JP3501477B2 - Method for producing sulfide compound - Google Patents

Description

Detailed Description of the Invention

FIELD OF THE INVENTION The present invention relates to an improved process for producing sulfide compounds useful as intermediates for herbicides.

[0002]

2. Description of the Related Art Various triazole compounds are known as active ingredients of herbicides in JP-A-1-121279, JP-A-2-1481, JP-A-2-233665, JP-A-3-279368 and the like. As the intermediate of the formula (3)

[0003]

[Chemical-4]

A sulfide compound represented by the formula (wherein R ₁ , R ₂ and R ₃ represent a hydrogen atom, a halogen atom, a lower alkyl group, a lower alkoxy group or a trifluoromethyl group, and X represents an anion residue). Is used.

As a method for producing the sulfide compound, a method of reacting a diazonium compound with a triazole compound has been described or suggested.
According to the methods described in these, the yield is low, and it cannot be said to be sufficient in industrial production. In these documents, for example, the relationship between the reaction temperature and the yield, the relationship between the reaction reagent charging method and the yield, and the like are not clarified, and particularly as a method for producing the target sulfide compound on an industrial scale. Is insufficient. The present inventors have found that it is difficult to industrially advantageously produce the sulfide compound represented by the general formula (3) by these known methods.

[0006]

DISCLOSURE OF THE INVENTION The present inventors first investigated the relationship between reaction temperature and yield, and measured the heat of reaction between a diazonium compound and a triazole compound.
In the present reaction, the lower the reaction temperature (preferably 10 ° C. or lower, more preferably 5 ° C. or lower), the higher the yield, and the charging time (or dropping time) of the diazonium compound or triazole compound. It was confirmed that the shorter the value was, the higher the yield.

On the other hand, when the desired sulfide compound is produced on an industrial scale, it takes a long time to remove heat, so that it is difficult to react the reaction at a low reaction temperature in a short time. From the above results, in this reaction, for example, a solution of the triazole compound represented by the general formula (2) was charged into the reactor, and the refrigerant was passed through the jacket of the reactor to keep the temperature low while cooling the diazonium compound represented by the general formula (1). It has been found that industrial production by a general method of dropping a solution requires a long time for dropping, resulting in a large decrease in yield and is not suitable. An object of the present invention is to provide a method for producing a desired sulfide compound on an industrial scale with a high yield and industrially advantageously.

[0008]

The present invention is based on the general formula (1)

[0009]

[Chemical-5]

(Wherein R ₁ , R ₂ and R ₃ represent a hydrogen atom, a halogen atom, a lower alkyl group, a lower alkoxy group or a trifluoromethyl group, and X represents an anion residue). Compounds and general formula (2)

[0011]

[Chemical-6]

## STR1 ## wherein M represents an alkali metal or an alkaline earth metal, and a triazole compound represented by the formula (3)

[0013]

[Chemical-7]

In the method for producing the sulfide compound represented by the formula (wherein R ₁ , R ₂ and R ₃ have the above meanings), one of the general formula (1) and the general formula (2) This is a method for producing a sulfide compound, characterized in that a reaction reagent is intermittently dropped and reacted.

The present inventors have earnestly studied and studied a method for industrially advantageously producing the sulfide compound represented by the general formula (3), and as a result, shown by the general formula (1) or the general formula (2). It was found that the yield drop is small even if the time from the start of the dropping to the end of the dropping is long if the substantial dropping time of the compound to be added is short, and either the general formula (1) or the general formula (2) It was found that the yield can be remarkably improved by intermittently dropping the reaction reagent of.

Further, the inventors of the present invention can provide a compound represented by the above general formula (1) or general formula (2) by a method of installing a heat exchanger outside the reactor and forcibly circulating it with a pump. It was found that it is effective to remove the heat of reaction by dropping the solution as short as possible, and this effectively acts to improve the yield. Note that, for example, a method of refluxing the reaction solvent under reduced pressure and removing the heat of reaction by the latent heat of vaporization can be considered, but in this reaction, nitrogen gas generates an equimolar amount with the diazonium compound represented by the general formula (1). However, the displacement of the vacuum system is enormous, which is not suitable.

