A method for preparing di-(2-hydroxyisopropyl)benzene, a key intermediate of hydroquinone

Abstract

A method for preparing di-(2-hydroxyisopropyl)benzene, a key intermediate of hydroquinone. The method comprises the following steps: (1) reacting diisopropylbenzene and an oxygen-containing gas in the presence of an alkali and an initiator to obtain a liquid containing solid di-(2-hydroxyisopropyl)benzene; (2) separating and purifying the solid di-(2-hydroxyisopropyl)benzene to obtain a di-(2-hydroxyisopropyl)benzene product with a content >99.95%, wherein the initiator includes one or more of azobisisobutyronitrile, diisopropylbenzene dipperoxide, and diisopropylbenzene peroxide, and the alkali includes sodium hydroxide, potassium hydroxide, or a combination thereof, and the oxidation reaction in step (1) is carried out at a temperature of 80-150°C and a pressure of 0.3-1.8 MPa.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis, and specifically to a novel method for preparing the key intermediate of hydroquinone, bis-(2-hydroxyisopropyl)benzene. Background Technology

[0002] Di-(2-hydroxyisopropyl)benzene (also known as α,α'-dihydroxy-diisopropylbenzene) is a key raw material for the preparation of hydroquinone. Hydroquinone can be used to synthesize insecticides (such as phosmet), herbicides (such as ethoxyflufenoxam), and can also be used to make ointments for topical treatment of fungal skin infections. Because hydroquinone itself is non-carcinogenic, non-teratogenic, and non-bioaccumulative, it has the advantage of good biocompatibility.

[0003] Reports of synthesis research and production by Hercules in the United States, Bayer in Germany, and Mitsui Petrochemicals in Japan have been published, but there are no reports in China. Therefore, it is very necessary to research and invent the synthesis of bis-(2-hydroxyisopropyl)benzene.

[0004] There are basically two routes for the preparation of DC, both of which use diisopropylbenzene (DIPB) as the starting material. The reaction formula below uses p-diisopropylbenzene as an example.

[0005] Route 1: Halogenation (e.g., bromination) of diisopropylbenzene to produce di(2-bromoisopropyl)benzene, which is then hydrolyzed to di-(2-hydroxyisopropyl)benzene.

[0006]

[0007] Route 2: In a special reactor, diisopropylbenzene is oxidized with oxygen in the presence of cobalt salt to obtain di-(2-hydroxyisopropyl)benzene.

[0008] CN103396292A discloses a novel method for preparing di-(2-hydroxyisopropyl)benzene, as follows:

[0009]

[0010] CN115403446A discloses a method for obtaining 1,3-diisopropylbenzene by reacting with oxygen in the air under the action of an active agent to produce di-(2-hydroxyisopropyl)benzene, etc. In this method, under the catalysis of cobalt ions, hydroperoxides decompose into alcohols and release free radicals to oxidize other raw materials, thereby achieving a one-step method for obtaining di-(2-hydroxyisopropyl)benzene.

[0011] Therefore, there is an urgent need in this field for a new method for synthesizing bis-(2-hydroxyisopropyl)benzene, which has a simple operation process, can obtain bis-(2-hydroxyisopropyl)benzene in high yield and with high selectivity, and has mild and easy-to-control reaction conditions, making it suitable for industrialization. Summary of the Invention

[0012] The purpose of this application is to provide a new method for synthesizing the key intermediate di-(2-hydroxyisopropyl)benzene of hydroquinone. The method has a simple operation process, can obtain di-(2-hydroxyisopropyl)benzene in high yield and with high selectivity, and the reaction conditions are mild and easy to control, making it suitable for industrialization.

[0013] The inventors of this application have discovered that di-(2-hydroxyisopropyl)benzene can be directly obtained by oxidizing diisopropylbenzene under a sufficient strong alkaline atmosphere without the need for a cobalt catalyst, and the conversion rate and selectivity of diisopropylbenzene are greatly improved, thereby simplifying the process and reducing costs.

[0014] This application provides a method for preparing the key intermediate of hydroquinone, bis-(2-hydroxyisopropyl)benzene, the method comprising the following steps:

[0015] (1) React diisopropylbenzene and oxygen-containing gas in the presence of a base and an initiator to obtain a liquid containing di-(2-hydroxyisopropyl)benzene solid;

[0016] (2) Separate and purify the di-(2-hydroxyisopropyl)benzene solid to obtain a di-(2-hydroxyisopropyl)benzene product with a purity >99.95%.

