TW201100015A - Microbicide - Google Patents

Abstract

Provided is a microbicide having 5-chloro-2-methyl-4-isothiazolin-3-one as the active component and a reduced amount of residual materials and hydrolysates from the organic solvents used in the industrial manufacturing method thereof. The microbicide, which includes 5-chloro-2-methyl-4-isothiazolin-3-one as the active component and has a total amount of the organic solvent and the hydrolysate thereof of no more than 200 ppm when the concentration of the active component is 10 wt%, is obtained by a manufacturing method involving a process for the cyclization of sulfide amides and a process for neutralizing hydrogen halide salts of a compound comprising a 3-isothiazolone ring, wherein acetic acid ester containing no more than 0.1 wt% of water is used as the reacting solvent for the cyclization process, a hydrocarbon compound having a water content of no more than 0.1 wt% is added to the hydrogen halide salt obtained by filtering the acetic ester fluid dispersions of the hydrogen halide salt and the resulting mixture is filtered, solvents are exchanged, and the processes are carried out in an atmosphere with a water content of no more than 0.1%.

Description

201100015 VI. Description of the Invention: [Technical Field to Be Invented by the Invention] The present invention relates to an active ingredient of 5-chloro-2-methylcyclotetracycline & ^^ 虱2 methyl-4-isothiazolin-3-yl The microbicide, more specifically, is a residue of an organic solvent used in the production step of the effect component and a microbicide whose content is reduced. 〇 5-Gas-2-methyl-4-isothiazoline-3-one is a preservative or bactericide for various sanitary products because it has a biological activity 1 for inhibiting the proliferation of microorganisms. In addition, it can also be used as an active ingredient of a biological slime controlling agent for preventing biological slime (sHme), which is derived from microorganisms or algae such as bacteria produced in a water treatment device or a cold fly X system. Composition of organic matter, etc., especially in a water treatment plant or a cooling water system, based on a water treatment process or a cooling water system (closed system, open system, etc.), etc., requires a water treatment step with biological slime Different performance than suppression. For example, in the water treatment for the high-purification of the final effluent or the reuse of various kinds of drainage, the clogging of the hole of the knife due to the fouling substance contained in the treated water is regarded as a big problem. Therefore, it is considered that the presence of a protein such as a protein in the water to be treated in the cause of a decrease in the flow rate of the separation membrane is considered to be a problem. Aggregation of proteins is removed (for example, refer to Patent Document 2). In addition, for the reuse of the factory drainage, in the water treatment of the 3 201100015 biological treatment water into the rod belly, ., ^, knife off treatment, there is gas caused by the membrane, or the total organic carbon caused by the killing of microorganisms ( T〇c, on! J reference special: 2) increased problems, and therefore seek to solve these problems (example). Moreover, in the production of the ultra-pure water for cleaning used in the manufacture of a semiconductor device, it is necessary to add two: a control agent to each of the plurality of membrane devices, and it is difficult to control the problem. Film) / (for example, refer to Patent Document 4). Furthermore, in the case of the treatment of the reverse osmosis membrane (C RG membrane), the "concentrated water is discharged to the outside of the system in the form of drainage", the industry seeks high water recovery (see, for example, Patent Document 5) . Further, in the use of the apparatus for the production of the apparatus, it is proposed to provide an ion exchange apparatus for reducing the ion permeation charge (10) of the membrane permeating water by using the pure water of the R membrane separation apparatus (see, for example, Patent Document 6). For such a process involving the treatment of biological slime; i, it is known that there are various requirements that can be considered as problems. Cold Wave # is a new topic, and the industry is seeking to reduce the height by step: tC. For the processing system of R 〇 film, in the case of high water quality, in the manufacturing of swill water, the TOC of the degree of _~number+ _ is regarded as the rhyme according to the use, and the 4 main 山山 shouts in particular for the manufacture of semiconductors. In the use of pure water, such as the use of pure water, etc., the problem has become severe in recent years. The sterilization treatment of the Legionella in the cold water system and the biological environment, pk A丨; 1 mud control 'has the following problem: low molecular organic compounds in the water system & Gil a ^, solution, but become a nutrient source of biological slime. In particular, the biological slime control in the Ή system is less than the Mblow water in the open-circuit cooling water system, so the residence time becomes longer, so it is difficult to exert the biological slime control effect when 201100015. If a low-knife organic compound component is mixed in such a system, it is rapidly absorbed by microorganisms, so it is necessary to avoid mixing the low molecular organic compound component into the system as much as possible.

