Trifluoromethylations trifluoroacetates

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... 

Trifluoromethyl-l-phenylethyl tosylate has been used to differentiate as shown in Table 1, the solvolytic power of three fluorinated solvents and to compare these with formic and acetic acids The three fluorinated solvents are trifluoroacetic acid, trifluoroethanol, and 1,1,1,3,3,3-hexafluoroisopropyl alcohol [55]... 

Trifluoromethylation of diethyl maleate or fumarate is performed via the electrochemical oxidation of sodium trifluoroacetate [742] (equation 123)... 

Table 12 [19, 56.101,102, fOJ],Table 13 [56. 73.104], and Table 14 [56,105, 106] cover six common CF -containing subunits of general interest and utility tnfluoroetbanes, trifluoroacetates, tnfluoroacetamides, tnfluorometbanesuLfon-ates, trifluoromethyl ketones, and trifluorometbyl carbinols. The majority of these data were acquired under uniform conditions (10% solutions in CDCI3 at room temperature [5(5]) to provide for a valid comparison of -NMR values within a narrow range of approximately 10 ppm. Most of these compounds are common,... 

The trifluoromethyl derivative 146 has been obtained as a minor product from the reaction of (l-methyhndol-3-yl)methanol with trifluoroacetic acid anhydride (TFAA), the major product (22% yield) being 6-trifluoromethylindolo[3,2-()]-carbazole [98LTC(B)841]. Several substituted indolo[2,3-()]carbazoles have also been encountered during studies on the reaction of 4,6-dimethoxyindole with... 

Similarly, iV,A/ -dimethyl-3,3 -bisindolylmethane (169) has been used in a related experiment, where treatment thereof with trifluoroacetic fflihydride (TFAA) in diethyl ether at room temperature yielded a mixture of products from which the trifluoromethyl-substituted indolo[3,2-b]carbazole 170 was isolated as the major pentacyclic component, accompanied by the hydroxy derivative 171 as well as small amounts of the indolo[2,3-h]carbazole 146 (Scheme 20). The precursor 169 could also be prepared in situ from A-methylindol-3-methanol under... 

Kolbe radicals can also be trapped by oxygen to yield dialkylperoxides, aldehydes, and ketones [97]. Furthermore methyl and trifluoromethyl radicals from acetic acid and trifluoroacetic acid are trapped, although inefficiently, by pyridine (3-20%) [234], benzotrifluoride and benzonitrile[ 235]. 

In analogy to this reaction, a substituted anilinouracil with CDI in trifluoroacetic acid was shown to yield the 5-deazaflavin with a trifluoromethyl group in the 5-position [151]... 

Attempted syntheses of trifluoromethyl derivatives of germanium, tin, and lead by thermal decarboxylation either resulted in decomposition of the trifluoroacetate without forming carbon dioxide (22,39,40) or gave carbon dioxide but no trifluoromethyl organometallic (22). In the latter case, the metal fluoride was detected. This suggests that the trifluoromethyl compound is thermally unstable and decomposes by fluoride abstraction. 

When colloidal selenium was heated with mercuric trifluoroacetate or silver trifluoroacetate, bis(trifluoromethyl)diselenide was formed (43). Later work with selenium/silver carboxylate, RC02Ag (R = CF3, C2F5, or C3F7), mixtures at 280° C in a vacuum produced a mixture of the bis(perfluoroalkyl)selenide and the bis(perfluoroalkyl)diselenide (44). Formation of a polyselenium trifluoroacetate, which decarboxylates to produce the trifluoromethylselenides, was the proposed mechanism for R = CF3 (44). However, silver trifluoroacetate is a source of trifluoromethyl radicals when heated above 260° C (21), hence the trifluoromethylselenides may be formed by reaction of trifluoromethyl radicals with selenium, as in the reaction of CF3I with selenium [Eq. (34)] (45). 

Mercuric carboxylates, which decarboxylate by a chain mechanism when initiated by peroxides, also decarboxylate under UV irradiation (123,128,129,131-140,142,144-146,153-155). In addition, decarboxylation was observed for mercuric benzoate and mercuric a-naphthoate (123). Side reactions [Eqs. (24), (25), (109)] observed in peroxide initiated reactions also occurred on UV irradiation, and mercurous salt formation [Eq.(24)] was more extensive under the latter conditions. Decarboxylation giving methylmercuric acetate occurred on irradiation of mercuric acetate in aqueous solution and is considered to be of environmental significance (156,157). Stepwise decarboxylation giving (CF3)2Hg occurred on irradiation of solid mercuric trifluoroacetate at -196° C (158), but, at 20° C, trifluoromethyl radicals diffused from the solid and dimerized (158). No other diorganomercurial has been formed by radical decarboxylation, and the reaction is not preparatively competitive with the thermal decarboxylation synthesis of (CF3)2Hg (26,27) (Section III,A). 

Reaction of the thia-amino acid 392 with trifluoroacetic anhydride gave the 2,2,2-trifluoro-l-[7-(trifluoromethyl)-l//-pyrrolo[l,2-c]-[l,3]thiazol-6-yl] ethanone pyrrole 395. The formation of the pyrrole can be rationalized by a sequence involving trifluoroacetylation of the enamine 392 affording dione 393 followed by loss of water and carbon dioxide to give the aromatic product 395. These decarboxylations afford fluorinated derivatives of heterocyclic skeletons known to exhibit interesting biological activity (Scheme 58) <2000T7267>. 

FIGURE 3. The NMR spectra of the two racemic diastereomers of lV-(4-methyl-2-pentyl)-a-methoxy-a-trifluoromethylphenylacetamide prepared from racemic a-methoxy-a-(trifluoromethyl)phenylacetic acid [MTPA, ( )-83] and racemic 4-methyl-2-pentylamine [( )-84] (A) 60-MHz proton spectrum in chloroform-4 with tetramethylsilane (TMS) as the internal standard (B) 94.1-MHz fluorine-19 spectrum in chloroform-4 with trifluoroacetic acid as the internal standard. Reprinted with permission from Reference 76. Copyright (1969) American Chemical Society... 

Another example of type iii-a is the trifluoromethylation of double bonds by electrolysis of trifluoroacetic acid in the presence of olefins. Methyl vinyl ketone, vinyl acetate, diethyl fumarate, diethyl maleate, Ai-ethylmaleimide, and 2,5-dihydrothiophene-l,1-dioxide were examined as olefins. The products were bis-trifluoromethylated additive dimers (66) (type iii-a) and monomers (67) (type... 

Scheme 119 Trifluoromethylation by anodic decarboxylation of trifluoroacetic acid in the presence of double bonds.

The anodic oxidation of trifluoroacetic acid affords the trifluoromethyl radical CFj. Addition of this radical to unsaturated heterocycles can produce bis(trifluoromethylated) compounds (Scheme 119) [225]. 

Under Dakin-West reaction conditions (trifluoroacetic anhydride-MeCN/80 °C/5 h), At-methoxycarbonylproline (128 R = Me) yielded Af-methoxycarbonyl-4-trifluoro-acetyl-2,3-dihydropyrrole (129 R = Me) and none of the expected Dakin-West product, the trifluoromethyl ketone (127). A possible mechanism proposed by the authors involves initial formation of a mesoionic l,3-oxazolium-5-olate (130 R = Me), but the pathway to the iV-methoxycarbonyl-2,3-dihydropyrrole (131 R = Me) and thence the final product (129 R = Me) was unexplained. ... 

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