[0017] The initiator includes one or more of azobisisobutyronitrile, dicumyl peroxide, and dicumyl peroxide.

[0018] The alkali includes sodium hydroxide, potassium hydroxide, or a combination thereof.

[0019] The oxidation reaction in step (1) is carried out at a temperature of 80-150℃ and a pressure of 0.3-1.8MPa.

[0020] Another aspect of this application provides a hydroquinone key intermediate, bis-(2-hydroxyisopropyl)benzene, which is prepared by the method of this application. Detailed Implementation

[0021] The "range" disclosed herein is defined by a lower limit and an upper limit. A given range is defined by selecting a lower limit and an upper limit, which define the boundaries of a particular range. Ranges defined in this way can include or exclude endpoints and can be arbitrarily combined; that is, any lower limit can be combined with any upper limit to form a range. For example, if ranges of 60-120 and 80-110 are listed for a specific parameter, it is expected that ranges of 60-110 and 80-120 are also expected. Furthermore, if minimum range values ​​of 1 and 2 are listed, and if maximum range values ​​of 3, 4, and 5 are listed, then the following ranges are all expected: 1-3, 1-4, 1-5, 2-3, 2-4, and 2-5. In this application, unless otherwise stated, the numerical range "ab" represents a shortened representation of any combination of real numbers between a and b, where a and b are real numbers. For example, the numerical range "0-5" indicates that all real numbers between "0-5" have been listed in this article; "0-5" is simply a shortened representation of these numerical combinations. Furthermore, when a parameter is stated as an integer ≥2, it is equivalent to disclosing that the parameter is, for example, an integer such as 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, etc.

[0022] Unless otherwise specified in this application, all embodiments and preferred embodiments mentioned herein can be combined to form new technical solutions.

[0023] Unless otherwise specified, all technical features and preferred features mentioned herein can be combined to form new technical solutions.

[0024] In this application, unless otherwise specified, all steps mentioned herein may be performed sequentially or randomly, but are preferably performed sequentially. For example, if the method includes steps (a) and (b), it means that the method may include steps (a) and (b) performed sequentially, or it may include steps (b) and (a) performed sequentially. For example, if the method may also include step (c), it means that step (c) may be added to the method in any order. For example, the method may include steps (a), (b), and (c), or it may include steps (a), (c), and (b), or it may include steps (c), (a), and (b), etc.

[0025] In this application, unless otherwise specified, the terms "comprising" and "including" as used herein are open-ended or closed-ended. For example, "comprising" and "including" may mean that other components not listed may also be included, or that only the listed components may be included.

[0026] In the description of this article, it should be noted that, unless otherwise stated, "above" and "below" include the number itself, and "several" in "one or more" means two or more.

[0027] In this description, unless otherwise stated, the term "or" is inclusive. For example, the phrase "A or B" means "A, B, or both A and B". More specifically, the condition "A or B" is satisfied by any of the following conditions: A is true (or exists) and B is false (or does not exist); A is false (or does not exist) and B is true (or exists); or both A and B are true (or exist).

[0028] Unless otherwise specified, percentages (%) or parts refer to weight percentages or parts relative to the composition.

[0029] Unless otherwise stated herein, the sum of the contents of the components in the composition is 100%.

[0030] Unless otherwise stated herein, the sum of the parts of each component in the composition may be 100 parts by weight.

[0031] In this document, unless otherwise stated, “combination of” means a multi-component mixture of the elements, such as two, three, four, and up to the maximum possible multi-component mixture.

[0032] Unless otherwise specified, the term "a" as used in this specification means "at least one".

[0033] In this paper, unless otherwise stated, all reactions were carried out at room temperature and pressure.

[0034] This application provides a method for preparing the key intermediate of hydroquinone, bis-(2-hydroxyisopropyl)benzene, the method comprising the following steps:

[0035] (1) React diisopropylbenzene and oxygen-containing gas in the presence of a base and an initiator to obtain a liquid containing di-(2-hydroxyisopropyl)benzene solid;

[0036] (2) Separate and purify the di-(2-hydroxyisopropyl)benzene solid to obtain a di-(2-hydroxyisopropyl)benzene product with a purity >99.95%.

[0037] The initiator includes one or more of azobisisobutyronitrile, dicumyl peroxide, and dicumyl peroxide.

