A process for the preparation of 4-(2-hydroxy-2-propyl) cumyl hydroperoxide

Abstract

The application relates to a preparation method of 4-(2-hydroxy-2-propyl) cumene hydrogen peroxide, which comprises carrying out an oxidation reaction on 4-isopropyl-alpha,alpha-dimethyl benzyl alcohol and an oxygen-containing gas in a nitrile solvent in the presence of a catalyst and an initiator, wherein the catalyst is selected from one or more of benzene dicarboximide compounds, and the initiator is selected from one or more of azo compounds. The preparation method provided by the application overcomes the problems of slow reaction speed, low reaction conversion rate and low product p-HHP yield in the prior art, and has the characteristics of easy availability of raw materials, high yield, cleanness and environmental protection, mild reaction condition and easy industrialization.

Description

Technical Field

[0001] This application belongs to the field of organic peroxide synthesis, specifically relating to a method for preparing 4-(2-hydroxy-2-propyl)isocumene hydrogen peroxide. Background Technology

[0002] 4-(2-hydroxy-2-propyl)isocumene hydrogen peroxide (p-HHP) is an important fine organic intermediate. Due to the presence of both tertiary alcohol hydroxyl and hydroperoxide groups in its molecular structure, it is widely used in pharmaceuticals, synthetic resins and other fine chemical fields.

[0003] HHP can be used not only as an initiator for the oxidation of diisopropylbenzene in air (oxygen), but also as an epoxidizing agent for the synthesis of propylene oxide or butylene oxide. For example, Japanese Patent No. 63-250333 discloses the epoxidation reaction of 1-butene with HHP in the presence of a molybdenum naphthenate catalyst and in a methyl isobutyl ketone solvent to obtain butylene oxide (BO) and butene oxide (DC). Furthermore, utilizing the reactivity of the hydroperoxygen and hydroxyl groups in its molecule, p-HHP can also be used as a raw material for the synthesis of other organic peroxides.

[0004] Traditional p-HHP preparation methods (such as...) Figure 1 As shown, 4-isopropylisopropylbenzene hydrogen peroxide (p-MHP) is obtained by air oxidation and separation purification using pure para-diisopropylbenzene as raw material. p-MHP is then reduced by a chemical reducing agent or catalytically hydrogenated to obtain 4-isopropyl-α,α-dimethylbenzyl alcohol (p-MC). Finally, p-MC is oxidized with pure oxygen (solvent-free) to obtain p-HHP.

[0005] British Patent GB641250 discloses a process using pure para-diisopropylbenzene as a raw material. An oxidation reaction with air (oxygen) under specific temperature and pressure produces an oxidation liquid containing para-diisopropylbenzene monohydroperoxide (p-MHP) and para-diisopropylbenzene dihydroperoxide (p-DHP). Cooling the oxidation liquid precipitates the generated DHP, which is then separated by filtration. The resulting oxidation liquid, free of DHP, contains both para-diisopropylbenzene and MHP. High-purity p-MHP is obtained through high-vacuum distillation at 0.025 mmHg pressure and 80-90°C. Reduction of p-MHP with sodium sulfite solution yields p-MC. However, this synthesis process requires high-vacuum distillation, placing extremely high demands on equipment. Furthermore, the safety of peroxide distillation is poor, making industrial-scale production impossible.

[0006] Japanese Patent JP 50004036 A discloses a method for preparing p-MC by catalytic hydrogenation of p-MHP in the presence of a palladium-on-carbon catalyst, followed by oxidation of p-MC with air (oxygen) to obtain p-HHP. This synthesis method involves numerous reaction steps and complex operations, especially the separation and purification process of the peroxide p-MHP, which poses significant safety risks and is unsuitable for large-scale production.

[0007] British Patent GB743210 discloses a synthesis method using 500 parts of p-isopropyl-α,α-dimethylbenzyl alcohol (p-MC) as a raw material, in the presence of 20 parts of calcium hydroxide and 0.5 parts of AIBN, under 90°C oil bath heating with pure oxygen for oxidation. This synthesis method exhibits low oxygen oxidation conversion of p-MC, requires numerous separation and purification steps for p-HHP, and necessitates the use of large quantities of highly toxic benzene solvent, which is detrimental to environmental protection. Summary of the Invention

[0008] To address the problems existing in the prior art, this application provides a method for preparing 4-(2-hydroxy-2-propyl)isocumene hydrogen peroxide (p-HHP). The preparation method provided in this application overcomes the problems of slow reaction rate, low reaction conversion rate, and low yield of p-HHP product in the prior art, while also having the advantages of readily available raw materials, high yield, clean and environmentally friendly operation, mild reaction conditions, and ease of industrialization.

[0009] Specifically, this application provides a method for preparing 4-(2-hydroxy-2-propyl)isocumene hydrogen peroxide, which includes oxidizing 4-isopropyl-α,α-dimethylbenzyl alcohol (p-MC) and an oxygen-containing gas in a nitrile solvent in the presence of a catalyst and an initiator, wherein the catalyst is selected from one or more phthalimide compounds, and the initiator is selected from one or more azo compounds.

