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    • 专利摘要:
    Antiinflammatory 4,5-dicyclic-2-(substituted thio)-imidazoles and their corresponding sulfoxides and sulfones, such as, 4-(4-fluorophenyl)-2-(1,1,2,2-tetrafluoroethylsulfonyl)-5-(2-thienyl)- 1H-imidazole, useful for treating arthritis and related diseases.
    公开号:SU803858A3
    申请号:SU782575954
    申请日:1978-02-08
    公开日:1981-02-07
    发明作者:Карль Черковски Сауль；Рей Шарп Томэс
    申请人:Е.И.Дюпон Де Немур Энд Компани(Фирма)；
    IPC主号:
    专利说明:

    This invention relates to a process for the preparation of new imidazole derivatives of the general formula T y5 (o) n-Ri o or 2, tetrafluoroethyl, -the same or different, and K and R, means 2-thienyl, 3-pyr dile, 2-furyl or a group General formulas where Y and Y2 are the same or different and denote a hydrogen atom, methoxy, chlorine or fluorine atoms, which can be used in | pharmaceutical-pharmaceutical industry. Alkylation of thiols and ftr with ij is known. The purpose of the invention is to develop a method for obtaining new compounds with anti-inflammatory properties on the basis of a known method. A method for the preparation of compounds of Formula 1 is proposed. The compound of the general formula Kg is J where Rj and R3 are as defined above, is subjected to alkylation with tetrafluoroethylene, and the resulting desired product is either isolated or oxidized and then isolated. The compound of formula 1 has an anti-inflammatory, namely, pproto-arthritic property of Example 1. 2-Dl, l, 2,2-Tetrapoftopethyl), 5-bis- (2-thienyl) -lH-imidazole. A. 4,5-Bis- (2-thienyl) -1H-imide A mixture of 31.6 g of ot-thienoin and 175 ml of dimethylformamide is heated for 2 hours with reverse cooling of the condenser with stirring. The resulting dark solution is poured into 600 ml of Hungry Water, stirred and filtered. The product is semi-solid and slowly solidifies. Exit 27.6 Then it is recrystallized from 35 ml of hot dimethylformamide. The precipitated crystals are filtered and washed with dimethylformamide and acetonitrile. yield 11.1 g t. pl. 218-221.5 ° When chromatographed on alumina, an additional amount is obtained (from filtrates),
    B. 4,5-Bis (2-thienyl) -lH-2-imidazolyl.
    A mixture of 12 g of 4,5-bis- (2-thienyl) -1H-imidazole, 250 ml of tetramethylene sulfone (purified) and 2.5 g of sulfur is heated for 24 hours at 170 ° C under nitrogen atmosphere, then another 2 g of sulfur is added and heated another 19 hours. The mixture is cooled, poured into 2 liters of water, filtered, progressed and dried. The dried product (9.8 g) is dissolved in dimethylformamide and purified on a silica gel column, eluting with dimethylformamide. The product is usually obtained in the first fractions and after distilling off the solvent, adding acetonitrile and filtering it is isolated in the amount of 5, 3 g, m.p. 213-218s. Using thin layer chromatography, it is determined that the product is a mixture of the starting material and the desired thiol. After chromatography by that; e by the method of a small portion of the crude product, 1.02 g of product with m.p. 283-290 ° C.
    A mixture of 27.9 g (0.25 mol) of 2-thienoia and 13.3 g of ammonium thiocyanate in 150 ml of 1-propanol is heated overnight under reflux, then cooled, and the precipitated crystals are filtered. Yield 4, 5-bis- (2-tie1P1l) -1I-2-imidazoltiola, 22.7 g, so pl. 294-303С (with decomposition and recrystallization from 1-butanol).
    C 50.15; H 3.15;
    Found 10.73.
    N
    H
    -} - (
    -.1 from 50, oo; H s, oz;
    Calculated, N 10,61.
