JPS5946506B2 - Method for producing 2-mercaptobenzimidazole compound - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing 2-mercaptobenzimidazole compounds, and more specifically, the present invention relates to a method for producing 2-mercaptobenzimidazole compounds, and more specifically, by reacting carbon disulfide with an 0-phenylenediamine (hereinafter abbreviated as OPD) derivative, 2-mercaptobenzimidazole compounds are produced. Mercaptobenzimidazole (
In producing the compound (hereinafter abbreviated as 2-MB),
In an aqueous medium, in the presence or absence of a surfactant,
A 2-MB compound characterized in that it is carried out in the presence of any one or more sodium or potassium salts selected from sodium or potassium carbonates, secondary and tertiary phosphates, and tetraborates. It pertains to the manufacturing method.

It is well known that 2-MB can be obtained by reacting OPD with carbon disulfide.

Industrially, 0-nitroaniline is reduced and the resulting OPD is then reacted with carbon disulfide to obtain 2-MB and oN.
H. However, in this PB method, the reaction with carbon disulfide after reduction to OPD is as long as 16 hours, and the theoretical yield for OPD is as low as 75 to 80%.

Furthermore, since 0-nitroaniline is reduced with sodium sulfide, the crude product contains impurities such as sodium thiosulfate and sulfur, so this is dissolved in alkali, treated with activated carbon, and reprecipitated with acid. A purification step is required. A method that can obtain a relatively good yield is to react 0PD with carbon disulfide in an ethanol solution in the presence of potassium hydroxide, and after treatment with activated carbon, neutralize with acetic acid (0rg.Synth.C011 .01.,56
9), but since this method uses ethanol as a solvent, recovery is expensive and it is difficult to adopt it as an industrial method for producing 2-MB.

2-MB by reacting 0PD and carbon disulfide in a solvent
It has been reported that the time required to complete the reaction can be shortened by conducting the reaction in the presence of quaternary ammonium hydroxide when synthesizing 0PD (Japanese Patent Publication No. 51-17552). Alternatively, the reaction of o-toluene diamine containing 4.4% of the isomer with carbon disulfide is exemplified, with a carbon disulfide addition time of 75-135 minutes and a total reaction time of 125-340 minutes. Methylbenzimidazole-2-thiol was obtained at a weight yield of 92.7 to 100% based on diamine (theoretical yield of 69.0 to 74.4% based on 0-toluenediamine).

The present inventors also tried this method, but found that the yield was as low as described, and the product was colored brown. Moreover, since the solvent is limited to organic liquids, recovery is still expensive. On the other hand, according to JP-A-48-78170, 0PD containing 2% impurities is used as 0PD by catalytic hydrogenation of o-nitroaniline.
A method has been proposed in which PD and carbon disulfide are reacted using benzothiazole as a solvent, but in this case, the solvent is benzothiazole, which is a special substance and is too difficult to use for industrial purposes. It's expensive. moreover,
The reaction conditions are harsh, at 130°C and under pressure.
After the reaction, a cumbersome method is used in which the organic layer such as benzothiazole is extracted with an alkali, washed with xylene, and then neutralized to obtain 2-MB. It was thought that 2-MB dissolves in the form of an alkali salt in an alkaline aqueous solution, but the present inventors previously investigated the reaction between 0PD and carbon disulfide in an aqueous medium in the presence of an alkali. It has surprisingly been found that when 0.5 to 2.5 gram equivalents of alkali oxide are used per mole of 0PD, 2-MB can be obtained in free form in very high yields.

As a result of further studies, the present inventors found that it is surprising that one or more selected from the group consisting of carbonates, phosphates, and borates of alkali metals such as sodium and potassium may be used as the base. The present invention was completed based on the discovery that a 2-MB compound can be obtained in extremely high yield by reacting an OPD compound with carbon disulfide. In the case of the method of the present invention, a highly purified product can be obtained by a simple operation of heating and reacting an OPD compound and carbon disulfide in the presence of these salts in an aqueous medium, followed by filtering and washing with water.

