JPH0525119A - Production of p-toluenesulfonylacetic acid - Google Patents

Abstract

PURPOSE:To obtain the subject compound in high yield by preparing an aqueous solution of sodium p-toluenesulfinate as an intermediate from inexpensive p- toluenesulfonyl chloride as a starting raw material and adjusting pH with a base and/or adding an iodide during reaction with chloroacetic acid. CONSTITUTION:For example, sodium sulfite and a base are dissolved or suspended in water and reacted with sodium p-toluenesulfonyl chloride to give an aqueous solution of sodium p-toluenesulfinate as an intermediate raw material. In reacting the aqueous solution with chloroacetic acid, the reaction solution is adjusted to pH1.0-4.0 with a base such as sodium hydroxide and/or an iodide such as lithium iodide or sodium iodide (preferably about 0.02-0.06mol based on 1.0mol sodium p-toluenesulfinate) to give p-toluenesulfonylacetic acid in high yield. p-Toluenesulfonylacetic acid is useful as an intermediate raw material for diiodomethyl-p-tolylsulfone suitable as industrial germicide and fungicide.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a method for producing p-toluenesulfonylacetic acid. p-Toluenesulfonylacetic acid is used as an intermediate raw material for the production of diiodomethyl-p-tolylsulfone. Diiodomethyl-p-tolylsulfone is a compound useful as an industrial bactericide and fungicide.

[0002]

2. Description of the Related Art A method for producing methyl p-toluenesulfonylacetate or p-toluenesulfonylacetic acid, which is a desired product, from sodium p-toluenesulfinate as a starting material (Zhurnal Organicheshoj Khimii, 20 , p. 6).
02-608, (1984)) is known. In these methods, sodium p-toluenesulfinate was added to N, N
-Methyl chloroacetate in dimethylformamide, or
Methyl p-toluenesulfonylacetate or p-toluenesulfonylacetic acid can be obtained by reacting an aqueous solution of alkali chloroacetate in water.

[0003]

However, in the method using methyl chloroacetate, the reaction is carried out in an organic solvent such as N, N-dimethylformamide, so that the target substance, p-toluenesulfonylacetic acid, is concentrated in order to recover it. It is not a preferable method because it requires operations such as the above and also causes a problem in waste liquid treatment.

On the other hand, in the method using an aqueous solution of alkali chloroacetate, the system is neutral to weakly alkaline. Therefore, the raw material chloroacetic acid is hydrolyzed and the target p-
By decomposition of toluenesulfonylacetic acid, p-
The yield of toluenesulfonylacetic acid is low at 50-60%. Furthermore, sodium p-toluenesulfinate, which is a raw material in either method, is not advantageous in industrial production because it is relatively expensive.

Therefore, it is an object of the present invention to provide a method for producing p-toluenesulfonylacetic acid in a high yield by using an industrially inexpensive raw material.

[0006]

Means for Solving the Problems As a result of intensive studies on the above problems, the present inventors have used p-toluenesulfonyl chloride as a starting material to obtain an aqueous sodium p-toluenesulfinate solution as an intermediate material. Furthermore, during the reaction of sodium p-toluenesulfinate and chloroacetic acid in this aqueous solution, the pH of the aqueous solution is 1.0 to 4.0.
The present invention has been completed by finding that it is effective to adjust i.d. and / or add iodide to an aqueous solution.

That is, according to the present invention, when p-toluenesulfonylacetic acid is produced from sodium p-toluenesulfinate and chloroacetic acid, the pH of the reaction solution is adjusted to 1.0 to 10 with a base.
A method for producing p-toluenesulfonylacetic acid, which comprises adjusting to 4.0 and / or adding iodide.

First, a conventional method (for example, Organic Syntheses
Collective Volume 1, p. 7, John Wiley & Sons, Inc. (1
941)), sodium sulfite and a base are dissolved or suspended in water, and p-toluenesulfonyl chloride as a starting material is added thereto to obtain p as an intermediate material.
-Prepare an aqueous solution of sodium toluenesulfinate.

