A highly selective preparation method for 4-(4-acetylcumyl)phenol ester compounds

Abstract

The present application proposes a highly selective preparation method of 4-(4-acetylcumyl)phenol ester compounds, which specifically comprises the following steps: A1, 4-cumylphenol is subjected to a pre-acylation reaction in a system containing a first acylating agent and an acid-binding base, and then a first quencher is added to the system to complete the pre-acylation reaction to prepare 4-cumylphenol ester; A2, 4-cumylphenol ester is subjected to a Friedel-Crafts acetylation reaction in a system containing a second acylating agent and an acylation catalyst, and then a second quencher is added to the system to complete the Friedel-Crafts acetylation reaction to prepare 4-(4-acetylcumyl)phenol ester; wherein the molecular formula of the first acylating agent is RCOCl or (RCO)2O, R is a large steric hindrance or / and strong electron-pulling group, and R is selected from C9~C20 substituted aromatic groups, C3~C10 branched hydrocarbon groups or C1~C10 perfluoroalkyl groups; and the second acylating agent is acetyl chloride or acetic anhydride. The highly selective preparation method of 4-(4-acetylcumyl)phenol ester compounds of the present application can at least avoid the generation of ortho-acetylated by-products of the ester group and improve the purity of the target product.

Description

Technical Field

[0001] The present application relates to the field of chemical synthesis, and in particular to a highly selective preparation method of 4-(4-acetylcumyl)phenol ester compounds. Background Art

[0002] As shown in the general formula (3), it is a 4-(4-acetylcumyl)phenol ester compound, which can be directly used in the fields of photoresist production, further used in the manufacture of integrated circuits and computer chips, and can also be used to prepare other high-purity electronic chemicals, especially high-purity 4,4'-[1-[4-[1-(4-hydroxyphenyl)-1-methylethyl]phenyl]ethylene]bisphenol (TPPA) and its analogs.

[0003] (3)

[0005] Honshu Chemical Industry Co., Ltd. (WO2010 / 134559) reported a method for preparing 4-(4-acetylcumyl)phenol acetate by Friedel-Crafts reaction of acetyl chloride and 4-cumylphenol acetate, and the reaction principle is as follows:

[0006]

[0007] The disadvantage of this method is that the product has a serious position selectivity problem. In addition to the normal acetylation product, a certain amount (about 10%) of ester ortho-acetylation byproduct is also generated. This byproduct is difficult to separate from the product, which not only requires the introduction of cumbersome post-processing and purification steps, but more importantly, it seriously affects the product quality and is difficult to meet the high chemical purity requirements required in the field of photoresists.

[0008] The purpose of the present invention is to provide a highly selective preparation method of 4-(4-acetylcumyl)phenol ester compounds, aiming to improve the synthesis process, fundamentally improve the position selectivity of the acetylation reaction, avoid the generation of ortho-acetylated by-products of the ester group, and improve the product quality and yield. Summary of the invention

[0009] In view of the deficiencies in the prior art, the purpose of the present application is to provide a highly selective preparation method for 4-(4-acetylcumyl)phenol ester compounds, which can at least avoid the formation of ortho-acetylated ester by-products and improve the purity of the target product.

[0010] To achieve the above-mentioned purpose and other related purposes, according to one aspect of the present application, a highly selective preparation method of 4-(4-acetylcumyl)phenol ester compounds is provided, and the synthesis route thereof is as follows:

[0011]

[0012] Specifically, the method comprises the following steps: A1, 4-cumylphenol (1) is subjected to a pre-acylation reaction in a system containing a first acylating agent and an acid-binding base, and then a first quencher is added to the system to complete the pre-acylation reaction, thereby preparing 4-cumylphenol ester (2); A2, 4-cumylphenol ester (2) is subjected to a Friedel-Crafts acetylation reaction in a system containing a second acylating agent and an acylation catalyst, and then a second quencher is added to the system to complete the Friedel-Crafts acetylation reaction, thereby preparing 4-(4-acetylcumyl)phenol ester (3); wherein the molecular formula of the first acylating agent is RCOCl or (RCO)2O, R is a large steric hindrance or / and strong electron-pulling group, and R is selected from C9~C20 substituted aromatic groups, C3~C10 branched hydrocarbon groups or C1~C10 perfluoro hydrocarbon groups; and the second acylating agent is acetyl chloride or acetic anhydride.

[0013] In some embodiments, R is selected from mesitylene, tert-butyl, isopropyl, trifluoromethyl, or perfluorobutyl.

[0014] In some embodiments, the acid binding agent is a weakly alkaline acid binding agent. In some embodiments, the acid binding agent can be selected from one of triethylamine, pyridine, and potassium carbonate.

[0015] In some embodiments, the first quencher is water or a saturated aqueous sodium bicarbonate solution.

[0016] In some embodiments, the acylation catalyst uses a Lewis acid. In some embodiments, the acylation catalyst can be selected from aluminum chloride, SnCl4, copper chloride or FeCl3.

[0017] In some embodiments, the first acylating agent is trimethylbenzoyl chloride, pivaloyl chloride, isobutyryl chloride, trifluoroacetyl chloride or trifluoroacetic anhydride, and 4-cumylphenol (1) reacts with the first acylating agent in the presence of a solvent at 10-30°C, the solvent is selected from alkyl halides, and the amount of the solvent is 1-20 times the weight of 4-cumylphenol (1). In some embodiments, 4-cumylphenol (1) reacts with the first acylating agent at 15-20°C.

