A method for rapidly preparing N-methylbenzisothiazolinone-1-oxide

Abstract

The present invention relates to the technical field of organic synthesis, and in particular to a method for rapidly preparing N-methylbenzisothiazolinone-1-oxide. At present, using p-benzisothiazolinone as a reaction raw material, benzisothiazolinone-1-oxide is synthesized by a non-direct oxidation method, and product yield is difficult to reach more than 80%. In view of the above problems, the present invention provides a method for rapidly preparing N-methylbenzisothiazolinone-1-oxide: at room temperature, 2-mercapto-N-methylbenzamide and N-chlorosuccinimide (NCS) are vigorously stirred in an organic solvent. After the reaction is completed, N-methylbenzisothiazolinone-1-oxide is obtained by concentration, extraction, and vacuum distillation. The inventive method has mild reaction conditions, short reaction time, high yield, and good application prospect.

Description

Technical Field

[0001] The present invention relates to the technical field of organic synthesis, and in particular to a method for rapidly preparing N-methylbenzisothiazolinone-1-oxide. Background Art

[0002] N-substituted benzisothiazolinones, as important sulfur- and nitrogen-containing six-membered heterocyclic compounds, are widely used in the pharmaceutical, agricultural, and food industries. Benzisothiazolinone-1-oxide, an important oxidized derivative, also exhibits promising antifungal, anxiolytic, and antipsychotic activities.

[0003] At present, the method for synthesizing benzisothiazolinone-1-oxide is mainly through direct oxidation reaction of benzisothiazolinone, while the method for preparing benzisothiazolinone-1-oxide by indirect oxidation method is rarely reported and the yield is not high. For example, 2-aminocarbamoylphenyl disulfide is used as raw material and NaIO4 is used as additive to prepare benzisothiazolinone-1-oxide, and the product yield is only 72% (Magyar Kemiai Folyoirat, 1989, 95, 455); for example, benzothiazinone is used as raw material and NaIO4 is used as additive to prepare benzisothiazolinone-1-oxide, and the product yield is only 71% (Tetrahedron, 1988, 44, 2985); and (3) 2-aminocarbamoylphenylsulfinic acid and trimethylchlorosilane are used as raw materials to synthesize benzisothiazolinone-1-oxide, and the product yield is also only 79% (Japanese patent JP2011162465). Summary of the Invention

[0004] A problem with the prior art is that, currently, when synthesizing benzisothiazolinone-1-oxide using p-benzisothiazolinone as a reaction raw material via direct oxidation, it is difficult to achieve a product yield exceeding 80%. To address this problem, the present invention provides a method for rapidly preparing N-methylbenzisothiazolinone-1-oxide, the preparation method comprising the following steps:

[0005] At room temperature, 2-mercapto-N-methylbenzamide and N-chlorosuccinimide (NCS) are vigorously stirred in an organic solvent. After the reaction, the reaction solution is concentrated, extracted, and distilled under reduced pressure to obtain N-methylbenzisothiazolinone-1-oxide. The structural formula of the N-methylbenzisothiazolinone-1-oxide is as follows:

[0006]

[0007] Preferably, the organic solvent comprises one or a combination of two or more of MeCN, ethyl acetate, DCM, toluene, and THF.

[0008] Preferably, the organic solvent is MeCN.

[0009] Preferably, the usage ratio of 2-mercapto-N-methylbenzamide to NCS and MeCN is 1 mmol:2-4 mmol:5-15 mL.

[0010] Preferably, the usage ratio of 2-mercapto-N-methylbenzamide to NCS and MeCN is 1 mmol:3-4 mmol:10-15 mL.

[0011] Preferably, the usage ratio of 2-mercapto-N-methylbenzamide to NCS and MeCN is 1 mmol:3 mmol:10 mL.

[0012] Preferably, the reaction time is at least 5 minutes.

[0013] Preferably, the reaction time is at least 10 min.

[0014] Preferably, the reaction time is 10 min.

[0015] The present invention has the following beneficial effects:

[0016] (1) The present invention uses 2-mercapto-N-methylbenzamide and NCS as reaction raw materials, and obtains the target product through rapid and intense reaction at room temperature. The reaction time is only 5 minutes, and the yield of the product can reach more than 90%, achieving good technical effects.

[0017] (2) The method of the present invention has mild reaction conditions, short reaction time, high yield, and good application prospects. DETAILED DESCRIPTION

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

[0019] Example 1

[0020] MeCN (10 mL), 2-mercapto-N-methylbenzamide (1.0 mmol), and chlorosuccinimide (NCS) (3.0 mmol) were added sequentially to a 50 mL round-bottom flask at room temperature and stirred vigorously for 10 minutes. After completion of the reaction, the reaction solution was heated and concentrated, and the organic phase was extracted (10 mL of ethyl acetate was added to the reaction solution, stirred and mixed thoroughly, then 30 mL of water was added to the reaction system, stirred and mixed thoroughly, and allowed to stand to separate). The ethyl acetate in the organic phase was removed by distillation under reduced pressure to obtain N-methylbenzisothiazolinone-1-oxide in a yield of 99%. The reaction equation is as follows:

[0021]

[0022] The NMR data of the obtained N-methylbenzisothiazolinone-1-oxide are as follows:

[0023] 1 H NMR (300MHz, CDCl3) δ7.94-7.91(m,1H),7.87-7.84(m,1H),7.77-7.69(m,2H),3.31(s,3H).

