Zirconium catalyst-based sulfoxide synthesis method
By using SOCl2 and zirconium catalysts under mild reaction conditions, the problems of harsh reaction conditions, strong catalyst dependence and insufficient environmental friendliness in the existing diaryl sulfoxide synthesis method are solved, and efficient and environmentally friendly diaryl sulfoxide synthesis is achieved.
Patent Information
- Application Number
- CN202411712505.0
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-11-27
- Publication Date
- 2025-03-14
AI Technical Summary
The existing synthesis method of diaryl sulfoxide has problems such as harsh reaction conditions, strong catalyst dependence and insufficient environmental friendliness, resulting in complex processes, poor safety, high costs and environmental pollution.
The sulfoxide synthesis method based on zirconium catalyst is adopted, and the efficient synthesis of diaryl sulfoxide is achieved by using SOCl2 as the sulfur source under mild reaction conditions and using zirconium catalyst as the catalyst. The method includes steps: preparing a solvent, adding reactants, adding SOCl2, adding zirconium catalyst, carrying out the reaction, post-treatment, organic phase purification and product purification.
High-purity diaryl sulfoxide is obtained under mild reaction conditions, which improves reaction efficiency and selectivity, reduces the risk of environmental pollution, and is suitable for industrial production.
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Figure CN119613371A_ABST
Abstract
Description
Technical Field
[0001] The invention relates to the field of chemical synthesis, and more particularly to a sulfoxide synthesis method based on a zirconium catalyst. Background Art
[0002] Diaryl sulfoxides are a class of widely used organic sulfides that play an important role in medicine, pesticides, material chemistry, and organic synthesis. Due to their unique chemical properties, diaryl sulfoxides are often used in high-performance polymer materials, drug molecule synthesis, and catalyst design.
[0003] Existing methods for synthesizing diaryl sulfoxides mainly include the following
[0004] ① Oxidation of sulfide: This is the traditional synthesis route of diaryl sulfoxide, and diaryl sulfide is usually oxidized using peroxide or other oxidants. However, oxidation reactions often require strong oxidants such as hydrogen peroxide (H2O2), perchloric acid (HClO4) or selenium dioxide (SeO2). The use of these oxidants will bring environmental problems, and the reaction conditions are harsh, which is not conducive to industrial production.
[0005] ② Reaction of aryl halides with aryl thiols: Diaryl sulfoxides can also be synthesized by nucleophilic substitution reactions of aryl halides with aryl thiols. However, such reactions often require high temperatures or strong base conditions and may generate a variety of by-products, making it difficult to separate and purify the products.
[0006] ③Metal-catalyzed coupling reaction: In recent years, with the development of organometallic catalytic technology, transition metal catalysts have been widely used in the synthesis of diaryl sulfoxides. Although metal-catalyzed coupling reactions have high selectivity and reaction efficiency, they usually require the use of precious metal catalysts, which has high reaction costs, and metal residues have a negative impact on the environment and product quality.
[0007] The problems existing in the prior art are mainly reflected in the following aspects:
[0008] ① Harsh reaction conditions: For example, oxidation reactions usually require strong oxidants or extreme temperature conditions, resulting in complex processes and poor safety.
[0009] ② Strong dependence on catalysts: Many methods rely on expensive metal catalysts, which increases the cost of synthesis and makes catalyst recovery difficult.
[0010] ③ Insufficient environmental friendliness: The large-scale use of oxidants and heavy metal catalysts will cause environmental pollution problems, restricting the green development of the process.