[0018] In some embodiments, the molar ratio of 4-cumylphenol (1) to the first acylating agent is 1:1-1.5.

[0019] In some embodiments, the molar ratio of the acid-binding agent to 4-cumylphenol (1) is 1-1.6:1.

[0020] In some embodiments, the first quenching agent is water, and the amount of water used is 1-20 times the weight of 4-cumylphenol (1).

[0021] In some embodiments, the molar ratio of the second acylating agent to 4-cumylphenol ester (2) is 0.8-2:1.

[0022] In some embodiments, the acylation catalyst is aluminum chloride, and the molar ratio of aluminum chloride to 4-cumylphenol ester (2) is 0.8-3:1.

[0023] In some embodiments, the acylation catalyst is aluminum chloride, and the contact reaction temperature of the mixture of 4-cumylphenol ester (2), acetyl chloride and aluminum chloride is 0-30°C.

[0024] In some embodiments, the second quencher is a hydrochloric acid solution, the mass percentage concentration of the hydrochloric acid solution is 1% to 10%, and the mass ratio of the hydrochloric acid solution to the aluminum chloride is 2 to 5:1.

[0025] The beneficial technical effects of this application are:

[0026] The highly selective preparation method of 4-(4-acetylcumyl)phenol ester compounds provided in the embodiments of the present application at least improves the synthesis process, and by using an acylating agent with special spatial and electronic effects, 4-cumylphenol is converted into a corresponding phenol ester derivative with special spatial and electronic properties, thereby fundamentally improving the position selectivity of the acetylation reaction, at least avoiding the generation of ortho-acetylated byproducts of the ester group, and improving product quality. The highly selective preparation method of 4-(4-acetylcumyl)phenol ester compounds provided in the embodiments of the present application can also improve the purity and yield of the target product, and the target product is suitable for application in the preparation field of photoresists and other electronic chemical materials.

[0027] The embodiments of the present application use an acylating agent with special stereoelectronic properties to pre-acylate 4-cumylphenol (1) in a simple one-step process, which has simple process operation, high product purity and less three wastes. DETAILED DESCRIPTION

[0028] In order to make the purpose, technical solutions and advantages of the present application clearer, the scope of the present application is fully conveyed to the technical personnel in the field, and the exemplary embodiments are fully described in detail below. However, these exemplary embodiments can be implemented in different ways, and should not be construed as being limited to the embodiments described in the present application. Obviously, the described embodiments are only a part of the embodiments of the present application, rather than all of the embodiments. Based on the embodiments in the present application, all other embodiments obtained by ordinary technicians in the field belong to the scope of protection of the present application. It should be understood that the technical features involved in the various embodiments of the present application described below can be combined with each other as long as they do not conflict with each other. The specific experimental conditions or operating conditions not specified in the embodiments can be made under conventional conditions, or made under the conditions recommended by the material supplier.

[0029] In addition, it should be understood that one or more method steps mentioned in the present invention do not exclude that other method steps may exist before or after the combination step or other method steps may be inserted between these explicitly mentioned steps, unless otherwise specified. In the following examples, the reagents, materials and instruments used are all commercially available unless otherwise specified.

[0030] The embodiments of the present application provide a highly selective preparation method of 4-(4-acetylcumyl)phenol ester compounds, and the synthesis route thereof is as follows:

[0031]

[0032] The specific steps include:

[0033] A1. 4-cumylphenol (1) is subjected to a pre-acylation reaction in a system containing a first acylating agent and an acid-binding base, and then a first quencher is added to the system to complete the pre-acylation reaction, thereby preparing 4-cumylphenol ester (2); A2. 4-cumylphenol ester (2) is subjected to a Friedel-Crafts acetylation reaction in a system containing a second acylating agent and an acylation catalyst, and then a second quencher is added to the system to complete the Friedel-Crafts acetylation reaction, thereby preparing 4-(4-acetylcumyl)phenol ester (3); wherein the molecular formula of the first acylating agent is RCOCl or (RCO)2O, R is a large steric hindrance or / and strong electron-withdrawing group, and R is selected from C9~C20 substituted aromatic groups, C3~C10 branched hydrocarbon groups or C1~C10 perfluoro hydrocarbon groups; and the second acylating agent is acetyl chloride or acetic anhydride.

[0034] The embodiments of the present application improve the synthesis process, and by using an acylating agent with special spatial and electronic effects, 4-cumylphenol is converted into a corresponding phenolic ester derivative with special spatial and electronic properties, thereby fundamentally improving the positional selectivity of the acetylation reaction, avoiding the generation of ortho-acetylated byproducts of the ester group, and improving product quality. The product has high purity and good quality, which is conducive to meeting the high chemical purity requirements required in the field of photoresists, and can also be used to prepare other high-purity electronic chemicals, especially high-purity 4,4'-[1-[4-[1-(4-hydroxyphenyl)-1-methylethyl]phenyl]ethylene]bisphenol (TPPA) and its analogs.

