A method for preparing N-n-butyl-1,2-benzisothiazolin-3-one-1-oxide

Abstract

The present invention relates to the technical field of fine chemicals, and discloses a method for preparing N-n-butyl-1,3-benzisothiazolin-3-one-1-oxide. Specific steps: using N-n-butyl-1,2-benzisothiazolin-3-one as a raw material, Selectfluor and DMF as important additives, reacting in a solvent to obtain the target product N-n-butyl-1,3-benzisothiazolin-3-one-1-oxide. This method is easy to operate, water can be used as a reaction solvent for the reaction, and the target compound can be obtained by simple extraction and separation, which conforms to the scope of green chemistry and has potential application value.

Description

Technical Field

[0001] The invention belongs to the field of fine chemicals and relates to a method for preparing N-n-butyl-1,3-benzisothiazolin-3-one-1-oxide. Background Art

[0002] N-n-Butyl-1,3-benzisothiazolin-3-one-1-oxide is an important class of sulfur-nitrogen-containing six-membered heterocyclic compounds and an important organic synthesis intermediate with potential biological activity, such as protein tyrosine phosphatase inhibitors, antianxiety agents, etc. In addition, it can also be used as a precursor for the synthesis of saccharin derivatives.

[0003] There is no literature report on the method of synthesizing N-n-butyl-1,3-benzisothiazolin-3-one-1-oxide. There are three methods for synthesizing its analog 1,3-benzisothiazolin-3-one-1-oxide: (1) using benzothiazinone as raw material and sodium periodate as oxidant to synthesize 1,3-benzisothiazolin-3-one-1-oxide with a yield of 71% (Tetrahedron, 1988, 44, 2985); (2) using 2-carbamoylphenyl disulfide as raw material and sodium periodate as oxidant to synthesize 1,3-benzisothiazolin-3-one-1-oxide with a yield of 72% (Magyar Kemiai Folyoirat, 1989, 95, 455); (3) 1,3-Benzisothiazoline-3-one-1-oxide was synthesized using 2-aminobenzoylbenzenesulfinic acid and trimethylchlorosilane as raw materials with a yield of 79% (Japanese patent JP2011162465).

[0004] This method uses N-n-butyl-1,2-benzisothiazolin-3-one, Selectfluor and DMF as additives to quickly and efficiently construct N-n-butyl-1,3-benzisothiazolin-3-one-1-oxide. Summary of the invention

[0005] The purpose of the present invention is to overcome the deficiencies of the prior art and provide an efficient method for synthesizing N-n-butyl-1,2-benzisothiazolin-3-one-1-oxide.

[0006] In order to achieve the purpose of the present invention, a method for preparing N-n-butyl-1,2-benzisothiazolin-3-one-1-oxide is provided, comprising the following steps: reacting N-n-butyl-1,2-benzisothiazolin-3-one, Selectfluor and an additive in a solvent, and purifying after the reaction to obtain N-n-butyl-1,2-benzisothiazolin-3-one-1-oxide;

[0007] The additive is DMF, and the molar ratio of DMF to N-n-butyl-1,2-benzisothiazolin-3-one is 1-5:1-1, preferably 2-4:1;

[0008] The molar ratio of Selectfluor to N-n-butyl-1,2-benzisothiazolin-3-one is 1-3:1.

[0009] The solvent is any one or more of water, DMF and MeCN.

[0010] Furthermore, the purification method comprises the following steps: after the reaction is completed, extraction and separation with ethyl acetate are performed in sequence, and ethyl acetate is removed by reduced pressure distillation. The target compound can be separated by simple extraction and separation, which conforms to the scope of green chemistry.

[0011] Furthermore, in the present invention, the molar ratio of N-n-butyl-1,2-benzisothiazolin-3-one, Selectfluor and DMF is 1.0:1.0:2.5.

[0012] Furthermore, the reaction temperature is at least 0 degrees Celsius, and the reaction time is 0.5 to 6.0 hours.

