A process for the preparation of bis(2,3-cyclopropylthio)disulfide

Abstract

The application discloses a preparation method of bis(2,3-cyclopropyl sulfide) disulfide and belongs to the technical field of organic synthesis. Epoxy chloropropane is reacted with thioacetate to obtain 2-(acetyl thiomethyl) oxirane; then, the acetyl group is removed by reaction with hydrochloric acid; then, the 2-(acetyl thiomethyl) oxirane is reacted with hydrogen peroxide under the catalysis of iodine or is reacted with sulfur powder and sodium hydroxide; finally, the 2-(acetyl thiomethyl) oxirane is reacted with thiourea to obtain bis(2,3-cyclopropyl sulfide) disulfide. In the application, chloroepoxy propane is used as a raw material, and intermediates in the whole reaction process can be purified, the purity of the final product is high, the obtained product can be used for high refractive index resin lenses (refractive index is greater than or equal to 1.70) and high-temperature-resistant optical coatings, and the product meets the requirements of the electronic and medical fields.

Description

TECHNICAL FIELD

[0001] The application relates to a preparation method of bis(2,3-dithiapropyl) disulfide and belongs to the technical field of organic synthesis. BACKGROUND

[0002] High-refractive resin lenses require light weight, high refractive index, and the addition of dithiapolyether resin can improve the refractive index. Bis(2,3-dithiapropyl) disulfide is a sulfur-containing cyclic compound, and its high sulfur content (50-85%) makes it have excellent refractive index and heat resistance in optical materials, and it is suitable for high-refractive resin lenses, medical intermediates, optical materials and electronic fields, and its main advantage is that it can significantly reduce the volume of optical elements, improve the optical path design, and improve the optical performance. However, the biggest problem of bis(2,3-dithiapropyl) disulfide is that the synthesis product has low purity, high nitrogen content and many by-products, and it is difficult to purify.

[0003] Mitsui Chemical (JP6200124; EP2805949) and South Korea KOC (KR2016100422) adopt bis(3-chloro-2-hydroxypropyl) disulfide to close ring under the action of sodium hydroxide, and then react with thiourea to obtain bis(2,3-dithiapropyl) disulfide. In this method, the raw material 1-chloro-3-mercapto-2-propanol is not easy to obtain. The reaction equation is expressed as follows:

[0004]

[0005] To solve the above problems, the application provides a preparation method of bis(2,3-dithiapropyl) disulfide. The raw material is easy to obtain, the operation is simple, the nitrogen content is reduced by double adsorption of activated carbon and anhydrous magnesium sulfate, and the purity is improved by low-temperature crystallization. The bis(2,3-dithiapropyl) disulfide with high purity and low nitrogen content is obtained, thereby meeting the demand. SUMMARY

[0006] In order to overcome the above technical defects, the application provides a preparation method of bis(2,3-dithiapropyl) disulfide. Epoxy chloropropane is reacted with thioacetate to obtain 2-(acetylthiomethyl) oxirane; then, the acetyl group is removed by reaction with hydrochloric acid to obtain 2-(methylthiol) oxirane; then, 2-[(oxirane-2-ylmethyl disulfanyl) methyl] oxirane is obtained by reaction with hydrogen peroxide under the catalysis of iodine or by reaction with sulfur powder and sodium hydroxide; finally, bis(2,3-dithiapropyl) disulfide is obtained by reaction with thiourea. The raw material is easy to obtain, the cost is low, and it is suitable for industrial production. The obtained product can be used for high-refractive resin lenses (refractive index > 1.70) and high-temperature-resistant optical coatings, and meets the demand of electronic and medical fields.

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

[0008]

[0009] comprising the following steps:

[0010] Step S1: mixing epichlorohydrin, thioacetate and tetrabutylammonium iodide in water, slowly adding potassium carbonate at room temperature, warming to 30-35℃, and reacting for 5-8 hours to obtain 2-(acetylthiomethyl)oxirane.

[0011] Step S2: mixing 2-(acetylthiomethyl)oxirane with an alcohol solvent, and adding concentrated hydrochloric acid to obtain 2-(methylthiol)oxirane.

[0012] Step S3: mixing 2-(methylthiol)oxirane with an alcohol solvent, adding iodine, and then adding hydrogen peroxide dropwise to control the temperature at 35-38℃ to obtain 2-[(oxirane-2-ylmethyl disulfanyl)methyl]oxirane; or mixing 2-(methylthiol)oxirane with ethanol, adding sulfur powder and sodium hydroxide, and refluxing to obtain 2-[(oxirane-2-ylmethyl disulfanyl)methyl]oxirane.

