Trifluoromethyl bromide, reaction

Another way to prepare fluorinated sulfides is the photochemical alkylation of sulfides or disulfides by perfluoroalkyl iodides [69, 70, 71] (equations 62-64). Reaction of trifluoromethyl bromide with alkyl or aryl disulfides in the presence of a sulfur dioxide radical anion precursor, such as sodium hydroxymethanesulfi-nate, affords trifluoromethyl sulfides [72] (equation 65). 

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. 

Tnfluoromethanesulfinate can be prepared from the reaction of trifluoromethyl bromide with sulfur dioxide and zinc [50] (equation 41) Similar insertion occurs when perfluoroalkyl iodides are used as precursors (equations 41 and 42)... 

There is another substitution reaction, not involving transition-metal complexes, namely, reaction of trifluoromethyl bromide with sulphur dioxide anion radicals (165) (Andrieux et al., 1990a) (this is an interesting route... 

Barbier conditions have been utilized by Wakselman et al. to carry out reactions of trifluoromethyl bromide with aldehydes, a-keto esters, activated esters and anhydrides in the presence of pyridine to give trifluoromethylated compounds [51,52] (Scheme 18). 

The production of industrially important perfluoroalkane sulfonic acids is generally accomplished by electrochemical fluorination. This method of preparation remains expensive and proceeds in good yields only for short hydrocarbon chains.30 Recently however, Wakselman and Tordeux have described a chemical method for the preparation of trifluoromethane sulfonic acid.31 The procedure involves reaction of a metal selected from zinc, cadmium, manganese, and aluminum with sulfur dioxide in DMF, followed by the introduction of trifluoromethyl bromide under slight pressure. The intermediate sulfinate is subsequently oxidized by hydrogen peroxide, and then hydrolyzed which leads to formation of the trifluoromethane sulfonic acid. Successful extension of the sulfination process to the modification of PCTFE should result in the formation of a sulfinated polymer which can ultimately be oxidized to give a sulfonic-acid modified polymer. 

Thiolates are powerful nucleophilic reagents. However, we observed no reaction when trifluoromethyl bromide is bubbled through a potassium thiophenoxide solution in DMF at room temperature. This failure was in agreement with the inertness reputation of this halide. Assuming that a mechanism involving radical anions (Fig. 4, X = Br) could occur, a minimal concentration of the halide should be necessary to maintain the chain process. In order to increase the amount of trifluoromethyl bromide in solution, we performed the reaction under pressure. Indeed, condensation occurred at room temperature in a glass apparatus under 2-3 bars (Fig. 5) (refs. 16,17). Inhibition of this condensation by nitrobenzene was clearly observed, in agreement with the SET process (Fig 4, X = Br). A similar trifluoromethylation of thiols by trifluoromethyl bromide in liquid ammonia under UV irradiation has also been described (ref. 18). 

In contrast to the carbonyl condensations, where no reaction occurred between the substrate and the metal, an initial attack on zinc by sulfur dioxide in DMF was actually observed. Then, introduction of trifluoromethyl bromide under slight pressure led to the formation of zinc triflinate. 

This condensation with sulfur dioxide is rather peculiar. To the difference with carbonyl electrophiles, sulfur dioxide is more easily reduced than trifluoromethyl bromide. As already pointed out, initial consumption of zinc by this anhydride was obvious, producing the sulfoxylate radical anion which is known to be in equilibrium with the dithionite anion (Fig. 15). Incidentally, this salt mixed with sodium bicarbonate in aqueous acetonitrile was used for the transformation of liquid perhalogenoalkyl halides into their corresponding sulfmates (ref. 24). We have been able to transform the gaseous and poorly reactive trifluoromethyl bromide into sodium trifluoromethanesulfinate. However, the reaction conditions (Fig. 16) (ref. 25) were modified because no transformation occurred in the medium employed for the sulfinato-dehalogenation of the liquid halides. 

Preparative Methods is prepared based on the original procedure of Ruppert, by the reaction of chlorotrimethylsUane with the complex of trifluoromethyl bromide and hexaethylphospho-rous triamide in benzonitrile (eq 1). Other less convenient procedures for its preparation are also reported. ... 

These reactions are more complicated than many authors give credit, since even if the iodine atom is electronically excited ( Pi), the trifluoromethyl radical must be thermally excited. The excess energy in the photolysis of trifluoromethyl iodide at 250 nm is about 37 kcal mol" while the excess energy in the photolysis of trifluoromethyl bromide at 185 nm is 85 kcal mol. Pass and Willard have shown that in the former reaction most of the excess energy appears as translation, whereas in the latter process most appears as vibration, so that "hot" trifluoromethyl radicals formed in the photolysis of trifluoromethyl iodide are less selective than the "hot" radicals formed in the photolysis of the bromide ( ). 

The Tcrom ester is prepared from the cesium salt of an N-protected amino acid by reaction with 2-(trifluoromethyl)-6-chromylmethyl bromide (DMF, 25°, 4 h, 53-89% yield). Cleavage of the Tcrom group is effected by brief treatment with n-propylamine (2 min, 25°, 96% yield). It is stable to HCl/dioxane, used to cleave a BOC group. ... 

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]... 

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). 

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. 

The indium-mediated allylation of trifluoroacetaldehyde hydrate (R = H) or trifluoroacetaldehyde ethyl hemiacetal (R = Et) with an allyl bromide in water yielded a-trifluoromethylated alcohols (Eq. 8.56).135 Lanthanide triflate-promoted indium-mediated allylation of aminoaldehyde in aqueous media generated (i-airiinoalcohols stereoselectively.136 Indium-mediated intramolecular carbocyclization in aqueous media generated fused a-methylene-y-butyrolactones (Eq. 8.57).137 Forsythe and co-workers applied the indium-mediated allylation in the synthesis of an advanced intermediate for azaspiracids (Eq. 8.58).138 Other potentially reactive functionalities such as azide, enone, and ketone did not compete with aldehyde for the reaction with the in situ-generated organo-indium intermediate. 

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