[0013] Compared with the prior art, the present invention provides a method for preparing N-n-butyl-1,2-benzisothiazolin-3-one-1-oxide, which has the characteristics of simplicity and high efficiency. BRIEF DESCRIPTION OF THE DRAWINGS

[0014] Figure 1 The hydrogen nuclear magnetic resonance spectrum of the product obtained in the example;

[0015] Figure 2 The carbon NMR spectrum of the product obtained in the example. DETAILED DESCRIPTION

[0016] The present invention is further described in detail below in conjunction with embodiments:

[0017] Example 1

[0018] The synthesis method of N-n-butyl-1,2-benzisothiazolin-3-one-1-oxide is as follows: water (2 mL), N-n-butyl-1,2-benzisothiazolin-3-one (0.2 mmol), Selectfluor (0.2 mmol) and DMF (0.5 mmol) are added to a 25 mL sealed tube in sequence, the temperature is controlled at 25 degrees Celsius, and the reaction is vigorously stirred for 1 hour. After the reaction is completed, ethyl acetate extraction is performed in sequence, and ethyl acetate is removed by vacuum distillation to obtain N-n-butyl-1,2-benzisothiazolin-3-one-1-oxide, and the separation yield is 90%.

[0019]

[0020] NMR data and mass spectrometry data of target product:

[0021] 1 H NMR (300MHz, CDCl3) δ7.92(d,J=7.3Hz,1H),7.83(d,J=7.1Hz,1H),7.76–7.66(m,2H),3.93– 3.83(m,1H),3.75–3.65(m,1H),1.75–1.69(m,2H),1.37–1.32(m,2H),0.90(t,J=7.3Hz,3H). 13 C NMR (75MHz, CDCl3) δ165.38,145.56,134.10,133.21,128.43,126.11,125.07,41.07,31.36,20.09,13.67.MS(EI)=223.0[M] + .

[0022] On the basis of this example, only the reaction time was adjusted, and the yields after reaction for 0.5 h and 6.0 h were 83% and 81%, respectively.

[0023] Based on this example, only the reaction temperature was adjusted, and the yields at 0 degrees Celsius and 50 degrees Celsius were 70% and 88%, respectively.

[0024] Example 2 (Selectfluor dosage screening)

[0025] Acetonitrile (2 mL), N-n-butyl-1,2-benzisothiazolin-3-one (0.2 mmol), Selectfluor (0-0.6 mmol), and DMF (0.5 mmol) were added to a 25 mL sealed tube in sequence, the temperature was controlled at 25 degrees Celsius, and the reaction was stirred vigorously for 1 hour. After the reaction was completed, ethyl acetate extraction and separation were performed in sequence, and ethyl acetate was removed by vacuum distillation. The specific situation is as follows:

[0026] (1) The dosage of Selectfluor was 0, and the yield of the target product was 0%;

[0027] (2) The dosage of Selectfluor was 0.1 mmol, and the yield of the target product was 44%;

[0028] (3) The dosage of Selectfluor was 0.2 mmol, and the yield of the target product was 90%;

[0029] (4) The dosage of Selectfluor was 0.3 mmol, and the yield of the target product was 81%;

[0030] (5) The dosage of Selectfluor was 0.4 mmol, and the yield of the target product was 80%;

[0031] (6) The dosage of Selectfluor was 0.6 mmol, and the yield of the target product was 80%;

[0032] Embodiment 3 (the amount screening of DMF)

[0033] Acetonitrile (2 mL), N-n-butyl-1,2-benzisothiazolin-3-one (0.2 mmol), Selectfluor (0.2 mmol), and DMF (0-0.8 mmol) were added to a 25 mL sealed tube in sequence, the temperature was controlled at 25 degrees Celsius, and the reaction was stirred vigorously for 1 hour. After the reaction was completed, ethyl acetate extraction was performed in sequence, and ethyl acetate was removed by vacuum distillation. The specific situation is as follows:

[0034] (1) The amount of DMF used was 0, and the yield of the target product was 40%;