    B 2- (1,1, 2, 2-tetrafluoroethyl) -thio} -4, 5-bis- (2-thienyl) -lFi-imidazole.
    A portion of 6.0 g of the above products is dissolved in 50 ml of dimethylformamide and 2 ml of diisopropylamine, placed in a sealed ampoule in which 5 g of tetrafluoroethylene are injected. The pressure is 15 atm, which when shaken for 23 min. Decreases to 11 atm. The temperature fluctuates between 25 and 28 ° C. The reactor is then shaken for an additional 4.5 hours, the pressure does not change more. The dimethylformamide solution is removed from the reactor, its contents are poured into water, filtered and the water is watered. The yield of the target product is 6.9 g, so pl. 131.5-142C. The product obtained is chromatographed on a column of silica gel and eluted with chloroform.
    Yield 3.1 g, so pl. 161, 5-163,. By recrystallization from toluene, an angshitically pure sample is obtained, mp16667 ° C.
    Found,%: C 42.86) H, 2.28, N 7, 76.
    WITH"
    Calculated,%: C 42.86 / H, 2.20;
    N 7.69.
    2- (1,1,2, 2-tetrafluoroethylsulfonyl) -4, 5-bis- (2-thienyl) -1H-imidazole.
    To a solution of 1.9 g of {(1, 1, 2, 2-tetrafluoroethyl), 5-bis (2-thienyl) -1H-imidazole in 100 ml of chloroform, 2.3 g of m-chloroperbenzoic acid are added with stirring. Solution
    5 becomes dark green. The mixture was allowed to stand at room temperature for one week, then another 2 g of m-chloroperbenzoic acid was added and allowed to stand overnight.
    0
    The excess oxidant is removed by stirring the reaction mass with 10 ml of methyl sulfide for 1 hour. And then it is concentrated. The residue is stirred with ether, filtered to remove insoluble solid by-product. The ether filtrate is concentrated, the residue is dissolved in chloroform and aqueous potassium bicarbonate is added to it, the layers are separated and the chloroform solution is concentrated. Output 1, the Product chromatographic on a column of silica gel (Silicar CC-A, diameter 3 cm, length 27 cm), crystallized from ethyl acetate and washed with 1-chlorobutane. Yield 0.282 g; m.p. 163-165 ° C. A second portion in an amount of 0.196 g is obtained from the filtrate.
    In another run, 4.0 g (11 mmol) 2 - (1,1, 2,2-tetrafluoroethylthio) -4, 5-bis- (2-thienyl) -1H-imidazole was oxidized in an ice bath of 7.3 g (34.8 mmol) of 82.2% m-chloroperbenzoic acid in methylene chloride. The m-chloroperbenzoic acid is removed by filtration, the filtrate prog / lb is from a 10% aqueous solution of sodium bicarbonate. The netilenchloride solution is dried with anhydrous potassium carbonate and evaporated to give 3.2 g of oil, which is crystallized by the addition of 1-chlorobutane. Recrystallization from a mixture of toluene ethyl acetate yields 1.5 g of 2- (1,1,2,2-tetrafluoroethylsulfonyl) -4,5-bis- (2-thienyl) -1H imidazole, the mass spectrum of which is 396.
    An analytically pure sample is obtained by chromatography (Silicar CC-7) using chloroform. Its melting point is 167-168 ° C.
    Found,%: C 4 O, 06, H 2, 06,
    7.42.
