Trifluoromethyl halides

The first long-lived fluorine-containing carbocation was discovered by Olah and coworkers.32 Thus, the fluorodimethylcarbcnium ion [Me2CF+] was obtained by protonation of 2-fluoropropene and also from 2,2-difluoropropane by reaction with antimony(V) fluoride. In the course of these investigations it was found that a-F stabilizes a cationic state, whereas fi-F is destabilizing. Attempts to prepare the simplest member of this class, the trifluoromethyl carbocation CF3+ failed. The ionization of trifluoromethyl halides with antimony(V) fluoride at — 80 C yielded only carbon tetrafluoride. 

The reaction of tris(trifluoromethyl)bismuthine with chlorine, bromine, or iodine, however, has been found to yield the corresponding bismuth trihalide and trifluoromethyl halide (61) ... 

Because of the high volatility of the trifluoromethyl halides and their inertness in the thermal Michaelis-Arbuzov reaction,2 the synthesis of diethyl trifluoromethylphosphonate under pho-tolytic conditions has been investigated. The modest yield initially obtained (51%) can be improved using vacuum Une techniques, and the desired trifluoromethylphosphonate is isolated in almost quantitative yield (Scheme 3.45). ... 

Trifluoromethyl halides CF3X (X = I, Br) are known to be resistant to nucleophilic attack on the carbon atom (refs. 6, 7). This behaviour is explained by the unusual polarisation of the C - X bond (Fig. 2) and also by steric effects and lone-pair repulsion forces associated with fluorine substituents. 

Trifluoromethyl alcohols have been synthesized in pyridine via Zn-Barbier reactions of carbonyl compounds with trifluoromethyl halides under a slight pressure [78, 79]. Some results are listed in Table 3.15... 

The halogen bond can be considered as analogous to the hydrogen bond and a very helpful conceptualization is due to the work of Murray, Politzer, and coworkers who suggested the now widely adopted idea of the a-hole. Thus, they considered the series of trifluoromethyl halides... 

We have analyzed NCI in a series of trifluoromethyl halides, CF3X, where X = Cl, Br, I with dimethyl ether (DME), dimethyl sulfide (DMS), trimethyl phosphine (TMP) and imidazolin-2-ylidene (NHC). All systems were optimized using second-order Moller-Plesset perturbation theory with the aug-cc-pVDZ(-PP) basis set [81]. The wavefunctions were obtained at DFT level using the B3LYP functional and the 6-31++G basis set except for iodine, where the pseudopotential LANL2DZ was used. 

Bogdanov B, McMahon TB (2006) Gas phase Sn2 reactions of halide ions with trifluoromethyl halides front- and back-side attack vs complex formation. J Phys Chem A 110 1350... 

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). 

Alkyl fluorides are more reactive than other alkyl halides under Friedel-Crafts conditions, whereas trifluoromethyl groups are less reactive than other trihalomethyl groups Thus, a bromoindane is prepared from 1-bromo-l-fluoro-2,2,3,3-tetramethylcyclopropane and benzene [5] (equation 8) whereas 3-tnfluo romethylphenyldiphenylchloromethane is obtained from 3-trifluoromethyl-benzotrichloride and benzene [9] (equation 9)... 

Fluorinated sulflnates are prepared from sodium dithionite and liquid per-fluoroalkyl halides [74] (equation 67). For the transformation of the gaseous and poorly reactive trifluoromethyl bromide, it is necessary to use moderate pressure [75] (equation 68) These reactions are interpreted by a SET between the intermediate sulfur dioxide radical anion and the halide The sodium trifluorometh-anesulfinate thus obtained is an intermediate for a chemical synthesis of triflic acid. 

Ullman type coupling occurs between aryl halides and trifluoromethyl copper species generated by the action of copper iodide on sodium tnfluoroacetate [168, 169] or on methyl fluorosulfonyldifluoroacetate [170] (equation 145) Similarly the pentafluoroethyl group can be introduced from potassium pentafluoropropion-ate [171] (equation 146)... 

Dialkylcadmium reagents are often useful alternatives to the more reactive Gngnard reagents in the preparation of ketones from acyl halides However, bis(trifluotomethyl)cadmium glyme is decomposed by acyl halides and does not give trifluoromethyl ketones [, 124] Nevertheless, this reaction can be used as a low-temperature source of difluorocarbene [S, 124] (equation 102)... 

The reaction of trifluoromethyl radicals, generated in a radio-frequency discharge process, with elemental mercury f/7i], mercury halides [174], dime-thylmercuiy [24], or HgO [175] has been used for the preparation of CFjHgX and (CF3)2Hg. Direct fluorination of dimethylmercury with elemental fluorine gives (CF3)2Hg [176],... 

