Preparation method of diphenyl disulfide
Diphenyldisulfide is directly synthesized by one pot method, using halogenated benzene and magnesium powder to form Grignard reagent, and then reacts with disulfide dichloride, solving the problem of complex use of highly toxic raw materials and processes in the prior art, realizing the An efficient, environmentally friendly and low-cost preparation method.
Patent Information
- Application Number
- CN202411586548.9
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-11-08
- Publication Date
- 2025-02-07
AI Technical Summary
The existing preparation methods for diphenyldisulfide have problems such as phenylthiophene, complex processes, and environmental pollution, and are difficult to recover catalysts and have high costs.
Diphenyl disulfide is directly synthesized by one pot method, and the reaction is carried out with halogenated benzene and magnesium powder to form Grignard reagent, and then react with disulfide dichloride. The reaction conditions are controlled through solvent dilution and slow drop addition to avoid side reactions. .
It realizes efficient preparation of heavy metal-free catalysts, with simple process, environmental protection, high yield and purity, and reduces production costs.
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Abstract
Description
Technical Field
[0001] The invention belongs to the technical field of organic synthesis and relates to a method for preparing diphenyl disulfide. Background Art
[0002] Diphenyl disulfide is an important type of pharmaceutical intermediate, widely used in medicine, pesticides, dye intermediates, chemical industry and other fields.
[0003] At present, the following methods are commonly used in industry to synthesize diphenyl disulfide: thiophenol oxidation method, halobenzene / sodium disulfide substitution method and benzenesulfonyl chloride reduction method. Among them, in the commonly used thiophenol oxidation method, benzenethiophenol is a colorless liquid with a foul odor at room temperature, with active chemical properties, highly toxic and explosive. The process synthesis route using benzenethiophenol as the starting material is long, the reaction conditions are demanding, and the environmental pollution is large; the halobenzene / sodium disulfide substitution method requires the introduction of a phase transfer catalyst due to the low reaction activity of halobenzene, which has problems such as difficulty in catalyst recovery and complex post-processing; the benzenesulfonyl chloride method is widely used due to its simple raw material source; the methods for preparing diphenyl disulfide from benzenesulfonyl chloride include hydrazine reduction method, metal / acid reduction method, metal / TiCl4 reduction method and low-valent oxygen-philic d-zone metal reduction method. Among them, the reducing agent used in the hydrazine reduction method is relatively expensive; the metal / acid and metal / TiCl4 reduction methods consume a large amount of metal, the process is not clean, the post-treatment is complicated, and the yield is not high; the halide boron / potassium iodide reduction method requires the addition of a phase transfer catalyst TBAI and the reaction time (16h) is relatively long; the reducing agent used in the low-valent oxygen-philic d-zone metal reduction method is sensitive to air oxidation, difficult to store on a large scale, and the reducing agent cost is also correspondingly high.
[0004] Based on this, it is necessary to study a low-cost and simple method for preparing diphenyl disulfide compounds. Summary of the invention
[0005] The invention provides a method for preparing diphenyl disulfide. The method does not require a heavy metal catalyst, can be directly synthesized in one pot, is green and environmentally friendly, has a high conversion rate, a high yield and a high purity, and a simple process.
[0006] The technical solution of the present invention is achieved in this way: A method for preparing diphenyl disulfide comprises the following steps: A. In a dry and inert atmosphere, mix halogenated benzene and magnesium powder to react to form a Grignard reagent, and cool to 0-15°C; B. Dissolve disulfur dichloride in a solvent, then drop it into the Grignard reagent obtained in step A, stir and react at 0-15° C., quench the reaction with a saturated aqueous ammonium chloride solution, extract, dry and concentrate the organic phase to obtain diphenyl disulfide; The molar ratio of the halogenated benzene, magnesium powder and disulfur dichloride is 2:1.8-2.1:1-1.2; The solvent is selected from one or two of 1,4-dioxane, tetrahydrofuran and N,N-dimethylacetamide; Preferably, the solvent is tetrahydrofuran and N,N-dimethylacetamide in a volume ratio of 1:2.
[0007] Preferably, the usage ratio of the disulfur dichloride and the solvent is 0.1 mol: 15-30 ml.
