Patent GB-736804-A (GB)
Title: Manufacture of mercury compounds of para-amino salicylic acid derivatives
IPC: C07C233/12
Filed: 1952-09-17
Abstract: The invention comprises organo-mercury compounds of the general formula <FORM:0736804/IV (b)/1> wherein R represents hydrogen or an alkyl or hydroxyalkyl radical containing up to 6 carbon atoms, R1 represents an aliphatic acyl radical containing up to 6 carbon atoms and n is 1, 2 or 3, and a process for the preparation thereof wherein a p-amino-salicylic acid ester, acylated in the amino group by an aliphatic carboxylic acid containing up to 6 carbon atoms, is heated with allylamine, the allylamide thus obtained is condensed in an alkaline medium with an aliphatic halocarboxylic acid containing up to 6 carbon atoms and the condensation product is reacted with a mercuric salt of an organic carboxylic acid in the presence of water or an aliphatic mono- or poly-hydric alcohol containing up to 6 carbon atoms.  The acyl radical attached to the nitrogen atom in the organomercury compound may be an acetyl, propionyl or butyryl radical.  The ester radical in the salicylic acid ester reactant may be derived from an aliphatic or aromatic alcohol or a phenol-particularly from a lower aliphatic alcohol such as methanol, ethanol, propanol, isopropanol or butanol or amyl alcohol.  Suitable aliphatic halocarboxylic acids are chloracetic, bromacetic, iodoacetic, chloropropionic, bromopropionic, iodopropionic, chlorobutyric, bromobutyric and iodobutyric acids.  Suitable mono- and polyhydric alcohols are methanol, ethanol, propanol, isopropanol, butanol, amyl alcohol, ethylene glycol, 1,3-propylene glycol, 1,2-propylene glycol, 1,4-butanediol and glycerol.  The alkali metal salts of the organo-mercury compounds are also referred to.  In the examples the following compounds are prepared using 4-acetylamino - 1 - (N - allylcarbamido) - phenoxyacetic acid-2 for the reaction with the mercuric salt of a carboxylic acid and which has been obtained by heating 4 - acetylamino - 2 - hydroxybenzoic acid methyl ester with allylamine and reacting the resulting 4-acetylamino-2-hydroxybenzallylamide with chloracetic acid in the presence of sodium hydroxide; 4-acetylamino-1 - [N - (31 - hydroxy - mercuri - 21 - methoxypropyl - 11) - carbamido] - 2 - phenoxyacetic acid and the sodium salt thereof, 4-acetylamino-1 - [N - (31 - hydroxy - mercuri - 21 - hydroxypropyl - 11) - carbamido] - 2 - phenoxyacetic acid and the sodium salt thereof, 4-acetylamino-1 - [N - (31 - hydroxy - mercuri - 21 - b  - hydroxyethoxy - propyl - 11) - carbamido] - 2 - phenoxyacetic acid and the sodium salt thereof, and 4-acetylamino - 1 - [N - (31 - hydroxy - mercuri - 21-b  - hydroxypropoxy - propyl - 11) - carbamido]-2-phenoxyacetic acid and the sodium salt thereof.ALSO:Medicines containing organo-mercury compounds are obtained by dissolving in water an alkali metal salt of a compound of the general formula <FORM:0736804/VI/1> wherein R represents hydrogen or an alkyl or hydroxyalkyl radical containing up to 6 carbon atoms, R1 represents an aliphatic acyl radical containing up to 6 carbon atoms and n is 1, 2 or 3, and adding theophylline.  In the examples compositions are prepared by forming aqueous solutions of each of the alkali metal salts of 4-acetylamino - 1 - [N - (31 - hydroxy - mercuri - 21 - methoxypropyl - 1) - carbamido] - 2 - phenoxyacetic acid, 4 - acetylamino - 1 - [N - (31-hydroxy - mercuri - 21 - hydroxypropyl - 11)-carbamido] - 2 - phenoxyacetic acid, 4 - acetylamino - 1 - [N - (31 - hydroxy - mercuri - 21 - b -hydroxyethoxy - propyl - 11) - carbamido] - 2-phenoxyacetic and 4 - acetylamino - 1 - [N - b 1-hydroxy - mercuri - 21 - b  - hydroxypropoxypropyl - 11) - carbamido] - 2 - phenoxyacetic acid, and then adding theophylline.