    N
    With ,, HB F4N ,,
    Calculated,%: C 39.39, H 2.02, N 7.07. Example 2. 4- (4-Fluorophenyl) -2- (1D, 2,2-tetrafluoroethylthio) -5- (2-thienyl) -1H-imidaeol. A. 2-Dimethylamino-2- (2-thienyl) -acetonitrile. A solution of 131.5 g of dimethylamine hydrochloride in 200 ml of water is stirred with the addition of 59 g of sodium cyanide. Then, keeping the temperature below, a solution of 112 g of 2-thiophenecarboxyde in 100 ml of methanol is added from a dropping funnel. The mixture is left to stand for another 4 hours at 30 ° C, after which it is added to 3 liters of water. Water is extracted with ether, the ether extract is washed with water, saturated with sodium bisulfite solution and then with water. The ether extract is dried with anhydrous magnesium sulphate and concentrated to give 156.5 g of a yellow oil. B. 2- (4-Fluorophenyl) -1- (2-thienyl) -ethanol. A suspension of 15 g of sodium hydride in 250 -vi dimethylformamide is mixed with the addition of 83.1 g of 2-dimethylamino -2- (2-thienyl) -acetonitrile in 300 ml of dimethylformamide. The mixture is then stirred for 1 hour until hydrogen is liberated. Within 1 hour, 72.3 g of 4-fluorobenzyl chloride was added to the mixed mixture. During the addition, the temperature is raised to 50 and the mixture is kept for another 1 hour at 40-45. After that, the mixture is partially concentrated under reduced pressure, poured into 500 ml of water, 500 r-in chloroform and 500 ml of concentrated hydrochloric acid are added. The mixture is stirred and heated under reflux for 24 hours, cooled and separated. The aqueous layer of trout is extracted with chloroform, chloro, the form extracts are collected and dried. anhydrous potassium carbonate. The dried extracts are filtered and concentrated to give 103.9 g of a dark oil. It is distilled at 0.2 mm Hg. and get 72.4 g of the product, t, pl. 6 62С. Similarly, 111.0 g (0.65 mol) of trifluoroacetic anhydride was added dropwise to a mixture of 75.0 g (0.5 mol) of 4-fluorophenyl acetic acid and 195.0 thiophene heated to 40 ° C. The reaction mixture is heated under reflux for 3 hours and then cooled, and then poured onto ice. The aqueous layer is alkalinized with sodium carbonate, the product is extracted with ether. The collected ether extracts are washed with water and, after drying with anhydrous potassium carbonate, evaporated: to give 112.0 g of oil. Crystallization from methanol yields 70.0 g of 2- (4-fluorophenyl) -1- (2-thienyl) ethanol, m.p. 61-62, C. Found,%: C 65.45, H 4.06. C, jH9FOS. Calculated,%: C 65.45, H 4.09, B. 2-BROM-2- (4-fluorophenyl) -1- (2-thienyl) -ethanon. : A solution of 71 g of 2- (4-1 trophenyl) -l- (2-thienyl) -ethanone B 300 MP chloroform is added to 160 g of copper bromide suspended in 500 ml of ethyl acetate, and heated at reflux for 2 h, the mixture is then cooled, filtered and dried with anhydrous potassium carbonate. The mixture was filtered and concentrated to give 96.0 g of residue, used without further purification. 