The most preferred embodiment of the present invention is a means for forcibly circulating in an external heat exchanger and the above-mentioned general formula (1).
Alternatively, it is a so-called combined method in which a method of intermittently dropping one of the reaction reagents of the compounds represented by the general formula (2) is combined. At this time, it is possible to additionally use a method of supplementary heat removal, such as installing a coil through which a refrigerant is passed in the reactor or passing a refrigerant through a jacket outside the reactor.

The present invention will be described in more detail below. The diazonium compound represented by the general formula (1) used in the present invention has the following general formula (4)

[0019]

[Chemical-8]

(In the formula, R ₁ , R ₂ and R ₃ represent a hydrogen atom, a halogen atom, a lower alkyl group, a lower alkoxy group or a trifluoromethyl group), an aniline derivative represented by a mineral such as hydrochloric acid or sulfuric acid. It can be obtained by a known method of diazotization with an acid and sodium nitrite. The anion residue represented by X in the diazonium compound represented by the general formula (1) includes a halogen atom, HSO ₄ , NO ₃ or C.
Represents lO ₄ etc.

Here, the aniline derivative represented by the general formula (1) is specifically aniline, 2-chloroaniline, 3-chloroaniline, 4-chloroaniline,
2-chloro-4-trifluoromethylaniline, 2-trifluoromethylaniline, 3-trifluoromethylaniline, 4-trifluoromethylaniline, 2-methylaniline, 3-methylaniline, 4-methylaniline,
4-ethylaniline, 2-methoxyaniline, 3-methoxyaniline, 4-methoxyaniline, 3,5-dichloroaniline, 2,4-difluoroaniline, 3,5-dimethylaniline, 2,4-dimethylaniline, 2 , 6-
Dimethylaniline, 2-methyl-6-ethylaniline,
2-methoxy-5-trifluoromethylaniline, 3-
Methoxy-5-trifluoromethylaniline, 2,4
Examples thereof include 6-trimethoxyaniline, 2,4,5-trimethylaniline and 2,4,5-trimethyl-6-methoxyaniline.

The alkali metal or alkaline earth metal represented by M of the triazole compound represented by the general formula (2) used in the present invention includes sodium, potassium, calcium, magnesium and the like. The method of the present invention comprises diazotizing an aniline derivative represented by the general formula (4) in a mineral acid, and reacting the diazonium solution with a salt of the triazole compound represented by the general formula (2) in an inert solvent. Done by Here, alcohols such as methanol and ethanol are used as the inert solvent, and if necessary, acetone, acetonitrile, 1,4-dioxane, sulfolane, tetrahydrofuran, N, N-
Other organic solvents such as dimethylacetamide can also be used together.

The following various methods can be considered as a method for charging the diazonium solution, the triazole compound represented by the general formula (2) and the alkali. A method of dropping a diazonium solution into a solution of an alkali salt of a triazole compound. A method of dropping an alkali into a mixed solution of a diazonium solution and a triazole compound. A method in which a triazole compound and an alkali are co-dropped into a diazonium solution. A method in which a diazonium solution and an alkali are co-dropped into a solution of a triazole compound.

Here, the reaction molar ratio of the respective reaction reagents is 0.9 to the diazonium compound represented by the general formula (1) with respect to the salt of the triazole compound represented by the general formula (2).
The molar ratio is 1.5, preferably 1.0 to 1.3. The amount of alkali necessary for the reaction is 1.0 to 3.5 mol ratio, preferably 2.2 to 2.6 mol ratio with respect to the triazole compound. The reaction temperature is −20 ° C.
It is 20 ° C, preferably -10 ° C to 10 ° C, and the reaction time is usually 5 to 60 minutes, preferably 10 to 30 minutes. The reaction ends almost at the same time as the dropping, but after the dropping, it is completed by stirring for several minutes to several hours.