In order to solve this problem, for example, it is possible to carry out research to improve the performance of the membrane separation apparatus', but it is technically difficult to sufficiently reduce T〇c. X, in order to reduce the treatment water "TGC", it is also possible to carry out research on the additional post-processing steps, but it will not only complicate the processing work, but also increase the processing cost. Therefore, the industry is seeking countermeasures that can be easily applied to previous processing steps. In addition, the step of cyclization of the 5-gas-2-methyl-4-isothiazoline-3 ruthenium amide intermediate and the use of hydrogen dentate to neutralize the 获得3_ The production step of the neutralization step of the compound of the oxime ketone ring (for example, refer to Patent Documents 7 and 8) is commercially available. In the production method, acetic acid vinegar is industrially used as a solvent for the cyclization reaction of the ruthenium sulfide intermediate. The original reaction is because the reaction conversion ratio is high when acetic acid vinegar is used. Further, an organic solvent is also used for the washing and extraction steps of the compound. These organic solvents, although removed in the final step of the manufacturing step, are difficult to completely remove, and may remain in the form of impurities in the most desired product. However, such a residue is a trace amount, for example, in the water for biological slime control, the 5_gas_2_methyl_4 is located in the treated water, usually in the treated water, and is usually several mg/L left and thus treated in water. The concentration of the residue is also low, which was not considered a problem in the past. [PRIOR ART DOCUMENT] [Patent Document 1] Japanese Patent Laid-Open Publication No. Hei. No. Hei. No. 2, No. Hei. [Patent Document 5] Japanese Patent Laid-Open Publication No. Hei No. Hei 9 294 〇 〇 〇 [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [Patent Document 7] Japanese Laid-Open Patent Publication No. SHO-59-31 No. 1772 (Patent Document 8). However, as a result of the confirmation, in the use of water treatment, particularly in the case where the trace residue is a problem, for example, in a residue used in a pure water production apparatus, the low molecular organic compound component passes through the membrane separation device. And leaked into the treated water. It was also confirmed that there was such a leak in the processing system of the R film. However, the performance of the microbicide itself has been improved as before: the subject matter is less. 'In order to prevent air pollution caused by the coating agent or the adhesive, it is known that the compound containing the 3-isothiazolinone ring is volatile. It is less in content, but it is not known to use it as a biological slime control agent. Therefore, it is an object of the present invention to provide a microbicide which is an organic solvent used in an industrial manufacturing step of the active ingredient, which is a gas, 2-methyl-4-isothiazolin-3-one. The content of the residue and its hydrolyzate is sufficiently reduced as compared with the previous product. [Means for Solving the Problem] 201100015: The invention relates to a microbicide which contains 5chloro-2-methyl and hydrazine: ketone as an active ingredient, and is characterized in that: organic dissolved hydrolyzate The total content and the concentration of the above-mentioned active ingredient 式 Formula C 1 ) 合 total content X ( 1 0 / B ) The organic solvent and its hydrolyzate expressed in ppm ^ 200 ppm ( 1 ) Value Ο In the formula (1), B represents Hydrocarbon compounding of the active ingredient concentration expressed in % by weight

In another aspect of the invention, an organic ester and a hydrocarbon compound. G I 2: In one aspect of the invention, the 'smoke compound is toluene. In one aspect of the invention,

At least 7 kinds of acid vinegars of the group consisting of vinegar and butyl vinegar are selected from the group consisting of acetonide acetate: loading, acetic acid vinegar and hydrolyzate thereof, and the concentration of the effective knives satisfying the following formula ( 1,) the total content X (