The OPD compound used in the method of the present invention has the general formula (1
) R1 [In general formula (1), Rl, R2, R3 and R4
is a hydrogen atom, a halogen atom, an alkyl group or alkoxy group having 1 to 12 carbon atoms, or a nitro group, which may be the same or different from each other.

Specifically, examples of OPD-based compounds include those having the following substituents as OPD and nuclear substituted products thereof.

3-or 4-chloro brome or iodo; 4-fluor; 3,4-, 3,5-, 3,6- or 4,5-
Dichlor or dibrome; 3,5-difluoro- or short; 3,4,6-trichlor; 4-brome
3,5-dichloro; 3,4,5,6-tetrachlor or tetrafluoro; 3-methyl or ethyl; 4-
Methyl, ethyl, isopropyl, n-butyl, Sec-
Butyl, t-butyl, isobutyl, t-amyl or dodecyl; 3,4-, 3,5-, 3,6- or 4,5
-dimethyl; 4,5-diethyl; 4-ethyl-5-propyl; 3,4,5-trimethyl; 4-ethyl-3,5,
6-trimethyl; 4-methoxy or ethoxy; 3,
6-dimethoxy, diethoxy, dipropoxy or dibutoxy; 4,5-dimethoxy, diisopropoxy or dibutoxy; 3,4,5-trimethoxy; 3,4
, 6-trimethoxy; 4-nitro; 3,5- or 4,
5-dinitro; 5-bromo-3,4-dimethyl; 3,
4-dichloro-5,6-dimethyl; 3,5-dichloro-
4,6 dimethyl; 4-chloro-3-methoxy; 5-bromo-3-methoxy; 4-chloro-5-methoxy; 4-chloro-5-nitro; 5-isopropyl-3,4-dimethoxy; 3,6 -dimethyl-4-nitro; 3-methoxy-
5-nitro; 4-methoxy-6-nitro; 5-methoxy-3-nitro; 5-ethoxy-3-nitro.

Each carbonate of an alkali metal used in the method of the present invention,
Specifically, the phosphates or borates include sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, tribasic sodium phosphate, tribasic potassium phosphate,
Examples include dibasic sodium phosphate, dibasic potassium phosphate, sodium tetraborate, and potassium tetraborate, and these can be used alone or in combination of two or more.

In the method of the present invention, each carbonate, phosphate or borate of an alkali metal is added (0.
5 to 5.0) x - molar equivalent (however, Nn is the number of alkali metal atoms contained in one molecule of the salt used, and if two or more types are used, the total amount of each) Preferably (0.6 to 3
．． 0)×1/n mole equivalent is used.

When the amount of these salts used is less than this, the reaction rate is very slow and the yield is low. Furthermore, it is uneconomical to use more than this, and in some cases it may be difficult to mix the mixture by force. In the method of the present invention, the amount of carbon disulfide used is 1.0 to 3.0 molar ratio, preferably 1.1 to 1.5 molar ratio to the 0PD compound.

If carbon disulfide is used in excess, recovery becomes a problem. Water is generally used as the aqueous medium, but in some cases a water-miscible solvent such as alcohol may be added to the raw material.
It is also possible to contain the amount derived from a PD-based compound or the like.

The amount of the aqueous medium to be used is 2 to 20 times, preferably 3 to 8 times, the amount of the 0PD compound.If it is less than this, stirring will be difficult due to a heterogeneous reaction, and if it is more than this, the reaction will occur. Slower speed and lower productivity. In the process of the present invention, additives are generally unnecessary, but in some cases additives may include cationic surfactants, such as lauryltrimethylammonium chloride, anionic surfactants, such as sodium dialkyl sulfonate. succinate, or a nonionic surfactant such as sorbitan monooleate, etc., to 0PD-based compounds.
Adding about 1 to 20% of carbon disulfide to the reaction can shorten the reflux time of carbon disulfide at about 40 to 45°C, suppress bubbling, or make the crystal form denser, so the concentration during the reaction can be increased. There are things you can do.

