CH403768A - 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 compounds with valuable pharmacological properties.



  Iminodibenzyl derivatives substituted in a benzene ring by an alkylsulfonyl radical have not yet become known.

   It has now been found that such compounds of the formula I,
EMI0001.0015
    in which R is a methyl or an ethyl radical, Z is a straight-chain or branched alkylene radical with 2-4 carbon atoms, and Am is a lower dialkylamino group,

       where an alkyl radical of Am can also be linked directly to the alkylene radical Z or both alkyl radicals of a dialkylamino group Am directly or via an oxygen atom, a lower alkylimino, hydroxyalkylimino or alkanoyloxyalkylimino group, and their salts with organic or organic acids, valuable pharmacological properties, especially anti-allergic,

       have antiemetic and sedative efficacy, as well as potentiate the effect of other drugs, especially narcotics.



  In the compounds of the formula I, Z is, for example, an ethylene, propylene, trimethylene, 1-methyl-trimethylene, 2-methyl-trimethylene or tetramethylene radical, and Am is z.

   B. a dimethylamino, methyl ethylamino, diethylamino, methyl-n-propylamino, methyl-isopropylamino, di-n-butylamino, di-isobutylamino, 1-pyrrolidinyl, piperidino, hexa- methylenimino, morpholino, 4-methyl-l-piperazinyl, 4-iso @ propyl-1 piperazinyl, 4- (ss-hydroxyethyl)

  - 1-piperazinyl, 4- (ss acetoxyethyl) -1-piperazmyl or 4-ss-hydroxypropyl-1-piperazinyl radical. Furthermore, Am together with Z z. B. the ss- (1-methyl-2-pyrrolidinyl) ethyl, 1-methyl-3-pyrrolidinylmethyl, ss- (1 methyl-piperidyl) -ethyl, 1-methyl-3-piperidylmethyl or 1-methyl-4-piperidyl radical.



       According to the invention, the new compounds of the formula I are obtained by adding a compound of the formula II,
EMI0001.0079
    in the presence of a basic condensing agent with a reactive ester of an amino alcohol of the formula III, HO-Z-Am (III).



  Sodium amide, lithium amide, potassium amide, sodium or potassium, butyllithium, phenyllithium or lithium hydride are particularly suitable as condensing agents. The reaction can be carried out in the presence or absence of an inert organic solvent, examples of which are benzene, toluene and xylenes.



       Starting materials of the formula II are 3-methylsulfonyl- and 3-ethylsulfonyl-iminodibenzyl, wel- before z. B. starting from 3-Anüno-5-acetyl-imino-dibenzyl can be obtained by converting this into the corresponding diazonium sulfate and treating the latter in sulfuric acid solution after adding copper powder with sulfur dioxide,

   the 5-acetyl-iminodibenzyl-3-sulfinic acid obtained is converted into its sodium salt, this is reacted with a suitable methyl or ethyl halide and finally the acetyl radical is removed by hydrolysis, e.g. B. by means of ethanolic or methanolic potassium hydroxide solution, split off.



  Particularly suitable reactive esters of amino alcohols of the formula III are the halides;

         f: -Dimethylamino-ethyl chloride, '> -diethylamino-ethyl chloride, P-methylethylamino-ethyl chloride, s-dimethylamino-propyl chloride, s-dimethylamino-isopropyl chloride, y-dimethylamino-propyl chloride, y-dimethylamino-butyl chloride, y-dimethylamino-butyl chloride -Dimethylamino-ss-methyl-propyl chloride, a-methyl-y-dimethylamino-n-amyl chloride, ss- (di-n-propylamino) -ethyl chloride, ss- (methyl-isopropyl-amino) -ethyl chloride,

            ss- (di-n-butylamino) ethyl chloride, P- (di-isobutylamino) ethyl chloride, ss- (1-pyrrolidinyl) ethyl chloride, ss-piperidinoethyl chloride, - (1-pyrrolidinyl) propyl chloride, γ-piperidino propyl chloride, ss-morpholino-ethyl chloride, y-morpholino-propyl chloride, ss- (4-methyl-l-piperazinyl) ethyl chloride, y- (4-methyl-l-piperazinyl) propyl chloride, ss- [4- (ss -Acetaxy-ethyl) -1-piperazinyll-ethyl chloride,

            y- [4- (ss-acetoxy-ethyl) -1 piperazinyl] -propyl chloride, ss- (1-methyl-2-pyrrolidinyl) -ethyl chloride, ss- (1-methyl-2-piperidyl) -ethyl chloride and ( 1-methyl-3-piperidyl) methyl chloride, and the corresponding. Bromides and iodides.



