GB935613A - Quaternary ammonium compounds and their preparation - Google Patents

Abstract

The invention comprises quaternary ammonium compounds containing a cation of the formula <FORM:0935613/IV(a)/1> (wherein R7 is methyl, ethyl or 2-hydroxyethyl, the group NR10R11 is dimethylamino, N-ethyl-N-methyl-amino, N-2-hydroxyethyl-N-methyl-amino, pyrrolidino, piperidino or morpholino, L and M are hydrogen or halogen atoms and G is a phenoxy group or an alkoxy group of at most 4 carbon atoms) and their preparation (1) by quaternization of an appropriate tertiary amine to introduce any of the groups phenoxyalkyl, R7, R10 or R11; or (2) for the preparation of compounds wherein NR10R11 is a heterocyclic group, by intramolecular rearrangement of the compound R7R16.NCH2QCH2X (wherein R16 is the appropriate phenoxy-alkyl group, X is a reactive atom or group, such as a halogen atom or a sulphonic ester group such as a p-toluenesulphonate group, and Q is -(CH2)2-, -(CH2)3- or -CH2.O.CH2-). The tertiary amines in process (1) and (2) may be formed in situ. Anions in the compounds of the invention may be exchanged by metathesis. Detailed examples are given. 1-(2-Bromo-4-phenoxy-phenoxy)-2-dimethyl-amino-ethane is prepared by reacting 3-bromo-4-hydroxy-diphenyl ether with ethylene dibromide to give 1-bromo-2-(2-bromo-4-phenoxy-phenoxy)-ethane and then reacting this with dimethylamine. 2-(2-Bromo-4-ethoxy-phenoxy)-1-dimethylaminoethane is prepared from 2-bromo-4-ethoxyphenol and 1-choro-2-dimethlyamino-ethane hydrochloride. Similarly are prepared 2-(4-ethoxyphenoxy)-1-dimethyl-aminoethane and 2-(2-bromo-4-methoxyphenoxy)-1-dimethylaminoethane. N-(2-21-bromo-41-ethoxyphenoxyethyl)-piperidine is prepared by reacting 2-bromo-4-ethoxy-phenol with ethylene dibromide to give 1-bromo-2-(2-bromo-4-ethoxyphenoxy)-ethane and then reacting this with piperidine. 1-Bromo-2-(2-bromo-4-methoxyphenoxy)-ethane and N-(2-21-bromo-41-ethoxyphenoxyethyl)- pyrrolidine and -morpholine are prepared similarly. The quaternary ammonium compounds containing a cation of the above general formula, which are stated to have sympatholytic action, may be made up into pharmaceutical compositions in admixture with suitable carriers. These may take the form of powders, granules, tablets, capsules, cachets, suspensions, solutions, pills, suppositories or pessaries and may contain dispersing, suspending, flavouring, preserving, thickening, emulsifying or solubilizing agents and anti-oxidants, buffers or bacteriostats. Tablets and injection solutions containing N-(2-21-bromo- 41-ethoxyphenoxyethyl)- N,N, N- trimethylammonium iodide and N-(2-21-bromo-41-methoxyphenoxyethyl)- N,N, N- trimethylammonium iodide are described.