JP5581312B2 - Microbicide - Google Patents

Description

  The present invention relates to a microbicide containing 5-chloro-2-methyl-4-isothiazolin-3-one as an active ingredient, and more particularly, a residue of an organic solvent used in the production process of the active ingredient, and The present invention relates to a microbicide having a reduced hydrolyzate content.

  5-Chloro-2-methyl-4-isothiazolin-3-one has biological activity that suppresses the growth of microorganisms, and is therefore used as a preservative and disinfectant for various industrial products. It is also used as an active ingredient in slime control agents for preventing slime composed of microorganisms such as bacteria and algae-derived organic matter generated in water treatment devices and cooling water systems.

  In particular, in the water treatment apparatus and the cooling water system, different performances other than the suppression of slime are required for the water treatment process depending on the purpose of the water treatment and the apparatus mode of the cooling water system (closed system or open system). For example, in water treatment for advanced purification of discharged water and reuse of various wastewater, clogging of separation membranes is a major problem due to the influence of fouling substances contained in the water to be treated. Reduction of valent metal ions is required (for example, refer to Patent Document 1), or the presence of proteins in the water to be treated is a problem as a flux lowering factor of the separation membrane, and its aggregation removal is required (for example, Patent Document 2). In addition, membrane treatment of biologically treated water for the recycling of industrial wastewater has problems with membrane degradation due to chlorine and increase in total organic carbon (TOC) due to microbial death due to chlorine. (For example, refer to Patent Document 3). In addition, in the production of ultrapure water for cleaning used in semiconductor device production, it is necessary to add a slime control agent to each of a plurality of membrane devices, and it is required to perform simply for the problem that control is difficult. (For example, see Patent Document 4). Further, in the reverse osmosis membrane (RO membrane) treatment method, high recovery of water is required for the problem that concentrated water is discharged out of the system as wastewater (see, for example, Patent Document 5). Furthermore, it has been proposed to provide an ion exchange device in order to further reduce the ion concentration of RO membrane permeated water in a pure water production apparatus using an RO membrane separation device (see, for example, Patent Document 6). Thus, it turns out that the performance requested | required in the water treatment process including a slime control and the subject made into a problem are various.

  In recent years, as a new issue, there has been a demand for further reduction of TOC in highly treated water. Even in RO membrane processing systems, TOC of several ppb to several tens of ppb is a problem in pure water production where high water quality is required, especially for the production of electronic materials such as semiconductors. In recent years, it has become a serious problem in applications that require high-purity pure water. Further, in the sterilization treatment and slime control of Legionella in the cooling water system, there is a problem that the low-molecular organic compound is decomposed in the aqueous system and, conversely, supplied as a slime nutrient source. In particular, slime control in a closed system has a longer residence time because the amount of blown water is smaller than that in an open circulation cooling water system, so that the slime control effect may be difficult to exert. Incorporation of low-molecular-weight organic compound components is rapidly taken up by microorganisms in such a system, and therefore it is necessary to avoid contamination in the system as much as possible.

  In order to cope with this, for example, it is possible to consider increasing the performance of the membrane separation apparatus, but it is technically difficult to sufficiently reduce the TOC. In addition, it is possible to consider adding a post-treatment process to reduce the TOC of the treated water, but not only the treatment work becomes complicated, but also the treatment cost increases. Accordingly, there is a demand for measures that can be easily applied to conventional processing steps.

  By the way, 5-chloro-2-methyl-4-isothiazolin-3-one has conventionally been a halogenated cyclization step of a sulfide amide intermediate and a hydrogen halide salt of a compound having a 3-isothiazolone ring obtained in the step. It is manufactured by a manufacturing process (for example, refer to Patent Documents 7 and 8) including a neutralization process. In this production method, acetate is used industrially because of its high reaction conversion rate as a halogenated cyclization reaction solvent for the sulfide amide intermediate. An organic solvent is also used in the compound washing and extraction process. These organic solvents are removed in the final step of the manufacturing process, but complete removal is difficult and may remain as impurities in the final product. However, such a residue is very small. For example, the concentration of 5-chloro-2-methyl-4-isothiazolin-3-one used for slime control in water treatment applications is usually several mg / L in the water to be treated. Therefore, the concentration of the residue in the water to be treated is low and has not been particularly problematic in the past.