4- (4-fluorophenyl) -5- (2-thienyl) -1H-imidazole. A mixture of 2-bromo-2- (4-fluorophenyl) -1- (2-thienyl) -ethanone with 400 ml of formamide is heated under reflux for 2 hours. The mixture is poured into 1.5 l of water-ice, the product is filtered and dried Yield 41.2 g. The product is chromatographed on 500 g of neutral alumina (degree of activity I) using dimethylformamide as a solvent and eluent. The first fraction was diluted with ethyl acetate and filtered to give 19.2 g, then the product was recrystallized from acetonitrile to obtain 14.8 g, mp. 163-164.5 p. After drying under vacuum overnight so pl. 198.5-200 C. After another treatment of the filtrates, another 4.5 g of solid product is obtained, so pl. 197-198s. The combined solid products are crystallized from 350 ml of acetonitrile and 16.4 g of product are obtained, mp. 199,200 ° C. D. 2- (Fluorophenyl) -2-hydroxy-1- (2-thienyl) -ethanone. A solution of 70.0 g (0.32 mol) of 2: - (4-fluorophenyl) -1- (2-thienyl) ethanol in 600 ml of ether was added dropwise a solution of 56.0 g (0.35 mol a) bromine in 120 ml of methylene chloride at room temperature. Concentrate the reaction mixture in vacuo to obtain 123.0 g of 2-bromo-2- (4-fluorophenyl) -1- (2-thienyl) ethanone as an oil. A solution of the oil in 275 ml of ethanol is added to a solution of 1 mol of sodium ethylate in 1 l of ethanol while stirring the mixture at room temperature. The reaction mixture was poured with 3 L of ice-water mixture, to obtain 63.4 g of 2- (4-fluorophenyl) -2-hydroxy-1- (2-thienyl) -ethanone, m.p. 90-92 ° C. E. 4- (4-Fluorophenyl) -5- (2-thienyl) -1H-2-imidazoltiol. A mixture of 16.0 g of 4- (4-fluorophenyl) -5- (2-thienyl) -1H-imidazole and 4 g of sulfur in 100 ml of tetramethylene sulfone (distilled again) is heated to 8 hours, cooled, poured into water, filtered and dried. The product is then chromatographed by dissolving in 125 ml of dimethylformamide and passing through a column (diametr 60 mm, length 200 mm) from neutral alumina (activity level according to Woelm 1). The same band is observed, then the dark bands, the outgoing fractions are collected and concentrate, obtaining 14., 3 g of substance, m.p. 228-237 ° C, which is a dimethylformamide solvate. Similar to the reaction of 63.4 (0.27 mol) of 2- (4-pyrphenyl) -2-hydroxy-1- (2-thienyl) ethanone with 29.0 g 1 (0.38 mol) ammonium thiocyanate in L-propanol gives 71.6 g of 4- (4-fluorophenyl) -5- (2-thienyl) -1H-2-imide zoltiol, t, pl. 275-277 ° C (with re-crystallization from 1-butanol). Found,%: C 56.55; H 3.42, N 10.18. Qjj, H „. Calculated,%: C 56.52; H 3.26, N 10.14. G. 4- (4-Fluorophenyl) -2- (1,1,2,2-te rafluoroethylthio) -5- (2-thienyl) -1H - they are a dazole. A solution of 14.0 g of 4- (4-fluorophenyl) -5 - (2-thienyl) -lH-2-imidazole thiol in 40 ml of dimethylformamide and 1.5 g of diisopropylamine are injected into the autoclave together with 4 g of tetrafluoroethylene. The pressure drops from 10.9 atm to normal in 1.5 hours. The solution is poured into water, stirred until the main oil solidifies, filtered and washed with water. The solid is dissolved in chloroform, dried with anhydrous sodium sulfate, concentrated and diluted with 1-chlorobutane. The crystalline product is collected. Yield 2.5 g; t, pl. 164168 ° C. The residue from the filtrate is chromatographed on silica gel using chloroform, and 4.1 g of product are obtained with a mp. 167.5-170 ° C. The collected product is crystallized from 1-chlorobutane, yielding 5.6 g; mp 167-168, C 48.24, H 2.58; Found,%; N 7, 83. - ffHoFj-Nj S With 47,87; H 2.39; Calculated, M 7/45. 