10/B acetic acid brewed with PPm and its hydrolyzate; ^ 6〇ppm ( 1') value Γ), B represents the concentration of the active ingredient expressed in % by weight. 7 201100015 The content of acetic acid expressed by p yang X (10/B) u 〇 ppm (i, value / In (), the table B does not indicate the concentration of the active ingredient expressed by 1% by weight. (4) In another aspect of the invention, the active ingredient is 5-gas-2-methyl or 4-isoketone, and the compound is as follows The method of obtaining the cyclization step including the intermediate of the sulfhydryl sulfide: , and, if necessary, the hydrogenation of the hydrogenated acid salt, and obtained by the above steps, and having 3 phases of the sitting phase ring In the step of producing a compound of chloro-2-methyl...Salina.3, the acetic acid having a moisture content of qi% by weight or less is used as the reaction solvent of the above-mentioned functional cyclization step, after the cyclization step, And in the case of performing the above neutralization step, before the step, the obtained acid acetate 3 dispersion is obtained (4), and the obtained thirsty filter cake is added with a moisture content of less than 5% by weight. Hydrocarbon compound is carried out and filtered, whereby the above-mentioned acetate solvent is exchanged for the above hydrocarbon compound; The cyclization step is carried out until at least the solvent exchange step is carried out in a gas atmosphere having a moisture content of (% by weight or less. In another aspect of the invention, the active ingredient is contained in an amount of 1% by weight. Providing a biological slime controlling agent, which is suitable for use in a pure water manufacturing device having a reverse osmosis membrane. Further, the present invention provides a biological slime controlling method for a pure water producing device having a reverse osmosis membrane, The above-mentioned microbicide is used. [Effect of the Invention] The present invention provides a microbicide which is effective as a raw material of the component 201100015, that is, 5-gas-2-methyl-4 isothiazoline-3-one. The solvent for the southern cyclization reaction of the ruthenium sulfide intermediate and the extraction of the reaction product, the residual amount of the organic solvent of the cleaning solvent and the hydrolyzate thereof, in other words, the organic solvent used in the production step of the above active ingredient and the hydrolyzate thereof The residual amount is sufficiently reduced. The present invention provides a microbicide by using the above composition, wherein even if an acetate having a high reaction conversion ratio is used as an active ingredient, that is, a gas mixture The halogenated cyclization reaction solvent of the guanidinium sulfonate intermediate, and the residual amount of the acetate and the hydrolyzate thereof are also sufficiently reduced. In particular, a microbicide having a reduced residual amount of acetic acid can be provided. Since the bioclay control is carried out by using the microbicide of the present invention in a membrane separation device such as an RO membrane separation device, the τ 〇c in the treated water can be greatly reduced as compared with the case of using the prior product. [Embodiment] ❹ & In the microbicide of the present invention, the concentration of the active ingredient, that is, the concentration of 5chloro-2-methylisoxanthene-3-one, and the total content of the organic solvent and the hydrolyzate used in the production step satisfy the following Since it is a formula (1), it does not contain the organic solvent and its hydrolysate used by the manufacturing process substantially. The total content of the organic solvent and its hydrolyzate expressed in ppm ^ 200 ppm (1) In the formula (1), B represents the value of the active ingredient concentration expressed by weight %. Preferably, the right side of the above formula (1) is 100 ppm, more preferably 9 201100015, and the right 'then the sensitivity of the machine is more preferably 40 ppm. It can also be formulated in the form of a salt in the form of a hydrogen blend. - an organic solvent or the like used in the t-step of the acid or the sulphuric acid, for example, acetic acid vinegar: the mixture is preferably acetic acid, the acetic acid butyl vinegar is more preferably acetic acid B, and the material = for example, toluene, hexane, Cyclohexene, etc.), or such mixed slag or other organic solvents (eg, acetic acid, ethanol, etc.). Further, the total content of the acetic acid brewing and the hydrolyzate thereof and the above-mentioned effective agricultural degree are preferably such that the following formula (1) is satisfied. The total content of acetate and its hydrolyzate expressed in ppm X ( ι〇/β ) $ 60 ppm ( 1 丨) The formula in (1) is not heavy! % indicates the value of the active ingredient concentration. On the right side of the formula (1), it is more preferably 40 ppm ° if the sensitivity of the measuring machine is allowed. Further, the content of the acetic acid and the concentration of the above-mentioned effective component preferably satisfy the following formula (丨, 1). The content of acetic acid expressed in ppm X (10/B) s10 ppm (1,,) In the formula (Γ'), B is not by weight. /. Indicates the value of the active ingredient concentration. The right side of the formula (1) is preferably 5 PPm if the sensitivity of the measuring machine is allowed. By reducing the content of acetic acid, for example, the amount of acetic acid which is easily permeated through the membrane separation device such as the R membrane separation device can be reduced. For the active ingredient, 5-gas-2-methyl-4-isothiazoline 10 201100015 3辋, compared with the commercially available product, the total content of the impurities as a substance is charged, and the solvent is hydrolyzed. I 厶 厶 。 。 。 。 。 。 。 。 作为 作为 作为 作为 作为 作为 作为 作为 作为 作为 作为 作为 作为 作为 作为 作为 作为 作为 作为 作为 作为 作为 作为 作为 作为 作为 作为 作为 作为 作为 作为 作为 作为 作为 作为 作为 作为The combined amount of the solution satisfies the above conditions in the present invention, the production method of 5- 5-methyl-2-...wow-phase, known as Ο heart = brewing: intermediate... cyclization step, and utilization of hydrogen halide The industrial manufacturing step of the 5-chloro-2-methyl- 4-salt salination phase of the neutralization step of the compound having the ^ ^ ^ 嗟 嗟 琳 酮 ketone ring obtained by the above steps. The isothiazolinone ring has the following structure.

