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    公开号:SU741795A3
    申请号:SU772535554
    申请日:1977-10-17
    公开日:1980-06-15
    发明作者:Сарджес Рейнхард
    申请人:Пфайзер Инк (Фирма)；
    IPC主号:
    专利说明:

    (54) METHOD FOR OBTAINING SPIROHYDANTHOIN COMPOUNDS OR THEIR SALTS The invention relates to a method for producing new spirohydantoin compounds of the general formula where: A is a group of the formula W is a group of the formula - (CH2) p; Xj is hydrogen; 6 10 15 2Q Xj - fluorine, hydroxy or 6-lower alkoxy or Xi and X2, taken separately, lower alkoxy groups, and taken together - a group of the formula -OCH2 (CH2) pO; Xs - hydrogen; X4 is fluorine, chlorine or bromine, or Xs and X4, chlorine atoms taken separately, and taken together form a group of the formula -OCH2 (CH2) pO; Xs is hydrogen; Xg - fluorine, hydroxy or lower alkoxygroup Xs and Hb, taken separately, chlorine atoms or lower alkoxy groups, and taken together the formmly -OCH2 (CH2) pO group; 1 is hydrogen; Xg is fluorine, chlorine, bromine or lower alkoxy, -: or X7 and Xg taken separately, hydrogen, chlorine or lower alkoxy, and taken together is a group of formula -OCHj (CH2) nO; Y is an oxygen or sulfur atom; Q is a group of the formula -SO - or SOj; B-0 or 1 or their salts with biological activity.  A method for the preparation of hydantoins by the interaction of the corresponding ketones with alkaline cyanide is widely known. metal and ammonium carbonate 11.  The purpose of the invention is the synthesis of new biologically active compounds.  This goal is achieved by the proposed method of obtaining spirohydantoic compounds of general formula D, based on the known reaction and the fact that the compound of formula OA where A has the indicated values is subjected to interaction with alkali metal cyanite and ammonium carbonate and isolates the desired product, where - a sulfur atom, in the case when A has the value of the formula D, the resulting product is oxidized, in the case when X2 and Xg are alkoxy groups, the resulting compound is converted into a compound where Xj and Xg are hydroxy groups, with a release of product in free form or in salt form.  The process is conducted predominantly in a solvent inert under the reaction conditions, for example, in cyclic ether, at 20-120it; .  Example 1  A mixture containing 13.2 g - (0.1 mol) schanson-1, 9.75 g (0.15 mol) of potassium cyanide and 28.8 g (0.3 mol) of powdered ammonium carbonate, in 200 ml A 50% aqueous ethanol is heated in an oil bath at 75 ° C for 24 hours.  The reaction mixture is then diluted with 700 ml of water, boiled for 15 minutes, then cooled to room temperature, poured into 600 ml of ice-cold concentrated hydrochloric acid. The precipitated crystalline precipitate is then collected using filtration under vacuum, washed with water, and then it is recrystallized from a mixture of methanol and dithyl ether to obtain 15.4 g (76%) of pure spiro- (dazolindin-4,4 -indane) -dione-2.5, t.  square  238240 ° C.  Calculated,%:.  C 65.33; H 4.98; N 13.86 Si HI Found;%: C 65.28; H 5.01; N 13.90.  Example 2  A mixture containing 2.5 g (0.15 mol) of 6-methoxyindanone-1, 1.5 g (0.23 mol) of potassium cyanide and 6. 7 g (0.07 mol) of ammonium carbonate in 20 ml of ethanol are placed in a stainless steel autoclave and heated at 110 ° C for 20 h.  After cooling to room temperature (approx.) But 25 ° C), the contents of the autoclave are diluted with 100 MP of water, and then acidified to pH 2.0 6 and.  hydrochloric acid solution.  The precipitate is collected using a vacuum under vacuum, and then recrystallized from ethanol to give 0.49 g (14%) of pure 6-methoxy-spiro- (imidazolidin 4, 1-indan) -dione-2.5, t.  PC.  192-194 ° C.  Calculated,%: C 62.06; H 5.21; N 12.06 Cntiu jOs Found:%: 61.94; H 5.26; N 12.01.  Example 3  The operations described in Example 2 are repeated, except that 6-Fluoro-indanone-1 is used instead of 6-methoxyindanone-1 as the starting material using the molar ratios indicated above.  In this case, the corresponding end product is b -fluoro-spiro- (imkdazolidin-4,1 -indane) -dione-2.5, t.  11L. 255257 S.  The yield of the pure product is 4.6% of the theoretically possible.  Calculated,%: C 60.00; H 4.12; N 12.72 CuHigFN Oj Found,%: C 59.86; H, 433; N 12.49.  Example 4  The operations described in Example 2 are repeated, except that 5,6-dimethoxyindanone-1 is used instead of 6-methoxyindanone-1 as the starting material, using the same molar ratios.  