A method for preparing 2,2'-dithiobis(benzonitrile)

Abstract

The present invention belongs to the field of fine chemical technology, and specifically relates to a method for preparing 2,2'-dithiobis(benzonitrile). The method comprises the following steps: using 3-chlorobenzisothiazole as a reaction raw material, and adding HI and NH4I as important additives into an organic solvent, and vigorously stirring and reacting to obtain the target product 2,2'-dithiobis(benzonitrile). The method provided by the present invention has the advantages of simple operation, fast reaction and high yield. In addition, the target product 2,2'-dithiobis(benzonitrile) can be obtained by simple extraction and liquid separation, which conforms to the scope of green chemistry and has potential application value.

Description

Technical Field

[0001] The present invention belongs to the field of fine chemicals, and particularly relates to a method for preparing 2,2'-dithiobis(benzonitrile). Background Art

[0002] 2,2'-Dithiobis(benzonitrile) is an important disulfide compound. It can be used as a pharmaceutical intermediate to synthesize anticoagulants and antipsychotic drugs, and can also be used alone as a fungicide to treat rice blast, and even as a lithium ion additive to improve the discharge capacity retention rate.

[0003] Currently, there are mainly two synthetic methods for 2,2'-dithiobis(benzonitrile) that can be consulted: (1) Using 2-iodobenzyl cyanide or 2-bromobenzyl cyanide and sulfur monochloride as raw materials, and using isopropylmagnesium chloride lithium chloride and zinc bromide, 2,2'-dithiobis(benzonitrile) is constructed through multi-step continuous low-temperature reactions, with yields of 78% and 63% respectively (Organic Letters, 2018, 2, 7581; Synlett, 2005, 1185). The defect of this reaction is that the reaction steps are cumbersome, and at the same time, low-temperature reactions and highly active Grignard reagents are required; (2) Using 3-methoxybenzisothiazole as the raw material and hydrazine hydrate as an additive, 2,2'-dithiobis(benzonitrile) is synthesized by heating under reflux in ethanol or methanol, and the reaction yield is 72% (Journal of Organic Chemistry, 2021, 86, 6381). The defect of this reaction is that the raw material 3-methoxybenzisothiazole is expensive. Summary of the Invention

[0004] In order to overcome the deficiencies of the prior art, the present invention provides a simple, rapid and efficient method for preparing 2,2'-dithiobis(benzonitrile). Using 3-chlorobenzisothiazole as the raw material and HI and NH4I as additives, 2,2'-dithiobis(benzonitrile) can be rapidly and efficiently synthesized through a one-step reaction. Among them, 3-chlorobenzisothiazole, HI and NH4I are all cheap and easily available raw materials and reaction reagents.

[0005] The technical solution adopted by the present invention is as follows:

[0006] A method for preparing 2,2'-dithiobis(benzonitrile), comprising the following steps: adding 3-chlorobenzisothiazole, HI and NH4I into a sealed tube containing a solvent, and stirring the reaction vigorously. After the reaction, ethyl acetate extraction and liquid separation are carried out, ethyl acetate is removed by reduced pressure distillation, column chromatography separation is carried out, and the product 2,2'-dithiobis(benzonitrile) is collected.

[0007] Preferably, the solvent is any one of acetonitrile or tetrahydrofuran.

[0008] Preferably, the molar ratio of 3-chlorobenzisothiazole, HI and NH4I is 2:(1 - 8):(0 - 8).

[0009] Preferably, the reaction temperature is 0 - 50 °C; the reaction time is 1 min - 6 h.

[0010] To improve the product yield, the molar ratio of 3-chlorobenzisothiazole, HI and NH4I is 1:1:2, the reaction temperature is 25 °C, and the reaction time is 5 min.

[0011] Compared with the prior art, the reaction steps of the present invention are simple, the reaction raw materials are cheap and easily available, and there is no need to use cumbersome column chromatography for product separation. The target compound can be separated by simple extraction and liquid separation, which conforms to the category of green chemistry. Detailed Embodiments

[0012] The following examples will help to illustrate the present invention, but are not limited to its scope.

[0013] Example 1

[0014] Synthesis method of 2,2'-dithiobis(benzonitrile): In a 25 mL sealed tube, add acetonitrile (1 mL), 3-chlorobenzisothiazole (0.2 mmol), HI (0.2 mmol) and NH4I (0.4 mmol) in sequence. Control the reaction temperature at 25 °C and stir the reaction vigorously for 5 min. After the reaction is completed, perform extraction and liquid separation with ethyl acetate in sequence, and distill off ethyl acetate under reduced pressure to obtain 2,2'-dithiobis(benzonitrile), and the separation yield is 95%.