[0010] In some embodiments, the preparation method includes the following steps:

[0011] S1: Under the presence of a catalyst and an initiator, 4-isopropyl-α,α-dimethylbenzyl alcohol and an oxygen-containing gas are oxidized in a nitrile solvent to obtain a reaction mixture;

[0012] S2: Sequentially remove the nitrile solvent and catalyst from the reaction mixture in step S1 to obtain a reaction solution containing 4-(2-hydroxy-2-propyl)isocumene hydrogen peroxide;

[0013] S3: Extract the reaction solution in step S2 with alkaline solution to obtain an extract. Adjust the pH of the extract to precipitate the solid and obtain a crude product containing 4-(2-hydroxy-2-propyl)isocumene hydrogen peroxide.

[0014] S4: Recrystallize the crude product from step S4 to obtain the 4-(2-hydroxy-2-propyl)isopropylbenzene hydrogen peroxide.

[0015] This application uses pure p-MC as a raw material. In a nitrile solvent, in the presence of a phthalimide catalyst and an azo initiator, an air oxidation reaction is carried out to oxidize the isopropyl group in the p-MC molecule to obtain p-HHP. After the reaction is complete, the nitrile solvent is evaporated under reduced pressure, a small amount of organic solvent such as toluene is added, and the catalyst is removed by cooling and filtration. Taking advantage of the weak acidity of the hydroperoxide group in the p-HHP molecule, the toluene solution is extracted four times with an alkaline solution such as dilute sodium hydroxide solution, and the alkaline extracts are combined. The alkaline solution in the extract is neutralized with an acid solution, and after cooling, the precipitated white solid is filtered to obtain crude p-HHP. The crude product is recrystallized with a mixed solvent to obtain pure p-HHP. This application solves the problems of slow reaction rate and low conversion rate of p-MC oxidation reaction.

[0016] In some embodiments, the mass ratio of the nitrile solvent to the 4-isopropyl-α,α-dimethylbenzyl alcohol is 3-20, for example, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, 11.5, 12, 12.5, 13, 13.5, 14, 14.5, 15, 15.5, 16, 16.5, 17, 17.5, 18, 18.5, 19, or any value between them. In some embodiments, the mass ratio of the nitrile solvent to the 4-isopropyl-α,α-dimethylbenzyl alcohol is 5-17. In some embodiments, the mass ratio of the nitrile solvent to the 4-isopropyl-α,α-dimethylbenzyl alcohol is 10-15.

[0017] In some embodiments, the nitrile solvent is selected from one or more nitrile compounds having 2-5 carbon atoms; in other embodiments, the nitrile solvent is selected from one or more acetonitrile, propionitrile, butyronitrile, and valerate.

[0018] In some embodiments, the initiator is 0.3%-6% of the mass of 4-isopropyl-α,α-dimethylbenzyl alcohol, for example, 0.5%, 0.7%, 1%, 1.3%, 1.5%, 1.7%, 2%, 2.3%, 2.5%, 2.7%, 3%, 3.3%, 3.5%, 3.7%, 4%, 4.3%, 4.5%, 4.7%, 5%, 5.3%, 5.5%, 5.7%, or any value between them. In some embodiments, the initiator is 0.5%-3% of the mass of 4-isopropyl-α,α-dimethylbenzyl alcohol. In some embodiments, the initiator is 1%-2% of the mass of 4-isopropyl-α,α-dimethylbenzyl alcohol.

[0019] In some embodiments, the initiator is selected from one or more of azobisisobutyronitrile, azobisisoheptanenitrile, and dimethyl azobisisobutyrate.

[0020] In some embodiments, the molar ratio of the catalyst to the 4-isopropyl-α,α-dimethylbenzyl alcohol is (1-15):100, for example, 1:100, 2:100, 3:100, 4:100, 5:100, 6:100, 7:100, 8:100, 9:100, 10:100, 11:100, 12:100, 13:100, 14:100, or any value between them. In some embodiments, the molar ratio of the catalyst to the 4-isopropyl-α,α-dimethylbenzyl alcohol is (5-10):100.

[0021] In some embodiments, the catalyst is selected from one or more of N-hydroxyphthalimide, N-hydroxy-4-nitrophthalimide, and N-hydroxy-4-chlorophthalimide.

[0022] In some embodiments, the oxygen-containing gas is selected from air.

[0023] In some embodiments, the oxidation reaction is carried out at a temperature of 60°C-100°C, for example, 65°C, 70°C, 75°C, 80°C, 85°C, 90°C, 95°C, or any value between them. In some embodiments, the oxidation reaction is carried out at a temperature of 70°C-90°C.

[0024] In some embodiments, during the oxidation reaction, the content of 4-(2-hydroxy-2-propyl)isopropylbenzene hydrogen peroxide in the reaction mixture is determined by chemical iodometric titration. When the content of 4-(2-hydroxy-2-propyl)isopropylbenzene hydrogen peroxide is greater than 60%, preferably greater than 65%, the reaction is stopped.

[0025] In some embodiments, in step S2, nitrile solvents in the reaction mixture are removed by means of reduced pressure.

[0026] In some embodiments, the reaction mixture product after removing nitric acid solvents is mixed with an organic solvent such as toluene, and then the catalyst is removed by filtration.

