Iodide, trifluoroethyl

Condensation of sodium phenoxide witli 2,2,2-trifluoroethyl iodide gives a product of direct substitution in a low yield, several other ethers are formed by eliminatton-addition reactions [7] Use of mesylate as a leaving group and hex amethyl phosphoramide (HMPA) as a solvent increases the yield of the substitution [S] Even chlorine can be replaced when the condensation is performed with potassium fluoride and acetic acid at a high temperature [9] (equations 6-8)... 

In the preparation of the thiazides containing more highly functionalized side chains (183-185), an acetal of the aldehyde is usually used rather than the free carbonyl compound. Thus, trichlomethiazide (183) is prepared by reaction of 160 with the dimethyl acetal from dichloroacetaldehyde. In a similar vein, alkylation of the acetalthiol, 190, with allyl bromide affords 191. This yields altizide (184) on condensation with 160. Alkylation of 190 with 2,2,2-trifluoroethyl iodide gives 192. This leads to epithiazide (185) on condensation with 160. 

Prepares solution of sodium methylate by dissolving 3.9 g of sodium metal in 500 ml of methanol. Add 39.0 g of 7-chloro-1,3-dihydro-5-phenyl-2H-1,4-benzodiazeplne-2-one. Evaporate the reaction mixture to a residue and dissolve the residue in 170 ml of dimethylformamide. Add 30 g of 2,2,2-trifluoroethyl Iodide and stir at room temperature for Vi hour, then heat to 60°C to 70°C for an additional 7 hours. Add 19 g of 2,2,2-trifluoroethyl iodide and resume the heating and stirring at 60°C to 70°C for an additional 16 hours. Filter off the solids and evaporate the filtrate to a residue in vacuo. Triturate the residue with water and extract with ethyl ether. Wash the ethereal extract with water, dry over anhydrous sodium sulfate and evaporate the solvent to a residue. 

Nakai, T. Tanaka, K. Ishikawa, N. The reaction of 2,2,2-trifluoroethyl iodide with sodium phenolate. A novel competition between substitution and elimination reactions. /. Fluorine Chem. 1977, 9, 89-93. 

Organoiodine compounds. lodoaienes, iodoaUcenes, and iodoalkynes are prepared from organolithiums by reaction with 2,2,2-trifluoroethyl iodide. 

N-alkylation of the amide NH group at a late stage in the synthesis with trifluoroethyl iodide and NaH went... 

Xenon difluoride is used to prepare methyliodine difluoride from methyl iodide [102, 128] as well as to convert miscellaneous aryl [103, 129, 110] heptafluorapropyl [129], and 2,2,2-trifluoroethyl [103] iodides to the corresponding organo iodine difluorides in yields ranging from 60 to 100% Elemental fluorine transforms aryl iodides to their corresponding aryliodine difluoride turn pounds [131 132], which are known to add fluorine to alkenes ]133] (equation 21)... 

Trifluoroethyl chloride, bromide, and iodide (but not fluoride) react with thio-late ions in DMF under laboratory illumination at 30-50 °C to give high yields of 2,2,2-trifluoroethyl thiol derivatives. Various features of the reactions show that they occur by the 5 rnI mechanism. The initiation may be spontaneous or thermal electron transfer between thiolate and halides, because the reactions can occur in the dark. 

Sulfur also reacts with fluoroalkyl mercurials and fluoroalkyl iodides to give fluorothioacyl halides. In the case of the reaction with mercurials, the halide formed is determined by substitution on the carbon attached to mercury. For example, bis(perfluoroethyl)mercury gives trifluorothioacetyl fluoride and bis-(l,l-dichloro-2,2,2-trifluoroethyl)mereury gives trifluorothioacetyl chloride. 

Symmetrical 3,5-dialkyl-l,2,4-trithiolanes (178) can be synthesized in reasonable yield by chlorination of dialkyl disulfides (175) to a-chiloroalkyl sulfenyl chlorides (176), which are then reacted with potassium iodide to give di-a-chloroalkyl disulfides (177). Subsequent cyclization with sodium sulfide gave (178) (72T3489). When (176) was treated with one molar equivalent of sodium sulfide, the reductive dimerization and cyclization was effected in one step (78HCA1404). Treatment of perfluoropropene with sodium hydrogen sulfide in THF resulted in the formation of 3,5-bis(2,2,2-trifluoroethyl)-l,2,4-trithiolane (179) (72IZV2517). 

