Patent GB-641605-A (GB)
Title: Manufacture of an imidazoline
Filed: 1947-07-11
Abstract: 2-(Benzhydryloxymethyl)-imidazoline is prepared by (1) treating a reactive ester, such as the halide, of 2-(hydroxymethyl)-imidazoline, e.g. 2-(chloromethyl)-imidazoline with a metal alcoholate of the constitution <FORM:0641605/IV (b)/1> where M is an alkali or an alkaline-earth metal, (2) treating a reactive ester, e.g. chloride, bromide or sulphonate of benzhydrol with a 2-(hydroxy methyl)-imidazoline or an alkali metal compound thereof, or (3) by reacting benzhydryloxy acetic acid or a reactive derivative thereof, such as an iminoether, iminohalide, thioamide, thioiminoether, amide, ester, halide or amidine or reactants which give rise to these in the course of the reaction (e.g. instead of a thioamide the corresponding nitrile may be used in the presence of hydrogen sulphide or agents yielding hydrogen sulphide such as carbon disulphide, phosphorus pentasulphide, an alkali metal sulphide, an ammonium sulphide, iron sulphide or aluminium sulphide with an aliphatic 1 : 2-diamine. Suitable 1 : 2-diamines are ethylene diamine, N-methyl-ethylene diamine, N-ethyl-ethylene diamine, N-propyl-ethylene diamine, 1-methyl-ethylene diamine, 1 : 2-dimethyl-ethylene diamine and 1-phenyl-ethylene diamine.  The reactions may be carried out in the presence or absence of a solvent or condensing agent.  In examples: (1) sodium benzhydrolate and 2-(chloromethyl)-imidazoline are refluxed in dioxane and the resulting 2-(benzhydryl-oxymethyl) imidazoline isolated as the picrate.  (2) 2-(Hydroxymethyl)-imidazoline is refluxed with diphenyl methyl bromide and the desired compound again isolated as the picrate.  (3) Benzhydrol is converted to sodium benzhydrolate which is reacted first with ethyl bromacetate and then with strong ammonia to give benzhydryloxyacetamide, which is then converted to benzhydryloxy-acetothioamide and treated with ethylene diamine to give the required product.  (4) Benzhydryloxyacetamide is dehydrated with phosphorus pentoxide in the presence of triethylamine to benzhydryloxyacetanitrile which is then reacted with ethylene diamine.  (5) Benzhydryloxyacetonitrile is treated with hydrochloric acid to form benzhydryloxyacetimidoether which is then refluxed with an ethanolic solution of ethylene diamine.  Benzyloxyacetonitrile is prepared by reacting chloracetonitrile and benzyl alcohol in the presence of an acid binding agent such as sodium.  b -Benxyloxypropionitrile is prepared by reacting benzyl alcohol with acrylonitrile in the presence of a catalytic quantity of sodium. Benhydryloxyacetonitrile is prepared by treating benzhydryloxyacetamide with phosphorus pentoxide in the presence of triethylamine or N-methyl-piperidine.  Benzyloxy-acetimido-ethyl ether hydrochloride is prepared by treating benzyloxyacetonitrile with ethanol and hydrogen chloride in chloroform.  b -Benzyloxy-propionimido-ethyl ether hydrochloride is prepared by treating b -benzyloxy-propionitrile with ethanol and hydrogen chloride.  b -Benzyloxy-propionamidine hydrochloride is prepared by treating b -benzyloxy-propionimido ethyl ether hydrochloride with alcoholic ammonia.  Ethyl benzhydryloxyacetate is prepared by reacting sodium benzhydrolate with ethyl bromacetate. Benzhydryloxyacetamide is prepared by treating ethyl benzhydryloxyacetate with concentrated aqueous ammonia. Benzhydryloxyacetothioamide is prepared by reacting benzhydryloxyacetamide with phosphorus pentasulphide and potassium sulphide in xylene or by treating benzhydryloxyacetonitrile with ammonia in ethanol saturated with hydrogen sulphide.  The Specification as open to inspection under Sect. 91 includes also the preparation of 2-(aralkoxy-alkyl)-imidazolines in general and the following additional examples are included: (1) Sodium benzylate and 2-(chloromethyl) imidazoline are reacted to form 2-(benzyloxymethyl)-imidazoline.  (2) Benzyloxyacetonitrile is treated with dry HCl and the product refluxed with ethylene diamine to form the same compound as in the previous example. (3) b -Benzyl-oxypropionitrile is treated with dry HCl and the product refluxed with ethylene diamine to form benzyloxyethyl imidazoline. (4) Phenyl-benzyl carbinol is converted into its sodium alcoholate and refluxed with 2-(chloromethyl) imidazoline. Additional carboxylic acids mentioned are benzyloxy-acetic acid, b -benzyloxypropionic acid and a  : b -diphenyl-ethoxy-acetic acid.  This subject-matter does not appear in the Specification as accepted.