A process for the preparation of 1,2-benzisothiazolin-3-one-1-oxide

Abstract

The application provides a preparation method of 1,2-benzisothiazolin-3-ketone-1-oxide and belongs to the technical field of compound synthesis. The application takes tetrabutylammonium bromide as a starting material, and through chlorination and oxidation reactions, 1,2-benzisothiazolin-3-ketone-1-oxide with high purity is obtained, which can be used for controlling the content of the impurity in the BIT production process and reducing the influence of the impurity on the BIT yield and quality. The whole preparation method has the advantages of mild conditions, good selectivity, simple purification, simplicity and controllability and strong operability.

Description

Technical Field

[0001] This invention relates to the field of compound synthesis technology, and in particular to a method for preparing 1,2-benzisothiazolin-3-one-1-oxide. Background Technology

[0002] 1,2-Benzisothiazolin-3-one (BIT) is an important new industrial bactericide. It exhibits outstanding inhibitory effects on the growth of fungi, molds, bacteria, and algae in organic media. It boasts advantages such as high efficiency, broad spectrum, low toxicity, and biodegradability, making it considered a safe and harmless green product. BIT has a wide range of applications, primarily in latex paints, oils, papermaking, inks, leather products, and water treatment.

[0003] BIT is typically produced using o-chlorobenzonitrile as a raw material. O-chlorobenzonitrile is condensed with sodium methanethiol in a solvent to obtain o-methylthiobenzonitrile. This o-methylthiobenzonitrile is then chlorinated with chlorine gas to achieve ring closure. Filtration yields crude 1,2-benzisothiazolin-3-one, which is usually purified using an acid-base method. However, this method often results in low yields and purity of some products. Comparison revealed that the reason for the decreased yield and quality is the high content of 1,2-benzisothiazolin-3-one-1-oxide in BIT. The chemical formula of 1,2-benzisothiazolin-3-one-1-oxide is shown in formula (2):

[0004]

[0005] Currently, 1,2-benzisothiazolin-3-one-1-oxide is inevitably generated during conventional BIT production. To improve product quality control, a simple and feasible method for preparing 1,2-benzisothiazolin-3-one-1-oxide is needed to prepare standards for qualitative and quantitative analysis of this impurity.

[0006] Patent JP2011162465 reports a method for synthesizing 1,2-benzisothiazolin-3-one-1-oxide, using o-sulfinylbenzamide as a raw material. A leaving group is introduced through reaction with trimethylchlorosilane, followed by cyclization to obtain the target product. However, the raw materials for this method are not readily available. The preparation process in this method is shown in formula (3):

[0007]

[0008] Janos et al. (Tetrahedron, 1988, 10, 2985-2992) reported a method for synthesizing 1,2-benzisothiazolin-3-one-1-oxide from dithiodibenzoamide in an aqueous phase using sodium periodate as an oxidant. This method uses relatively expensive sodium periodate as a raw material, and the yield is low and purification is difficult.

[0009] Patents CN115677613, CN115677614, and CN111718312 report a method for preparing saccharin using BIT as a raw material. The method uses hypochlorite, hydrogen peroxide, nitric acid, or chlorine as oxidants to oxidize BIT to obtain saccharin. 1,2-Benzisothiazolin-3-one-1-oxide is used as an intermediate in the oxidation process. However, this oxidation reaction has poor selectivity and is difficult to stop at the 1,2-benzisisothiazolin-3-one-1-oxide stage, making it unsuitable as a method for synthesizing its pure form.

[0010] Klyuev et al. reported a method for synthesizing 1,2-benzisothiazolin-3-one-1-oxide using o-formic acid benzenesulfinic acid as a starting material. The method involves reacting o-formic acid benzenesulfinic acid with thionyl chloride, followed by cyclization with ammonia. However, this method suffers from difficult-to-obtain starting materials, harsh reaction conditions, and numerous byproducts. The preparation process in this method is shown in equation (4):

[0011]

[0012] Based on the above problems, there is a need to provide an easy-to-operate, mild, selective and simple-to-purify synthetic method to prepare a standard of 1,2-benzisothiazolin-3-one-1-oxide for quantitative analysis of this impurity in the BIT production process. Summary of the Invention

[0013] In view of this, the present invention provides a method for preparing 1,2-benzisothiazolin-3-one-1-oxide, which solves the problems existing in the prior art and improves and stabilizes product quality.

[0014] The preparation method of 1,2-benzisothiazolin-3-one-1-oxide of the present invention is as follows:

[0015]

[0016] First, tetrabutylammonium bromide, solvent, and water are mixed and reacted in the presence of chlorine to obtain a reaction solution. Then, solid BIT (1,2-benzisothiazolin-3-one) is added to the reaction solution and reacted. After the reaction, the organic phase is removed, the aqueous phase is retained, and the product is filtered to obtain crude 1,2-benzisothiazolin-3-one-1-oxide. Finally, the crude product is purified to obtain pure 1,2-benzisothiazolin-3-one-1-oxide.