Here, as the intermediate of the ruthenium sulfide, there are known an intermediate in a monosulfide-branched amine (for example, an anthracene-alkyl group), and an intermediate of a ruthenium disulfide (for example, ruthenium, ruthenium). - a dialkyl group - 3,3, -dithiopropane #; as a production step using a monosulfide-branched amine intermediate, for example, the production disclosed in Japanese Laid-Open Patent Publication No. 59-M772, etc. The method is characterized in that, for example, esterification of 3- thiopropionic acid as a starting material is first carried out, and the obtained 3-thiopropionate is subjected to guanamidation to prepare guanidinium monosulfide. The amination is usually carried out in an organic solvent such as decyl alcohol or toluene. Since the slurry containing guanidinium monosulfide is obtained after completion of the reaction, the solvent is removed from the slurry. Then, the sulfonium monosulfide is dispersed again. It is preferably an ethyl acetate or a butyl acetate 201100015 ester or the like in an organic solvent such as acetic acid to form a slurry, which is then reacted with hydrogen dentate to carry out a halogenation cyclization reaction. The thus obtained hydrohalide salt In the middle of t, the target compound is obtained as the main product. At this time, in order to make the target It does not contain a metal salt and a water jet derived from the neutralization of a dentate. It is also known to use a method of dissolving an organic compound having a 3-isothiazolinone ring compound and not dissolving an alkali metal salt. The solvent is subjected to neutralization, and is subjected to a method of dehydration and distillation of an organic solvent. Further, as a production step of using a ruthenium disulfide intermediate, for example, US Patent No. 3849430 and European Patent No. 〇959〇7 are known. The production method disclosed in Japanese Laid-Open Patent Publication No. SHO 59-31772, etc., as a general example, for example, the first diced dithiodipropionic acid as a starting material is cooled, and the obtained dithiodipropionic acid is further obtained. Vinegar is brewed and aminated, and made into two

Ammonium sulfide. The amide amination is usually carried out in an organic solvent such as methanol or toluene. Since the body containing the decylamine disulfide is obtained after completion of the reaction, the solvent is removed from the steroid. Next, the sulfonium sulfonamide is again dispersed in an organic solvent such as acetic acid such as ethyl acetate or butyl acetate, and the polymer is further reacted with hydrogen hydride to carry out a functional cyclization reaction. . The hydrogen dentate obtained as described above was neutralized to obtain a target compound as a main product. At this time, in order to prevent the target compound from substantially containing the metal salt and water derived from the hydrogen: acid dish, it is known that the compound having the 胄3_isoindolinone ring can be dissolved and dissolved. Metal inspection

Organic dissolved (four) towel and water-repellent and (four) agent "division method. J However, there is a 5_ gas armor 12 201100015 -4-isoteron material_3_嗣 obtained by such a manufacturing method as an active ingredient In the microbicide, the total content of the organic solvent and the hydrolyzate as the impurity 's usually cannot satisfy the above conditions. That is, even if the hydrocarbon-based organic solvent such as toluene is removed by steaming, it is difficult to remove the acetic acid vinegar from the base. Residual solvent remains in the final product. According to the analysis of the present inventors, the residual amount in the concentration of 1 () thiol_4_M (tetra) _3 ketone 'total is about to be measured = known vinegar is usually easy to remain, so the value It can be used as a standard for the total amount of residual organic solvent and hydrolyzate of 5·chloro-2·methyl-line: π 3 produced by acetic acid vinegar previously prepared. S, in the present invention, Preferably, 5-oxa-2-methyl-4-isothialin-3-one is produced by the following as an active ingredient. That is, 5-chloro-2-ketone obtained by the following method can be used: Including guanidinium sulfide, the sulphate ' ' ' ' oxazoline-3-into... And, if necessary, the sodium chloroformate of the neutralization step of the compound having the porphyrin-ring obtained by the above steps. In the well-known production step of 3-ketone, the ruthenium osmium is preferably 〇.〇1% by weight or less of two: "1 is 0.1% by weight/%. The following, acetic acid butyl, more preferably 乙二, for example, preferably acetic acid,

