Process for the preparation of organometallic complexes.
AS AFRICAN AND MALAGASY P. 887 Yaounde (Cameroon) Patent International Patent Classification: 07 no. 01360 C. the O of £milliwatts. 8 To 40 hr 26 December 1964 requested Mn to the OA m P. I-. (G.P. no. 51,035) called by the business: F Hoffman the strata and companion (anonymous company), resident of Switzerland. Delivered 15 February 1969, published at The preparation of metal complexes between the 2.3-to-dimercapto-succinic acid and a metal, such as the bismuth, antimony, mercury or gold, is known. Is for example reacting acid 2.3-to-dimercapto - with a metal compound suitable succinic, by example dual (OH-)has , The SB2 03 , MmHg (OOCCH3 )2 or AuC13 AND HC1.. The 2.3-to-dimercapto-succinic acid is used in the meso-form. These organometallic complexes that have pre - cieuses therapeutic qualities. Thus, for example, the complexes are distinguished as antimonious schis - tosomiacides. The complexes mercuric accounted - dants have for example been proposed as diuretics, while the gold complexes have the property the disturbance to influence favorably rhumatis - headache. Gold, the inventors have found that metal complexes métalli - er were much more active when they contain the 2.3-to-dimercapto-succinic acid form racémi - that or optically active. Thus, for example, when the experimental treatment of schistosomiasis to the mouse, the complex antimonious Rae acid. 2, 3 - dimercapto succinic is 5 - 10 times more active. The present invention therefore provides a method for the preparation of organo-metallic complexes, by reacting a compound of the general formula: -R-CH(SHUSH) - HUMAN GH (SHUSH) - THE R ' (I-) in which R and R ' represent a group free carboxylic or modified, with a compound of redefined - nICs, antimony, bismuth or mercury in a liquid reaction medium, characterized in that is used as compound of the general formula I a 2.3-to-dimercapto-succinic acid racemic or throughput opti - active quement, carboxylic groups therein - little wind be modified. Rae acid. 2.3-to-dimercapto succinic used as the raw material can for example be prepared by coupling acid acetylene-the dicarboxy - lic and thioacetic acid, hydrolyzing the product obtained and separates, before or after the hydrolysis, by for example by fractional crystallization, the form handsome - the meso form and Economic also formed. The form racemic may, if desired, be shared in the optically active forms. The 2.3-to-dimercapto-succinic acid racemic or optically active carboxylic groups carrying modified also used as the raw material can for example be achieved by treating the acid with alkylating agent, e.g. with diazomethane or alcohols, preferably lower alkanols, in the presence of mineral acids, dialkyl esters thereof are thus formed. Other derivatives usable acid 2.3-to-dimercapto succinic are for example those whose carboxylic groups are salified with alkaline or alkaline earth metals or amines, such as methylamine, ethylamine, dimethylamine, diethylamine, diethanolamine, glucosamine or piperidine, or derivatized groups carbonamidino carbonamido or substituted or unsubstituted amino or imino groups. For carrying out the aforesaid method, can be reacted, in a liquid reaction medium, a dimercaptane of general formula I with a salt, complex, oxide, hydroxide or organometallic compound of arsenic, antimony, bismuth or mercury. As the compound of the general formula I, used for example acid EAR. 2.3-to-dimercapto succinic, or as a salt, preferably in aqueous solution. These salts can be prepared by reaction of the acid RACs. 2.3-to-dimercapto succinic free with hydroxides, metal carbonates, alkali metal bicarbonates, oxides are hydroxides of alkaline earth, ammonia, organic bases, such as methylamine, ethylamine, dimethylamine, diethylamine, diethanolamine, glucosamine, piperidine, amidines, such as pentamidine, like the reaction can also be carried out in organic solvents, such as methanol, the glycol, propylene glycol or glycerin. In the final products of the aforesaid method, the one or two carboxylic groups can be free or substituted. The products may be isolated from the reaction mixture by evaporation of