Patent GB-924961-A (GB)
Title: Quaternary ammonium compounds, the preparation thereof and pharmaceutical compositions thereof
Inventor: COPP FREDERICK CHARLES
IPC: C07D295/155
Filed: 1959-03-13
Abstract: The invention comprises quaternary amino compounds containing a cation of the formula R.W.CH2CH2.N+XY.CH2.L, wherein R is a phenyl ring, substituted in the m- or p-positions by a halogen, alkyl, alkoxy, hydroxy, formyl, acetyl, alkoxycarbonyl, amino, acetamido, cyano or nitro substituent when L is a phenyl ring optionally bearing a halogen, alkyl, alkoxy, cyano or nitro substituent or a thienyl or furyl ring optionally bearing a 5-halo or 5-nitro substituent; or R is a phenyl ring optionally substituted in the o-position by a halogen, alkyl, alkoxy, hydroxy, formyl, acetyl, alkoxy-carbonyl, amino, acetamido, cyano or nitro substituent when L is a phenyl ring substituted in the m- or p-position by a halogen, alkyl, alkoxy cyano or nitro substituent; W is a straight saturated chain containing 1-3 nonadjacent oxygen atoms and 0-16 carbon atoms and X and Y are each an alkyl or alkyl group or NXY forms a pyrrolidino, piperidino or morpholino ring, the terms "alkyl", "alkoxy" and "alkoxycarbonyl" denoting groups of 1-4 carbon atoms; with the exception of compounds containing a N-5-p-chlorophenoxy-3-oxapentyl-N-p-chlorobenzyl-N, N-dimethylammonium, N - p - t - butylphenoxyethoxyethyl-N-benzyl-N,N-dimethylammonium, N - benzyl-N-5-p-methylphenoxy-3-oxapentyl-N,N-dimethylammonium, N - benzyl - N,N-diethyl - N-2-m-methoxyphenoxyethylammonium or N - benzyl - N, N - diethyl - N - 2 - m butoxyethylammonium cation. It comprises also a process for preparing these compounds by reacting the corresponding tertiary amine with a reactive ester of the hydroxy derivative of the group it is desired to introduce, e.g. with an alkylating agent.  Alternatively a secondary amine may be treated with two equivalents of an alkylating agent or with an a ,o -disubstituted butane, pentane or 3-oxapentane (to form the pyrrolidine, piperidine or morpholine groups).  Similarly the products may also be made by internal quaternisation of a tertiary amine R.W.CH2CH2.N(XYZ).  CH2L wherein XY is a tetramethylene pentamethylene or 3-oxapentamethylene chain bearing a terminal ester group Z.  When R is a phenyl ring bearing an amino substituent it is necessary to protect the amine group with an acyl, alkoxycarbonyl or hydrocarbonsulphonyl group which is subsequently removed by hydrolysis of the quaternary compound.  Salts of the products are made by conventional processes of salt - formation, double decomposition and anion exchange.  Secondary and tertiary amines, corresponding to the above quaternary compounds, are prepared by standard methods.  p-2-Bromoethoxyacetophenone is made by the action of ethylene dibromide on p-hydroxyacetophenone  Phenoxy alkyl halides of the formula R2-C6H4.W.CH2CH2Z, wherein R2 is Br, CH3, CH3O or NO2 and Z is Br or Cl are described.  1-o-Bromobenzyloxy-2-chloroethane is made by reacting o-bromobenzyl bromide with ethylene glycol and chlorinating the resulting 1-o-bromobenzyloxy-2-hydroxyethane. Pharmaceutical preparations for the treatment of nematode infestations comprise the above quaternary compounds (including the compounds specifically excluded from the product claims), suitably in the form of salts with borofluoride, perchlorate, laurylsulphate, dodecylsulphonate, p-toluenesulphonate, p-chlorobenzenesulphonate, p-bromobenzenesulphonate, p-acylaminobenzenesulphonate, acylaminocarboxylate, diphenylsulphonate, naphthalene mono- and di-sulphonate, naphthoate, dihydroxydiarylmethane dicarboxylate, piperazine-1,4-bis-carbodithioate, diaminostilbenedisulphonate, phenate or trichlorophenate anions, and a pharmaceutical carrier. The preparations may suitably take the form of tablets, granules, capsules, cachets, suspensions, emulsions or a draft or drench in water or a syrup.