Synthesis method of 4-(2-hydroxy-2-propyl) cumene hydroperoxide

Abstract

The invention discloses a synthesis method of 4-(2-hydroxy-2-propyl) cumene hydroperoxide. The synthesis method comprises the following steps: adding a catalyst into a reaction kettle; the method comprises the step of carrying out selective oxidation reaction on para-di-(2-hydroxy isopropyl) benzene and hydrogen peroxide in the presence of a solvent and an acid catalyst to obtain 4-(2-hydroxy-2-propyl) cumene hydrogen peroxide, and the solvent is a ketone compound or a mixed solution of the ketone compound and aromatic hydrocarbon. The method provided by the invention has the advantages of easily available synthesis raw materials, no potential safety hazard, simple preparation steps, one-step synthesis, greatly shortened process period, remarkable product yield and purity, simple product separation, clean and environment-friendly production process, mild reaction conditions and easiness in industrialization.

Description

Technical Field

[0001] The invention belongs to the field of synthesis of organic peroxides, and specifically relates to a method for synthesizing 4-(2-hydroxy-2-propyl)isopropylbenzene hydroperoxide. Background Art

[0002] 4-(2-Hydroxy-2-propyl)isopropylbenzene hydroperoxide (p-HHP) is an important fine organic intermediate. Since it contains both hydroxyl and hydroperoxide groups in its molecular structure, it is widely used in fine chemical industries such as pharmaceuticals and synthetic resins. GB910735A discloses the synthesis of hydroquinone using p-HHP as a raw material through hydrogen peroxide oxidation and sulfuric acid-catalyzed acidolysis reaction. GB744425A discloses the preparation of m-(p-) (2-hydroxy-2-propyl) phenol by acidolysis of p-HHP under sulfuric acid or solid acid catalysis, and the acid-catalyzed dehydration of p-(2-hydroxy-2-propyl) phenol to obtain p-isopropenyl phenol. US4207265A and US4258219A disclose the synthesis of hydroquinone using p-isopropenyl phenol. US5990362A discloses the synthesis of bisphenol A by reaction with phenol and 4-(2-hydroxy-2-propyl)phenol as raw materials, wherein 4-(2-hydroxy-2-propyl)phenol is prepared by the addition hydrolysis reaction of methyl p-hydroxybenzoate and methyl lithium (yield 28%). p-HHP can not only be used as an initiator for the oxidation reaction of diisopropylbenzene with air (oxygen), but also as an epoxidant for the synthesis of propylene oxide or butylene oxide. JP63250333A discloses the epoxidation reaction of 1-butene and p-HHP in the presence of a molybdenum naphthenate catalyst in a methyl isobutyl ketone solvent to obtain BO and m-DC. Utilizing the activity of hydroperoxide and hydroxyl, p-HHP can also be used as a raw material for the synthesis of other organic peroxides.

[0003] The traditional p-HHP preparation method is to use pure p-diisopropylbenzene (p-DIPB) as the raw material, obtain p-diisopropylbenzene monohydroperoxide (p-MHP) through air oxidation, and then reduce p-MHP through chemical reducing agent or catalytic hydrogenation to obtain p-isopropyl dimethylbenzyl alcohol (p-MC), and finally oxidize p-MC through pure oxygen (or air) to obtain p-HHP. The reaction process is as follows:

[0004]

[0005] GB641250A discloses that pure p-diisopropylbenzene (p-DIPB) is used as a raw material, and an air (oxygen) oxidation reaction is carried out at a certain temperature and pressure to generate an oxidation liquid containing p-diisopropylbenzene monohydroperoxide (p-MHP) and diisopropylbenzene dihydroperoxide (DHP). The generated DHP is precipitated by cooling the oxidation liquid, and the DHP solid is separated by suction filtration. The oxidation liquid used as the filtrate is used to extract the residual DHP with a 10% sodium hydroxide solution. The obtained DHP-free oxidation liquid contains diisopropylbenzene and MHP, which can be separated by high vacuum distillation (under a pressure of 0.025 mmHg and a temperature of 80-90° C.) to obtain p-MHP with high purity. The p-MHP can be reduced with a sodium sulfite solution to obtain p-MC. Since the synthesis process requires high vacuum distillation, the equipment requirements are extremely high, and the peroxide distillation has poor safety, so it is impossible to experiment with industrial production.