In this particular case, the final product obtained is 5, b-dImethoxy-spiro- (imidazolidin-4,1-indan) -dione-2.5, t.  silt  246-248 ° C.  The yield of pure product is 48% of the theoretically possible.  Calculated,%: C 59.53; H 538; N 10.68 Cl3Hi4N204; Found: C 59.26; H 5.49; . N 10,54. Example 5.  The operations described in Example 2 are repeated, except that instead of b-methoxyindanone-1, 5,6-methylenedioxyindanone-1 is used as the starting material using the same molar ratios.  In this particular case, the corresponding final product obtained is blinded with 5, 6-methylenedioxy-spiro- (imidazolidin-4,1-shchchan) -dione-2.5, t.  square  248-250 ° C.  The yield of pure product is 29% of the theoretically possible.  Calculated,%: C 58.53; H 4.09; N 1138 Ci2H, oN204; Found: C 58.44; H 4.14; N 11.25.  Example 6  The operations described in Example 2 are repeated, except that 5-methoxyindanon-1 is used as the starting material instead of b-methoxyindanone-1 using the same molar ratio of 1x1x ratio.  In this particular case, the corresponding final product obtained is 5-methoxy-spiro- (imidazolidin-4,1-indan) -dione 2, 5, t.  square  1b7-169 ° C.  The yield of pure product is 19% of the theoretically possible.  57 Calculated,%: C, 62.06; H 5.21; N 12.06 CizhijNjOs Found,%: C 61.77; H 5.23; N 12.14.  Example 7  Operators described in Example 2 are repeated except that thiochromans are used instead of 6-methoxyindanone-1 using the same molar ratios as the starting material. In this particular case, the corresponding final product 1 is spiro- (imidazolidin-4,4 - thiochroman) -dione-2. 5, t.  square  225-227 ° C.  The yield of pure product is 44% of the theoretically possible.  Example 8  The operations described in Example 2 are repeated, except that 6-methoxythiochromium-4 is used as the starting material instead of 6-methoxyindanone-1 using the same molar ratios.  In this particular corresponding final product obtained, is 6-methoxy-spiro- (imidazolidin-4,4-thiochroman) -dione-2.5, t.  square  170-172 ° C.  The yield of pure product is 41% of the theoretically possible.  Calculated,%: C 54.53; H 4.58; N 10.61 CiaHiji iOj Found,%: C 54.64; H 4.67; N 10.66.  Example 9  The operations described in Example 2 are repeated, except that 6-chlorothiochromanone-4 is used instead of 6-methoxane indanone-1 as the starting material using the same molar ratios.  In this particular corresponding final product obtained is b-chloro-spiro- (imidazolidin-4,4-thiochroman) -dione-2.5, t.  square  244-246 ° C.  The yield of pure product is 53% of the theoretically possible.  Calculated,%: C 49.16; H 3.38; N 10.43 CiiHgCElMjOj Found;%: C 49.23; H 3.40; N, 10.39. The operations described in Example 2 are repeated, except that 6-bromothiochromanon-4 is used instead of 6-methoxyindanone-1 as the starting material using the external molar ratios.  In this particular case, the corresponding final product obtained is 6-bromo-spiro- (imidazolidin-4,4-thiochroman) -dione-2.5, t.  Ш1.  234-236 ° C.  The yield of pure product is 56% of the theoretically possible.  Calculated,%: C 42.18; H 2.90; N 8.95 CjiHgBrNjOj Found,%: C 41.98; H 2.92; N 8.95.  Example 10  The operations described in Example 2 are repeated, except that 6,7-dichlorothiochromanone-4 is used instead of 6-methoxyindanone-1 as the starting material using the same molar ratios.  In this special case, the corresponding final product obtained is 6, 7-dichloro-spiro (imidazolidine-4,4-thioxoproman) -dione-2.5, t.  square  2 8-300 ° C.  The yield of pure product is 49% of theoretically possible.  Calculated,%: C 43.59; H 2.66; N 9D4.  CnMeC NiOi Found;%; C 43.77; H 2.85; N 938.  Example 11  The operations described in Example 2 are repeated except that 6-fluorothiochromanone-4 is used instead of 6-methoxyidanone-1 using the same molar ratios.  In this particular case, the corresponding final product obtained is b-fluoro-spiro- (imidazolidin-4,4-thiochroman) -dione-2.5, t.  square  200-202 ° C.  The yield of pure product is 60% of the theoretically possible.  Calculated,%: C, 52.37; H 3.60; N 11.11.  SCN 9FN202 Found,%: C 52.36; H 3.73; N P, 05.   Example 12  The operations described in Example 2 are repeated except that 8-chlorothiochroman-4 is used instead of 6-methoxyindanone -1 using the same molar ratios.  In this particular case, the corresponding final product obtained is 8-chloro-spiro- (imidazolidin-4,4-thiochroman) -dione-2, 5, t.  square  265-267 ° C.  