4- (4-fluorophenyl) -2- (1,1,2,2-tetra fluoroethylsulfonyl) -5- (2-thienyl) -1H-imidazole. A mixture of 6.6 g of 4- (4-fluorophenyl) -2- (1,1,2,2-tetrafluoroethylthio) -5- (2-nyl) -1H-imidazole in 160 ml of chloroform is stirred with the addition of 9 g of 85 % m-chloroperoxybenzoic acid. There is an increase in temperature. The mixture was incubated for two days, then 30 ml of dimethyl sulfide was added, and the temperature increased. The mixture is cooled and filtered, the filtrate is stirred with water, the aqueous phase is made alkaline with sodium bicarbonate. The organic layer is separated, dried with sodium sulfate and concentrated. The solid product is dissolved in 40 ml of hot 1-chlorobutane, treated with activated organic charcoal, filtered and concentrated to 1/3 volume. Crystals are available. Yield 2.1 g; . square 192193 ° C. C, 44.5; H 2.46; Found, N 7.04, Ci5 c 44.11; H 2.22; Calculated,% N 6.86. Example 3. 4-14-Chlorophenyl) -2- (1,1, 2, 2-tetrafluoroethylthio) -5 -, (2-thienyl) -1H-imidazole. I A. 2- (4-Chlorophenyl) -1- (2-thienyl) -ethanone. A mixture of 85.3 g of p-chlorophenylacetic acid and 200 ml of thiophene was stirred at 40 ° C and 105 g of trifluoroacetic anhydride was added to it, then heated under reflux for 4 hours, poured onto a mixture of ice and water, and alkalized with sodium carbonate. The mixture is extracted with dichloromethane, dried with sodium carbonate and concentrated. Crude yield: 126.4 g. Crude product is recrystallized from 300 ml of methanol, yielding 103 g; m.p. 98-99s. B .. 2-Bromo-2- (4-chlorophenyl) -1- (2-thienyl) -ethanone. A solution of 100 g of 2- (4-chlorophenyl) -1- (2-thienyl) ethanone in 400 ml of chloroform is poured to a suspension of 200 g of copper bromide in 650 ml of ethyl acetate. At the end of the addition, the mixture is heated under reflux for 3 hours. It is then cooled in an ice bath and filtered, and the filtrate is stirred with SUE ice - water. The pH of the solution is neutralized by the addition of sodium bicarbonate. The organic layer is separated, water is extracted twice with chloroform. The collected extracts are dried with anhydrous potassium carbonate, filtered and concentrated. Output 142, the Product is used without additional purification. B. 4- (4-Chlorophenyl) -5- (2-thienyl) -1H-imidazl. A mixture of 35 g of 2-bromo-2- (4-chlorophenyl) -1- (2-thienyl) ethanone with 200 fvui formamide is heated for 2 hours under reflux, then cooled, poured into water and the pH is adjusted to 8-9 by ammonium hydroxide added. Thereafter, chloroform is added to the solution. A solid is isolated which is filtered and washed with chloroform. Yield 19.3 g. Then the product is recrystallized from dimethylformamide, filtered and washed with acetonitrile. Yield 14.7 g; m.p. 244-245 ° C. G. 4- (4 Chlorophenyl) -5- (2-thienyl) -lH-2-imidazoltiol. A mixture of 9.4 g of 4- (4-chlorophenyl) -5- (2-thienyl) -1H-imidazole, 2 g of sulfur and 50 ml of tetramethylene sulfone is stirred under a nitrogen atmosphere and heated for 8 hours to 200c. It is then cooled, poured into water, filtered and washed thoroughly with water to obtain 11.5 g of product. The latter is dissolved in dimethylformamide and chromatographed on a column (diameter 6 cm, length 125 cm) from neutral alumina (degree of activity according to Woelm 1), using dimethylformamide for elution. The output of 5.6 g in the form of dimethylformamide adduct. The image is dried in a high vacuum, so pl. 274 21 f, C, D. 4- (4-Chlorophenyl) -2- (1,1,2,2-those rafluoroethylthio) -5- (2-thienyl) -1H-imidazole. A solution of 6.9 g of 4- (4-chlorophenyl) -5- (2-thienyl) -lH-2-imidazoltiol in 40 ml of dimethylformamide and 1.5 ml of diisopropylamine is injected into an autoclave with 3 g of tetrafluoroethylene, agitated until the pressure drops. . The contents of the autoclave were poured into water, the pH was adjusted to 8, the solution was extracted with chloroform. The extract is dried and dried: then chromatographed on silica gel to give 5.5 g of a fraction, which is dissolved in hot 1-chlorobutane. By cooling the solution, 4.5 g of product are obtained, mp., 16 -5-1bЗ ° С. Found,%: C 46.06; H 2.49; N 7.40; S 16.44. H „S1P M2.52. Calculated,%: C 45.86; H 2.31; N 7.13; S 16.33. Example 4. 4- (3,4-Dichlorophenyl) -2- (1,1,2,2-tetrafluoroethylthio) -5- (2-thienyl) -1H-imidazole. A.2- (3,4-Dichlorophenyl) -1- (2-tie, nyl) -ethanon. By the method of Example 4A, using 100.0 g of 3,4-dichlorophenyl-oxus acid, 242.0 g of thiophene and 144.0 g of trifluoroacetic anhydride, and methanol, 61.7 g of 2- (3,4-di-chlorophenyl ) -1- (2-thienyl) ethanone, m.p. 59.5-BS, 6 ° C. Found,%: C, 53.24; H, 2.95; iC2; 5Calculated,%: C, 53.14; H, 2.95. B. 2- (3,4-Dichlorophenyl) -2-hydroxy-1 - (2-thienyl) -ethanone. 2- (3,4-Dichlorophenyl) -1- (2-thienyl-ethanone (57.0 g, 0.21 mol) was transferred to 49.8 g of 2- (3,4-dichlorophenyl) -2-OXI -1- (2-thienyl) ethanone, mp 108-109C (recrystallized from 1-chlorobutane), following the procedure of Example 2D Found: C 50, 34 H 2, 86, C oHfiClnOoS. Calculated,%: C 50.17, H 2.99. B.4- (3,4-Dichlorophenyl) -5- (2-nie nyl) -lH-2-imidazoltiol. Following the procedure of example 2E, 45.0 g (0.16 mol) 2- (3,4-dichlorophenyl) -2-oxy-l- (2-thienyl) -ethanone is reacted with ammonium thiocyanate in 1-propanol under reflux to give 32.6 g of 4- ( 3,4-dichlorophenyl) -5- (2-tyJHyl) -lH-2-imidazoltiol, mp 263-265 with (recrystallized from 1- Butano a). Found: C 46.10; H 2.82; N 8.23; C, HgClj N Sj-llZHjO. Calculated,%: C 46.42; H 2.69, N 8.33. G. 4- (3,4-Dichlorophenyl) -a- (1,1,2,2-tetrafluoroethylthio) -5- (2-thienyl) -1H-imidazole. 4- (3,4-dichlorophenyl) -5- (2-Thienyl) -lH-2-imidazoltiol (30.0 g, 92 mol): subjected to interaction with 15.0 g of tetrafluoroethylene, similar to the method of Example 4D, after chromatographing on silica gel using chloroform, 19.1 g of 4- (3 , 4-dn-chloro-phenyl) -2- (l, 1,2, 2-tetrafluoresylthio) -5- (2-thienyl) 1H-imidazole, mp. 178180 ° C (recrystallized from toluene) .. O Found,%: C 42.88; H 2.03; N 6.57. C, 5 H8F4CliN2S2. Calculated: C 42.15} H 1.87. N 6.56. 