[0035] Specifically, when the R group in the 4-cumylphenol ester (2) is a large steric hindrance or / and a strong electron-pulling group, the energy barrier of the acetylation reaction of the 4-cumylphenol ester (2) at the ortho position of the ester group can be significantly increased, thereby improving the positional selectivity of the acylation reaction and significantly reducing the generation of the ortho-acetylated by-product (4) of the ester group. The 4-(4-acetylcumyl)phenol ester (3) prepared in this way can obtain high chemical purity and is suitable for application in the preparation of photoresists and other electronic chemical materials.

[0036]

[0037] In some embodiments, R can be selected from mesitylene, tert-butyl, isopropyl, trifluoromethyl or perfluorobutyl, and accordingly, the first acylating agent can be mesitylene trimethylbenzoyl chloride, pivaloyl chloride, isobutyryl chloride, trifluoroacetyl chloride or trifluoroacetic anhydride. Among them, trimethylphenyl, tert-butyl, isopropyl, trifluoromethyl or perfluorobutyl has a large steric hindrance effect or a strong electron-withdrawing effect, which can effectively prevent acetylation from occurring at the ortho position of the ester group, thereby improving the position selectivity of the acetylation reaction. At the same time, the first acylating agent (mesitylene trimethylbenzoyl chloride, pivaloyl chloride, isobutyryl chloride, trifluoroacetyl chloride or trifluoroacetic anhydride) has the characteristics of easy availability of raw materials, low cost and relatively simple structure. It has been experimentally verified that the acetylation product 4-(4-acetylcumyl)phenol ester (3) has high yield and chemical purity, that is, the reaction has satisfactory position selectivity, and the acetylation product shown in formula (3) is almost exclusively generated, and the ortho-acetylation product of the ester group shown in formula (4) is not generated.

[0038] Preferably, in some embodiments, the first acylating agent can be one of mesitylene trimethylbenzoyl chloride, pivaloyl chloride, isobutyryl chloride, trifluoroacetyl chloride or trifluoroacetic anhydride, and 4-cumylphenol (1) reacts with the first acylating agent in the presence of a solvent at 10-30°C, the solvent is selected from alkyl halides, and the amount of the solvent is 1-20 times the weight of 4-cumylphenol (1), for example, 1-3 times, 3-10 times, 10-20 times, more preferably 3-10 times, and the amount of the solvent is determined according to factors such as the solubility of the reactants and the reaction rate. Among them, 4-cumylphenol (1) and the first acylating agent can react at 10-15°C, 15-20°C, 20-25°C, 25-30°C, and the more preferred reaction temperature is 15-20°C. The alkyl halide can be specifically selected from dichloromethane, chloroform, carbon tetrachloride, dichloroethane, trichloroethane, tetrachloroethane, etc., and more preferably carbon tetrachloride and dichloroethane. In the embodiment of the present application, when 4-cumylphenol (1) reacts with the first acylating agent, if the temperature is too high, the salt will wrap the raw material and reduce the purity of the product; if the temperature is too low, the reaction time needs to be extended to wait for the raw material to react completely.

[0039] Preferably, in some embodiments, the molar ratio of 4-cumylphenol (1) to the first acylating agent is 1:1-1.5, wherein the molar ratio of 4-cumylphenol (1) to the first acylating agent can be 1:1, 1:1-1.2, 1:1.2-1.4, 1:1.4-1.5, and more preferably 1:1-1.2. In the embodiments of the present application, if the amount of the first acylating agent is too low, the conversion of 4-cumylphenol (1) is incomplete, affecting the yield, and if the amount of the first acylating agent is too high, the production cost will increase.

[0040] Preferably, in some embodiments, the acid binding agent is a weakly alkaline acid binding agent. Preferably, the acid binding agent can be selected from one of triethylamine, pyridine and potassium carbonate. Preferably, in some embodiments, the molar ratio of the acid binding agent to 4-cumylphenol (1) is 1 to 1.6:1, wherein the molar ratio of the acid binding agent to 4-cumylphenol (1) can be 1:1, 1 to 1.2:1, 1.2 to 1.4:1, 1.4 to 1.6:1, and more preferably 1.2 to 1.4:1. In the embodiments of the present application, if the amount of the acid binding agent is too low, the reaction conversion rate will be affected, and if the amount of the acid binding agent is too high, the reaction cost will be increased.

[0041] In some embodiments, the first quencher can be water or a saturated sodium bicarbonate aqueous solution. Preferably, in some embodiments, the first quencher is water, and the amount of water used is 1-20 times the weight of 4-cumylphenol (1).

[0042] In step A1, after the reaction of 4-cumylphenol (1) and the first acylating agent is completed, 4-cumylphenol ester (2) can be obtained by desalting and concentrating. For example, the salt can be removed by conventional technical means in the art, such as washing with water, and the solvent can be further removed to obtain a crude product. The salt can be dissolved in water and then dehydrated for the next reaction, or a purification method can be further used to obtain a purer product, for example, the crude product can be dispersed in a solvent, and the solvent can be used to dissolve and remove impurities, thereby obtaining a purer 4-cumylphenol ester (2).

