2,5-dichlorophenylthioglycolic acid derivative and method for its production

Abstract: The present invention is directed to novel 2,5-dichlorophenylthioglycolic acid derivative, a process for their production and a process for producing the desired product 2,5-dichlorophenylthioglycolic acid derived from said novel compounds. 2,5-dichlorophenylthioglycolic acid derivative of the present invention can be obtained by reacting 2,4,5-trichlorobenzensulfonates and thioglycolic acid in the presence of base, and said desired product can be obtained by desulfonating said compound in an aqueous solution of mineral acid. Novel 4-carboxymethylthio-2,5-dichlorobenzenesulfonates of the present invention can be used advantageously as an intermediate for the production of 2,5-dichlorophenylthioglycolic acid. The use of said intermediate makes it possible to obtain the desired product in a decreased process steps with high yield. In addition, it poses no problem of environmental pollution as pointed out with conventional methods because it uses no heavy metals.

Description: The present invention relates to 2,5-dichlorophenylthioglycolic acid derivatives. More specifically, the invention relates to novel substances 4-carboxymethylthio-2,5-dichlorobenzenesulfonates, methods for their productions, and a method for producing 2,5-dichlorophenylthioglycolic acid derived from said novel substances. 2,5-dichlorophenylthioglycolic acid is a compound which is useful as an intermediate for thioindigo pigments, chemicals for the electronic industry, pharmaceuticals and agricultural chemicals. Particularly, 4,4',7,7'-tetrachlorothioindigo derived from said compound is widely used as a pigment for its high color fastness. There are some conventional methods for producing 2,5-dichlorophenylthioglycolic acid, including the following: (a) the method in which 1,4-dichlorobenzene is sulfochlorinated with chlorosulfonic acid and then reduced to 2,5-dichlorothiophenol with zinc powder under acidic conditions, followed by reaction with monochloroacetic acid to yield 2,5-dichlorophenylthioglycolic acid (US Patent No. 3440288), (b) the method in which 2,5-dichloroaniline is diazotized and then reacted with thiourea in the presence of copper sulfate and subsequently hydrolyzed to 2,5-dichlorothiophenol, followed by reaction with monochloroacetic acid to yield 2,5-dichlorophenylthioglycolic acid (DE-A-3 715 508), (c) the method in which 1,2,4-trichlorobenzene and sodium hydrosulfide are reacted in the presence of copper acetate catalyst in liquid ammonia solvent under increased pressure to yield 2,5-dichlorothiophenol, followed by reaction with monochloroacetic acid to yield 2,5-dichlorophenylthioglycolic acid [Kogyo Kagaku, 70, 1384 (1967)]. However, these known methods respectively have the following drawbacks. In the method of (a) above, a large amount of waste effluent which contains harmful heavy metals poses a major problem of environmental pollution. In the method of (b) above, the copper compound used is difficult to dispose as in (a) and the production efficiency is low; it cannot be said to be an economic method for production. In the method of (c) above, liquid ammonia is difficult to handle and the copper compound used is difficult to dispose, and in addition special equipment is required because the reaction is carried out under high pressure. Also, there is a problem of very low yield. As stated above, all these known methods have various drawbacks and cannot be said to be industrially advantageous. For this reason, attempts have been made to develop an industrially advantageous method for producing 2,5-dichlorophenylthioglycolic acid in the relevant field, but there is no satisfactory method. It is an object of the present invention to provide a method for producing 2,5-dichlorophenylthioglycolic acid easily and economically using no harmful heavy metals. It is another object of the present invention to provide a novel intermediate which serves well for the production of 2,5-dichlorophenylthioglycolic acid. It is still another object of the present invention to provide a method for producing the intermediate. These objects could be achieved on the basis of the finding that the desired product 2,5-dichlorophenylthioglycolic acid can be prepared by reacting 2,4,5-trichlorobenzenesulfonates and thioglycolic acid in the presence of base (Process A) to yield novel 4-carboxymethylthio-2,5-dichlorobenzenesulfonates represented by formula (I), and desulfonating them using an aqueous solution of mineral acid (Process B). Accordingly, the present invention essentially relates to: (1) novel 4-carboxymethylthio-2,5-dichlorobenzenesulfonates, (2) a method for producing novel 4-carboxymethylthio-2,5-dichlorobenzenesulfonates characterized by reacting 2,4,5-trichlorobenzenesulfonates and thioglycolic acid in the presence of base, (3) a method for producing 2,5-dichlorophenylthioglycolic acid characterized by desulfonating 4-carboxymethylthio-2,5-dichlorobenzenesulfonates using an aqueous solution of mineral acid, and (4) a method for producing 2,5-dichlorophenylthioglycolic acid characterized by reacting 2,4,5-trichlorobenzenesulfonates and thioglycolic acid in the presence of base and subsequently reacting the reaction mixture with mineral acid or an aqueous solution of mineral acid. The method for producing 2,5-dichlorophenylthioglycolic acid according to the present invention is a totally novel method and is characterized in that: (1) the use or 2,4,5-trichlorobenzenesulfonates as a starting material offers improvement in the reactivity of the 4-position chlorine atom due to the strong electron attracting property of the sulfone group and thus makes reaction with thioglycolic acid in the presence of base easy to permit direct introduction of the thioglycol group (Process A), and (wherein M represents hydrogen, sodium or potassium) (2) the novel 4-carboxymethylthio-2,5-dichlorobenzenesulfonates thus obtained, which are 2,5-dichlorophenylthioglycolic acid derivatives, can easily be desulfonated to the desired 2,5-dichlorophenylthioglycolic acid by reacting with an aqueous solution of a mineral acid due to the action of the thioglycol group, which is an electron donor (Process B), and the reaction proceeds with high yield in both processes. In accordance with the above-mentioned Process A, the 2,4,5-trichlorobenzenesulfonates used as the starting material are 2,4,5-trichlorobenzenesulfonic acid or alkali metal salts such as the sodium or potassium salt of said sulfonic acid. (wherein M represents hydrogen, sodium or potassium) As stated above, the method of the present invention is a unique method utilizing skillfully the chemical nature of the sulfo group and can be said to be both economically and industrially advantageous because its process steps are decreased and it gives a high yield of the desired product 2,5-dichlorophenylthioglycolic acid. In addition, the method of the present invention is free of environmental pollution problem because it uses no heavy metals. 2,4,5-trichlorobenzenesulfonates, starting materials for the present invention, can easily be obtained by a known method, for example, by sulfonating 1,2,4-trichlorobenzene. The reaction mixture obtained through the above sulfonation process can be used as such in Process A for the present invention. Specifically, Process A is a process in which 2,4,5-trichlorobenzenesulfonates are reacted with thioglycolic acid in the presence of base to yield novel 4-carboxymethylthio-2,5-dichlorobenzenesulfonates, which are derivatives of 2,5-dichlorophenylthioglycolic acid, with high yield. Examples of bases include hydroxides of alkali metals such as sodium hydroxide and potassium hydroxide, carbonates of alkali metals such as sodium carbonate and potassium carbonate and alcoholates of alkali metals such as sodium methylate and sodium ethylate, with preference given to sodium hydroxide because it is less expensive. When using a sodium salt as base, sodium 4-carboxymethylthio-2,5-dichlorobenzenesulfonate can be obtained. When using a potassium salt as base, potassium 4-carboxymethylthio-2,5-dichlorobenzenesulfonate can be obtained. Acidifying said obtained sodium salt or potassium salt by ion-exchange method yields 4-carboxymethylthio-2,5-dichlorobenzenesulfonic acid as shown below. When using an alkali metal salt of 2,4,5-trichlorobenzenesulfonic acid as the starting material, the same kind of alkali metal salt is preferably used as base. The amount of base used is normally in the range from 2.0 to 6.0 mol, preferably 3.0 to 5.5 mol per mol of 2,4,5-trichlorobenzenesulfonate. If the amount is less than 2.0 mol, the yield of the desired product 4-carboxymethylthio-2,5-dichlorobenzenesulfonate decreases; if the amount of base used is more than 6.0 mol, no corresponding effect is obtained so that it is economically disadvantageous. The amount of thioglycolic acid used is normally in the range from 0.9 to 2.0 mol, preferably 1.0 to 1.5 mol per mol of 2,4,5-trichlorobenzenesulfonate. If the amount is less than 0.9 mol, the yield of the desired product 4-carboxymethylthio-2,5-dichlorobenzenesulfonate decreases; if the amount exceeds 2.0 mol, no corresponding effect is obtained