A-trifluoromethylation

Because substitution m (trifluoromethyl)benzene occurs primarily at positions meta to the substituent we say that a trifluoromethyl group is a meta director... 

Turning now to electrophilic aromatic substitution in (trifluoromethyl)benzene we con sider the electronic properties of a trifluoromethyl group Because of their high elec tronegativity the three fluorine atoms polarize the electron distribution m their ct bonds to carbon so that carbon bears a partial positive charge... 

Unlike a methyl group which is slightly electron releasing a trifluoromethyl group is a powerful electron withdrawing substituent Consequently a CF3 group destabilizes a car bocation site to which it is attached... 

Our analysis of substituent effects has so far centered on two groups methyl and triflu oromethyl We have seen that a methyl substituent is activating and ortho para directing A trifluoromethyl group is strongly deactivating and meta directing What about other substituents ... 

Because the carbon atom attached to the ring is positively polarized a carbonyl group behaves m much the same way as a trifluoromethyl group and destabilizes all the cyclo hexadienyl cation intermediates m electrophilic aromatic substitution reactions Attack at any nng position m benzaldehyde is slower than attack m benzene The intermediates for ortho and para substitution are particularly unstable because each has a resonance structure m which there is a positive charge on the carbon that bears the electron withdrawing substituent The intermediate for meta substitution avoids this unfavorable juxtaposition of positive charges is not as unstable and gives rise to most of the product... 

Nucleophilic Displacement Reactions. The strong electron-withdrawing effect of a trifluoromethyl group activates ortho and para halogen toward nucleophilic attack. Such chlorine labiUty is utili2ed in the manufacture of crop control chemicals containing trifluoromethyl and nitro groups. 

Herbicides can be grouped according to common stmctural features. Sometimes the assignment is arbitrary when there are a multitude of functional groups, eg, acifluorfen which is a diphenyl ether (phenoxy compound) as well as a trifluoromethyl compound. 

Triethylbenzylammonium chloride and potassium fluoride containing 1% water can provide chlorine-fluorine exchange of activated halides in the absence of a solvent. This mixture also can displace the chlorine of a chlorodifluoromethyl group to form a trifluoromethyl group [62] (equation 36). 

Carboxylic acids react both with fluoroaminosulfiiranes such as DAST and with sulfur tetrafluonde. Whereas DAST converts the acids to acyl fluorides only, sulfur tetrafluonde further fluorinates the primarily formed acyl fluorides and ultimately converts the carboxyl group to a trifluoromethyl group. 

The reaction ot tormamides with sulfur tetrafluoride in the presence of potassium fluoride leads to replacement of both carbonyl oxygen and hydrogen with fluorine. The formyl group is directly converted into the trifluoromethyl group A-(trifluoromethyl)amines are formed in near quantitative yields [233] (equation 121)... 

Besides sulfur tetrafluonde, only a very few reagents can convert a carboxylic group into a trifluoromethyl group... 

Lithium silylamides react smoothly with tiifluoronitrosomethane to give diazenes Traces ot water initiate the decomposition of the latter with liberation of a trifluoromethyl carbanion, which is trapped by carbonyl compounds [775] (equation 116) Desilylation of trialkyl(trifluoromethyl)silanes by fluoride ion produces also a trifluoromethyl carbanion, which adds to carbonyl carbon atoms [136, 137] (equations 117 and 118)... 

UV irradiation of steroidal dienones in the presence of Irifluoromethyl iodide allows the selective introduction of a trifluoromethyl group ct to the carbonyl function [140] (equation 121)... 

The photochemical introduction of a trifluoromethyl group into aromatic and heteroaromatic rings, such as uracil, can be performed also with trifluoromethyl bromide [/5/] (equation 131)... 

In similar work, CF3CCI2CO2CH3 yields methyl a-trifluoromethyl-a,(i-un-saturated carboxylates when reacted with a zinc-copper couple, aldehydes, and acetic anhydride [67] (equation 55). This methodology gives (Z)-a-fluoro-a- -un-saturated carboxylates from the reaction of carbonyl compounds with CFCI2CO2CH3 and zinc and acetic anhydride [6 ]. 

Similarly, 1-alkylpyrroles, indoles, furans, thiophenes [60], a-picoline [61], enols, malonates [76], and organometallic compounds [56, 62] react with acyl imines of trifluoropyruvates to give derivatives of a-trifluoromethyl a-amino acids... 

