KR100493934B1 - The manufacturing process for a salt of 2-methyl-4-isothiazoline-3-one - Google Patents

Abstract

The present invention relates to a method for preparing 2-methyl-4-isothiazolin-3-one salt, and more particularly, to dilute sulfyl halide, a chlorinating agent, in an organic halogen solvent at a ratio of 1.5 to 2.5 times, and then To the N, N'-dimethyl-3,3'-dithiodipropionamide solution was added dropwise at a temperature of 20 to 30 ° C. for 10 to 14 hours, by-product 5-chloro-2-methyl-4-isothiazoline-3 It relates to a novel production method that can significantly suppress the production of-warm salt.

Description

The manufacturing method of 2-methyl-4-isothiazolin-3-one salt {THE MANUFACTURING PROCESS FOR A SALT OF 2-METHYL-4-ISOTHIAZOLINE-3-ONE}

The present invention relates to a method for preparing a 2-methyl-4-isothiazolin-3-one salt, and more particularly, to the production of a by-product 5-chloro-2-methyl-4-isothiazolin-3-one salt. A novel process for inhibiting and producing high purity 2-methyl-4-isothiazolin-3-one salts is provided.

2-Methyl-4-isothiazolin-3-one represented by the following general formula (1) is a known compound widely used as an industrial preservative or bactericide.

          Formula (1) Formula (2)

In general, the 2-methyl-4-isothiazolin-3-one is prepared by first preparing a 2-methyl-4-isothiazolin-3-one salt and then neutralizing it with an alkali salt to remove hydrogen chloride. Conventionally, various methods for producing 2-methyl-4-isothiazolin-3-one salt are known. However, a problem of the prior arts is that 5-chloro-2-methyl-4-iso of formula (2), which is known to be toxic for mutagenicity when preparing 2-methyl-4-isothiazolin-3-one salts It is a fact that thiazolin-3-one salts are inevitably produced as by-products. Therefore, a common problem of the prior arts is to suppress the production of 5-chloro-2-methyl-4-isothiazolin-3-one salt as a by-product as much as possible and to prepare only 2-methyl-4-isothiazolin-3-one of high purity. Was to develop a way.

Looking at the known method for preparing 2-methyl-4-isothiazolin-3-one or its salts, European Patent Publication No. 0095907 discloses N, N'-dimethyl-3,3'-dithiodipropionamide as chlorine. A method of reacting with a gas to proceed with chlorolation and cyclization reactions is introduced. However, this method produces a large amount of by-product 5-chloro-2-methyl-4-isothiazolin-3-one salt together with the target compound 2-methyl-4-isothiazolin-3-one salt. Among these, 5-chloro-2-methyl-4-isothiazolin-3-one salt, which is a by-product, is highly toxic as described above, which makes it difficult to apply to the human body and reduces stability at room temperature. However, there was a problem that the validity is lost.

In addition, Korean Patent Application No. 91-7541 discloses N, N'-dimethyl-3,3'-dithiodipropionamide in an organic halogen solvent and sulfyl halide as a chlorinating agent to react at a temperature of -20 to 10 ° C. Techniques are disclosed. According to the patented technology, it is possible to drastically reduce the content of 5-chloro-2-methyl-4-isothiazolin-3-one salts, but still a considerable amount of 5-chloro-2-methyl-4-isothiazoline-3- Because it contains warm salt, it has not reached the level of industrial use.

Korean Patent Application No. 2001-62688 discloses a high-purity 2-methyl-4-isothiazolin-3-one salt using chlorine gas as a chlorinating agent in a solvent in which hydrogen chloride is insoluble or poorly soluble, and then the salt is used as an inorganic base or an organic solvent. The method of neutralizing with amines and then extracting to obtain 2-methyl-4-isothiazolin-3-one is introduced. This method also contains 5-chloro-2-methyl-4-isothiazolin-3-one, which is relatively high purity but still ranges from 0.1% to as high as 1.0%, especially where the reaction process uses gaseous chlorine gas. Because of this, there was a disadvantage that the operation is not easy industrially.

