JP2789400B2 - 2,5-Dichlorophenylthioglycolic acid derivative and method for producing the same - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to 2,5-dichlorophenylthioglycolic acid derivatives. More specifically, the present invention relates to a novel substance, 4-carboxymethylthio-2,5-dichlorobenzenesulfonic acid, a method for producing the same, and a method for producing 2,5-dichlorophenylthioglycolic acid derived from the novel substance. 2,5-Dichlorophenylthioglycolic acid is a compound useful as an intermediate for thioindigo pigments, electronic industrial chemicals, pharmaceuticals, agricultural chemicals and the like.
In particular, 4,4 ', 7,7'-tetrachlorothioindigo derived from this compound is widely used as a pigment due to its high color fastness.

[0002]

2. Description of the Related Art Conventionally, several methods for producing 2,5-dichlorophenylthioglycolic acid have been known. For example,
(A) 1,4-Dichlorobenzene is sulfochlorinated with chlorosulfonic acid, and then reduced with zinc dust under acidic conditions to give 2,5-dichlorothiophenol, and then reacted with monochloroacetic acid to give 2,5-dichlorophenylthioglycol. Method for preparing acid (US Pat. No. 3,440,288), (b)
After diazotizing 2,5-dichloroaniline, it is reacted with thiourea in the presence of copper sulfate, and then hydrolyzed to 2,5-dichlorothiophenol, and then reacted with monochloroacetic acid to give 2,5. -Dichlorophenylthioglycolic acid (Ger. Offe
n. DE 3715508), (c) 1,2,4- in a liquid ammonia solvent under pressure, in the presence of copper acetate as a catalyst.
A method in which trichlorobenzene is reacted with sodium hydrosulfide to give 2,5-dichlorothiophenol and then monochloroacetic acid is reacted to give 2,5-dichlorophenylthioglycolic acid (Koka Kagaku, 70, 1384 (196)
7)) and the like are known.

[0003]

However, each of the above-mentioned known methods has the following problems. That is, in the method (a), since a large amount of wastewater containing heavy metals harmful to the human body is discharged, environmental pollution is a serious problem. In the method (b), a copper compound which is difficult to dispose is used as in (a), the production efficiency is low, and it cannot be said that the production method is inexpensive. In the method (c), liquid ammonia that is difficult to handle and a copper compound that is difficult to dispose are used, and a special apparatus is required because of the high-pressure reaction. There is also a problem that the yield is extremely low. As described above, all of the known methods have various problems, and cannot be said to be industrially advantageous. Therefore, in the technical field, the development of an industrially advantageous method for producing 2,5-dichlorophenylthioglycolic acid is expected, but a satisfactory method has not yet been found.

[0004]

SUMMARY OF THE INVENTION An object of the present invention is to provide a method for producing 2,5-dichlorophenylthioglycolic acid simply and economically without using heavy metals harmful to the human body. is there. Another object of the present invention is to provide a novel intermediate useful for producing the above-mentioned 2,5-dichlorophenylthioglycolic acid. Still another object of the present invention is to provide a method for producing the above intermediate. That is, the present inventors have proposed a novel 4-carboxy represented by the general formula (1) obtained by reacting 2,4,5-trichlorobenzenesulfonic acid with thioglycolic acid in the presence of a base (step A). It has been found that the desired 2,5-dichlorophenylthioglycolic acid can be obtained by subjecting methylthio-2,5-dichlorobenzenesulfonic acid to a desulfonation reaction (step B) with an aqueous solution of a mineral acid, leading to the present invention. .

That is, the gist of the present invention is to provide (1) novel 4-carboxymethylthio-2,5-dichlorobenzenesulfonic acids and (2) the presence of 2,4,5-trichlorobenzenesulfonic acids and thioglycolic acid in the presence of a base. (3) 4-carboxymethylthio-2,4-carboxymethylthio-2,5-dichlorobenzenesulfonic acid;
(4) a method for producing 2,5-dichlorophenylthioglycolic acid, which comprises desulfonating 5-dichlorobenzenesulfonic acids with a mineral acid aqueous solution;
2,5-dichlorophenyl characterized by reacting 2,4,5-trichlorobenzenesulfonic acid with thioglycolic acid in the presence of a base, and then adding a mineral acid or an aqueous solution of a mineral acid to the reaction solution. The present invention relates to a method for producing thioglycolic acid.

