GB924146A - Quaternary ammonium compounds and their preparation - Google Patents

Abstract

The invention comprises compounds containing a cation of the general formula <FORM:0924146/IV(a)/1> wherein R1 is an ethyl, 2-hydroxyethyl, isopropyl, or allyl group when NR2R3 is a dimethylamino or pyrrolidino group, or R1 is a methyl group when R2 and R3 are the same or different and each is an ethyl or 2-hydroxyethyl group; the preparation thereof by reacting a tertiary amine having all but one of the groups desired in the quaternary ammonium cation attached directly to the nitrogen atom, with a reactive ester of the hydroxy derivative of the group it is desired to introduce; and pharmaceutical compositions containing them. The quaternisation reaction includes the intramolecular rearrangement of a tertiary n-butylamine O-CF3,C6H4,CH2,NR1 ,(CH2)4,Z (where Z is a reactive ester group) by heating to form the compound where NR2R3 is a pyrrolidino group. The teritary butylamine is formed in situ from the secondary amine and a 1,4-disubstituted-butane Z,(CH2)4,Z. The salts of the quaternary ammonium cation may be converted by double decomposition in solution or on an ion exchange column into the salt of another anion. o- Trifluoromethylbenzyldimethylamine is prepared by reducing o-trifluoromethylbenzoic acid with lithium aluminium hydride to give o-trifluoromethylbenzyl alcohol forming the bromide with hydrobromic acid and reacting this with dimethylamine. Pharmaceutical compositions useful for the treatment of hypertension, comprise the quaternary ammonium compounds of the invention together with an acceptable carrier therefor, and may be formulated as powders, granules, capsules, cachets, tablets, suspensions, solutions, emulsions, suppositories or pessaries.