The yield of the product is 66% of the theoretically possible.  Calculated,%: C 49.16; H 3.38; N, 10.43; CjiHsCCNjOj; Found: C 4932; H 3.50; N 10.38.  Example 13  The operations described in Example 2 are repeated except that, instead of 6-methoxynndanone-1, -chlorothiochromanone-4 is used as the starting material using the same molar ratios.  In this particular case, the corresponding final product obtained is 7 -.  chloro-spiro- (imidazolidin-4,4-thiochroman) -dione-2, 5, t.  square  235-237 ° C.  The yield of pure product is 67% of the theoretically possible.  Calculated,%: C 49.16; H 3.38; N 10.43 CjiHgCENjOa Found: C49.32; H 336; N 10.03.  Example 14  The operations described in example 2 are repeated, except that, instead of 6-methoxyindanone-1, 7, 8 -dihydroinolinone-5 (6H) is used as a similar material using the previous sea five ratios.  In this particular case, the corresponding final product obtained is l, 8 -dihydro-spiro (4,5 (6H) quinoline) -dione-2, 5, t.  square  275-277 ° C.  The yield of the resulting product is 39% of the theoretical value.  Vrgasleio,%: C 60.82; H 5.10; N 1935.  CiiHiiMz Found,%: C 60.41; H 5.28; N 19.29.  Example 15  The operations described in Example 2 are repeated, except that instead of 6-methoxyivdanone-1, 7-methoxytetraloyl-1 is used as the starting material using the same molar ratios.  In this particular case, the corresponding final product obtained is h, 4-dihydro-7-methoxy-spiro- (imidazolidin-4,1 (2H) naphthalene) -dione-2.5, t.  square  227-229 ° C.  The yield of pure product is 59% of the theoretically possible.  Calculated,%: C, 63.40; H 5.73; N 1138 C 1 C H D 4 20 C Found:%: C 63.19; : H 5.68; N 11.30.   Example 16  The operations described in example 2 are repeated, except that instead of 6-methoxyindanone-1, 6,7-dimethoxy tetraolone is used as the starting material using the same molar ratios.  In this particular case, the corresponding final product obtained is from 4-dihydro-6, 7-dimethoxy-spiro- / imidazolidin-4, 1 (2 1G) naphthalene / -dione-2.5, t.  Ш1.  238-240 ° C.  The yield of pure product is 49% of the theoretically possible.  Calculated,%: C 60.86; H 5.84; N 10.14% Found: C 60.94; H 6.04; N 10.48.  Example 17  The operations described in Hfimer 2 are repeated except that, instead of 6-methoxyindanone-1, 6-methoxytetralone-1 is used as the starting material using the same molar ratios.  In this particular case, the corresponding final product obtained is h, 4-dihydro-b-methoxy-spiro- / imidazol-idin-4, 1 (2H) naphthalene / -dione-2.5, t.  square  21922GS.  Example 18  A solution of 1.18 g (0.005 m 6-methoxy-spiro- (imidazolidine. . 4,1-mdan) -dione-2, 5 (obtained by the method described in example 2) is cooled in 10 ml of dichloromethane and cooled (; 6S) ° C, and then to the resulting solution is added dropwise a solution containing 1, 44 ml (0.015 mol) of boron tribromide dissolved in 10 ml of dichloromethane while stirring the entire reaction mixture under nitrogen atmosphere.  The resulting mixture is gradually brought to a temperature of about 1 ° C (about 25 ° C) by removing the cooling bath, after which this temperature is maintained for 7 hours.  After the completion of this, 30 ml of water are added dropwise and the separated organic layer is then collected and dried over anhydrous magnesium sulphate.  After removal of the organic solvent (m.  ".  dichloromethane) by evaporation under reduced pressure eventually obtain a residue, which is then recrystallized from ethanol to obtain 240 mg (22%) of pure 6-hydroxy-spiro- (imidazolidin-4,1-indan) dione-2, 5, t.  square  253-25. WITH.  Calculated,%: C 60,54; H 4.62; N 12.84 CiiHjoblaOa; Found: C, 60.29; H 4.66; N 12.93.  An example. nineteen.  A mixture containing 5.0 g (0.033 mol) of chromanone-4, 2.8 g (0.043 mol) of potassium cyanide 8.26 g (0.076 mol) of powdered ammonium carbonate in 40 ml of ethanol is placed in a stainless steel autoclave and heated to 60 ° C in an oil bath for 24 hours  The reaction mixture is then.  diluted with water, boiled for 15 minutes, then cooled to room temperature with acidified 6 and.  hydrochloric acid solution.  The precipitated product is then collected using filtration under vacuum and recrystallized from ethanol to give 2.5 g (35%) of pure spiro- (chroman-4,4-imidazolidine) -dione-2, 5, t.  GO1  236-238 ° C.  