JP 2006-95425 A JP 2004-267830 A Japanese Patent Laid-Open No. 11-33371 Japanese Patent Application Laid-Open No. 09-294989 JP-A-10-202066 JP 2000-317457 A JP 59-31772 A Japanese Patent Publication No. 45-38330

  However, even in water treatment applications, in applications where a trace amount of residue is a problem, for example, in applications used in pure water production equipment, among these residues, low molecular organic compound components are used in membrane separation devices. The present inventors have confirmed that it leaks into the treated water. It was confirmed that such a leak also exists in the RO membrane processing system. However, improvement of the performance of the microbicide itself is rarely a problem in the past, and a compound having a 3-isothiazolone ring and a low content of volatile components in order to prevent air contamination by a coating agent or an adhesive. However, there is no known one intended to be used as a slime control agent.

  Accordingly, an object of the present invention is to provide a microbicide containing 5-chloro-2-methyl-4-isothiazolin-3-one as an active ingredient, and an organic solvent used in the industrial production process of the active ingredient. An object of the present invention is to provide a microbicide having a sufficiently reduced content of the residue and its hydrolyzate as compared with conventional products.

The present invention is a microbicide containing 5-chloro-2-methyl-4-isothiazolin-3-one as an active ingredient, the total content of the organic solvent and its hydrolyzate, and the concentration of the active ingredient Is a microbicide that satisfies the following formula (1).

Total content of organic solvent and its hydrolyzate expressed in ppm × (10 / B) ≦ 200 ppm (1)

In the formula (1), B represents the numerical value of the active ingredient concentration expressed in% by weight.
In the present specification, ppm and ppb are weight specific concentrations.
In one embodiment of the present invention, the organic solvent is an acetate ester and / or a hydrocarbon compound.
In another embodiment of the present invention, the organic solvent is an acetate ester, or an acetate ester and a hydrocarbon compound.
In one embodiment of the present invention, the hydrocarbon compound is toluene.
In one aspect of the present invention, in particular, the acetate ester is at least one selected from the group consisting of ethyl acetate and butyl acetate.
Furthermore, in one embodiment of the present invention, the total content of acetate ester and its hydrolyzate and the concentration of the active ingredient satisfy the following formula (1 ′).

Total content of acetate and its hydrolyzate expressed in ppm × (10 / B) ≦ 60 ppm (1 ′)

In the formula (1 ′), B represents a numerical value of the active ingredient concentration expressed in weight%.

Furthermore, in another embodiment of the present invention, the content of acetic acid and the concentration of the active ingredient satisfy the following formula (1 ″).

Acetic acid content in ppm × (10 / B) ≦ 10 ppm (1 ″)

In the formula (1 ″), B represents a numerical value of the active ingredient concentration expressed in weight%.
In another aspect of the invention, the active ingredient is
A step of halogenating cyclization of a sulfide amide intermediate, and a step of neutralizing a hydrogen halide salt of the compound having a 3-isothiazolone ring obtained in the above step, which is performed as necessary, In the production process of methyl-4-isothiazolin-3-one,
Acetic acid ester having a water content of 0.1% by weight or less was used as a reaction solvent in the halogenated cyclization step, and was obtained after the cyclization step and before the neutralization step. By adding a hydrocarbon compound having a water content of 0.1% by weight or less to a wet cake obtained by filtering the acetate dispersion of the hydrogen halide salt, the acetate is dissolved in the hydrocarbon compound by filtration. As well as exchange
5-chloro-2-methyl-4-isothiazolin-3-one obtained by carrying out from the halogenated cyclization step to at least the solvent exchange step in an atmosphere having a water content of 0.1% by weight or less. .
In another embodiment of the present invention, the active ingredient is contained in an amount of 1 to 30% by weight.
In this invention, the slime control agent suitable for the pure water manufacturing apparatus which has a reverse osmosis membrane is provided.
Moreover, in this invention, the slime control method of the pure water manufacturing apparatus which has a reverse osmosis membrane using the said microbicide is provided.