[0027] In some embodiments, in step S3, the alkaline solution is selected from sodium hydroxide solution and / or potassium hydroxide solution.

[0028] In some embodiments, the mass concentration of the alkaline solution is 1%-10%, for example, 2%, 3%, 4%, 5%, 6%, 7%, 8%, or 9%. In some embodiments, the mass concentration of the alkaline solution is 5%-8%.

[0029] In some embodiments, an acid solution is used to adjust the pH of the extract to 6-7, causing the solid to precipitate.

[0030] In some embodiments, the acid solution is selected from one or more inorganic acids. In some embodiments, the acid solution is selected from one or more of sulfuric acid, hydrochloric acid, nitric acid, and phosphoric acid.

[0031] In some embodiments, recrystallization is performed in step S4 using a mixed solvent of water and C1-C4 alcohol. In some embodiments, recrystallization is performed using a mixed solvent of water and ethanol. In some embodiments, the volume ratio of water to ethanol in the mixed solvent is 1:(0.5-2), for example, 1:1.

[0032] In some embodiments, the preparation of the 4-isopropyl-α,α-dimethylbenzyl alcohol includes the following steps:

[0033] Step 1: In the presence of N-hydroxyphthalimide, p-diisopropylbenzene is reacted with air to obtain a reaction solution;

[0034] Step 2: The reaction solution from Step 1 is subjected to a reduction reaction with a reducing agent solution, preferably an aqueous sodium sulfide solution, to obtain an oil phase containing 4-isopropyl-α,α-dimethylbenzyl alcohol;

[0035] Step 3: Wash and filter the oil phase from Step 2 to obtain the 4-isopropyl-α,α-dimethylbenzyl alcohol.

[0036] In some embodiments, the sodium sulfide aqueous solution contains 5%-30% sodium sulfide by mass, for example, 7%, 9%, 10%, 11%, 13%, 15%, 17%, 19%, 20%, 23%, 25%, or 27%. In some embodiments, the sodium sulfide aqueous solution contains 10%-20% sodium sulfide by mass.

[0037] In some embodiments, the reduction reaction is carried out at a temperature of 90°C-100°C, for example, 93°C, 95°C or 97°C.

[0038] In some implementations, in step 3, the oil phase is washed with water until it becomes neutral.

[0039] In some embodiments, the preparation of the 4-isopropyl-α,α-dimethylbenzyl alcohol includes the following specific steps:

[0040] M1: p-Diisopropylbenzene and AIBN were oxidized under water bath heating with air introduced. The reaction progress was monitored by iodometric titration of the hydroperoxide content. The reaction was stopped when the hydroperoxide content (MHP) reached 65%. After cooling to room temperature, a small amount of DHP was extracted from the oil phase with a small amount of 5% sodium hydroxide solution, yielding a p-diisopropylbenzene oxidized solution with an MHP content of approximately 45%.

[0041] M2: Under water bath heating, sodium sulfide aqueous solution was slowly added dropwise to p-diisopropylbenzene oxidizing solution, controlling the reduction reaction temperature at 90-96℃. The MHP content in the oil phase was 0.8%, and the reaction was stopped. The aqueous phase was separated by cooling, and the oil phase was washed three times with a small amount of water until it was neutral. The oil phase was cooled, filtered to obtain a white precipitate, and vacuum dried to remove p-diisopropylbenzene, yielding p-MC.

[0042] In some embodiments, the method for preparing the 4-(2-hydroxy-2-propyl)isocumene hydrogen peroxide includes the following steps:

[0043] Step 1: In the presence of N-hydroxyphthalimide, p-diisopropylbenzene is reacted with air to obtain a reaction solution;

[0044] Step 2: The reaction solution from Step 1 is subjected to a reduction reaction with a reducing agent solution, preferably an aqueous sodium sulfide solution, to obtain an oil phase containing 4-isopropyl-α,α-dimethylbenzyl alcohol;

[0045] Step 3: Wash and filter the oil phase from Step 2 to obtain the 4-isopropyl-α,α-dimethylbenzyl alcohol;

[0046] Step 4: In the presence of a catalyst and an initiator, 4-isopropyl-α,α-dimethylbenzyl alcohol and oxygen-containing gas from Step 3 are oxidized in a nitrile solvent to obtain a reaction mixture;

[0047] Step 5: Sequentially remove the nitrile solvent and catalyst from the reaction mixture in Step 4 to obtain a reaction solution containing 4-(2-hydroxy-2-propyl)isocumene hydrogen peroxide;

[0048] Step 6: Extract the reaction solution from Step 5 with alkaline solution to obtain an extract. Adjust the pH of the extract to precipitate the solid and obtain a crude product containing 4-(2-hydroxy-2-propyl)isocumene hydrogen peroxide.

[0049] Step 7: Recrystallize the crude product from Step 6 to obtain the 4-(2-hydroxy-2-propyl)isocumene hydrogen peroxide.