[0038] The alkali includes sodium hydroxide, potassium hydroxide, or a combination thereof.

[0039] The oxidation reaction in step (1) is carried out at a temperature of 80-150℃ and a pressure of 0.3-1.8MPa.

[0040] In this application, the diisopropylbenzene may be a commonly used diisopropylbenzene product in the art, which may be prepared according to methods commonly used in the art, or it may be a commercially available product. Typically, diisopropylbenzene is in liquid form, but it may also be in solution form.

[0041] In this application, the initiator includes one or more of azobisisobutyronitrile, diisopropylbenzene dipperoxide, and diisopropylbenzene peroxide. This application selects an initiator with a similar structure to the starting material diisopropylbenzene, which exhibits higher oxidative activity during the reaction, thereby improving the selectivity and yield of di-(2-hydroxyisopropyl)benzene.

[0042] In one example of this application, the amount of the initiator, based on the weight of the diisopropylbenzene, can be 0.01%-20%, preferably 0.05-15%, and more preferably 0.1-10%.

[0043] In this application, the oxygen-containing gas refers to any gas containing oxygen, such as a gas containing 1-100% by volume of oxygen, and also includes gases that can generate oxygen during a reaction. In one example of this application, the oxygen-containing gas refers to a gas containing 10-100% by volume of oxygen. In another example of this application, the oxygen-containing gas refers to air.

[0044] In this application, the amount of oxygen used is 0.2-6 times, for example 0.5-5 times or 1-4 times, the weight of oxygen in the oxygen-containing gas.

[0045] In this application, the base is a strong base to improve reactivity, such as increasing the selectivity, yield, and conversion rate of the reaction. In one example of this application, the base includes sodium hydroxide, potassium hydroxide, or a combination thereof. The base can be in the form of a solution or a solid. In the case of a base solution, the solvent can be a solvent commonly used in the art, including but not limited to water. In a preferred embodiment of this application, the base is an aqueous solution of sodium hydroxide and potassium hydroxide, with a mass content of 1-20%. Based on the weight of diisopropylbenzene, the amount of the base (in the case of a base solution, based on the weight of the base in the solution) is 10%-100% of the weight of diisopropylbenzene, preferably 20-90%, and more preferably 30-70%.

[0046] In the method of this application, in order to obtain better results, the temperature of the oxidation reaction in step (1) is 80-150℃ (preferably 80-120℃) and the pressure is 0.3-1.8MPa (preferably 0.5-1.5MPa).

[0047] In the method of this application, step (1) preferably does not use a cobalt-containing catalyst. The applicant has found that, unlike prior art, under the specific raw materials and reaction conditions of this application, better technical effects, such as higher conversion, selectivity and yield, can be obtained without using a cobalt-containing catalyst.

[0048] In the method of this application, the separation step in step (2) can be performed by methods commonly used in the art, including but not limited to filtration and centrifugation. The separation step can be performed at room temperature or under heating conditions. In one example of this application, the temperature of the separation step is 10-100℃, preferably 20-70℃.

[0049] In the method of this application, the purification step in step (2) can be a purification method commonly used in the art, including but not limited to recrystallization. The recrystallization method can be carried out using solvents commonly used in the art, including but not limited to one or more combinations of methanol, ethanol, acetone, methyl isobutyl ketone, methyl acetate, ethyl acetate, and butyl acetate, in an amount of 1 to 10 times the weight of the product, and at a crystallization temperature of 30 to 80°C.

[0050] Another aspect of this application provides a hydroquinone key intermediate, bis-(2-hydroxyisopropyl)benzene, which is prepared by the method of this application.

[0051] In one example of this application, the purity of the bis-(2-hydroxyisopropyl)benzene is greater than 99.5%.

[0052] The present invention is further illustrated below by way of embodiments, but the invention is not limited to the scope of the embodiments described herein. Experimental methods in the following embodiments that do not specify specific conditions were performed according to conventional methods and conditions, or as selected according to the product instructions.

[0053] Main reagents for the experiment

[0054] reagents type Manufacturer p-Diisopropylbenzene Analytical Pure Chengdu McCarthy Chemical Co., Ltd., etc. m-Diisopropylbenzene Analytical Pure Chengdu McCarthy Chemical Co., Ltd., etc. Azobisisobutyronitrile Analytical Pure Chengdu McCarthy Chemical Co., Ltd., etc. Sodium hydroxide Analytical Pure Jiangsu Yangnong Chemical Group Co., Ltd., etc. ethanol Analytical Pure Chengdu McCarthy Chemical Co., Ltd., etc.

