CH498135A - Pharmaceutical furazan derivs prodn - Google Patents

Abstract

Pharmaceutical furazan derivs. prodn. Compounds possessing depressant, anticonvulsive and muscle-relaxing properties have formula: (in which R1 is H or a lower alkyl, and R2 is a lower alkyl in the m- or o-position). These compounds are produced by boiling in a strong mineral acid a compound of formula: (where R3 is a lower alkyl).

Description

  

  
 



  Process for the production of new furazan derivatives
The invention relates to a process for the preparation of new Furazauderivate.



   Compounds of general formula I,
EMI1.1
 in which Rt is hydrogen or a lower alkyl group and R2 is a lower alkyl group which is in the o or m position, have not yet become known.



   As has now been found, these compounds have valuable pharmacological properties. They have a central damping, anticonvulsant and muscle relaxant effect.



   The new compounds of general formula I can be used to calm weak states of excitement and to relieve muscle stiffness, e.g. B. in rheumatic diseases, fibrositis, bursitis, myositis, spondylitis, discopathies and torticollis can be used.



   In the compounds of general formula I, Rt and R2 can be, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec. Butyl, tert. Butyl, pentyl, isopentyl or the 2,2-dimethylpropyl groups, R1 can take the o-, m- or p-position.



   Furazan derivatives of the general formula 1 are prepared by adding a compound of the general formula II,
EMI1.2
 in which Rt and R2 have the meaning given under the general formula I and R3 is a lower alkyl radical, converted to a compound of the general formula 1 by boiling with a strong mineral acid.



   Starting compounds of the general formula II can be prepared by starting with phenylglyoximes substituted in the benzene nucleus according to the definition for Rt and R2. These phenylglyoximes are halogenated in the 2-position using chlorine or bromine. The halogenated compound can then be reacted with ammonia to give the corresponding 2-aminophenylglyoxime. By acylating this substance with a carboxylic acid anhydride or halide, the O, O-diacyl-2-aminophenylglyoxy (ss-isomer) is obtained -Phenyl-5-alkyl-1-oxa-2,4-diazole of the general formula II.



   The new active ingredients can be administered orally, rectally or parenterally. The daily doses range between 56,000 mg.



   The following example explains the preparation of the new compounds of the general formula I and of intermediates not previously described, but is not intended to restrict the scope of the invention in any way. The temperatures are given in degrees Celsius.



   example
2.6 g of 2- (oWTo1yl) -5-methyl-1-oxa-2,4-diazol-exim are suspended in 65 ml of 6N hydrochloric acid and the suspension is refluxed for 1 hour. After half an hour, the crystals have melted into an oil. It is cooled and the mixture is extracted with ether. The organic phase is separated off, dried with sodium sulphate and evaporated. Crystals remain and are recrystallized four times in benzene. This gives pure 3-amino-4- (o-tolyl) furazan with a melting point of 86-880 C.



   The 3-amino-4- (3,4-xylyl) furazan obtained in an analogous manner melts at 111-1130.



   The mother liquor is evaporated and the residue is recrystallized several times in isopropanol, some 2- (p-chlorobenzoyl) -5-methyl-1-oxa-2,4-diazole with a melting point of 107-1090 ° C. being recovered.



   The starting material is prepared as follows: a) Chlorine gas is blown through a solution of 33 g of o-tolyl in 250 ml of vinegar with stirring over a period of 45 minutes until 12.9 g of chlorine are absorbed. It is cooled with ice water to keep the temperature below 25 ° C. The solution is then stirred for 4 hours at room temperature, a crystalline white product precipitating out. The suspension is evaporated to a third, cooled well and filtered.



  The o-tolyl-chloro-glyoxime obtained is purified by boiling with chloroform.



   The o-tolyl-chloro-glyoxime is represented analogously.



     b) A solution of 18.0 g of o-tolylchloro-glyoxime in 600 ml of ether is mixed with 30 ml of conc. Ammonia solution. The emulsion obtained is stirred for 11/2 hours at room temperature. The organic phase is then washed several times with water and evaporated. The crystals obtained are recrystallized from benzene and a little methanol. Aminoo-tolyl-glyoxime (p-isomer) is obtained.



   c) 7.0 g of β-amino- (o-tolyl) -glyoxime are dissolved in 50 ml of acetic anhydride. Then 1 g of anhydrous sodium acetate is added and the mixture is left to stand for 11/2 hours at room temperature. Finally, the acetic anhydride is evaporated in vacuo at 600 and the residue is dissolved in hot benzene.

 

  The undissolved sodium acetate is filtered off and the diacetate is crystallized from the β-amino- (o-tolyl) -glyoxime by adding cyclohexane and cooling.



  Pure diacetate is obtained in this way.



   d) 7.7 g of the diacetate obtained according to c are suspended in 100 ml of 200% sodium hydroxide solution. The mixture is heated to about 800 ° C. in a water bath while stirring, and everything goes into solution. Then it is cooled and the solution is acidified with conc. Hydrochloric acid. The precipitated crystals are filtered off, washed with water and recrystallized from acetone and methanol. Pure 3- (o-tolyl) -5 methyl-1-oxa-2,4-diazole oxime is obtained in this way.

 

Claims (1)

PATENT CLAIM Process for the preparation of new furazan derivatives of the general formula 1, EMI2.1 in which R1 is hydrogen or a lower alkyl group and R2 is a lower alkyl group which is in the o or m position, characterized in that a compound of the general formula II, EMI2.2 in which R1 and R2 have the meaning given in claim 1 under formula 1 and R5 is a lower alkyl group, converted to a compound of general formula 1 by boiling in a strong mineral acid.