Patent GB-770247-A (GB)
Title: Hydroxy-alkyl-bis(3-cyclohexylpropyl) amines and the preparation thereof
Filed: 1955-05-10
Abstract: The invention comprises compounds of the formula <FORM:0770247/IV(b)/1> wherein R is hydrogen or an alkyl group of 1 to 4 carbon atoms and R1 is an alkyl group having 1 to 8 carbon atoms and bearing from 1 to 3 hydroxy groups attached to different carbon atoms, and acid-addition salts thereof; and their preparation by heating the appropriate 3-cyclohexylpropyl chloride, bromide or iodide with an amine H2NR1 in an inert solvent in the presence of an acid acceptor such as sodium carbonate.  Reference is also made to their preparation by condensing a secondary amine (RC6H10CH2CH2CH2)2NH with an alkyl halide R1X or, for compounds bearing a hydroxyl group on the carbon atom adjacent to the nitrogen atom, by reaction of an aldehyde with said secondary amine. Salt-forming acids referred to are hydrohalic, nitric, phosphoric, sulphuric, acetic, citric, tartaric, lactic, ethanesulphonic, quinic and sulphamic acids.  In example: (1) malonic acid and a mixture of o-, p- and m-tolualdehydes, the last predominating, are condensed and the reaction product is decarboxylated by boiling with HCl to give methyl cinnamic acid, this is catalytically hydrogenated to b -(methylcyclohexyl) propionic acid which on reduction with LiAlH4 gives 3-(methylcyclohexyl) propanol, this with HBr gives 3-(methylcyclohexyl) propyl bromide and this with 2-aminoethanol gives 2-hydroxyethyl-bis-[3-(methylcyclohexyl) propyl] amine, the 3-methyl cyclohexyl isomer predominating throughout; (2) Example (1) is repeated using pure m-tolualdehyde, and reference is made to the use of 2-ethyl-, 3-propyl and 4-butylbenzaldehydes; (3) b  - (3 - methylcyclohexyl) - propionic acid is converted via its chloride to b -(3-methylcyclohexyl) propionamide, purified by repeated recrystallization from methanol as the cisisomer; this isomer is decomposed in the cold with sulphuric acid and sodium nitrite solution to cis-b -(3-methylcyclohexyl) propionic acid which is then treated as in Example (1) to give successively the corresponding propanol, propyl bromide and finally cis-2-hydroxyethyl-bis-[3-(3 - methylcyclohexyl) propyl] amine; (4) 2-hydroxyethyl - bis -[3 - (4 - methylcyclohexyl)-propyl] amine is prepared from 4-methyl-cinnamic acid using the procedure of Example (1); (5) 3-cyclohexylpropyl bromide and 2-aminoethanol give 2-hydroxyethyl-bis-(3-cyclohexylpropyl) amine; (6) hydrogenolysis of benzyl-bis-(3-cyclohexylpropyl) amine gives bis-(3-cyclo hexylpropyl) amine and this with 2,3-dihydroxypropyl chloride gives bis-(3-cyclohexylpropyl)-2,3-dihydroxypropylamine; (7) 3-cyclohexylpropyl bromide and tris-[hydroxymethyl] methylamine give bis-(3-cyclohexylpropyl)-[tris-(hydroxymethyl) methyl] amine (obtained via its hydrochloride), the ethanesulphonate and quinate of which are described, and some 3-cyclohexylpropyl - [tris - (hydroxymethyl) methyl] amine; (8) 3-(3-methylcyclohexyl)-propyl bromide and tris-(hydroxymethyl) methylamine give bis - [3 - (3 - methylcyclohexyl) propyl]- [tris - (hydroxymethyl) methyl] amine and some 3 - (3 - methylcyclohexyl) propyl - [tris-(hydroxymethyl) methyl] amine.  Secondary amines (6RCH10CH2CH2CH2)2NH are prepared from ammonia and RC6H10 CH2CH2CH2Br or by hydrogenolysis of the tertiary amine (RC6H10CH2CH2CH2)2NCH2 C6H5, itself prepared from benzylamine and RC6H10CH2CH2CH2Br.  Secondary amines (RC6H10CH2CH2CH2)NH R1 are formed as well as the tertiary amines of the invention when the process of the invention is carried out; they are separated from the tertiary amines by fractional distillation or by fractional crystallization or by selective extraction of their acid-addition salts.