Specifically, an aqueous solution of sodium p-toluenesulfinate is produced as follows. Sodium sulfite is dissolved in water. The amount of sodium sulfite is p-
0.9-1 against 1.0 mol of toluenesulfonyl chloride.
It is 0 mol. For the synthesis of sodium p-toluenesulfinate, it is necessary to use a base. As the type of base, alkali metal carbonates, alkali metal hydroxides and the like can be used. Specific examples include sodium carbonate, potassium carbonate, sodium hydrogen carbonate, sodium hydroxide, potassium hydroxide, lithium hydroxide and the like. These bases are added as solids or aqueous solutions. The total amount of the base can be added at the initial stage, or the base can be continuously added little by little according to the addition of p-toluenesulfonyl chloride. When adding the base continuously, adjust the pH to 6.0 or above. If the pH is less than 6.0, the amount of p-toluenesulfonic acid produced as a by-product increases, and the yield of sodium p-toluenesulfinate decreases. The amount of base is p-
1.5--2 for 1.0 mol of toluenesulfonyl chloride.
It is 0 mol. The reaction temperature is preferably 60 to 100 ° C. The reaction time varies depending on the reaction temperature, but is usually 1 to 3 hours.

Then, using the aqueous solution of sodium p-toluenesulfinate obtained by the above method, chloroacetic acid is reacted, the pH of the reaction solution is adjusted with a base, and the reaction is carried out in order to further increase the yield. Iodide is added to the solution to produce the desired product, p-toluenesulfonylacetic acid. The concentration of the sodium p-toluenesulfinate aqueous solution used is
It is usually 10 to 20% by weight, preferably 10 to 17% by weight.

Chloroacetic acid remains an aqueous solution or solid, and p
-Add to the aqueous solution of sodium toluenesulfinate.
When chloroacetic acid is an aqueous solution, it is preferably used at a concentration of 30% by weight or more. If the concentration of the aqueous chloroacetic acid solution is less than 30% by weight, the amount of water increases and the productivity decreases, which is not preferable. The amount of chloroacetic acid is preferably 1.00 to 1.35 mol per 1.0 mol of sodium p-toluenesulfinate. If the amount of chloroacetic acid is less than 1.00 mol, the reaction will not be completed, and even if it exceeds 1.35 mol, there is no difference in its effect.

The pH of the aqueous solution after adding chloroacetic acid is
Adjust to 1.0 to 4.0. When pH exceeds 4.0, hydrolysis of chloroacetic acid as a raw material becomes remarkable, and when pH is less than 1.0, disproportionation reaction of sodium p-toluenesulfinate as a raw material occurs, and in either case Some p-
The yield of toluenesulfonylacetic acid decreases. P of aqueous solution
The H adjustment is performed by adding a base. As the type of base, alkali metal carbonate and alkali metal hydroxide are desirable. Specific examples include sodium carbonate, potassium carbonate, sodium hydrogen carbonate, sodium hydroxide, potassium hydroxide and the like. These bases can be used alone or in a mixture of two or more. The form of the base is an aqueous solution or a solid. It is desirable to add the base all at once at the same time as the addition of chloroacetic acid, but it is also possible to continuously add the base before or after adding chloroacetic acid while adjusting the pH. Alternatively, the base may be previously added all at once to the aqueous solution of chloroacetic acid. The amount of base required for pH adjustment or batch addition varies depending on the type of base and the pH value, but is about 0.3 to 1.0 mol with respect to 1.0 mol of sodium p-toluenesulfinate.

Although the addition of a base as described above can improve the yield of p-toluenesulfonylacetic acid,
More effectively, iodide is added. As the type of iodide, alkali metal iodide, alkaline earth metal iodide, or the like is used. Specific examples include lithium iodide, sodium iodide, potassium iodide, rubidium iodide, magnesium iodide, calcium iodide, strontium iodide and barium iodide. These iodides may be used alone or in a mixture of two or more. The form of iodide is an aqueous solution or a solid. The amount of these iodides is normally 1.0 mol of sodium p-toluenesulfinate.
It is 0.01 to 0.10 mol, preferably 0.02 to 0.06 mol.
The iodide may be added immediately after the addition of chloroacetic acid, but is preferably between 30 minutes and 2 hours after the addition of chloroacetic acid. Even if iodide is added more than 2 hours after the addition of chloroacetic acid, there is no effect of increasing the yield of the desired product, and the effect is low even before addition of chloroacetic acid.