The method for producing 2,5-dichlorophenylthioglycolic acid according to the present invention is a completely novel method which has not been heretofore described. Its features are as follows: (1) Use of 2,4,5-trichlorobenzenesulfonic acid as a raw material As a result, the reactivity of the chloro group at the 4-position is improved due to the strong electron-withdrawing property of the sulfone group, so that it can easily react with thioglycolic acid in the presence of a base and directly introduce the thioglycol group. (Step A),

[0007]

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(2) The novel 4-carboxymethylthio-2,5-dichlorobenzenesulfonic acid, which is a 2,5-dichlorophenylthioglycolic acid derivative obtained as described above, can be converted into a mineral by a thioglycol group having an electron donating property. The desulfonation reaction is easily carried out by the action of an aqueous acid solution to obtain the desired 2,5-dichlorophenylthioglycolic acid (Step B), and the reaction proceeds in high yield in both steps. It is in.

[0009]

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The 2,4,5-trichlorobenzenesulfonic acid used as a raw material in the above (Step A) is
2,4,5-trichlorobenzenesulfonic acid and alkali metal salts of the sulfonic acid such as sodium and potassium.

2,4,5 of the raw materials used in the present invention
-Trichlorobenzenesulfonic acids can be easily obtained by a known method, for example, by sulfonating 1,2,4-trichlorobenzene. Further, the reaction solution obtained in the sulfonation step can be used as it is in step A in the present invention. That is, step A comprises reacting 2,4,5-trichlorobenzenesulfonic acid with thioglycolic acid in the presence of a base to produce a novel 4-carboxymethylthio-2,2,5-dichlorophenylthioglycolic acid derivative. In this step, 5-dichlorobenzenesulfonic acids are obtained in high yield.

Examples of the base include alkali metal hydroxides such as sodium hydroxide and potassium hydroxide, alkali metal carbonates such as sodium carbonate and potassium carbonate, and alkali metal alcoholates such as sodium methylate and sodium ethylate. However, usually, inexpensive sodium hydroxide is preferably used. When a sodium salt is used as a base, sodium 4-carboxymethylthio-2,5-dichlorobenzenesulfonate is obtained, and when a potassium salt is used, potassium 4-carboxymethylthio-2,5-dichlorobenzenesulfonate is obtained. Acidification by a known method such as an ion exchange method gives 4-carboxymethylthio-2,5-dichlorobenzenesulfonic acid as shown in the following examples.

[0013]

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When an alkali metal salt of 2,4,5-trichlorobenzenesulfonic acid is used as a raw material, the same type of alkali metal salt is preferably used as the base. The amount of the base to be used is generally 2.0 to 6.0 moles, preferably 3.0 to 5.5 moles, per 2,4,5-trichlorobenzenesulfonic acid. .
If the molar ratio is less than 2.0 times, the yield of the target 4-carboxymethylthio-2,5-dichlorobenzenesulfonic acid decreases, and even if the molar ratio exceeds 6.0 times, the effect corresponding thereto cannot be obtained. Economically disadvantaged. The amount of thioglycolic acid used is usually in the range of 0.9 to 2.0 moles, preferably in the range of 1.0 to 1.5 moles, per 2,4,5-trichlorobenzenesulfonic acid. It is.
If the molar ratio is less than 0.9 times, the yield of the target 4-carboxymethylthio-2,5-dichlorobenzenesulfonic acid is reduced. Economically disadvantaged.

The reaction solvent is not particularly limited, but may be water, alcohols such as methanol, ethanol, propanol, butanol, ethylene glycol, N, N-dimethylformamide, N-methyl-2-.
Examples thereof include polar solvents such as pyrrolidone, dimethylsulfoxide, and sulfolane, and the like, and mixtures thereof, but water is preferably used for economic reasons. The reaction temperature is usually in the range of 70C to 250C, preferably 90C.
~ 180 ° C. If the reaction temperature exceeds 250 ° C., the yield of 4-carboxymethylthio-2,5-dichlorobenzenesulfonic acid decreases due to side reactions, while if the reaction temperature is lower than 70 ° C., the reaction rate is practically too slow. It is. This reaction proceeds at normal pressure, that is, 1 kg / cm ² (hereinafter, the unit of pressure is indicated by absolute pressure), but in this case, the reaction time requires 10 to 50 hours. When the reaction is carried out under pressure and the reaction temperature is raised, the reaction time can be shortened. In other words, this reaction is also possible to react under pressure, when the reaction under pressure, the pressure range is usually 20 kg / cm ² or less, preferably 2 to 10 kg / cm ^2. 20kg / c
If the reaction is performed under a pressure exceeding m ² , the reaction rate is too high, and it is difficult to control the reaction. Thus, the reaction is, as described in the Examples below,
The reaction can be completed within an arbitrary reaction time by selecting the reaction pressure and the reaction temperature within the above ranges. The thus obtained 4-carboxymethylthio-2,5-
Dichlorobenzenesulfonic acids can be obtained and isolated by acidifying the reaction solution and appropriately using known means, for example, means such as filtration and extraction.