[0043] In step A2, 4-cumylphenol ester (2) is subjected to Friedel-Crafts acetylation reaction to obtain 4-(4-acetylcumyl)phenol ester (3). Optionally, the specific operation is to contact and react a mixture containing 4-cumylphenol ester (2) and a second acylating agent and an acylation catalyst. For example, a solution of 4-cumylphenol ester (2) can be dripped into a mixture containing a second acylating agent and an acylation catalyst. The solvent used to dissolve the mixture of 4-cumylphenol ester (2), the second acylating agent and the acylation catalyst can be a halogenated hydrocarbon solvent, specifically dichloromethane.

[0044] Preferably, in some embodiments, the molar ratio of the second acylating agent to 4-cumylphenol ester (2) is 0.8-2:1, wherein the molar ratio of the second acylating agent to 4-cumylphenol ester (2) can be 0.8-1:1, 1-1.5:1, 1.5-2:1, and more preferably 1-1.5:1. In the embodiments of the present application, if the amount of the second acylating agent is too low, the conversion of 4-cumylphenol ester (2) is incomplete; if the amount of the second acylating agent is too high, the reaction cost will increase.

[0045] Preferably, in some embodiments, the acylation catalyst uses a Lewis acid. Preferably, the acylation catalyst can be selected from aluminum chloride, SnCl4, copper chloride or FeCl3, and FeCl3 is anhydrous ferric chloride.

[0046] Preferably, in some embodiments, the acylation catalyst is aluminum chloride, and the molar ratio of aluminum chloride to 4-cumylphenol ester (2) is 0.8-3:1, wherein the molar ratio of aluminum chloride to 4-cumylphenol ester (2) can be 1-1.5:1, 1.5-2:1, 2-3:1, and more preferably 1.5-2:1. In the embodiments of the present application, if the amount of aluminum chloride is too low, the conversion rate of the Friedel-Crafts reaction decreases, and if the amount of aluminum chloride is too high, the reaction cost and chlorine-containing wastewater will increase.

[0047] Preferably, in some embodiments, the acylation catalyst may be aluminum chloride, and the contact reaction temperature of the mixture of 4-cumylphenol ester (2), acetyl chloride and aluminum chloride is 0-30° C. The contact reaction temperature of the mixture of 4-cumylphenol ester (2), acetyl chloride and aluminum chloride may be 0-10° C., 10-20° C., 20-30° C., and more preferably 0-10° C. If the reaction temperature is too low, the reaction rate will decrease; if the reaction temperature is too high, the side reactions will increase and the selectivity will decrease.

[0048] Preferably, in some embodiments, the second quencher is a hydrochloric acid solution, the mass percentage concentration of the hydrochloric acid solution is 1%-10%, and the mass ratio of the amount of the hydrochloric acid solution to the amount of the aluminum chloride is 2-5:1. Among them, the mass percentage concentration of the hydrochloric acid solution can be 1%-3%, 3%-6%, 6%-10%, and more preferably 6%-10%. Among them, the mass ratio of the amount of the hydrochloric acid solution to the amount of the aluminum chloride can be 2-2.5:1, 2.5-3:1, 3-4:1, and more preferably 2.5-3:1. In the embodiments of the present application, if the amount of hydrochloric acid is too low, the reaction quenching is incomplete, which affects the separation of the product. If the amount of hydrochloric acid is too high, the production cost will increase.

[0049] In the embodiment of the present application, 4-cumylphenol ester (2) and a mixture of acetyl chloride and aluminum chloride are contacted and reacted, and the obtained mixture system is then contacted with hydrochloric acid to complete acid hydrolysis. The process of contacting with hydrochloric acid can be to drop the solution of the above reaction system into an acid solution (hydrochloric acid solution). The temperature of contacting with hydrochloric acid can be 10~40°C, and can be 10~20°C, 20~30°C, 30~40°C, and more preferably 20~30°C. After the contact reaction with hydrochloric acid is completed, the reaction solution is layered, washed, desolventized, and crystallized to obtain a high-purity acetylated product 4-(4-acetylcumyl)phenol ester (3).

[0050] The present application will be described in more detail below through examples.

[0051] Example 1

[0052] Preparation of 4-(4-acetylcumyl)phenyl trimethylbenzoate

[0053]

[0054] Step (1-1): Under nitrogen protection, add 200 g of 4-cumylphenol, 189 g of trimethylbenzoyl chloride and 400 g of dichloromethane to a 2 L four-necked reaction bottle, control the system temperature to 10-15 ° C, and slowly add 105 g of triethylamine at this temperature. After the addition is completed, continue to stir and react at this temperature for 2 hours. After the reaction is complete, add 200 g of pure water, stir and separate after stirring for 1 hour, and repeat twice. Shortly evaporate under reduced pressure until there is no obvious fraction, add 200 g of dichloromethane to the residue in the kettle, stir and dissolve for standby use. According to liquid chromatography analysis, the main product A accounts for more than 99%.

[0055] The structural identification data of the main product A of step (1-1) of Example 1 are as follows:

[0056] H NMR 1 H NMR (600 MHz, CDCl3): δ 7.28–7.33 (m, 6 H), 7.21 (t, J = 8.4 Hz, 1 H), 7.16 (d, J = 8.4 Hz, 2 H), 6.94 (s, 2 H), 2.47 (s, 6 H), 2.34(s, 3 H), 1.73 (s, 6 H); 13 C NMR (151 MHz, CDCl3): δ 168.5, 150.2,148.5, 139.9, 135.6, 130.0, 128.6, 128.0, 127.9, 126.7, 125.7, 120.9, 42.1,28.7, 25.6, 21.7, 20.2.