[0024] 13 C NMR (75MHz, CDCl3) δ165.5,145.5,134.2,133.3,128.1,126.1,125.1,27.0.

[0025] Example 2 is the same as Example 1, except that the amount of NCS used in Example 2 is 0. The yield of N-methylbenzisothiazolinone-1-oxide is 0.

[0026] Example 3 is the same as Example 1, except that the amount of NCS used in Example 3 is 1 mmol. The yield of N-methylbenzisothiazolinone-1-oxide is 0.

[0027] Example 4 is the same as Example 1, except that the amount of NCS used in Example 4 is 2 mmol. The yield of N-methylbenzisothiazolinone-1-oxide is 75%.

[0028] Example 5 is the same as Example 1, except that the amount of NCS used in Example 5 is 4 mmol. The yield of N-methylbenzisothiazolinone-1-oxide is 99%.

[0029] Example 6 is the same as Example 1, except that the reaction time in Example 6 is 5 minutes. The yield of N-methylbenzisothiazolinone-1-oxide is 90%.

[0030] Example 7 is the same as Example 1, except that the reaction time in Example 7 is 30 minutes. The yield of N-methylbenzisothiazolinone-1-oxide is 99%.

[0031] Example 8 is the same as Example 1, except that the reaction time in Example 8 is 60 min. The yield of N-methylbenzisothiazolinone-1-oxide is 99%.

[0032] Example 9 is the same as Example 1, except that the same volume of ethyl acetate is used instead of MeCN as the reaction solvent in Example 9. The yield of N-methylbenzisothiazolinone-1-oxide is 95%.

[0033] Example 10 is the same as Example 1, except that the same volume of DCM is used as the reaction solvent instead of MeCN. The yield of N-methylbenzisothiazolinone-1-oxide is 95%.

[0034] Example 11 is the same as Example 1, except that the same volume of toluene is used as the reaction solvent instead of MeCN. The yield of N-methylbenzisothiazolinone-1-oxide is 92%.

[0035] Example 12 is the same as Example 1, except that the same volume of THF is used as the reaction solvent instead of MeCN. The yield of N-methylbenzisothiazolinone-1-oxide is 90%.

[0036] Example 13 is the same as Example 1, except that the same volume of DMF is used instead of MeCN as the reaction solvent in Example 13. The yield of N-methylbenzisothiazolinone-1-oxide is 0%.

[0037] Example 14 is the same as Example 1, except that the amount of MeCN used in Example 14 is 5 mL. The yield of N-methylbenzisothiazolinone-1-oxide is 93%.

[0038] Example 15 is the same as Example 1, except that the amount of MeCN used in Example 15 is 15 mL. The yield of N-methylbenzisothiazolinone-1-oxide is 97%.

[0039] With the above-described preferred embodiments of the present invention as a guide, and with reference to the above description, relevant personnel are fully capable of making various changes and modifications without departing from the technical scope of this invention. The technical scope of this invention is not limited to the contents of the specification and must be determined according to the scope of the claims.

Claims

1. A method for rapidly preparing N-methylbenzisothiazolinone-1-oxide, characterized in that: The preparation method comprises the following steps: At room temperature, 2-mercapto-N-methylbenzamide and NCS are vigorously stirred in an organic solvent to react. After the reaction, the reaction solution is concentrated, extracted, and distilled under reduced pressure to obtain N-methylbenzisothiazolinone-1-oxide. The structural formula of the N-methylbenzisothiazolinone-1-oxide is as follows: ； The organic solvent is MeCN; The usage ratio of 2-mercapto-N-methylbenzamide to NCS and MeCN is 1 mmol: 2-4 mmol: 5-15 mL.

2. The method for rapidly preparing N-methylbenzisothiazolinone-1-oxide according to claim 1, wherein: The usage ratio of 2-mercapto-N-methylbenzamide to NCS and MeCN is 1 mmol: 3-4 mmol: 10-15 mL.

3. The method for rapidly preparing N-methylbenzisothiazolinone-1-oxide according to claim 2, characterized in that: The usage ratio of 2-mercapto-N-methylbenzamide to NCS and MeCN is 1 mmol:3 mmol:10 mL.

4. The method for rapidly preparing N-methylbenzisothiazolinone-1-oxide according to claim 1, wherein: The reaction time is at least 5 minutes.

5. The method for rapidly preparing N-methylbenzisothiazolinone-1-oxide according to claim 1, characterized in that: The reaction time is at least 10 minutes.

6. The method for rapidly preparing N-methylbenzisothiazolinone-1-oxide according to claim 1, characterized in that: The reaction time is 10 minutes.

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