CH467743A - Process for the preparation of dibenzocycloheptenes - Google Patents

Description

  

  
 



  Process for the preparation of dibenzocycloheptenes
The present invention relates to a process for the preparation of new 5H-dibenzo (a, d) cycloheptenes and 10,11-dihydro-5H-dibenzo (a, d) cycloheptenes and their salts, soft on the carbon of the 5-position are substituted by an aminopropyl radical.



     These compounds can be used to treat gel disease, because they are effective as a remedy for states of depression or to cheer up the mind and as a psychic energy donor. For such cases, the daily dose can be 5 to 250 mg, which is preferably taken in divided doses. These compounds are preferably administered in the form of their salts obtainable with acids.



   The dibenzocycloheptenes which can be prepared by the process according to the invention have the following formula
EMI1.1
 wherein X and X 'are hydrogen; an alkyl group or an alkenyl group of up to 6 carbon atoms; a perfluoroalkyl group with ibis of 4 carbon atoms; a phenyl or substituted phenyl radical, an acyl group, or a perfluoroacyl group of up to 4 carbon atoms; an amino group, an alkylamino group with up to 4 carbon atoms; a dialkylamino group with up to 6 ohienstoffatomen; ; an acylamino group or a perfluoroacylamino group or an alkylsulfonylamino group having up to 4 carbon atoms;

   Halogen; Hydroxyl; an alkoxy group or a perfluoroalkoxy group having up to 4 carbon atoms; Cyan; Carboxy; Carbamyl; an alkylcarbamyl group of up to 5 carbon atoms; a dialkyl oarbamyl group of up to 9 carbon atoms; a carbalkoxy group of up to 6 carbon atoms; Mercapto or an alkyl mercapto group or an alkylsulfonyl group or a perfluoroalkylsulfonyl group with up to 4 carbon atoms; Sulfamyl; an alkylsulfamyl group of up to 4 carbon atoms; or a dialkylsulfamyl group with up to 6 carbon atoms and R an alkyl group with up to 6 carbon atoms.



   The dotted line between positions 10 and 11 means that the compounds at this point can be saturated or unsaturated, the saturated compound being referred to as the 10,11-dihydro compound.



   The process according to the invention for the preparation of dibenzocycloheptenes of the formula given is only characterized in that a compound of the formula
EMI1.2
 with an alkylbenzylamine in absolute alcohol to react, with a compound of the formula
EMI1.3
 arises, whereupon this compound is hydrogenated in the presence of palladium and hydrogen.



   When the secondary amine is obtained by catalytic debenzylation of the corresponding addition compound, the following procedure can be used, for example: The iodine compound is allowed to react slowly with an N-alkylbenzylamine so that there is no significant increase in temperature above room temperature, with abs. Alcohol is used.



  The reaction mixture is then refluxed for 15 to 60 minutes and the solvent is evaporated. By hydrogenation with the aid of hydrogen and palladium as a catalyst, a selective debenzylation takes place, the corresponding secondary amine being obtained.



   The free base can easily be converted into an acid addition salt, e.g. B. in the oxalate. Here you can proceed in such a way that one in warm abs. Ethanol-dissolved base is reacted with an equimolar amount of oxalic acid dissolved in ethanol. The acid salt formed is precipitated by adding ether and then recrystallized from a methanol-ethyl acetate mixture.



   The preparation of the 3-jo'dpropyl starting material from the corresponding alkoxypropyl compound with hydrogen iodide is described in more detail in Swiss Patent No. 464,900.



   example 1
Preparation of 5- (3-ethylaminopropyl) -5H-dib enzo (a, d) cycloheptene
1. Gradually add 5- (3-iodopropyl) -5H diblenzo- (a, d) cycloheptene to an excess of N-ethylbenzylamine in abs. Add alcohol with stirring and cooling.



  The reaction mixture is then heated to the rüdkfiuss for 30 minutes and the alcohol is then evaporated off under reduced pressure. The residue is taken up in warm, dilute acid, filtered, the aqueous layer is made alkaline and the liberated base is extracted with ether. Evaporation of the ether leaves 5- (3- [N-benzyl-N-ethylamino] propyl) -5Hdibenzo (a, d) cycloheptene.



   2. The product thus obtained is dissolved in abs. Alcohol and hydrogenated by means of a palladium-alumina catalyst at 40-60 ° C. The desired product is obtained as the residue after separation from the catalyst and evaporation of the solvent.



   Example 2
If the 10,1 1-dihydro compound is used as the starting material in accordance with the method according to Example 1, the corresponding 10,11-dihydro derivative is obtained as the end product, namely 10,11-dihydro-5- (3-ethylaminopropyl) -dibenzo (a , d) cycloheptene.

 

Claims (1)

PATENT CLAIM Process for the preparation of a compound of the formula EMI2.1 and their salts, wherein X and X 'are hydrogen; an alkyl group or an alkenyl group of up to 6 carbon atoms; a perfluoroalkyl group of up to 4 carbon atoms; a phenyl or substituted phenyl radical, an acyl group or a perfluoroacyl group with up to 4 carbon atoms; an amino group, an alkylamino group of up to 4 carbon atoms; a dialkylamino group of up to 6 carbon atoms; an acylamino group or a perfluoroacylamino group or an alkylsulfonylamino group with up to 4 carbon atoms; Halogen, hydroxyl; an alkoxy group or a perfluoroalkoxy group having up to 4 carbon atoms; Cyan; Carboxy; Carbamyl; an alkyicarbamyl group of up to 5 carbon atoms; a dialkylcarbamyl group of up to 9 carbon atoms; a carbalkoxy group of up to 6 carbon atoms; Mercapto or an alkyl mercapto group or an alkylsulfonyl group or a perfluoroalkylsulfonyl group with up to 4 carbon atoms; Sulfamyl; an alkylsulfamyl group with up to 4 carbon atoms or a dialkylsulfamyl group with up to 6 carbon atoms and R denotes an alkyl group with up to 6 carbon atoms, characterized in that a compound of the formula EMI2.2 with an alkylbenzylamine in absolute alcohol to react, a compound of the formula EMI2.3 is obtained, whereupon this compound is hydrogenated in the presence of palladium and hydrogen.