  According to the present invention, according to the above-described configuration, the active component 5-chloro-2-methyl-4-isothiazolin-3-one is a halogenated cyclization reaction solvent of a raw material sulfide amide intermediate and a reaction product extraction / washing solvent. The present invention provides a microbicide having a sufficiently reduced residual amount of an organic solvent and a hydrolyzate thereof, in other words, an organic solvent and a hydrolyzate thereof used in the production process of the active ingredient. Can do.

  The present invention has a high reaction conversion rate as a halogenated cyclization reaction solvent of a raw material sulfide amide intermediate of 5-chloro-2-methyl-4-isothiazolin-3-one, which is an active ingredient, due to the above-described configuration. Even when an acetate ester is used, a microbicide having a sufficiently reduced residual amount of the acetate ester and its hydrolyzate can be provided. In particular, a microbicide having a reduced residual amount of acetic acid can be provided.

  Further, by controlling the slime using the microbicide of the present invention in a membrane separation apparatus such as an RO membrane separation apparatus, the TOC in the treated water can be greatly reduced as compared with the case where a conventional product is used.

In the microbicide of the present invention, the concentration of the active ingredient 5-chloro-2-methyl-4-isothiazolin-3-one and the total content of the organic solvent and its hydrolyzate used in the production process are as follows. It satisfies the following formula (1) and is therefore substantially free of the organic solvent and its hydrolyzate used in the production process.

Total content of organic solvent and its hydrolyzate expressed in ppm × (10 / B) ≦ 200 ppm (1)

In the formula (1), B represents the numerical value of the active ingredient concentration expressed in% by weight.
The right side of the above formula (1) is preferably 100 ppm, more preferably 60 ppm, and even more preferably 40 ppm if the sensitivity of the measuring instrument allows.

  The active ingredient 5-chloro-2-methyl-4-isothiazolin-3-one may be formulated as a free compound or as a hydrogen halide (eg, hydrogen chloride, hydrogen bromide, etc.) salt. May be.

As the organic solvent, for example, an organic solvent or the like used in the 5-chloro-2-methyl-4-isothiazolin-3-one manufacturing process, for example, acetic acid esters (e.g., ethyl acetate, butyl acetate is preferred , Ethyl acetate is more preferred), hydrocarbon compounds (eg, toluene, hexane, cyclohexane, etc.), or mixtures thereof, or other organic solvents (eg, acetic acid, alcohols, etc.).

Moreover, it is preferable that the total content of acetate ester and its hydrolyzate and the concentration of the active ingredient satisfy the following formula (1 ′).

Total content of acetate and its hydrolyzate expressed in ppm × (10 / B) ≦ 60 ppm (1 ′)

In the formula (1 ′), B represents a numerical value of the active ingredient concentration expressed in weight%. More preferably, the right side of equation (1 ′) is 40 ppm if the sensitivity of the measuring instrument allows.

Furthermore, it is preferable that the content of acetic acid and the concentration of the active ingredient satisfy the following formula (1 ″).

Acetic acid content in ppm × (10 / B) ≦ 10 ppm (1 ″)

In the formula (1 ″), B represents a numerical value of the active ingredient concentration expressed in weight%. The right side of the formula (1 ″) is more preferably 5 ppm if the sensitivity of the measuring device allows. By reducing the content of acetic acid, for example, the amount of acetic acid that can easily pass through a membrane separation device such as an RO membrane separation device can be reduced.

  In the present invention, 5-chloro-2-methyl-4-isothiazolin-3-one, which is an active ingredient, has a sufficiently reduced total content of an organic solvent as an impurity and a hydrolyzate thereof as compared with a commercially available product. . As such 5-chloro-2-methyl-4-isothiazolin-3-one, the total content of the organic solvent and its hydrolyzate satisfies the above conditions in the present invention, regardless of the production method. Can be used as long as possible.