[0011] Therefore, further optimization of the synthesis method is urgently needed. Summary of the invention
[0012] The present invention aims to provide a more optimized method for synthesizing diaryl sulfoxide in view of the deficiencies in the prior art. By this method, high-purity diaryl sulfoxide can be obtained under mild reaction conditions, and has high reaction efficiency and good environmental friendliness. The specific scheme is as follows:
[0013] A sulfoxide synthesis method based on a zirconium catalyst, the synthesis method comprising the following steps:
[0014] S1. Prepare the solvent: add anhydrous dichloromethane as the solvent into the reaction flask;
[0015] S2, adding reactants: adding the starting aromatic compound to the solvent at a molar ratio of 1:1;
[0016] S3, adding the reagent SOCl2: slowly add SOCl2 dropwise to the reaction mixture, and keep the temperature low to control the reaction exotherm;
[0017] S4, catalyst addition: adding zirconium catalyst;
[0018] S5, reaction: the reaction system is heated from low temperature to room temperature, and then gradually heated to between 60 and 80°C;
[0019] S6. Post-reaction treatment: After the reaction is completed, cool to room temperature, add an appropriate amount of water to quench the reaction, and decompose the residual SOCl2 into harmless by-products; separate the organic phase from the aqueous phase by a separatory funnel, and collect the organic phase;
[0020] S7, organic phase purification: drying and concentrating the organic phase;
[0021] S8. Product purification: Purify the crude product using column chromatography.
[0022] The preparation process of the zirconium catalyst is as follows:
[0023] 1. Synthesis of 3,5-di-tert-butyl salicylaldehyde
[0024] Add 12.5 g (61 mmol) of 2,4-di-tert-butylphenol, 17 g (121 mmol) of urotropine and 30 ml of glacial acetic acid to a 200 ml single-mouth bottle, heat to 130 degrees in an oil bath and stir for 2 hours, cool to 75 degrees in an oil bath, add a solution prepared by 10 ml of sulfuric acid and 20 ml of water, reheat to 100-105 degrees and stir for 1 hour. Cool to 20 degrees, add TBME (50 ml) and water (30 ml), separate the layers, extract the aqueous phase with TBME (20 ml*2), combine the organic phases, wash twice with brine, dry with sodium sulfate, and concentrate to obtain a yellow oil with an acetic acid smell. Add 30 ml of toluene to azeotropically evaporate to remove acetic acid to obtain a yellow transparent liquid. Simply purify by column chromatography (PE / EA=20 / 1) to obtain a yellow liquid, which solidifies after freezing and is dried by oil pump to obtain 11.53 g of off-white solid, with a yield of 81%.
[0025] 2. Synthesis of Schiff base
[0026] Add 0.6 g (10 mmol) of anhydrous ethylenediamine and 50 ml of ethanol into a 250 ml three-necked flask, heat to 70-80 degrees, and begin to drop 4.68 g of 3,5-di-tert-butyl salicylaldehyde (20 mmol) dissolved in 50 ml of ethanol. Add all the solution in half an hour, continue stirring in an 80-degree oil bath for 2 hours to obtain a bright yellow suspension. Add 40 ml of water dropwise while cooling. After the temperature drops to 20-25 degrees, filter, wash thoroughly with water (40 ml*2), then rinse with ethanol, dry to obtain a yellow solid, and dry under reduced pressure with an oil pump to obtain 3.85 g of a yellow solid with a yield of 78%.
[0027] 3. Reduction of Schiff's base
[0028] In a 100 ml single-necked round-bottom flask, 2 g of Schiff's base and 22 ml of THF were added and stirred to dissolve to obtain a yellow solution. 1.6 g of sodium borohydride (10 equivalents) was added and the temperature was raised to 65 degrees in an oil bath with stirring. 10 ml of methanol was slowly added dropwise within 1 hour. Reflux and stirring were continued for 3 hours. TLC showed that the raw material reaction was complete. 20 ml of water was added, the layers were separated, and the aqueous layer was extracted 3 times with 30 ml of ethyl acetate. The organic phases were combined, washed with water, washed with brine, dried, concentrated, and purified by column chromatography (PE / EA=10 / 1) to obtain 1.6 g of a white solid product with a yield of 80%.
[0029] 4. Synthesis of zirconium complex
[0030] 39 mg (0.08 mmol) of zirconium acetylacetonate, 50 mg (0.1 mmol) of ligand and 2 ml of toluene were mixed and heated to 50 degrees and stirred for 0.5 hours, and concentrated to dryness under reduced pressure. The generated acetylacetone was pulled dry by a high vacuum oil pump to obtain a white solid.
[0031] Furthermore, the starting aryl compound in S2 is phenyl or substituted phenyl.
[0032] Furthermore, the molar ratio of SOCl2 in S3 is twice that of the aromatic compound.
[0033] Furthermore, the molar ratio of the catalyst in S4 is 5-10% of the total amount of reactants.
