Method for preparing broad-spectrum bactericide 2-n-butylbenzo [d] isothiazole-3 (2H)-ketone by molecular editing method

Abstract

The invention belongs to the technical field of fine chemical engineering, and particularly discloses a method for preparing a broad-spectrum bactericide 2-n-butylbenzo [d] isothiazole-3 (2H)-ketone by a molecular editing method. The preparation method comprises the following specific steps: taking 3H-1, 2-benzodisulfophenol-3-ketone and n-butylamine as raw materials, taking Selectfluor as an additive, adding the raw materials and the additive into a mixed solvent, and carrying out heating and stirring reaction, so as to obtain the target product 2-n-butylbenzo [d] isothiazole-3 (2H)-ketone (BBIT). The method is simple and convenient to operate, the raw materials are easy to obtain, the yield is high, thiophenol raw materials or excessive alkali are prevented from being used, and potential application value is achieved.

Description

Technical Field

[0001] This invention belongs to the field of fine chemical technology, specifically relating to a method for preparing the broad-spectrum bactericide 2-n-butylbenzo[d]isothiazol-3(2H)-one using molecular editing. Background Technology

[0002] 2-Butylbenzo[d]isothiazol-3(2H)-one (BBIT), a broad-spectrum bactericide, is an important class of organic sulfur-containing heterocyclic compounds with significant biological activity. This substance can be widely used in the production of liquid, powder, or solid antibacterial products. It can be directly added to plastics or coatings to protect plastic products from microbial degradation and can also impart antibacterial properties to their surfaces. The synthesis of this compound typically requires the use of thiophenolic raw materials with an unpleasant odor or an excess of alkali.

[0003] Molecular editing is a technique that modifies the original structure of molecules at the atomic level, significantly simplifying drug synthesis and reducing the difficulty of new drug development. Based on this, we designed a method for preparing 2-n-butylbenzo[d]isothiazol-3(2H)-one (BBIT) using molecular editing, providing a novel synthetic approach for this type of active compound. Summary of the Invention

[0004] This invention provides a method for preparing 2-n-butylbenzo[d]isothiazol-3(2H)-one (BBIT), which is a molecular editing method involving the conversion of sulfur atoms to nitrogen atoms. Using 3H-1,2-benzodisulfonyl-3-one and n-butylamine as raw materials and Selectfluor as an additive, 2-n-butylbenzo[d]isothiazol-3(2H)-one (BBIT) is prepared. The method includes the following steps: Selectfluor, 3H-1,2-benzodisulfonyl-3-one, and n-butylamine are added to a mixed solvent of acetonitrile and water; the mixture is heated and stirred to react; and then separated and purified to obtain 2-n-butylbenzo[d]isothiazol-3(2H)-one (BBIT).

[0005] Furthermore, the mixed solvent is prepared by mixing acetonitrile and water in a volume ratio of 9:(0-9), preferably 9:1.

[0006] Furthermore, the molar ratio of 3H-1,2-benzodisulfonyl-3-one, n-butylamine, and Selectfluor is 1:(1-4):(1-2), preferably 1:3:1.5.

[0007] Furthermore, the temperature of the heating and stirring reaction is 80-120℃, preferably 80-100℃.

[0008] Furthermore, the heating and stirring reaction time is 12-48 hours, preferably 36-48 hours.

[0009] Furthermore, the separation and purification process includes reaction solution concentration and column chromatography separation.

[0010] The beneficial effects of this invention are as follows: This invention provides a method for preparing 2-n-butylbenzo[d]isothiazol-3(2H)-one (BBIT), which is a molecular editing method involving the conversion of sulfur atoms to nitrogen atoms. Using 3H-1,2-benzodisulfonyl-3-one and n-butylamine as raw materials and Selectfluor as an additive, 2-n-butylbenzo[d]isothiazol-3(2H)-one (BBIT) is prepared. This method uses readily available raw materials and additives, is simple to operate, requires minimal equipment, avoids the use of thiophenolic raw materials or excessive alkali, is environmentally friendly, and yields high results. Detailed Implementation

[0011] Example 1

[0012] 3H-1,2-benzodisulfonyl-3-one (0.2 mmol, 33.6 mg), n-butylamine (0.6 mmol, 60.0 μL), Selectfluor (0.3 mmol, 106.3 mg), acetonitrile (1.8 mL), and water (0.2 mL) were added sequentially to a 25 mL sealed tube. The reaction was stirred at 100 °C for 36 hours until the reaction was complete. After the reaction was complete, the reaction solution was concentrated and separated by column chromatography to obtain 2-n-butylbenzo[d]isothiazol-3(2H)-one (BBIT) in 85% yield. The structure of the product was confirmed by 1H NMR and mass spectrometry. The reaction formula is shown in Formula I below.