[0006] GB646102A discloses that p-diisopropylbenzene oxidation liquid can be used for salt formation reaction with 50% concentrated sodium hydroxide solution to prepare sodium salt of p-MHP first, and then introduce carbon dioxide gas or acidify with dilute acid to obtain pure p-MHP. Pure p-MHP is reduced by chemical reducing agent or catalytically hydrogenated to obtain p-MC. JP50004036A discloses that p-MC is prepared by catalytic hydrogenation of p-MHP in the presence of palladium carbon catalyst.

[0007] p-MC is oxidized with air (oxygen) to obtain p-HHP, and pure p-HHP is obtained by alkali extraction, acidification and recrystallization. This synthesis method not only has many reaction steps and complicated operations, but also has great safety hazards in the separation and purification process of peroxide p-MHP as the raw material of p-MC, and is not suitable for large-scale production.

[0008] The above process has the following disadvantages: 1. The synthesis of p-HHP has many steps, the operation is complicated, and the reaction conversion rate and yield are not high; 2. The salt formation and separation and purification of the peroxide p-MHP as the raw material of p-MC have great safety hazards and are not suitable for large-scale production; 3. In order to prevent the high-temperature dehydration side reaction of the raw material p-MC, its separation and purification also needs to adopt high vacuum distillation, which has high requirements on equipment and is not suitable for industrial production; 4. The conversion rate of the oxygen oxidation reaction of p-MC is not high, and the separation and purification steps of p-HHP are relatively large, requiring a large amount of highly toxic benzene solvent, which is not conducive to environmental protection. Summary of the invention

[0009] In order to solve the problems existing in the above-mentioned prior art, the present invention provides a method for preparing 4-(2-hydroxy-2-propyl)isopropylbenzene hydroperoxide. The synthetic raw materials of the method are easily available, there is no potential safety hazard, and the preparation steps are simple, the one-step synthesis greatly shortens the process cycle, and also has significant product yield and purity, simple product separation, clean and environmentally friendly production process, mild reaction conditions, and easy industrialization.

[0010] The invention provides a method for synthesizing 4-(2-hydroxy-2-propyl)isopropylbenzene hydroperoxide, comprising the steps of selectively oxidizing para-di-(2-hydroxyisopropyl)benzene with hydrogen peroxide in the presence of a solvent and an acidic catalyst to obtain 4-(2-hydroxy-2-propyl)isopropylbenzene hydroperoxide, wherein the solvent is a ketone compound or a mixed solution of a ketone compound and an aromatic hydrocarbon.

[0011] In the above technical scheme, the reaction process of selectively oxidizing para-di-(2-hydroxyisopropyl)benzene (p-DC) with hydrogen peroxide to synthesize 4-(2-hydroxy-2-propyl)isopropylbenzene hydroperoxide (p-HHP) is as follows:

[0012]

[0013] In the above technical solution, the mass content of p-di-(2-hydroxyisopropyl)benzene in the p-di-(2-hydroxyisopropyl)benzene raw material is greater than 98%.

[0014] In the above technical solution, the ketone compound in the solvent is a ketone compound with 3-6 carbon atoms, preferably at least one of acetone, methyl ethyl ketone, and methyl isobutyl ketone, and more preferably methyl isobutyl ketone. The aromatic hydrocarbon is an aromatic hydrocarbon with 7-10 carbon atoms, preferably at least one of toluene, xylene, ethylbenzene and isopropylbenzene, and more preferably toluene.