[0050] This application uses p-diisopropylbenzene as a raw material. Through air oxidation, a p-diisopropylbenzene oxidized solution is obtained. Without separation and purification to prepare pure p-MHP, the oxidized solution is directly reduced with sodium sulfide aqueous solution to obtain a p-diisopropylbenzene reduced solution. This reduced solution is then crystallized upon cooling to obtain p-MC. Using pure p-MC as a raw material, in a nitrile solvent in the presence of a phthalimide catalyst and an azo initiator, the isopropyl group in the p-MC molecule is oxidized to p-HHP through air oxidation. After the reaction is complete, the nitrile solvent is distilled off under reduced pressure, and a small amount of organic solvent, such as toluene, is added. The catalyst is removed by cooling and filtration. Utilizing the weak acidity of the hydroperoxide group in the p-HHP molecule, the toluene solution is extracted four times with an alkaline solution, such as dilute sodium hydroxide solution. The alkaline extracts are combined. The alkaline solution in the extract is neutralized with an acid solution, and after cooling, the precipitated white solid is filtered to obtain crude p-HHP. The crude product is recrystallized with a mixed solvent to obtain pure p-HHP. This application avoids the separation and purification of m-MHP peroxides and the high-vacuum distillation separation of p-MC, while solving the problems of slow reaction rate and low conversion rate of p-MC oxidation.

[0051] In some embodiments, the preparation method of the 4-(2-hydroxy-2-propyl)isocumene hydrogen peroxide includes the following specific steps:

[0052] A. Add p-MC, nitrile solvent, NHPI and AIBN to a three-necked flask equipped with a thermometer, reflux condenser and air inlet tube, and carry out an air oxidation reaction under certain temperature and pressure.

[0053] B. When the p-HHP content in the reaction solution (excluding nitrile solvents) is greater than 60% as determined by iodometric titration, the reaction should be stopped.

[0054] C. Cool the reaction mixture to room temperature and remove acetonitrile under reduced pressure. Add a small amount of toluene, filter to remove NHPI, and extract p-HHP with dilute sodium hydroxide solution, taking advantage of the weak acidity of the hydroperoxide group in p-HHP. Combine the alkaline extracts, neutralize with dilute sulfuric acid, and filter the precipitated white precipitate to obtain crude p-HHP. Recrystallize from a 50:50 mixture of ethanol and water to obtain p-HHP.

[0055] The beneficial technical effects of this application are as follows:

[0056] This application uses p-MC as a raw material to prepare p-HHP via air oxidation in a nitrile solvent under specific temperature and pressure conditions, in the presence of an NHPI catalyst and an AIBN initiator. The resulting p-HHP exhibits not only high yield but also high purity. The reaction conditions are mild, the reaction is easy to control, the reaction steps are few, and the amount of waste generated is low, making it clean and environmentally friendly, and suitable for industrial application. Attached Figure Description

[0057] Figure 1 The synthesis reaction process of p-HHP in the prior art is shown.

[0058] Figure 2 The synthesis reaction process of p-HHP in some embodiments of this application is shown. Detailed Implementation

[0059] To make the objectives, technical solutions, and advantages of this application clearer, the following detailed description is provided in conjunction with embodiments. The specific embodiments described herein are for illustrative purposes only and are not intended to limit the scope of this application. Furthermore, descriptions of well-known structures and technologies are omitted in the following description to avoid unnecessarily obscuring the concepts of this disclosure. Such structures and technologies have also been described in numerous publications.

[0060] The endpoints and any values ​​of the ranges disclosed herein are not limited to the precise ranges or values, and these ranges or values ​​should be understood to include values ​​close to these ranges or values. For numerical ranges, the endpoint values ​​of the various ranges, the endpoint values ​​of the various ranges and individual point values, and individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be considered as specifically disclosed herein.

[0061] like Figure 1 As shown, the traditional method for preparing p-HHP uses pure p-diisopropylbenzene as raw material, which is then oxidized and separated in air to obtain p-MHP. p-MHP is then reduced with a reducing agent or catalytically hydrogenated to obtain pure p-MC. Finally, p-MC is oxidized with pure oxygen to obtain p-HHP. Existing technologies have the following drawbacks: 1. The reaction steps are numerous and cumbersome; p-MHP requires high-vacuum distillation, posing significant safety hazards. 2. The salt formation and separation purification of peroxide p-MHP also pose significant safety hazards, generating large amounts of alkaline and saline wastewater, which is detrimental to environmental protection and unsuitable for large-scale production. 4. During the purification of p-MC, to prevent the high-temperature dehydration side reaction, the separation and purification of MC requires high-vacuum distillation, placing high demands on equipment and making it unsuitable for industrial production. 5. The oxygen oxidation reaction of p-MC has low conversion and yield.

[0062] This application, if Figure 2 As shown, p-MC is used as a raw material to prepare p-HHP via air oxidation in a nitrile solvent under specific temperature and pressure conditions, in the presence of an NHPI catalyst and an AIBN initiator. The obtained p-HHP not only has a high yield but also high purity. The reaction conditions are mild, the reaction is easy to control, the reaction steps are few, and the amount of waste generated is low, making it clean and environmentally friendly, and suitable for industrial application.

[0063] The present application will be described in detail below through examples.

[0064] Unless otherwise specified, the pressures mentioned in the following examples and comparative examples are gauge pressures.

