CH407128A - Process for the preparation of new iminodibenzyl derivatives - Google Patents

Description

  

  Process for the preparation of new iminodibenzyl derivatives The present invention relates to a process for the preparation of new N-heterocyclic ones. Compounds with valuable pharmacological properties.



  Iminodibenzyl derivatives substituted in a benzene ring by a disubstituted sulfamoyl radical have not yet become known. It has now been found, surprisingly, that such compounds of the formula I
EMI0001.0008
    in which R1 and R2 are lower alkyl radicals, which can be linked directly or via an oxygen atom,

   Z is a straight-chain or branched alkylene radical with 2-6 carbon atoms and Am is a lower alkylamino or dialkylamino group, both alkyl radicals of a dialkylamino group Am, directly or via an oxygen atom, an imino group, a lower alkyl imino,

          Hydroxyalkylimino or alkanoyloxyalkyl imino group connected. can be, have valuable pharmacological properties, in particular anti-allergic, anti-emetic and sedative effectiveness, as well as the effect of other drugs, especially narcotics, potentiate.



  In the compounds of the formula I, R and R2 are embodied, for example, by methyl, ethyl, n-propyl or n-butyl radicals or, together with the adjacent nitrogen atom, form e.g. B. the 1-pyrrolidinyl, piperidino or 4-morpholinyl radical.



  Z is, for example, an ethylene, propylene, trimethylene, 1-methyl-trimethylene, 2-methyl-trimethylene, 1,3-dimethyl-trimethylene, 2,2-dimethyl-trimethylene, tetramethylene, pentamethylene or hexamethylene radical , and On z.

   B. a methylamino, ethylamino, n-propylamino, isopropylamino, n-butylamino, dimethylamino, methyl-ethylamino, diethylamino, methyl-n-propylamino, methyl-isopropylamino, di-n-butylamino -, di-isobutylamino, 1-pyrrolidinyl, piperidino, hexamethyleneimino, 4 morpholinyl,

          1-piperazinyl, 4-methyl, 1-piperazinyl-, 4-isopropyl-1-piperazinyl-, 4- (ss-hydroxyethyl) -1-piperazinyl-, 4- (ss-acetoxyethyl) -1-piperazinyl- or 4; B. Hydroxypropyl 1-piperazinyl radical.



  The new compounds of the formula I are prepared according to the invention by adding a reactive ester of a compound of the formula 1I,
EMI0001.0081
    in particular a halide, such as, for example, a chloride or bromide, or also a p-toluenesulfonic acid ester, with an amine of the formula III Am —H (11I). The reaction can, for example, at a moderately high temperature of, for.

   B. 60-120 in an inert solvent, such as. B. a low molecular alkanol or alkanone, it is useful to use an excess of the amine to be reacted as an acid-binding agent. Depending on the boiling point of the amine used and the solvent and the required reaction temperature, the reaction may have to be carried out in a closed vessel.



  Reactive esters of compounds of the formula 1I are obtained, for example, by reacting alkali metal derivatives of suitable 3-sulfamoyl-iminodibenzylene, the sulfamoyl radical of which is disubstituted, with alkylene oxides and reacting the hydroxyalkyl derivatives obtained with inorganic acid halides, mothanesulfonic acid chloride or aryl sulfonic acid chlorides,

      5-haloalkyl-, 5-methanesulfonyloxyalkyl- or 5-arylsulfonyloxyalkyl-3-sulfamoyl-imino-dibenzyls disubstituted in the sulfamoyl group are obtained.

   Such compounds can, however, also be obtained in one step by reacting alkali metal compounds of 3-dialkylsulfamoyl-iminodibenzylene with nongeminal dihaloalkanes, in particular those having two different halogen atoms, or with arylsulphonic acid haloalkyl esters.

   The reactive esters of compounds of the formula II can, for example, with dimethylamine, methylethylamine, diethylamine, di-n-butylamine, methylamine, ethylamine, n-propylamine, n-butylamine, pyrrolidine, piperidine, hexamothylenimine, morpholine, 4-methyl-piperazine, 4 - (ss-hydroxyethyl)

  -piperazine or 4- (ss-acetoxy-ethyl) -piperazine are implemented.



