A method for the room temperature preparation of 2-methylbenzisothiazolin-3-one with the participation of ncs

Abstract

The present application relates to the technical field of organic synthesis, and particularly relates to a method for preparing 2-methylbenzoisothiazolin-3-ketone at room temperature by NCS participation. In the prior art, 2-methylbenzoisothiazolin-3-ketone is obtained by an organic synthesis method, the reaction condition is relatively harsh, the steps are relatively complicated, and the production efficiency is low. In view of the above technical problems, the present application provides a method for preparing 2-methylbenzoisothiazolin-3-ketone at room temperature by N-chlorosuccinimide (NCS) participation. NCS is used as a key additive, and 2-methylbenzoisothiazolin-3-ketone is successfully prepared by reacting 2-methylbenzoisothiazolin-3-ketone with 2-methylbenzoisothiazolin-3-ketone in a solvent at room temperature under the condition of severe stirring. The synthesis method of the present application is more efficient, the reaction condition is more mild, and has a good application prospect.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis technology, specifically to a method for preparing 2-methylbenzisothiazolin-3-one at room temperature using NCS. Background Technology

[0002] 2-Methylbenzisothiazolin-3-one is an important industrial bactericide, preservative and enzyme inhibitor that can effectively inhibit the growth of microorganisms such as fungi, bacteria and algae.

[0003] Currently, there are many methods for synthesizing 2-methylbenzisothiazolin-3-one. Among them, the one-step construction of N-substituted benzisothiazolin-3-one from N-substituted 2-mercaptobenzamide requires the use of transition metal Cu or Co catalysts and oxygen (see references J.Org.Chem.2013, 78, 733 and Eur.J.Org.Chem.2019, 1281, 1281), or the use of unstable high-valent iodine reagents at low temperatures (see reference Org.Lett.2006, 8, 4811).

[0004] The synthesis of N-substituted benzisothiazolin-3-one from N-substituted 2-mercaptobenzamide can also be catalyzed using KBr and oxygen, but this requires high-temperature reactions (see Tetrahedron Lett. 2017, 58, 2084). Alternatively, the synthesis of N-substituted benzisothiazolin-3-one from N-substituted 2-mercaptobenzamide can also be achieved using an additional electrochemical device and n-butylammonium iodide (see Tetrahedron Lett. 2021, 80, 153323). Summary of the Invention

[0005] The existing technology has the following problems: the organic synthesis of 2-methylbenzisisothiazolin-3-one in the existing technology involves relatively harsh reaction conditions, complicated steps, and low production efficiency. To address the above technical problems, this invention provides a method for preparing 2-methylbenzisisothiazolin-3-one at room temperature using N-chlorosuccinimide (NCS), the preparation method comprising the following steps:

[0006] 2-Mercapto-N-methylbenzamide reacted with NCS in a solvent under vigorous stirring at room temperature. After the reaction was completed, the resulting reaction solution was purified to obtain N-methyl-2,3-dihydrobenzothiazin-4-one.

[0007] Preferably, the reaction time is 1-24 hours.

[0008] Preferably, the reaction time is 6-24 hours.

[0009] Preferably, the reaction time is 12 hours.

[0010] Preferably, the molar ratio of 2-mercapto-N-methylbenzamide to NCS is 1:1 during the reaction.

[0011] Preferably, the ratio of 2-mercapto-N-methylbenzamide to solvent is 0.2 mol: 1-3 mL.

[0012] Preferably, the ratio of 2-mercapto-N-methylbenzamide to solvent is 0.2 mol: 2 mL.

[0013] Preferably, the solvent is at least one selected from acetonitrile, ethyl acetate, toluene, N,N-dimethylformamide, dimethyl sulfoxide, and methanol.

[0014] Preferably, the solvent is acetonitrile.

[0015] Preferably, the purification method includes sequentially performing vacuum concentration, extraction, or column chromatography separation.

[0016] The present invention has the following beneficial effects:

[0017] This invention utilizes NCS as a key additive to react with 2-mercapto-N-methylbenzamide in a solvent under vigorous stirring at room temperature to successfully prepare 2-methylbenzisisothiazolin-3-one. The synthesis method of this invention is more efficient and the reaction conditions are milder, showing good application prospects. Detailed implementation method:

[0018] The present invention will be described in detail below with reference to embodiments. However, it should be understood that the following embodiments are merely illustrative examples of implementation of the present invention and are not intended to limit the scope of the present invention.