the liquid into the vacuum, preferably at low temperature, or by precipitation with a suitable organic solvent. The invention comprises the organic metal complexes of a racemic or optically active 2,3-dimercapto-succinic acid wherein one or both hydrogen atoms of the mercapto groups is or are replaced by arsenic, antimony, bismuth or mercury, and the alkali- and alkaline earth-metal salts thereof, and the preparation of these compounds by reacting a racemic or optically active 2,3-dimercapto-succinic acid or an alkali- or alkaline earth-metal salt thereof with an oxide, hydroxide, or acid salt of arsenic, antimony, bismuth or mercury in a liquid reaction medium. The alkali- and alkaline earth-metal salts may be formed by reacting the required free acid with an alkali- and alkaline earth-metal base or oxide such as an alkali metal hydroxide, bicarbonate or carbonate or an alkaline earth metal or oxide or hydroxide. In an example a complex of the formula [HOOC-CH(S-Sb/3)-CH(S-Sb/3)-COOH]3 and sodium, potassium and calcium salts thereof are prepared. Therapeutic compositions suitable for oral or parenteral administration in solid form (tablets, dragees, suppositories or capsules) or in liquid form (solutions, emulsions or suspensions) contain as the active ingredient an organic metal complex defined above. Rac-2,3-dimercapto-succinic acid is prepared by dropping thioacetic acid into a mixture of hydrochloric acid in ethyl acetate and the monopotassium salt of acetylene dicarboxylic acid, separating the resulting water and ethyl acetate layers, concentrating the water layer, adding petroleum ether to the water layer to precipitate rac-2,3-diacetylthio-succinic acid, and treating this acid with sodium hydroxide. The racemic form of the acid may be resolved into its optical isomers. By concentrating the ethyl acetate layer referred to above it is possible to precipitate mesco-2,3-diacetylthio-succinic acid. then to 0 °c, saturated with sodium chloride, makes acid at plaques using hydrochloric acid, then extracted with ether. The residue obtained after concentration of the ethereal solution is again in isopropyl ether. This gives 10.5 g acid RACs. 2.3-to-dimercapto succinic melts at 126 - 127 °c. The novel substances of the invention can be processed to pharmaceutical preparations containing the active substance in admixture with a pharmaceutical carrier which can be organic or inorganic, solid or liquid, suitable for oral or parenteral administration. As pharmaceutical carrier, may be used substances that do not react with the novel compounds, for example water, gelatin, lactose, starch, magnesium stearate, talc, gums, the polyalcoylèneglycols, vaseline, and other types of vehicle usage in the medicinal preparations. These preparations may be in the form of tablets, dragees, suppositories, capsules or solutions (e.g. for intravenous injection or intramuscular), suspensions or emulsions. If desired, the preparations can be sterilized and/or may contain excipients, for example preservatives, stabilizers, wetting or emulsifying. They can also include salts a conserved osmotic pressure or compounds buffer, and be combined with other substances therapeutically useful, such as for example local anesthetics. These preparations are obtained by the conventional method, illustrated hereinafter. Rae acid, 2.3 to-dimercapto succinic 80 grams oxide antimonious 43.2 grams sodium hydroxide 4n 210 ml ABSTRACT The invention concerns a process for the preparation of organometallic complexes by reacting a compound of the general formula: (Shush)-R-CH - CH2 - (shush) the R '(the I) in which R and R' represent a group free carboxylic or modified, with a compound of arsenic, antimony, bismuth or mercury in a liquid reaction medium, characterized by the following features, separately or in combination: 1° is used as compound of the general formula I a 2.3-to-dimercapto-succinic acid racemic or optically active, whose carboxylic groups can be modified; 2° racemic acid is used to 2.3 to-dimercaptosuccinic. Company said: F & C. Hoffman-to-rock " (company anonymous) proxy: Office CazenaveEO INDUSTRIAL PROPERTY
Process for the preparation of organo-metallic complexes.