On the other hand, the present applicant has introduced a technique using N-halogensuccinimide represented by the following formula (3) as a chlorinating agent in the Republic of Korea Patent Application 2002-54204.

    Formula (6)

(Wherein X represents Cl or Br).

In the above technique, by using N-halogensuccinimide, which is a solid raw material, as a combustor, it is excellent in workability, and it is possible to prevent the generation of harmful gases to the human body in the manufacturing process, but it is 5-chloro-2-methyl-4 as a by-product. -There is a merit that can drastically reduce the occurrence of isothiazolin-3-one salt, but there is still room for improvement in terms of economics because N-halogensuccinimide, a chlorinating agent, is rather expensive.

Therefore, the present inventors are trying to improve the problems of the prior art as described above, when reacting the sulfyl halide organic sulfide when reacting the sulfyl halide with N, N'-dimethyl-3,3'-dithiodipropionamide After diluting in a solvent and reacting dropwise, an unexpected fact was found that the production rate of 5-chloro-2-methyl-4-isothiazolin-3-one salt varies greatly depending on the dilution ratio and the dropping rate of the sulfyl halide. It came to invention.

The present invention provides a novel method for preparing 2-alkyl-4-isothiazolin-3-one, in which a very small amount of 5-chloro-2-methyl-4-isothiazolin-3-one salt is contained in an amount of 100 ppm or less. It is an object to provide a manufacturing method.

Hereinafter, the present invention will be described in detail.

The present invention is prepared by reacting N, N'-dimethyl-3,3'-dithiodipropionamide with sulfyl halide to prepare 2-methyl-4-isothiazolin-3-one salt of the following formula (1). ,

First, N, N'-dimethyl-3,3'-dithiodipropionamide is dissolved in an organic halogen solvent, and the sulfyl halide is separately diluted in an organic halogen solvent at a ratio of 1.5 to 2.5 times, and then the N, N ' The dimethyl-3,3'-dithiodipropionamide solution is added dropwise with the sulfyl halide dilution at a temperature of 20 to 30 ℃ for 10 to 14 hours.

N, N'-dimethyl-3,3'-dithiodipropionamide used as a starting material in the present invention can be prepared according to a conventional method. For example, 3,3'-dithiodipropionyldichloride is prepared by first reacting 3,3'-dithiodipropionic acid with thionyl chloride, which is reacted with methylamine to give N, N'-dimethyl-3,3 '. Dithiodipropionamide can be prepared.

A characteristic of the present invention is that when reacting the N, N'-dimethyl-3,3'-dithiodipropionamide and the sulfyl halide, which is a chlorinating agent, the sulfyl halide is diluted in an organic halogen solvent and then gradually cooled for 10 to 14 hours. React as you add. At this time, the starting material N, N'-dimethyl-3,3'-dithiodipropionamide is first dissolved in an organic halogen solvent, and a distillation solution of sulfyl halide is added dropwise thereto to N, N'-dimethyl-3,3'- It is suitable that the reaction ratio of sulfyl halide to dithiodipropionamide is in a molar ratio of 1: 2.5 to 3.5. If the reaction ratio is less than 2.5 molar ratio, the reaction yield is low, and if the reaction ratio is more than 3.5 molar ratio, there is no effect according to the increase.

In addition, the dilution ratio of sulfyl halide to the organic halogen solvent is 1.5 to 2.5 times the ratio of the organic halogen solvent. If the dilution ratio of the sulfyl halide is 1.5 times or less, the content of 5-chloro-2-methyl-4-isothiazolin-3-one salt as a by-product is greatly increased. Does not appear

In the present invention, as the organic halogen solvent, ethylene dichloride, methylene dichloride, ethyl acetate or chloroform may be used, but ethylene dichloride is best used. In addition, it is best to use sulfyl chloride as the sulfyl halide.