And the agent is subjected to the above-mentioned neutralization C liquid after the cyclization step, and the amount of the dispersion is determined. "Underly, it is preferred to add a hydrocarbon compound having a moisture content of hexane, cyclohexane or the like to the cake, such as toluene, by replacing the above-mentioned alkylation with the above solvent, and from the above-mentioned tooth ring Steps to at least the above 13 201100015

The solvent exchange step is at least 5% by weight, preferably 0% by weight. /. The following gas atmospheres are carried out, for example, in a dry inert gas (e.g., nitrogen, argon, etc.) or in dry air. Furthermore, from the above-described cyclization step to at least the solvent exchange step, the gas content is in a gas atmosphere having a moisture content of 01% by weight or less, preferably 0.05% by weight or less, which means that the system is blown in advance by the system. After the moisture content is 〇1% by weight or less, preferably 0.001% by weight or less, the water is removed, and then the water content is 0.01% by weight or less, preferably 〇〇〇1% by weight or less. The gas 'is managed to carry out the work at the same time. In the above-described production steps, a known method can be employed for the cyclization step, the neutralization step, the concentration, and the like. In the above solvent exchange step, specifically: the tongue' can be obtained by filtering the above-mentioned hydrogen "salt acetic acid s dispersion": a humidified filter cake, adding a 5-fold amount of a hydrocarbon compound and filtering the vehicle 1 to 2 times, whereby the solvent is exchanged from the acetate to the hydrocarbon compound, preferably by filtration or centrifugation, more preferably by centrifugation, and the functionalization cyclization step to at least the solvent exchange step. The operation so far,

It is preferably carried out in a dry inert atmosphere. According to the above manufacturing steps, the obtained organic solvent and its hydrolyzate which are substantially not used in the 5-chloro-2-methyl-4-isothiazoline-3-one can be obtained, in particular, 5-gas 2-methyl-4-isoindole _3-ketone which does not contain acetate and acetic acid and ethanol as hydrolysates. Further, in the above-mentioned manufacturing step, the concentration step time may be from 10 to 15 sec. and usually takes 20 hours or more (four), so that H50% is required. In addition, the yield of 5_gas·2_methyl ice sighs sings 14 嗣 14 14 201100015 can be increased by 5 to 10%. The microbicide of the present invention may be used as long as the above-mentioned active ingredient is dissolved in water, and may be used as a stabilizer such as calcium, magnesium, manganese or nickel as needed. Nitrate or gasification of metals such as steel and zinc. Such a method is known, for example, from U.S. Patent No. 3,870,795 and the like. In the microbicide of the present invention, the concentration of the above active ingredient is usually from 1 to 30% by weight, preferably from 5 to 2% by weight. When the concentration of the above-mentioned active ingredient is high, for example, when the above-mentioned effective component exceeds 3% by weight, when a stabilizer is used, the possibility of precipitation of a metal nitrate or a vapor as a stabilizer is increased. Further, when the concentration of the above active ingredient is low, for example, the above active ingredient is not full! In the case of % by weight, the stability of the above-mentioned active ingredient tends to be deteriorated, and further, it has to be used in a large amount at the time of use, and it is inefficient in terms of commercials and blending. Therefore, in terms of practicality, the concentration of the above 0 active ingredient is preferably 5 to 2% by weight. The amount of the stabilizer to be used is, for example, 1 part by weight to 5 parts by weight based on 100 parts by weight of the aqueous solution of 5_gas_2_methyl_4·isoindol-3-one, preferably 15 to 25 parts by weight. The microbicide of the present invention can be used for coatings or adhesives, and water treatment. Examples thereof include an antibacterial agent, a water treatment application, an antifungal agent, and an antibacterial/anti-path. For coating applications or adhesive applications, such as anti-fungal agents, antibacterial/mold inhibitors, preservatives, etc. For example, biological slime control agents, antibacterial agents, fungicides, and preservatives can be cited. 15 201100015 The microbicide of the present invention can be handled. As a water treatment device, the (4)::: or cold device of the present invention is well-known as a device for manufacturing a pure water such as a membrane, for example, using a membrane separation membrane: For example, the super-film (film) separation device and the R-film separation device are as follows: as in the previous stage, the medium separation device is used and the latter is made: water:::r has a "film pure two-set", "physical slime" The control agent, for example, can also be used as a preservative for the closed system. The reagent used in the water treatment device or the like is used as the microbicide of the present invention in the biological slime control agent, anti-u, anti-mold agent, The amount of the active ingredient in the water to be treated, such as an antibacterial/mold inhibitor or a preservative, is usually gi mg/L to mg/L, preferably 0·1 mg/L to 1 〇 mg/in the treated water. L, more preferably (M mg / L ~ 5 . And 'can be added once in the treated water, or divided into multiple times (1) for the water treatment device, can be added to the membrane separation device eight Jc towel car乂 preferably is added to at least the supply water to the R membrane separation device - as a coating or adhesive application The amount of the active ingredient in the coating or the adhesive is usually (10) is 7~(10)(10) mg/kg, preferably 5〇〇mg/kg~2000 mg/kg. [Examples] Hereinafter, the present invention is further exemplified by the examples. The specific description is given below, but the following is mainly used for explanation, and the present invention is not limited to the examples. 16 201100015 Example 1 5-Chloro-2-mercapto-4-isothiazolin-3 - Manufacture of ketones using 100 g of ethyl acetate with a moisture content of 0.05% by weight to dilute N,N'-dimethyl-3,3'-dithiodipropionamide (150 g, 0.54 mol, moisture content) 0·1% by weight), and chlorinated with a moisture content of 0.001% by weight, and reacted to obtain 5-acetic acid-2-methyl-4-iso-sevolin-3--3-hydrochloride acetic acid Ethyl ester slurry.