  As a method for producing 5-chloro-2-methyl-4-isothiazolin-3-one, a halogenated cyclization step of a sulfide amide intermediate and a hydrogen halide salt of a compound having a 3-isothiazolone ring obtained in the above step An industrial production process of 5-chloro-2-methyl-4-isothiazolin-3-one including a neutralization process is known. The 3-isothiazolone ring has the following structure:

  Here, as the sulfide amide intermediate, monosulfide amide intermediate (for example, N-alkyl-3-mercaptopropionic acid amide), disulfide amide intermediate (for example, N, N′-dialkyl-3,3′-dithio). Propionic acid diamide) is known, and as a production process using a monosulfide amide intermediate, for example, a production method disclosed in JP-A-59-31772 is known. As an outline, for example, first, 3-thiopropionic acid ester obtained by esterifying 3-thiopropionic acid as a starting material is amidated to produce a monosulfide amide. This amidation is usually carried out in an organic solvent such as methanol or toluene. Since a slurry containing monosulfide amide is obtained upon completion of the reaction, the solvent is removed from this slurry. Subsequently, this monosulfide amide is dispersed again in an organic solvent such as an acetate such as ethyl acetate or butyl acetate to form a slurry, and a hydrogen halide is allowed to act on this to carry out a halogenated cyclization reaction. The hydrogen halide salt thus obtained is neutralized to obtain the target compound as the main product. At this time, the compound having a 3-isothiazolone ring is soluble so that the target compound does not substantially contain the alkali metal salt derived from neutralization of the hydrogen halide salt and moisture, and It is also known to employ a method of neutralization using an organic solvent in which the alkali metal salt is insoluble, followed by dehydration and distillation of the organic solvent.

  In addition, as a production process using a disulfide amide intermediate, production methods disclosed in, for example, US Pat. As an outline, for example, first, dithiodipropionic acid ester obtained by esterifying dithiodipropionic acid as a starting material is amidated to form disulfide amide. This amidation is usually carried out in an organic solvent such as methanol or toluene. Since a slurry containing disulfide amide is obtained upon completion of the reaction, the solvent is removed from this slurry. Subsequently, this disulfide amide is dispersed again in an organic solvent such as an acetate such as ethyl acetate or butyl acetate to form a slurry, and a hydrogen halide is allowed to act on this to carry out a halogenated cyclization reaction. The hydrogen halide salt thus obtained is neutralized to obtain the target compound as the main product. At this time, the compound having a 3-isothiazolone ring is soluble so that the target compound does not substantially contain the alkali metal salt derived from neutralization of the hydrogen halide salt and moisture, and It is also known to employ a method of neutralization using an organic solvent in which the alkali metal salt is insoluble, followed by dehydration and distillation of the organic solvent.

  However, the microbicide containing 5-chloro-2-methyl-4-isothiazolin-3-one obtained by such a production method as an active ingredient is a total content of an organic solvent as an impurity and a hydrolyzate thereof. The amount usually cannot meet the above conditions. That is, even if a hydrocarbon-based organic solvent such as toluene is distilled off, it is difficult to distill off the acetate ester, and it remains as a residual solvent in the final product. According to the analysis of the present inventors, the residual amount is approximately 5000 to 15000 ppm in total in 5-chloro-2-methyl-4-isothiazolin-3-one having a concentration of about 10% by weight. This value is included in 5-chloro-2-methyl-4-isothiazolin-3-one produced using acetate in a conventional production process since it is generally known that acetate is likely to remain. It can be said that it is a measure of the total amount of residual organic solvent and its hydrolyzate.