General embodiments of the present invention include OPD-based compounds,
The carbonate, phosphate or borate salt and water are placed in a reaction vessel equipped with a stirrer, a condenser and a thermometer, and carbon disulfide is added dropwise while stirring.

When heated gradually, carbon disulfide refluxes at 40 to 50°C, but the reflux stops in about 30 minutes to 1 hour, and the temperature starts to rise again. Then, it is gradually heated to 90°C. Generally, the reaction is carried out sufficiently at 60 to 70°C, and then the temperature is raised to 90°C. Of course, at this time, 90
It is also possible to raise the temperature to ℃. Therefore, the reaction is completed in a short time of 1 to 3 hours from the start of heating until the temperature reaches 90°C. Even if the reaction is stopped at 70℃ midway, 2-
The MB derivative can be obtained in a considerable yield, but at this time there is still some unreacted 0PD derivative, so it is preferable to raise the temperature to 90° C. to obtain a preferable result. The reaction product is filtered at room temperature to 90°C, then washed and dried to obtain a very highly purified 2-MB compound.
Since the liquid is alkaline, it needs to be neutralized with sulfuric acid, hydrochloric acid, etc., but hydrogen sulfide is generated at this time, so after the reaction, neutralize with an acid such as sulfuric acid or hydrochloric acid to chase away the hydrogen sulfide. It is also possible to heat the mixture at room temperature to 90°C.
During this neutralization, the precipitated crystals are accompanied by the generated hydrogen sulfide, resulting in intense foaming, but foaming can be suppressed by adding a surfactant such as sodium dialkyl sulfosuccinate. be able to. Of course, it is also effective to add a surfactant to the reaction system from the beginning. Hydrogen sulfide generated during the reaction and neutralization can be absorbed into an aqueous sodium hydroxide solution and used as sodium bisulfide or sodium sulfide. In the method of the present invention, even when a crude 0PD compound that has not been purified and is colored blackish brown is used, a highly pure 2-MB compound can be obtained. In this case, an alkali is added, or the crude product once taken out is dissolved in an alkali again and treated with activated carbon, and the P solution is treated with an inorganic acid such as sulfuric acid, hydrochloric acid, or acetic acid. When acidified with an organic acid such as, a colorless 2-MB compound can be easily obtained.

In addition, the 0PD-based compound obtained by sodium sulfide reduction contains water-soluble impurities, but in the method of the present invention, since the reaction occurs in an aqueous medium, there is no effect and it is used as a raw material 0PD-based compound. It is possible. In addition,
The 2-MB compound produced by the method of the present invention is important as an anti-aging agent for rubber or a stabilizer for polymer compounds.

Next, the present invention will be specifically explained with reference to Examples.

Example 10PD54.1f! , sodium carbonate26.
5f! , sodium dialkyl sulfosuccinate 0.0
A mixture of 759 and 200 Tne of water was placed in a flask with an internal volume of 11, equipped with a stirrer, a reflux condenser, and a charging port, and heated to 35°C.
And carbon disulfide 50.0f! was dripped.

When carbon disulfide is added dropwise, heat is generated, and after about 10 minutes, 46
The temperature reached ℃ and reflux started. The dropping of carbon disulfide was completed after about 30 minutes. The internal temperature reached 60° C., and the suspension, which was light yellowish brown at first and was in a considerably dissolved state, began to precipitate crystals near the end of the dropwise addition. After stirring at 60 to 70°C for 1.5 hours, the temperature was raised to 90°C.