Next, 2,5-dichlorophenylthioglycolic acid, which is the target substance, is obtained by the above-mentioned step A in step 4.
-Carboxymethylthio-2,5-dichlorobenzenesulfonic acid can be obtained by desulfonation by heating in a mineral acid aqueous solution (step B). As the mineral acid aqueous solution used in the step B, a sulfuric acid aqueous solution, a hydrochloric acid aqueous solution, a phosphoric acid aqueous solution and the like can be used, but a sulfuric acid aqueous solution is preferably used. The concentration of the aqueous solution of mineral acid at the time of the present desulfonation reaction cannot be unconditionally determined depending on the type of each mineral acid, but a preferable result is usually obtained in the range of 30 to 80%. If the concentration of the aqueous solution of the mineral acid is lower than 30%, the reaction rate is practically too slow, and if it is higher than 80%, the yield of 2,5-dichlorophenylthioglycolic acid, which is the target product, decreases due to side reactions, which is not preferable. .

The amount of the mineral acid used is usually in the range of 0.05 to 50 moles, preferably 0.1 to 50 moles per mole of 4-carboxymethylthio-2,5-dichlorobenzenesulfonic acid.
It is in the range of 1 to 30 times mol. The amount of mineral acid used is 0.05
If the molar ratio is less than twice, the reaction rate is slow, and conversely, the amount of the mineral acid used is 5
Even if it is 0 mole or more, not only the effect corresponding thereto is not obtained but also the amount of discarded mineral acid increases, which is not preferable. The reaction temperature in step B is usually 100 ° C to 200 ° C.
° C, preferably in the range of 120 ° C to 160 ° C. If the reaction temperature exceeds 200 ° C., the yield of 2,5-dichlorophenylthioglycolic acid, which is the target product, decreases due to side reactions. Conversely, if the reaction temperature is lower than 100 ° C., the reaction rate is practically too slow. . In step B, it is not necessary to use a solvent, and a mineral acid aqueous solution can also serve as the solvent. However, if the amount of the mineral acid used is small, a solvent can be added. When using a solvent,
The solvent is not particularly limited as long as it is inert in the present desulfonation reaction. Examples thereof include halogenated aromatic compounds such as chlorobenzene, dichlorobenzene, and trichlorobenzene, and 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 by isolating the 4-carboxymethylthio-2,5-dichlorobenzenesulfonic acid obtained in step A and using it in step B as described above. , Without isolating 4-carboxymethylthio-2,5-dichlorobenzenesulfonic acid in step A
A mineral acid or an aqueous solution of a mineral acid can be added to the reaction solution of (1) to lead to the desulfonation reaction (step B) in the next step. Accordingly, production of 2,5-dichlorophenylthioglycolic acid by a one-pot reaction is also possible. In this case, the amount of the mineral acid used and the reaction conditions are the same as those described above. The 2,5-dichlorophenylthioglycolic acid thus obtained can be easily obtained, for example, by diluting the reaction solution with water and then filtering.

As described above, according to the present invention, 2, 4, 5
2,5 obtained by reacting trichlorobenzenesulfonic acid with thioglycolic acid in the presence of a base
The desired 2,5-dichlorophenylthioglycolic acid can be easily prepared by desulfonating a novel 4-carboxymethylthio-2,5-dichlorobenzenesulfonic acid, which is a dichlorophenylthioglycolic acid derivative, in a mineral acid aqueous solution. can get.