[0013] Step S4: mixing thiourea, acetonitrile, montmorillonite and trifluoroethanol, and adding 2-[(oxirane-2-ylmethyl disulfanyl)methyl]oxirane dropwise while controlling the temperature at 0-10℃, and then warming to 30-35℃ and reacting 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 the 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 the 2-(acetylthiomethyl)oxirane and 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 the 2-(methylthiol)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 the 2-(methylmercapto)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 the thiourea, trifluoroethanol and 2-[(oxirane-2-ylmethyl disulfanyl)methyl]oxirane is 2.2-2.3:0.1-0.3:1.

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

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

[0024] 1. The inexpensive and readily available chloro-propylene oxide is used as the raw material, the intermediates in the whole reaction process can be purified, the purity of the final product is high, and the economic benefit is good.

[0025] 2. The combination of iodine and hydrogen peroxide is used for catalysis, the yield is high, and the catalytic effect is good.

[0026] 3. The raw materials of the process are easily available in the market, the process is simple, safe and stable, and is suitable for industrial scale-up. BRIEF DESCRIPTION OF DRAWINGS

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

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

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

[0030] Example 1

[0031]

[0032] Epoxy chloropropane (9.25 g, 0.1 mol), sodium thioacetate (13.7 g, 0.14 mol) and tetrabutyl ammonium iodide (0.74 g, 0.002 mol) were mixed in 200 mL water under nitrogen protection, potassium carbonate (26.3 g, 0.19 mol) was added slowly at room temperature, the temperature was raised to 30-35 °C, the reaction was carried out for 7 hours, the temperature was lowered to room temperature, 80 mL dichloromethane was added and extracted twice, concentrated, distilled under reduced pressure, 2-(acetylthiomethyl) oxirane 11.2 g was obtained, the yield was 85.2%. LC-MS [M+H] + = 133.2.

[0033] Example 2

[0034]

[0035] Epoxy chloropropane (9.25 g, 0.1 mol), sodium thioacetate (13.7 g, 0.14 mol) and tetrabutyl ammonium iodide (0.74 g, 0.002 mol) were mixed in 200 mL water under nitrogen protection, potassium carbonate (26.3 g, 0.19 mol) was added slowly at room temperature, the temperature was raised to 30-35 °C, the reaction was carried out for 7 hours, the temperature was lowered to room temperature, 80 mL dichloromethane was added and extracted twice, concentrated, distilled under reduced pressure, 2-(acetylthiomethyl) oxirane 11.2 g was obtained, the yield was 85.2%. LC-MS [M+H]

[0036] Example 3

[0037]

[0038] Epoxy chloropropane (9.25 g, 0.1 mol), sodium thioacetate (13.7 g, 0.14 mol) and tetrabutyl ammonium iodide (0.74 g, 0.002 mol) were mixed in 200 mL water under nitrogen protection, potassium carbonate (26.3 g, 0.19 mol) was added slowly at room temperature, the temperature was raised to 30-35 °C, the reaction was carried out for 7 hours, the temperature was lowered to room temperature, 80 mL dichloromethane was added and extracted twice, concentrated, distilled under reduced pressure, 2-(acetylthiomethyl) oxirane 11.2 g was obtained, the yield was 85.2%. LC-MS [M+H] + = 133.2.

[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 reaction was refluxed for 3 hours. After cooling to room temperature, saturated aqueous sodium bicarbonate solution was added, the pH was adjusted to 6-7, methanol was removed by distillation under reduced pressure, 70 mL of dichloromethane was added and extracted twice, the organic layer was concentrated and distilled under reduced pressure to obtain 2-(methylthio)oxirane 8.0 g, yield 89.2%, GC analysis was consistent with the standard.

[0042] Example 5

[0043]

[0044] Under nitrogen protection, 2-(methylthio)oxirane (9 g, 0.1 mol) was mixed with 90 mL of ethanol solvent, 0.38 g of iodine (0.0015 mol) was added, followed by dropwise addition of 13.6 g of hydrogen peroxide (30%), the temperature was controlled at 35-38°C, the reaction was carried out for 5 hours, and then cooled to room temperature. Subsequently, 30 mL of saturated aqueous sodium thiosulfate solution was added, 30 mL of saturated aqueous sodium bicarbonate solution was added, 100 mL of dichloromethane was extracted twice, the organic layer was combined, concentrated, and the crude product was distilled under reduced pressure to obtain 2-[(oxirane-2-ylmethyl disulfanyl)methyl]oxirane 8.5 g, yield 95.1%, GC analysis was consistent with the standard. LC-MS [M+H] + = 179.3.

