Patent GB-744061-A (GB)
Title: Improvements in new bis-alkylammonium ethers
Filed: 1953-03-25
Abstract: The invention comprises compounds of the general formula <FORM:0744061/IV(a)/1> or salts thereof, wherein R1 and R2 are identica and each stands for an alkyl group containing not more than 4 carbon atoms, R3 stands for an alkyl group containing not more than 2 carbon atoms, R4 and R5 are identical and each stands for an alkyl group containing not more than 4 carbon atoms different from R1 and R2, R6 stands for an alkyl group containing not more than 2 carbon atoms, Q1 and Q2 each stand for hydrogen or a methyl group and n is an integer not higher than 2.  Such compounds are obtained by reacting a compound of the formula <FORM:0744061/IV(a)/2> with a compound of the formula <FORM:0744061/IV(a)/3> and quaternizing the bis-alkyl amine thus formed, or by condensing an alkoxide of a quaternary alkyl-ammoniumalkyl alcohol with a quaternary alkylammoniumalkyl halide.  As a further alternative, an alkoxide of a tertiary aminoalcohol is condensed with an excess of an alkylene halide to give a dialkyl aminoalkyl haloalkyl ether which is then either reacted with a secondary amine to give a bis-dialkyl aminoalkyl ether which is then quaternized by reaction with an alkylating agent, or the dialkylaminoalkyl haloalkyl ether is reacted with a tertiary amine to give a mono-quaternary compound which is alkylated to give a bisquaternary compound. The products, when free hydroxide compounds, form salts with acids such as hydrochloric, hydrobromic, hydriodic, sulphuric, phosphoric, alkylsulphuric, arylsulphonic, citric, tartaric, lactic, fumaric and maleic acids. The hydroxides can be set free from such salts by reaction with silver oxide or barium hydroxide or by hydrolysis with sulphuric acid followed by treatment with barium hydroxide.  The preferred method of effecting the reaction is to employ the aminoalcohol in the form of its alkoxide, to employ a solvent medium and to isolate the aminoalkyl halide from its hydrochloride immediately before use.  In examples: (1) the sodium derivative of diethylamino-ethanol and dimethylaminoethyl chloride are reacted in toluene to give 2-dimethyl-aminoethyl 21-diethylaminoethyl ether which is reacted with methyl iodide and ethyl bromide, respectively, to give the corresponding bis-methiodide and bis-etho-bromide; (2) the sodium alkoxide of dimethylamino ethanol and dipropylaminoethyl chloride are reacted to give 2 - dimethylaminoethyl - 21-dipropylaminoethyl ether, which is isolated as to hydrochloride, reconverted to the free base and quaternated by reaction with methyl iodide in ethanol; (3) 2-dimethylaminoethyl - 21 - diethylaminoethyl ethyl ether is converted by reaction with ethyl sulphate to the bis-ethosulphate, which is boiled with 25 per cent sulphuric acid, and the product is then treated with barium hydroxide.  After filtration the solution is treated with tartaric acid solution to give, on evaporation, the acid bis-tartrate; (4) the sodium derivative of diethylaminoethyl chloride are reacted in toluene to give 2-dimethylaminoethyl-31-diethylaminopropyl ether which is converted to its methiodide and ethobromide; (5) 2-diethylaminoethyl - 21 - dimethylamino - isopropyl ether is prepared similarly and converted to the di-ethosulphate.  The latter is converted to the hydrooide (similarly to example 3) from which the corresponding bis-mono-hydrogen succinate is prepared; (6) the methosulphate of trimethylammonium ethanol and the ethosulphate of triethyl-ammoniumethyl chloride are reacted to give the ether, which is boiled with sulphuric acid to form 2-trimethyl-ammoniumethyl-21-triethylammonium-ethyl hydroxide, and the latter compound is reacted with tartaric acid; (7) the sodium derivative of dimethylaminoethanol is reacted in toluene with 1-chloro-2-bromo-ethane and the product (2-dimethylamino-21-chloroethyl ether obtained is treated with diethylamine to form 2-dimethylaminoethyl-21-diethylaminoethyl ether. This compound is then alkylated; (8) 2-dimethylamino-21-chloroethyl ether (obtained as in example 7) is transformed by treatment with ethyl bromide into 2-dimethylethyl ammoniumethyl-21-chlorethyl ether bromide. This compound is converted into a bis-quaternary ammonium compound by reaction with triethyl amine and the product is treated with silver oxide to give the corresponding hydroxide which is then converted to the tartrate.  Additional starting compounds mentioned are dimethylamino-isopropanol, dipropylaminoethanol and dibutylaminoethanol.