[0015] In the above technical solution, when the solvent is a mixture of ketone compounds and aromatic hydrocarbons, the mass content of the ketone compounds is 10% to 80%, and the mass content of the aromatic hydrocarbons is 20% to 90%.

[0016] In the above technical solution, the acidic catalyst is selected from an inorganic acid. Preferably, the inorganic acid is selected from at least one of sulfuric acid, perchloric acid, nitric acid, and phosphoric acid, wherein the sulfuric acid can be concentrated sulfuric acid.

[0017] In the above technical solution, the mass content of hydrogen peroxide in the hydrogen peroxide is 10% to 60%, preferably 20% to 40%.

[0018] In the above technical solution, the molar ratio of the hydrogen peroxide to para-di-(2-hydroxyisopropyl)benzene is (1.0-4.0):1, preferably (1.5-3.0):1.

[0019] In the above technical solution, the weight ratio of the p-di-(2-hydroxyisopropyl)benzene to the acidic catalyst is 1:(0.01-0.25).

[0020] In the above technical solution, the ratio of the solvent to p-di-(2-hydroxyisopropyl)benzene is (10-100) mL: 1 g.

[0021] In the above technical scheme, the reaction conditions of the selective oxidation reaction are: the reaction temperature is 30-70°C, the reaction pressure is normal pressure, and the reaction time is 2-6 hours; the preferred reaction temperature is 45-55°C, and the preferred reaction time is 2-4 hours.

[0022] In the above technical solution, after the selective oxidation reaction is completed, the product p-HHP can be obtained by a conventional extraction and purification method in the art. Specifically, the extraction and purification method can be oil-water separation after stopping the reaction, removing the water phase, extracting the byproduct DHP from the oil phase with a dilute alkaline solution, and then extracting the generated p-HHP with a concentrated alkaline solution, neutralizing the acid and alkali to precipitate p-HHP, and after the precipitate is filtered, it is crystallized with a solvent to obtain p-HHP.

[0023] In the above technical solution, the reaction is stopped when the mass content of p-DC in the reaction solution is less than 5.0% as determined by gas chromatography. Preferably, the reaction is stopped when the mass content of p-DC is less than 3.0%.

[0024] In the above technical solution, the mass concentration of the diluted alkaline solution used in the extraction is 0.5% to 3%, and the mass concentration of the concentrated alkaline solution is 4% to 10%. The alkaline solution is preferably a sodium hydroxide solution.

[0025] In the above technical solution, the solvent used in the crystallization is preferably a mixed solvent of ethanol and water.

[0026] Beneficial effects of the present invention:

[0027] The synthesis method provided by the present invention has not only significant yield and purity, but also mild reaction conditions, easy reaction control, few reaction steps, little three wastes generated, clean and environmentally friendly, and suitable for industrialization. As an intermediate for producing the organic peroxide product para-BIPB, p-DC has been produced on a large scale in industrial scale. The raw materials of the present invention are very easy to obtain, low in cost, simple in process, greatly improve industrial production efficiency, and suitable for industrial application. DETAILED DESCRIPTION

[0028] The present invention will be further described below in conjunction with specific embodiments, but they do not constitute any limitation to the present invention.

[0029]

[0030]

[0031] [Example 1]

[0032] In a 250 ml three-necked flask equipped with a stirrer, a thermometer, an oil-water separator and a reflux condenser, 100 ml of methyl isobutyl ketone, 5 g of p-di-(2-hydroxyisopropyl)benzene (p-DC), 5.84 g of hydrogen peroxide (30% by weight), and 0.6 g of concentrated sulfuric acid (98wt%) catalyst were added, and the mixture was heated in a water bath at 45°C, and stirring was started to react. During the reaction, the reaction progress was detected by gas chromatography. The reaction lasted for 3 hours. When the p-DC content in the reaction solution was less than 5.0% as determined by gas chromatography, the reaction was stopped. The mixture was cooled to room temperature, allowed to stand and the water layer was separated. The oil phase was extracted with a 2% sodium hydroxide solution to remove the byproduct DHP, and then the p-HHP in the organic phase was extracted with an 8% sodium hydroxide solution. The alkaline extracts were combined, and neutralized with 10% dilute sulfuric acid to a pH of 6-7 to precipitate white p-HHP, which was filtered to obtain a crude p-HHP product. p-HHP was recrystallized with a mixed solvent of ethanol and water, filtered, washed and dried to obtain p-HHP with a melting point of 91-92° C. The conversion rate of p-DC was 96%, the yield of p-HHP was 73%, and the purity of p-HHP was 98%.