  Therefore, in the present invention, 5-chloro-2-methyl-4-isothiazolin-3-one obtained by the following production method can be preferably used as an active ingredient. That is, the method includes a halogenated cyclization step of a sulfide amide intermediate and a neutralization step of a hydrogen halide salt of a compound having a 3-isothiazolone ring obtained in the above step, which is performed as necessary. In a known production process of -methyl-4-isothiazolin-3-one, an acetic acid ester having a water content of 0.1% by weight or less, preferably 0.01% by weight or less as a reaction solvent for the halogenated cyclization step ( For example, ethyl acetate and butyl acetate are preferable, and ethyl acetate is more preferable.) After the cyclization step and, if applicable, before the neutralization step, the obtained hydrohalide acetate ester The wet cake obtained by filtering the dispersion is added to a hydrocarbon compound having a water content of 0.1% by weight or less, preferably 0.01% by weight or less (eg, toluene, hexane). The dispersion is solvent-exchanged with the hydrocarbon compound by adding cyclohexane and the like, and the water content from the halogenated cyclization step to at least the solvent exchange step is 0.1% by weight or less, preferably 5-chloro-2-methyl-4-isothiazoline obtained by carrying out in an atmosphere of 0.05% by weight or less, for example, in a dry inert gas (eg, nitrogen, argon, etc.) or in dry air -3-one can be used. In addition, when the process from the halogenated cyclization step to at least the solvent exchange step is performed in an atmosphere having a moisture content of 0.1% by weight or less, preferably 0.05% by weight or less, the moisture content is 0.01% by weight or less. Preferably, after removing moisture by blowing a gas of 0.001% by weight or less into the system in advance, a gas having a moisture content of 0.01% by weight or less, preferably 0.001% by weight or less is blown into the system. This means that the work is carried out while controlling the moisture.

  In the above production process, known methods can be employed for the halogenated cyclization process, neutralization process, concentration process, and the like. Specifically, in the solvent exchange step, 1 to 5 times the amount of the hydrocarbon compound is added to a wet cake obtained by filtering the acetate dispersion of the hydrogen halide salt, and 1 to 5 The solvent can be exchanged from an acetate ester to a hydrocarbon compound by filtering once, preferably once or twice. Filtration is preferably vacuum filtration or centrifugal filtration, and centrifugal filtration is more preferred. The operation from the halogenated cyclization step to at least the solvent exchange step is preferably performed in a dry inert gas atmosphere. According to the above production process, the obtained 5-chloro-2-methyl-4-isothiazolin-3-one is substantially free of the organic solvent used in the production process and its hydrolyzate. In particular, 5-chloro-2-methyl-4-isothiazolin-3-one containing almost no acetic acid ester or its hydrolyzate, acetic acid or alcohols, can be obtained.

  Further, in the above production process, the concentration process time is usually 10 to 15 hours compared to the time required for 20 hours or more, and the required time is reduced by 25 to 50%. Further, the yield of 5-chloro-2-methyl-4-isothiazolin-3-one can be improved by 5 to 10% than usual.

  The microbicide of this invention should just melt | dissolve the said active ingredient in water.

  If necessary, as a stabilizer, a divalent metal salt, for example, a nitrate or chloride of a metal such as calcium, magnesium, manganese, nickel, copper, zinc, etc., in an amount that does not inhibit the purpose of the present invention. Can be used. Such a technique is known and is described in, for example, US Pat. No. 3,870,795.

  In the microbicide of the present invention, the concentration of the active ingredient is usually 1 to 30% by weight, preferably 5 to 20% by weight. When the active ingredient is thick, for example, when the active ingredient exceeds 30% by weight, when using a stabilizer, the metal nitrate or chloride used as the stabilizer may be precipitated. Becomes higher. In addition, when the active ingredient is thin, for example, when the active ingredient is less than 1% by weight, the stability of the active ingredient tends to deteriorate, and it must be used in a large amount at the time of use. Inefficient in formulation. Therefore, in terms of practical use, 5 to 20% by weight is preferable.

  The amount of the stabilizer used is, for example, 1 to 30 parts by weight, preferably 15 to 25 parts by weight with respect to 100 parts by weight of the 5-chloro-2-methyl-4-isothiazolin-3-one aqueous solution. .

  The microbicide of the present invention can be used for paints, adhesives, and water treatment applications. Examples of paint applications and adhesive applications include antibacterial agents, antifungal agents, antibacterial / antifungal agents, and antiseptics. Examples of water treatment applications include slime control agents, antibacterial agents, antifungal agents, antibacterial / antifungal agents, and antiseptics.

