JP2001270869A - Method for producing liquid composition of 3-isothiazolone compound - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a stable liquid composition containing 3-isothiazolone compound and without substantially containing metal salts. SOLUTION: This method for producing a liquid composition of 3- isothiazolone is to add and mix a hydrohalogenic acid salt of 3-isothiazolone compound to phenol and then blowing an inert gas into the mixture or reducing pressure and deaerating the mixture while heating.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a method for producing a liquid composition of a 3-isothiazolone compound which is useful as a microbicide and has excellent stability.

[0002]

2. Description of the Related Art (3-Isothiazolone compounds) 3-Isothiazolone compounds are effective industrial microbicides. Among them, 5-chloro-2-methyl-4-isothiazoline-
3-one (also referred to herein as "CL-MIT")
Is effective as a microbicide for various water-based industrial products such as water treatment field, latex emulsion and emulsion paint.

[0003] CL-MIT is very reactive, extremely unstable, and has the property of being rapidly decomposed. For this reason, magnesium nitrate or the like is widely added as a stabilizer. Therefore, CL-MIT is commercially distributed in a form containing a large amount of metal salts such as magnesium nitrate as a stabilizer.

However, CL containing such a metal salt
-When MIT is added to a latex emulsion, an emulsion paint, or the like, there has been a problem (so-called emulsion shock) that an emulsion phase is destroyed due to the action of polyvalent metal ions such as calcium and magnesium, resulting in phase separation and coagulation. Therefore, development of a preparation containing no metal salts and stabilizing CL-MIT has been desired.

(Method for producing hydrohalide of 3-isothiazolone compound) A general method for synthesizing CL-MIT is as follows.
For example, U.S. Pat. No. 3,849,430, Japanese Patent Publication No. 6-57
No. 701. According to this manufacturing method,
CL-MIT is synthesized as a hydrohalide. The reaction product includes 2-methyl-4-
Includes the hydrohalide salt of isothiazolin-3-one (also referred to herein as "MIT"). MIT
Is a compound having microbicidal properties like CL-MIT, and has properties similar to CL-MIT. For this reason, even if the MIT is mixed with the CL-MIT,
Since there is no particular disadvantage, industrially, CL-MIT and MIT are generally used without separating MIT generated by a side reaction.
Provided and used as a mixture with Generally sold products include MIT at a rate of about 10% to 40% of the sum of CL-MIT and MIT.

(Neutralization Method from Hydrohalide) The 3-isothiazolone compound obtained by the above-mentioned method is neutralized to give hydrohalic acid in a form in which the hydrohalic acid is liberated. As a method for obtaining an isothiazolone compound, various methods are conventionally known.

[0007] Japanese Patent Publication No. 45-38330 discloses a method of neutralizing with a tertiary amine such as pyridine and triethylamine. In this method, it is difficult to stop the addition of the organic amine at the neutralization point (equivalent point) due to the neutralization reaction between hydrochloric acid, which is a strong acid, and amine, which is a weak base. Also, the solubility of the resulting amine hydrochloride is high,
To mix in a solution containing a 3-isothiazolone compound,
It is difficult to remove. When an organic amine is excessively added, the excess amine chemically reacts with the 3-isothiazolone compound to decompose the 3-isothiazolone compound.

Japanese Patent Publication No. 45-38330 also discloses that
It is described that a hydrohalic acid is eliminated in water from a hydrohalide of a 3-isothiazolone compound. However, there is no disclosure of a method for preparing in phenol.

[0009] Japanese Patent Publication No. 6-102654 describes a method using anhydrous ammonia. Even when using this method, it is difficult to adjust the end point of neutralization. Moreover, if an excess of anhydrous ammonia is used, the excess of anhydrous ammonia easily reacts with the 3-isothiazolone compound. For this reason, the yield of the target 3-isothiazolone compound decreases. Furthermore, good quality cannot be obtained because by-products that significantly color the 3-isothiazolone compound are easily formed. In addition, since ammonia is a combustible gas having a peculiar odor, if it remains, it not only causes a bad smell but also has a risk of explosion.