[0033] [Example 2]

[0034] In a 250 ml three-necked flask equipped with a stirrer, a thermometer, an oil-water separator and a reflux condenser, 50 ml of toluene, 50 ml of acetone, 5 g of p-di-(2-hydroxyisopropyl)benzene (p-DC), 4.38 g of hydrogen peroxide (30% by weight) and 1.0 g of concentrated sulfuric acid (98wt%) as a catalyst were added, and the mixture was heated in a 55°C water bath with stirring. During the reaction, the reaction progress was monitored by gas chromatography. The reaction was continued for 2 hours. When the p-DC content of the reaction solution was less than 5% as determined by chromatography, the reaction was stopped. Cool down to room temperature, stand and separate the water layer, extract the byproduct DHP from the oil phase with 1.5% sodium hydroxide solution, and then extract the p-HHP in the organic phase with 5% sodium hydroxide solution, combine the alkaline extracts, neutralize with 10% dilute sulfuric acid to pH 6-7, precipitate white p-HHP, filter to obtain p-HHP crude product, recrystallize p-HHP with a mixed solvent of ethanol and water, filter, wash and dry to obtain p-HHP, melting point 91-92°C. The conversion rate of p-DC is 95%, the yield of p-HHP is 70%, and the purity of p-HHP is 98%.

[0035] [Example 3]

[0036] In a 250 ml three-necked flask equipped with a stirrer, a thermometer, an oil-water separator and a reflux condenser, 50 ml of toluene, 50 ml of methyl isobutyl ketone, 5 g of p-di-(2-hydroxyisopropyl)benzene (p-DC), 8.76 g of hydrogen peroxide (30% by weight of hydrogen peroxide) and 0.5 g of concentrated sulfuric acid (98wt%) as a catalyst were added, and the mixture was heated in a 55°C water bath with stirring. During the reaction, the reaction progress was detected by gas chromatography. The reaction was continued for 2 hours. When the p-DC content of the reaction solution was less than 5% as determined by chromatography, the reaction was stopped. Cool down to room temperature, stand and separate the water layer, extract DHP from the oil phase with 2% sodium hydroxide solution, and then extract p-HHP from the organic phase with 5% sodium hydroxide solution, combine the alkaline extracts, neutralize with dilute sulfuric acid to pH 6-7, precipitate white p-HHP, filter to obtain p-HHP crude product, recrystallize p-HHP with a mixed solvent of ethanol and water, filter, wash and dry to obtain p-HHP, melting point 91-92°C. The conversion rate of p-DC is 98%, the yield of p-HHP is 76%, and the purity of p-HHP is 98%.

[0037] [Example 4]