so that it is economically disadvantageous. The reaction solvent used is not subject to limitation. Examples of reaction solvents which can be used for the present invention include water, alcohols such as methanol, ethanol, propanol, butanol and ethylene glycol, polar solvents such as N,N-dimethylformamide, N-methyl-2-pyrrolidone, dimethylsulfoxide and sulfolane and mixtures thereof, with preference given to water because it is economic. Reaction temperature is normally in the range from 70 to 250°C , preferably 90 to 180°C . Temperature exceeding 250°C results in reduction in the yield of 4-carboxymethylthio-2,5-dichlorobenzenesulfonates due to side reaction; when the reaction temperature is under 70°C , the reaction velocity obtained is too low for practical use. The reaction proceeds under a normal pressure of 98 kPa (1 kg/cm²) (hereinafter all figures for pressure are shown in absolute unit). In this case, a reaction time of 10 to 50 hours is required. When the reaction is carried out under increased pressure at increased temperature, the reaction time can be shortened. In other words, the reaction can be carried out under increased pressure. In this case, the pressure is normally under 1962 kPa (20 kg/cm²), preferably between 196 and 980 kPa (between 2 and 10 kg/cm²). Under increased pressures exceeding 1962 kPa (20 kg/cm²), the reaction velocity is too high to control the reaction; therefore, such high pressures are undesirable from the viewpoint of operability. Consequently, the reaction can be completed in any reaction time by selecting appropriate reaction pressure and temperature within the above-mentioned ranges, as described in the examples given below. The 4-carboxymethylthio-2,5-dichlorobenzenesulfonates thus obtained can be isolated by an appropriately selected known means such as filtration or extraction under acidic conditions. The desired product 2,5-dichlorophenylthioglycolic acid can be obtained by heating and desulfonating the 4-carboxymethylthio-2,5-dichlorobenzenesulfonates obtained in aforementioned Process A in an aqueous solution of mineral acid (Process B). Examples of the aqueous solution of mineral acid used in Process B include aqueous solutions of sulfuric acid, those of hydrochloric acid and those of phosphoric acid, with preference given to those of sulfuric acid. Although the concentration of the aqueous solution of mineral acid for the desulfonation varies depending on the type of the mineral acid, good results are obtained when the concentration is in the range from 30 to 80%. Concentrations lower than 30% or higher than 80% are undesirable; if the concentration of the aqueous solution of mineral acid is lower than 30%, the reaction velocity is too low for practical use; if it exceeds 80%, the yield of the desired product 2,5-dichlorophenylthioglycolic acid decreases due to side reaction. The amount of mineral acid used is normally in the range from 0.05 to 50 mol, preferably 0.1 to 30 mol per mol of 4-carboxymethylthio-2,5-dichlorobenzenesulfonates. Amounts lower than 0.05 mol or higher than 50 mol are undesirable; if the amount is less than 0.05 mol, the reaction rate is too low; if the amount exceeds 50 mol, no corresponding effect is obtained so that the amount of mineral acid disposed increases. Reaction temperature for Process B is normally in the range from 100 to 200 °C, preferably 120 to 160°C. Reaction temperature exceeding 200°C results in reduction in the yield of the desired product 2,5-dichlorophenylthioglycolic acid due to side reaction; if the reaction temperature is lower than 100°C, the reaction rate obtained is too low for practical use. Process B requires no solvent, but an aqueous solution of mineral acid can be used as a solvent. When the amount of mineral acid is low, a solvent may be added. When using a solvent, its kind is not subject to limitation, as long as it is inert in the desulfonation reaction. Examples of such solvents include halogenated aromatic compounds such as chlorobenzene, dichlorobenzene and trichlorobenzene, ethylene glycol derivatives such as diethylene glycol dimethyl ether and polar solvents such as sulfolane. The production of 2,5-dichlorophenylthioglycolic acid is carried out in Process B after isolating the 4-carboxymethylthio-2,5-dichlorobenzenesulfonates obtained in Process A as stated above. In Process A, the 4-carboxymethylthio-2,5-dichlorobenzenesulfonates may also be used as such without isolation; mineral acid or an aqueous solution of mineral acid is added to the reaction mixture of Process A, followed by desulfonation reaction in the next process (Process