[0034] Furthermore, the reaction time in S5 is 4 to 6 hours.
[0035] Furthermore, the mobile phase of the S8 column chromatography was a mixture of petroleum ether and ethyl acetate in a volume ratio of 10:1.
[0036] Furthermore, the organic phase in S7 is dried using anhydrous sodium sulfate, allowed to stand for 30 minutes, and then filtered; the filtered organic phase is concentrated using a rotary evaporator to obtain a crude product.
[0037] Beneficial effects:
[0038] The present invention provides a sulfoxide synthesis method based on a zirconium catalyst, which has the following advantages:
[0039] (1) The present invention avoids the need to use a strong oxidant in a conventional oxidation reaction, and achieves the synthesis of sulfoxide under relatively mild reaction conditions by using SOCl2 as a sulfur source. The reaction can be carried out at a temperature ranging from room temperature to 60-80°C, without the need for extreme high or low temperatures, thus simplifying the operation and reducing energy consumption.
[0040] (2) The present invention significantly improves the reaction selectivity and yield by optimizing the molar ratio (SOCl2 is twice that of the aromatic compound) and rationally selecting the zirconium catalyst. Under the conditions of appropriate catalyst dosage and reaction time, the occurrence of side reactions can be effectively avoided, ensuring the high purity and high yield of the target product.
[0041] (3) Traditional synthesis methods often use toxic strong oxidants or noble metal catalysts, while the SOCl2 and zirconium catalysts used in the present invention have less impact on the environment. In particular, through the quenching step, the residual SOCl2 can be decomposed into harmless byproducts, reducing the risk of environmental pollution. In the post-reaction treatment process, no toxic waste is generated, which complies with the principles of green chemistry and is suitable for large-scale industrial production. BRIEF DESCRIPTION OF THE DRAWINGS
[0042] Figure 1 It is the synthesis process of zirconium catalyst;
[0043] Figure 2 It is a catalytic reaction process. DETAILED DESCRIPTION
[0044] In order to deepen the understanding of the present invention, the present invention will be further described in detail below in conjunction with examples. The examples are only used to explain the present invention and do not constitute a limitation on the protection scope of the present invention.
[0045] Example
[0046] The preparation process of zirconium catalyst is as follows:
[0047] 1. Synthesis of 3,5-di-tert-butyl salicylaldehyde
[0048] Add 12.5 g (61 mmol) of 2,4-di-tert-butylphenol, 17 g (121 mmol) of urotropine and 30 ml of glacial acetic acid to a 200 ml single-mouth bottle, heat to 130 degrees in an oil bath and stir for 2 hours, cool to 75 degrees in an oil bath, add a solution prepared by 10 ml of sulfuric acid and 20 ml of water, reheat to 100-105 degrees and stir for 1 hour. Cool to 20 degrees, add TBME (50 ml) and water (30 ml), separate the layers, extract the aqueous phase with TBME (20 ml*2), combine the organic phases, wash twice with brine, dry with sodium sulfate, and concentrate to obtain a yellow oil with an acetic acid smell. Add 30 ml of toluene to azeotropically evaporate to remove acetic acid to obtain a yellow transparent liquid. Simply purify by column chromatography (PE / EA=20 / 1) to obtain a yellow liquid, which solidifies after freezing and is dried by oil pump to obtain 11.53 g of off-white solid, with a yield of 81%.
[0049] 2. Synthesis of Schiff base
[0050] Add 0.6 g (10 mmol) of anhydrous ethylenediamine and 50 ml of ethanol into a 250 ml three-necked flask, heat to 70-80 degrees, and begin to drop 4.68 g of 3,5-di-tert-butyl salicylaldehyde (20 mmol) dissolved in 50 ml of ethanol. Add all the solution in half an hour, continue stirring in an 80-degree oil bath for 2 hours to obtain a bright yellow suspension. Add 40 ml of water dropwise while cooling. After the temperature drops to 20-25 degrees, filter, wash thoroughly with water (40 ml*2), then rinse with ethanol, dry to obtain a yellow solid, and dry under reduced pressure with an oil pump to obtain 3.85 g of a yellow solid with a yield of 78%.
