Preparation method of bis (2, 3-epithiopropyl) disulfide

Abstract

The invention discloses a preparation method of bis (2, 3-epithiopropyl) disulfide, and belongs to the technical field of organic synthesis. The preparation method comprises the following steps: reacting epichlorohydrin with thioacetate to obtain 2-(acetylthiomethyl) ethylene oxide; then reacting with hydrochloric acid for deacetylation protection; reacting with hydrogen peroxide under the catalysis of iodine, or reacting with sulfur powder and sodium hydroxide; and finally, reacting with thiourea to obtain the bis (2, 3-epithiopropyl) disulfide. The chloropropylene oxide is used as the raw material, the intermediate in the whole reaction process can be purified, the final product is high in purity, and the obtained product can be used for high-refractive-index resin lenses (the refractive index is larger than or equal to 1.70) and high-temperature-resistant optical coatings and meets the requirements of the electronic and medical fields.

Description

Technical Field

[0001] The present invention relates to a method for preparing bis(2,3-epithiopropyl) disulfide, belonging to the technical field of organic synthesis. Background Art

[0002] High-refractive-index resin lenses are required to be light in weight and have a high refractive index. The addition of episulfide resin can increase its refractive index. Bis(2,3-epithiopropyl) disulfide is a sulfur-containing cyclic compound. Its high sulfur content (50-85%) gives it excellent refractive index and heat resistance in optical materials, making it suitable for high-refractive-index resin lenses, pharmaceutical intermediates, optical materials, and the electronic field, and has important applications. Its main advantage is that it can significantly reduce the volume of optical components, improve the optical path design, and enhance the optical performance. However, the biggest problem with bis(2,3-epithiopropyl) disulfide is the low purity of the synthetic product, high nitrogen content, and many by-products, making purification difficult.

[0003] Mitsui Chemicals (JP6200124; EP2805949) and Korea KOC (KR2016100422) use bis(3-chloro-2-hydroxypropyl) disulfide to cyclize under the action of sodium hydroxide, and then react with thiourea to obtain bis(2,3-epithiopropyl) disulfide. In this method, the raw material 1-chloro-3-mercapto-2-propanol is not easily available. The reaction equation is expressed as follows:

[0004]

[0005] To solve the above problems, the present invention provides a method for preparing bis(2,3-epithiopropyl) disulfide. The method has easily available raw materials and simple operation. By double adsorption with activated carbon and anhydrous magnesium sulfate, its nitrogen content is reduced, and the purity can be improved by low-temperature crystallization, obtaining bis(2,3-epithiopropyl) disulfide with high purity and low nitrogen content, thereby meeting its requirements. Summary of the Invention

[0006] To overcome the above technical defects, the present invention provides a method for preparing bis(2,3-epithiopropyl) disulfide. Epichlorohydrin reacts with thioacetate to obtain 2-(acetylthiomethyl)oxirane; then it reacts with hydrochloric acid to remove the acetyl protection to obtain 2-(methylthiol)oxirane; then it reacts with hydrogen peroxide under the catalysis of iodine or reacts with sulfur powder and sodium hydroxide to obtain 2-[(oxirane-2-ylmethyldisulfanyl)methyl]oxirane; finally, it reacts with thiourea to obtain bis(2,3-epithiopropyl) disulfide. The raw materials of the present invention are easily available, low in cost, and suitable for industrial production. The obtained product can be used for high-refractive-index resin lenses (refractive index ≥ 1.70) and high-temperature-resistant optical coatings, meeting the needs of the electronic and medical fields.

[0007] A preparation method of bis(2,3-epithiopropyl) disulfide, and the reaction route is shown as follows:

[0008]

[0009] It includes the following steps:

[0010] Step S1: Mix epichlorohydrin, thioacetate and tetrabutylammonium iodide in water, slowly add potassium carbonate at room temperature, heat up to 30 - 35 °C, and react for 5 - 8 hours to obtain 2-(acetylthiomethyl)oxirane.

[0011] Step S2: Mix 2-(acetylthiomethyl)oxirane with an alcohol solvent, add concentrated hydrochloric acid to obtain 2-(methylsulfanyl)oxirane.

[0012] Step S3: Mix 2-(methylsulfanyl)oxirane with an alcohol solvent, add iodine, and then dropwise add hydrogen peroxide, control the temperature at 35 - 38 °C for reaction to obtain 2-[(oxirane-2-ylmethyldisulfanyl)methyl]oxirane; or mix 2-(methylsulfanyl)oxirane with ethanol, add sulfur powder and sodium hydroxide, and reflux for reaction to obtain 2-[(oxirane-2-ylmethyldisulfanyl)methyl]oxirane.