Cheaper sources of tnfluoromelhyl groups have been the goal of several groups The use of sodium tnfluoroacetate and copper (1) iodide in dipolar aprotic solvents gave regiospecific trifluoromethylation of aromatic halides [202] (equation 136)... 

Aryl bromides were also perfluoroethylated under these conditions [205] The key to improved yields was the azeotropic removal of water from the sodium perfluoroalkylcarboxylate [205] Partial success was achieved with sodium hepta-fluorobutyrate [204] Related work with halonaphthalene and anthracenes has been reported [206 207] The main limitation of this sodium perfluoroalkylcarboxylate methodology is the need for 2 to 4 equivalents of the salt to achieve reasonable yields A trifluoromethylcopper solution can be prepared by the reaction of bis(tri-fluoromethyl)mercury with copper powder in /V-methylpyrrolidone (NMP) at 140 °C [208] (equation 138) or by the reaction of N-trifluoromethyl-A-nitro-sotnfluoromethane sulfonamide with activated copper in dipolar aprotic solvents [209] This trifluoromethylcopper solution can be used to trifluoromethylate aro matic [209], benzylic [209], and heterocyclic halides [209]... 

Tnfluorometltylation of aryl, alkenyl, and alkyl halides can be accomplished by heating methyl fluorosulfonyldifluoroacetate and the appropriate halide precursor with copper(I) iodide at 60-80 °C in DMF [27 7] (equation 145). Similar trifluoromethylations of aryl, benzyl, and vinyl halides can be carried out with fluorosulfonyldifluoromethyl iodide and copper metal in DMF at 60-80 °C [2 75] (equation 146). 

Codeposition of silver vapor with perfluoroalkyl iodides at -196 °C provides an alternative route to nonsolvated primary perfluoroalkylsilvers [272] Phosphine complexes of trifluaromethylsilver are formed from the reaction of trimethyl-phosphme, silver acetate, and bis(trifluoromethyl)cadmium glyme [755] The per-fluoroalkylsilver compounds react with halogens [270], carbon dioxide [274], allyl halides [270, 274], mineral acids and water [275], and nitrosyl chloride [276] to give the expected products Oxidation with dioxygen gives ketones [270] or acyl halides [270] Sulfur reacts via insertion of sulfur into the carbon-silver bond [270] (equation 188)... 

Alkylzinc halides have also been prepared under microwave irradiation. The Reformatsky reagents (2-t-butoxy-2-oxoethyl)zinc bromide and [(2-dibenzylamino)-2-oxoethyl]zinc bromide were synthesized from the corresponding bromides via reaction with zinc in THF (Scheme 5) [24], The oxidative addition was executed at 100 °C in 5 min. The obtained reagents were subsequently used in Negishi reactions on 2-bromopyridine, 3-bromopyridine, 2-bromo-5-nitropyridine, and 2-bromo-5-trifluoromethyl-pyridine using Pd(PPh3)4 as a catalyst (Scheme 5). 

G. Reactions of Trifluoromethyl Radicals with Organic Halides. 189... 

The reactions of mercuric iodide, mercuric bromide, and mercuric chloride with the excited species produced in the hexafluoroethane plasma were examined first, as the expected products were known to be stable and had been well characterized 13). Thus, these reactions constituted a "calibration of the system. Bis(trifluoromethyl)mercury was obtained from the reaction of all of the mercuric halides, but the highest yield (95%, based on the amount of metal halide consumed) was obtained with mercuric iodide. The mole ratios of bis(trifluoro-methyDmercury to (trifluoromethyl)mercuric halides formed by the respective halides is presented in Table I, along with the weight in grams of the trifluoromethyl mercurials recovered from a typical, five-hour run. 

Although belonging to a slightly different class of reactions, the reaction of trifluoromethyl radicals with sulfur vapor has been shown to provide a route to trifluoromethyl polysulfide compounds (20). Instead of using sulfur halides, which undoubtedly would also give positive results, elemental sulfur (Ss) was vaporized and dissociated into atomic and polyatomic sulfur species. 

The preparative reactions were conducted in sealed tubes in which — 1-3 g of the reagents had been placed. After the vessels had been maintained at the indicated temperatures for the designated times, the contents were removed, to be separated by fractional condensation and GLC. In addition to the (trifluoromethyl)Group 4A halides reported next, each sample contained unreacted (CFalaHg, the expected (tri-fluoromethyDmercuric halide, and the mercuric halide, identified by fluorine-NMR spectroscopy and mass spectrometry. 

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