[0008] Preferably, the dropping speed of the disulfur dichloride should be controlled at 15-30 drops per minute.
[0009] Preferably, in the step A, halogenated benzene is dissolved in an organic solvent to obtain a halogenated benzene solution, and then one-fifth to one-third of the halogenated benzene solution is mixed with magnesium powder, and then iodine is added to initiate the reaction, and the remaining halogenated benzene solution is added dropwise. During the process, the temperature is controlled at 40-60° C. After the addition is completed, the reaction is continued to stir for 1.5-2 hours to generate a Grignard reagent.
[0010] Preferably, the mass ratio of the iodine element to the magnesium powder is 0.005-0.1:1.
[0011] Preferably, the organic solvent is tetrahydrofuran and / or diethyl ether.
[0012] Preferably, the usage ratio of the halogenated benzene and the organic solvent is 0.2 mol: 100-180 ml.
[0013] Preferably, the halogenated benzene is iodobenzene, bromobenzene or chlorobenzene.
[0014] Preferably, in step B, ethyl acetate is used to extract the organic phase, and anhydrous sodium sulfate or anhydrous magnesium sulfate is used for drying.
[0015] The working principle and beneficial effects of the present invention are: 1. In the present invention, cheap and readily available halogenated benzene is used as a synthetic raw material to synthesize a Grignard reagent, which is then reacted with disulfur dichloride to obtain diphenyl disulfide. The entire method process does not require a heavy metal catalyst, is directly synthesized in one pot, is green and environmentally friendly, and has high yield and purity.
[0016] 2. In the present invention, disulfur dichloride is dissolved in a solvent and then dripped into the Grignard reagent. In this step, the solvent can well dissolve disulfur dichloride and the Grignard reagent, so that the reactants can fully contact and react with each other; at the same time, through solvent dilution, the reactants can be mixed more evenly, so that the reaction is easier to carry out, the occurrence of side reactions is reduced, and the yield is improved; the diluted solution can make the reaction more gentle and avoid the by-products generated by the overly violent reaction; and the slow dripping can better control the reaction rate and make the reaction more controllable and uniform; the solvents 1,4-dioxane, tetrahydrofuran and N,N-dimethylacetamide used in the present invention are very stable under anhydrous conditions and will not have unnecessary side reactions with the Grignard reagent; further, on the premise of improving the mutual solubility of disulfur dichloride and the Grignard reagent and maintaining their reaction activity, the temperature can be controlled at 0-15°C, which effectively reduces the occurrence of side reactions and improves the selectivity and yield of the product. BRIEF DESCRIPTION OF THE DRAWINGS
[0017] The present invention will be further described in detail below in conjunction with the accompanying drawings and specific embodiments.
[0018] Figure 1 This is the 1H NMR characterization spectrum of diphenyl disulfide synthesized in Example 1 of the present invention. DETAILED DESCRIPTION
[0019] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.
[0020] Example 1 A method for preparing diphenyl disulfide comprises the following steps: A. Dissolve 0.2 mol bromobenzene in 120 ml tetrahydrofuran to obtain a bromobenzene solution. Add 5.1 g magnesium powder to a dry three-necked flask filled with nitrogen gas, then add a quarter of the halogenated benzene solution, and then add 0.05 g of iodine to initiate the reaction. Stir vigorously. After the reaction system starts to bubble, add the remaining halogenated benzene solution dropwise within 20 minutes. During the process, control the temperature at 50 ° C. After the addition is completed, continue to stir the reaction for 1.5 hours and cool to 5 ° C. B. Dissolve 0.1 mol of disulfur dichloride in 7 ml of tetrahydrofuran and 14 ml of N,N-dimethylacetamide, and then drip into the Grignard reagent obtained in step A at a rate of 20 drops per minute, stir and react at 5°C for 2 h, quench the reaction with saturated aqueous ammonium chloride solution, extract the organic phase with ethyl acetate, dry the organic phase with anhydrous sodium sulfate, and concentrate the organic phase to obtain 20.42 g of solid diphenyl disulfide, with a yield of 93.52% and a purity of 97.25%.
