Patent GB-690429-A (GB)
Title: Improvements in and relating to quaternary ammonium compounds
IPC: C07D295/088
Filed: 1949-12-29
Abstract: The invention comprises bis-tertiary bis-aminoalkoxy alkanes of formula <FORM:0690429/IV (b)/1> and their diquaternary ammonium salts of formula <FORM:0690429/IV (b)/2> where R is the same or different alkyl radicles with 1-4 C atoms, or two R radicles together with the N atom are a saturated heterocyclic radicle of 5-6 members, e.e. pyrrolidino, piperidino, 2-methyl piperidino or morpholino, Hal is Cl, Br or I, m and m1 are integers of 2-4 and n is an integer of at least 2 and m, n and m1 are together at least 8.  The bases may be made by reacting a corresponding bis-halogenalkoxy alkane with a secondary amine of formula R2NH, by tetra-alkylating the corresponding diamine, by reacting an a  : o  alkane diol OH (CH2)nOH in the presence of an acid-binding agent in the form of an alcoholate with 2 mols. of a tertiary aminoalkoxy halide R2N-(CH2)m-Hal and by reacting an a  : o  dihalogen alkane Hal-(CH2)n-Hal with 2 mols. of a tertiary aminoalcohol of formula R2N-(CH2)m-OH in the presence of an acid-binding agent and as an alcoholate. The latter reaction is favoured for the production of bis-tertiary bis-(d -aminobutoxy)-alkanes.  In the above reactions when one mol. of a tertiary aminoalkyl halide or aminoalcohol is used another mol. of an analogous compound may be added to yield unsymmetrical products. Many alkane-diols are specified, representative being glycol, 1,6-hexane diol and 1,10-decane diol. Many aminoalkyl halides are specified including b  - chlorethyl- and g  - bromopropyl - dimethylamine, -methyl-isobutylamine, -ethylbutylamine and -diisobutylamine and N-(b -chlorethyl) - or N - (g  - bromopropyl) - pyrrolidine, -piperidine and -morpholine.  The quaternary ammonium salts may be made by reacting at least 2 mols. of an alkyl halide R-Hal with the bis-tertiary bis-aminoalkoxy alkane or at least two mols. of an amine (R)3N with a bis-halogen alkoxyalkane Hal-(CH2)m-O-(CH2)n-O-(CH2) m1-Hal.  Heat may be necessary and solvents, many of which are specified, may be present.  Quaternary ammonium iodides or bromides may be converted to the chlorides with silver chloride.  Methyl and ethyl bromides and iodides are specified alkyl halides.  Alkylation and quaternization may be performed together when starting with bis-primary di-amines.  The compounds, e.g. 1,10-bis-(b -triethyl-ammonium-ethoxy)-decane-di-iodide or dibromide, influence the muscle tonus.  In examples: (1) 1,10-decane diol and diethylaminoethyl chloride are reacted in toluene with sodium amide or aqueous caustic soda to yield 1,10 - bis - (b  - diethylaminoethoxy) decane which is quaternated in (2) with ethyl iodide or bromide in acetone; (3) dimethylaminoethanol is treated with sodium in toluene containing a little methanol which latter is removed and 1,4-dibromobutane added at the boiling-point to yield 1,4 - bis - (b  - dimethylamino - ethoxy) - butane, which is quaternated in (4) with methyl iodide in acetone; (5) 1,6-dibromohexane and d -diethylaminobutanol are reacted in toluene with sodium amide to give 1,6-bis-(d -diethylaminobutoxy)hexane which is quaternated in (6) with ethyl iodide in acetone; (7) 1,4-di-(g -aminopropoxy)-butane is reacted with formic acid and aqueous formaldehyde to yield the corresponding dimethylamino derivative which is quaternated in (8) with methyl iodide in acetone; (9) 1,10-decane diol is reacted with diethylaminoethyl chloride-hydrochloride and aqueous caustic soda to yield 10-(b -diethylamino-ethoxy)-decanol-1 which is reacted with g -dimethylamino propyl chloride and sodium amide in toluene to yield 1-(b -diethylamino-ethoxy) - 10 - (g  - dimethylamino - propoxy) - decane which is treated with methyl iodide to yield the diiodomethylate and in (10) 1,10-decane-diol is reacted with g -diethylaminopropyl chloride in toluene to yield 10-(g -diethylamino-propoxy)-decanol-1 which on reaction with dimethylamino-ethyl chloride and sodium amide in toluene yields 1-(b -dimethylamino-ethoxy) - 10 - (g  - diethylamino - propoxy) - decane, the diiodomethylate of which is also prepared.  A large number of products are specified, representative being 1,3-bis-(g -dimethylamino-propoxy)-propane and its diiodomethylate, 1,4-bis (b -piperidino-ethoxy)-butane, 1,5 - (b  - diethylamino - ethoxy) - pentane diiodoethylate, 1,6 - bis - (b  - morpholino - ethoxy)-hexane, 1,6 - bis - (g  - dibutylamino - propoxy) - hexane, 1,8 - bis - (b  - diethylamino - ethoxy) - octane diiodoethylate, 1,10 - bis - (b  - dimethylamino-ethoxy)-decane dibromobutylate, 1,14-bis - (b  - diethylamino - ethoxy) - tetradecane, 1,20 - bis - (b  - dimethyl - amino - ethoxy) - eicosane, 1,4 - bis - (b  - pyrrolidino - ethoxy) - butane dichloroethylate and 1,6-bis-(b -[21-methyl-piperidino]-ethoxy)-hexane.  The bis-halogen alkoxyalkane starting materials are made by reacting bis-(o -hydroxyalkoxy)-alkanes with phosphorus halides and the starting substituted butane of example (7) is made by hydrogenating 1,4 - di - (b  - cyanoethoxy) - butane prepared by reacting acrylonitrile with 1,4-butane diol.  Specification 581,994 is referred to.