[0013] Step S4: Mix thiourea, acetonitrile, montmorillonite and trifluoroethanol, control the temperature at 0 - 10 °C and dropwise add 2-[(oxirane-2-ylmethyldisulfanyl)methyl]oxirane, then heat up to 30 - 35 °C and react for 6 hours to obtain bis(2,3-epithiopropyl) disulfide.

[0014] Further, in the above step S1, the thioacetate is selected from potassium thioacetate or sodium thioacetate.

[0015] Further, in the above step S1, the molar ratio of epichlorohydrin, thioacetate, tetrabutylammonium iodide and potassium carbonate is 1:1.3 - 1.5:0.01 - 0.03:1.8 - 2.0.

[0016] Further, in the above step S2, the alcohol solvent is selected from methanol or ethanol.

[0017] Further, in the above step S2, the molar ratio of 2-(acetylthiomethyl)oxirane to concentrated hydrochloric acid is 1:1.4 - 1.6.

[0018] Further, in the above step S3, the alcohol solvent is selected from ethanol or isopropanol.

[0019] Further, in the above step S3, the molar ratio of 2-(methylsulfanyl)oxirane, iodine and hydrogen peroxide is 1:0.01 - 0.02:1.1 - 1.3.

[0020] Further, in the above step S3, the molar ratio of 2-(methylthio)oxirane, sulfur powder and sodium hydroxide is 1:8-9:1.0-1.3.

[0021] Further, in the above step S4, the molar ratio of thiourea, trifluoroethanol and 2-[(oxirane-2-ylmethyldisulfanyl)methyl]oxirane is 2.2-2.3:0.1-0.3:1.

[0022] Further, in the above step S4, the mass ratio of 2-[(oxirane-2-ylmethyldisulfanyl)methyl]oxirane to montmorillonite is 1:0.01-0.02.

[0023] The present invention has the following beneficial effects:

[0024] 1. Using cheap and easily available chloropropylene oxide as the raw material, the intermediates in the whole reaction process can be purified, and the purity of the final product is high, with good economic benefits.

[0025] 2. Using the catalytic combination of iodine and hydrogen peroxide, the yield is high and the catalytic effect is good.

[0026] 3. The raw materials of this process are easily available in the market, the process is simple, safe and stable, and it is suitable for industrial scale-up. Description of the Drawings

[0027] Figure 1 1H-NMR of bis(2,3-epithiopropyl) disulfide in Example 7 1 1H-NMR;

[0028] Figure 2 13C-NMR of bis(2,3-epithiopropyl) disulfide in Example 7 13 13C-NMR. Specific Embodiments

[0029] The present invention will be further described below through specific examples. These examples should be understood as only for illustrating the present invention and not for limiting the protection scope of the present invention. After reading the content recorded in the present invention, those skilled in the art can make various changes or modifications to the present invention, and these equivalent changes and modifications also fall within the scope defined by the claims of the present invention.

[0030] Example 1

[0031]

[0032] Under nitrogen protection, epichlorohydrin (9.25 g, 0.1 mol), sodium thioacetate (13.7 g, 0.14 mol) and tetrabutylammonium iodide (0.74 g, 0.002 mol) were mixed in 200 mL of water. Potassium carbonate (26.3 g, 0.19 mol) was slowly added at room temperature. The temperature was raised to 30 - 35 °C and the reaction was carried out for 7 hours. Then the temperature was cooled to room temperature. 80 mL of dichloromethane was added for extraction twice. After concentration and vacuum distillation, 11.2 g of 2-(acetylthiomethyl)oxirane was obtained with a yield of 85.2%. LC-MS [M+H] + = 133.2.

[0033] Example 2

[0034]

[0035] Under nitrogen protection, epichlorohydrin (9.25 g, 0.1 mol), potassium thioacetate (13.7 g, 0.14 mol) and tetrabutylammonium iodide (0.74 g, 0.002 mol) were mixed in 200 mL of water. Potassium carbonate (26.3 g, 0.19 mol) was slowly added at room temperature. The temperature was raised to 30 - 35 °C and the reaction was carried out for 6 hours. Then the temperature was cooled to room temperature. 80 mL of dichloromethane was added for extraction twice. After concentration and vacuum distillation, 11.6 g of 2-(acetylthiomethyl)oxirane was obtained with a yield of 88.1%.