[0065] In the following examples and comparative examples, 4-isopropyl-α,α-dimethylbenzyl alcohol (p-MC) was prepared as follows:

[0066] In a 250 mL three-necked flask equipped with a stirrer, thermometer, and reflux condenser, 200 mL of p-diisopropylbenzene and 1.0 g of AIBN were added. The mixture was heated in a 95 °C water bath with stirring and air introduced (flow rate 800 mL / min) to initiate the oxidation reaction. The reaction progress was monitored by iodometric titration of the hydroperoxide content. The reaction was stopped after 10 hours when the hydroperoxide content (MHP) reached 65%. The mixture was cooled to room temperature, and a small amount of DHP was extracted from the oil phase with a small amount of 5% sodium hydroxide solution to obtain a p-diisopropylbenzene oxidation solution with an MHP content of approximately 45%.

[0067] In a 500 mL three-necked flask equipped with a stirrer, thermometer, and reflux condenser, a solution of 56 g of sodium sulfide nonahydrate dissolved in 280 g of water was added. Under a 90 °C water bath, p-diisopropylbenzene oxidizing solution was slowly added dropwise over approximately one hour. The reduction reaction temperature was controlled at 90–96 °C. After four hours, the MHP content in the oil phase was 0.8%, at which point the reaction was stopped. The mixture was cooled to 40 °C, the aqueous phase was separated, and the oil phase was washed three times with a small amount of water until neutral. The oil phase was placed in a refrigerator to cool overnight. The precipitated white precipitate was filtered, dried as much as possible under vacuum, and p-diisopropylbenzene was removed to obtain p-MC with a purity of 96%. Melting point: 42–43 °C, yield: 45%.

[0068] Example 1

[0069] Synthesis of p-HHP

[0070] Step A: In a 250 mL three-necked flask equipped with a stirrer, thermometer, and reflux condenser, add 9.8 g of p-MC (96%), 0.86 g of NHPI, 0.20 g of AIBN, and 90 g of acetonitrile. Heat in an 80 °C water bath with stirring, and introduce air (500 mL / min) to carry out the oxidation reaction. During the reaction, the temperature of the reaction solution should be maintained at 65–67 °C. The reaction progress is monitored by iodometric titration. After 20 hours of reaction, the reaction is stopped when the p-HHP content in the reaction solution reaches 61% (excluding the solvent acetonitrile).

[0071] Step B: Cool the reaction solution to room temperature, evaporate acetonitrile under reduced pressure, add 50 mL of toluene, cool to room temperature, and filter to remove NHP. Extract the p-HHP from the organic phase with 5% sodium hydroxide solution, combine the alkaline extracts, neutralize with dilute sulfuric acid to pH 6-7, precipitating white p-HHP. Filter to obtain crude p-HHP product. Recrystallize with a 50:50 mixture of ethanol and water, filter, wash, and dry to obtain p-HHP with a melting point of 91-92℃ and a yield of 55%.

[0072] Example 2

[0073] Synthesis of p-HHP

[0074] Step A: In a 250 mL three-necked flask equipped with a stirrer, thermometer, and reflux condenser, add 9.8 g of p-MC (96%), 0.43 g of NHPI, 0.10 g of AIBN, and 90 g of acetonitrile. Heat in an 85°C water bath with stirring, and introduce air (500 mL / min) to carry out the oxidation reaction. During the reaction, the temperature of the reaction solution should be maintained at 70–72°C. The reaction progress is monitored by iodometric titration. After 18 hours, the reaction is stopped when the p-HHP content in the reaction solution reaches 65% (excluding the solvent acetonitrile).

[0075] Step B: Cool the reaction solution to room temperature, evaporate acetonitrile under reduced pressure, add 50 mL of toluene, cool to room temperature, and filter to remove NHP. Extract the p-HHP from the organic phase with 8% sodium hydroxide solution, combine the alkaline extracts, neutralize with dilute sulfuric acid to pH 6-7, precipitating white para-HHP. Filter to obtain crude p-HHP. Recrystallize with a 50:50 mixture of ethanol and water, filter, wash, and dry to obtain p-HHP with a melting point of 91-92℃ and a yield of 60%.

[0076] Example 3

[0077] Synthesis of p-HHP

[0078] Step A: In a 250 mL three-necked flask equipped with a stirrer, thermometer, and reflux condenser, add 9.8 g p-MC, 0.86 g NHPI, 0.10 g AIBN, and 90 g acetonitrile. Heat in a 90°C water bath with stirring, and introduce air (500 mL / min) to carry out the oxidation reaction. During the oxidation reaction, the reaction solution temperature should be maintained at 73–75°C. The reaction progress is monitored by iodometric titration. After 16 hours, the reaction is stopped when the p-HHP content in the reaction solution reaches 68% (excluding the solvent acetonitrile).

[0079] Step B: Cool the reaction solution to room temperature, evaporate acetonitrile under reduced pressure, add 50 mL of toluene, cool to room temperature, and filter to remove NHP. Extract the p-HHP from the organic phase with 10% sodium hydroxide solution, combine the alkaline extracts, neutralize with dilute sulfuric acid to pH 6-7, precipitating white p-HHP. Filter to obtain crude p-HHP product. Recrystallize with a 50:50 mixture of ethanol and water, filter, wash, and dry to obtain p-HHP with a melting point of 91-92℃ and a yield of 63%.