Japanese Unexamined Patent Publication (Kokai) No. 5-43563 describes liberation with a weak base anion exchange resin. However, according to the method using an ion-exchange resin, a special facility such as a column is required for performing an ion-exchange treatment on a solution containing a 3-isothiazolone compound, and there is an economic disadvantage that a large cost is required. .

Japanese Patent Application Laid-Open No. 6-65221 describes a method in which water is added to a hydrochloride, and a slurry of aqueous magnesium oxide or calcium oxide is added to neutralize the water. According to this method, since a neutralizing salt and a nitrate as a stabilizer remain in the composition, emulsion shock is liable to occur when the method is used for an emulsion-based material.

JP-A-3-95103 describes a method in which a hydrochloride is heated in an organic solvent to release hydrochloric acid and take out isothiazolone. According to this method, the amount of nitrosamine in the preparation when the isothiazolone compound is stabilized with a nitrate is reduced. The organic solvents used here are chloroform, methylene chloride, carbon tetrachloride or ethyl acetate and toluene used as chlorination reaction solvents. However, no example using phenol is described.

[0013]

SUMMARY OF THE INVENTION An object of the present invention is to solve the above-mentioned problems. Specifically, an object of the present invention is to substantially contain no metal salts, for example, 0.1 to
An object of the present invention is to provide a method for producing a stable liquid composition containing 40% of CL-MIT.

[0014]

Means for Solving the Problems As a result of earnest studies, the present inventors have conducted an operation of mixing a hydrochloride of a 3-isothiazolone compound and phenol and blowing in an inert gas while heating, or decompression while heating. It has been unexpectedly discovered that a liquid composition of a stable 3-isothiazolone compound substantially free of water can be efficiently prepared by a care operation.

Specifically, in a first aspect, the method of the present invention is a method for producing a liquid composition of a 3-isothiazolone compound, wherein a hydrohalide of the 3-isothiazolone compound is dissolved in phenol. Heating the process and the resulting solution to remove the hydrohalic acid,
A step of obtaining a liquid composition of the isothiazolone compound.

In a second aspect, the method of the present invention comprises the steps of:
A method for producing a liquid composition of an isothiazolone compound, comprising the steps of: dissolving a hydrohalide salt of a 3-isothiazolone compound in phenol; and blowing an inert gas while heating to remove hydrohalic acid. , 3
-Obtaining a liquid composition of the isothiazolone compound.

[0017] In one embodiment of the second aspect, the aforementioned 3
The isothiazolone compound is 5-chloro-2-methyl-4
A mixture of -isothiazolin-3-one and 2-methyl-4-isothiazolin-3-one.

[0018] In one embodiment of the second aspect, the temperature at which the inert gas is blown is 40 ° C to 100 ° C.

[0019] In one embodiment of the second aspect, the hydrohalic acid is hydrochloric acid.

In a third aspect, the method of the present invention comprises:
A method for producing an isothiazolone compound, comprising the steps of dissolving a hydrohalide salt of a 3-isothiazolone compound in phenol, and degassing under reduced pressure while heating to remove hydrohalic acid. Obtaining a liquid composition of the compound.

In one embodiment of the third aspect, the above-mentioned 3
The isothiazolone compound is 5-chloro-2-methyl-4
A mixture of -isothiazolin-3-one and 2-methyl-4-isothiazolin-3-one.

In one embodiment of the third aspect, the temperature at the time of degassing under reduced pressure is 40 ° C. to 100 ° C.

[0023] In one embodiment of the third aspect, the hydrohalic acid is hydrochloric acid.

[0024]

BEST MODE FOR CARRYING OUT THE INVENTION (Isothiazolone compound) In the method of the present invention, an arbitrary isothiazolone compound can be used as a 3-isothiazolone compound. Specifically, 4
-Isothiazolin-3-one and any derivatives thereof. As such a derivative, for example, the 2-position of 4-isothiazolin-3-one is substituted with a methyl group,
And / or a compound in which the 5-position is substituted with a halogen atom. Specifically, for example, 5-chloro-2
-Methyl-4-isothiazolin-3-one, 2-methyl-4-isothiazolin-3-one, 2-n-octyl-
4-isothiazolin-3-one, 2-ethyl-4-isothiazolin-3-one, 2-propyl-4-isothiazolin-3-one, 2-butyl-4-isothiazoline-3
-On and the like.