Calculated,%: C 64.38; H5.40; N6.83.  C, f N „MOz Found,%: C 64.18; H 6.38; N 6.83.  Example 20  The operations described in 1E in Example 20 are repeated except that instead of chromanone-4, 6-methoxychromanone-4 is used as the starting material using the same molar ratios.  In this particular case, the corresponding final product obtained is 6-methoxy-spiro- (chroman-4,4-imidazolidine) -dione-2.5, t.  square  170-172 ° C.  The yield of pure product is 32% of the theoretically possible.  Calculated,%: C 58.06; H 4.87; N 11.29 0 Found,%: C 58.04; H 4.98; N 11.17.  P r and m e 21.  The operations described in Example 19 are repeated except that instead of chromanone -4, 6-fluorochloromanone-4 is used as the starting material with the same mole ratios used.  In this particular case, the corresponding final product obtained is 6-fluoro-spiro- (chroman-4,4-imidazolidine) -dione-2.5, t.  square  239-241 ° C.  The yield of pure product is 36% of the theoretically possible.  Calculated,%: C 55.93; H 3.84; N 11.86 С “Found,%: С 55.54; H 3.88; N 12.12.  Example 22  The operations described in Example 19 are repeated, except for "instead of chromanone-4 as the original. the material used is 6,7-dichlorochromanone-4 using the previous molar ratios.  9 In this particular case, the corresponding food product of the final product is 6,7-di chloro-spiro- (chromium and 4,4-imndazolidine) -dione-2, 5, t.  square  263-265 ° C.  The net product yield is 8% of the theoretically possible. Calculated,%: C 46.02; H 2.81; N 9.76 С, 1 Hg CejNjOa Found,%: C 45.83; H 2.94; N 9.65.  Example 23  The operations described in Example 20 are repeated except that instead of chromanone-4, 6,8-dichlorochromanone-4 is used as the starting material using the previous molar ratios. In this particular case, the corresponding final product obtained is 6.8- dichloro-spiro- (chroman-4,4-imidazolidine) -dione-2, 5, t.  square  234-235 ° C.  The yield of pure product is 20% of the theoretically possible.  Calculated,%: C 46.02; H 2.81; N 9.76 c H Found,%: C 45.81; H 2.74; N 9, 69  .  Example 24  A mixture containing 4, 57 g (0.025 mol) of 6-chlorochromanone -4, 2.8 g (0.043 mol) of potassium cyanide and 9.6 g (0.1 mol) of poro-asbestos-like ammonium carbonate in 62.5 ml of 50% aqueous ethanol, heated to 60 ° C for 48 h.  The reaction mixture is cooled to room temperature (about 25 ° C), diluted with 3 ml of water, and then acidified with 6 and.  hydrochloric acid solution.  The precipitated precipitate is then collected using filtration under vacuum, after which it is recrystallized from ethanol to obtain 5.1 g (81%) of pure 6-chloro-spiro- (chroman-4,4 -Mylazolidine) -dione-2.5, t .  square  268-270 ° C.  Calculated,%: C, 52.29; H 3.59; N 11.09 C «9 5 Found: C 52.15; H 3.73; N 10.99.  Example 25  The operations described in Example 25 are repeated except that instead of 6-chlorochromanone-4, 5-methoxytetralone-1 is used as the starting material using the previous molar motions.  In this particular case, the corresponding final product obtained is C, 4-dihydro-5-methoxy-Shro- (imidazolidine-4, l (2H) naphthalene-dione-2.5, t.  square  243-243.5 ° C. Calculated,%: C, 63.40; H 5.73; f 11.38 Found: C 63.10; H 5.70; N 11.47.  Example 26  The operations described in example 25 are repeated, except that instead of 6-chlorochromanone-4, 8-chlorochromanone-4 is used as the starting material using the previous molar ratios. In this particular case, the corresponding final 5-10% of the final product is 8-chloro-spiro- (chroman-4,4-imidazolidine) -Dion-2, 5, t.  Ш1.  231-233 C.  The yield of pure product is 34% of the theoretically possible.  Calculated,%: C, 52.29; H: 3.59; N 11.09 Cy Hg CENgOj Found,%: C 52.21; H 3.74; N 11.12.  Example 27  The operations described in Example 25 are repeated except that instead of 6-chlorochromanone-4, 6-bromochromanone-4 is used as the starting material using the previous molar ratios at a reaction temperature of 55 ° C instead of 60 ° C.  In this particular case, the corresponding final product obtained is 6-bromo-spiro- (chroman-4,4-imidazolidine) -dione-2, 5.  The yield of pure product is 15% of the theoretically possible.  Example 28  To a solution of 1.09 g (Oj005 mol) of spiro- (chroman-4,4-imidazoin) dione-2, 5 (obtained by the method described in example 20) and.  10 g of ferric chloride in 6 ml of dry dimethylformamide cooled to (-40) ° C is added dropwise with constant stirring a solution containing 355 mg of chlorine dissolved in 4 ml of dry dimethylformamide.  