The reaction temperature with chloroacetic acid is usually 50 to 120.
℃, preferably 60 to 100 ℃. Of course, under pressure, the reaction can be carried out even if the temperature exceeds 120 ° C, but this is not necessary because the reaction proceeds sufficiently under normal pressure. If the reaction temperature is less than 50 ° C, the reaction proceeds slowly, which is not advantageous. The reaction time varies depending on the reaction temperature, but is usually 1 to 5 hours.

After completion of the reaction, the reaction solution is neutralized with a base, and the insoluble matter in the solution is removed by a simple operation such as filtration to obtain a uniform p-
An aqueous toluenesulfonylacetic acid solution is obtained. This aqueous solution
It can be subjected to the subsequent iodination step.

[0016]

EXAMPLES The present invention will be described in detail below with reference to examples. In the following, "%" is based on weight, unless otherwise specified. Further, the target substance was quantified by HPLC.

Example 1 215.7 g of water and 40.7 g (0.321 mol) of sodium sulfite were placed in a flask (four-neck, volume: 500 ml) and the temperature was raised to 70 ° C. p-toluenesulfonyl chloride 62.8 g (0.33
0 mol) and 35% sodium hydroxide aqueous solution 69.8 g (0.6
(Corresponding to 09 mol) was introduced over 1 hour to obtain a 14% sodium p-toluenesulfinate aqueous solution. The temperature was raised to 90 ° C., and 71.2 g (corresponding to 0.377 mol) of 50% aqueous chloroacetic acid solution and 19.3 g (corresponding to 0.169 mol) of 35% aqueous sodium hydroxide solution were simultaneously added over 10 minutes. Further, this aqueous solution was stirred at 90 ° C. for 3 hours for reaction. The final pH of the reaction solution was 2.5. Cool the reaction to 30 ° C,
The solution was neutralized with sodium hydroxide and the insoluble matter in the solution was filtered. When the obtained uniform solution was quantified, the yield of p-toluenesulfonylacetic acid was 91.5 mol%. The reaction conditions and yield of p-toluenesulfonylacetic acid are summarized in Table 1.

Example 2 In Example 1, 71.2 g (0.3% of 50% chloroacetic acid aqueous solution) was added.
77 moles equivalent of 48% aqueous chloroacetic acid solution 68.2 g (0.346
The same operation as in Example 1 was carried out except that the amount was changed to (corresponding to mol). As a result, the final pH of the reaction solution was 3.0, and the yield of p-toluenesulfonylacetic acid was 90.5 mol%. p-
The reaction conditions and yield of toluenesulfonylacetic acid are summarized in Table 1.

Example 3 The same operation as in Example 2 was carried out except that the temperature at the time of addition of the 48% chloroacetic acid aqueous solution and the temperature at the time of reaction was changed to 100 ° C. As a result, the pH of the reaction solution is final.
At 2.5, the yield of p-toluenesulfonylacetic acid was 91.7 mol%. The reaction conditions and yield of p-toluenesulfonylacetic acid are summarized in Table 1.

Example 4 In Example 1, when the 50% chloroacetic acid aqueous solution was added,
The same operation as in Example 1 was carried out except that 5% aqueous sodium hydroxide solution was added continuously instead of simultaneously to adjust the pH to 2.5 to 3.0. As a result, the yield of p-toluenesulfonylacetic acid was 90.5 mol%. The reaction conditions and yield of p-toluenesulfonylacetic acid are summarized in Table 1.

Comparative Example 1 In Example 1, 3% was added when a 50% chloroacetic acid aqueous solution was added.
The procedure of Example 1 was repeated except that the 5% aqueous sodium hydroxide solution was not added. As a result, the pH of the reaction solution
Was less than 1.0 at the end, and the yield of p-toluenesulfonylacetic acid was 82.3 mol%. The reaction conditions and yield of p-toluenesulfonylacetic acid are summarized in Table 1.

COMPARATIVE EXAMPLE 2 In Example 1, when the 50% chloroacetic acid aqueous solution was added,
5% aqueous sodium hydroxide solution 45.3g (0.402 mol equivalent)
Was continuously added to adjust the pH to 4.5, and the same operation as in Example 1 was performed. As a result, the yield of p-toluenesulfonylacetic acid was 84.2 mol%. The reaction conditions and yield of p-toluenesulfonylacetic acid are summarized in Table 1.