Then, while hot, 24.5% sulfuric acid 1009 was added dropwise to neutralize it, and the precipitated crystals were filtered off and washed twice with 500ml of water. The weight of the wet mass is 74.49. It was dried under reduced pressure at 80° C. overnight to obtain 2-MB74.39. Theoretical yield 99.0% o colorless prismatic crystals based on 0PD.

Mp296~8℃o Example 2 In Example 1, sodium carbonate was 26.5f! 2-MB74. was subjected to the same reaction and post-treatment except that sodium carbonate 53.09 was used instead of 2-MB74. I got 19.

Theoretical yield based on 0PD 98.7%.

Mp 292 ~ 4 ° C o Note that in this example, when the sodium dialkyl sulfosuccinate was not used at all and the reaction was performed using 300 me of water instead of 200 me of water, the temperature was raised to 60 ° C. 1.5
It took hours.

Yield is 74.0f! The theoretical yield based on 0PD is 98.
The temperature was 5% 0mp294-6°C. Furthermore, in this case, even if the product was subjected to \F-filtration without being neutralized with sulfuric acid, the yield, Mp, etc. were almost the same.

Example 3 In Example 1, sodium carbonate 26.59
Instead of using trisodium phosphate (decahydrate)
A similar reaction was carried out using 63.39.

50.09 g of carbon disulfide was added dropwise over 30 minutes. The suspension (PH
About 11.0), the liquid color changes to light brown and the pH is about 6.0.
~7.0 was shown. The internal temperature reached 60°C. Then 60
Stir at ~70°C for 2 hours. After about 30 minutes, crystals began to precipitate and the color of the liquid changed to light orange.
Finally, the temperature was raised to 90°C. The pH at the end of the reaction is approximately 1
It was 0.0. Neutralize by dropping 24.5% sulfuric acid 1001 when hot, filter the precipitated crystals, and add 500Tt of water.
Washed twice with e. The weight of the wet mass is 74.59. Dry under reduced pressure at 80°C overnight to obtain 2-MB74. Obtained O9. 0
Theoretical yield based on PD 98.5% 0mp 293-5°C.

Example 4 In Example 3, trisodium phosphate (1
A similar reaction was carried out using 190.01 tertiary sodium phosphate instead of 63.39 (dihydrate).

Carbon disulfide was added dropwise to 60°C for 30 minutes, then stirred at 60-70°C for 1.5 hours, and finally heated to 90°C.
The temperature was raised to ℃. PH before the start of the reaction and at the end of the reaction
Both were 11.0. 24.5% sulfuric acid 2069
and washed three times with 500 liters of water.

The weight of the wet abyss mass is 74.19. It was dried under reduced pressure at 80° C. overnight to obtain 2-MB73.99. Theoretical yield based on 0PD 98.401).

Mp: 294-6°C Example 5 The reaction was carried out in the same manner as in Example 1, except that 179.19 y of dibasic sodium phosphate (decahydrate) was used instead of 26.5 y of sodium carbonate.

50.09 g of carbon disulfide was added dropwise over 30 minutes, and the internal temperature reached 48° C. and reflux continued. The temperature gradually rose and reached 60°C approximately 50 minutes after the start of the reaction, and soon crystals began to precipitate. Then, the mixture was stirred at 60 to 70°C for 3 hours, and finally the temperature was raised to 90°C. The color of the reaction solution was light yellow from beginning to end, with almost no change. Furthermore, the pH was 8.0 to 8.5 before the reaction, and was 8.0 at the end of the reaction, with almost no change. It was neutralized with dilute sulfuric acid while hot and washed with water. The wet mass weighed 74.5y and was dried overnight at 80°C under reduced pressure to obtain 2-MB74.2y. Theoretical yield based on 0PD 98.8%.

Mp293~5℃o Example 6 Same as Example 1, a mixture of 0PD54.1y1 sodium tetraborate (Na2B4O7.10H20) 95.49, sodium dialkyl sulfosuccinate 0.075y and water 300me was heated to 35℃, Stirred (P
H9. O).