In the present invention, the method of intermittently dropping the reaction reagent of either the compound of the general formula (1) or the general formula (2) is carried out by, for example, the following method. Be seen. First, a methanol solution of an alkali salt of a triazole compound represented by the general formula (2) is added to a reactor, and the temperature of the reaction solution is adjusted by cooling with a jacket or the like. Next, the reaction is started by dropwise adding a diazonium salt solution obtained by diazotizing the aniline derivative represented by the general formula (4) at low temperature. At this time,
Although the reaction temperature rises due to the heat of reaction, the dropping time is adjusted by intermittent dropping so that it falls within a predetermined temperature range.

After the first dropping in the intermittent dropping of the present invention is completed, the second dropping is performed when the temperature of the reaction solution reaches a predetermined temperature again by external cooling of the jacket or the like. In this way, the reaction is completed by repeating intermittent dropping while maintaining the predetermined reaction temperature. The number of intermittent drops is the scale of the reaction,
Although it depends on the degree of temperature adjustment and the like and is not particularly limited, it is usually carried out 3 to 10 times, particularly 5 to 7 times advantageously. In addition, in the above case, a heat exchanger, for example, a plate heat exchanger is installed outside the reactor and forcedly circulated by a pump to further reduce the substantial dropping time and the time from the start of dropping to the end of dropping. You can
It is a preferred embodiment of the present invention.

[0027]

According to the method of the present invention, on an industrial scale,
The target sulfide compound can be produced in good yield and industrially advantageously. In addition, in particular, the method of the present invention,
Further preferable results can be obtained by using the above-mentioned method of using an external heat exchanger in combination, that is, the method of installing a heat exchanger outside the reactor and forcibly circulating it with a horn or the like.

[0028]

EXAMPLES The method of the present invention will be described in more detail below with reference to examples, but the present invention is not limited to these examples.

Example 1 Methanol 2 was added to a 300-liter stainless steel reaction kettle.
0.4 kg and 8.66 kg of 3-mercapto-1H-1,2,4-triazole are charged, and 13.25 kg of 95% caustic potash is gradually added while cooling with stirring. After the addition, add -12 ° C to the jacket of the 300-liter reaction kettle.
Through brine and cool to -5 ° C. On the other hand, 200
Methanol 82 in a liter glass lined reaction kettle
kg, 2,4,6-trimethylaniline 11.65k
g, 35% hydrochloric acid 18.75 kg were charged, and cooled under 0-5.
14.6 kg of a 40.7% sodium nitrite aqueous solution is added dropwise at 0 ° C. to obtain a diazonium salt.

The solution of the diazonium salt is added dropwise to the triazole reaction kettle by a metering pump in 6 divided portions.
Dropping time is 1.5 minutes for the first time, 2 minutes for the second time, and 2.5 for the third time.
Minutes, 4th 3 minutes, 5th 4 minutes, 6th 5 minutes Total 18 minutes. After the first dropping, the temperature rose to 6 ° C, but after 30 minutes, the temperature reached -2 ° C, and the second dropping was performed. In this way, the solution was dropped until the sixth time. The time from the start of the first dropping to the end of the sixth dropping was 210 minutes. The reaction solution was heated to distill off methanol, 150 liters of water was added, and the mixture was neutralized to pH 7 with 35% hydrochloric acid. Precipitated crystals are filtered, washed with water and dried to obtain the desired sulfide compound 1
3.5 kg was obtained. Yield: 72% (based on 3-mercapto-1H-1,2,4-triazole) Purity: 87% (LC area percentage value)

Example 2 Methanol 2 was placed in a 300-liter stainless steel reaction kettle.
0.4 kg and 8.66 kg of 3-mercapto-1H-1,2,4-triazole are charged, and 13.25 kg of 95% caustic potash is gradually added while cooling with stirring. After the addition, add 10m to the jacket of 8m ² plate heat exchanger installed in the external circulation system and 300 liter reaction kettle.
Pass the brine at ℃, circulate the pump, and
Cool to ° C. Meanwhile, 98 kg of methanol, 14 kg of 2,4,6-trimethylaniline and 22.55 kg of 35% hydrochloric acid were charged in a 200 liter glass-lined reaction kettle, and 40.7% sodium nitrite aqueous solution 17. 5 kg is added dropwise to obtain a diazonium salt.