[0051] 3. Reduction of Schiff's base
[0052] In a 100 ml single-necked round-bottom flask, 2 g of Schiff's base and 22 ml of THF were added and stirred to dissolve to obtain a yellow solution. 1.6 g of sodium borohydride (10 equivalents) was added and the temperature was raised to 65 degrees in an oil bath with stirring. 10 ml of methanol was slowly added dropwise within 1 hour. Reflux and stirring were continued for 3 hours. TLC showed that the raw material reaction was complete. 20 ml of water was added, the layers were separated, and the aqueous layer was extracted 3 times with 30 ml of ethyl acetate. The organic phases were combined, washed with water, washed with brine, dried, concentrated, and purified by column chromatography (PE / EA=10 / 1) to obtain 1.6 g of a white solid product with a yield of 80%.
[0053] 4. Synthesis of zirconium complex
[0054] 39 mg (0.08 mmol) of zirconium acetylacetonate, 50 mg (0.1 mmol) of ligand and 2 ml of toluene were mixed and heated to 50 degrees and stirred for 0.5 hours, and concentrated to dryness under reduced pressure. The generated acetylacetone was pulled dry by a high vacuum oil pump to obtain a white solid.
[0055] The overall sulfoxide preparation reaction process is as follows:
[0056] Step S1: Prepare solvent
[0057] In a 250mL reaction flask, add 50mL of anhydrous dichloromethane (DCM) as the reaction solvent. DCM is a commonly used inert solvent with a low boiling point (39.6°C) and good solubility, which can ensure that the reactants are fully dissolved and easy to remove later. Using anhydrous conditions can avoid the hydrolysis reaction of water on SOCl2, ensuring reaction efficiency and product purity.
[0058] Step S2: Add reactants
[0059] Weigh 1.0 mol of phenyl or substituted phenyl compound (e.g., anisole) and add it to an anhydrous dichloromethane solution. Phenyl or substituted phenyl compounds are easy to obtain and have good reactivity to generate the target diaryl sulfoxide. The substituent can be adjusted by regulating the reactivity and the properties of the final product.
[0060] Adding aromatic compounds in a 1:1 molar ratio ensures accurate reaction ratios, helps improve yield and reaction selectivity, and avoids waste of excess reagents or the occurrence of side reactions.
[0061] Step S3: Addition of SOCl2
[0062] Slowly drop 2.0 mol of sulfuryl trichloride (SOCl2) while keeping the reaction system at a low temperature of 0-5°C, cool it down in an ice water bath, and control the drop time to about 30 minutes. SOCl2, as a sulfur source, can efficiently participate in the reaction to generate diaryl sulfoxides. At the same time, low temperature operation can effectively suppress the violent exothermic phenomenon of the reaction and reduce the occurrence of side reactions. 2 times the molar ratio of SOCl2 can ensure sufficient reaction with the aromatic compound while avoiding the unreacted SOCl2 affecting the subsequent steps. Slowly drop and control at 0-5°C to avoid the formation of by-products caused by too fast reaction.
[0063] Step S4: Addition of catalyst
[0064] Operation: Add 0.05 mol of zirconium catalyst to the reaction system. The amount of catalyst is 5% of the total amount of reactants.
[0065] Step S5: Reaction
[0066] The reaction system was slowly heated from 0°C to room temperature (25°C), stirred for 30 minutes, then gradually heated to 60-80°C and maintained at this temperature for 4-6 hours.
[0067] The slow heating process helps to avoid violent reactions, and stirring at room temperature allows the reactants to fully contact and react. 60-80℃ is the optimal reaction temperature range, which can maintain the reaction rate and avoid side reactions.
[0068] Step S6: Post-reaction treatment
[0069] After the reaction is completed, cool to room temperature, add 50mL of water to quench the reaction and decompose the residual SOCl2. Separate the organic phase and the aqueous phase through a separatory funnel and collect the organic phase. Water can effectively decompose the residual SOCl2 into harmless byproducts such as SO2 and HCl, avoiding contamination of the final product. The liquid separation operation is simple and easy, and can efficiently separate the aqueous phase and the organic phase.