[0020]

EXAMPLES The present invention will be described in more detail with reference to the following Examples, which should not be construed as limiting the present invention. Example 1 2,4,5-Trichlorobenzenesulfonic acid 2 was placed in a 300 ml three-necked flask equipped with a stirrer, a thermometer, and a cooler.
6.15 g (0.100 mol), thioglycolic acid 9.
66 g (0.105 mol), sodium hydroxide 12.6
g (0.315 mol) and 200 ml of water.
Stirred at C for 10 hours. After cooling to room temperature, insolubles were removed by filtration, and the filtrate was acidified with concentrated hydrochloric acid, and the precipitated crystals were collected by filtration to obtain 23.8 g of crude crystals. This was dissolved in methanol and separated and purified from by-product inorganic salts to obtain 23.7 g of a white powder. This was identified as sodium 4-carboxymethylthio-2,5-dichlorobenzenesulfonate from the following physical data. The yield based on 2,4,5-trichlorobenzenesulfonic acid was 70.0%. Melting point of sodium 4-carboxymethylthio-2,5-dichlorobenzenesulfonate, elemental analysis, N
The data of MR spectrum and IR spectrum are shown. Melting point: 300 ° C. or more Elemental analysis: CHClSNa measured 28.4% 1.5% 20.8% 18.7% 6.7% calculated 28.3% 1.5% 20.9% 18.9% 6.8% NMR (δ ppm, CD ₃ OD): 7.98 (S , 1H)
7.46 (S, 1H) 3.98 (S, 2H) IR (cm ⁻¹ , KBr method): 3500, 3000, 1730,
1220, 1190

Example 2 The procedure of Example 1 was repeated, except that 17.6 g (0.315 mol) of potassium hydroxide was used instead of sodium hydroxide, and the mixture was separated and purified to obtain 25.7 g of a white powder. Was. This was identified as potassium 4-carboxymethylthio-2,5-dichlorobenzenesulfonate from the following physical data. The yield based on 2,4,5-trichlorobenzenesulfonic acid was 72.5%. Melting point: 300 ° C. or more Elemental analysis: CHClSK measured 27.2% 1.5% 19.9% 17.8% 10.8% Calculated 27.0% 1.4% 20.0% 18.0% 11.0% NMR (δ ppm, CD ₃ OD): 7.98 (S , 1H)
7.46 (S, 1H) 3.98 (S, 2H) IR (cm ⁻¹ , KBr method): 3500, 3000, 1730,
1220, 1190

Example 3 4-Carboxymethylthio-2,5 obtained in Example 1
After acidifying 10.0 g of sodium dichlorobenzenesulfonate with a cation exchange resin, the mixture was separated and purified to obtain 8.2 g of a white powder. This was identified as 4-carboxymethylthio-2,5-dichlorobenzenesulfonic acid from the following physical property data. Melting point: 300 ° C. or more Elemental analysis: CHClS measured 30.4% 1.9% 22.1% 20.0% Calculated 30.3% 1.9% 22.4% 20.2% NMR (δ ppm, CD ₃ OD): 7.98 (S, 1H)
7.46 (S, 1H) 3.98 (S, 2H) IR (cm ⁻¹ , KBr method): 3500, 3000, 1730,
1220, 1190

Example 4 In a 300 ml autoclave equipped with a stirrer and a thermometer, 12.6 g (0.315 mol) of sodium hydroxide and 20 ml of water were added.
Then, 26.15 g (0.100 mol) of 2,4,5-trichlorobenzenesulfonic acid and 9.66 g (0.105 mol) of thioglycolic acid were added.
The mixture was stirred at 150 ° C for 6 hours in a sealed state. The pressure at this time was 5.0 kg / cm ² . After the reaction, the reaction solution cooled to room temperature was quantified by high performance liquid chromatography to find that 33.3 g of 4-carboxymethylthio-2,5-
Sodium dichlorobenzenesulfonate was produced. The reaction yield was 98.1% based on 2,4,5-trichlorobenzenesulfonic acid.

Examples 5 to 8 In the same manner as in Example 4 except that the reaction was carried out at the reaction pressure, reaction temperature and reaction time shown in Table 1, 4-carboxymethylthio-2,5-dichlorobenzenesulfonic acid was used. Sodium was obtained. Table 1 shows the results.