The resulting reactive mixture was then kept at (-40) ° C for 30 minutes (with stirring), and then the temperature was gradually brought to room temperature (approximately 25 ° C).  After being kept at this temperature for 2.5 hours, the mixture is poured into 250 ml of ice-cold water, which results in precipitation, which is then collected using vacuum filtration and the precipitate is dried with air to constant weight.  Recrystallization of the product from glacial acetic acid (6 ml) yields 0.31 g (25%) of pure 6-chloro-spiro- (chroman-4, 4-imidazolidine) -dione-2.5, identical in any respect with the product obtained by the method of example 24.  Example 29  A mixture containing 252 mg (0.001 mol) of 6-fluoro-spiro- (imvdazolidin-4, 4thiochroman) -dione-2.5 (obtained by the method described in example 12) in 10 ml of dichloromethane, as well as 50 mg 40% - tetrabutylammonium hydroxide and 224 mg (0.01 mol) of sodium periodate in 5 ml of water, stirred at room temperature (approximately 25 ° C) for 1 h.  The precipitated precipitate is collected by filtering under vacuum, and then recrystallized from ethanol (3 MJ with the acquisition of 60 mg (22%) of 1-oxide-6; -fluorospiro- (imidazalidine-4,4-thiochroman) -dione-2.5 .  square  289-291С.  II74 Calculated,%: C 49.25; H 3.38; N 10.44 C / 1 H FNgOj Found;%; C 49.27; H 3.35; N 1035; Example 30  To a suspension of 0.595 g (0.00236 mol) of 6-fluoro-spiro- (imidazolidin-4,4-thiochroman) -dione-2.5 (obtained by the method described in example 18) in 50 ml of chloroform placed in a three-necked round-bottomed A 250 ml flask is added in small portions over 1 hour with 1.00 g (0.00579 mol) m-chlorobenzoic acid.  The resulting slurry is stirred at room temperature (about 25 ° C) for 36 hours and then diluted with 500 ml of ethyl acetate.  The resulting yellow organic layer is washed four times with 50 ml of saturated aqueous sodium bicarbonate solution, dried over anhydrous magnesium sulfate, filtered and part of the solvent is removed under vacuum.  0.50 g (74.5%) of crude 6-fluoro-spiro- (imidazolidin-4, 4-thiochroman) -dione-2,5-dioxin-2.5 is obtained in the form of white crystals.  Recrystallization from a mixture of ethanol, ethyl acetate, and n-hexane yields a pure product (t.  square  179-180 ° C with decomposition) in the form of the first portion of small white crystals (yield 0.295 g).  Additional recrystallization from ethanol / ethyl acetate helps to increase the melting point of the analytical sample to 184-196 ° C (with decomposition).  Calculated,%: C 47.55; H, 3.99; N 8.53 Ci, HgFN; Found: C, 47.54; H 3.93; N 8.56.  Example 31  The operations described in example 30 are repeated, except that 0.234 g (0.001 mol) of spiro- (imidazolidin-4,4-thiochroman) -dione-2.5 (prepared according to the procedure described in example 7) is reacted ) and 0.426 g (0.0027 mol) of m-chloroperbenzoic acid to obtain 0.20 g (75%) of pure 1, l-dioxide of spiro- (imidazolidin-4,4-thiochroman) -dione-2.5.  Recrystallization from a mixture of methanol, ethanol and n-hexane yields an analytical sample (t. square 280 28GS).  Calculated,%: C 49.61, H 3.78; N 10.52 H (jN504; Found: C 49.82; H 3.85; N 10.19.  PRI me R 32.  A mixture containing 1.0 g (0.00549 mol) of thioindandion-3 1,1-dioxide, 0613 g (0.0094 mol) of potassium cyanide and 21.9 (0.021 mol) of ammonium carbonate in 14 MP of 50% aqueous ethanol, placed in a 50 ml round bottom flask and heated for 48 hours under nitrogen.  The reaction mixture was then diluted with 70 ml of water, traces of solids were removed by filtration, and the filtrate was acidified with 6N.  hydrochloric acid solution.  The resulting precipitate is recovered by filtration and redissolved in 4N.  an aqueous solution of potassium hydroxide, and finally, again acidified with 6N.  hydrochloric acid solution.  The acidified solution containing the product is saturated with sodium chloride and then extracted with six portions of 150 ml of fresh ethyl acetate, the resulting organic layers are combined and dried over anhydrous sulfate.  After removing the drying agent by filtration and removing the organic solvent in vacuo, 0.50 g (36%) of pure spiro- (imidazolidin-3, 3-thioindane) -dione-2.5, t.  square  287 ° C (with decomposition) after two recrystallizations from a mixture of ethanol, ethyl acetate and n-hexane.  