  With inorganic or organic acids, such as hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, methanesulphonic acid, ethane disulphonic acid, β-hydroxyethanesulphonic acid, acetic acid, succinic acid, fumaric acid, maleic acid, malic acid, tartaric acid, citric acid, benzoic acid,

          Salicylic acid and mandelic acid form the tertiary base salts, some of which are water-soluble.



  In the following example, parts mean parts by weight which are related to parts by volume as g to cm '. The temperatures are given in degrees Celsius.



  <I> Example </I> a) 25.2 parts of 3-amino-5-acetyl-iminodibenzyl are concentrated in 150 parts by volume of water and 30 parts by volume. Dissolved sulfuric acid and diazotized at 0 with stirring with 7 parts of sodium nitrite in 20 parts by volume of water. The solution is then saturated with sulfur dioxide while cooling in an ice / salt bath.

       Copper powder is added in small portions with a further weak passage of sulfur dioxide. After the evolution of nitrogen has ended, the sulfinic acid is extracted with chloroform and the dried extract is concentrated. Recrystallized from acetone ether, 5-acetyl-iminodibenzyl-3-sulfinic acid melts with decomposition at 154.



  b) 30.1 parts of 5-acetyl-iminodibenzyl-3-sulfinic acid are abs to dissolve 2.3 parts of sodium in 250 parts by volume. Given ethanol and mixed with 16 parts of methyl iodide. After one hour of refluxing, the ethanol is distilled off. The residue is taken up in chloroform and washed with a little water.

   The dried chloroform solution is concentrated and petroleum ether is added. The deposited crystals melt at 153 to 154 and are pure 3-methylsulfonyl-5-acetyl-iminodibenzyl.



  c) 31.5 parts of 3-methylsulfonyl-5-acetyl-iminodibenzyl are hydrolyzed in 500 parts by volume of ethylene glycol containing 25 parts of potassium hydroxide by refluxing for 16 hours. The reaction mixture is poured into water and the crystals are suction filtered. Pure 3-methylsulfonylinlinodibenzyl melts, recrystallized from ether, at 175-176.



  d) 27.3 parts of 3-methylsulfonyl-iminodibenzyl who abs at 80 in 800 parts by volume. Dissolved xylene and treated with 20.9 parts of 3-dimethylamino-2-methyl-1-propyl chloride hydrochloride.

   Then 8.6 parts of sodium amide pulverized in toluene are added dropwise and the reaction mixture is stirred at 135 for 17 hours. After cooling, the base with 2-n. Hydrochloric acid extracted, the extract made alkaline and taken up in ether. After evaporating the dried ether solution, the base remains as an oil.

   The hydrochloride is prepared from this base in the usual way and this is recrystallized from a large amount of methyl ethyl ketone. The. 3-Methyl sulfonyl-5 - [(3-dimethylamino-2-methyl) propyl] -imino-dibenzyl hydrochloride melts at <B> 229-231 '. </B>

 

Claims (1)

PATENT CLAIM Process for the production of new Iminodiben- zylderivaten of formula I. EMI0002.0155 in. R is a methyl or ethyl radical, Z is a straight-chain or branched alkylene radical with 2-4 carbon atoms, and Am is a lower dialkylan ino group, an alkyl radical of Am also being directly linked to the alkylene radical Z, or both alkyl radicals of the dialkylamino group Am can be linked directly or via an oxygen atom, an alkylimino-hydroxyalkylimino or alkanoyloxyalkylimino group, characterized in that that a compound of formula II EMI0003.0018 in the presence of a basic condensing agent with a reactive ester of an amino alcohol of the formula III HO-Z-Am (III). SUBCLAIM Method according to patent claim, characterized in that that the compounds of the formula I thus obtained are converted into their addition salts with organic and inorganic acids.