The reaction is mainly used to prepare dialkyl 3-cyano-2-propenylphosphonates, which are used as precursors for retinal and derivatives. Thus, diethyl and Z w(trifluoroethyl) 3-cyano-2-methyl-2-propenylphosphonates are conveniently prepared in good to excellent yields (75-90%) by heating at 180-200°C 4-chloro--- or 4-brorno-3-rncthylcrotonitriles- and the corresponding phosphite. Similarly, diethyl 3-cyano-2-butenylphosphonate is obtained in 95% yield from triethyl phosphite and 4-chloro-2-methylcrotonitrile (Scheme 6.31 ). In a further example, 4-bromo-3-methyl-2-hex-enenitrile has been reacted with triethyl phosphite at 170-180°C to prepare diethyl 3-cyano-2-methyl-l-ethyl-2-propenyIphosphonate in fair yield (44%).- The reaction of a polyfunctional iodide, 3-amino-2-(iodoacetyl)crotonitrile, with triethyl phosphite affords the expected 3-cyanoalkylphosphonate in 78% yield. 

The potassium salt of /2z 5(2,2,2-trifluoroethyl) 1-(methoxycarbonyl)methylphosphonate is alkylated with homogeranyl iodide in THF-HMPA in the presence of 18-crown-6 (1 eq). The use of Et2O or toluene at reflux- gives less satisfactory results. Treatment of diethyl 1-(ethoxycarbo-nyl)methylphosphonate with [ C]methyl iodide and allyl bromide" using EtONa in absolute EtOH produces diethyl l-[ - C]methyl and l-allyl-l-(ethoxycarbonyl)methylphosphonates in good yields. The tandem Michael addition-alkylation of l-(ethoxycarbonyl)vinylphosphonate has been reported with methyl cuprate, but the alkylation is complete only in the presence of Lewis bases like HMPA or TMl. "... 

Trifluoroethyl chloride, bromide, and iodide (but not fluoride) react with thio-late ions in DMF under laboratory illumination at 30-50 °C to give high yields of... 

The construction of the alkenyl side chain and the control of the C9, CIO and Cll stereogenic centers was achieved from (5)-(+)-methyl 3-hydroxy-2-methylpropionate 1. (Scheme 21) This compound was transformed to aldehyde 99 in three steps. Bis(2,2,2)trifluoroethyl)[(methoxycabonyl)methyl]-phosphonate [23] was employed for the selective formation of the cA-a, 3-unsaturated ester 100. From this Z-unsaturated ester 100, the three consecutive asymmetric units were constructed via epoxide 101 (m-CPBA), which was selectively opened by lithium dimethylcuprate to produce 102. After deprotection-protection, the alcohol 102 was converted to the phosphonium iodide 103 via a tosylate intermediate(Scheme 21). 

The first catalytic version of the Hofmann rearrangement using aryl iodides as catalysts and mCPBA as terminal oxidant was reported by Ochiai and coworkers in 2012 [72], A study of the catalytic efficiency of substituted iodobenzenes and some aliphatic alkyl iodides in the iodane(III) catalyzed Hofmann rearrangement of benzylic carboxamides has demonstrated that iodobenzene is the best catalyst. The introduction of both electron-donating (4-methyl, 3,5-dimethyl and 2,4,6-trimethyl) and electron-withdrawing groups (4-Cl and 4-CF3) into iodobenzene decreased the yield of rearranged products. Aliphatic iodides such as methyl, trifluoroethyl and 1-adamantyl iodides showed no catalytic efficiency. Under optimized reaction conditions,... 

The 5 -(trifluoromethyl)sulfonium salt can be applied to copper-mediated trifluoromethylation. Trifluoromethylation of heteroaryl iodides with the sulfonium salt proceeds in presence of stoichiometric copper under mild condition (eqs 17 and 18). Boronic acids also react with sulfonium salt (eqs 19 and 20), though 1 equiv of NaHCOs is needed as the base. These reactions furnish corresponding trifluoromethylated products in high yield. The copper-mediated trifluoromethylation reaction advances not only with aromatic compounds, but also at a benzylic position (eq 21). Trifluoromethylation reaction of benzyl bromides with S -(trifluoromethyl) sulfonium salt provides (trifluoroethyl)arenes in high yields. 

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