KR0180563B1 - Method for preparing 4,5-dichloro-2-methyl-4-isothiazolin-3-one - Google Patents

Abstract

The present invention relates to a method for preparing 4,5-dichloro-2-methyl-4-isothiazolin-3-one, and more particularly, to industrial cooling water, metal covalent, paint, surfactant, and biocide. An improved method for selectively preparing only 4,5-dichloro-2-methyl-4-isothiazolin-3-one represented by the following structural formula (I) is useful.

Description

Method for preparing 4,5-dichloro-2-methyl-4-isothiazolin-3-one

The present invention relates to a method for preparing 4,5-dichloro-2-methyl-4-isothiazolin-3-one, and more particularly, to industrial cooling water, metal covalent, paint, surfactant, and biocide. An improved method for selectively preparing only 4,5-dichloro-2-methyl-4-isothiazolin-3-one represented by the following structural formula (I) is useful.

The synthesis method of 4,5-dichloro-2-methyl-4-isothiazolin-3-one represented by the above formula (I) is known from European Patent No. 95907. The synthesis method is summarized in the following scheme The amidation reaction of (1) and the chlorolation and cyclization reaction of the following reaction formula (2) take place to prepare as a mixture of two kinds.

According to the method described in the above European patent, it is prepared in the form of a mixture of two kinds of mixtures, that is, 2-methyl-4-isothiazoline-3-one salt and 5-chloro-2-methyl-4-isothiazoline-3-one salt. And a small amount of 4,5-dichloro-2-methyl-4-isothiazolin-3-one are mixed.

Further, another method for synthesizing 4,5-dichloro-2-methyl-4-isothiazolin-3-one represented by the above structural formula (I) is known from J. Heterocycle (August 1971). The method is prepared by the chlorolation reaction of the following reaction formula (3).

However, in the case of the reaction of the reaction formula (3) as described above it is uneconomical to lower the temperature to -70 ℃.

As described above, the conventional methods for preparing only 4,5-dichloro-2-methyl-4-isothiazolin-3-one represented by the structural formula (I) have much room for improvement in the manufacturing method. Even if the structural formula (I) was prepared, the manufacturing conditions were not economical, and the reaction process was complicated, and thus, it was not actually used industrially.

Therefore, in the present invention, unlike the prior art, in the preparation of the compound of formula (I), a novel preparation method capable of selectively preparing only the compound of formula (I) in high yield by renewing the reactants and reaction conditions. The purpose is to provide.

Hereinafter, the present invention will be described in detail.

The present invention is to prepare 4,5-dichloro-2-methyl-4-isothiazolin-3-one represented by the above structural formula (I) by chlorolation and cyclization reaction from 3,3'-dithiodipropionic acid In the process, 3,3'-dithiodipropionic acid and thionyl chloride are reacted to prepare 3,3'-dithiodipropionyldichloride represented by the following structural formula (II), which is reacted with methylamine to give the following structural formula N, N'-dimethyl-3,3'-dithiodipropionamide represented by (III) was prepared, and then sulfyl chloride was added thereto, followed by cyclization to selectively cyclize 4,5- of Structural Formula (I). It is characterized by a process for producing only dichloro-2-methyl-4-isothiazolin-3-one.

Referring to the present invention in more detail as follows.

The present invention provides 4,5-dichloro-2-methyl-4-isothiazolin-3-one of formula (I) using 3,3'-dithiodipropionic acid, thionyl chloride, methylamine and sulfyl chloride. The method for selectively preparing the 3,3'-dithiodipropionic acid and thionyl chloride reacted in a 1: 2 to 1: 4 molar ratio, but reacted at 10 to 30 ℃ 3 represented by the formula (II) Prepare 3'-dithiodipropionyldichloride.

If the reaction molar ratio of 3,3'-dithiodipropionic acid and thionyl chloride is less than 1: 2, unreacted impurities are generated. .

In addition, if the reaction temperature is lower than 10 ℃ the reaction time is too long to lose the economical efficiency, if it exceeds 30 ℃, the toxic thionyl chloride vapor is severely generated, which is not good because there is an operational risk.

The methylamine is reacted with the compound of the above formula (II), wherein the above formula (II) and the methylamine are preferably reacted in a molar ratio of 1: 2 to 1: 6, and the reaction temperature is -10 ° C to It is preferable to keep it at 35 degreeC, Preferably it is -10 degreeC-30 degreeC, More preferably, it is 15 degreeC-normal temperature.

If the reaction temperature is lower than -10 ° C economically disadvantageous and there is a risk of explosion due to exothermic reaction above 35 ° C. If the reaction molar ratio is less than 1: 2, an unreacted substance is produced, and if the reaction molar ratio is more than 1: 6, methylamine is unnecessarily supplied in excess and economic efficiency is low. At this time, it is preferable to use toluene or benzene as the reaction solvent.