[0057] Step (1-2): Add 251 g of aluminum chloride to the reaction solution prepared in step (1-1), stir and control the temperature to drop to 0-10°C, drop 81 g of acetyl chloride, and stir until the solid particles of aluminum chloride are almost gone. Control the temperature below 0-10°C and stir for 4 hours.

[0058] In another 2 L four-necked reaction bottle, add 600 g of water and 200 g of 30% concentrated hydrochloric acid, stir evenly, then drip the reaction solution of step (1-2), control the temperature at 30-40°C, and continue to reflux for 2 hours. Layer the organic layer, wash it with 600 g of 5% dilute hydrochloric acid and 1000 g×2 water. The organic layer is concentrated to obtain a crude product. According to liquid chromatography analysis, the ratio of the target product A' to the ester group ortho-acetylation byproduct is 99:1. The crude product is recrystallized with 400 g of toluene, filtered and dried to obtain 347.1 g of a white solid with a yield of 92% and a purity of 99.6%.

[0059] The structural identification data of the target product A' in step (1-2) of Example 1 are as follows:

[0060] H NMR 1 H NMR (600 MHz, CDCl3): δ 7.81 (d, J = 8.4 Hz, 2 H), 7.28 (d, J = 8.4 Hz, 2 H), 7.19 (d, J = 8.4 Hz, 2 H), 7.06 (d, J = 8.4 Hz, 2 H), 6.84 (s, 2 H), 2.51 (s, 3 H), 2.36 (s, 6 H), 2.24 (s, 3 H), 1.64 (s, 6 H); 13 C NMR (151 MHz, CDCl3): δ 197.8, 168.5, 155.9, 148.8, 147.4,140.0, 135.6, 134.8, 129.9, 128.6, 128.3, 127.9, 127.0, 121.1, 42.1, 28.7,25.6, 21.7, 20.2.

[0061] Example 2

[0062] Preparation of 4-(4-acetylcumyl)phenyl pivalate

[0063]

[0064] Step (1-1): Under nitrogen protection, add 200 g of 4-cumylphenol, 125 g of pivaloyl chloride and 400 g of dichloromethane to a 2 L four-necked reaction bottle, control the system temperature to 10-15°C, and slowly add 105 g of triethylamine at this temperature. After the addition is completed, continue to stir and react at this temperature for 2 hours. After the reaction is complete, add 200 g of pure water, stir and separate after stirring for 1 hour, and repeat twice. Shortly evaporate under reduced pressure until there is no obvious fraction, add 200 g of dichloromethane to the residue in the kettle, stir and dissolve for standby use. According to liquid chromatography test, the main product B accounts for more than 99%.

[0065] The structural identification data of the main product B in step (1-1) of Example 2 are as follows:

[0066] H NMR 1H NMR (400 MHz, CDCl3): δ 7.22–7.29 (m, 6 H), 7.18 (m, J= 8.4 Hz, 1 H), 6.96 (d, J = 8.4 Hz, 2 H), 1.68 (s, 6 H), 1.35 (s, 9 H); 13 C NMR (100.1 MHz, CDCl3): δ 177.1, 150.4, 148.9, 147.9, 128.0, 127.8, 126.7, 125.7, 120.7, 42.7, 39.0, 30.8, 27.1.

[0067] Step (1-2): Add 251 g of aluminum chloride to the reaction solution prepared in step (1-1), stir and control the temperature to drop to 0-10°C, drop 81 g of acetyl chloride, and stir until the solid particles of aluminum chloride are almost gone. Control the temperature below 0-10°C and stir for 4 hours.

[0068] In another 2 L four-necked reaction bottle, add 600 g of water and 200 g of 30% concentrated hydrochloric acid, stir evenly, then drip the reaction solution of step (1-2), control the temperature at 30-40°C, and continue to reflux for 2 hours. Layer the organic layer, wash it with 600 g of 5% dilute hydrochloric acid and 1000 g×2 water. The organic layer is concentrated to obtain a crude product. According to liquid chromatography analysis, the ratio of the target product B' to the ortho-acetylated byproduct of the ester group is 99:1. The crude product is recrystallized with 400 g of toluene, filtered and dried to obtain 296.6 g of a white solid with a yield of 93% and a purity of 99.6%.

[0069] The structural identification data of the target product B' in step (1-2) of Example 2 are as follows:

[0070] H NMR 1 H NMR (400 MHz, CDCl3): δ 7.77 (d, J = 8.0 Hz, 2 H), 7.22 (d, J = 8.0 Hz, 2 H), 7.10 (d, J = 8.0 Hz, 2 H), 6.88 (d, J = 8.0 Hz, 2 H), 2.47 (s, 3 H), 1.59 (s, 6 H), 1.25 (s, 9 H). 13C NMR (100.1 MHz, CDCl3): δ 197.5, 177.0, 156.0, 149.1, 146.9, 134.8, 128.2, 127.6, 126.9, 121.0, 43.0, 39.0, 30.9, 27.0, 26.4.

