Verfahren zur Herstellung von neuen heterocyclischen Aminen

摘要

The invention comprises compounds of the formula (wherein R is pyrrolidino, piperidino or hexa methyleneimino which may be substituted by alkyl groups containing at most 4 carbon atoms, and their acid-addition salts. They may be prepared by reacting a 1-R-1-cyano-cyclohexane with a phenyl alkali metal compound in the presence of Lewis acids such as magnesium halides, BF3, FeCl3, AlCl3 or ZnCl2 or wit a phenyl magnesium halide and hydrolysing the product; by reacting a quaternary ammonium compound of the formula (wherein Y is an alkylene radical of 4 to 6 carbon atoms and Z is an anion) with a phenyl magnesium halide; or by reacting a compound R-CO-C6H5 with a compound Me-(CH2)5-Me (wherein Me is an alkali metal or a magnesium halide) and hydrolysing the product. In examples: (1) 1-piperidinocyclohexanecarbonitrile and phenyl magnesium bromide yield 1-(1-phenylcyclohexyl)-piperidine; (2) magnesium bromide etherate and phenyl lithium replace the phenyl magnesium bromide of (1), the product being the same; (3) cyclohexanone cyanohydrin and pyrrolidine in benzene yield, on azeotropic distillation, 1-(1-pyrrolidino) cyclohexane carbonitrile and this with phenyl magnesium bromide yields 1-(1-phenylcyclohexyl)-pyrrolidine; (4) cyclohexanone cyanohydrin and 3 - ethyl - 3 - methyl - pyrrolidine (prepared by lithium aluminium hydride reduction of x - methyl - x - ethylsuccinimide) yield 1 - (3-ethyl - 3 - methyl - pyrrolidino) - cyclohexane carbonitrile and this with phenyl magnesium bromide yields 1-(1-phenylcyclohexyl)-3-ethyl3 - methyl - pyrrolidine; (5) cyclohexanone cyanohydrin and hexamethyleneimine yield 1-(1 - hexamethyleneimino) - cyclohexane carbonitrile and this with phenyl magnesium bromide yields 1 - (1 - phenylcyclohexyl) - hexamethyl leneimine; (6) 1 - (3 - and 4 - methyl - 1 piperidino) - cyclohexane carbonitriles and 1 - (1-phenyl - cyclohexyl) - 3 - and 4 - methylpiperidines are similarly prepared; (7) pentamethylene-bis-magnesium bromide and Nbenzoyl-piperidine are heated together and the product hydrolysed to give the product of (1); and (8) piperidine and cyclohexane in benzene yield, on azeotropic distillation, N-(1-cyclohexenyl)-piperidine, this is mixed with a toluene solution of p-toluenesulphonic acid and this mixture with phenyl magnesium bromide in ether yields, on hydrolysis, the product of (1). Hydrochlorides, hydrobromides, p-toluenesulphonates and sulphates of some of the products are described and other salt-forming acids are also referred to.ALSO:Pharmaceutical compositions comprise compounds of the formula (wherein R is pyrrolidino, piperidino or hexamethyleneimino which may be substituted by alkyl groups containing at most 4 carbon atoms) or their acid-addition salts made up as tablets, dragees, capsules, syrups, suppositories or parenteral solutions. Typical salts are the hydrochloride, succinate, benzoate, p-toluene, sulphonate and sulphamate.