Calculated,%: C 47.61; H 3.20; N, 11.11. Found: C, 47.77; H 3.28, N 10.85.  Example 33  A mixture containing 2.75 g (0.01562 mol) of 6.8-dimethylchromanon-4, 3.5 g (0.0538 mol) of potassium cyanide and 10.5 g (0.109 mol) of ammonium carbonate in 60 ml of 50% - Aqueous ethanol was placed in a 125 ml round-bottomed flask heated with a 1B water bath at 65 ° C for 48 hours in a nitrogen atmosphere.  The reaction mixture is then cooled to room temperature (about 25 ° C) and filtered, and the resulting filtrate is then extracted with 50 ml of diethyl ether.  The resulting aqueous layer is then stored and then acidified to pH 2.0 3 n.  hydrochloric acid solution (if necessary; cooled).  The resulting turbid mixture is then extracted three times to 200 ml of ethyl acetate and the combined organic layers are re-extracted three times with 50 ml of 4N.  an aqueous solution of sodium hydroxide.  The combined basic aqueous layers are acidified again to pH 2.0 3 n.  hydrochloric acid solution in the same manner as shown above, and then saturated with sodium chloride, and then extracted three times with 200 ml of fresh ethyl acetate.  The combined organic layers were then dried over anhydrous magnesium sulphate and filtered.  After removing the solvent from the filtrate by evaporation under vacuum, 2.50 g (65%) 6.8 is obtained.  -dimethyl-spiro- (chroman-4,4-imidazolidine) -dione-2, 5, t.  square  185-190 C (with decomposition).  Recrystallization from aqueous ethanol yields an analytically pure material (t.  square  188--189 ° C).  Calculated,%: C, 63.40; H 5.73; N 11.38 ,, Found,%: C 63.05; H 5.69; N 1U3.  Example 34  When using the techniques described in the preceding examples, from easily accessible in each case, the material is 13 74179514
    The following spiro-hydatoin 7 (n-6-butyl) -spiro- (imidazolidin-44-tno
    compounds: chroman) -dion-2.5,
    b-chloro-spiro- (imidazolidin-4,1 -shadan) (n-butoxy) -saro- (imidazolidin-4,4-thio-dione-2, 5, chromai) -dione-2;
    b-bromo-spiro- (imidazolidnn-4,1-indan) - 5 b-isopropoxy-spiro- (imidazolidin-4,4-dione-2, 5, -thiochroman) -dione.-2,5,
    s -fluoro-spiro- (imidazolidin-4,1-indan) -dichloro-spiro- (imidazolidin-4,4-thio-dione-2, 5, chroman) -dione-2,5,
    5-methyl-spiro- (imidazolidin-4,1-indan) -6, -dimethyl-spiro- (imidazolidin-4,4 dione-2, 5, fO thiochroman) -dione-2.5,
    b- (n-butyl) -spiro- (imidazolidin-4, 1 -indane) -b, (n-butyl) -spiro- (nmidazolidin-dion-2, 5, -4,4-thiochroman) -dione-2 ,five,
    5 - hydroxy-spiro- (and shdazolidin-4,1-indan) -b, 7-dkmethoxy-spiro- (imvdazolidnn-4,4-dione-2, 5, -thiochroman) -dione-2,5,
    b-ethoxy-spiro- (imidazolidin-4, l-indan) - is b, 7-diethoxn-spiro (imidazolidin-4,4-dione-2, 5, -thiochroman) -dione-2,5,
    5 - (n-butoxy) -spiro- (imidazolidin-4,1-yn-6, 8-di- (n-butoxy) -spiro- (imidazolidindan) -dione-2,5, 4,4-thiochroman) - Dion-2,5,
    5 b-dichloro-spiro- (imidazolidin-4,1 -indan) -6, 7-methylenedioxy-spiro- (imidazolidin-dione-2, 5, 20-4,4-thiochroman) -dnon-2.5,
    5,6-dimethyl-spiro- (imidazolidin-4,1-indan) -6, 7-ethylenedioxy-spiro- (imidazolidine dion-2.5, -4.4-thiochroman) dione-2.5,
    5, 6-di- (n-propyl) -spiro- (imidazolidin-1-spiro- (imidazolidin-4,4-thiochro-4, 1 -indane) -dione-2.5, man) -dione-2 oxide ,five,
    5, b-di- (n-propoxy) -spiro- (imidazolidin-251-oxide-8-chloro-spiro- (imidazolidin-4,4 4, 1 -indane) -dione-2.5, -thiochroman) - Dione-2.5,
    5, b-ethylenedioxy-spiro- (imidazolidin-1-oxide-b-bromo-spiro- (nmidazolidin-4,4-4, 1 -indane) -dione-2,5, thiochroman) -dione-2,5,
    8-bromo-spiro- (chroman-4,4-imidazolidine) -,
    -dione-2, 5, 301-oxide-6-methyl-spiro- (imidazolidin-4,4 6- (n-butyl) -spiro (chroman-4,4 -imvdazolidine) -thiochroman) -dione-2,5 ,
    -dione-2,5,1-oxide-7- (n-butyl) -spiro- (imidazolidin-7-methyl-spiro- (chroman-4,4 -imidazolidin) - 4,4-thiochroman) -dione-2, five,
    .dione-2, 5,1-oxide-b-methoxy-sgcro- (imidazolidin6-oxy-spiro- (chroman-4,4 -imidazolidine) -, - 4 4 -thiochroman) -dione-2,5,
    -dione-2, 5, 1-oxide -7- (n-butoxy) -spiro- (imidazol6-ethoxy-cshfo- (chroman-4,4-imidazolidin) -din-4,4-thiochroman) -dione-2 ,five,
    -dione-2, 5, l-oxide-6,7-dichloro-spiro- (imidazolidin6- (n-butoxy) -spiro- (chroman-4,4 -imidazo-4,4-thiochroman) -dione-2, five,
    Lidin) -dione-2, 5, 401-oxide-6, b-dimethyl-spiro- (imidazolidin7-isopropoxy-spiro- (chroman-4,4-imidazo-4,4-tichroman) -dione-2, five.
