Patent GB-805884-A (GB)
Title: Olefinic derivatives of 8-alkylnortropanes and the acid and quaternary ammonium salts thereof
Filed: 1956-06-27
Abstract: The invention comprises the dehydration products of tertiary alcohols of the general formula <FORM:0805884/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-thienyl, 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 by treatment of the tertiary alcohols with a dehydration agent (e.g. a mineral or organic acid, a lower fatty acid anhydride or a carboxylic acid chloride).  The products consist of compounds, or isomeric mixtures thereof, containing the grouping <FORM:0805884/IV (b)/2> wherein the double bond may be in position a, b or c when neither R2 or R3 is aromatic (though this represents only two possible isomers if R2 and R3 are identical), in position a or b when R3 only is aromatic, but in position a only when R2 and R3 are both aromatic. Examples describe the following dehydrations: (1) diphenyl-3-tropanecarbinol, by refluxing with a mixture of glacial acetic and dilute hydrochloric acids, to 3-benzhydrylidenetropane hydrochloride, which is converted to the free base and the latter to its picrate, methobromide and etho-ethylsulphate; (2) di-(2-thienyl)-3-tropanecarbinol, by passing in dry hydrogen chloride in the cold, to 3-[di-(2-thienyl) - methylene] - tropane hydrochloride; (3) 1 : 1 - di - (2 - thienyl) - 2 - (3 - tropane)-ethanol, by refluxing with an aqueous solution of oxalic acid, to 1 : 1-di-(2-thienyl) - 2 - (3-tropane)-ethylene the picrate, hydrochloride and methobromide of which are described; (4) 1 : 1 - diphenyl - 2 - (3 - tropane) - ethanol hydrochloride as in (1) to 1 : 1-diphenyl-2-(3-tropane)-ethylene hydrochloride, which is converted to the free base and the latter to its methobromide, maleate and metho-p-toluenesulphonate; (5) 1-phenyl-1-(2-thienyl)-2-(3-tropane)-ethanol as in (3) to 1-phenyl-1-(2-thienyl) - 2 - (3 - tropane) - ethylene, the tartrate and methobromide of which are described; (6) 1-phenyl-1-(2-pyridyl)-2-(3-tropane)-ethanol, by heating with 85 per cent sulphuric acid, to 1-phenyl-1-(2-pyridyl)-2-(3-tropane)-ethylene, the methobromide and tartrate of which are described; (7) 1-ethyl-1-phenyl-2-(3-tropane)-ethanol by heating with conc. hydrochloric acid; (8) 1-(2-cyclohexylethyl)-1-phenyl - 2 - (3 - tropane) - ethanol as in (1); (9) 1 - cyclohexyl - 1 - phenyl - 2 - (3 - tropane) - ethanol similarly, the base liberated from the product being converted to its hydriodide, methobromide and butyl iodide; (10) 1-p-anisyl - 1 - phenyl - 2 - [3 - (N - isopropylnortropane)] - ethanol as in (3) to 1 - p - anisyl - 1 - phenyl - 2 - [3 - (N - isopropylnortropane)] - ethylene; (11) 1 : 1-diphenyl-3-(3-tropane)-propanol, by heating with 37 per cent hydrochloric acid, to 1 : 1-diphenyl-3-(3-tropane)-1-propene, the citrate of which is described; (12) 1-(2-pyridyl) - 1 - (p - tolyl) - 4 - (3 - tropane) - 1 - butanol as in (6) to 1-(2-pyridyl)-1-(p-tolyl)-4-(3-tropane)-1-butene; (13) dimethyl-3-tropanecarbinol as in (1); (14) 1 : 1-di-n-hexyl-2-[3-(N - isopropylnortropane)] - ethanol similarly; (15) 1 - cyclopentyl - 1 - phenyl - 4 - (3 - tropane)-butanol similarly.  Other salt-forming and quaternating agents specified are: camphorsulphonic, acetic, propionic, butyric, succinic, glutaric, adipic, ascorbic, lactic, levulinic, malic, mandelic, cinnamic, gluconic, methanesulphonic, benzenesulphonic, fumaric, citraconic, itaconic, lauric, stearic, myristic, palmitic, linoleic, aspartic, sulphoacetic, hydrobromic, sulphuric, sulphamic, phosphoric and nitric acids; methyl, ethyl, butyl, isobutyl, benzyl and naphthylmethyl chlorides, methyl iodide, propyl, allyl, methallyl, crotyl, benzyl and phenethyl bromides, ethylene brom- and chlor-hydrin, dimethyl sulphate, methyl benzenesulphonate and ethyl toluenesulphonate.  The products are useful as therapeutic agents acting on the parasympathetic and central nervous systems or as intermediates for such agents. Specification 805,883 is referred to.