(Preparation of hydrohalide of 3-isothiazolone compound) The hydrohalide of 3-isothiazolone compound is prepared by a conventionally known method. For example, U.S. Pat. No. 3,849,430 and JP-B-6-57.
No. 701 can be manufactured.

In the method disclosed in US Pat. No. 3,849,430 and Japanese Patent Publication No. 6-57701, 2-methyl-4-isothiazolin-3-one produced by a side reaction (herein referred to as a reaction product) is used as a reaction product. "MIT")). Such mixtures can also be used in the method of the present invention. Specifically, for example, CL
-A product containing MIT at a ratio of about 10% to 40% based on the sum of MIT and MIT can be used in the method of the present invention.

(Dissolution in Phenol) In the method of the present invention, first, a hydrohalide of a 3-isothiazolone compound is dissolved in phenol. The operation of dissolution may be performed at room temperature or under heating. The amount of the phenol used is preferably 30 to 500 parts by weight, more preferably 40 to 300 parts by weight, and still more preferably 50 to 300 parts by weight, based on 100 parts by weight of the hydrohalide of the 3-isothiazolone compound. It is 250 parts by weight, particularly preferably 60 to 200 parts by weight.

(Heating) Next, the obtained phenol solution of a hydrohalide salt of a 3-isothiazolone compound is heated. The lower limit of the heating temperature is preferably 40 ° C. or higher, more preferably 45 ° C. or higher, and further preferably 50 ° C. or higher. Particularly preferably, it is 60 ° C. or higher. If the heating temperature is too low, it is difficult to sufficiently remove hydrohalic acid. The upper limit of the heating temperature is preferably 100 ° C. or lower, more preferably 90 ° C. or lower, and further preferably 80 ° C. or lower. If the heating temperature is too high, phenol is liable to evaporate.

According to the method of the present invention,
By heating in a phenol solution of a hydrohalide salt of an isothiazolone compound, hydrohalic acid is eliminated, and a 3-isothiazolone compound can be obtained. For example, if heating is performed for about 20 hours to 100 hours,
A 3-isothiazolone compound from which hydrohalic acid has been sufficiently eliminated can be obtained.

Therefore, the effects of the present invention can be sufficiently obtained without performing the blowing of the inert gas or the degassing under reduced pressure, which will be described later. However, if the inert gas is blown or degassed under reduced pressure as described later, the desorbed hydrohalic acid can be removed more quickly, and therefore, the reaction can be completed in a very short time. It is advantageous.

(Blowing of inert gas) In the second aspect, in the method of the present invention, the 3
-Inert gas is blown into the phenol solution of the hydrohalide salt of the isothiazolone compound. Here, the inert gas may be blown into the liquid, or may be blown into the air in a container containing the solution. It is preferable to blow into the liquid.

As the inert gas, any gas inert to the hydrohalide of the 3-isothiazolone compound can be used. Specifically, for example, nitrogen gas,
Argon gas, helium gas and the like can be used.

The rate at which the inert gas is blown is preferably such that the rate of the inert gas is from 1 milliliter to 50 liters per minute per liter of the solution, and more preferably from 10 milliliters per minute to 1 liter of the solution. 2
The rate is such that the amount of inert gas is 0 liter, more preferably the rate is 100 ml / min to 10 liters of inert gas per minute of the solution, and particularly preferably the rate is 100 ml / liter of solution. Min 200
This is the rate at which the volume of the inert gas is from milliliter to 5 liters.

The time for blowing the inert gas is preferably 10 minutes to 24 hours, more preferably 30 minutes.
Minutes to 12 hours, more preferably 1 hour to 1 hour.
0 hours. Particularly preferably, it is 3 hours to 8 hours.

At the time of blowing, the solution may be stirred, if necessary. As the stirring method, any conventionally known stirring method can be used.

(Vacuum Degassing) In another aspect, in the method of the present invention, a phenol solution of a hydrohalide salt of a 3-isothiazolone compound obtained by the above method is decompressed under reduced pressure at the above-mentioned heated temperature. Do care.

