Patent GB-646204-A (GB)
Title: Manufacture of new basic esters of 1-aryl-cycloalkyl-1-monothio-carboxylic acids
Filed: 1947-07-01
Abstract: Basic esters of the formula <FORM:0646204/IV (b)/1> where R1 and R2 are hydrogen, methyl or methoxy, n is 2-6 and Am represents the radical of a secondary aliphatic, cycloaliphatic or heterocyclic amine are prepared by (1) reacting an acid of the formula <FORM:0646204/IV (b)/2> or its anhydride or ester, or halide in the case of a carboxylic acid with a mercaptan HS-CnH2n-Am or a metallic salt thereof; (2) reacting a metallic salt of a thio-carboxylic acid of the above formula with a halo-amine Hal-CnH2n-Am; or (3) reacting a halo-ester of the formula <FORM:0646204/IV (b)/3> with a secondary amine.  The products may be converted into salts with inorganic and organic acids, and may be treated with alkyl halides, dialkyl sulphates or aralkyl halides to give quaternary salts; the latter may be obtained directly by using a tertiary amine in method (3) above. The halo-esters of the formula above are obtained by treating thio-carboxylic acids of the above formula with di-halogen compounds Hal-CnH2n-Hal.  In method (1) above, the acid chloride is preferably used, when the hydrochloride of the basic ester is obtained directly if the reactants are used in equimolecular proportions; an inert organic solvent may be present.  If the free acid is used, an esterification catalyst is preferably added, and when an ester is employed (phenyl ester being preferred) a catalyst such as the corresponding sodium mercaptide may be present.  Preferred products are those derived from dimethylamine, diethylamine and piperidine, in which n is 2 or 3.  Other specified starting materials are: Carboxylic acids thio-carboxylic acids and derivatives in which the aryl group is phenyl, o-, m- or p-tolyl, 3 : 4-dimethylphenyl, o-, m-or p-anisyl, veratryl and 3-methyl-4-methoxy-phenyl; secondary amines: dipropylamine, di-isopropylamine, diallylamine, methylethylamine, cyclopentylethylamine, cyclohexyl-methylamine, pyrrolidine and morpholine; and mercapto-amines where CnH2n is <FORM:0646204/IV (b)/4> , <FORM:0646204/IV (b)/5> <FORM:0646204/IV (b)/6> Salts of the basic esters that may be prepared are the hydrochloride, sulphate, phosphate, acetate, citrate, maleate and ethane-1 : 2-di-sulphonate.  Examples are given of typical products obtained by methods (1) and (2), and samples have been furnished under Sect. 2 (5) of 1 - phenyl - cyclopentane - 1 - thiocarboxylic acid g -diethylamino-propyl ester prepared from (a) 1 - phenyl - cyclopentane - 1 - thiocarboxylic acid S-phenyl ester and g -diethylamino-propyl mercaptan; and (b) 1-phenyl-cyclopentane-1-thiocarboxylic acid g -bromopropyl ester and diethylamine; the bromo-ester is obtained from the free acid and 1 : 3-dibromopropane.  1 - Phenyl - cyclopentane - 1 - monothiocarboxylic acid is obtained from 1-phenyl-cyclopentane-1-carboxylic acid chloride and hydrogen sulphide in pyridine.  The Provisional Specification refers generally to the condensation of acids <FORM:0646204/IV (b)/7> or their functional derivatives with amino-alcohols HO-CnH2n-Am or their functional derivatives, at least one of the reactants being in the form of a derivative containing a thio group.