[0038] In a 250 ml three-necked flask equipped with a stirrer, a thermometer, an oil-water separator and a reflux condenser, 100 ml of methyl isobutyl ketone, 5 g of p-di-(2-hydroxyisopropyl)benzene (p-DC), 5.84 g of 30% hydrogen peroxide, and 0.5 g of perchloric acid (70wt%) catalyst were added, and the mixture was heated in a water bath at 45°C, and stirring was started to react. During the reaction, the reaction progress was detected by gas chromatography. The reaction lasted for 3.5 hours. When the p-DC content in the reaction solution was less than 5.0% as determined by gas chromatography, the reaction was stopped. The mixture was cooled to room temperature, allowed to stand and the water layer was separated. The oil phase was extracted with a 2% sodium hydroxide solution to remove the byproduct DHP, and then the p-HHP in the organic phase was extracted with an 8% sodium hydroxide solution. The alkaline extracts were combined, neutralized with dilute sulfuric acid to a pH of 6-7, p-HHP was precipitated, and p-HHP was obtained by suction filtration to obtain a crude p-HHP product. p-HHP was recrystallized with a mixed solvent of ethanol and water, filtered, washed and dried to obtain p-HHP with a melting point of 91-92° C. The conversion rate of p-DC was 96%, the yield of p-HHP was 74%, and the purity of p-HHP was 97%.

[0039] [Comparative Example 1]

[0040] In a 250 ml three-necked flask equipped with a stirrer, a thermometer, an oil-water separator and a reflux condenser, 100 ml of methyl isobutyl ketone, 5 g of p-di-(2-hydroxyisopropyl)benzene (p-DC), 17.5 g of hydrogen peroxide (30% by weight), and 0.6 g of concentrated sulfuric acid (98wt%) catalyst were added, and the mixture was heated in a water bath at 45°C, stirred, and reacted. During the reaction, the reaction progress was detected by gas chromatography. The reaction was continued for 3 hours. When the p-DC content in the reaction solution was less than 5.0% by gas chromatography, the reaction was stopped. The gas chromatography data showed that the main product of the reaction was DHP. The reaction mixture was cooled to room temperature, allowed to stand to separate the water layer, and p-DHP and a small amount of p-HHP in the organic phase were extracted with a 5% sodium hydroxide solution. The alkaline extracts were combined, neutralized with 10% dilute sulfuric acid to a pH of 6-7, p-DHP (including a small amount of p-HHP) was precipitated, and p-DHP crude product was obtained by suction filtration. p-DHP was recrystallized from methanol, filtered, washed and dried to obtain p-DHP with a melting point of 143-145° C. The conversion rate of p-DC was 98% and the yield of p-DHP was 61%.

[0041] It can be seen from Comparative Example 1 that when the molar ratio of DC to hydrogen peroxide is 1:6, the main product obtained by the oxidation reaction is DHP.

[0042] [Comparative Example 2]

[0043] In a 250 ml three-necked flask equipped with a stirrer, a thermometer, an oil-water separator and a reflux condenser, 100 ml of toluene solvent, 5 g of p-di-(2-hydroxyisopropyl)benzene (p-DC), 5.84 g of hydrogen peroxide (30% by weight), and 0.6 g of concentrated sulfuric acid (98wt%) catalyst were added, and the mixture was heated in a water bath at 45°C, and stirring was started to react. During the reaction, the reaction progress was detected by gas chromatography. The reaction lasted for 3 hours. When the p-DC content in the reaction liquid was less than 5.0% as determined by gas chromatography, the reaction was stopped. The mixture was cooled to room temperature, allowed to stand and the water layer was separated. The oil phase reaction mixture was neutralized to neutrality with an alkali solution. The crude p-HHP product obtained by suction filtration had the following liquid chromatography analysis results: DHP 75.43%, p-HHP 23.69%, p-DC 0.26%, and the remainder was other trace impurities. The conversion rate of p-DC was 97%, and the content of DHP was greater than that of p-HHP.

[0044] It can be seen from Comparative Example 2 that when toluene is used as the reaction solvent, the main product obtained by the oxidation reaction is DHP, and the content of DHP is much greater than that of p-HHP.

