Reactions trifluoromethoxy

An example of cleavage ol the sulfur-oxygen bond in trifluoromethane-sulfonic ester has been reported Tnfluororaethyl triflate reacts with neutral or anionic nucleophiles with elimination of carbonyl difluoride and formation of trifluoromethanesulfonyl fluoride [57] (equation 32) The mechanism of this reaction involves elimination of fluoride ion, which is a chain carrier in the substitution of fluorine for the trifluoromethoxy group... 

Benzene (32, R = H) reacts under photochemical conditions with trifluoromethyl hypofluorite giving fluorobenzene as the main product together with (trifluoromethoxy)benzene,15 while the reaction with toluene (32, R = Me) also gives sidc-chain-substituted products.2,3,15... 

In the low-temperature fluorination of benzofuran (39, Y = O) and 1-acetylindole (39. Y = NAc), addition reactions are observed as well as vicinal fluoro trifluoromethoxy adducts 40A and 40B, vicinal difluoridcs 41 are formed.63 Trichloromethiazide is converted into the 5-fluoro derivative 42 in tetrahydrofuran/hydrogen fluoride at 0 C (in dichloromethanc/acetone 42 is accompanied by two nonfluorinated products).64... 

In the reaction with bis(trifluoromethyl) trioxide (10), addition of both CF30 and CF300 groups to the sulfur tetrafluoride molecule occurs to give a mixture of . v-(trifluoromethoxy)(tri-fluoromethylperoxy)sulfur tetrafluoride, s-bis(trifluoromethoxy)sulfur tetrafluoride (11) and (trifluoromethoxy)sulfur pentafluoride.215... 

The photolytic reaction of trifluoromethyl hypochlorite gives s-bis(trifluoromethoxy)sulfur tetrafluoride (11) in very high yield.216... 

In fluorinated agrochemicals, the difluoromethoxy group is less commonly encountered than the trifluoromethoxy group. The difluoromethoxy group is readily available from the reaction of a phenoxy group and difluorocarbene, generated from chlorodifluoromethane and a base (Fig. 27) [6,107-109]. 

The reaction of diazo compounds with an electrophilic fluorinating reagent, tri-fluoromethyl hypofluorite. has also been studied (Tabic 8, entries 9 13). ° The reactions are carried out at — 70 C using trichlorofluoromethane as solvent and mixtures of g /n-difluoro compounds and fluoro(trifluoromethoxy) derivatives are obtained. Although conversion is generally complete, the yields of isolated products are low, due to their difficult separation. In some cases (entries 9, 11, and 12), ketones and epoxides arc formed as byproducts. Consequently, this method is not a useful alternative for the preparation ofgcw-difluoro compounds. 

The same mechanism has been proposed for the reaction of diazo compounds with either fluorine or trifluoromethyl hypofluorite (Scheme 3). Thus, nucleophilic attack of the polarized diazo compound at the fluorine atom of fluorine or trifluoromethyl hypofluorite, followed by reaction of the intermediate with X (F or CF3O ) yields the g w-diIluoro compound or the fluoro(trifluoromethoxy) derivative. 

The strong electronegative trifluoromethyl group in trifluoromethyl hypofluorite stabilizes the hypofluorite function and activates the O —F bond for electrophilic reaction. Thus, trifluoromethyl hypofluorite undergoes addition to oletinic centers the trifluoromethoxy group often can be hydrolyzed to leave a monofluorinated product. 

The addition of trifluoromethyl hypofluoritc to diphenylacetylene has been noted but the major reaction product l,l,2-trifluoro-l,2-dipheiiyl-2-(trifluoromethoxy)ethane, can arise either from the addition of trifluoromethyl hypofluoritc to the acetylene followed by the addition of fluorine to the ethene, or from the addition of fluorine to the diphenylacetylene followed by the addition of trifluoromethyl hypofluorite to the difluorodiphenylethene. 

Trifluoromethyl hypofluorite, CF3OF, the first organic hypofluorite, reacts as if the O-F bond is homolyzed to the trifluoromethoxy radical and a fluorine radical in many reactions, but it has been used effectively as a selective electrophilic fluorination reagent in organic chemistry. It has limited selectivity as a fluorination reagent in inorganic chemistry bnt it can be oxidatively added to numerous compounds. 

The base-catalyzed reaction of benzyl cyanides with p-chloronitro-benzenes is widely used as a preparative route to 3-arylanthranils (Eq. 8), and hence, by reductive ring opening, o-aminobenzophenones, the valuable precursors of the pharmacologically important benzodiazepinones. By this method 3-phenylanthranils bearing trifluoromethoxy,173 (trifluoromethyl)-thio,173 sulfonamido,174 methoxy- and ethoxycarbonyl,175,176 cyano,175 methylsulfonyl,175 halo,176 difluoromethoxy,177 and acetyl (protected as the... 

Maes and co-workers have synthesized 5//-pyridazino[4,5-6]indole skeleton 39 through an intramolecular Heck reaction. Intermediate 38, 5-(2-bromo-4-(trifluoromethoxy)phenylamino)-2-benzyl-l,2-dihydropyridazin-3-(6//)-one was prepared via chemoselective Pd-catalyzed amination of 2-benzyl-5-iodopyridazin-3(2//)-one 36 and 2-bromo-4-(trifluoromethoxy)-benzenamine 37 in 66% yield and followed by an intra molecular cyclozition to yield the desired target compound 39 by a microwave iradiations. ... 

Maligres and co-workers noted that the enamine 50 was formed by TFA catalyzed reaction of 2-iodo-5-(trifluoromethoxy)aniline with 49. The intramolecular Heck reaction of 50 was successfully performed with DABCO or NaHCOa in the presence of Pd(OAc)2 or Pd on charcoal in DMF at 90 °C to provide the benzoyl indole 51 directly, in 70-74% yields, after crystallization from heptane/EtOAc. ... 

Several reagents were used for the electrophilic fluorination of indole. The first one used for this aim was trifluoromethyl hypofluorite (CF3OF). Treatment of V-acylindole 1 with trifluoromethyl hypofluorite in CF3CI at -78 °C afforded a mixture of 2-fluoro-3-trifluoromethoxy- and 2,3-difluoroindoline derivatives 2-4 in high combined yield. Subsequent treatment of difluoride 4 with potassium hydroxide in methanol afforded quantitatively 3-fluoroindole 5. Similarly, starting from l-formyl-2-methylindole reaction with trifluoromethyl hypofluorite resulted in formation of 2-methyl-3-fluoroindole 7 in low yield in mixture with 2-methyl-3-trifluormethoxyindole 8 [7]. 

Other addition/elimination sequence was utilized for monofluorination of benzofuran and its derivatives. Thus, the reaction of benzofuran 11 with trifluoromethyl hypofluorite (CF3OF) furnished 2-fluoro-3-trifluoromethoxy-2,3-dihydrobenzofurans 16 (43 % cis- and 15 % franx-isomer) and dx-difluoroderivative 17 (19 %). Treatment of the derivative 17 with ethanohc potassium hydroxide produced 3-fluorobenzofuran 18 in 61 % yield [20], 3-Fluorobenzofuran 18 was also synthesized from the compound 19 using silver fluoride as fluorinating and dehydrohalogenating reagent at the second step [21],... 

Preparation by reaction of pyridinium dichromate with 4-trifluoromethoxy-2-(a-hydroxyethyl)phenol in the presence of Celite in methylene chloride at r.t. (85%) [2478,2479]. 

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