Method for rapidly preparing N-methylbenzisothiazolinone-1-oxide

Abstract

The invention relates to the technical field of organic synthesis, in particular to a method for rapidly preparing N-methylbenzisothiazolinone-1-oxide. At present, p-benzisothiazolinone is used as a reaction raw material, benzisothiazolinone-1-oxide is synthesized through an indirect oxidation method, and the product yield is very difficult to reach 80% or above. In order to solve the problems, the invention provides a method for rapidly preparing N-methylbenzisothiazolinone-1-oxide, which comprises the following steps of: at room temperature, vigorously stirring 2-sulfydryl-N-methyl benzamide and N-chlorosuccinimide (NCS) to react in an organic solvent, and after the reaction is finished, separating and purifying to obtain the N-methylbenzisothiazolinone-1-oxide. And sequentially carrying out concentration, extraction and reduced pressure distillation to obtain the N-methylbenzisothiazolinone-1-oxide. The method disclosed by the invention is mild in reaction condition, short in reaction time and high in yield, and has a relatively good application prospect.

Description

Technical Field

[0001] The 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 benzisothiazolinone, as an important sulfur-nitrogen-containing six-membered heterocyclic compound, is widely used in medicine, agriculture and food industry. Benzisothiazolinone-1-oxide, as an important oxidized derivative, also has good 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, benzisothiazolinone-1-oxide is prepared by using 2-carbamoylphenyl disulfide as raw material and NaIO4 as additive, and the product yield is only 72% (Magyar Kemiai Folyoirat, 1989, 95, 455); for another example, benzisothiazolinone-1-oxide is prepared by using benzothiazinone as raw material and NaIO4 as additive, and the product yield is only 71% (Tetrahedron, 1988, 44, 2985); and (3) benzisothiazolinone-1-oxide is synthesized by using 2-carbamoylbenzenesulfinic acid and trimethyl monochlorosilane as raw materials, and the product yield is also only 79% (Japanese patent JP2011162465). Summary of the invention

[0004] The problem in the prior art is that, currently, when benzisothiazolinone is used as a reaction raw material to synthesize benzisothiazolinone-1-oxide by direct oxidation, the product yield is difficult to reach more than 80%. In view of the above problem, the present invention provides a method for rapidly preparing N-methylbenzisothiazolinone-1-oxide, and the preparation method comprises the following steps:

[0005] At room temperature, 2-mercapto-N-methylbenzamide and N-chlorosuccinimide (NCS) are vigorously stirred and reacted in an organic solvent. After the reaction is completed, 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 min.

[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 by 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 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] At room temperature, MeCN (10 mL), 2-mercapto-N-methylbenzamide (1.0 mmol), and chlorosuccinimide (NCS) (3.0 mmol) were added to a 50 mL round-bottom flask in sequence, and the mixture was stirred vigorously for 10 min. After the reaction, the reaction solution was heated and concentrated, and the organic phase was extracted in sequence (10 mL of ethyl acetate was first added to the reaction solution, stirred and mixed evenly, and then 30 mL of water was added to the reaction system, stirred and mixed evenly, and allowed to stand for stratification). The ethyl acetate in the organic phase was removed by vacuum distillation to obtain N-methylbenzisothiazolinone-1-oxide, and the yield was 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 min. 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 min. 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 to replace 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 to replace MeCN as the reaction solvent in Example 10. 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 to replace MeCN as the reaction solvent in Example 12. 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 to replace 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] 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 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 for reaction. After the reaction is completed, the reaction solution is sequentially 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:

2. A method for rapidly preparing N-methylbenzisothiazolinone-1-oxide according to claim 1, characterized in that: The organic solvent includes one or a combination of two or more of MeCN, ethyl acetate, DCM, toluene and THF.

3. A method for rapidly preparing N-methylbenzisothiazolinone-1-oxide according to claim 2, characterized in that: The organic solvent is MeCN.

4. A method for rapidly preparing N-methylbenzisothiazolinone-1-oxide according to claim 3, characterized in that: The usage ratio of 2-mercapto-N-methylbenzamide to NCS and MeCN is 1mmol:2-4mmol:5-15mL.

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

6. A method for rapidly preparing N-methylbenzisothiazolinone-1-oxide according to claim 5, characterized in that: The usage ratio of 2-mercapto-N-methylbenzamide to NCS and MeCN is 1mmol:3mmol:10mL.

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

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

9. 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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