4- (3,4-Dichlorophenyl) -2- (1,1,2,2-tetrafluoroethylsulfonyl) -5- (2-thienyl) -1H-imidazole. 4- (3,4 Dichlorophenyl) -2- (l, l, 2,2-tetrafopoethylthio) -5-2.-thienyl) -1H-imidazole (5.0 g, 11.7 mol) oxide, 6 , 1 g (29 mol) of 82.2% m-chloroperbenzoic acid, followed by the method of Example 5. The crude product is purified by chromatography on silica gel using chloroform to obtain 1.4 g of 4- (3,4-dichlorophenyl) -2 - (1,1,2,2-tetrafluoroethylsulfonyl) -5- (2-thienyl) -1H-imidazole, mp 1558159, 5 ° C (recrystallized from toluene). Found,%: C 39.83; H 1.96; N 6.07. HgCliF4N, iO, iS2. Calculated,%: C 39.2; H 1.74; N 6.1. Example 5. 4- (4-Methoxyphenyl) -2- (1,1,2,2-tetrafluoroethylthio) -5- (2-thienyl) -1H-imidazole. Analogously to Example 6, using 4-methoxyphenylacetic acid, the following compounds are obtained: 2- (4-Methoxyphenyl) -1- (2-thienyl) -ethanone, m.p. JS-lTC (recrystallized from methanol). Found,%: C 67.11; H 5.29. with,, . Calculated,%: C, 67.24; H 5.17. . 2- (4-Methoxyphenyl) -2-hydroxy-1- (2-thienyl) -ethanone, mp. 69-73 0 (with recrystallization from 1-chlorobutane). Found,%: C 62.15, H 4.78. , H, 2. . Calculated,%: C 62.90) P 4.84. 4- (4-Methoxyfennl) -5- (2-thienpl) -lH-2-imidazoltiol, so pl. 266-268 (with recrystallization from ethanol) Found,%: C 58.37; H 4.27, N 9.49. . Calculated,%: C 58.33; M 4.17; N 9.72. 4- (4-Methoxyfekyl) -2- (1,1,2, 2-t rafluoroethylthio) -5- (2-thienyl) -1 and they dazole, t. 1-sh. 112-113.5 ° C (with chromatography on silica gel using chloroform and recrystallization from 1-chlorobutane). Found,%: with 49.92; H 3.21; N 7.21. H ,,.,. Calculated,%: C 49.48; H 3.09, N 7.22. Example 6. 4- (4-methoxy-secreta-2- (1,1, 2,2-tetrafluoroethylsulfonyl-5- (2-thienyl) -1H-imidazole. 4- (4-methoxyphenyl) -2- (1, 1, 2, 2-Tep aph or ethyl ethyl yew) -5- (2-thione and h) -111-im dazole (4.0 g, 10.3 mol) is oxidized with 6.1 g (29 mol) of 82.2 % m-chloroper benzoic acid. The crude product is purified by chromatography on silica gel using chloroform. The yield is 4- (4-methoxyphenyl) -2- (1, 1, 2, 2-tetraterothylsulfonyl) -5- (2-thienyl ) -1I-imidazole 1.3 g, mp 163-164.5 (recrystallized from hdorbutane) Found: C 45.20; II 2.92 ;; N 6.82. N H F P ft) (-L t- 3 C 55,71-, Calculated, W 6, 67, Example 7. 4, 5-Bis- (2-furi -2- (1, 1, 2, 2-tetr. fluoroet ylthio) -1P-imidazole. A. 4, 5-Epc- (2-furi) -1H-2-im11 ;;: azolthiol, 19.2 g (0.1 mol) a-furo:; on bale t with 11.5 g (0.15 mol) of thio-diade a 2vio with ethanol Yield 4,5-bis - (2-furyl) -lH-2-imidazoltiol 11.4 Analytically pure sample no.ny-ia by chromatography on alumina using ethanol and recrystallization from nitromethane; m.p. 279380 ° C (with dec,). Found,%: C 57.20; H 3.86; N 11.72. C HgNjOsS. Calculated,%: C 56.90, P 3.45, N 12.07, B. 4,5-Bis- (2-furyl) -2- (1, 1,2,2-tetrafluoroethylthio) -1H-imidazole , 4, 5 - BIS- (2-furyl,) -lH-2-imidazoltiol (8.1 g, 39.4 mol) is reacted with 7.0 g of tetrafluoroethylene, the