Method for preparing 2-methylbenzisothiazolin-3-one at room temperature by using NCS (N-Chlorosuccinimide)

Abstract

The invention relates to the technical field of organic synthesis, in particular to a method for preparing 2-methylbenzisothiazolin-3-one at room temperature through participation of NCS. In the prior art, 2-methylbenzisothiazolin-3-one is obtained through an organic synthesis method, the reaction conditions are relatively harsh, the steps are relatively complicated, and the production efficiency is relatively low. In order to solve the technical problem, the invention provides the method for preparing the 2-methylbenzisothiazolin-3-one by using N-chlorosuccinimide (NCS) at room temperature, which comprises the following steps: reacting the NCS serving as a key additive with 2-sulfydryl-N-methyl benzamide in a solvent under the condition of violently stirring at room temperature, thereby obtaining the 2-methylbenzisothiazolin-3-one. The 2-methylbenzisothiazolin-3-one is successfully prepared by using the 2-methylbenzisothiazolin-3-one as a raw material, and the synthetic method disclosed by the invention is more efficient, milder in reaction condition and better in application prospect.

Description

Technical Field

[0001] The invention relates to the technical field of organic synthesis, and in particular to a method for preparing 2-methylbenzisothiazolin-3-one with the participation of NCS at room temperature. Background Art

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

[0003] At present, there are many methods for the synthesis of 2-methylbenzisothiazolin-3-one. Among them, N-substituted-2-mercaptobenzamide is used as a raw material to construct N-substituted benzisothiazolin-3-one in one step, which 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 for details), or the use of unstable high-valent iodine reagents at low temperatures (see reference Org.Lett.2006,8,4811 for details).

[0004] KBr as a catalyst and combined with oxygen can also be used to catalyze the synthesis of N-substituted-2-mercaptobenzamides into N-substituted benzisothiazoline-3-ones, but high temperature reactions are required (see reference Tetrahedron Lett. 2017, 58, 2084). In addition, N-substituted-2-mercaptobenzamides can also be synthesized into N-substituted benzisothiazoline-3-ones using an additional electrochemical device and n-butylammonium iodide bromide (see reference Tetrahedron Lett. 2021, 80, 153323). Summary of the invention

[0005] The problem in the prior art is that 2-methylbenzisothiazolin-3-one is obtained by organic synthesis in the prior art, and the reaction conditions are relatively harsh, the steps are relatively complicated, and the production efficiency is low. In view of the above technical problems, the present invention provides a method for preparing 2-methylbenzisothiazolin-3-one at room temperature with the participation of N-chlorosuccinimide (NCS), and the preparation method comprises the following steps:

[0006] Under vigorous stirring at room temperature, 2-mercapto-N-methylbenzamide reacts with NCS in a solvent. After the reaction is completed, the obtained reaction solution is purified to obtain N-methyl-2,3-dihydrobenzothiazin-4-one.

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

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

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

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

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

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

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

[0014] Preferably, the solvent is acetonitrile.

[0015] Preferably, the purification method comprises sequentially performing reduced pressure concentration, extraction or column chromatography separation.

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

[0017] The invention uses NCS as a key additive to react with 2-mercapto-N-methylbenzamide in a solvent under the condition of vigorous stirring at room temperature to successfully prepare 2-methylbenzisothiazolin-3-one. The synthesis method of the invention is more efficient, the reaction conditions are milder, and the invention has good application prospects. DETAILED DESCRIPTION

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

[0019] Example 1

[0020] In a 10mL round-bottom flask, 2-mercapto-N-methylbenzamide (0.2mmol, 33.45mg), NCS (0.2mmol) and acetonitrile (2.0mL) were added in sequence. The mixture was stirred vigorously at room temperature (25°C) for 12h. After the reaction was completed, the reaction solution was concentrated under reduced pressure and separated by extraction to obtain the target product 2-methylbenzisothiazolin-3-one in 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 2-methylbenzisothiazolin-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 2-methylbenzisothiazolin-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-methylbenzisothiazolin-3-one is 99%.

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

[0027] Example 6 is the same as Example 1, except that in Example 6, an equal amount of dichloromethane is used to replace the acetonitrile 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, an equal amount of toluene is used to replace the acetonitrile in Example 1. The yield of the obtained 2-methylbenzisothiazolin-3-one is 65%.

[0029] Example 8 is the same as Example 1, except that in Example 8, an equal amount of N,N-dimethylformamide is used to replace the acetonitrile in Example 1. The yield of the obtained 2-methylbenzisothiazolin-3-one is 65%.

[0030] Example 9 is the same as Example 1, except that in Example 9, an equal amount of dimethyl sulfoxide is used to replace the acetonitrile in Example 1. The yield of the obtained 2-methylbenzisothiazolin-3-one is 62%.

[0031] Example 10 is the same as Example 1, except that in Example 10, an equal amount of methanol is used to replace the acetonitrile in Example 1. The yield of the obtained 2-methylbenzisothiazolin-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 2-methylbenzisothiazolin-3-one obtained 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 2-methylbenzisothiazolin-3-one obtained 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 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 is 20%.

[0036] Based on the above ideal embodiments of the present invention, the relevant staff can make various changes and modifications without departing from the technical concept of the present invention through the above description. The technical scope of the present invention is not limited to the contents of the specification, and its technical scope 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 comprises the following steps: Under vigorous stirring at room temperature, 2-mercapto-N-methylbenzamide reacts with NCS in a solvent. After the reaction is completed, the obtained reaction solution is purified to obtain N-methyl-2,3-dihydrobenzothiazin-4-one.

2. The method for preparing 2-methylbenzisothiazolin-3-one at room temperature using NCS according to claim 1, characterized in that: The reaction time is 1-24h.

3. The method for preparing 2-methylbenzisothiazolin-3-one at room temperature using NCS according to claim 2, characterized in that: The reaction time is 6-24h.

4. The method for preparing 2-methylbenzisothiazolin-3-one at room temperature using NCS according to claim 3, characterized in that: The reaction time is 12h.

5. The method for preparing 2-methylbenzisothiazolin-3-one at room temperature using NCS according to claim 1, characterized in that: The molar ratio of 2-mercapto-N-methylbenzamide to NCS during the reaction was 1:

1.

6. The method for preparing 2-methylbenzisothiazolin-3-one at room temperature using NCS according to claim 5, characterized in that: The usage ratio of 2-mercapto-N-methylbenzamide to the solvent is 0.2 mol:1-3 mL.

7. The method for preparing 2-methylbenzisothiazolin-3-one at room temperature using NCS according to claim 6, characterized in that: The usage ratio of 2-mercapto-N-methylbenzamide to the solvent is 0.2 mol:2 mL.

8. The method for preparing 2-methylbenzisothiazolin-3-one at room temperature using NCS according to claim 1, characterized in that: The solvent is at least one of acetonitrile, ethyl acetate, toluene, N,N-dimethylformamide, dimethyl sulfoxide and methanol.

9. The method for preparing 2-methylbenzisothiazolin-3-one at room temperature using NCS according to claim 8, characterized in that: The solvent is acetonitrile.

10. The method for preparing 2-methylbenzisothiazolin-3-one at room temperature using NCS according to claim 1, characterized in that: The purification method includes sequentially performing reduced pressure concentration, extraction or column chromatography separation.