The slurry obtained by W was filtered, and the obtained wet cake was washed with a moisture content of 0.05% by weight, and the ethyl acetate solvent was exchanged to toluene. The obtained crystal of 5_gas_2-methyl-4-isothiazoline-3-inone hydrochloride 200 g was dissolved in water, and magnesium nitrate 6 water and magnesium oxide, hydrochloric acid were added to adjust the pH. Adjust to Bu 4 to obtain an aqueous solution. The obtained water: = concentrated under reduced pressure for 3 hours under reduced pressure. After cooling to room temperature, natural filtration was carried out to obtain 13 g of the target product. The step of the solvent-to-solvent exchange step A is carried out in the above-described rolling mill environment in which the moisture content is 〇.〇5 wt%. 5_Chloro-2-methyl-2 in the use of Lili/〇~······································· From the high-performance liquid layer% aqueous solution. Η) Weight % I was prepared by quantification. Needle·Chlorinyl-4-isolated saliva agent and its hydrolyzate, by means of the residual organic soluble ethanol and butanol 1 benzene in the gas phase, the amount of J ethyl hydrazine, acetonitrile, and the amount. Will result in 14 tables]. Capillary electrophoresis for the analysis of acetamidine by Southern liquid chromatography. The conditions are as follows. 17 201100015 Device: Shimadzu HPLC system column: ODS column detector: UV gas chromatography analysis condition device: Shimadzu GC system column: polar column detector: FID capillary electrophoresis analysis condition device: HP capillary Electrophoresis system column: coated capillary column detector: UV Example 2 5-Gas-2-mercapto-4-isothiazolin-3-one was produced as a solvent in the chlorination reaction, using a moisture content of 0.05 The target product was obtained in the same manner as in Example 1 except that butyl acetate was used in an amount of 0.05% by weight of ethyl acetate. Preparation of 5-Ga-2-methyl-4-isothiazolin-3- in the same manner as in Example 1 using 5-hexane-2-methyl-4-isothiazolin-3-one obtained A 10% by weight aqueous solution of a ketone was used, and its 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 Production of 5-chloro-2-indolyl-4-isothiazolin-3-one Gasification reaction Using ethyl acetate 800 g of water content of 0.5% by weight to dilute hydrazine, Ν'- 18 201100015 dimethyl Base _3,3'·dithiodipropionamide (150 g, 0.54 mol, moisture content 〇.8 wt%), and blown into the gas to react, thereby obtaining 5-chloro_2_曱Ethyl acetate slurry of keto-4-isoindole_3_ketone hydrochloride. Filtration, neutralization and concentration, the obtained slurry is filtered, and the obtained crystallized chloro 2_methyl-4-isothiazoline_3__ hydrochloride 18 〇g is dissolved in water, and magnesium nitrate is added. 6 water and matter, magnesium oxide, hydrochloric acid and the pH was adjusted to 丨~4 to obtain an aqueous solution. The obtained aqueous solution was concentrated under reduced pressure at 40 to 8 (TC) for 6 hours, and then cooled to room temperature, and then subjected to natural filtration to obtain a target product of 115 〇g. Further, from the above-mentioned functional cyclization step to solvent exchange The step was carried out in a gas atmosphere having a moisture content of 0.05% by weight. Using the obtained 5-gas-2-mercapto-4-isoindole _3_嗣, in the same manner as in Example 1. A 1% by weight aqueous solution of 5-gas-2-methyl-4-isothiazoline-3-one was prepared, and the residual organic bath and its hydrolyzate were quantified in the same manner as in Example 1. The results are shown in Table 1. Comparative Synthesis Example 2 Production of 5-chloro-2-methyl-4-isothiazolin-3 ketone As a solvent in the chlorination reaction, butyl acetate having a moisture content of 0.5% by weight was used instead. The target product was obtained in the same manner as in Comparative Synthesis Example 1 except that the moisture content was 5% by weight of ethyl acetate. The obtained 5_gas_2_mercapto-4_isothiazoline was used. 3_ketone, by the same method as in Example 1, the preparation of 5_gas_2_methyl_4_isothiazoline·3_ steel 1〇重里/〇水' liquid mixture, and borrowed The residual organic/treat and its hydrolyzate were quantified in the same manner as in Example 1. The results are shown in Table 1. 201100015 [Table 1] Organic solvent and its hydrolyzate Example 1 Example 2 Comparative Synthesis Example 1 Comparative Synthesis Example 2 Ethyl acetate < 10 ppm < 10 ppm 2200 ppm < 10 ppm butyl acetate < 10 ppm < 10 ppm < 10 ppm 5000 ppm acetic acid < 10 ppm < 10 ppm 3200 ppm 3500 Ppm Ethanol < 10 ppm < 10 ppm 2200 ppm 20 ppm Butanol < 10 ppm < 10 ppm < 10 ppm 1000 ppm Toluene < 10 ppm < 10 ppm < 10 ppm < 10 ppm Example 3 Comparative Example 1 and Comparative Example 2 The TOC reduction effect of the permeated water in the RO membrane module The bioadhesive control agent used was the 5-gas-2-methyl group produced in Example 1 and Comparative Synthesis Examples 1 and 2. a 10% by weight aqueous solution of -4-isothiazolin-3-one. The RO membrane system is a 4 吋 module of BW-10 manufactured by DOW, and the operating pressure is set to 1.5 MPa. The water supply system for the RO membrane module is used. Dechlorinated water of activated carbon. The residual free gas concentration of degassed water is confirmed by DPD method to be zero. The biological slime control agent is 5-gas-2- Yl-4-isothiazolin-3-one in the supply of water to achieve a concentration of 0.1 5 mg / L was added manner. The TOC of the treated water passing through the RO membrane module was measured. The results (ppb) are shown in Table 2. [Table 2] Example 3 Comparative Example 1 Comparative Example 2 Manufacturing Method Example 1 Comparative Synthesis Example 1 Comparative Synthesis Example 2 TOC (ppb) 5 to 11 20 to 46 32 to 44 20 201100015 It is understood from Table 1 that the present invention The amount of residual organic solvent and its hydrolyzate of the biological slime control agent is greatly reduced as compared with the previous one. Further, as is apparent from Table 2, in the case of using such a biological slime controlling agent, the T 〇 C of the permeated water of the R 膜 membrane separating apparatus is extremely low at a value of 5 to ppb. Example 4, Comparative Example 3 The toc reduction effect of the permeated water in the R〇 system The supply of the 0·1 ppm method is used as a biological slime control agent to achieve about 〇