product is purified by chromatography on silica gel using chlorine form . Output 4, (2-furyl) -2- (1,1,2,2-tetrafluoroethylthio) -1H-imidazole 3 g, so pl. 166-167 ° С (with a human crystal and a position from 1-chlorobutane) Found, F 2 5 Calculated, C 47.99; ii 2.4: 3.43. Example dil) -2- (1,1, 2, 2-tetrafluoroeth; -; ltio) -1H-imidazole. A, 4-Phenyl-5- (3-pyridyl) -111-2;; dazolthiol. A solution of 30.0 g (0.15 mol) 3-pi) -) m. dilbenzylketone B 300 glp of acetic acid is treated dropwise with a solution of 25.0 g (0.16 mol) of bromine in 240 ml of vinegar acid at room temperature. After stirring overnight, the precipitate (26.8 i-) 3-pyridyl-ci -bro-benzyl ketsn-g1-stromide is filtered. A mixture of 5.0 g (14.0 mol) i: aiK p :: added salt with a solution of 0.1 MOJ: ;; sodium ethylate in 100 g-hl ethanol is stirred for no-n-; at ks: -.- 1 temperature and poured into 0.5 M aqueous hydrochloric Kl-i Slot. After stirring for several hours, the acidic acid solution is alkalinized with solid sodium carbonate, extracting the product with ether. The ether was dried with anhydrous potassium carbonate ii and removed in vacuo to give 4.5 g of 3-pyridyl-ci-hydroxybenzyl ketone. Then a mixture of 20.0 g (56.0 mol) of 3-pyridyl-OL-bromobenzyl ketone-hydrobromide and 24.0 g (0.24) of potassium acetate in 100 NUT of acetic anhydride: at night; ; at ;; oh temperature. The reaction mass is poured into water, the product is extracted with ether. Collect ;;: le ethereal extracts prog-go to water ;,::.; 10% - ;: SMI bi water solution ;; arbs;: on that sodium. Ether layer with ::. ;;; at -; ars;.; Natium potassium and evaporated; art. OTC:., K is dissolved in 140 g of 1N. in ;; |: oG-: hydrochloric acid; - O ACID:., g AGRV: st 30 min with reverse holsd1-flax and ps: ,, le cooling under; dochchivayut solid ;. karsyunatom sodium. . Produ; t extracted with ether, collected s; ; mrm ;;; e extracts; sprinkled vods; suivanide with anhydrous carbonyl saline, obtaining 8.15 g of 3-pyridyl-o-oxybysyl ketone. 3-Pyridyl-ci-oxybenzylkettsn (8.15 g, 38.3 mol) is reacted with 7.5 g (0.1 mol) of ammonium thiocyanate in 1-propanol (with heating with reflux ;; IC) and 4.3 g of p-phenyl-5-v3-pyridyl) -lH-2-imidazoltiol are obtained; mp. 317-323С (with a recrystall; - setting from a mixture of DMF-H.O. into a sotno; 2: 1). %: C 65.92; Found, N 16.34,
    H (.
    Calculated,%: C, 66.40; H 4.35; N 16.60.,
    B. 4-Phenyl-5- (pyridyl) -2- {1,1,2-tetrafluoroethylthio) -1H-imidazole.
    4-Phenyl-5- (3-pyridyl) -HH-2-imidazolothiol (2.0 g, 7.9 mol) is reacted with 5.0 g (50 mol) of tetrafluoroethylene, the crude product is purified by chromatography on silica gel using chloroform 800 mg of 4-phenyl-5- (3-pyri, dil) -2- (1,1,2, 2-tetrafluoroethylthio) -1H-imidazole are obtained, m.p. 153-154 ° C (recrystallized from toluene).
    C, 54.69; H 3.37;
    Found 11, 69.
    WITH,,
    C 54.39; H 3.12;
    Calculated 11.90.
    权利要求:
    Claims (1)
    [1]
    1. D.S. Jngland et al. NucleophiMs Reaction of Fluoroolefins, 30 j. Am. Chem. See. , 1960, 82, 5116.
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