When the reaction is carried out as described above, N, N'-dithiodipropionamide of the structural formula (III) is produced, and the addition of sulfyl chloride to the cyclization reaction gives the desired 4,5-dichloro of the structural formula (I). Only 2-methyl-4-isothiazolin-3-one is optionally prepared.

In this case, the compound of the formula (III) and the sulfyl chloride is preferably reacted in a molar ratio of 1: 8.1 to 1: 20, if the sulfyl chloride is used in an amount less than 1: 8.1 molar ratio, the yield is lowered, 1: 20 When used excessively, purity and economy are inferior.

In addition, the reaction temperature at this time is -20 ℃ to 100 ℃, more preferably 50 ℃ to 80 ℃ reaction, it is good, if it is lower than -20 ℃ due to low temperature maintenance economical and at a temperature higher than 100 ℃ final There is a problem that the purity of the product is significantly lowered. However, considering the economics and workability, 50 ℃ ~ 80 ℃ is the best.

The solvent of this final reaction is an organic solvent, ie CH ₂ X ₂ , CHX ₃ , CX ₃ CH ₃ , CHX ₂ CHX ₂ , toluene, benzene. It is preferable to use ethyl acetate or the like (where X is a halogen element).

As described above, 4,5-dichloro-2-methyl-4-isothiazolin-3-one of the above formula (I) synthesized according to the present invention is produced with only pure compounds by a selective preparation method, and the yield is 70 Obtained in mol% or more.

The target compound of the above formula (I) is a bioside having stability and persistence, and general industrial preservatives such as algae inhibitors, paint preservatives, industrial metal-based preservatives, cosmetics and shampoo additives, paper additives, surfactant preservatives and pesticides It is very useful as a fungus and fungicide.

In addition, since the preparation method is simpler and more economical than the conventional method, the target compound can be manufactured in a high yield without a separate separation process because the target material is selectively prepared.

Hereinafter, the present invention will be described in detail with reference to Examples.

Example 1

A 1 L three-necked flask was equipped with a thermometer, a dropping funnel, and a stirrer, and 23.6 g (0.1 mol) of N, N'-dimethyl-3,3'-dithiodipropionamide and 350 ml of ethyl acetate were added. 135 g (1.0 mole) of sulfyl chloride are added to the mixture with slow stirring for 3 hours.

After the addition of the sulfyl chloride, the reaction temperature was raised to 70 ± 2 ° C. for 3 hours, followed by stirring at 70 ± 2 ° C. for 3 hours.

As the reaction proceeds, a white precipitate is formed. If it proceeds further, it becomes a yellow clear liquid. After removing the white solid completely, the yellow clear liquid is distilled at 60 ° C. using a vacuum pump to precipitate a needle-shaped white solid. .

The needle-like white solid was kept at 50 DEG C in a vacuum oven to completely remove the solvent, thereby obtaining 35 g (95 mol%) of 4,5-dichloro-2-methyl-4-isothiazolin-3-one.

¹ HN.MR (300 MHz, CDCl ₃ ); δ 3.37 (s).

Example 2

A 1 L three-necked flask was equipped with a thermometer, a dropping funnel, and a stirrer, and 23.6 g (0.1 mol) of N, N'-dimethyl-3,3'-dithiodipropionamide and 350 ml of ethyl acetate were added. 162 g (1.2 mole) of sulfyl chloride are added with stirring slowly for 3 hours.

After the addition of the sulfyl chloride, the reaction temperature was raised to 70 ± 2 ° C. for 3 hours, followed by stirring at 70 ± 2 ° C. for 3 hours.

As the reaction proceeds, a white precipitate is formed. If it proceeds further, it becomes a yellow clear liquid. After removing the white solid completely, the yellow clear liquid is distilled at 60 ° C. using a vacuum pump to precipitate a needle-shaped white solid. .

This needle-like white solid was kept at 50 DEG C in a vacuum oven to completely remove the solvent, thereby obtaining 35.1 g (95.3 mol%) of 4,5-dichloro-2-methyl-4-isothiazolin-3-one.

¹ HN.MR (300 MHz, CDCl ₃ ); δ 3.38 (s).

Example 3

A 1 L three-necked flask was equipped with a thermometer, a dropping funnel, and a stirrer, and 23.6 g (0.1 mol) of N, N'-dimethyl-3,3'-dithiodipropionamide and 350 ml of ethyl acetate were added. 189 g (1.4 mole) of sulfyl chloride is added to the mixture with stirring slowly for 3 hours.