Four-membered heterocycles are easily formed via [2-I-2] cycloaddition reac tions [65] These cycloaddmon reactions normally represent multistep processes with dipolar or biradical intermediates The fact that heterocumulenes, like isocyanates, react with electron-deficient C=X systems is well-known [116] Via this route, (1 lactones are formed on addition of ketene derivatives to hexafluoroacetone [117, 118] The presence of a trifluoromethyl group adjacent to the C=N bond in quinoxalines, 1,4-benzoxazin-2-ones, l,2,4-triazm-5-ones, and l,2,4-tnazin-3,5-diones accelerates [2-I-2] photocycloaddition processes with ketenes and allenes [106] to yield the corresponding azetidine derivatives Starting from olefins, fluonnaied oxetanes are formed thermally and photochemically [119, 120] The reaction of 5//-l,2-azaphospholes with fluonnated ketones leads to [2-i-2j cycloadducts [121] (equation 27)... 

An unusual 1,4-migration of a trifluoromethyl group was observed when azomethine imines were synthesized from hexafluoroacetone azine and alkoxy-acetylenes The rearrangement, which occurs at temperatures as low as 0 "C, results in the formation of A-(perfluoro-ferf-butyl)pyrazoles [207] (equation 46)... 

Display and compare electrostatic potential maps for methanol, ethanol, 2-propanol and trifluoroethanol. Identify the acidic sites as those where the potential is most positive and, assuming that the more positive the potential the more acidic the site, rank the acidities of the compounds. Does increased alkyl substitution have a significant effect on acid strength What is the effect of replacing the methyl group in ethanol by a trifluoromethyl group Why Do you find a correlation between the most positive value of the potential and the experimental pKa ... 

Secondary aziridines bearing a trifluoromethyl group were prepared via the Hoch-Campbell reaction of Grignard reagents and oximes bearing a trifluoromethyl... 

A trifluoromethyl moiety is a strong electron-withdrawing group which dominates the direction of indolization in the Nenitzescu process. ... 

Chen, F.-Q., et al. (1994). Synthesis and preliminary chemi- and bioluminescence studies of a novel photolabile coelenterazine analogue with a trifluoromethyl diazirine group. Chem. Commun. 2405-2406. 

The enantiomeric excesses of the cyanohydrins obtained are determined via the diastereomcric Mosher esters with (/ )-a-methoxy-a-(trifluoromethyl)phenylacetyl chloride16 by GC. 

The enantiomeric excess values of the (S)-cyanohydrins are obtained from the ( + )-(R)-Mosher ester derivatives [a-methoxy-a-(trifluoromethyl)phenylacetates], whereas the corresponding benzeneacetic acids are first converted into their isopropyl carboxylates which then yield the ( + )-(ft)-Mosher ester derivatives. 

When the reaction between a-trifluoromethyl sulfone 286 and paraformaldehyde was carried out in the presence of potassium carbonate, the vinyl sulfone was obtained quantitatively upon elimination of triflate anion368. Such a deacylative methylenation was observed in the reaction between /J-ketosulfones 287 and 288 and paraformaldehyde3 69 3 71. 

Studies upon o-Tnfluoromethyl aery lie Acid, a-Trifluoromethyl-propionic Acid, and some Derived Compounds, M. W. Buxton, M. Stacey, and J. C. Tatlow, J. Chem. Soc., (1954) 366 -374. 

When strong electron-withdrawing substituents were introduced at the a-or )S-carbon of the vinyl group, the styrenes acted as dienophiles. Thus cycloaddition of a-trifluoromethyl styrene (58) with Danishefsky s diene 59 afforded regioselectively a 1 1 mixture of cycloadducts which were then converted (Equation 2.20) into 4-phenyl-4-trifluoromethyl-2-cyclohexen-l-one [54]. 

However, when an electron-withdrawing group, e.g., a trifluoromethyl group, is attached to the anilines this procedure is not applicable. A way to circumvent this problem was enlightened by Glasnov et al. [53] who treated the malondianilide 14 with Eaton s reagent, a 7.7% solution of phosphorus pen-toxide in methanesulfonic acid (a. Scheme 6) [54]. This reaction is, however, sensitive to time, temperature, and concentration. More reactive malondian-... 

Ci4H,jC1F,N02 177530-93-7) see Efavirenz (c[5)-5-chIoro-a-(cyclopropylethynyl)-2-[[(4-methoxyphe-nyI)methyl]amino]-a-(trifluoromethyl)benzenemethanol C21HJ9CIF3NO2 173676-60-3) see Efavirenz... 

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