[0015] The equation involved in the reaction is as follows:

[0016]

[0017] The NMR data and mass spectrum data of the target product are as follows:

[0018] 1 H NMR(300 MHz, CDCl3) δ 7.75(d, J = 8.0 Hz, 2H), 7.64(d, J = 7.7 Hz, 2H), 7.58(t, J = 7.8 Hz, 2H), 7.39(t, J = 7.6 Hz, 2H). 13 C NMR(75 MHz, CDCl3) δ 140.01, 133.90, 133.72, 130.02, 128.52, 116.34, 113.26. MS(EI) = 268.0[M] + .

[0019] Example 2

[0020] Screening of the dosage of HI:

[0021] In a 25 mL sealed tube, add acetonitrile (2 mL), 3-chlorobenzisothiazole (0.2 mmol), HI (0 - 0.8 mmol), and NH4I (0.6 mmol) in sequence. Control the reaction temperature at 25 °C and stir the reaction vigorously for 5 min. After the reaction is completed, perform extraction and liquid separation with ethyl acetate in sequence, and remove ethyl acetate by vacuum distillation (or column chromatography separation). The specific situation of obtaining the target product 2,2'-dithiobis(benzonitrile) is as follows:

[0022] (1) When the dosage of HI is 0, the yield of the target product 2,2'-dithiobis(benzonitrile) is 0%;

[0023] (2) When the dosage of HI is 0.1 mmol, the yield of 2,2'-dithiobis(benzonitrile) is 86%;

[0024] (3) When the dosage of HI is 0.2 mmol, the yield of 2,2'-dithiobis(benzonitrile) is 88%;

[0025] (4) When the dosage of HI is 0.4 mmol, the yield of 2,2'-dithiobis(benzonitrile) is 82%;

[0026] (5) When the dosage of HI is 0.6 mmol, the yield of 2,2'-dithiobis(benzonitrile) is 80%;

[0027] (6) When the dosage of HI is 0.8 mmol, the yield of 2,2'-dithiobis(benzonitrile) is 70%.

[0028] Example 3

[0029] Screening of the dosage of NH4I:

[0030] In a 25 mL sealed tube, add acetonitrile (2 mL), 3-chlorobenzisothiazole (0.2 mmol), HI (0.2 mmol), and NH4I (0 - 0.8 mmol) in sequence. Control the reaction temperature at 25 °C and stir the reaction vigorously for 5 min. After the reaction is completed, perform extraction and liquid separation with ethyl acetate in sequence, and remove ethyl acetate by vacuum distillation (or column chromatography separation). The specific situation of obtaining the target product 2,2'-dithiobis(benzonitrile) is as follows:

[0031] (1) When the dosage of NH4I is 0, the yield of 2,2'-dithiobis(benzonitrile) is 46%;

[0032] (2) When the dosage of NH4I is 0.2 mmol, the yield of 2,2'-dithiobis(benzonitrile) is 85%;

[0033] (3) The amount of NH4I used is 0.4 mmol, and the yield of 2,2'-dithiobis(benzonitrile) is 90%;

[0034] (4) The amount of NH4I used is 0.6 mmol, and the yield of 2,2'-dithiobis(benzonitrile) is 88%;

[0035] (5) The amount of NH4I used is 0.8 mmol, and the yield of 2,2'-dithiobis(benzonitrile) is 71%.

[0036] Example 4

[0037] Screening of the amount of solvent acetonitrile:

[0038] In a 25 mL sealed tube, acetonitrile (0.5 - 4 mL), 3-chlorobenzisothiazole (0.2 mmol), HI (0.2 mmol), and NH4I (0.4 mmol) were added in sequence. The reaction temperature was controlled at 25 °C, and the reaction was vigorously stirred for 5 min. After the reaction, ethyl acetate extraction and liquid separation were carried out in sequence, and ethyl acetate was removed by vacuum distillation (or column chromatography separation). The specific conditions for obtaining the target product 2,2'-dithiobis(benzonitrile) are as follows:

[0039] (1) The amount of acetonitrile used is 0.5 mL, and the yield of 2,2'-dithiobis(benzonitrile) is 90%;

[0040] (2) The amount of acetonitrile used is 1.0 mL, and the yield of 2,2'-dithiobis(benzonitrile) is 95%;

[0041] (3) The amount of acetonitrile used is 2.0 mL, and the yield of 2,2'-dithiobis(benzonitrile) is 90%;

[0042] (4) The amount of acetonitrile used is 3.0 mL, and the yield of 2,2'-dithiobis(benzonitrile) is 87%;

[0043] (5) The amount of acetonitrile used is 4.0 mL, and the yield of 2,2'-dithiobis(benzonitrile) is 73%.

