CH490414A - Process for the preparation of an imidazole derivative - Google Patents

Description

  

  Process for the preparation of an imidazole derivative The invention relates to a process for the preparation of 1- (2 ', 3'-epoxypropyl) -2-nitro-imidazole of the formula
EMI0001.0000
    and of acid addition salts of the compound of the formula I, characterized in that a compound of the formula
EMI0001.0001
    where X1 is halogen or a removable sulfonyloxy group, or a salt of such a compound is treated with alkali metal hydroxide. The reaction product, if it is obtained as a base, can also be converted into acid addition salts.



  The compound of formula II used as starting material can be, for. B. be prepared by reacting 2-nitroimidazole with a corresponding 1,2-epoxy-3-substituted-propane.



  If the substituent X1 of compounds of the formula II is a sulfonyloxy group (such as the tosyloxy, mesyloxy or phenylsulfonyloxy group), this group is converted to 1- (2 ', 3'-epoxypropyl) -2-nitro- cleaved imidazole.



  The cleavage can preferably be carried out with an aqueous alkali metal hydroxide, e.g. B. aqueous sodium hydroxide, are carried out. Compounds of the formula II in which X1 is a halogen atom can, if desired, be subjected to the dehydrohalogenation under the same reaction conditions, with 1- (2 ', 3'-epoxypropyl) -2-nitroimidazole likewise forming.



  The obtained by the inventive method Liche compound as well as its acid addition salts are effective against bacteria, pathogenic yeasts and protozoa and can be used accordingly, z. B. for the treatment of infections caused by Trichomonas vaginalis or Histomonas malegradis. 1- (2 ', 3'-epoxypropyl) -2-nitro-imidazole is characterized by no particularly high activity against Trichomonas vaginalis.



  The products can be used as remedies in the form of pharmaceutical preparations which they contain as a mixture with a pharmaceutical, organic or inorganic inert carrier material suitable for enteral or parenteral administration. The pharmaceutical preparations can be in solid form or in liquid form. If necessary, they contain auxiliaries such as preservatives, stabilizers, wetting agents or emulsifiers, salts for changing the osmotic pressure or buffers. They can also contain other therapeutically valuable substances. In the following example, the temperatures are given in degrees Celsius.



       Example 250 ml of a 10% strength aqueous sodium hydroxide solution are stirred at room temperature, and 38.13 g of finely powdered 1- (2'-nitro-1'-imidazolyl) -3-chloro-2-propanol are added. Solution occurs in 1-2 minutes and a new crystalline precipitate forms after 2-3 minutes. The mixture is stirred for 5-15 minutes at room temperature and then cooled in a dry rice bath until it begins to freeze.

   Then the mixture is filtered. The solid substance is washed with 40 ml of ice-cold water, slurried in 50 ml of ice-cold, distilled water, filtered again, washed twice with 40 ml of ice-cold water each time and finally dried. The pale yellow crystalline substance melts at 53-55. The combined filtrates (including washing liquids) are extracted twice with 600 ml of chloroform each time and the chloroform is evaporated at room temperature.

   The crystalline residue obtained is dissolved in 50 ml of distilled water at 60, the solution is treated with animal charcoal, and the filtrate is cooled. The 1- (2 ', 3'-epoxypropyl) -2-nitro-imidazole obtained melts at 53.5-55. The 1- (2'-nitro-1'-imidazolyl) -3-chloro-2-propanol used as starting material can be obtained as follows: A mixture containing 52.3 g of powdered, sublimed 2-nitro-imidazole, 315 ml of epichlorohydrin and 5.25 g of anhydrous potassium carbonate are heated with stirring. The mixture is kept boiling briskly for 10 minutes and then filtered. The insoluble material is washed with boiling ethanol. 65.3 g of crude product are obtained from the cooled filtrate.

    After recrystallization of this crude product from 1100 ml of boiling ethanol, 59.1 g of yellow crystals with a melting point of 156-158 are obtained. The epichlorohydrin filtrate is evaporated to dryness and the resulting 12.5 g of solid substance is recrystallized from ethanol with the addition of animal charcoal. The ethanol filtrates obtained from the recrystallization of the crude product are evaporated to dryness and the residue is recrystallized using animal charcoal. Yellow crystalline 1- (2'-nitro-1'-imidazolyl) -3-chloro-2-propanol with a melting point of 156-158 is obtained in this way.

 

Claims (1)

PATENT CLAIM Process for the preparation of 1- (2 ', 3'-epoxypropyl) -2-nitro-imidazole of the formula EMI0002.0029 characterized in that a compound of the formula II g i EMI0002.0030 where X1 is halogen or a removable sulfonyloxy group, or a salt of such a compound is treated with alkali metal hydroxide. SUBClaims 1. Process according to claim, characterized in that the compound of formula I obtained is converted into an acid addition salt. 2. Method according to claim and sub-claim 1, characterized in that a 1- (2'-nitro-1'-imidazolyl) -3-halo-2-propanol with aqueous alkali metal hydroxide in 1- (2 ', 3' -Epoxypropyl) - 2- nitro-imidazole transferred. 3. The method according to claim and the subordinate claims 1 and 2, characterized in that 1- (2-nitro-1'-imidazolyl) -3-chloro-2-propanol by splitting off hydrogen chloride in 1- (2 ', 3'-epoxypropyl) - 2-nitro-imidazole transferred.