[0013] (Formula I)

[0014] NMR data of the target product: 1 H NMR (400 MHz, CDCl3) δ 7.94 (d, J = 7.9 Hz, 1H),7.56 – 7.45 (m, 2H), 7.37 – 7.27 (m, 1H), 3.82 (t, J = 7.2 Hz, 2H), 1.70 –1.63 (m, 2H), 1.36 – 1.30 (m, 2H), 0.88 (t, J = 7.3 Hz, 3H). MS (EI) = 207.0[M + ].

[0015] Example 2

[0016] With all other conditions remaining unchanged, only the amount of Selectfluor used in Example 1 was changed, as follows: The amount of Selectfluor used was 0 mmol, and the yield of the target product was 0%. The amount of Selectfluor used was 0.2 mmol, and the yield of the target product was 73%. The amount of Selectfluor used was 0.3 mmol, and the yield of the target product was 85%. The amount of Selectfluor used was 0.4 mmol, and the yield of the target product was 75%.

[0017] Example 3

[0018] With all other conditions remaining unchanged, only the ratio of acetonitrile and water in the mixed solvent of Example 1 was changed, as follows: Using acetonitrile as a solvent, the yield of the target product was 37%. Using water as a solvent, the yield of the target product was 0%. Using acetonitrile:water = 9:1 (1.8 mL acetonitrile and 0.2 mL water) as the solvent, the yield of the target product was 85%. Using acetonitrile:water = 1:1 (1 mL acetonitrile and 1 mL water) as the solvent, the yield of the target product was 50%. Using acetonitrile:water = 1:9 (0.2 mL acetonitrile and 1.8 mL water) as solvent, the yield of the target product was 0%.

[0019] Example 4

[0020] With all other conditions remaining unchanged, only the reaction temperature in Example 1 was changed, as follows: The reaction temperature was 80℃, and the yield of the target product was 80%. The reaction temperature was 100℃, and the yield of the target product was 85%. The reaction temperature was 120℃, and the yield of the target product was 45%. Example 5 With all other conditions remaining unchanged, only the reaction time in Example 1 was changed, as follows: The reaction time was 12 hours, and the yield of the target product was 32%. The reaction time was 24 hours, and the yield of the target product was 65%. The reaction time was 36 hours, and the yield of the target product was 85%. The reaction time was 48 hours, and the yield of the target product was 85%.

[0021] Example 6

[0022] With all other conditions remaining unchanged, only the amount of n-butylamine in Example 1 was changed, as follows: The amount of n-butylamine used was 0.2 mmol, and the yield of the target product was 62%. The amount of n-butylamine used was 0.4 mmol, and the yield of the target product was 78%. The amount of n-butylamine used was 0.6 mmol, and the yield of the target product was 85%. The amount of n-butylamine used was 0.8 mmol, and the yield of the target product was 83%.

[0023] 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 the broad-spectrum bactericide 2-n-butylbenzo[d]isothiazol-3(2H)-one using molecular editing, characterized in that: 3H-1,2-benzodisulfonyl-3-one, n-butylamine, and Selectfluor were added to a mixed solvent, heated and stirred, and the mixture was purified to obtain 2-n-butylbenzo[d]isothiazol-3(2H)-one.

2. The method for preparing the broad-spectrum bactericide 2-n-butylbenzo[d]isothiazol-3(2H)-one by molecular editing according to claim 1, characterized in that: The separation and purification process includes reaction solution concentration and column chromatography separation.

3. The method for preparing the broad-spectrum bactericide 2-n-butylbenzo[d]isothiazol-3(2H)-one by molecular editing as described in claim 1, characterized in that: The temperature of the heating and stirring reaction is 80-120℃.

4. The method for preparing the broad-spectrum bactericide 2-n-butylbenzo[d]isothiazol-3(2H)-one by molecular editing as described in claim 1, characterized in that: The heating and stirring reaction time is 12-48 hours.

5. The method for preparing the broad-spectrum bactericide 2-n-butylbenzo[d]isothiazol-3(2H)-one by molecular editing as described in claim 1, characterized in that: The molar ratio of 3H-1,2-benzodisulfol-3-one, n-butylamine, and Selectfluor is 1:(1-4):(1-2).

6. The method for preparing the broad-spectrum bactericide 2-n-butylbenzo[d]isothiazol-3(2H)-one by molecular editing as described in claim 1, characterized in that: The mixed solvent is a mixture of acetonitrile and water in a volume ratio of 9:(0-9).