[0080] Example 4

[0081] Synthesis of p-HHP

[0082] Step A: In a 250 mL three-necked flask equipped with a stirrer, thermometer, and reflux condenser, add 9.8 g p-MC, 0.43 g NHPI, 0.20 g AIBN, and 90 g acetonitrile. Heat in a 95°C water bath with stirring, and introduce air (500 mL / min) to carry out the oxidation reaction. During the oxidation reaction, the reaction solution temperature should be maintained at 75–77°C. The reaction progress should be monitored using iodometric titration. After 15 hours, the reaction should be stopped when the p-HHP content in the reaction solution reaches 70% (excluding the solvent acetonitrile).

[0083] Step B: Cool the reaction solution to room temperature, evaporate acetonitrile under reduced pressure, add 50 mL of toluene, cool to room temperature, and filter to remove NHP. Extract the p-HHP from the organic phase with 10% sodium hydroxide solution, combine the alkaline extracts, neutralize with dilute sulfuric acid to pH 6-7, precipitating white p-HHP. Filter to obtain crude p-HHP product. Recrystallize with a 50:50 mixture of ethanol and water, filter, wash, and dry to obtain p-HHP with a melting point of 91-92℃ and a yield of 65%.

[0084] Example 5

[0085] Step A: In a 250 mL three-necked flask equipped with a stirrer, thermometer, and reflux condenser, add 9.8 g of p-MC (96%), 0.86 g of NHPI, 0.20 g of AIBN, and 45 g of acetonitrile. Heat in an 80 °C water bath with stirring, and introduce air (500 mL / min) to carry out the oxidation reaction. During the reaction, the temperature of the reaction solution should be maintained at 65–67 °C. The reaction progress is monitored by iodometric titration. After 20 hours of reaction, the reaction is stopped when the p-HHP content in the reaction solution reaches 55% (excluding the solvent acetonitrile).

[0086] Step B: Same as in Example 1, finally obtaining p-HHP with a melting point of 91-92℃ and a yield of 50%.

[0087] Example 6

[0088] Step A: In a 250 mL three-necked flask equipped with a stirrer, thermometer, and reflux condenser, add 9.8 g of p-MC (96%), 0.86 g of NHPI, 0.20 g of AIBN, and 80 g of acetonitrile. Heat in an 80 °C water bath with stirring, and introduce air (500 mL / min) to carry out the oxidation reaction. During the reaction, the temperature of the reaction solution should be maintained at 65–67 °C. The reaction progress is monitored by iodometric titration. After 20 hours of reaction, the reaction is stopped when the p-HHP content in the reaction solution reaches 57% (excluding the solvent acetonitrile).

[0089] Step B: Same as in Example 1, the final p-HHP obtained has a melting point of 91-92℃ and a yield of 53%.

[0090] Example 7

[0091] Step A: In a 250 mL three-necked flask equipped with a stirrer, thermometer, and reflux condenser, add 9.8 g of p-MC (96%), 0.86 g of NHPI, 0.20 g of AIBN, and 125 g of acetonitrile. Heat in an 80 °C water bath with stirring, and introduce air (500 mL / min) to carry out the oxidation reaction. During the reaction, the temperature of the reaction solution should be maintained at 65–67 °C. The reaction progress is monitored by iodometric titration. After 20 hours of reaction, the reaction is stopped when the p-HHP content in the reaction solution reaches 65% (excluding the solvent acetonitrile).

[0092] Step B: Same as in Example 1, finally obtaining p-HHP with a melting point of 91-92℃ and a yield of 60%.

[0093] Example 8

[0094] Step A: In a 250 mL three-necked flask equipped with a stirrer, thermometer, and reflux condenser, add 9.8 g of p-MC (96%), 0.86 g of NHPI, 0.20 g of AIBN, and 165 g of acetonitrile. Heat in an 80 °C water bath with stirring, and introduce air (500 mL / min) to carry out the oxidation reaction. During the reaction, the temperature of the reaction solution should be maintained at 65–67 °C. The reaction progress is monitored by iodometric titration. After 20 hours of reaction, the reaction is stopped when the p-HHP content in the reaction solution reaches 59% (excluding the solvent acetonitrile).

[0095] Step B: Same as in Example 1, the final p-HHP obtained has a melting point of 91-92℃ and a yield of 53%.

[0096] Example 9

[0097] Step A: In a 250 mL three-necked flask equipped with a stirrer, thermometer, and reflux condenser, add 9.8 g of p-MC (96%), 0.86 g of NHPI, 0.10 g of AIBN, and 90 g of acetonitrile. Heat in an 80 °C water bath with stirring, and introduce air (500 mL / min) to carry out the oxidation reaction. During the reaction, the temperature of the reaction solution should be maintained at 65–67 °C. The reaction progress is monitored by iodometric titration. After 20 hours of reaction, the reaction is stopped when the p-HHP content in the reaction solution reaches 50% (excluding the solvent acetonitrile).