[0070] Step S7: Purification of organic phase
[0071] The organic phase was dried with anhydrous sodium sulfate, allowed to stand for 30 minutes, and then filtered through filter paper. The filtered organic phase was concentrated by rotary evaporation. Anhydrous sodium sulfate can effectively remove trace water in the solution to avoid its influence on subsequent purification steps. Rotary evaporation can quickly remove the solvent to obtain a crude product.
[0072] Step S8: Product purification
[0073] The crude product was purified by column chromatography. The mobile phase was a mixture of petroleum ether and ethyl acetate in a volume ratio of 10:1. After column chromatography, the pure diaryl sulfoxide was collected. Column chromatography is a commonly used method for separation and purification of organic products. A mixture of petroleum ether and ethyl acetate helps to effectively separate the target product from impurities. A mobile phase with a volume ratio of 10:1 can provide a better separation effect.
[0074] Finally, using H NMR spectroscopy ( 1 The product was characterized by H-NMR, infrared spectroscopy (IR) and mass spectrometry (MS). The product had a correct structure and a purity of more than 95%.
[0075] As a further improvement, the above is only a preferred embodiment of the present invention and is 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 sulfoxide synthesis method based on a zirconium catalyst, characterized in that: The synthetic method comprises the following steps: S1. Preparation of zirconium-based catalyst: raw materials include 2,4-di-tert-butylphenol, urotropine and glacial acetic acid; S2. Prepare the solvent: add anhydrous dichloromethane as the solvent into the reaction flask; S3, adding reactants: adding the five-membered sulfur ring compound to the solvent at a molar ratio of 1:1; S4, adding reagent H2O2: slowly add H2O2 dropwise to the reaction mixture, and keep the temperature low to control the reaction exotherm; S5, catalyst addition: adding the zirconium-based catalyst prepared in step S1; S6, reaction: the reaction system is heated from low temperature to room temperature, and then gradually heated to between 40 and 60°C; S7, post-reaction treatment: After the reaction is completed, cool to room temperature, add an appropriate amount of water to quench the reaction, and decompose the residual SOCl2 into harmless by-products; separate the organic phase from the aqueous phase by a separatory funnel, and collect the organic phase; S8, organic phase purification: drying and concentrating the organic phase; S9. Product purification: Purify the crude product using column chromatography.
2. A sulfoxide synthesis method based on a zirconium catalyst according to claim 1, characterized in that: S1 Preparation of zirconium-based catalyst comprises the following sub-steps: S101: Add 2,4-di-tert-butylphenol, urotropine and glacial acetic acid into a reaction container, raise the temperature to 130° C., and stir to react for 2 hours; S102: After cooling to 75° C., a solution prepared by sulfuric acid and water is added, and the mixture is heated to 100-105° C. and stirred for 1 hour to obtain 3,5-di-tert-butyl salicylaldehyde; S103: reacting 3,5-di-tert-butyl salicylaldehyde with anhydrous ethylenediamine to generate a Schiff base; S104: using sodium borohydride to reduce the Schiff base to obtain an amine-containing ligand; S105: The ligand reacts with zirconium acetylacetonate in toluene to form a zirconium-based catalyst.
3. The method for synthesizing sulfoxide based on a zirconium catalyst according to claim 1, characterized in that: The starting aryl compound in S2 is phenyl or substituted phenyl.
4. The method for synthesizing sulfoxide based on a zirconium catalyst according to claim 1, characterized in that: The molar ratio of SOCl2 in S4 is twice that of the aromatic compound.
5. The method for synthesizing sulfoxide based on a zirconium catalyst according to claim 1, characterized in that: The molar ratio of the catalyst in S5 is 5-10% of the total amount of reactants.
6. The method for synthesizing sulfoxide based on a zirconium catalyst according to claim 1, characterized in that: The reaction time in S6 is 4 to 6 hours.
7. The method for synthesizing sulfoxide based on a zirconium catalyst according to claim 1, characterized in that: The mobile phase of S9 column chromatography was a mixture of petroleum ether and ethyl acetate in a volume ratio of 10:
1.
8. The method for synthesizing sulfoxide based on a zirconium catalyst according to claim 1, characterized in that: The organic phase in S8 was dried over anhydrous sodium sulfate, allowed to stand for 30 minutes and then filtered; the filtered organic phase was concentrated by a rotary evaporator to obtain a crude product.