[0036] Example 3

[0037]

[0038] Under nitrogen protection, 2-(acetylthiomethyl)oxirane (13.2 g, 0.1 mol) was mixed with 80 mL of methanol solvent. 14.8 g of concentrated hydrochloric acid (37%) was added and the mixture was refluxed for 5 hours. Then the temperature was cooled to room temperature. A saturated aqueous solution of sodium bicarbonate was added to adjust the pH to 6 - 7. Methanol was removed by vacuum distillation. 70 mL of dichloromethane was added for extraction twice. The organic layer was concentrated and vacuum distilled to obtain 8.3 g of 2-(methylmercapto)oxirane with a yield of 92.0%. The GC analysis showed the same peak as the standard product. LC-MS [M+H] + = 91.3.

[0039] Example 4

[0040]

[0041] Under nitrogen protection, 2-(acetylthiomethyl)oxirane (13.2 g, 0.1 mol) was mixed with 80 mL of ethanol solvent, 14.8 g of concentrated hydrochloric acid (37%) was added, and the mixture was refluxed for 3 hours. After cooling to room temperature, saturated sodium bicarbonate aqueous solution was added to adjust the pH to 6 - 7. Methanol was removed by vacuum distillation. The mixture was extracted twice with 70 mL of dichloromethane. The organic layer was concentrated and then distilled under reduced pressure to obtain 8.0 g of 2-(methylsulfanyl)oxirane, with a yield of 89.2%. The GC analysis showed the same peak as the standard product.

[0042] Example 5

[0043]

[0044] Under nitrogen protection, 2-(methylsulfanyl)oxirane (9 g, 0.1 mol) was mixed with 90 mL of ethanol solvent, iodine (0.38 g, 0.0015 mol) was added, and then 13.6 g of hydrogen peroxide (30%) was added dropwise while controlling the temperature at 35 - 38 °C. The reaction was carried out for 5 hours. After cooling to room temperature, 30 mL of saturated sodium thiosulfate aqueous solution and 30 mL of saturated sodium bicarbonate aqueous solution were added. The mixture was extracted twice with 100 mL of dichloromethane. The organic layers were combined, concentrated, and the crude product was distilled under reduced pressure to obtain 8.5 g of 2-[(oxirane-2-ylmethyldisulfanyl)methyl]oxirane, with a yield of 95.1%. The GC analysis showed the same peak as the standard product. LC-MS [M + H] + = 179.3.

[0045] Comparative Example 5

[0046]

[0047] Under nitrogen protection, 2-(methylsulfanyl)oxirane (9 g, 0.1 mol) was mixed with 200 mL of ethanol solvent, sulfur powder (27.3 g, 0.85 mol) and sodium hydroxide (4.8 g, 0.12 mol) were added, and the mixture was refluxed for 10 hours. After cooling to room temperature, the mixture was filtered. The filtrate was concentrated and then distilled under reduced pressure to obtain 7.1 g of 2-[(oxirane-2-ylmethyldisulfanyl)methyl]oxirane, with a yield of 79.1%.

[0048] Example 6

[0049]

[0050] Under nitrogen protection, 2-(methylthio)oxirane (9 g, 0.1 mol) was mixed with 90 mL of isopropanol solvent, iodine (0.38 g, 0.0015 mol) was added, and then 13.6 g of hydrogen peroxide (30%) was added dropwise. The temperature was controlled at 35 - 38 °C, and the reaction was carried out for 5 hours. After cooling to room temperature, 30 mL of saturated sodium thiosulfate aqueous solution and 30 mL of saturated sodium bicarbonate aqueous solution were added for neutralization. The mixture was extracted twice with 100 mL of dichloromethane. The organic layers were combined, concentrated, and the crude product was distilled under reduced pressure to obtain 8.2 g of 2-[(oxiran-2-ylmethyldisulfanyl)methyl]oxirane, with a yield of 92.4%. The GC analysis showed the same peak as the standard product.