  With inorganic or organic acids, such as hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, methanesulfonic acid, ethanesulfonic acid, β-hydroxyethanesulfonic acid, acetic acid, succinic acid, fumaric acid, maleic acid, malic acid, tartaric acid, citric acid, benzoic acid, saccylic acid and mandelic acid;

      tertiary base salts, some of which are water-soluble.



  In the following examples, parts mean parts by weight; these are related to parts of volume as g to cm3. The temperatures are given in degrees Celsius.



  <I> Example 1 </I> 40 parts of 3-dimethylsulfamoyl-5- (3'-chloro-propyl) - iminodibenzyl are heated to 110 for 12 hours in an autoclave with 30 parts by volume of dimethylamine and 50 parts by volume of methanol. The reaction mixture is freed from excess dimethylamine and methanol and taken up in ether. The ether solution is washed with water and then extracted with 2N hydrochloric acid.

    The hydrochloric acid extract is mixed with conc. Sodium hydroxide solution made alkaline and the precipitated base was extracted with ether. The extract is dried with water and over sodium sulfate. After the solvent has been distilled off, 34 parts of crude reaction product remain, from which 3-dimethylsulfamoyl-5- (γ-dimethylaminopropyl) iminodibenzyl is isolated as the hydrochloride with a melting point of 189.



  In an analogous manner, the reaction of dimethylsulfamoyl-5- (3'-chloropropyl) - iminodibenzyl with methylamine gives 3-dimethylsulfamoyl-5- (3'-methylaminopropyl) -iminodibenzyl, the hydrochloride of which melts at 133.



  <I> Example 2 </I> 25 parts of 3-dimethylsulfamoyl - 5 - (2'-methyl-3'-chloro-propyl) -iminodibenzyl are dissolved in 200 parts by volume of butanone and mixed with 16 parts of N- (2-Hy - Droxy-ethyl) piperazine and 15 parts of sodium iodide boiled with vigorous stirring for 18 hours. The solvent is then distilled off under reduced pressure and the residue is taken up in chloroform.

   After working up analogously as in Example 1, 3-dimethylsulfamoyl-5- [2'-methyl-3 '- (4 "hydroxyethyl-1" -piperazinyl) propyl] - iminodibenzyl is obtained.



  The oxalate of the base melts at 158 with decomposition.



  In a manner analogous to that described in the above examples, the following compounds can also be prepared: 3-dimethylsulfamoyl-5- (ss-dimethylamino-ethyl) - iminodibenzyl hydrochloride, m.p. 210; 3-dimethylsulfamoyl-5- (γ-dimethylamino-f-methyl-propyl) -iminodibenzyl of melting point 11; 3-dimethylsulfamoyl-5- (γ-dimethylamino-n-butyl) -iminodibenzyl of m.p. 90;

         3-dimethylsulfamoyl-5- [γ- (4'-methyl-piperazinyl) -ss-methyl-propyl] -iminodibenzyl, the oxalate of which melts at 193; 3-Dimethy @ sulfamoyl-5- (γ-methylamino-f-methyl-propyl) -iminodibenzyl, the oxalate of which melts at 216; 3-Dimethylsulfamoyl-5- [y- (1'-piperazinyl) -ss-methyl-propyl] -iminodibenzyl, the oxalate of which melts at 168.

 

Claims (1)

PATENT CLAIM Process for the production of new imino dibenzyl derivatives of the formula I. EMI0003.0001 in which R1 and R2 are lower alkyl radicals which can be linked directly or via an oxygen atom, Z is a straight-chain or branched alkylene radical with 2-6 carbon atoms and Am is a lower alkylamino or dialkylamino group, or both alkyl radicals of a dialkylamino group Am can be linked directly or via an oxygen atom, an imino group, a lower alkyl imino, hydroxyalkyhmino or alkanoyloxyalkyl imino group, characterized in that a reactive ester of a compound of Formula II, EMI0003.0023 with an amine of the formula III, Am-H (III) converts. SUBClaims 1. The method according to claim, characterized in that dimethylamine is used as the amine ver. 2. The method according to claim, characterized in that the amine used is N- (2-hydroxyethyl) piperazine. 3. The method according to claim, characterized in that the tertiary bases of the formula I obtained are converted into their salts with inorganic or organic acids.