    din) -dione- 2, 5,1-oxide-6, 8 -di- (n-butyl) -spiro- (imidazo,
    6,8-di- (n-butyl) -spiro- (chroman-4,4-imidazolidin-4,4-thiochroman) -dione-2.5,
    lkdin) -Dion-2, 5,1-oxide-6, 7-dimethoxy-spiro- (imvdazoli 6 | 7-dimethoxy-cshfo- (chroman-4,4-imndazoli- jdin-4,4-thiochroman) -dione- 2,5, din) -dione-2, 5,1-oxide-b, 7-diethoxy-spiro-l (imidazolidine 6, 8-di- (n-butoxy) -cryptro (chrome-4,4-imidazo- -4,4-thiochroman) -dione-2,5, lidin) -dione-2, 5, I-oKHCb-6, 8-di-. (N-butoxy) -spiro- (imidazo6, 7-ethylenedioxy-spnro - (chroman-4,4-imidazol-din) - (4,4-taochroman) -dione-2.5,
    Lidin) -dione-2, 5, 501-oxide-b J-methylenedioxy-spiro- (imidazo-8-fluoro-cshfo- (nmidazolidin-4,4-thiochroman) -lidane-4,4-thiochroman) -dione-2, five,
    -dione-2,5 -1-oxide-6, 7 -zetilenedioxy-spiro- (imidazoli7 -bromo-spiro- (imidazolidin-4,4-thiochroman) -Ij -dvuox-8-chloro-spiro- (imidazolidine-dione -2, 5, -thiochroman) -dione-2.5,
    6-hydroxy-cshfo- (nmidazolidin-4,4-thiochroman) -1., 1 -two-6-methyl-spiro- (midazolidine-dione-2, 5,.-4,4-thiochroman) -dione-2 ,five,
    6-methyl-spiro- (imndazolidin-4,4-thnochroman) -. 1, 1-dioxide-7- (n-butyl) -sgofo- (imidvzo
    权利要求:
    Claims (3)
    [1]
    -dione-2.5, lidin-4,4 -thiochroman) dione-2.5. DN-4,4-thiochroman) -dione-2,5, 157 G, l-dvuoxis-b-methoxy-spiro- (imvdazolidin-4, 4-thiochroman) -dione-2,5, 1, 1 -two-oxide - 7 - (n-butoxy) -spiro- (imidazolidin-4, 4-thiochroman) -dione-2,5, l, l-dioxide 6,7-dichloropropio-p-(imidazo / lidin-4,4-thiochroman) -dione-2,5, 1, 1-dioxide -b, 7 -dimethyl-spiro- (imidazolidin-4, 4 -thiochroman) -dione-2,5, l, l -dvuox b, 7, - dimethoxch-spiro - (imidazolidin-4, 4-thiochroman) -dione-2,5, 1, l-dioxide b, 7 -diethoxy-CIspo- (imide zolidin-4,4-thiochroman) -dione-2,5, 1, 1 - dvuoxis-b, 8 -di- (n-butoxy) -spiro - (imidazopidin-4,4-thiochroman) -dione-2,5, 1, l-dioxide b, 7-methylenedioxy-spiro- (imide zlidine-4,4-thiochroman) -dione-2,5, l, 1 -dvuoxis-b, 7-ethylenedioxy-spiro- (imidazolidin-4,4 -thiochroman) -dione-2,5, 1,1 -two oxide Spiro- (imidazolidin-4,4-iso-thiochroman) -daone; 2,5, 3,4-dihydro-7-fluoro-spiro- (imidazolidin4, 1 G2H) -naphthalene / -dione-2,5, 3, 4-dihydro-7-chloro-spiro- (imidazolidin-4, l (2H) naphthalene / -dione-2.5, 3, 4-dihydro-b-bromo-spiro- / imidazolides -4.1 (2H ) naphthalene / -dione-2,5, 3, 4-dihydro-5-isopropyl-CIshpo- / imidazo-dn-4, l - (2H) naphthalene / -dion-2,5, З, 4-dihydro-6 - methyl spiro- / imidazolidine -4.1 (2H) naphthalene / -dione-2.5, 3, 4 -dihydr6-7 - (n-butyl) -spiro- / ymidazolium-4,1- (2H) naphthalene / -dione-2.5, 3, 4-dihyd ro-5-oxy-spiro- / imidazolidin4, l (2H) naphthalene / -dione-2,5, 3, 4 -dihydro-5-toxo-spiro- / imidazolidin-4, 1 (2H) naphthalene / -dione- 2,5, 3, 4-dihydro-7 - (n-butoxy) -spiro- / imidazo lndin-4,1 - (2H) naphthalene / -dione-2,5, З, 4-dihydro-b, 7- dichloro-spiro- / imidazolidin-4, 1 (2 H) naphthalene / -dione-2,5, З, 4 -dihydro-6, 7 -dizthyl-1-thro / imidazolidin-4, 1 (2H) naphthalene / -dione -2,5, 3, 4 -dihydro-6, 7-dimethoxy-spiro- / imidazole-4, 1- (2H) naphthapine / -dione-2,5, 3,4 -dihydro-6,7 -di- (n-Propoxy) -c1shro / nmidazolidin-4, 1 (LH) naphthalene / -dione-2,5, 3, 4 -digkdro-6, 7 -methylenedioxy-spiro- / Idazolide Iffl-4, l (2 N ) naphthalene / -dione-2.5, 3, 4-dig1gdro-6, 7-ethyl dihydroxy-spiro / imidazolidin-4 1 (2 H) -naphthalene /-2,5 -dione, 6, 7-dihydro-s1Shro- / imidazolidine-4,5 (5H) pyridine / 2.5-dione. Example35. The