[0055] Main instruments for the experiment

[0056] Instrument Name model Manufacturer Electronic balance JA31002 Shanghai Yitian Scientific Instruments Co., Ltd. 1L reactor J2-04 Yantai Songling Chemical Equipment Co., Ltd., etc. liquid chromatograph LC Agilent Technologies, etc.

[0057] Experimental methods:

[0058] Diisopropylbenzene conversion rate: (Amount of diisopropylbenzene converted / Amount of diisopropylbenzene added to the total reaction) * 100%

[0059] Di-(2-hydroxyisopropyl)benzene selectivity: (Amount of di-(2-hydroxyisopropyl) actually generated / Amount of diisopropylbenzene converted) * 100%

[0060] Di-(2-hydroxyisopropyl)benzene yield: p-diisopropylbenzene conversion * di-(2-hydroxyisopropyl)benzene selectivity

[0061] Yield of bis-(2-hydroxyisopropyl)benzene crystallization: (mass after recrystallization * corresponding content) / (mass before recrystallization * corresponding content) * 100%

[0062] Liquid phase testing conditions

[0063]

[0064] Example 1

[0065] 162.2 g of p-diisopropylbenzene, 0.2 g of azobisisobutyronitrile (AIBN), and 405.5 g of 20% sodium hydroxide aqueous solution were added to a 1 L reactor and heated to 80 °C. 3244.0 g of air was introduced at 0.5 MPa for 12 h, after which the reaction was stopped, yielding a reaction solution containing α,α'-dihydroxy-1,4-diisopropylbenzene (HPLC elution times are shown in Table 4). The conversion rate of p-diisopropylbenzene was 97.0%, the selectivity of α,α'-dihydroxy-1,4-diisopropylbenzene was 99.0%, and the yield was 96.0%.

[0066] The reaction mixture was separated into solid and liquid phases. Then, the incompletely converted p-diisopropylbenzene from the upper oil layer and the lower alkali layer were reused in the reactor. The crude α,α'-dihydroxy-1,4-diisopropylbenzene obtained by filtration was recrystallized from ethanol at 50°C to obtain 178.8 g of α,α'-dihydroxy-1,4-diisopropylbenzene (HPLC elution times are shown in Table 4). The crystallization yield was 96.0%, the overall yield was 92.2%, and the product purity was 99.98%.

[0067] Example 2

[0068] 162.2 g of m-diisopropylbenzene, 0.2 g of azobisisobutyronitrile (AIBN), and 405.5 g of 20% sodium hydroxide aqueous solution were added to a 1 L reactor and heated to 80 °C. 3244.0 g of air was introduced at 0.5 MPa for 12 h, after which the reaction was stopped, yielding a reaction solution containing α,α'-dihydroxy-1,3-diisopropylbenzene (HPLC elution times are shown in Table 5). The conversion rate of m-diisopropylbenzene was 95.0%, the selectivity of α,α'-dihydroxy-1,3-diisopropylbenzene was 97.0%, and the yield was 92.2%.

[0069] The reaction solution was separated into solid and liquid phases. Then, the incompletely converted m-diisopropylbenzene from the upper oil layer and the lower liquid alkali layer were reused in the reactor. The crude α,α'-dihydroxy-1,3-diisopropylbenzene obtained by filtration was recrystallized from methanol at 50°C to obtain 169.8 g of α,α'-dihydroxy-1,3-diisopropylbenzene (liquid chromatographic peak times are shown in Table 5), with a crystallization yield of 95.0%, an overall yield of 87.5%, and a product purity of 99.96%.

[0070] Examples 3-12

[0071] Based on Example 1, different initiators were used:

[0072] Table 1. Initiator Evaluation Results

[0073]

[0074] Table 1 shows that azobisisobutyronitrile, 1,4-diisopropylbenzene disperoxide, and 1,4-mono-diisopropylbenzene exhibit high oxidizing activity and α,α'-dihydroxy-1,4-diisopropylbenzene selectivity. This indicates that all free radical initiators can promote the oxidation reaction, and initiators with structures similar to the starting materials can further enhance the reactivity.