B). It is therefore possible to produce 2,5-dichlorophenylthioglycolic acid by a one-pot reaction. In this case, the amount of mineral acid used, reaction conditions and other factors are the same as above. The 2,5-dichlorophenylthioglycolic acid thus obtained can easily be separated, for example, by diluting the reaction mixture with water and then filtering it. As stated above, according to the present invention, the desired product 2,5-dichlorophenylthioglycolic acid can easily be obtained by desulfonating in an aqueous solution of mineral acid novel 4-carboxymethylthio-2,5-dichlorobenzenesulfonates, which are derivatives of 2,5-dichlorophenylthioglycolic acid obtained by reacting 2,4,5-trichlorobenzenesulfonates and thioglycolic acid in the presence of base. Novel 4-carboxymethylthio-2,5-dichlorobenzenesulfonates can be used advantageously as an intermediate for the production of 2,5-dichlorophenylthioglycolic acid. The use of said intermediate makes it possible to obtain the desired product 2,5-dichlorophenylthioglycolic acid in a decreased number of process steps with high yield. The method of the present invention is thus both economically and industrially advantageous and poses no problem of environmental pollution as pointed out with conventional methods because it uses no heavy metals. EXAMPLES The present invention is hereinafter described in more detail by means of the following working examples, but the invention is not limited by these examples. Example 1 To a 300 ml three-necked flask equipped with a stirrer, a thermometer and a condenser were charged 26.15g (0.100 mol) of 2,4,5-trichlorobenzenesulfonic acid, 9.66g (0.105 mol) of thioglycolic acid, 12.6 g (0.315 mol) of sodium hydroxide and 200 ml of water, followed by stirring at 100°C for 10 hours. Then, after cooling to room temperature, the insoluble substances were filtered out. Then, the filtrate was acidified with concentrate hydrochloric acid. The resulting crystal was collected by filtration to yield 23.8 g of a crude crystal. This crude crystal was dissolved in methanol. After separation from the side product inorganic salts, the crystal was purified to yield 23.7 g of a white powder, which was identified as sodium 4-carboxymethylthio-2,5-dichlorobenzenesulfonate from the physical property data shown below. Its yield relative to 2,4,5-trichlorobenzenesulfonic acid was 70.0%. The melting point, elemental analysis data, NMR spectrum data and IR spectrum data of sodium 4-carboxymethylthio-2,5-dichlorobenzenesulfonate are shown below. melting point : more than 300 °C elemental analysis C H Cl S Na found 28.4% 1.5% 20.8% 18.7% 6.7% calculated 28.3% 1.5% 20.9% 18.9% 6.8% NMR( δ ppm, CD₃OD) : 7.98(S, 1H), 7.46(S, 1H), 3.98(S, 2H) IR(cm⁻¹, KBr) : 3500, 3000, 1730, 1220, 1190 Example 2 25.7 g of white powder was obtained in the same manner as in Example 1 except that the sodium hydroxide was replaced with 17.6 g (0.315 mol) of potassium hydroxide, followed by separation and purification. The white powder thus obtained was identified as potassium 4-carboxymethylthio-2,5-dichlorobenzenesulfonate from the physical property data shown below. The yield relative to 2,4,5-trichlorobenzenesulfonic acid was 72.5%. melting point : more than 300 °C elemental analysis C H Cl S K found 27.2% 1.5% 19.9% 17.8% 10.8% calculated 27.0% 1.4% 20.0% 18.0% 11.0% NMR( δ ppm, CD₃OD) : 7.98(S, 1H), 7.46(S, 1H), 3.98(S, 2H) IR(cm⁻¹, KBr) : 3500, 3000, 1730, 1220, 1190 Example 3 10.0 g of sodium 4-carboxymethylthio-2,5-dichlorobenzenesulfonate obtained in Example 1 was acidified by cation exchange resin. After separation and purification, 8.2 g of white powder was obtained. The white powder thus obtained was identified as 4-carboxymethylthio-2,5-dichlorobenzenesulfonic acid from the physical property data shown below. melting point : more than 300 °C elemental analysis C H Cl S found 30.4% 1.9% 22.1% 20.0% calculated 30.3% 1.9% 22.4% 20.2% NMR( δ ppm, CD₃OD) : 7.98(S, 1H), 7.46(S, 1H), 3.98(S,2H) IR(cm⁻¹, KBr) : 3500, 3000, 1730, 1220, 1190 Example 4 To a 300 ml autoclave equipped with a stirrer and a thermometer were charged 12.6 g (0.315 mol) of sodium hydroxide and 200 ml of water, followed by addition of 26.15 g (0.100 mol) of 2,4,5-trichlorobenzenesulfonic acid and 9.66 g (0.105 mol) of thioglycolic acid and stirring at 150°C under hermetic conditions for 6 hours. Through the reaction time pressure showed 490 kPa (5.0 kg/cm²). After completion of the reaction, the reaction mixture was cooled to room temperature and then assayed by high performance liquid chromatography; it was found that 33.3 g of