[0045] [Comparative Example 3]

[0046] In a 250 ml three-necked flask equipped with a stirrer, a thermometer, an oil-water separator and a reflux condenser, 100 ml of methyl isobutyl ketone, 5 g of p-di-(2-hydroxyisopropyl)benzene (p-DC), 5.84 g of hydrogen peroxide (30% by weight), and 1.6 g of concentrated sulfuric acid (98wt%) catalyst were added, and the mixture was heated in a water bath at 45°C, and stirring was started to react. During the reaction, the reaction progress was detected by gas chromatography. The reaction lasted for 3 hours. When the p-DC content in the reaction liquid was less than 5.0% as determined by gas chromatography, the reaction was stopped. The mixture was cooled to room temperature, allowed to stand and the water layer was separated. The oil phase was neutralized to neutrality with a 2% sodium hydroxide solution. The liquid chromatography analysis results of the organic matter in the oil phase except the solvent were: DHP% 28.31, p-HHP 67.66%, DC 3.53%, and the rest were other trace impurities.

[0047] It can be seen from Comparative Example 3 that methyl isobutyl ketone is used as the reaction solvent, the weight ratio of DC to the acid catalyst is 1:0.32, and the content ratio of p-HHP to DHP in the mixture after the reaction is 2.39:1. It is difficult to separate and purify high-content p-HHP by alkali solution extraction and crystallization methods.

[0048] The embodiments described above are only used to explain the present invention and do not constitute any limitation to the present invention. The present invention has been described with reference to typical embodiments, but it should be understood that the words used therein are descriptive and explanatory words, rather than restrictive words. The present invention may be modified as specified within the scope of the claims of the present invention, and the present invention may be revised without departing from the scope and spirit of the present invention. Although the present invention described therein relates to specific methods, materials and embodiments, it does not mean that the present invention is limited to the specific examples disclosed therein, on the contrary, the present invention can be extended to all other methods and applications with the same functions.

Claims

1. A method for synthesizing 4-(2-hydroxy-2-propyl)isopropylbenzene hydroperoxide, comprising the steps of selectively oxidizing p-di-(2-hydroxyisopropyl)benzene with hydrogen peroxide in the presence of a solvent and an acidic catalyst to obtain 4-(2-hydroxy-2-propyl)isopropylbenzene hydroperoxide, wherein: The solvent is a ketone compound, or a mixed liquid of a ketone compound and aromatic hydrocarbons.

2. The synthesis method according to claim 1, characterized in that The ketone compound in the solvent is a ketone compound having 3 to 6 carbon atoms, preferably at least one of acetone, methyl ethyl ketone and methyl isobutyl ketone.

3. The synthesis method according to claim 1 or 2, characterized in that The aromatic hydrocarbon is an aromatic hydrocarbon having 7 to 10 carbon atoms; preferably, the aromatic hydrocarbon is at least one of toluene, xylene, ethylbenzene and isopropylbenzene.

4. The synthesis method according to claim 1, characterized in that The acid catalyst is selected from inorganic acids, and preferably the inorganic acid is selected from at least one of sulfuric acid, perchloric acid, nitric acid and phosphoric acid.

5. The synthesis method according to any one of claims 1 to 4, characterized in that When the solvent is a mixture of ketone compounds and aromatic hydrocarbons, the mass content of the ketone compounds is 10% to 80%, and the mass content of the aromatic hydrocarbons is 20% to 90%.

6. The synthesis method according to claim 1, characterized in that The mass content of hydrogen peroxide in the hydrogen peroxide is 10% to 60%.

7. The synthesis method according to claim 1, characterized in that The molar ratio of the hydrogen peroxide to p-di-(2-hydroxyisopropyl)benzene is (1.0-4.0):

1.

8. The synthesis method according to claim 1, characterized in that The weight ratio of the p-di-(2-hydroxyisopropyl)benzene to the acidic catalyst is 1:(0.01-0.25).

9. The synthesis method according to claim 1, characterized in that The ratio of the solvent to p-di-(2-hydroxyisopropyl)benzene is (10-100) mL: 1 g.

10. The synthesis method according to claim 1, characterized in that The reaction conditions of the selective oxidation reaction are: the reaction temperature is 30-70° C., the reaction pressure is normal pressure, and the reaction time is 2-6 hours.

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