[0045] Comparative Example 5

[0046]

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

[0048] Example 6

[0049]

[0050] Thionyl chloride (0.5 mL, 0.007 mol) was added to 2-[(oxirane-2- ylmethyl disulfanyl)methyl]oxirane (1.0 g, 0.005 mol) in 10 mL of dichloromethane at 0-5°C. The reaction mixture was stirred for 2 hours at 0-5°C, then warmed to room temperature and stirred for 6 hours. The reaction mixture was cooled to 0-5°C and quenched with 10 mL of saturated sodium bicarbonate solution. The organic layer was separated and concentrated under reduced pressure. The crude product was purified by column chromatography using 10% ethyl acetate in hexane to obtain 2-[(oxirane-2-ylmethylsulfanyl)methyl]oxirane (0.8 g, 0.004 mol, 80% yield) which was confirmed by GC analysis with the standard.

[0051] Example 7

[0052]

[0053] Thiourea (17.1 g, 0.225 mol), montmorillonite clay 0.27 g and trifluoroethanol (2 g, 0.02 mol) were mixed in 150 mL of acetonitrile under nitrogen atmosphere. The temperature was maintained at 0-10°C and 2-[(oxirane-2-ylmethyl disulfanyl)methyl]oxirane (17.8 g, 0.1 mol) was added dropwise. The temperature was then raised to 30-35°C and the reaction mixture was stirred for 6 hours. The reaction mixture was cooled to room temperature, filtered and concentrated. The crude product was diluted with 120 mL of cyclohexane and washed with 60 mL of deionized water twice. The organic layer was concentrated and distilled under reduced pressure to obtain bis(2,3-dithiapropyl) disulfide (17.9 g, 85.1% yield) which was confirmed by GC analysis with the standard. 1 H NMR (400 MHz, CDC13): 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 (101 MHz, CDC13): 45.3, 33.3, 25.9.

[0054] The above description is merely preferred embodiments of the present application, but the protection scope of the present application is not limited thereto. Any person skilled in the art, according to the technical range disclosed in the present application and the inventive concept, can make equivalent replacements or changes, and all of them should be covered in the protection scope of the present application.

Claims

1. A method for preparing bis(2,3-cyclothiopropyl) disulfide, characterized in that, Includes the following steps: Step S1: Epichlorohydrin, thioacetate, and tetrabutylammonium iodide are mixed in water, and potassium carbonate is slowly added at room temperature. The mixture is heated to 30-35°C and reacted for 5-8 hours to obtain 2-(acetylthiomethyl)epoxyethylene. The thioacetate is selected from potassium thioacetate or sodium thioacetate. 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. Step S2: Mix 2-(acetylthiomethyl)ethylene oxide with an alcohol solvent, add concentrated hydrochloric acid, and obtain 2-(methanethiol)ethylene oxide; Step S3: Mix 2-(methanethiol)ethylene oxide with an alcohol solvent, add iodine, then add hydrogen peroxide dropwise, and react at a controlled temperature of 35-38℃ to obtain 2-[(ethylene oxide-2-ylmethyldithioalkyl)methyl]ethylene oxide; or mix 2-(methanethiol)ethylene oxide with ethanol, add sulfur powder and sodium hydroxide, and reflux to obtain 2-[(ethylene oxide-2-ylmethyldithioalkyl)methyl]ethylene oxide; Step S4: Thiourea, acetonitrile, montmorillonite, and trifluoroethanol are mixed, and 2-[(ethylene oxide-2-ylmethyldithioalkyl)methyl]ethylene oxide is added dropwise while controlling the temperature at 0-10℃. Then, the temperature is raised to 30-35℃ and reacted for 6 hours to obtain bis(2,3-cyclothiopropyl)disulfide. The molar ratio of thiourea, trifluoroethanol, and 2-[(ethylene oxide-2-ylmethyldithioalkyl)methyl]ethylene oxide is 2.2-2.3:0.1-0.3:

1. The mass ratio of 2-[(ethylene oxide-2-ylmethyldithioalkyl)methyl]ethylene oxide to montmorillonite is 1:0.01-0.

02.

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

3. The method for preparing bis(2,3-cyclothiopropyl) 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.

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

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

3.

6. The method for preparing bis(2,3-cyclothiopropyl) disulfide according to claim 1, characterized in that: In step S3, the molar ratio of 2-(methanethiol) ethylene oxide, sulfur powder, and sodium hydroxide is 1:8-9:1.0-1.3.

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