Patent GB-805885-A (GB)
Title: 3-substituted-8-alkylnortropanes and the acid and quaternary ammonium salts thereof
Filed: 1956-06-27
Abstract: The invention comprises compounds of the tropane series of the general formula <FORM:0805885/IV (b)/1> (wherein R represents a straight or branched chain alkyl radical of 1-4 carbon atoms, n is from 0 to 3, and R2 and R3 each represent alkyl of 1-6 carbon atoms, cycloalkyl of 5 or 6 carbon atoms, cycloalkyl-alkyl of 6-10 carbon atoms, 2-pyridyl, or phenyl which may be substituted by an alkyl or alkoxy group of 1-4 carbon atoms) and their acid addition and quaternary ammonium salts, and the preparation thereof from tertiary alcohols of the general formula <FORM:0805885/IV (b)/2> by (a) reduction with phosphorus and hydriodic acid, or (b) dehydration by the process of Specification 805,884, followed by hydrogenation of the resulting products.  In examples: (1) 3-benzhydrylidenetropane is hydrogenated in ethanol in the presence of "Raney" nickel (the word "Raney" is a Registered Trade Mark) to produce 3-benzhydryltropane, which is converted to its hydrochloride, methobromide and etho-ethylsulphate; similarly prepared are (2) 1 : 1-diphenyl-2-(3-tropane) ethane (and its hydrochloride, methobromide, metho-p-toluene-sulphonate and maleate) from 1 : 1-diphenyl-2-(3 - tropane) - ethylene, (4) 1-ethyl-1-phenyl-2-(3-tropane)-ethane (and its hydrochloride) from the dehydration product of 1-ethyl-1-phenyl-2-(3 - tropane) - ethanol, (6) 1 - cyclohexyl - 1 - phenyl - 2 - (3 - tropane) - ethane (and its hydrochloride, citrate and butyliodide) from the dehydration product of 1-cyclohexyl-1-phenyl - 2 - (3 - tropane) - ethanol, (7) 1 - p - anisyl - 1 - phenyl - 2 - (3 - N - isopropylnortropane)-ethane (and its methobromide) from 1 - p - anisyl - 1 - phenyl - 2 - (3 - N - isopropylnortropane) - ethylene, (8) 1 : 1 - diphenyl - 3 - (3 - tropane) - propane (and its citrate and methobromide) from 1 : 1-diphenyl-3-(3-tropane)-1-propene, (10) 3-isopropyltropane from the product obtained by refluxing dimethyl - 3 - tropanecarbinol with acetic and hydrochloric acids and treating the resulting hydrochloride with sodium carbonate in ether, (11) 2 - n - hexyl - 1 - (3 - N - isopropylnortropane)-octane from the product obtained by similarly neutralizing the hydrochloride of the dehydration product of 1 : 1-di-n-hexyl-2-(3-N - isopropylnortropane) - ethanol, and (12) 1 - cyclopentyl - 1 - phenyl - 4 - (3 - tropane)-butane from the dehydration product of 1-cyclopentyl - 4 - (3 - tropane) - butanol. In further examples: (3) 1-phenyl-1-(2-pyridyl)-2-(3-tropane)-ethylene is refluxed with cyclohexene and palladium-on-charcoal catalyst to form 1 - phenyl - 1 - (2 - pyridyl) - 2 - (3 - tropane)-ethane, which is converted to its dipicrate and tartrate; (5) 1-(2-cyclohexylethyl)-1-phenyl - 2 - (3 - tropane) - ethanol is refluxed with hydriodic acid and red phosphorus in acetic acid to produce 1-(2-cyclohexylethyl)-1-phenyl - 2 - (3 - tropane) - ethane hydriodide, which is converted to the free base and the latter to its hydrochloride; (9) 1-(2-pyridyl)-1-p-tolyl-4-(3-tropane)-1-butene is reduced as in (3) to 1 - (2 - pyridyl) - 1 - p - tolyl - 4 - (3 - tropane)-butane. Additional salt-forming and and quaternizing agents are listed as in Specifications 805,883 and 805,884.  The products are useful as therapeutic agents acting on the parasympathetic and central nervous systems.  Ethyl b -(3-tropane)-propionate (from which the starting material of Example (8) is obtained by successive application of the processes of Specifications 805,883 and 805,884) is prepared by acid hydrolysis of the corresponding nitrile (obtained by the action of potassium cyanide on 1 - chloro - 2 - (3 - tropane) - ethane in aqueous alcohol in the presence of sodium iodide), followed by esterification with ethanol in the presence of conc. H2SO4. 1-Chloro-2-(3-tropane)-ethane is prepared by refluxing 2-(3-tropane)-ethanol with thionyl chloride in chloroform and treating the resulting hydrochloride with potassium carbonate. 2-(3-Tropane)-ethanol is prepared by reducing ethyl 3-tropaneacetate with lithium aluminium hydride in ether.