Patent GB-577843-A (GB)
Title: Biguanide derivatives
IPC: C07C279/26
Filed: 1944-05-10
Abstract: Substituted biguanides of the general formula A-NX-C(NH)-NH-C(NH)-NRR1, wherein A represents an aryl group, X represents hydrogen or an alkyl group, R represents a hydrocarbon radical and R1 represents hydrogen or a hydrocarbon radical or, alternatively, R and R1 may be joined together to form a divalent aliphatic hydrocarbon chain, and wherein the groups A, R and R1 may bear one or more non-acidic constituents, are obtained by the interaction of an aryl-dicyandiamide of the general formula A-NX-C(NH)-NH-CN with an amine of the general formula NHRR1.  The aryl-dicyandiamide components may be prepared as described in Specification 576,401.  Examples relate to (1) the preparation of Na -p-chlorophenyl - No  - diethyl - biguanide by the interaction of p-chlorophenyl-dicyandiamide and diethylamine aqueous ethyl alcohol containing copper sulphate, separation of the copper complex, treatment of this with aqueous hydrochloric acid and sodium sulphide, separation of the copper as sulphide and treatment of the solution with caustic soda to precipitate the biguanide; (2) to (28), the preparation similarly of (2) Na -p-chlorophenyl-No -dimethyl-biguanide; (3) Na -p-chlorophenyl-No -methyl-No -isopropyl-biguanide, (4) Na -p-chlorophenyl-No -dibutyl-biguanide, (5) Na -p-chlorophenyl-No -ethyl-No -b -diethylaminoethyl-biguanide, (7) Na  - p - chlorophenyl - No  : No  - tetramethylene - biguanide, (8) Na  - phenyl - No  - diethyl - biguanide, (9) Na  - p - tolyl - No  - dimethyl - biguanide, (10) Na  - p - anisyl - No  - dimethyl - biguanide, (11) Na  - p - anisyl - No  - diethyl - biguanide, (12) Na - p - nitrophenyl - No  - di - methyl - biguanide, (13) Na -p-nitrophenyl-Na -diethyl-biguanide, (14) Na -3 : 4-dimethylphenyl-No -diethyl-biguanide, (15) Na -p-chlorophenyl-No -allyl-biguanide, (16) Na -p-chlorophenyl-No -ethyl-biguanide, (17) Na -p-chlorophenyl-No -n-amyl-biguanide, (18) Na -p-chlorophenyl-No - n - propyl - biguanide, (19) Na  - p - chlorophenyl - No  - isopropyl - biguanide, (20) Na  - p - chlorophenyl - No  - n - butyl - biguanide acetate, (21) Na -p-chlorophenyl-No -isobutyl-biguanide hydrochloride, (22) Na  - p - chlorophenyl - No  - tert.-butyl-biguanide hydrochloride, (23) Na -p-chlorophenyl - No  - ethyl - No  - b  - diethylamino - ethyl - biguanide, (24) Na  - p - chlorophenyl - No  - methyl - No  - n - propyl - biguanide, (25) Na - p - acetylaminophenyl - No  - methyl - No  - isopropyl - biguanide acetate, (26) Na -p-chlorophenyl-No -methyl-biguanide, (27) Na -p-chlorophenyl-No -(1 - methyl - 4 - diethylamino) - butyl - biguanide carbonate, (28) Na -p-chlorophenyl-Na -methyl-No -diethyl-biguanide, (29) the preparation of Na  - p - chlorophenyl - No  : No  - pentamethylene biguanide by the interaction of p-chlorophenyl-dicyandiamide and piperidine in aqueous b -ethoxyethanol containing copper sulphate and isolation of the product as in (1); (3) to (33) the preparation similarly of (3) Na -p-chlorophenyl-No  - cyclohexyl - biguanide, (31) Na  - p - chlorophenyl - No  - b  - diethylaminoethyl - biguanide, (32) Na  - p - chlorophenyl - No  - b  - diethylamino - propyl - biguanide, (33) Na  - p - anisyl - No  : No  - pentamethylene-biguanide; (34) the preparation of Na  : No -diphenyl-biguanide hydrochloride by the interaction of phenyldicyandiamide with aniline hydrochloride in aqueous dioxane; (35) to (40) the preparation similarly of (35) Na -p-chlorophenyl-No -phenyl-biguanide, (36) Na  - p - chlorophenyl - No  - b  - naphthyl - biguanide, (37) Na  - p - chlorophenyl - No  - p - anisyl - biguanide, (38) Na  : No  - di - p - tolyl - biguanide, (39) Na  : No -di-p-anisyl-biguanide hydrochloride, (40) Na  - p - anisyl - No  : No  - pentamethylene - biguanide; (41) the preparation of Na -p-chlorophenyl-No  : No -pentamethylene-biguanide by the interaction of p-chlorophenyldicyandianide and piperidine in aqueous ethyl alcohol containing bronze powder, dilution of the reaction mixture with aqueous hydrochloric acid, removal of the copper bronze, and isolation of the product as in (1); (42) the preparation of Na  - p - chlorophenyl - No  - iso - propyl-biguanide acetate by the interaction of p-chlorophenyl dicyandiamide and isopropylamine hydrochloride in aqueous ethyl alcohol, containing hydrated copper oxide, removal of the alcohol by distillation, isolation of the product as in (1) and conversion into the acetate; (43) the preparation of Na -p-chlorophenyl-N -isopropyl-biguanide acetate by the interaction of p-chlorophenyldicyandiamide and isopropylamine in aqueous ethyl alcohol containing zinc chloride removal of the alcohol by distillation, treatment of aqueous caustic soda to obtain the biguanide and conversion into the acetate; (44) the preparation of Na -p-chlorophenyl-No  : No -pentamethylene-biguanide by heating under reflux p-chlorophenyldicyandiamide and piperidine.  The salts of the biguanides with acetic, lactic, methanesulphonic, methylene - disalicylic, methylene - bis - 2 : 3 - hydroxynaphthoic and hydrochloric acids are referred to.  Na -p-chlorophenyl-Na -methyl-dicyandiamide (example 28) is obtained by reaction of p-chlorophenyl-dicyandiamide with dimethyl sulphate in methyl alcohol containing caustic soda.