[0071] Example 3

[0072] Preparation of 4-(4-acetylcumyl)phenyl isobutyrate

[0073]

[0074] Step (1-1): Under nitrogen protection, add 200 g of 4-cumylphenol, 110 g of isobutyryl chloride and 400 g of dichloromethane to a 2 L four-necked reaction bottle, control the system temperature to 10-15°C, and slowly add 105 g of triethylamine at this temperature. After the addition is completed, continue to stir and react at this temperature for 2 hours. After the reaction is complete, add 200 g of pure water, stir and separate after stirring for 1 hour, and repeat twice. Shortly evaporate under reduced pressure until there is no obvious fraction, add 200 g of dichloromethane to the residue in the kettle, stir and dissolve for standby use. According to liquid chromatography analysis, the main product C accounts for more than 99%.

[0075] The structural identification data of the main product C of step (1-1) of Example 3 are as follows:

[0076] H NMR 1 H NMR (400 MHz, CDCl3): δ 7.15–7.24 (m, 7 H), 6.96 (d, J= 8.4 Hz, 2 H), 2.79 (sept., J = 6.8 Hz, 1 H), 1.67 (s, 6 H), 1.30 (d, J =6.8 Hz, 6 H); 13 C NMR (100.1 MHz, CDCl3): δ 175.7, 150.4, 148.7, 148.0, 128.0, 127.8, 126.7, 125.7, 120.8, 42.7, 34.1, 30.8, 18.9.

[0077] Step (1-2): Add 251 g of aluminum chloride to the reaction solution prepared in step (1-1), stir and control the temperature to drop to 0-10°C, drop 81 g of acetyl chloride, and stir until the solid particles of aluminum chloride are almost gone. Control the temperature below 0-10°C and stir for 4 hours.

[0078] In another 2 L four-necked reaction bottle, add 600 g of water and 200 g of 30% concentrated hydrochloric acid. After stirring evenly, add the reaction solution of step (1-2) dropwise, control the temperature at 30-40°C, and continue to reflux for 2 hours. Layer the organic layer, wash it with 600 g of 5% dilute hydrochloric acid and 1000 g×2 water. The organic layer is concentrated to obtain a crude product. According to liquid chromatography analysis, the ratio of the target product C' to the ortho-acetylated byproduct of the ester group is 96:4. After the crude product is concentrated, it is recrystallized with 400 g of toluene, filtered, and dried to obtain 275.1 g of a white solid with a yield of 90% and a purity of 99.2%.

[0079] The structural identification data of the target product C' in step (1-2) of Example 3 are as follows:

[0080] H NMR 1 H NMR (400 MHz, CDCl3): δ 7.87 (d, J = 8.8 Hz, 2 H), 7.32 (d, J = 8.8 Hz, 2 H), 7.20 (d, J = 8.8 Hz, 2 H), 6.99 (d, J = 8.8 Hz, 2 H), 2.81 (sept., J = 7.1 Hz, 1 H), 2.57 (s, 3 H), 1.69 (s, 6 H), 1.30 (d, J = 7.2Hz, 6 H); 13 C NMR (100.1 MHz, CDCl3): δ 197.7, 175.6, 156.0,148.9, 147.0, 134.8, 128.2, 127.7, 127.0, 121.0, 43.1, 34.1, 30.5, 26.5,18.9.

[0081] Example 4

[0082] Preparation of 4-(4-acetylcumyl)phenyl trifluoroacetate

[0083]

[0084] Step (1-1): Under nitrogen protection, add 200 g of 4-cumylphenol, 218 g of trifluoroacetic anhydride and 400 g of dichloromethane to a 2 L four-necked reaction bottle, control the system temperature to 10-15°C, and slowly add 105 g of triethylamine at this temperature. After the addition is completed, continue to stir and react at this temperature for 2 hours. After the reaction is complete, add 200 g of pure water, stir and separate after stirring for 1 hour, and repeat twice. Shortly evaporate under reduced pressure until there is no obvious fraction, add 200 g of dichloromethane to the residue in the kettle, stir and dissolve for standby use. According to liquid chromatography analysis, the main product D accounts for more than 99%.

[0085] The structural identification data of the main product D of step (1-1) of Example 4 are as follows:

[0086] H NMR 1 H NMR (600 MHz, CDCl3): δ 7.30 (t, J = 7.8 Hz, 4 H), 7.24(d, J = 7.8 Hz, 2 H), 7.21 (t, J = 7.8 Hz, 1 H), 7.12 (d, J = 7.8 Hz, 2 H),1.70 (s, 6 H); 13 C NMR (100.1 MHz, CDCl3): δ 155. 9 (q, J = 43.2Hz), 150.1, 149.9, 147.2, 128.3, 128.1, 126.7, 125.9, 119.8, 114.6 (q, J =286.0 Hz), 42.8, 30.7.

[0087] Step (1-2): Add 251 g of aluminum chloride to the reaction solution prepared in step (1-1), stir and control the temperature to drop to 0-10°C, drop 81 g of acetyl chloride, and stir until the solid particles of aluminum chloride are almost gone. Control the temperature below 0-10°C and stir to react for 4 hours.

