CH507237A - Indoles prepd from indole-2 3 3 4-dihydrothiophens - Google Patents

Abstract

(A) Indole derivs. (I) R1=H, halogen, OH, alkyl, alkoxy, NH2, alkyl/acylamino; R2,3=H, alkyl R4=H, halogen, NH2, OH, alkyl (B) Intermediates of formula (II), below (I) have anti-inflammatory and antipyretic props. (a) A mixture of N'-(p-methoxyphenyl)-N'-(p-chlorobenzoyl)hydrazine. HCl (3.2 g), 4-thio-phenone-2-carboxylic acid (2g) and AcOH (15 ml) is heated at 80 deg. for 3 hr. to give (N-(p-chloro-benzoyl)-5-methoxy)indole-2,3:3', 4'-(2'-carboxy)-dihydrothiophen, crystd. from t-BuOH. (b) This (3 g) is gently refluxed with a suspn. of Raney Ni (30 g) in EtOH (500 ml) for 4 hr. to give N-(p-chlorobenzoyl)-5-methoxy-2-methyl -3-indolyl acetic acid, m.p 151 deg. (t-BuOH).

Description

  

  
 



  Process for the preparation of indole derivatives
The present invention relates to a new process for the preparation of indole derivatives of the general formula
EMI1.1
 wherein Rl is hydrogen, halogen, a hydroxy, an alkoxy, an amino, alkylamino or an acylamino group, R2 is hydrogen or an alkyl group, R3 is hydrogen or an alkyl group and R4 is hydrogen, halogen, an amino, hydroxy or an alkyl group is.



  These 2-methyl-indole derivatives of the above formula I produced according to the invention have anti-inflammatory and antipyretic properties.



   According to the invention, the compounds of the above formula I are produced in this way that indole-2,3: 3 ', 4'-dihydrothiophene derivatives of the general formula
II
EMI1.2
 catalytically reduced with hydrogen.



   Said reduction with the aid of hydrogen is advantageously carried out with Raney nickel in alcohol in a water-alcohol mixture or in an aqueous sodium bicarbonate solution, preferably at room temperature or at reflux temperature.



   The compounds of the general formula II used as starting materials can be prepared by the following reaction.
EMI1.3
  
EMI2.1




   The method according to the invention described above is explained in more detail below by means of an example.



   Example
3 g of [n- (p-chlorobenzoyl) -5-methoxy] -indole-2,3: 3 ', 4'- ·' -carboxy) .dihydrothiophene were added to a suspension of 30 g of Raney nickel in 500 ml of ethanol and that The mixture was heated gently for 4 hours at the boil: this leads to a reduction process which is attributable to the hydrogen that is found adsorbed on the surface of the catalyst.



   After cooling, the reaction mixture is filtered.



  The clear solution is concentrated to dryness in vacuo. The residue is crystallized from tert-butanol and pure N- (p-chlorobenzoyl) -5-methoxy-2-methyl-3-indolylacetic acid is obtained, with an F of 151 cd.

 

   Similarly, N-benzoyl-5-methoxy-2-methyl-3-indolylacetic acid with F = 172-1730C and N- (p-chlorobenzoyl) -5-methoxy-2-methyl-3-indolyl-, sc-pro - pionic acid, with F = 87 - 88 C.



   The dihydrothiophene used as a starting material can be prepared in the following ways:
3.2 g of N '- (p-methoxyphenyl) -N' - (p-chlorobenzoyl) hydrazine hydrochloride and 2 g of 4-thiophanone-2-carboxylic acid in 15 ml of acetic acid were heated with stirring at 80 ° C. for 3 hours. After cooling to room temperature, the mixture was poured into 50 ml of water. The crystals formed were filtered and dried in vacuo at 60.degree. The crude [N- (p-chlorobenzoyl) .5.methoxy] -indole-2,3: 3 ', 4' - (2'-carboxy) -dihydrothiophene obtained in this way is then recrystallized from tert-butanol.

 

Claims (1)

PATENT CLAIM Process for the preparation of indole derivatives of the formula EMI2.2 wherein R1 is hydrogen, halogen or a hydroxy, alkyl, alkoxy, amino, alkylamino or acylamino group, R2 is hydrogen or an alkyl group, R3 is hydrogen or an alkyl group and R4 is hydrogen, halogen or a hydroxy, amino or alkyl group , characterized in that indole-2,3: 3,4-dihydrothiophene derivatives of the formula II EMI2.3 catalytically reduced with hydrogen.