Another feature of the invention is that the dropping reaction is carried out at a temperature of 20 to 30 ℃. If the reaction temperature is 20 ° C or less, the reaction yield is lowered, and when the reaction temperature is 30 ° C or more, side reactions may occur.

The 2-methyl-4-isothiazolin-3-one salt prepared according to the present invention is neutralized with an alkali salt according to a known method to remove hydrogen chloride, and thus 2-methyl-4 is used as an industrial preservative or bactericide. Isothiazolin-3-ones can be prepared.

On the other hand, the correlation between the dropping rate and dilution ratio of the sulfyl halide and the amount of 5-chloro-2-methyl-4-isothiazolin-3-one salt (called CMIT) is as follows. Table 1 shows the 5-chloro-2-methyl-4-isothia with increasing the dropping time of 100 g of sulfyl chloride stock solution from 2.9 hours (dropping rate: 35 g per hour) to 20 hours (dropping rate: 5 g per hour). The change in the amount of production of the zolin-3-one salt was measured and shown, and FIG. 1 is a graph showing the results of Table 1. FIG.

SO ₂ Cl ₂ addition Dropping speed Dropping time CMIT production amount 100 g 35 g / hour 2.9 hours 5,000 to 10,000 ppm 100 g 30 g / hour 3.3 hours 3,400-5,400 ppm 100 g 25 g / hour 4.0 hours 1,400-2,600 ppm 100 g 20 g / hour 5.0 hours 850-1,350 ppm 100 g 10 g / hour 10.0 hours 550 to 850 ppm 100 g 7 g / hour 14.3 hours 430-800 ppm 100 g 5 g / hour 20.0 hours 320 to 720 ppm

As can be seen from Table 1 and FIG. 1, when the sulfyl chloride was reacted by increasing the dropping time without diluting the organic solvent, 5-chloro-2-alkyl-4-isothiazoline-3 was added for up to 10 hours. -The content of warm salt gradually decreased to 550 ~ 850ppm, but there was little effect of inhibiting the production of 5-chloro-2-alkyl-4-isothiazolin-3-one salt even if the drop time was extended more than 14 hours. Appeared. In addition, it is practically impossible to reduce the amount of 5-chloro-2-alkyl-4-isothiazolin-3-one salt to 320 ppm or less when the sulfyl chloride is added dropwise without dilution with an organic solvent. appear.

On the other hand, the following Table 2 is added dropwise by diluting the sulfyl chloride in ethylene dichloride, wherein the dilution ratio of the sulfyl chloride from 0.5 to 3 times in order to change the 5-chloro-2-methyl-4 for each dilution ratio -The change of the production amount of the isothiazolin-3-one salt was measured and shown, and the accompanying FIG. 2 shows the result of Table 2 graphically.

SO ₂ Cl ₂ addition Ethylenedichloride addition amount Dropping speed Dropping time CMIT content 100 g 50 g 25 g / hour 6 hours 750-1,050 ppm 100 g 75 g 25 g / hour 7 hours 300 to 750 ppm 100 g 100 g 25 g / hour 8 hours 150 to 250 ppm 100 g 150 g 25 g / hour 10 hours 45 to 85 ppm 100 g 200 g 25 g / hour 12 hours 25 to 36 ppm 100 g 250 g 25 g / hour 14 hours 20-30 ppm 100 g 300 g 25 g / hour 16 hours 15 to 25 ppm

As can be seen in Table 2 and FIG. 2, when the sulfyl chloride is added dropwise to ethylene dichloride and added dropwise, 5-chloro-2 when the dilution ratio of sulfyl chloride to ethylene dichloride is 1.5 to 2.5 times. It has been shown to most effectively inhibit the production of -alkyl-4-isothiazolin-3-one salts.