[0019] Example 1

[0020] 2-Mercapto-N-methylbenzamide (0.2 mmol, 33.45 mg), NCS (0.2 mmol), and acetonitrile (2.0 mL) were added sequentially to a 10 mL round-bottom flask. The mixture was stirred vigorously at room temperature (25 °C) for 12 h. After the reaction was completed, the reaction solution was concentrated under reduced pressure and extracted to obtain the target product 2-methylbenzisisothiazolin-3-one, with a yield of 99%.

[0021] The NMR data of the target product are as follows:

[0022] 1H NMR (300MHz, Chloroform-d): δ7.97-7.94(m,1H),7.55-7.45(m,2H),7.34-7.29(m,1H),3.36(s,3H).

[0023] Example 2 is the same as Example 1, except that the reaction time in Example 2 is 6 hours. The yield of the obtained 2-methylbenzisisothiazolin-3-one is 95%.

[0024] Example 3 is the same as Example 1, except that the reaction time in Example 3 is 12 hours. The yield of the obtained 2-methylbenzisisothiazolin-3-one is 99%.

[0025] Example 4 is the same as Example 1, except that the reaction time in Example 4 is 24 hours. The yield of 2-methylbenzisisothiazolin-3-one is 99%.

[0026] Example 5 is the same as Example 1, except that in Example 5, acetonitrile is replaced with the same amount of ethyl acetate as in Example 1. The yield of the obtained 2-methylbenzisisothiazolin-3-one is 50%.

[0027] Example 6 is the same as Example 1, except that in Example 6, dichloromethane is added in the same amount instead of acetonitrile as in Example 1. The yield of the obtained 2-methylbenzisothiazolin-3-one is 0%.

[0028] Example 7 is the same as Example 1, except that in Example 7, toluene is added in the same amount instead of acetonitrile as in Example 1. The yield of the obtained 2-methylbenzisisothiazolin-3-one is 65%.

[0029] Example 8 is the same as Example 1, except that in Example 8, N,N-dimethylformamide is added in the same amount instead of acetonitrile in Example 1. The yield of the obtained 2-methylbenzisisothiazolin-3-one is 65%.

[0030] Example 9 is the same as Example 1, except that in Example 9, the same amount of dimethyl sulfoxide was added instead of acetonitrile in Example 1. The yield of the obtained 2-methylbenzisothiazolin-3-one was 62%.

[0031] Example 10 is the same as Example 1, except that in Example 10, methanol is added in the same amount instead of acetonitrile as in Example 1. The yield of the obtained 2-methylbenzisisothiazolin-3-one is 40%.

[0032] Example 11 is the same as Example 1, except that the amount of acetonitrile used in Example 11 is 1 mL. The yield of the obtained 2-methylbenzisisothiazolin-3-one is 90%.

[0033] Example 12 is the same as Example 1, except that the amount of acetonitrile used in Example 12 is 3 mL. The yield of the obtained 2-methylbenzisisothiazolin-3-one is 95%.

[0034] Example 13 is the same as Example 1, except that the amount of NCS used in Example 13 is 0.1 mmol. The yield of the obtained 2-methylbenzisothiazolin-3-one is 0%.

[0035] Example 14 is the same as Example 1, except that the amount of NCS used in Example 14 is 0.3 mmol. The yield of 2-methylbenzisothiazolin-3-one obtained is 20%.

[0036] Based on the above-described preferred embodiments of the present invention, and through the foregoing description, those skilled in the art can make various changes and modifications without departing from the inventive concept. The technical scope of this invention is not limited to the contents of the specification, but must be determined according to the scope of the claims.

Claims

1. A method for preparing 2-methylbenzisothiazolin-3-one at room temperature using NCS, characterized in that, The preparation method includes the following steps: 2-Mercapto-N-methylbenzamide reacted with NCS in a solvent under vigorous stirring at room temperature. After the reaction was completed, the resulting reaction solution was purified to obtain N-methyl-2,3-dihydrobenzothiazin-4-one. During the reaction, the molar ratio of 2-mercapto-N-methylbenzamide to NCS was 1:1; The solvent is acetonitrile; The reaction time is 12-24 hours; The ratio of 2-mercapto-N-methylbenzamide to solvent is 0.2 mol: 1-3 mL.

2. The method for preparing 2-methylbenzisothiazolin-3-one at room temperature using NCS according to claim 1, characterized in that, The ratio of 2-mercapto-N-methylbenzamide to solvent is 0.2 mol: 2 mL.

3. The method for preparing 2-methylbenzisothiazolin-3-one at room temperature using NCS according to claim 1, characterized in that, Purification methods include sequentially performing vacuum concentration, extraction, or column chromatography separation.