sodium salt of 6-fluorocroipo- (chroman-4,4-imidazolidine) -diot-2.5 is obtained by dissolving the indicated compound in water containing an equimolar amount of sodium hydroxide, after which the mixture is dried. As a result, the target alkali metal salt of hydantoin is obtained in the form of an amorphous powder, readily soluble in water. Similarly, the potassium and lithium salts, as well as the alkali metal salts of all the other spirogandantoin compounds of the invention, which are reported respectively in Examples 1-21 and 23-35, can be easily obtained. Example. 36. The 6-fluoro-spiro- (chroman-4,4-imidazolidine) -dione-2, 5 salt of calcium is obtained by dissolving the indicated compound in water containing an equimolar amount of hydrochloride hydroxide, after which the lyophilic essence of the mixture is performed. Magnesium salt is obtained in a similar way, as well as all other salts of not only the indicated compound with alkaline earth metals, but also other spirohydantoin compounds, which are reported to be corresponding. in examples 1-21 and 23-35. Claims 1. Method for producing spirohydantoin compounds of general formula O: A-group A of formula W — a group of formula (CH2) p; Xj is hydrogen; X2-fluorine, hydroxy- or 6-lower alkoxy, Xj and Xj, taken separately, lower alkoxy groups, and taken together - a group of the formula -OGH2 (CH2) nO-: Xs is hydrogen; X4 - fluorine, chlorine or bromine, or Xs and X4, taken separately; chlorine atoms, taken together form a group of the formula -OCH2 (CH,) n0-; Xj is hydrogen; Hb is fluoro, hydroxy or зша alkoxy; or Xj and Xg, taken separately, chlorine atoms are wide alkoxy groups, and together a group of the formula -OGH2 (CH2) nO; XT is hydrogen; Xg — fluorine, chlorine, bromine or lower alko-group, or X and Xd, taken separately, hydrogen, chlorine or lower alkoxy groups, and taken together the group of the formula OCH2 (CH2) Y Y is an oxygen or sulfur atom; Q is a group of the formula -SO- or S02; p O or 1, or their salts, characterized in that the compound of the formula where A has the indicated values, is reacted with the metal alkali metal carbonate and ammonium carbonate and the desired product is isolated, where Y is a sulfur atom, in the case when A has the formula T , the resulting product is oxidized, in the case when X2 Xg is alkoxy, the resulting compound is converted to a compound, where X2 and Xg are hydroxy groups, to release the desired product in free form or as a salt.
    [2]
    2. A method according to claim 1, characterized in that the process is carried out in an environment of a solvent inert under the reaction conditions, at 20-120 ° C.
    [3]
    3. The method according to PPL and 2, characterized in that the solvent used is a cyclic ether. Sources of information accepted into the examination under examination 1. Elderfield R. Heterocyclic compounds, M., Izd. I.L., 1961, p. 205.
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    同族专利:
    公开号 | 公开日
    PL108339B1|1980-04-30|
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    BE859824A|1978-04-17|
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    CS199690B2|1980-07-31|
    IN147056B|1979-10-27|
    ZA775907B|1978-05-30|
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    法律状态:
    优先权:
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    US73306276A| true| 1976-10-18|1976-10-18|
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