Tnfluoromethyl compounds

Table 15 [S 19 56, 59 93 107 108 109, 110, 111, 112 113, 114] contams NMR data for a vanety of tnfluoromethyl compounds that do not fit into the more common categones already covered Most carbon-attached tnfluoromethyl (CF3-C) F-NMR signals fall in the 25 ppm range from -60 to -85 ppm, a notable exception being trifluoromethylacetylenes, with signals at approximately -50 ppm Trifluoromethylated compounds in which the CFj is directly bonded to an atom orlier carton are considered in Table 16 [57 59,95 109,115,116 117 118,119,120 121 122, 123 124, 125] These heteroatom contaming compounds are of interest to both organic and morganic chemists and have been studied by NMR for numerous reasons...

Basic data coverage in this section commences with fluonnated methanes, ethanes, ethylenes, acrylates, aliphatic monofluondes (pnmary, secondary, and tertiary), and geminal difluondes (pnmary and secondary) The compilation continues with six categones of tnfluoromethylated compounds and finishes with aromatic fluondes 19F-NMR applications extend greatly beyond simple structure determination Six of these special topics are bnefly surveyed, including analytical NMR methods and biochemical NMR studies... 

Electron releasing substituents attached to the ring have a negligible effect on the acidity of phenols Strongly electron withdrawing groups increase the acidity The compound 4 nitro 3 (tnfluoromethyl)phenol for example is 10 000 times more acidic than phenol... 

The conversion of cyclic sulfides to sulfones is accompbshed by more energetic oxidations. Perhalogenated thiolanes [106] and 1,3-dithietanes [107] are oxidized to sulfones and disulfones, respectively, by a mixture of chromium trioxide and nitric acid (equation 98) The same reagent converts 2,4-dichloro-2,4-bis(tnfluoromethyl)-l,3-dif/u cto cs to disulfone derivatives [107], whereas trifluoromethaneperoxysulfonic acid converts the starting compound to a sul-fone-sulfoxide derivative [2(equation 99). 

The presence of a tnalkylsUyl group in a fluonnated organic compound may be useful to direct further transformations of that matenal Yet m some instances it IS the fluonnated substituent that controls the reactions of the tnalkylsdyl group Contrary to predictions, treatment of tert-hnlyX 3-tnfluoromethyl-6-tnmethylsilyl-phenyl carbamate with rert-butyllithium results m metallation of one of the methyl groups attached to silicon rather than that of the aromatic nng [90] (equation 75)... 

A bnef paper by Kobayashi indicated some of the potential of this cycli7ation for making fluonne compounds [56] (equation 57) Watanabe et al provided examples of incorporation of a tnfluoromethyl group into a five-membered ring [57] (equation 58) Nevertheless, the full potential of this methodology m preparing fluorine-containing materials has not been realized... 

Hexafluoroacetone azine accepts nucleophiles (ROH, RSH, R NH) in positions 1 and 2 to yield hydrazones [27] Phosphites give open-chain products via a skeletal rearrangement [22] Radical addition reactions are also reported [22] Treatment of tnfluoropyruvates with tosylhydrazine and phosphorus oxychlo-ride-pyndme yields tnfluoromethyl-substituted diazo compounds [24] (equation 3)... 

The reaction of tnfluoromethyl-substituted A -acyl umnes toward nucleophiles in many aspects parallels that of the parent polyfluoro ketones Heteronucleophiles and carbon nucleophiles, such as enarmnes [37, 38], enol ethers [38, 39, 40], hydrogen cyanide [34], tnmethylsilylcarbomlnle [2,47], alkynes [42], electron-nch heterocycles [43], 1,3-dicarbonyl compounds [44], organolithium compounds [45, 46, 47, 48], and Gngnard compounds [49,50], readily undergo hydroxyalkylation with hexafluoroace-tone and amidoalkylation with acyl imines denved from hexafluoroacetone... 

Three skeleton atoms of a hetero-l,3-diene are incorporated into a five-membered ring system on reaction with 1,2 [n,n] compounds (e.g., hydrazines, reaction type 4, equation 10). On further heating in the presence of azobisiso-butyronitrile (AIBN), the bis(trifluoromethyl)-substituted 1,2,4-triazolines are transformed into 5-tnfluoromethyl-l,2,4-triazoles in high yield [t02 (equation 22). 

Of all known [4+1] cycloadducts, the ttn heterocycles exhtbit the most interesting preparative potential [I33 On heating they are transformed into 5-fluoro-4-tnfluoromethyl-l,3 azoles [132, 133] The fluorine atom at C-5 can be replaced by various nucleophiles By this route, the 4-trifluoromethyl-l 3-azole moiety can be introduced into many compounds of biological interest (equation 31)... 

Trifluoromethyl-substitutedazimines are surprisingly stable compounds. They are accessible by 1,3-dipole metathesis from tnfluoromethyl-substituted azomethine imines and certain nitroso compounds [187, 188] On photolysis, an electrocyclic ring closure first gives the triaziridines, which are stable at room temperature. On heating above 80-100 C, a valence tautomenzation takes place and azimines are formed [189] (equation 43). 

An adjacent tnfluoromethyl group sharply increases the electrophilic character of the carbonyl carbon Compounds that readily form hydrates and hemiacetals show a time-dependent reversible mhibition of the en yme acetylcholinesterase (equation 2), in which the tight complex makes inhibition only partially reversible [75] In comparison with a nonfluormated analogue, several aliphatic ketones flanked by CFj and CF2 groups, are exceptionally potent reversible inhibitors of acetylcholinesterase, as documented by companson of inhibition constants shown in equation 3 [16 ... 

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. 

FLUORINECOMPOUNDS,ORGANIC - FLUORINATED AROMATIC COMPOUNDS] (Volll) Bis(tnfluoromethyl)fluorobismuthine[124252-79-5]... 

Ene Reaction of Tnfluoromethyl Carbonyl Compounds (Jap) Nagai, T, Kumadaki, 1 Yuki Gosei Kagaku Kyokaishi 49, 624-635 50... 

Fluoroalkylamines react with nitrous acid to produce the corresponding unstable fluoroahphatic diazomum ions Placement of the tnfluoromethyl group at a carbon position a, (i, or y to a diazomum ion was used to probe the inductive effect on the chemistry of the transient carbocation resulting from dediazomation [7] If the fluoroalkyl group is bound to the same carbon as the amino group, conversion to the more stable diazo compound occurs For example, 4-diazo-l,l,l,2,2-pentafluoro-3-pentafluoroethyl-3-tnfluoromethylbutane is obtained from the reaction of the poly-fluoroalkylamine salt with sodium nitrite [8, 9] (equation 8)... 

Lithium silylamides react smoothly with trifluoromtrosomethane to give diazenes Traces ot water initiate the decomposition of the latter with liberation of a trifluoromethy] carbamon, which is trapped by carbonyl compounds [755] (equation 116) Desilylation of tnalkyl(tnfluoromethyl)silanes by fluoride ion produces also a trifluoromethyl carbamon, which adds to carbonyl carbon atoms [136, 137] (equations 117 and 118)... 

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