The 5-chloro-2-methyl-4-isothiazolin-3-one produced in Example 1 and Comparative Synthesis Example 1 was added to water. The water supply system is used in a heat exchanger at 25 <>, using pH of caustic soda and sulfuric acid to adjust the pH of the industrial water to 7, and passing it through a 10 ym female full filter as the R 〇 film. Supply water. The single 兀* system is connected to three columns (three banks) by connecting the 吋 缩 膜 以前 以前 以前 以前 以前 , , , , , , , , , , , , , , , , , , , The operation was carried out under the conditions of a supply water of n8 m3/h and a permeate water of 135 m / h (recovery rate of 75.8%). First, 5-chloro-2-indolyl-4-isothiazoline-3-enone produced in Comparative Synthesis Example i is added to the supply water in a manner of about 〇·1 ppm in the above RO unit. And continuous operation for 45 days. Thereafter, the pump was set to the same state, and the 5-gas-2-methyl-4-isothiazoline-3-one produced in Example 1 was continuously added and continuously operated for 45 days. The change in tOC of the permeated water (sinking the permeated water of the three rows of membrane modules) in each operation period was measured. The results of the analysis of T〇c through water are shown in Table 3 below. 21 201100015 [Table 3] '^----- % Example 4 ——--1 Comparison n____ Manufacturing method % Example 1 Comparative Synthesis Example 1 TOC (ppb) _ 8 ～ 19 50 ～ 75 In the comparative example In 3, 'treated water/|, bite a, m, π w"v PPM ', but by changing to Example 4, even if the recovery rate is 75%, the TOC of treated water is greatly reduced, and the treated water is reached. Target value. [Simple description of the diagram] None [Key component symbol description] 22