The lower limit of the reduced pressure by the reduced pressure degassing is preferably 1 mmHg or more, more preferably 5 mmHg.
g or more, more preferably 10 mmHg or more, and particularly preferably 30 mmHg or more. If the pressure is reduced too much, phenol tends to evaporate. The upper limit of the pressure by degassing under reduced pressure is preferably 300 mmHg or less, more preferably 200 mmHg or less, further preferably 150 mmHg or less, and particularly preferably 120 mmHg or less. When the pressure reduction is small, hydrohalic acid is not easily sufficiently eliminated.

The time for performing vacuum degassing while heating is preferably from 10 minutes to 24 hours, more preferably
The duration is 30 minutes to 12 hours, more preferably 1 hour to 10 hours. Particularly preferably, it is 3 hours to 8 hours.

At the time of degassing under reduced pressure, the solution may be stirred if necessary. As the stirring method, any conventionally known stirring method can be used. The stirring may be performed by blowing the inert gas into the liquid. Further, the stirring blade may be rotated, and the stirring rotor may be magnetically rotated.

(Combination of Inert Gas Blowing and Decompression Degassing) In this specification, for the sake of easy understanding, the blowing of the inert gas and the decompression degassing are separately described above. However, it is needless to say that the blowing of the inert gas and the degassing under reduced pressure may be performed in combination.

(Use of the obtained liquid composition) The liquid composition of the 3-isothiazolone compound thus obtained by the method of the present invention can be used for a conventionally known use of a 3-isothiazolone compound. .

[0042]

EXAMPLES Examples of the present invention and comparative examples are shown below.
However, the invention is not limited to these examples.

(Example 1) According to the method described in JP-B-6-57701, 5-chloro-2-methyl-4
-Isothiazolin-3-one (CL-MIT), 2-
A suspension of the hydrochloride salt of methyl-4-isothiazolin-3-one (MIT) in ethyl acetate was prepared. Filter this,
The hydrochloride salt of the 3-isothiazolone compound was isolated. 20 g of this hydrochloride (CL-MIT: 55.2%, MIT: 2
4.5% HCl, containing 20.3% HCl).
g.

The phenol solution was stirred at 50-60 ° C. for 20 hours while blowing nitrogen gas as an inert gas at a rate of approximately 200 ml / min.

96.0 g of a violet viscous phenol solution containing 11.5% of CL-MIT was obtained. CL
-MIT yield was 100%. The removal rate of hydrochloric acid was quantitative.

Example 2 In the same manner as in Example 1, 20 g of the hydrochloride of the 3-isothiazolone compound was dissolved in 80 g of phenol. The phenol solution was stirred at 50-60 ° C. for 6 hours while blowing nitrogen gas as an inert gas at a rate of approximately 200 ml / min.

95.2 g of a viscous, red-purple phenol solution containing 11.6% CL-MIT was obtained. CL
-MIT yield was 100%. The removal rate of hydrochloric acid was quantitative.

Example 3 The same operation as in Example 2 was performed except that the amount of phenol used was changed to 50 g.

A red-purple viscous phenol solution containing 16.4% of CL-MIT was obtained in an amount of 65.9 g. CL
-MIT yield was 98%. The removal rate of hydrochloric acid was 96%.

Example 4 The same operation as in Example 2 was performed except that the amount of phenol used was changed to 35 g.

50.9 g of a viscous, red-purple phenol solution containing 20.8% of CL-MIT was obtained. CL
-MIT yield was 96%. The removal rate of hydrochloric acid was 94%.

Example 5 The same operation as in Example 2 was performed except that the amount of phenol used was changed to 20 g.

36.0 g of a red-purple viscous phenol solution containing 28.8% of CL-MIT was obtained. CL
-MIT yield was 94%. The removal rate of hydrochloric acid was 93%.

Example 6 The same operation as in Example 2 was performed except that the amount of phenol used was changed to 15 g.

31.0 g of a violet viscous phenol solution containing 33.4% of CL-MIT was obtained. CL
-MIT yield was 94%. The removal rate of hydrochloric acid was 90%.