The solution of the diazonium salt is added dropwise to the triazole reaction kettle in 5 divided portions with a metering pump.
Dropping time is 2 minutes for the first time, 2.5 minutes for the second time, 3 minutes for the third time,
Fourth 4 minutes, 5th 5 minutes Total 16.5 minutes. After the first dropping, the temperature rose to 7 ° C, but after 30 minutes the temperature was -3.
The temperature reached 0 ° C., and the second time was added dropwise. In this way, the solution was dropped until the fifth time. The time from the start of the first dropping to the end of the fifth dropping was 155 minutes. Methanol was distilled off in the same manner as in Example 1, diluted with water, and neutralized to pH 7 with 35% hydrochloric acid. The precipitated crystals were filtered, washed with water and dried to obtain 14.3 kg of a sulfide compound. Yield: 78% (based on 3-mercapto-1H-1,2,4-triazole) Purity: 89% (LC area percentage value)

Comparative Example 1 A 300-liter stainless steel reaction kettle was charged with methanol 2
0.4 kg and 8.66 kg of 3-mercapto-1H-1,2,4-triazole are charged, and 13.25 kg of 95% caustic potash is gradually added while cooling with stirring. After the addition, add -12 ° C to the jacket of the 300-liter reaction kettle.
Through brine and cool to -5 ° C. On the other hand, 200
Methanol 82 in a liter glass lined reaction kettle
kg, 2,4,6-trimethylaniline 11.65k
g, 35% hydrochloric acid 18.75 kg were charged, and cooled under 0-5.
14.6 kg of a 40.7% sodium nitrite aqueous solution is added dropwise at 0 ° C. to obtain a diazonium salt.

When the solution of this diazonium salt was added dropwise to the triazole reaction vessel while maintaining the internal temperature at 0 to 10 ° C., it took 2 hours from the start to the end of the addition. The reaction solution was heated to distill off methanol, 150 liters of water was added, and the mixture was neutralized to pH 7 with 35% hydrochloric acid. The precipitated crystals were filtered, washed with water and dried to obtain 7.7 kg of the desired sulfide compound. Yield: 41% (based on 3-mercapto-1H-1,2,4-triazole) Purity: 76% (LC area percentage value)

Front page continuation (72) Inventor Osamu Kimura 4-2-11 Nishimikuni, Yodogawa-ku, Osaka City Taoka Chemical Industry Co., Ltd. (56) Reference JP-A-1-121279 (JP, A) (58) Field (Int.Cl. ⁷ , DB name) C07D 249/12 CA (STN)

Claims (4)

(57) [Claims] 1. The following general formula (1): (Wherein R ₁ , R ₂ and R ₃ represent a hydrogen atom, a halogen atom, a lower alkyl group, a lower alkoxy group or a trifluoromethyl group, and X represents an anion residue) and a general diazonium compound Formula (2) (In the formula, M represents an alkali metal or an alkaline earth metal), and the compound is reacted with a triazole compound represented by the general formula (3): (In the formula, R ₁ , R ₂ and R ₃ have the above meanings)
In the method for producing a sulfide compound represented by
A method for producing a sulfide compound, characterized in that the reaction reagent of either the general formula (1) or the general formula (2) is intermittently dropped into a reaction solution at a temperature of -20 ° C to 20 ° C to react. . 2. The method for producing a sulfide compound according to claim 1, wherein the diazonium compound represented by the general formula (1) is added dropwise to the reaction solution charged with the triazole compound represented by the general formula (2). 3. The method for producing a sulfide compound according to claim 1, wherein the triazole compound represented by the general formula (2) is added dropwise to the reaction solution charged with the diazonium compound represented by the general formula (1). 4. The method according to claim 1, wherein the temperature of the reaction liquid is adjusted to −20 ° C. to 20 ° C. by forcibly circulating the reaction liquid through an external heat exchanger. Of the sulfide compound of.