Claims (1)

201100015 VII. Patent application scope: 1. A microbicide consisting of 5_gas_2_mercapto-4-isothiazolin-3-one as an active ingredient, characterized by a total of organic solvents and hydrolyzates thereof The content and the concentration of the active ingredient satisfy the following formula (1): the total content of the organic solvent and its hydrolyzate expressed in ppm. i 〇 / b ) ^ 200 ppm ( 1 ) (In the formula (1), B represents The weight % indicates the value of the active ingredient concentration). 2. A microbicide as claimed in claim 1 wherein the organic solvent is acetic acid vinegar and/or a smoky compound. 3. The microbicide of claim 2, wherein the organic solvent is acetate, or acetate and a hydrocarbon compound. 4. A microbicide as claimed in claim 2, wherein the hydrocarbon compound is toluene. 5. The microbicide according to claim 2 or 3, wherein the acetate is selected from the group consisting of ethyl acetate and butyl acetate, at least i 〇 insertion 0 6 · as claimed in the patent scope The microbicide of item 2 or 3, wherein the total content of the acetate and the hydrolyzate thereof and the concentration of the active ingredient satisfy the following formula (1'): the total of the acetate and its hydrolyzate expressed in ppm Content x (lo/B) g 60 ppm (1') (In the formula (B), B represents the value of the active ingredient concentration expressed in % by weight). In the case of the microbicide of any one of the items 1 to 3, the content of the acetic acid and the concentration of the active ingredient satisfy the following formula (Γ,). The content of acetic acid expressed by Ppm x ( ι〇 / Β) $ 1 〇 ppm (in the formula (1 ") Β represents the value of the concentration of the active ingredient expressed in % by weight.) 8- If the scope of patent application is 2 Or the microbicide of item 3, wherein the active ingredient is obtained by the following method: 5-gas-2-methyl-4-isothiazolin-3-indole: in a toothed ring including an intermediate of sulfonium sulfide a step of 'and optionally using a dentate salt to neutralize the 3-isomer obtained by the previous step. 5 - gas - 2 - thiol of the neutralization step of the compound of the genus In the manufacturing step of 4_isoindole 3, acetic acid having a water content of 〇1% by weight or less is used as a reaction solvent for the cyclization step, after the cyclization step, and during the 4 neutralization step. Before the step, the obtained acetate dispersion of the hydrohalide is filtered, and a hydrocarbon compound having a moisture content of less than 9% by weight is added to the obtained wet cake, and filtered. The solvent is solvent exchanged to the hydrocarbon compound; and from the toothing cyclization step to at least the solvent The microbicide according to any one of the above-mentioned items of the present invention, which contains 1 to 30% by weight of the active ingredient, is carried out in a gas atmosphere having a moisture content of 0.1% by weight or less. 10. The microbicide according to any one of claims 1 to 3, which contains 5-gas-2-mercapto-4-isothiazolin-3-one as an active ingredient, 24 f 201100015 And used as a biological slime control agent. 11. A biological slime control method for a pure water producing device having a reverse osmosis membrane, which is the microbicide according to any one of claims 1 to 3. , pattern · no D 25