[0075] Examples 13-19

[0076] Based on Example 1, different reaction temperatures and pressures were used:

[0077] Table 2 Evaluation results of temperature and pressure

[0078]

[0079]

[0080] As can be seen from the data in Table 2, when the reaction temperature is 80-100℃ and the pressure is 0.1-1.5MPa, the raw material diisopropylbenzene has a high conversion rate and the product α,α'-dihydroxy-1,4-diisopropylbenzene has high selectivity.

[0081] Examples 20-27

[0082] Based on Example 1, different crystallization temperatures and solvents were used:

[0083] Table 3 Evaluation results of the effects of temperature and solvent on crystallization

[0084] Example Temperature / °C solvent α,α'-Dihydroxy-1,4-Diisopropyl crystallization yield / % 20 50 methanol 95.3 21 50 acetone 94.7 22 50 Methyl isobutyl ketone 96.0 23 50 Methyl acetate 93.2 24 50 Ethyl acetate 96.0 25 50 Butyl acetate 95.1 26 30 ethanol 76.8 27 70 ethanol 98.5

[0085] Table 4. Components and Peak Time

[0086]

[0087] Table 5. Components and Peak Time

[0088]

[0089]

[0090] The content described herein is not limited to the embodiments described herein.

[0091] The above are merely preferred embodiments of the present invention. It should be noted that the above preferred embodiments should not be considered as limitations on the present invention, and the scope of protection of the present invention should be determined by the scope defined in the claims. For those skilled in the art, several improvements and modifications can be made without departing from the spirit and scope of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A method for preparing the key intermediate di-(2-hydroxyisopropyl)benzene of hydroquinone, the method comprising the following steps: (1) React diisopropylbenzene and oxygen-containing gas in the presence of a base and an initiator to obtain a liquid containing di-(2-hydroxyisopropyl)benzene solid; (2) Separate and purify the di-(2-hydroxyisopropyl)benzene solid to obtain a di-(2-hydroxyisopropyl)benzene product with a purity >99.95%. The initiator includes one or more of azobisisobutyronitrile, dicumyl peroxide, and dicumyl peroxide. The alkali includes sodium hydroxide, potassium hydroxide, or a combination thereof. The oxidation reaction in step (1) is carried out at a temperature of 80-150℃ and a pressure of 0.3-1.8 MPa. Step (1) does not use a cobalt-containing catalyst.

2. The method of claim 1, wherein, The amount of the initiator is 0.01%-20% based on the weight of the diisopropylbenzene.

3. The method of claim 1, wherein, The amount of the initiator is 0.05-15% based on the weight of the diisopropylbenzene.

4. The method of claim 1, wherein, The amount of the initiator is 0.1-10% based on the weight of the diisopropylbenzene.

5. The method of claim 1, wherein, The oxygen-containing gas is a gas containing oxygen or a gas that can produce oxygen during the reaction.

6. The method of claim 1, wherein, The oxygen-containing gas is a gas containing 1-100% by volume oxygen.

7. The method of claim 1, wherein, The oxygen-containing gas refers to a gas containing 10-100% by volume oxygen.

8. The method of claim 1, wherein, The oxygen-containing gas refers to air.

9. The method of claim 1, wherein, The amount of oxygen used is 0.2-6 times the weight of the diisopropylbenzene, based on the weight of oxygen in the oxygen-containing gas.

10. The method of claim 1, wherein, The amount of oxygen used is 0.5-5 times the weight of the diisopropylbenzene, based on the weight of oxygen in the oxygen-containing gas.

11. The method of claim 1, wherein, The amount of oxygen used is 1-4 times the weight of the diisopropylbenzene, based on the weight of oxygen in the oxygen-containing gas.

12. The method of claim 1, wherein, The base is in the form of a solution.

13. The method of claim 1, wherein, The alkali is an aqueous solution of sodium hydroxide and potassium hydroxide.

14. The method of claim 1, wherein, The amount of alkali used is 10%-100% of the weight of diisopropylbenzene.

15. The method of claim 1, wherein, The amount of alkali used is 20-90% of the weight of diisopropylbenzene.

16. The method of claim 1, wherein, The amount of alkali used is 30-70% of the weight of diisopropylbenzene.

17. The method of claim 1, wherein, The oxidation reaction in step (1) is carried out at a temperature of 80-150℃ and a pressure of 0.3-1.8MPa.

18. The method of claim 1, wherein, The oxidation reaction in step (1) is carried out at a temperature of 80-120℃ and a pressure of 0.5-1.5MPa.

19. The method of claim 1, wherein, The purification step in step (2) includes recrystallization.

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