[0017] Preferably, the method for preparing the 1,2-benzisothiazolin-3-one-1-oxide includes the following steps:

[0018] 1) Mix tetrabutylammonium bromide, solvent and water, cool to 10-15°C, introduce chlorine gas to keep the reaction solution temperature at 10-20°C, after the chlorine gas is introduced, introduce nitrogen gas to blow away the residual chlorine gas to obtain tetrabutylammonium dichlorobromide; the reaction is an exothermic reaction. In the specific embodiment, the reaction solution temperature is kept at 10-20°C by adjusting the rate of chlorine gas introduction.

[0019] 2) Add solid BIT to the reaction solution obtained in step 1), then heat to 50-60℃ and stir to react. If the BIT content in the reaction solution is <0.5% by liquid phase detection, stop the reaction.

[0020] 3) Separate the reaction solution obtained in step 2) to remove the organic phase, retain the aqueous phase, cool the aqueous phase to 5-15℃ and stir for 30 minutes, filter to obtain crude 1,2-benzisothiazolin-3-one-1-oxide;

[0021] 4) The crude 1,2-benzisothiazolin-3-one-1-oxide obtained after step 3) is recrystallized with a mixed solvent of methanol and water to obtain pure 1,2-benzisothiazolin-3-one-1-oxide.

[0022] Preferably, the solvent in step 1) includes one or more of chloroform, dichloromethane, carbon tetrachloride, 1,2-dichloroethane, toluene, xylene, chlorobenzene, n-hexane, cyclohexane, n-heptane, and tetrachloroethylene.

[0023] Preferably, the mass ratio of tetrabutylammonium bromide, solvent and water in step 1) is 1-1.5:1.50-3.00:1.00; and the mass ratio of chlorine gas to tetrabutylammonium bromide is 0.2-0.4:1.

[0024] Preferably, the mass ratio of the BIT solid added in step 2) to tetrabutylammonium bromide is 0.4 to 0.5:1.

[0025] Preferably, in step 4), the mass ratio of methanol to water in the mixed solvent is 1-2:1-2.

[0026] Compared with existing technologies, the present invention has the following advantages: The present invention provides a method for preparing 1,2-benzisothiazolin-3-one-1-oxide, an impurity in BIT. Using tetrabutylammonium bromide as the starting material, a high-purity 1,2-benzisothiazolin-3-one-1-oxide is obtained through chlorination and oxidation reactions. This method can be used to control the content of this impurity during BIT production, reducing its impact on BIT yield and quality. The entire preparation method is mild, selective, simple to purify, and easy to control, with high operability. Attached Figure Description

[0027] Figure 1This is the mass spectrum of tetrabutylammonium dichlorobromide.

[0028] Figure 2 Tetrabutyldichloroammonium bromide 1 HNMR spectrum.

[0029] Figure 3 The liquid phase spectrum is for 1,2-benzisothiazolin-3-one-1-oxide.

[0030] Figure 4 This is the mass spectrum of 1,2-benzisothiazolin-3-one-1-oxide.

[0031] Figure 5 The 1H NMR spectrum of 1,2-benzisothiazolin-3-one-1-oxide is shown. Detailed Implementation

[0032] The present invention will be further described below with reference to the embodiments.

[0033] Example 1

[0034] A method for preparing 1,2-benzisothiazolin-3-one-1-oxide, comprising the following steps:

[0035] 1) Add 322g of tetrabutylammonium bromide, 500g of chlorobenzene, and 300g of water to a four-necked flask equipped with a mechanical stirrer, thermometer, and tail gas absorption device. Cool to 10-15℃, then introduce chlorine gas, controlling the rate of chlorine introduction to maintain the reaction solution temperature at 10-20℃. Continue introducing chlorine gas until the reaction solution turns light green, then stop introducing chlorine. The total amount of chlorine gas introduced is approximately 71g. Purge residual chlorine gas with nitrogen gas. Take a small amount of the intermediate layer and recrystallize it from methanol to obtain a yellow-green solid (tetrabutyldichloroammonium bromide), melting point: 61.9-63.7℃. Perform mass spectrometry and nuclear magnetic resonance (NMR) tests. The mass spectrum of tetrabutyldichloroammonium bromide is shown below. Figure 1 , 1 HNMR spectrum as follows Figure 2 ;

[0036] 2) Add 151g of solid BIT to the above reaction solution, heat to 50-60℃ and stir for 2 hours. If the BIT content in the reaction solution is <0.5% by liquid phase detection, stop the reaction.