[0021] Example 2 A method for preparing diphenyl disulfide comprises the following steps: A. Dissolve 0.2 mol of chlorobenzene in 100 ml of tetrahydrofuran to obtain a chlorobenzene solution. Add 4.4 g of magnesium powder to a dry three-necked flask filled with nitrogen gas, then add one-fifth of the halogenated benzene solution, and then add 0.03 g of iodine to initiate the reaction. Stir vigorously. After the reaction system starts to bubble, add the remaining halogenated benzene solution dropwise within 20 minutes. During the process, control the temperature at 60 ° C. After the addition is completed, continue to stir the reaction for 2 hours and cool to 15 ° C. B. Dissolve 0.11 mol of disulfur dichloride in 17 ml of N,N-dimethylacetamide, then drip into the Grignard reagent obtained in step A at a rate of 30 drops per minute, stir and react at 15°C for 3 hours, quench the reaction with saturated aqueous ammonium chloride solution, extract the organic phase with ethyl acetate, dry the organic phase with anhydrous sodium sulfate, and concentrate the organic phase to obtain 19.91 g of solid diphenyl disulfide, with a yield of 91.19% and a purity of 97.12%.
[0022] Example 3 A method for preparing diphenyl disulfide comprises the following steps: A. Dissolve 0.2 mol iodobenzene in 180 ml ether to obtain iodobenzene solution. Add 4.5 g magnesium powder to a dry three-necked flask filled with nitrogen gas, then add a quarter of the halogenated benzene solution, and then add 0.03 g iodine to initiate the reaction. Stir vigorously. After the reaction system starts to bubble, add the remaining halogenated benzene solution dropwise within 20 minutes. Control the temperature at 40 ° C during the process. After the addition is completed, continue to stir the reaction for 1.5 hours and cool to 0 ° C. B. Dissolve 0.12 mol of disulfur dichloride in 30 ml of 1,4-dioxane, then drip into the Grignard reagent obtained in step A at a rate of 15 drops per minute, stir and react at 0°C for 1 hour, quench the reaction with saturated aqueous ammonium chloride solution, extract the organic phase with ethyl acetate, dry the organic phase with anhydrous sodium sulfate, and concentrate the organic phase to obtain solid diphenyl disulfide 19.72 with a yield of 90.32% and a purity of 97.08%.
[0023] Example 4 A method for preparing diphenyl disulfide comprises the following steps: A. Dissolve 0.2 mol bromobenzene in 120 ml tetrahydrofuran to obtain a bromobenzene solution. Add 5.1 g magnesium powder to a dry three-necked flask filled with nitrogen gas, then add a quarter of the halogenated benzene solution, and then add 0.05 g of iodine to initiate the reaction. Stir vigorously. After the reaction system starts to bubble, add the remaining halogenated benzene solution dropwise within 20 minutes. During the process, control the temperature at 50 ° C. After the addition is completed, continue to stir the reaction for 1.5 hours and cool to 5 ° C. B. Dissolve 0.1 mol of disulfur dichloride in 21 ml of tetrahydrofuran, then drip into the Grignard reagent obtained in step A at a rate of 20 drops per minute, stir and react at 5° C. for 2 h, quench the reaction with saturated aqueous ammonium chloride solution, extract the organic phase with ethyl acetate, dry the organic phase with anhydrous sodium sulfate, and concentrate the organic phase to obtain 19.49 g of solid diphenyl disulfide, with a yield of 89.26% and a purity of 97.26%.
[0024] Example 5 A method for preparing diphenyl disulfide comprises the following steps: A. Dissolve 0.2 mol bromobenzene in 120 ml tetrahydrofuran to obtain a bromobenzene solution. Add 5.1 g magnesium powder to a dry three-necked flask filled with nitrogen gas, then add a quarter of the halogenated benzene solution, and then add 0.05 g of iodine to initiate the reaction. Stir vigorously. After the reaction system starts to bubble, add the remaining halogenated benzene solution dropwise within 20 minutes. During the process, control the temperature at 50 ° C. After the addition is completed, continue to stir the reaction for 1.5 hours and cool to 5 ° C. B. Dissolve 0.1 mol of disulfur dichloride in 21 ml of N,N-dimethylacetamide, then drip into the Grignard reagent obtained in step A at a rate of 20 drops per minute, stir and react at 5°C for 2 hours, quench the reaction with saturated aqueous ammonium chloride solution, extract the organic phase with ethyl acetate, dry the organic phase with anhydrous sodium sulfate, and concentrate the organic phase to obtain 19.70 g of solid diphenyl disulfide, with a yield of 90.23% and a purity of 97.04%.