[0051] Example 7

[0052]

[0053] Under nitrogen protection, thiourea (17.1 g, 0.225 mol), montmorillonite 0.27 g and trifluoroethanol (2 g, 0.02 mol) were mixed in 150 mL of acetonitrile. The temperature was controlled at 0 - 10 °C, and 2-[(oxiran-2-ylmethyldisulfanyl)methyl]oxirane (17.8 g, 0.1 mol) was added dropwise. Then the temperature was raised to 30 - 35 °C, and the reaction was carried out for 6 hours. After cooling to room temperature, the mixture was filtered and concentrated. The crude product was diluted with 120 mL of cyclohexane and washed twice with 60 mL of deionized water. The organic layer was concentrated and distilled under reduced pressure to obtain 17.9 g of bis(2,3-epithiopropyl) disulfide, with a yield of 85.1%. The GC analysis showed the same peak as the standard product. 1 H NMR(400MHz,CDCl3):3.20 - 3.16(m,2H),2.76 - 2.69(m,1H),2.60 - 2.59(m,1H),2.36 - 2.35(m,1H); 13 C NMR(101MHz,CDCl3):45.3,33.3,25.9。

[0054] As described above, it is only the preferred specific embodiment of the present invention, but the protection scope of the present invention is not limited thereto. Any person skilled in the art within the technical scope disclosed by the present invention, according to the technical solution and inventive concept of the present invention, makes equivalent substitutions or changes, and all should be covered within the protection scope of the present invention.

Claims

1. A method for preparing bis(2,3-epithiopropyl)disulfide, characterized in that: The steps include: Step S1: epichlorohydrin, thioacetate and tetrabutylammonium iodide are mixed in water, potassium carbonate is slowly added at room temperature, the temperature is raised to 30-35° C., and the reaction is carried out for 5-8 hours to obtain 2-(acetylthiomethyl)ethylene oxide. Step S2: Mix 2-(acetylthiomethyl)oxirane with an alcohol solvent, add concentrated hydrochloric acid to obtain 2-(methylthiol)oxirane. Step S3: Mix 2-(methylmercaptan)ethylene oxide with an alcohol solvent, add iodine, then drop hydrogen peroxide, and control the temperature to react at 35-38°C to obtain 2-[(oxirane-2-ylmethyldisulfanyl)methyl]ethylene oxide; or mix 2-(methylmercaptan)ethylene oxide with ethanol, add sulfur powder and sodium hydroxide, and reflux to obtain 2-[(oxirane-2-ylmethyldisulfanyl)methyl]ethylene oxide. Step S4: thiourea, acetonitrile, montmorillonite and trifluoroethanol are mixed, 2-[(oxiran-2-ylmethyldisulfanyl)methyl]oxirane is added dropwise at a temperature of 0-10°C, and then the temperature is raised to 30-35°C for reaction for 6 hours to obtain bis(2,3-epithiopropyl)disulfide.

2. The method for preparing bis(2,3-epithiopropyl)disulfide according to claim 1, characterized in that: In step S1, the thioacetate is selected from potassium thioacetate or sodium thioacetate.

3. The method for preparing bis(2,3-epithiopropyl)disulfide according to claim 1, characterized in that: In step S1, the molar ratio of epichlorohydrin, thioacetate, tetrabutylammonium iodide and potassium carbonate is 1:1.3-1.5:0.01-0.03:1.8-2.

0.

4. The method for preparing bis(2,3-epithiopropyl)disulfide according to claim 1, characterized in that: In step S2, the alcohol solvent is selected from methanol or ethanol.

5. The method for preparing bis(2,3-epithiopropyl)disulfide according to claim 1, characterized in that: In step S2, the molar ratio of 2-(acetylthiomethyl)ethylene oxide to concentrated hydrochloric acid is 1:1.4-1.

6.

6. The method for preparing bis(2,3-epithiopropyl)disulfide according to claim 1, characterized in that: In step S3, the alcohol solvent is selected from ethanol or isopropanol.

7. The method for preparing bis(2,3-epithiopropyl)disulfide according to claim 1, characterized in that: In step S3, the molar ratio of the 2-(methylmercaptan)ethylene oxide, iodine and hydrogen peroxide is 1:0.01-0.02:1.1-1.

3.

8. The method for preparing bis(2,3-epithiopropyl)disulfide according to claim 1, characterized in that: In step S3, the molar ratio of the 2-(methylmercaptan)ethylene oxide, sulfur powder and sodium hydroxide is 1:8-9:1.0-1.

3.

9. The method for preparing bis(2,3-epithiopropyl)disulfide according to claim 1, characterized in that: In step S4, the molar ratio of thiourea, trifluoroethanol and 2-[(oxirane-2-ylmethyldisulfanyl)methyl]oxirane is 2.2-2.3:0.1-0.3:

1.

10. The method for preparing bis(2,3-epithiopropyl)disulfide according to claim 1, characterized in that: In step S4, the mass ratio of the 2-[(oxirane-2-ylmethyldisulfanyl)methyl]oxirane to montmorillonite is 1:0.01-0.02.

Images