[0044] Example 5

[0045] Screening of the solvent:

[0046] In a 25 mL sealed tube, solvent (1 mL), 3-chlorobenzisothiazole (0.2 mmol), HI (0.2 mmol), and NH4I (0.4 mmol) were added in sequence. The reaction temperature was controlled at 25 °C, and the reaction was vigorously stirred for 5 min. After the reaction, ethyl acetate extraction and liquid separation were carried out in sequence, and ethyl acetate was removed by vacuum distillation (or column chromatography separation). The specific conditions for obtaining the target product 2,2'-dithiobis(benzonitrile) are as follows:

[0047] (1) Using MeCN as the solvent, the yield of 2,2′-dithiobis(benzonitrile) is 95%;

[0048] (2) Using THF as the solvent, the yield of 2,2′-dithiobis(benzonitrile) is 86%;

[0049] (3) Using DCM, DMF, DMSO, toluene, or methanol as the solvent, 2,2′-dithiobis(benzonitrile) cannot be separated.

[0050] Example 6

[0051] Screening of reaction time:

[0052] In a 25 mL sealed tube, add acetonitrile (1 mL), 3-chlorobenzisothiazole (0.2 mmol), HI (0.2 mmol), and NH4I (0.4 mmol) in sequence. Control the reaction temperature at 25 °C and stir vigorously for 1 min, 5 min, and 6 h respectively. After the reaction, perform ethyl acetate extraction and liquid separation in sequence, and remove ethyl acetate by distillation under reduced pressure (or column chromatography separation). The specific situation of obtaining the target product 2,2′-dithiobis(benzonitrile) is as follows:

[0053] (1) When the reaction time is controlled at 1 min, the yield of 2,2′-dithiobis(benzonitrile) is 80%;

[0054] (2) When the reaction time is controlled at 5 min, the yield of 2,2′-dithiobis(benzonitrile) is 95%;

[0055] (3) When the reaction time is controlled at 6 h, the yield of 2,2′-dithiobis(benzonitrile) is 85%.

[0056] Example 7

[0057] Screening of reaction temperature:

[0058] In a 25 mL sealed tube, add acetonitrile (1 mL), 3-chlorobenzisothiazole (0.2 mmol), HI (0.2 mmol), and NH4I (0.4 mmol) in sequence. Control the reaction temperature at 0 °C, 25 °C, and 50 °C respectively, and stir vigorously for 5 min. After the reaction, perform ethyl acetate extraction and liquid separation in sequence, and remove ethyl acetate by distillation under reduced pressure (or column chromatography separation). The specific situation of obtaining the target product 2,2′-dithiobis(benzonitrile) is as follows:

[0059] (1) When the reaction temperature is controlled at 0 °C, the yield of 2,2′-dithiobis(benzonitrile) is 86%;

[0060] (2) When the reaction temperature is controlled at 25 °C, the yield of 2,2′-dithiobis(benzonitrile) is 95%;

[0061] (3) The reaction temperature was controlled at 50 °C, and the yield of 2,2'-dithiobis(benzonitrile) was 93%.

Claims

1. A method for preparing 2,2'-dithiobis(benzonitrile), characterized in that, It includes the following steps: adding 3-chlorobenzisothiazole, HI and NH4I into a sealed tube containing a solvent, and stirring the reaction vigorously; the solvent is any one of acetonitrile or tetrahydrofuran.

2. The method for preparing 2,2'-dithiobis(benzonitrile) according to claim 1, characterized in that, The method further includes liquid-liquid extraction with ethyl acetate after the reaction, removing ethyl acetate by vacuum distillation, column chromatography separation, and collecting the product 2,2'-dithiobis(benzonitrile).

3. The method for preparing 2,2'-dithiobis(benzonitrile) according to claim 1, characterized in that, The molar ratio of 3-chlorobenzisothiazole, HI and NH4I is 2:(1-8):(0-8).

4. The method for preparing 2,2'-dithiobis(benzonitrile) according to claim 3, characterized in that, The molar ratio of 3-chlorobenzisothiazole, HI and NH4I is 1:1:

2.

5. The method for preparing 2,2'-dithiobis(benzonitrile) according to claim 1, characterized in that, The reaction temperature is 0-50 °C; the reaction time is 1 min-6 h.

6. The method for preparing 2,2'-dithiobis(benzonitrile) according to claim 5, characterized in that, The reaction temperature is 25 °C; the reaction time is 5 min.

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