Example 7 In the same manner as in Example 1, 20 g of the hydrochloride of the 3-isothiazolone compound was dissolved in 80 g of phenol.

This phenol solution is heated to 50 to 100 mmH
The mixture was stirred at 50 to 60 ° C for 6 hours under reduced pressure of g.

94.6 g of a violet viscous phenol solution containing 11.4% of CL-MIT was obtained. CL
-MIT yield was 98%. The removal rate of hydrochloric acid was quantitative.

(Comparative Example 1) Without heating the phenol solution,
The same operation as in Example 1 was performed except that the operation of blowing nitrogen gas was performed at room temperature. As a result, hydrochloric acid could not be removed. That is, a free 3-isothiazolone compound could not be obtained.

(Comparative Example 2) The same operation as in Example 1 was performed except that phenol was changed to toluene. 20 ° C at 50-60 ° C while blowing nitrogen gas as an inert gas
After stirring for an hour, a dark brown, viscous toluene solution was obtained. When this toluene solution was analyzed by HPLC, CL-M
The IT was 0% and had been completely decomposed.

(Evaluation of Stability) The samples obtained in the above Examples were placed in a sealed glass container and left in a constant temperature bath at 40 ° C. CL-MIT content was measured by HPLC analysis. Table 1 shows the results.

[0062]

[Table 1]

[0063]

According to the production method of the present invention, a stable liquid composition containing 0.1 to 40% of CL-MIT substantially without containing metal salts is provided. This liquid composition is effective as a material for preparing a CL-MIT preparation.

According to the present invention, without using an inorganic or organic base for neutralization, a phenol is added with a hydrohalide of a 3-isothiazolone compound, mixed and heated, and an inert gas is blown into the phenol. By the operation or the operation of degassing under reduced pressure while heating, liberation and stabilization can be performed simultaneously, and a liquid composition of the 3-isothiazolone compound can be obtained in high yield. Thus, effects not expected from the prior art are achieved by the method of the present invention.

 ──────────────────────────────────────────────────続 き Continued on the front page (72) Inventor Keiji Noguchi 236 Nakai, Tatsuno-cho, Tatsuno-shi, Hyogo Nagase Kasei Kogyo Co., Ltd. F-term (reference) 4C033 AA06 AA08 AA09 AA18 4H011 AA02 BB10

Claims (9)

[Claims] 1. A method for producing a liquid composition of a 3-isothiazolone compound, comprising the steps of: dissolving a hydrohalide of the 3-isothiazolone compound in phenol; and heating the obtained solution to obtain a halogenated compound. A method comprising the step of removing hydrogen acid to obtain a liquid composition of a 3-isothiazolone compound. 2. A method for producing a liquid composition of a 3-isothiazolone compound, comprising the steps of: dissolving a hydrohalide salt of the 3-isothiazolone compound in phenol; A method comprising removing hydrohydric acid to obtain a liquid composition of a 3-isothiazolone compound. 3. The method according to claim 2, wherein the 3-isothiazolone compound is 5-chloro-2-methyl-4-isothiazolin-3-one and 2
3. The process according to claim 2, which is a mixture with -methyl-4-isothiazolin-3-one. 4. The temperature at which the inert gas is blown is:
3. The method according to claim 2, wherein the temperature is between 40C and 100C. 5. The hydrohalic acid is hydrochloric acid,
The method according to claim 2. 6. A method for producing a liquid composition of a 3-isothiazolone compound, comprising the steps of: dissolving a hydrohalide salt of the 3-isothiazolone compound in phenol; A method comprising the step of removing hydrogen acid to obtain a liquid composition of a 3-isothiazolone compound. 7. The method of claim 1, wherein the 3-isothiazolone compound is 5-chloro-2-methyl-4-isothiazolin-3-one and 2
7. The method according to claim 6, which is a mixture with -methyl-4-isothiazolin-3-one. 8. The temperature for degassing under reduced pressure is 40 ° C. or more.
7. The method of claim 6, wherein the temperature is 100 <0> C. 9. The hydrohalic acid is hydrochloric acid,
The method of claim 6.