[0098] Step B: Same as in Example 1, finally obtaining p-HHP with a melting point of 91-92℃ and a yield of 48%.

[0099] Example 10

[0100] Step A: In a 250 mL three-necked flask equipped with a stirrer, thermometer, and reflux condenser, add 9.8 g of p-MC (96%), 0.86 g of NHPI, 0.27 g of AIBN, and 90 g of acetonitrile. Heat in an 80 °C water bath with stirring, and introduce air (500 mL / min) to carry out the oxidation reaction. During the reaction, the temperature of the reaction solution should be maintained at 65–67 °C. The reaction progress is monitored by iodometric titration. After 20 hours of reaction, the reaction is stopped when the p-HHP content in the reaction solution reaches 65% (excluding the solvent acetonitrile).

[0101] Step B: Same as in Example 1, finally obtaining p-HHP with a melting point of 91-92℃ and a yield of 62%.

[0102] Example 11

[0103] Step A: In a 250 mL three-necked flask equipped with a stirrer, thermometer, and reflux condenser, add 9.8 g of p-MC (96%), 0.86 g of NHPI, 0.32 g of AIBN, and 90 g of acetonitrile. Heat in an 80 °C water bath with stirring, and introduce air (500 mL / min) to carry out the oxidation reaction. During the reaction, the temperature of the reaction solution should be maintained at 65–67 °C. The reaction progress is monitored by iodometric titration. After 20 hours of reaction, the reaction is stopped when the p-HHP content in the reaction solution reaches 67% (excluding the solvent acetonitrile).

[0104] Step B: Same as in Example 1, finally obtaining p-HHP with a melting point of 91-92℃ and a yield of 64%.

[0105] Example 12

[0106] Step A: In a 250 mL three-necked flask equipped with a stirrer, thermometer, and reflux condenser, add 9.8 g of p-MC (96%), 0.86 g of NHPI, 0.5 g of AIBN, and 90 g of acetonitrile. Heat in an 80 °C water bath with stirring, and introduce air (500 mL / min) to carry out the oxidation reaction. During the reaction, the temperature of the reaction solution should be maintained at 65–67 °C. The reaction progress should be monitored by iodometric titration. After 20 hours of reaction, the reaction should be stopped when the p-HHP content in the reaction solution reaches 67% (excluding the solvent acetonitrile).

[0107] Step B: Same as in Example 1, finally obtaining p-HHP with a melting point of 91-92℃ and a yield of 64%.

[0108] Comparative Example 1

[0109] Synthesis of p-HHP

[0110] Step A: In a 100 mL three-necked flask equipped with a stirrer, thermometer, and reflux condenser, add 20 g of p-MC, 1.72 g of NHPI, and 0.5 g of AIBN (without acetonitrile). Heat in a 95 °C water bath with stirring, and purge with air (500 mL / min) to maintain the oxidation reaction temperature at 90 °C. During the oxidation reaction, the progress is monitored using iodometric titration. The reaction is stopped after 20 hours when the p-HHP content in the reaction solution reaches 25%.

[0111] Step B: Cool the reaction solution to room temperature, add 50 mL of toluene, and after cooling to room temperature, filter to remove NHP. Extract the p-HHP from the organic phase with 8% sodium hydroxide solution, combine the alkaline extracts, neutralize with dilute sulfuric acid to pH 6-7, precipitating white para-HHP. Filter to obtain crude p-HHP product. Recrystallize with a 50:50 mixture of ethanol and water, filter, wash, and dry to obtain p-HHP with a melting point of 91-92℃ and a yield of 20%.

[0112] As can be seen from Comparative Example 1, when p-MC uses NHPI catalyst and AIBN as initiator and does not add acetonitrile solvent, the oxidation reaction proceeds very slowly even at a temperature of 90°C.

[0113] Comparative Example 2

[0114] Synthesis of p-HHP

[0115] Step A: In a 250 mL three-necked flask equipped with a stirrer, thermometer, and reflux condenser, add 9.8 g p-MC, 0.86 g NHPI, 0.20 g AIBN, and 90 g o-dichlorobenzene. Heat in a 95 °C water bath with stirring, and purge with air (500 mL / min) to maintain the reaction temperature at 90 °C. During the oxidation reaction, monitor the progress using iodometric titration. Stop the reaction after 20 hours when the p-HHP content in the reaction solution reaches 20% (excluding the solvent dichlorobenzene).

[0116] Step B: Cool the reaction solution to room temperature and filter to remove NHP. Extract the p-HHP from the organic phase with 8% sodium hydroxide solution. Combine the alkaline extracts and neutralize with dilute sulfuric acid to pH 6-7, precipitating white p-HHP. Filter to obtain crude p-HHP product. Recrystallize with a 50:50 mixture of ethanol and water, filter, wash, and dry to obtain p-HHP with a melting point of 91-92℃ and a yield of 15%.

[0117] As can be seen from Comparative Example 2, when p-MC uses NHPI catalyst and AIBN as initiator and o-dichlorobenzene as solvent to carry out air oxidation reaction, the oxidation reaction proceeds very slowly even at a temperature of 90℃.