  The microbicide of the present invention can be applied to water treatment devices and cooling water systems. As the water treatment device, for example, a water treatment device using a membrane separation device, for example, an ultrafiltration membrane (UF membrane) separation device, a Micro Filtration membrane (MF membrane) separation device, an RO membrane separation device, or these A combination, for example, can be suitably used for a known pure water production apparatus including a pure water production apparatus using a UF membrane separation apparatus in the former stage and an RO membrane separation apparatus in the latter stage, and particularly has an RO membrane. Suitable for pure water production equipment. Further, as a slime control agent, for example, it can be used in a closed circulation cooling water system, or it can be used as a preservative for a chemical used in a water treatment apparatus or the like.

  The use amount of the microbicide, slime control agent, antibacterial agent, antibacterial agent, antibacterial / antifungal agent, preservative, etc. of the microbicide of the present invention is usually 0. 1 mg / L to 20 mg / L, preferably 0.1 mg / L to 10 mg / L, more preferably 0.1 mg / L to 5 mg / L. Further, the addition can be performed once or plural times in the water to be treated. For example, in the case of a water treatment device, the addition may be performed in the feed water to the membrane separation device, and preferably, the addition is performed so as to be contained at least in the feed water to the RO membrane separation device. The amount used in paints and adhesives is usually 100 mg / kg to 5000 mg / kg, preferably 500 mg / kg to 2000 mg / kg in active ingredient concentration in paints and adhesives.

  EXAMPLES Hereinafter, although an Example demonstrates this invention further more concretely, the following description is only for description and the present invention is not limited to these Examples.

Example 1
Preparation of 5-chloro-2-methyl-4-isothiazolin-3-one N, N′-dimethyl-3,3′-dithiodipropionamide (150 g, 0.54 mol, water content 0.1% by weight) Is diluted with 800 g of ethyl acetate having a water content of 0.05% by weight, and reacted by blowing chlorine gas having a water content of 0.001% by weight to give 5-chloro-2-methyl-4-isothiazolin-3-one hydrochloric acid. An ethyl acetate slurry of salt was obtained.

  The obtained slurry was filtered, and the obtained wet cake was washed with toluene having a water content of 0.05% by weight, and the solvent of ethyl acetate was changed to toluene. 200 g of the obtained crystalline 5-chloro-2-methyl-4-isothiazolin-3-one hydrochloride is dissolved in water, and adjusted to pH 1-4 by adding magnesium nitrate hexahydrate, magnesium oxide and hydrochloric acid, An aqueous solution was obtained. The obtained aqueous solution was concentrated under reduced pressure at 40 to 80 ° C. for 3 hours, cooled to room temperature, and then naturally filtered to obtain 1300 g of the desired product. The halogen cyclization step to the solvent exchange step were performed in an atmosphere having a water content of 0.05% by weight.

Using the obtained 5-chloro-2-methyl-4-isothiazolin-3-one, a 10% by weight aqueous solution of 5-chloro-2-methyl-4-isothiazolin-3-one was prepared. A 10% by weight aqueous solution was prepared by quantifying 5-chloro-2-methyl-4-isothiazolin-3-one by high performance liquid chromatography. The residual organic solvent and the hydrolyzate thereof in the obtained aqueous solution were quantified by gas chromatography for ethyl acetate, butyl acetate, ethanol, butanol, and toluene, respectively, and acetic acid by capillary electrophoresis. The results are shown in Table 1. The measurement conditions are as follows.
Analytical conditions for high performance liquid chromatography Device: Shimadzu HPLC system Column: ODS column Detector: UV
Gas chromatography analysis conditions Device: Shimadzu GC system Column: Polar column Detector: FID
Capillary electrophoresis analysis conditions Equipment: HP capillary electrophoresis system Column: Coating capillary column Detector: UV

Example 2
Preparation of 5-chloro-2-methyl-4-isothiazolin-3-one As a solvent in the chlorination reaction, butyl acetate having a water content of 0.05% by weight was used instead of ethyl acetate having a water content of 0.05% by weight. The target product was obtained in the same manner as in Example 1 except that it was used.