After the addition of the sulfyl chloride, the reaction temperature was stirred for 3 hours at 65 ± 2 ℃ and maintained at 65 ± 2 ℃ for 3 hours.

As the reaction proceeds, a white precipitate is formed. If it proceeds further, it becomes a yellow clear liquid. After removing the white solid completely, the yellow clear liquid is distilled at 60 ° C. using a vacuum pump to precipitate a needle-shaped white solid. .

The needle-like white solid was kept at 50 DEG C in a vacuum oven to completely remove the solvent, thereby obtaining 35 g (95 mol%) of 4,5-dichloro-2-methyl-4-isothiazolin-3-one.

¹ HN.MR (300 MHz, CDCl ₃ ); δ 3.37 (s).

Example 4

A 1 L three-necked flask was equipped with a thermometer, a dropping funnel and a stirrer, and 23.6 g (0.1 mol) of N, N'-dimethyl-3,3'-dithiodipropionamide and 350 ml of toluene were added. 243 g (1.8 mole) of sulfyl chloride are added with stirring slowly for 3 hours.

After the addition of the sulfyl chloride, the reaction temperature was stirred for 3 hours at 65 ± 2 ℃ and maintained at 65 ± 2 ℃ for 3 hours.

As the reaction proceeds, a white precipitate is formed. If it proceeds further, it becomes a yellow clear liquid. After removing the white solid completely, the yellow clear liquid is distilled at 60 ° C. using a vacuum pump to precipitate a needle-shaped white solid. .

This needle-like white solid was kept at 50 DEG C in a vacuum oven to completely remove the solvent, to obtain 35.5 g (96.4 mol%) of 4,5-dichloro-2-methyl-4-isothiazolin-3-one.

¹ HN.MR (300 MHz, CDCl ₃ ); δ 3.38 (s).

Example 5

A 1 L three-necked flask was equipped with a thermometer, a dropping funnel and a stirrer, and 23.6 g (0.1 mol) of N, N'-dimethyl-3,3'-dithiodipropionamide and 350 ml of benzene were added to the dropping funnel at room temperature. 175 g (1.3 mole) of sulfyl chloride are added with stirring slowly for 3 hours.

After the addition of the sulfyl chloride, the reaction temperature was raised to 70 ± 2 ° C. for 3 hours, followed by stirring at 70 ± 2 ° C. for 3 hours.

As the reaction proceeds, a white precipitate is formed. If it proceeds further, it becomes a yellow clear liquid. After removing the white solid completely, the yellow clear liquid is distilled at 60 ° C. using a vacuum pump to precipitate a needle-shaped white solid. .

The needle-like white solid was kept at 50 DEG C in a vacuum oven to completely remove the solvent, to obtain 35.2 g (95.6 mol%) of 4,5-dichloro-2-methyl-4-isothiazolin-3-one.

¹ HN.MR (300 MHz, CDCl ₃ ); δ 3.37 (s).

Example 6

A 1 L three-necked flask was equipped with a thermometer, a dropping funnel and a stirrer, and 23.6 g (0.1 mol) of N, N'-dimethyl-3,3'-dithiodipropionamide and 350 ml of benzene were added to the dropping funnel at room temperature. 229.5 g (1.7 mole) of sulfyl chloride are added with stirring slowly for 3 hours.

After the addition of the sulfyl chloride, the reaction temperature was raised to 60 ± 2 ° C. for 3 hours, followed by stirring at 60 ± 2 ° C. for 3 hours.

As the reaction proceeds, a white precipitate is formed. If it proceeds further, it becomes a yellow clear liquid. After removing the white solid completely, the yellow clear liquid is distilled at 60 ° C. using a vacuum pump to precipitate a needle-shaped white solid. .

This needle-like white solid was kept at 50 DEG C in a vacuum oven to completely remove the solvent, to obtain 34.8 g (94.5 mol%) of 4,5-dichloro-2-methyl-4-isothiazolin-3-one.

¹ HN.MR (300 MHz, CDCl ₃ ); δ 3.38 (s).

Claims (1)

In preparing 4,5-dichloro-2-methyl-4-isothiazolin-3-one represented by the following structural formula (I) by chlorolation and cyclization reaction from 3,3'-dithiodipropionic acid, 3.3 Reacting '-dithiodipropionic acid with thionyl chloride to prepare 3,3'-dithiodipropionyldichloride represented by the following structural formula (II) and reacting it with methylamine to form N, represented by the following structural formula (III) N'-dimethyl-3,3'-dithiodipropionamide was prepared, and then sulfyl chloride was added to the compound in a molar ratio of 1: 8.1 to 1:20, and cyclized in an organic solvent to selectively prepare only the target product. Method for producing 4,5-dichloro-2-methyl-4-isothiazolin-3-one represented by the following structural formula (I)