[0025]

[Table 1]

Example 9 A 300 ml three-necked flask equipped with a stirrer, a thermometer and a condenser was charged with the 4-carboxymethylthio-
Sodium 2,5-dichlorobenzenesulfonate 33.
9 g (0.10 mol), 200 g of 60% sulfuric acid (1.22 mol)
Mol), and the mixture was stirred at 140 to 145 ° C for 10 hours. After cooling to room temperature, the reaction solution was diluted with water, filtered, washed with water, and dried to obtain 22.2 g of 2,5-dichlorophenylthioglycolic acid as a white powder. The yield based on sodium 4-carboxymethylthio-2,5-dichlorobenzenesulfonate was 93.6%.

Example 10 The reaction was carried out in the same manner as in Example 9 except that the amount of 60% sulfuric acid was changed to 90 g (0.55 mol) to obtain 21.8 g of 2,5-dichlorophenylthioglycolic acid. The yield based on sodium 4-carboxymethylthio-2,5-dichlorobenzenesulfonate was 92.0%.

Example 11 4-Carboxymethylthio-2,5 obtained in Example 3
22.1 g of white powdered 2,5-dichlorophenylthioglycolic acid in the same manner as in Example 9 except that 31.7 g (0.10 mol) of dichlorobenzenesulfonic acid was used.
I got The yield based on 4-carboxymethylthio-2,5-dichlorobenzenesulfonic acid was 93.2%.

Example 12 80 g of 98% concentrated sulfuric acid was added to the reaction solution obtained in Example 4 while stirring.
(0.80 mol), and the temperature was raised to the range of 140 to 145 ° C. During this time, 150 g of water distilled. Stirring was further continued at this temperature for 10 hours. After cooling to room temperature, the reaction solution was diluted with water, filtered, washed with water, and dried to obtain a white powder of 2,5-dichlorophenylthioglycolic acid 2
1.1 g were obtained. The yield based on 2,4,5-trichlorobenzenesulfonic acid was 89.0%.

[0030]

The method of the present invention is an epoch-making method utilizing the chemical properties of a sulfone group, and is a novel 4-method.
By using carboxymethylthio-2,5-dichlorobenzenesulfonic acid as an intermediate, the process is short, and the desired product, 2,5-dichlorophenylthioglycolic acid, can be obtained in high yield. It can be said that this method is also advantageous. Furthermore, since the method of the present invention does not use any heavy metals, there is no problem such as environmental pollution.

──────────────────────────────────────────────────続 き Continuing from the front page (72) Katsuhiko Yoshida, inventor, 346, Miyanishi, Harima-cho, Kako-gun, Hyogo Pref. (58) Field surveyed (Int. Cl. ⁶ , DB name) C07C 323/52 C07C 323/66 CA (STN) REGISTRY (STN)

Claims (10)

(57) [Claims] 1. A compound of the general formula (1) (In the formula, M represents a hydrogen atom, sodium or potassium.) 4-carboxymethylthio-2,5-
Dichlorobenzene sulfonic acids. 2. A compound of the general formula (2) (2) wherein 2,4,5-trichlorobenzenesulfonic acid represented by the formula (M represents a hydrogen atom, sodium or potassium) is reacted with thioglycolic acid in the presence of a base. A method for producing the described compound. 3. The method according to claim 2, wherein the base is sodium hydroxide.
The manufacturing method as described. 4. The method according to claim 2, wherein the base is potassium hydroxide. 5. The method according to claim 2, wherein the amount of the base used is 2.0 to 6.0 times the molar amount of 2,4,5-trichlorobenzenesulfonic acid. 6. The method according to claim 2, wherein the reaction is performed under a pressure of 20 kg / cm ² or less. 7. A compound of the general formula (1) (In the formula, M represents a hydrogen atom, sodium or potassium.) 4-carboxymethylthio-2,5-
A method for producing 2,5-dichlorophenylthioglycolic acid, comprising desulfonating dichlorobenzenesulfonic acids with a mineral acid aqueous solution. 8. The method according to claim 7, wherein a sulfuric acid aqueous solution is used as the mineral acid aqueous solution. 9. The amount of the mineral acid used is based on 4-carboxymethylthio-2,5-dichlorobenzenesulfonic acid.
The production method according to claim 7, wherein the molar ratio is in the range of 0.05 to 50 times. 10. A compound of the general formula (2) (Wherein M represents a hydrogen atom, sodium or potassium), and thioglycolic acid is reacted with a thioglycolic acid in the presence of a base. Alternatively, a method for producing 2,5-dichlorophenylthioglycolic acid, wherein a reaction is performed by adding an aqueous solution of a mineral acid.