50.0 f1 of carbon disulfide was added dropwise for about 30 minutes. The temperature rose to 49°C and the pH changed to 6.0.
During the dripping process, gas generation began to increase. gradually 60
After raising the temperature to 60-70°C, the mixture was stirred for 3 hours. Finally, the temperature was raised to 90℃. PH is again 8.5-9.0
It was back to . The mixture was neutralized with 24.5% sulfuric acid 1009 at the same temperature, and while hot, the precipitate was filtered and washed with 1500 m of water. The weight of the wet mass is 72.590. After drying at 90°C for 20 hours, the weight is 2-MB72.2f! I got it. Theoretical yield 96.1% based on 0PD 0mp 291-3°C.

Example 7 A by-product during the production of m-tolylenediamine.

-Tolylene diamine mixture (this one contains 53.8 (:!) of 3,4-tolylene diamine, 45.4 α of 2,3-tolylene diamine, and 0.601 of m-tolylene diamine)
), contains 0.2% of other impurities) 61.19
A mixture of 26.59 me of sodium carbonate, 0.159 me of sodium dialkyl sulfosuccinate and 400 me of water was placed in a flask with an internal volume of 11, and 50.0 me of carbon disulfide was added.
9 was added dropwise.

After heating to 60℃ for about 1 hour, 60~70℃
Stir at ℃ for 2 hours. Finally, after raising the temperature to 90℃, 100f of 24.5% sulfuric acid at the same temperature! was added dropwise to neutralize it. The deposited precipitate was filtered under hot water and washed with 500 d of water. The weight of the wet block is 99.190 When dried at 90°C, the mixture of 4-methyl-2-mercaptobenzimidazole and 5-methyl-2-mercaptobenzimidazole is 80.7f! I got it. Yield 98.3% 0mp275~
285°C Example 8 4-Chlor-0PD71.89, sodium carbonate 26.
59, sodium dialkyl sulfosuccinate 0.07
59 and 300 me of water were mixed and heated to 35°C.

At the same temperature, 50.09 g of carbon disulfide was added dropwise. As carbon disulfide was added dropwise, the color of the liquid changed from brown to light brown to blackish brown, and an increase in temperature due to heat generation was observed. temperature is 43
At around ~46°C, gas generation became active and a little bubbling occurred. After the carbon disulfide was added dropwise for about 30 minutes, the temperature was gradually heated to 60°C, and the hot water was heated to 200m. After adding , the mixture was stirred at 60 to 70°C for 2 hours, and finally the temperature was raised to 90°C. Filter the precipitated crystals at 80°C and add 10% water.
I washed it in Gallery 00. The weight of the wet mass of F is 118.19.9
Dry at 0°C for 20 hours to obtain 91 ml of 5-chloro-2-MB. 3
I got a 9.

The theoretical yield for 4-chloro-0PD is 98.9%0m
p295-7°C.

Example 9 In Example 1, sodium carbonate 26.59
2-M
B74.2y was obtained.

Theoretical yield based on 0PD 98.8%.

Claims (1)

[Claims] 1 General formula (I) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(I) [However, in formula (I), R_1, R_2, R_3 and R_4
are the same or different and represent a hydrogen atom, a halogen atom, an alkyl group having 1 to 12 carbon atoms, an alkoxy group, or a nitro group] and react with carbon disulfide to obtain 2-mercapto. In producing benzimidazole compounds, sodium or potassium carbonate, diphosphoric acid or tertiary phosphoric acid is added to 1 mol of O-phenylenediamine compound in an aqueous medium in the presence or absence of a surfactant. (0.5
~5.0) x 1/n mole equivalent (where n is the number of sodium or potassium atoms contained in one molecule of the salt used, and if two or more types are used, the total amount of each)
1. A method for producing a 2-mercaptobenzimidazole compound, the method being carried out in the presence of.