  Using the resulting 5-chloro-2-methyl-4-isothiazolin-3-one, a 10% by weight aqueous solution of 5-chloro-2-methyl-4-isothiazolin-3-one was prepared in the same manner as in Example 1. The residual organic solvent and its hydrolyzate were quantified in the same manner as in Example 1. The results are shown in Table 1.

Comparative Synthesis Example 1
Preparation of 5-chloro-2-methyl-4-isothiazolin-3-one Chlorination reaction N, N'-Dimethyl-3,3'-dithiodipropionamide (150 g, 0.54 mol, moisture content 0.8) %) Was diluted with 800 g of ethyl acetate having a water content of 0.5% by weight and reacted by blowing in chlorine gas to give an ethyl acetate slurry of 5-chloro-2-methyl-4-isothiazolin-3-one hydrochloride. Obtained.

Filtration, neutralization and concentration Crystalline 5-chloro-2-methyl-4-isothiazolin-3-one hydrochloride obtained by filtering the resulting slurry was dissolved in water, magnesium nitrate hexahydrate, Magnesium oxide and hydrochloric acid were added to adjust to pH 1 to 4 to obtain an aqueous solution. The obtained aqueous solution was concentrated under reduced pressure at 40 to 80 ° C. for 6 hours, cooled to room temperature, and then naturally filtered to obtain 1150 g of the desired product. The halogen cyclization step to the solvent exchange step were performed in an atmosphere having a water content of 0.05% by weight.

  Using the resulting 5-chloro-2-methyl-4-isothiazolin-3-one, a 10% by weight aqueous solution of 5-chloro-2-methyl-4-isothiazolin-3-one was prepared in the same manner as in Example 1. The residual organic solvent and its hydrolyzate were quantified in the same manner as in Example 1. The results are shown in Table 1.

Comparative Synthesis Example 2
Preparation of 5-chloro-2-methyl-4-isothiazolin-3-one As a solvent in the chlorination reaction, butyl acetate having a water content of 0.5% by weight was used instead of ethyl acetate having a water content of 0.5% by weight. The target product was obtained in the same manner as in Comparative Synthesis Example 1 except that it was used.

  Using the resulting 5-chloro-2-methyl-4-isothiazolin-3-one, a 10% by weight aqueous solution of 5-chloro-2-methyl-4-isothiazolin-3-one was prepared in the same manner as in Example 1. The residual organic solvent and its hydrolyzate were quantified in the same manner as in Example 1. The results are shown in Table 1.

Example 3 and Comparative Examples 1 and 2
TOC reduction effect of permeated water in RO membrane module 10% by weight aqueous solution of 5-chloro-2-methyl-4-isothiazolin-3-one produced in Example 1 and Comparative Synthesis Examples 1-2 as a slime control agent Using. The RO membrane was a DOW BW-10 4-inch module, and the operating pressure was 1.5 MPa. As the supply water to the RO membrane module, dechlorinated water permeated through activated carbon was used. The residual free chlorine concentration in the dechlorinated water was confirmed to be zero by the DPD method. The slime control agent was added such that the concentration of 5-chloro-2-methyl-4-isothiazolin-3-one in the feed water was 0.15 mg / L. The TOC of treated water that passed through the RO membrane module was measured. The results (ppb) are shown in Table 2.

  From Table 1, in the slime control agent of this invention, it turns out that the quantity of a residual organic solvent and its hydrolyzate is reducing significantly compared with the conventional product. And from Table 2, when such a slime control agent was used, the TOC of the permeated water of the RO membrane separator could be set to a very low value of 5 to 11 ppb.

