Patent GB-769976-A (GB)
Title: Poly[3-(lower-alkylcyclohexyl)propyl]amines and preparation thereof
Filed: 1955-05-10
Abstract: The invention comprises poly-3-(alkyl-cyclohexyl) propyl amines and their acid addition salts, the amines having the formula <FORM:0769976/IV(b)/1> wherein R is a lower alkyl group (i.e. having 1 to 4 carbon atoms) and R1 is hydrogen, an alkyl radical having 1 to 8 carbon atoms or a 3-(loweralkylcyclohexyl)-propyl radical.  Such compounds are obtained by the reaction of 2 or more equivalents of a 3-(lower-alkylcyclohexyl) propyl halide, preferably bromide, with ammonia or a primary amine H2NR1.  Primary, secondary and tertiary amines are formed from ammonia.  The reaction product with the amine usually contains a mixture of secondary and tertiary amines which can be separated by fractional distillation or crystallization or by selective extraction of the acid addition salts.  Separation of the products into cis and trans isomers can also be effected.  In an alternative method benzylamine is reacted with RC6H10-CH2CH2CH2Br, the benzyl substituted tertiary amine (RC6H10CH2CH2CH2)2 NCH2C6H5 being hydrogenated to remove the benzyl group.  The secondary amine obtained can then be condensed with the appropriate halide R1X. Salts of the products referred to are the hydrochloride, hydrobromide, hydriodide, nitrate, phosphate or acid phosphate, sulphate or bisulphate, acetate, citrate or acid citrate, tartrate or bitartrate or lactate.  In examples (1) and (2) 3-(methylcyclohexyl) propyl bromide (a mixture of 2-, 3- and 4-methyl and cis and trans isomers) is reacted with alcoholic ammonia at 143-148 DEG  C. in an autoclave. The product is separated by extraction of the hydrochloride with petroleum ether into bis-[3-(methylcyclohexyl)-propyl] amine and tris-(3-(methylcyclohexyl) propyl] amine (mixtures of 2-, 3- and 4-methyl and cis and trans isomers); (3) 3-(methylcyclohexyl) propyl bromide and ethylamine are reacted in ethanol in the presence of sodium carbonate to give ethyl-bis-[3-(methylcyclohexyl) propyl] amine (mixed isomers). In similar examples there are prepared (from pure starting materials) (4) ethyl-bis-[3-(3-methylcyclohexyl) propyl] amine; (5) ethyl-bis-[3-(4-methylcyclohexyl) propyl] amine. The butyl-, hexyl-, octyl- and isohexyl-bis-[3-(4-methylcyclohexyl)-propyl] amines and ethyl-bis-[3-(2-ethyl, 3-propyl and 4-butyl-cyclohexyl) propyl] amines are also referred to.  In Example (6) benzylamine and 3-(4-methylcyclohexyl) propyl bromide are reacted to give benzyl - bis - [3 - (4 - methylcyclohexyl) propyl] amine, which by hydrogenation with a palladium catalyst gives bis-[3-(4-methylcyclohexyl) propyl] amine.  The latter is alkylated with methyl bromide to give methyl-bis-[3-(4-methylcyclohexyl) propyl] amine.  Similarly to (6) are prepared in Example (7) benzyl-bis-[3-(3-methylcyclohexyl) propyl] amine and bis-[3-(3-methylcyclohexyl) propyl] amine.  Starting materials. Malonic acid and tolualdehyde heated in pyridine give methylcinnamic acid, reduction of which gives b -methylcyclohexyl) propionic acid. The latter is reduced with lithium aluminium hydride to 3-(methylcyclohexyl) propanol which with hydrogen bromide gas gives 3-(methylcyclohexyl) propyl bromide.  These reactions are effected with mixed 2-, 3- and 4-methylcinnamic acids or with pure 3-methylcinnamic acid giving mixed cis and trans isomers of 3-methyl or mixed 2-, 3- and 4-methyl derivatives respectively.  Similarly obtained are b -(4-methylcyclohexyl) propionic acid (by reduction of 4-methylcinnamic acid with platinum oxide), 3-(4-methylcyclohexyl) - propanol and 3 - (4 - methylcyclohexyl) - propyl bromide.  Reference is also made to preparing 2-ethyl-, 3-propyl- or 4-butyl-cinnamic acids by condensing malonic acid with the appropriately substituted benzaldehyde.