[0088] In another 2 L four-necked reaction bottle, add 600 g of water and 200 g of 30% concentrated hydrochloric acid, stir evenly, then drip the reaction solution of step (1-2), control the temperature at 30-40°C, and continue to reflux for 2 hours after dripping. Layer the organic layer, wash with 600 g of 5% dilute hydrochloric acid and 1000 g×2 water. The organic layer is concentrated to obtain a crude product. According to liquid chromatography analysis, the ratio of the target product D' to the ortho-acetylated byproduct of the ester group is 94:6. The crude product is recrystallized with 400 g of toluene, filtered and dried to obtain 290.4 g of a white solid with a yield of 88% and a purity of 99.1%.

[0089] The structural identification data of the target product D' in step (1-2) of Example 4 are as follows:

[0090] H NMR 1 H NMR (400 MHz, CDCl3): δ 7.86 (d, J = 8.0 Hz, 2 H), 7.32(d, J = 8.0 Hz, 2H), 7.07 (d, J = 8.0 Hz, 2 H), 6.77 (d, J = 8.0 Hz, 2 H),2.58 (s, 3 H), 1.69 (s, 6 H); 13 C NMR (100.1 MHz, CDCl3): δ 198.4,156.8, 155.6 (q, J = 32.5 Hz), 153.8, 141.8, 134.5, 128.2, 127.9, 127.0,114.9, 114.4 (q, J = 267.5 Hz), 42.7, 30.6, 26.6.

[0091] In summary, the analysis of the NMR data can confirm the structure of the product, so it can be inferred that the products of formula (2) and formula (3) are both the expected main products shown in the synthesis route in this application.

[0092] Comparative Example 1

[0093] Preparation of 4-(4-acetylcumyl)phenyl acetate

[0094] Step (1-1): Under nitrogen protection, add 200 g of 4-cumylphenol and 81 g of acetyl chloride to a 2 L four-necked reaction bottle, control the system temperature to 10-15°C, and slowly add 105 g of triethylamine at this temperature. After the addition is completed, continue to stir and react at this temperature for 2 hours. After the reaction is complete, add 200 g of pure water, stir and separate after stirring for 1 hour, and repeat twice. Shortly evaporate under reduced pressure until there is no obvious fraction, add 200 g of dichloromethane to the residue in the kettle, stir and dissolve for standby use. According to liquid chromatography analysis, the main product accounts for more than 99%.

[0095] Step (1-2): Add 251 g of aluminum chloride to the reaction solution prepared in step (1-1), stir and control the temperature to drop to 0-10°C, drop 81 g of acetyl chloride, and stir until the solid particles of aluminum chloride are almost gone. Control the temperature below 0-10°C and stir for 4 hours.

[0096] In another 2 L four-necked reaction bottle, add 600 g of water and 200 g of 30% concentrated hydrochloric acid, stir evenly, then drip the reaction solution of step (1-2), control the temperature at 30-40°C, and continue to reflux for 2 hours. Layer the organic layer, wash it with 600 g of 5% dilute hydrochloric acid and 1000 g × 2 water. After the organic layer is concentrated, the ratio of the target product to the ester ortho-acetylated by-product is 90:10. The crude product is recrystallized with 300 g of toluene, filtered and dried to obtain 237 g of white solid, with a yield of 85% and a purity of 98.5%.

[0097] Comparative Example 2

[0098] Preparation of 4-(4-acetylcumyl)phenyl trimethylbenzoate

[0099] Step (1-1): Under nitrogen protection, add 200 g of 4-cumylphenol, 189 g of trimethylbenzoyl chloride and 400 g of dichloromethane to a 2 L four-necked reaction bottle, control the system temperature to 35°C, and slowly add 105 g of triethylamine at this temperature. After the addition is completed, continue to stir and react at this temperature for 2 hours. After the reaction is complete, add 200 g of pure water, stir and separate after stirring for 1 hour, and repeat twice. Shortly evaporate under reduced pressure until there is no obvious fraction, add 200 g of dichloromethane to the residue in the kettle, stir and dissolve for standby use. According to liquid chromatography analysis, the main product accounts for more than 95%.

[0100] Step (1-2): Add 251 g of aluminum chloride to the reaction solution prepared in step (1-1), stir and control the temperature to drop to 0-10°C, drop 81 g of acetyl chloride, and stir until the solid particles of aluminum chloride are almost gone. Control the temperature below 0-10°C and stir for 4 hours.

[0101] In another 2 L four-necked reaction bottle, add 600 g of water and 200 g of 30% concentrated hydrochloric acid. After stirring evenly, add the reaction solution of step (1-2) dropwise, control the temperature at 30-40°C, and continue to reflux for 2 hours. Layer the organic layer, wash it with 600 g of 5% dilute hydrochloric acid and 1000 g×2 water. The organic layer is concentrated to obtain a crude product. According to liquid chromatography analysis, the ratio of the target product to the ortho-acetylated byproduct of the ester group is 99:1. The crude product is recrystallized with 400 g of toluene, filtered, and dried to obtain 335.8 g of a white solid with a yield of 89% and a purity of 99.4%.