Example 4, Comparative Example 3
TOC reduction effect of permeated water in RO system As a slime control agent, 5-chloro-2-methyl-4-isothiazolin-3-one produced in Example 1 and Comparative Synthesis Example 1 was supplied to about 0.1 ppm. Added to. The feed water was adjusted to pH 7 with industrial water at 25 ° C. using a heat exchanger, caustic soda and sulfuric acid, and passed through a 10 μm safety filter as feed water for the RO membrane. The RO unit uses an 8-inch ultra-low pressure membrane module manufactured by Nitto Denko, with the concentrated water from the previous membrane module connected in 3 rows (3-bank configuration) to serve as the feed water for the subsequent membrane module. ³ / h, permeated water 135 m ³ / h (recovery rate: 75.8%). First, 5-chloro-2-methyl-4-isothiazolin-3-one produced in Comparative Synthesis Example 1 was added to the above-mentioned RO unit in the feed water so as to have a concentration of about 0.1 ppm, and the operation was continued for 45 days. Thereafter, 5-chloro-2-methyl-4-isothiazolin-3-one produced in Example 1 was continuously added under the same pump setting, and the operation was continued for 45 days. The transition of the TOC of the permeated water (collected permeated water of three rows of membrane modules into one) during each operation period was measured. The analysis results of the TOC of the permeated water are shown in Table 3 below.

In Comparative Example 3, the TOC of the treated water did not reach the target value (less than 30 ppb), but by changing to Example 4, the TOC of the treated water was greatly reduced even at a recovery rate of 75%, and the target value of the treated water Was achieved.

Claims (9)

A microbicide containing 5-chloro-2-methyl-4-isothiazolin-3-one as an active ingredient, wherein the total content of the organic solvent and its hydrolyzate and the concentration of the active ingredient are as follows: using microbicides satisfying the equation (1), slime control method of the pure water production system having a reverse osmosis membrane.

Total content of organic solvent and its hydrolyzate expressed in ppm × (10 / B) ≦ 200 ppm (1)
(In formula (1), B represents the numerical value of the active ingredient concentration expressed in weight%.) The slime control method according to claim 1, wherein in the microbicide used, the organic solvent is an acetate ester and / or a hydrocarbon compound. 3. The slime control method according to claim 2, wherein in the microbicide used, the organic solvent is an acetate ester or an acetate ester and a hydrocarbon compound. The slime control method according to claim 2 or 3, wherein in the microbicide used, the hydrocarbon compound is toluene. The slime control method according to claim 2 or 3, wherein in the microbicide used, the acetate is at least one selected from the group consisting of ethyl acetate and butyl acetate. The slime control method according to any one of claims 2 to 5, wherein in the microbicide to be used, the total content of the acetate ester and its hydrolyzate and the concentration of the active ingredient satisfy the following formula (1 ').

Total content of acetate and its hydrolyzate expressed in ppm × (10 / B) ≦ 60 ppm (1 ′)
(In the formula (1 ′), B represents the numerical value of the active ingredient concentration expressed in weight%.) The slime control method according to any one of claims 2 to 5, wherein in the microbicide used, the content of acetic acid and the concentration of the active ingredient satisfy the following formula (1 ").

Acetic acid content in ppm × (10 / B) ≦ 10 ppm (1 ″)
(In the formula (1 ″), B represents the numerical value of the active ingredient concentration expressed in weight%.) In the microbicide used, the active ingredient is
A step of halogenating cyclization of a sulfide amide intermediate, and a step of neutralizing a hydrogen halide salt of the compound having a 3-isothiazolone ring obtained in the above step, which is performed as necessary, In the production process of methyl-4-isothiazolin-3-one,
Acetic acid ester having a water content of 0.1% by weight or less was used as a reaction solvent in the halogenated cyclization step, and was obtained after the cyclization step and before the neutralization step. By adding a hydrocarbon compound having a water content of 0.1% by weight or less to a wet cake obtained by filtering the acetate dispersion of the hydrogen halide salt, the acetate is dissolved in the hydrocarbon compound by filtration. As well as exchange
5-chloro-2-methyl-4-isothiazolin-3-one obtained by carrying out from the halogenated cyclization step to at least the solvent exchange step in an atmosphere having a water content of 0.1% by weight or less. The slime control method in any one of Claims 1-7. 9. The slime control method according to claim 1 , wherein the microbicide used contains 1 to 30% by weight of an active ingredient.