Example 5 The procedure of Example 1 was repeated to obtain a 14% aqueous solution of sodium p-toluenesulfinate. The temperature was raised to 90 ° C., and 71.2 g (corresponding to 0.377 mol) of 50% chloroacetic acid aqueous solution and 19.3 g (corresponding to 0.169 mol) of 35% aqueous sodium hydroxide solution were simultaneously added over 10 minutes. Furthermore, after 1 hour, 0.99 g (0.0
066 mol) was added, and the mixture was stirred at 90 ° C. for 2 hours for reaction. The final pH of the reaction solution was 2.5. 30 reaction mixture
The mixture was cooled to ° C, neutralized with sodium hydroxide, and the insoluble matter in the solution was filtered. When the obtained uniform solution was quantified,
The yield of p-toluenesulfonylacetic acid was 95.5 mol%. The reaction conditions and yield of p-toluenesulfonylacetic acid are summarized in Table 1.

Example 6 In Example 5, 71.2 g (0.3% of 50% chloroacetic acid aqueous solution) was added.
77 moles equivalent of 48% aqueous chloroacetic acid solution 68.2 g (0.346
The same operation as in Example 5 was performed except that the amount was changed to (corresponding to mol). As a result, the final pH of the reaction solution was 3.0, and the yield of p-toluenesulfonylacetic acid was 95.5 mol%. p-
The reaction conditions and yield of toluenesulfonylacetic acid are summarized in Table 1.

Example 7 The same operation as in Example 6 was carried out except that the temperature at the time of addition of the 48% chloroacetic acid aqueous solution and the reaction time was changed from 90 ° C. to 100 ° C. As a result, the pH of the reaction solution is final.
At 2.5, the yield of p-toluenesulfonylacetic acid was 95.6 mol%. The reaction conditions and yield of p-toluenesulfonylacetic acid are summarized in Table 1.

Example 8 In Example 5, 0.99 g (0.0066) of sodium iodide was used.
(Mole) was changed to 1.09 g (0.0066 mole) of potassium iodide, and the same operation as in Example 5 was carried out. As a result, the final pH of the reaction solution was 2.5, and the yield of p-toluenesulfonylacetic acid was 94.4 mol%. The reaction conditions and yield of p-toluenesulfonylacetic acid are summarized in Table 1.

[0027]

[Table 1] * 1 Molar ratio of chloroacetic acid or iodide to 1.00 mol of sodium p-toluenesulfinate

[0028]

INDUSTRIAL APPLICABILITY According to the present invention, p-toluenesulfonylacetic acid, which is an intermediate raw material during the production of diiodomethyl-p-tolylsulfone, which is an industrial sterilizing and fungicidal agent, and inexpensive p-toluenesulfonyl chloride are starting raw materials. Can be economically manufactured by using Also, during the reaction of sodium p-toluenesulfinate and chloroacetic acid, p
By adjusting H to 1.0 to 4.0 and / or adding iodide to the aqueous solution, p-toluenesulfonylacetic acid can be obtained in high yield. Furthermore, since the amount of by-products in the reaction solution is small, the reaction solution is neutralized with a base, insoluble matter in the solution is removed by a simple operation such as filtration, and the obtained p-toluenesulfonylacetic acid aqueous solution is obtained. It can be subjected to the subsequent iodination step.

Continued front page    (72) Inventor Yoshinori Tanaka             1900 Togo, Mobara-shi, Chiba Mitsui Toatsu Chemical             Within the corporation

Claims (3)

[Claims] 1. When producing p-toluenesulfonylacetic acid from sodium p-toluenesulfinate and chloroacetic acid, the pH of the reaction solution is adjusted to 1.0 to 4.0 with a base. Manufacturing method. 2. An iodide is added to the reaction solution when p-toluenesulfonylacetic acid is produced from sodium p-toluenesulfinate and chloroacetic acid.
-Method for producing toluenesulfonylacetic acid. 3. When producing p-toluenesulfonylacetic acid from sodium p-toluenesulfinate and chloroacetic acid, the pH of the reaction mixture is adjusted to 1.0 to 4.0 with a base, and iodide is added to the reaction mixture. P- characterized by
Method for producing toluenesulfonylacetic acid.