[0035] (2) The amount of DMF used was 0.2 mmol, and the yield of the target product was 62%;

[0036] (3) The amount of DMF used was 0.4 mmol, and the yield of the target product was 80%;

[0037] (4) The amount of DMF used was 0.5 mmol, and the yield of the target product was 90%;

[0038] (5) The amount of DMF used was 0.6 mmol, and the yield of the target product was 85%;

[0039] (6) The amount of DMF used was 0.8 mmol, and the yield of the target product was 80%;

[0040] Example 4 (Screening of different reaction solvents)

[0041] Different reaction solvents (2 mL), N-n-butyl-1,2-benzisothiazolin-3-one (0.2 mmol), Selectfluor (0.2 mmol), and DMF (0.5 mmol) were added to a 25 mL sealed tube in sequence, the temperature was controlled at 25 degrees Celsius, and the reaction was stirred vigorously for 1 hour. After the reaction was completed, ethyl acetate extraction and separation were performed in sequence, and ethyl acetate was removed by vacuum distillation. The specific situation is as follows:

[0042] (1) Using DMF as solvent, the yield of the target product is 85%;

[0043] (2) Using MeCN as solvent, the yield of the target product was 80%;

[0044] (3) The target product could not be isolated using DCM, DCE, THF, 1,4-Dioxane, DMSO, toluene, and methanol as solvents.

[0045] Example 5 (using sodium periodate instead of Selectfluor)

[0046] Water (2 mL), N-n-butyl-1,2-benzisothiazolin-3-one (0.2 mmol), NaIO4 (0.2 mmol), and DMF (0.5 mmol) were added to a 25 mL sealed tube, the temperature was controlled at 25 degrees Celsius, and the reaction was stirred vigorously for 1 hour. After the reaction was completed, ethyl acetate extraction was performed in sequence, ethyl acetate was removed by vacuum distillation, and the target product N-n-butyl-1,2-benzisothiazolin-3-one-1-oxide was obtained by column chromatography, and the separation yield was 25%.

[0047] The above describes the optional embodiments of the present invention to teach those skilled in the art how to implement and reproduce the present invention. In order to teach the present invention, some conventional technical aspects have been simplified and omitted. Those skilled in the art should understand that variations derived from this aspect are all within the scope of protection of the present invention.

Claims

1. A method for preparing N-n-butyl-1,2-benzisothiazolin-3-one-1-oxide, characterized in that: The method comprises the following steps: reacting N-n-butyl-1,2-benzisothiazolin-3-one, Selectfluor and an additive in a solvent, and purifying after the reaction to obtain N-n-butyl-1,2-benzisothiazolin-3-one-1-oxide; The additive is DMF, and the molar ratio of the additive DMF to N-n-butyl-1,2-benzisothiazolin-3-one is 1-5:1; The molar ratio of Selectfluor to N-n-butyl-1,2-benzisothiazolin-3-one is 1-3:1; The solvent is any one or more of water, DMF and MeCN.

2. The method for preparing N-n-butyl-1,2-benzisothiazolin-3-one-1-oxide according to claim 1, characterized in that: The purification method comprises the following steps: after the reaction is completed, extraction and separation of liquids with ethyl acetate are performed in sequence, and ethyl acetate is removed by distillation under reduced pressure.

3. The method for preparing N-n-butyl-1,2-benzisothiazolin-3-one-1-oxide according to claim 1, characterized in that: The molar ratio of N-n-butyl-1,2-benzisothiazolin-3-one, Selectfluor and additive DMF is 1.0:1.0:2.

5.

4. The method for preparing N-n-butyl-1,2-benzisothiazolin-3-one-1-oxide according to claim 1, characterized in that: The molar ratio of the additive DMF to N-n-butyl-1,2-benzisothiazolin-3-one is 2-4:

1.

5. The method for preparing N-n-butyl-1,2-benzisothiazolin-3-one-1-oxide according to claim 1, characterized in that: The reaction temperature is at least 0 degrees Celsius and the reaction time is 0.5~6.0h.

Images