[0025] Comparative Example 1 A method for preparing diphenyl disulfide comprises the following steps: A. Dissolve 0.2 mol bromobenzene in 120 ml tetrahydrofuran to obtain a bromobenzene solution. Add 5.1 g magnesium powder to a dry three-necked flask filled with nitrogen gas, then add a quarter of the halogenated benzene solution, and then add 0.05 g of iodine to initiate the reaction. Stir vigorously. After the reaction system starts to bubble, add the remaining halogenated benzene solution dropwise within 20 minutes. During the process, control the temperature at 50 ° C. After the addition is completed, continue to stir the reaction for 1.5 hours and cool to 5 ° C. B. Add 0.1 mol of disulfur dichloride to the Grignard reagent obtained in step A at a rate of 20 drops per minute, stir and react at 5° C. for 2 h, quench the reaction with saturated aqueous ammonium chloride solution, extract the organic phase with ethyl acetate, dry the organic phase with anhydrous sodium sulfate, and concentrate the organic phase to obtain 18.63 g of solid diphenyl disulfide, with a yield of 85.33% and a purity of 93.02%.
[0026] The above are only preferred embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the protection scope of the present invention.
Claims
1. A method for preparing diphenyl disulfide, characterized in that: The following steps are involved: A. In a dry and inert atmosphere, mix halogenated benzene and magnesium powder to react to form a Grignard reagent, and cool to 0-15°C; B. Dissolve disulfur dichloride in a solvent, then dropwise add it into the Grignard reagent obtained in step A, stir and react at 0-15° C., quench the reaction with a saturated aqueous ammonium chloride solution, extract, dry and concentrate the organic phase to obtain diphenyl disulfide; The molar ratio of the halogenated benzene, magnesium powder and disulfur dichloride is 2:1.8-2.1:1-1.2; The solvent is selected from one or two of 1,4-dioxane, tetrahydrofuran and N,N-dimethylacetamide.
2. The method for preparing diphenyl disulfide according to claim 1, characterized in that: The solvent is tetrahydrofuran and N,N-dimethylacetamide in a volume ratio of 1:
2.
3. The method for preparing diphenyl disulfide according to claim 1, characterized in that: The usage ratio of the disulfur dichloride and the solvent is 0.1 mol: 15-30 ml.
4. The method for preparing diphenyl disulfide according to claim 1, characterized in that: The dropping speed of the disulfur dichloride should be controlled at 15-30 drops per minute.
5. The method for preparing diphenyl disulfide according to claim 1, characterized in that: In the step A, halogenated benzene is dissolved in an organic solvent to obtain a halogenated benzene solution, and then one-fifth to one-third of the halogenated benzene solution is mixed with magnesium powder, and then iodine is added to initiate the reaction, and the remaining halogenated benzene solution is added dropwise. During the process, the temperature is controlled at 40-60° C. After the addition is completed, the reaction is continued to stir for 1.5-2 hours to generate a Grignard reagent.
6. The method for preparing diphenyl disulfide according to claim 5, characterized in that: The mass ratio of the iodine element to the magnesium powder is 0.005-0.1:
1.
7. The method for preparing diphenyl disulfide according to claim 5, characterized in that: The organic solvent is tetrahydrofuran and / or ether.
8. The method for preparing diphenyl disulfide according to claim 5, characterized in that: The usage ratio of the halogenated benzene and the organic solvent is 0.2 mol: 100-180 ml.
9. The method for preparing diphenyl disulfide according to claim 1, characterized in that: The halogenated benzene is iodobenzene, bromobenzene or chlorobenzene.
10. The method for preparing diphenyl disulfide according to claim 1, characterized in that: In step B, the organic phase is extracted with ethyl acetate and dried with anhydrous sodium sulfate or anhydrous magnesium sulfate.