GB923727A - Benzoylphenalkyl quaternary ammonium compounds and their preparation - Google Patents

Abstract

The invention comprises quaternary ammonium compounds containing a cation of the formula <FORM:0923727/IV(a)/1> (wherein L is a hydrogen or halogen atom or a methyl or ethyl group, n is 1, 2 or 3 and R1 and R2 are methyl or ethyl groups) and their preparation by reaction of a compound R6Q (wherein R6 is an appropriate 4-benzoylphenyl radical, or a methyl or ethyl radical and Q is a reactive ester residue or halogen atom) with an appropriate tertiary amine. The last named may be formed in situ from an appropriate secondary amine and an alkylating agent. Suitable alkylating agents are sulphates, halides and toluene sulphonate. Anions Q may be exchanged by metathesis. Examples are given. 3-Bromo- 4-dimethylaminomethylbenzophenone is prepared by brominating phenyl p-tolyl ketone with N-bromosuccinimide to give 3-bromo-4-bromomethylbenzophenone and reacting this with dimethylamine. 4-(3-Dimethylaminopropyl)-benzophenone is prepared by reacting benzoyl chloride with phenylpropyl benzoate in presence of aluminium chloride to give, on hydrolysis, 4-(3-hydroxypropyl)-benzophenone, reacting this with hydrobromic acid to give 4-(3-bromopropyl)-benzophenone and reacting this with dimethylamine. The quaternary ammonium compounds, which are stated to have a sympatholytic action, may be formulated as pharmaceutical compositions in admixture with suitable carriers. These may take the form of powders, capsules, cachets, suspensions, tablets, pills, suppositories, pessaries or injection solutions and may contain dispersing and surface active, suspending, flavouring, solubilizing, preserving, thickening and emulsifying agents, antioxidants, buffers and bacteriostats. Examples of tablets and injection solutions containing N-3-(4-benzoylphenyl) - propyl - N,N,N - trimethylammonium iodide are provided. The Provisional Specification describes quaternary ammonium compounds containing a cation of the above formula wherein L may additionally represent a methoxy group, there may be a further substituent ortho to the quaternary ammonium alkyl side chain which may have any of the values of L, n is 1, 2, 3, 4, 5 or 6, and the quaternary ammonium group may have the formula -NR2R3R4 wherein R2 is ethyl, 2-hydroxyethyl, isopropyl or allyl when NR3R4 is pyrrolidino, or R2 is methyl and R3 and R4 are methyl, ethyl or 2-hydroxyethyl. The pyrrolidino compounds may be prepared by intramolecular quaternization of corresponding tertiary amines containing a side chain of the formula -(CH2)nN.(R2).(CH2)4 (where) Q is for example a halide or sulphonic ester group, these being prepared from the corresponding compounds wherein Q is a hydroxy group and a halogenating agent or a sulphonyl chloride) or by reaction of a corresponding secondary amine containing a side chain of the formula -(CH2)n-NHR2 with a dihalide or disulphonate Q(CH2)4Q.