoroacetyl chloride is thought to be the reactive intermediate (see chap. 7). 

The aerobic pathway of metabolism (pathway 1) (Fig. 7.77) produces trifluoroacetyl chloride, a highly reactive acyl chloride, which can react with nucleophiles such as amino groups similar to those on proteins. Alternatively, reaction with water yields trifluoroacetic acid. Trifluoroacetylchloride is the probable reactive metabolite that trifluoroacylates protein, most probably at lysine residues (Fig. 7.77). Removal of the trifluoroacyl moiety from the... 

Acetylation of amino groups is necessary to promote volatility and trifluoroacetyl derivatives (N-TFA) formed from trifluor-oacetic anhydride or acyl derivatives formed from acetic anhydride have both been used with success (Table 9.3). Excess reagent must be removed with care at this point since the derivatives are highly volatile. Gehrke and co-workers have studied a number of stationary phases in detail as summarized in Figure 9.8 (41). They have suggested the use of Apiezon M and a rapid GLC... 

All amino groups can be trifluoroacetylated with ethyl thioltrifluoro-acetate (105). The product has no enzymic activity toward RNA. The modifying groups can be removed with 1 M piperidine at 0°. Interestingly, the resulting protein had little activity, was sensitive to trypsin, and had altered spectral properties. All of these properties were normalized after reduction and reoxidation of the disulfide bonds. 

The dibenzazonine (21), related to a biosynthetic precursor of Erythrina alkaloids, was obtained in 36% yield by intramolecular oxidative coupling of tetramethoxytrifluoroacetamide (20) by thallium(in) trifluoroacetate in tri-fluoroacetic acid at 25 °C.17 The trifluoroacetyl group was readily removed by alkaline hydrolysis, and the H n.m.r. spectrum of the free base confirmed that coupling had taken place para-para (with respect to the 3-methoxy-group of each aromatic ring). 

Large 1-alkyl substituents increase -substitution in the Vilsmeier formylation of pyrroles. A similar trend occurs in trifluoroacetylation of N-alkyl pyrroles. The trifluoroacetylation, formylation, and bromination of 1-tritylpyrrole occur regioselectively at the 3-position in high yield. The same effect is seen in 1-triisopropylsilylpyrrole and the ease of removal of the fV-silyl substituent makes the use of such substitutions for the synthesis of 3-substituted N-unsubsti-... 

Removal of the endo methylene bridge of Troger s bases could be achieved with or without concomitant methylation of the nitrogen(s). Thus, trifluoroacetylation of 215b with trifluoroacetic anhydride did not give the expected bis(tri-fluoroacetamide) 217 (R1 = R2 = CF3CO) but rather the trifluoroacetamide trifluoroacetate salt 216 in 79% yield. 

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