Patent GB-476611-A (GB)
Title: Manufacture of new amidines
Filed: 1936-06-19
Abstract: Therapeutically-active amidines are prepared from phenyloxy-fatty acid nitriles, amides or thioamides which are substituted in the phenyl nucleus or from quinoline-oxy-fatty acid nitriles, amides or thioamides in which the oxy-fatty acid nitrile, amide or thioamide residue is a substituent of the isocyclic ring by (a) converting the nitrile into its imido-ether and treating it with ammonia or a primary or secondary amine, (b) heating the nitrile with a salt of ammonia or of a primary or secondary amine, (c) converting the amide into its imido-chloride and treating it with ammonia or a primary or secondary amine, or (d) reacting the thioamide in free or nascent form with ammonia or a primary or secondary amide.  According to the examples: (1) 2 - methoxyphenoxy - ethenylamidine is obtained when 2-methoxyphenoxyacetonitrile is treated in cold alcoholic solution with hydrogen chloride or bromide and the resulting acetimido-ether reacted with ammonia; in the same way 2-methoxy-6-allylphenoxy-ethenylamidine is prepared from 2-methoxy - 6 - allylphenoxy - acetonitrile; (2) 2-ethoxyphenoxy-acetonitrile is converted as in (1) into its imido-ether and the latter treated with piperidine to give 2-ethoxyphenoxyethenylpiperidineamidine; (3) quinoline-8-oxyethenylamidine is prepared by introducing hydrogen chloride into an alcoholic solution of quinoline-8-oxyacetonitrile and treating the resulting acetimido-ether with ammonia; the same product may be obtained from quinoline-8-oxyacet-amide or -thioamide; (4) quinoline-8-oxy-n-butenylamidine is prepared from quinoline-8-oxy-n-butyronitrile by conversion into the butyrimido-ether and treatment with ammonia; an isomeric imido-ether of the formula <FORM:0476611/IV/1> may be similarly treated; (5) 2-methoxyphenoxyacetamide is heated with phosphorus pentachloride in xylene and the imido-chloride so formed heated with diethylamine to give 2-methoxyphenoxy-ethenyl-as-diethylamidine; other halogenating agents, e.g. phosphorus pentabromide or thionyl chloride, may replace the phosphorus pentachloride; (6) 2-methoxyphenoxy-ethenylamidine is obtained by treating 2 - methoxyphenoxy - thioacetamide with alcoholic ammonia or by heating a solution of 2 - methoxyphenoxy - acetonitrile in alcoholic ammonium sulphide.  In like manner the following amidines may be prepared: 2-methoxyphenoxyethenyl - as - diethylamidine, -as-n-dibutylamidine, -as - diallylamidine, -benzylamidine, -b  : b  : b -diethylphenylethylamidine, -N-diethylaminoethylamidine and -phenylamidine; 2-methoxyphenoxy-butenylamidine; 2 - methoxy - 6 - allylphenoxyethenyl - as - diethylamidine and -piperidineamidine; 2-ethoxy and 3 - methoxy - phenoxy - ethenylamidines; 3 - methoxyphenoxy - ethenylpiperidineamidine; 4 - methoxyphenoxyethenyl - amidine, -benzylamidine, -b -phenylethylamidine and -piperidineamidine; 4 - allyl - 2 - methoxyphenoxyethenyl-amidine, -as-diethylamidine and -piperidineamidine; quinoline - 8 - oxyethenyl - piperidineamidine and -phenylethylamidine; and quinoline-6-oxyethenylamidine.  Nitriles.--2-Methoxyphenoxy - acetonitrile is prepared by treating pyrocatechol monomethyl ether with chloracetonitrile in the presence of an acid-binding agent.  In a similar way, 2 - methoxy - 6 - allylphenoxy - acetonitrile, 2-ethoxyphenoxy-acetonitrile, quinoline-8-oxyacetonitrile, quinoline-8-oxy-n-butyronitrile, 3- and 4-methoxyphenoxy-acetonitriles, 4-allyl-2-methoxyphenoxy-acetonitrile and quinoline-6-oxyacetonitrile are prepared. 2-Methoxyphenoxy-thioacetamide is obtained by the reaction of 2-methoxyphenoxy-acetamide with phosphorus pentasulphide and potassium sulphide in xylene.