[0037] 3) Separate the water layer at 50-60℃, cool the water layer to 5-15℃ and stir for 30 minutes, filter and wash with a small amount of deionized water to obtain crude 1,2-benzisothiazolin-3-one-1-oxide;

[0038] 4) The crude product was recrystallized with a 1:1 mixture of 500g methanol and water, and dried to obtain 145g of pure 1,2-benzisothiazolin-3-one-1-oxide, with a yield of 87% and a liquid phase purity of >99%.

[0039] The liquid phase spectrum of the obtained 1,2-benzisothiazolin-3-one-1-oxide is shown below. Figure 3 Mass spectrum as shown Figure 4 ; 1H NMR spectrum as shown Figure 5 .

[0040] Example 2

[0041] A method for preparing 1,2-benzisothiazolin-3-one-1-oxide, comprising the following steps:

[0042] 1) Add 322g of tetrabutylammonium bromide, 900g of tetrachloroethylene and 300g of water to a four-necked flask equipped with a mechanical stirrer, thermometer and tail gas absorption device. Cool down to 10-15℃, introduce chlorine gas, control the rate of chlorine introduction to keep the temperature of the reaction solution at 10-20℃, and stop introducing chlorine when the reaction solution turns light green. The total amount of chlorine introduced is about 71g. Introduce nitrogen gas to blow away the residual chlorine gas.

[0043] 2) Add 151g of solid BIT to the above reaction solution, heat to 50-60℃ and stir for 2 hours. If the BIT content in the reaction solution is <0.5% by liquid phase detection, stop the reaction.

[0044] 3) Separate the water layer at 50-60℃, cool the water layer to 5-15℃ and stir for 30 minutes, filter and wash with a small amount of deionized water to obtain crude 1,2-benzisothiazolin-3-one-1-oxide;

[0045] 4) The crude product was recrystallized with a 1:1 mixture of 500g methanol and water, and dried to obtain 151g of pure 1,2-benzisothiazolin-3-one-1-oxide, with a yield of 91%, a liquid phase purity of >99%, and a melting point of 156.5~158.1℃.

[0046] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A method for preparing 1,2-benzisothiazolin-3-one-1-oxide, characterized in that, The specific preparation process is as shown in formula (1): （1） First, tetrabutylammonium bromide, solvent, and water are mixed and reacted in the presence of chlorine to obtain a reaction solution. Then, solid BIT is added to the reaction solution to react. After the reaction, the organic phase is removed, the aqueous phase is retained, and the solution is filtered to obtain crude 1,2-benzisothiazolin-3-one-1-oxide. Finally, the crude product is purified to obtain pure 1,2-benzisothiazolin-3-one-1-oxide. The method for preparing the 1,2-benzisothiazolin-3-one-1-oxide includes the following steps: 1) Mix tetrabutylammonium bromide, solvent and water, cool to 10~15℃, introduce chlorine gas to keep the temperature of the reaction solution at 10~20℃, after the chlorine gas is introduced, introduce nitrogen gas to blow away the residual chlorine gas to obtain tetrabutylammonium dichlorobromide; 2) Add solid BIT to the reaction solution obtained in step 1), then heat to 50~60℃ and stir to react. If the BIT content in the reaction solution is <0.5% by liquid phase detection, stop the reaction. 3) Separate the reaction solution obtained in step 2) to remove the organic phase, retain the aqueous phase, cool the aqueous phase to 5~15℃ and stir for 30 minutes, filter to obtain crude 1,2-benzisothiazolin-3-one-1-oxide; 4) The crude 1,2-benzisothiazolin-3-one-1-oxide obtained after step 3) is recrystallized with a mixed solvent of methanol and water to obtain pure 1,2-benzisothiazolin-3-one-1-oxide.

2. The method for preparing 1,2-benzisothiazolin-3-one-1-oxide according to claim 1, characterized in that, The solvent mentioned in step 1) is one or more of the following: chloroform, dichloromethane, carbon tetrachloride, 1,2-dichloroethane, toluene, xylene, chlorobenzene, n-hexane, cyclohexane, n-heptane, and tetrachloroethylene.

3. The method for preparing 1,2-benzisothiazolin-3-one-1-oxide according to claim 1, characterized in that, In step 1), the mass ratio of tetrabutylammonium bromide, solvent, and water is 1~1.5:1.50~3.00:1.00; the mass ratio of chlorine gas to tetrabutylammonium bromide is 0.2~0.4:

1.

4. The method for preparing 1,2-benzisothiazolin-3-one-1-oxide according to claim 1, characterized in that, In step 2), the mass ratio of the added BIT solid to tetrabutylammonium bromide is 0.4~0.5:

1.

5. The method for preparing 1,2-benzisothiazolin-3-one-1-oxide according to claim 1, characterized in that, In step 4), the mass ratio of methanol to water in the mixed solvent is 1~2:1~2.

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