sodium 4-carboxymethylthio-2,5-dichlorobenzenesulfonate was produced. The reaction product ratio was 98.1% relative to 2,4,5-trichlorobenzenesulfonic acid. Examples 5 through 8 Sodium 4-carboxymethylthio-2,5-dichlorobenzenesulfonate was obtained in the same manner as in Example 4 except that reaction was carried out using the reaction pressures, reaction temperatures and reaction times shown in Table 1. The results are shown in Table 1. Exam. No. reaction pressure (kg/cm²) reaction temperature ( °C ) reaction time (Hr) production ratio of sodium 4-carboxymethylthio-2,5-dichlorobenzenesulfonate 5 (1) 98 kPa 100 15 83.6 6 (2) 196 kPa 120 6 84.7 7 (10) 980 kPa 170 1.5 98.0 8 (14) 1372 kPa 180 0.8 97.8 Example 9 To a 300 ml three-necked flask equipped with a stirrer, a thermometer and a condenser were charged 33.9 g (0.10 mol) of sodium 4-carboxymethylthio-2,5-dichlorobenzenesulfonate obtained in Example 1 and 200 g(1.22 mol) of 60% sulfuric acid, followed by stirring at 140 to 145 °C for 10 hours. Then, after cooling to room temperature, the reaction mixture was diluted with water and then filtered, washed with water and dried to yield 22.2 g of a white powder of 2,5-dichlorophenylthioglycolic acid. Its yield relative to sodium 4-carboxymethylthio-2,5-dichlorobenzenesulfonate was 93.6%. Example 10 Using the same procedure as in Example 9 except that the amount of 60% sulfuric acid was changed to 90 g (0.55 mol), 21.8 g of 2,5-dichlorophenylthioglycolic acid was obtained. Its yield relative to sodium 4-carboxymethylthio-2,5-dichlorobenzenesulfonate was 92.0%. Example 11 22.1 g of the white powder, 2,5-dichlorophenylthioglycolic acid was obtained in the same manner as in Example 9 except that 31.7 g (0.10 mol) of 4-carboxymethylthio-2,5-dichlorobenzenesulfonic acid obtained in Example 3 was used. Its yield relative to 4-carboxymethylthio-2,5-dichlorobenzenesulfonic acid was 93.2%. Example 12 To the reaction mixture obtained in Example 4 was added 80 g (0.80 mol) of 98% concentrate sulfuric acid with stirring, followed by heating to 140 to 145°C . During this process, 150 g of water was distilled off. Stirring was continued for 10 more hours at this temperature. Then, after cooling to room temperature, the reaction mixture was diluted with water and then filtered, washed with water and dried to yield 21.1 g of a white powder of 2,5-dichlorophenylthioglycolic acid. Its yield relative to 2,4,5-trichlorobenzenesulfonic acid was 89.0%.

Claims: 4-carboxymethylthio-2,5-dichlorobenzenesulfonates represented by the formula: wherein M represents hydrogen, sodium or potassium. A process for producing a compound of claim 1 which comprises reacting a 2,4,5-trichlorobenzenesulfonate represented by the formula : wherein M represents hydrogen, sodium or potassium, and thioglycolic acid in the presence of base. A process according to claim 2 wherein said base is sodium hydroxide. A process according to claim 2 wherein said base is potassium hydroxide. A process according to any one of claims 2 to 4 wherein the amount of said base used is 2.0 to 6.0 mol per mol of 2,4,5-trichlorobenzenesulfonate. A process according to claim 2 wherein the reaction proceeds under a pressure of not more than 1962 kPa (20kg/cm²). A process for producing 2,5-dichlorophenylthioglycolic acid comprising the step of desulfonating a 4-carboxymethylthio-2,5-dichlorobenzenesulfonate represented by the formula: wherein M represents hydrogen, sodium or potassium, using an aqueous solution of a mineral acid. A process according to claim 7 wherein said aqueous solution of mineral acid is aqueous solution of sulfuric acid. A process according to claim 7 wherein the amount of said aqueous solution of mineral acid used is 0.05 to 50 mol per mol of 4-carboxymethylthio-2,5-dichlorobenzenesulfonates. A process for producing 2,5-dichlorophenylthioglycolic acid which comprises reacting 2,4,5-trichlorobenzenesulfonates represented by the formula : wherein M represents hydrogen, sodium or potassium, and thioglycolic acid in the presence of base; and then reacting the reaction mixture with a mineral acid or an aqueous solution of a mineral acid.

Inventors: GODA HIROSHI C O SUMITOMO SEIK, KIMURA NARIO C O SUMITOMO SEIK, YOSHIDA KATSUHIKO C O SUMITOMO, YOSHIKAWA NAOHIRO C O SUMITOMO, GODA, HIROSHI, C/O SUMITOMO SEIKA CHEMICALS, KIMURA, NARIO, C/O SUMITOMO SEIKA CHEMICALS, YOSHIDA, KATSUHIKO, C/O SUMITOMO SEIKA CHEMICALS, YOSHIKAWA, NAOHIRO, C/O SUMITOMO SEIKA CHEMICALS
Applicants: SUMITOMO SEIKA CHEMICALS, SUMITOMO SEIKA CHEMICALS CO., LTD.
Application year: 1992
Main classification: C07C323
IPC codes: C07C323