[0118] The preferred embodiments of this application have been described in detail above; however, this application is not limited thereto. Within the scope of the technical concept of this application, various simple modifications can be made to the technical solution of this application, including combining various technical features in any other suitable manner. These simple modifications and combinations should also be considered as the content disclosed in this application and are all within the protection scope of this application.

Claims

1. A method for preparing 4-(2-hydroxy-2-propyl)isocumene hydrogen peroxide, comprising, in the presence of a catalyst and an initiator, carrying out an oxidation reaction of 4-isopropyl-α,α-dimethylbenzyl alcohol and an oxygen-containing gas in a nitrile solvent, wherein, The catalyst is selected from one or more phthalimide compounds, and the initiator is selected from one or more azo compounds.

2. The preparation method according to claim 1, characterized in that, The preparation method includes the following steps: S1: Under the presence of a catalyst and an initiator, 4-isopropyl-α,α-dimethylbenzyl alcohol and an oxygen-containing gas are oxidized in a nitrile solvent to obtain a reaction mixture; S2: Sequentially remove the nitrile solvent and catalyst from the reaction mixture in step S1 to obtain a reaction solution containing 4-(2-hydroxy-2-propyl)isocumene hydrogen peroxide; S3: Extract the reaction solution in step S2 with alkaline solution to obtain an extract. Adjust the pH of the extract to precipitate the solid and obtain a crude product containing 4-(2-hydroxy-2-propyl)isocumene hydrogen peroxide. S4: Recrystallize the crude product from step S4 to obtain the 4-(2-hydroxy-2-propyl)isopropylbenzene hydrogen peroxide.

3. The preparation method according to claim 1 or 2, characterized in that, The mass ratio of the nitrile solvent to the 4-isopropyl-α,α-dimethylbenzyl alcohol is 3-20, preferably 5-17, more preferably 10-15; and / or The nitrile solvent is selected from one or more nitrile compounds having 2-5 carbon atoms, preferably from one or more of acetonitrile, propionitrile, butyronitrile, and valerate.

4. The preparation method according to any one of claims 1-3, characterized in that, The initiator is 0.3%-6% of the mass of 4-isopropyl-α,α-dimethylbenzyl alcohol, preferably 0.5%-3%, more preferably 1%-2%; and / or The initiator is selected from one or more of azobisisobutyronitrile, azobisisoheptanenitrile, and dimethyl azobisisobutyrate.

5. The preparation method according to any one of claims 1-4, characterized in that, The molar ratio of the catalyst to the 4-isopropyl-α,α-dimethylbenzyl alcohol is (1-15):100, preferably (5-10):100; and / or The catalyst is selected from one or more of N-hydroxyphthalimide, N-hydroxy-4-nitrophthalimide and N-hydroxy-4-chlorophthalimide.

6. The preparation method according to any one of claims 1-5, characterized in that, The oxygen-containing gas is selected from air; and / or The oxidation reaction is carried out at a temperature of 60℃-100℃, preferably 70℃-90℃; and / or During the oxidation reaction, the content of 4-(2-hydroxy-2-propyl)isopropylbenzene hydrogen peroxide in the reaction mixture is determined by chemical iodometric titration. When the content of 4-(2-hydroxy-2-propyl)isopropylbenzene hydrogen peroxide is greater than 60%, preferably greater than 65%, the reaction is stopped.

7. The preparation method according to any one of claims 1-6, characterized in that, In step S2, nitrile solvents in the reaction mixture are removed by vacuum treatment; and / or The reaction mixture product after removing nitrile solvents is mixed with an organic solvent such as toluene, and then filtered to remove the catalyst.

8. The preparation method according to any one of claims 1-7, characterized in that, In step S3, the alkaline solution is selected from sodium hydroxide solution and / or potassium hydroxide solution, preferably, the mass concentration of the alkaline solution is 1%-10%, more preferably 5%-8%; and / or The pH of the extract is adjusted to 6-7 using an acid solution to induce solid precipitation. Preferably, the acid solution is selected from one or more inorganic acids, such as sulfuric acid, hydrochloric acid, nitric acid, and phosphoric acid.

9. The preparation method according to any one of claims 1-8, characterized in that, In step S4, recrystallization is carried out using a mixed solvent of water and C1-C4 alcohol, preferably a mixed solvent of water and ethanol.

10. The preparation method according to any one of claims 1-9, characterized in that, The preparation of the 4-isopropyl-α,α-dimethylbenzyl alcohol includes the following steps: Step 1: In the presence of N-hydroxyphthalimide, p-diisopropylbenzene is reacted with air to obtain a reaction solution; Step 2: The reaction solution from Step 1 is subjected to a reduction reaction with a reducing agent solution, preferably an aqueous sodium sulfide solution, to obtain an oil phase containing 4-isopropyl-α,α-dimethylbenzyl alcohol; Step 3: Wash and filter the oil phase from Step 2 to obtain the 4-isopropyl-α,α-dimethylbenzyl alcohol; Preferably, the sodium sulfide aqueous solution contains 5%-30% sodium sulfide by mass, more preferably 10%-20%; Preferably, the temperature of the reduction reaction is 90℃-100℃.

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