GB774635A - New benzoic acid derivatives, and processes for their preparation - Google Patents

Abstract

The invention comprises compounds of the formula: <FORM:0774635/IV(b)/1> where R1 is a hydrogen atom, an alkyl radical of 1 to 5 carbon atoms or a hydroxyalkyl radical of 1 to 4 carbon atoms, R2 is a hydrogen atom or an alkyl radical of 1 to 5 carbon atoms or NR1R2 forms a heterocyclic ring, R3 is hydrogen or halogen, R4 is a straight or branched chain alkyl group or a carboxy methylene group, X and Z are sulphur or oxygen and m and n are integers from 1 to 3. When NR1R2 is a heterocyclic ring it may suitably be a piperidine, pyrrolidine or morpholine ring. The compounds may be prepared by reacting a compound of the formula: <FORM:0774635/IV(b)/2> with a compound of the formula: Y-[(CH2)m.Z]q.R4, where R5 is either the group -CO.N(R1)R2 or a substituent capable of transformation to such a group, for example a carboxylic acid group -COOH, a carboxylic acid halide group -CO Halogen, an ester group -COO Alkyl or a nitrile radical -CN, Y is a reactive radical such as a halogen atom or a p-toluene sulphonyl radical and p and q are integers from 1 to 3 or zero, the sum of p and q being between 1 and 3, and converting the group R5 into the group -CON(R1)R2 where required. The reaction is suitably carried out in an inert solvent such as ethyl alcohol or toluene at a temperature of 60-150 DEG C. When R5 is a group convertible to the group -CON(R1)R2 it may suitably be a carboxylic acid ester group which is converted by direct amidation, or is saponified to give a free carboxylic group, converted to the amine salt and dehydrated by heating to 100 DEG to 200 DEG C., or is treated with a thionyl halide to give the corresponding acid halide which is then reacted with the amine HNR1R2. Alternatively R5 may be a nitrile group which is converted by partial hydrolysis in the presence of strong mineral acids to give the group -CONH2. Benzoic acid derivatives of the formula: <FORM:0774635/IV(b)/3> wherein r is an integer from 1 to 3 may be made by reacting a compound of the formula M.S. (CH2)n.COOH wherein M is an alkali metal, with the corresponding salicylamide halo-alkyl ether. Examples describe the preparation according to the invention of the 2-ethoxy-ethyl-, 2-propoxyethyl -, 2 - butoxyethyl -, 2 - [(21 - ethoxy) ethoxy] ethyl - 2 - [(21 - butoxy) - ethoxy]-ethyl -, 2 - methyl - thioethyl -, 2 - ethyl - thioethyl - and 2 - carboxymethyl - thioethyl ethers of salicylamide; the 2-propoxyethyl-and 2-carboxymethyl-thioethyl ethers of 5-bromosalicylamide, the 2-ethoxyethyl ethers of salicylic acid and diethylamide, salicylic acid hydroxy-ethylamide, and salicylic acid piperidide, the 2-carboxymethyl-thioethyl ether of salicylic acid methylamide and o-(2-propoxyethylthio) benzoic acid amide. Starting materials. Salicylic ester-ethers, viz. the 2-ethoxyethyl-, 2-[(21-ethoxy)ethoxy] ethyl and 2-[(21-butoxy) ethoxy] ethyl ethers of salicylic acid methyl ester are made by the reaction of methyl salicylate with the appropriate alkoxyethyl bromides.