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

Example 1

60.7 g (0.256 mol) of N, N'-dimethyl-3 and 3'-dithiopropionamide were dissolved in 250 g of ethylene dichloride in a 1 L three-neck flask, followed by stirring while maintaining 20 to 30 ° C. To this solution was added dropwise a solution of 100 g (0.738 mol) of sulfyl chloride in 250 g of ethylene dichloride for 10 to 12 hours. After reacting at the same temperature for 12 hours, the mixture was cooled to 5 ° C. and filtered. The filtered crystals are dried in an oven to give 70.2 g (90.5 mol%) of 2-methyl-4-isothiazolin-3-one salt.

Example 2

In a 1 L three-necked flask, 60.7 g (0.256 mol) of N, N'-dimethyl-3 and 3'-dithiopropionamide were dissolved in 250 g of methylene chloride, followed by stirring while maintaining 20 to 30 ° C. To this solution was added dropwise a solution of 100 g (0.738 mol) of sulfyl chloride in 250 g of methylene chloride for 12-14 hours. After reacting at the same temperature for 12 hours, the mixture was cooled to 5 ° C. and filtered. The filtered crystals are dried in an oven to give 68.5 g (88.4 mol%) of 2-methyl-4-isothiazolin-3-one salt.

Example 3

In a 1 L three-necked flask, 60.7 g (0.256 mol) of N, N'-dimethyl-3, 3'-dithiopropionamide was dissolved in 250 g of ethyl acetate, followed by stirring while maintaining 20 to 30 ° C. To this solution was added dropwise a solution of 100 g (0.738 mol) of sulfyl chloride in 250 g of ethyl acetate for 10 to 12 hours. After reacting at the same temperature for 12 hours, the mixture was cooled to 5 ° C. and filtered. The filtered crystals are dried in an oven to give 68.9 g (88.9 mol%) of 2-methyl-4-isothiazolin-3-one salt.

Example 4

In a 1 L three-necked flask, 60.7 g (0.256 mol) of N, N'-dimethyl-3 and 3'-dithiopropionamide was dissolved in 250 g of chloroform, followed by stirring while maintaining 20 to 30 ° C. To this solution was added dropwise a solution of 100 g (0.738 mol) of sulfaryl chloride in 250 g of chloroform for 13 to 14 hours. After reacting at the same temperature for 12 hours, the mixture was cooled to 5 ° C. and filtered. The filtered crystals are dried in an oven to give 69.4 g (89.5 mol%) of 2-methyl-4-isothiazolin-3-one salt.

In the preparation of the 2-alkyl-4-isothiazolin-3-one salt according to the present invention, the content of 5-chloro-2-methyl-4-isothiazolin-3-one salt is contained in an amount of 100 ppm or less. 2-alkyl-4-isothiazolin-3-one salts can be prepared that can be used.

1 is a graph showing the correlation between the dropping time of a sulfyl chloride stock solution and the amount of 5-chloro-2-methyl-4-isothiazolin-3-one salt (CMIT);

2 is a graph showing the relationship between the dilution ratio of sulfyl chloride to ethylene dichloride and the amount of 5-chloro-2-methyl-4-isothiazolin-3-one salt (CMIT).

Claims (3)

In the reaction of N, N'-dimethyl-3,3'-dithiodipropionamide with sulfyl halide to prepare 2-methyl-4-isothiazolin-3-one salt, First, N, N'-dimethyl-3,3'-dithiodipropionamide is dissolved in an organic halogen solvent, and the sulfyl halide is separately diluted in an organic halogen solvent at a ratio of 1.5 to 2.5 times, and then the N, N ' The dimethyl-3,3'-dithiodipropionamide solution is added dropwise with the sulfyl halide dilution at a temperature of 20 to 30 ℃ for 10 to 14 hours. A process according to claim 1, wherein the reaction ratio of sulfyl halide to N, N'-dimethyl-3,3'-dithiodipropionamide is in a molar ratio of 1: 2.5 to 3.5. The method of claim 1, wherein the organic halogen solvent is any one selected from ethylene dichloride, methylene dichloride, ethyl acetate or chloroform.