[0102] Comparative Example 3

[0103] Preparation of 4-(4-acetylcumyl)phenyl trimethylbenzoate

[0104] Step (1-1): Under nitrogen protection, add 200 g of 4-cumylphenol, 189 g of trimethylbenzoyl chloride and 400 g of dichloromethane to a 2 L four-necked reaction bottle, control the system temperature to 40°C, and slowly add 105 g of triethylamine at this temperature. After the addition is completed, continue to stir and react at this temperature for 2 hours. After the reaction is complete, add 200 g of pure water, stir and separate after stirring for 1 hour, and repeat twice. Shortly evaporate under reduced pressure until there is no obvious fraction, add 200 g of dichloromethane to the residue in the kettle, stir and dissolve for standby use. According to liquid chromatography analysis, the main product accounts for more than 92%.

[0105] Step (1-2): Add 251 g of aluminum chloride to the reaction solution prepared in step (1-1), stir and control the temperature to drop to 0-10°C, drop 81 g of acetyl chloride, and stir until the solid particles of aluminum chloride are almost gone. Control the temperature below 0-10°C and stir for 4 hours.

[0106] In another 2 L four-necked reaction bottle, add 600 g of water and 200 g of 30% concentrated hydrochloric acid. After stirring evenly, add the reaction solution of step (1-2) dropwise, control the temperature at 30-40°C, and continue to reflux for 2 hours. Layer the organic layer, wash it with 600 g of 5% dilute hydrochloric acid and 1000 g×2 water. The organic layer is concentrated to obtain a crude product. According to liquid chromatography analysis, the ratio of the target product to the ortho-acetylated byproduct of the ester group is 99:1. The crude product is recrystallized with 400 g of toluene, filtered, and dried to obtain 324.5 g of a white solid with a yield of 86% and a purity of 99.0%.

[0107] The present application provides an improved preparation process route. When the R group in 4-cumylphenol ester (2) is a large steric hindrance or / and a strong electron-withdrawing group, the position selectivity in the subsequent Friedel-Crafts acetylation reaction is significantly improved, especially the introduction of the large steric hindrance group. The positional isomers of 4-(4-acetylcumyl)phenol ester (3) prepared by Friedel-Crafts acetylation are extremely small. In addition, the preparation of 4-(4-acetylcumyl)phenol ester (3) as shown in formula (3) by using the process route requires less post-treatment, less three wastes, and high product purity. The product is particularly suitable for application in the preparation of photoresists and other electronic chemical materials.

[0108] The above embodiments are merely illustrative of the principles and effects of the present application and are not intended to limit the present application. Anyone familiar with the technology may modify or change the above embodiments without violating the spirit and scope of the present application. Therefore, all equivalent modifications or changes made by a person of ordinary skill in the art without departing from the spirit and technical ideas disclosed in the present application shall still be covered by the claims of the present application.

Claims

1. A highly selective preparation method of 4-(4-acetylcumyl)phenol ester compounds, characterized in that: The synthetic route is as follows: The specific steps include: A1, 4-cumylphenol (1) is subjected to a pre-acylation reaction in a system containing a first acylating agent and an acid binding agent, and then a first quenching agent is added to the system to complete the pre-acylation reaction to prepare 4-cumylphenol ester (2); A2, the 4-cumylphenol ester (2) is subjected to a Friedel-Crafts acetylation reaction in a system containing a second acylating agent and an acylation catalyst, and then a second quencher is added to the system to complete the Friedel-Crafts acetylation reaction to prepare 4-(4-acetylcumyl)phenol ester (3); Wherein, the molecular formula of the first acylating agent is RCOCl or (RCO)2O, R is a large steric hindrance or / and strong electron-pulling group, and R is selected from mesitylene, C3-C10 branched hydrocarbon group or C1-C10 perfluorocarbon group; the second acylating agent is acetyl chloride or acetic anhydride; Wherein, the acylation catalyst uses Lewis acid.

2. The highly selective preparation method of 4-(4-acetylcumyl)phenol ester compounds according to claim 1, characterized in that: R is selected from mesitylene, tert-butyl, isopropyl, trifluoromethyl or perfluorobutyl.

3. The highly selective preparation method of 4-(4-acetylcumyl)phenol ester compounds according to claim 1, characterized in that: The acid binding agent is a weakly alkaline acid binding agent.

4. The highly selective preparation method of 4-(4-acetylcumyl)phenol ester compounds according to claim 1, characterized in that: The acid binding agent is selected from one of triethylamine, pyridine and potassium carbonate.

5. The highly selective preparation method of 4-(4-acetylcumyl)phenol ester compounds according to claim 1, characterized in that: The first quenching agent is water or a saturated sodium bicarbonate aqueous solution.

6. The highly selective preparation method of 4-(4-acetylcumyl)phenol ester compounds according to claim 1, characterized in that: The acylation catalyst is selected from aluminum chloride, SnCl4, copper chloride or FeCl3.

7. The highly selective preparation method of 4-(4-acetylcumyl)phenol ester compounds according to claim 2, characterized in that: The first acylating agent is trimethylbenzoyl chloride, pivaloyl chloride, isobutyryl chloride, trifluoroacetyl chloride or trifluoroacetic anhydride. The 4-cumylphenol (1) reacts with the first acylating agent in the presence of a solvent at 10-30° C. The solvent is selected from a haloalkane, and the amount of the solvent used is 1-20 times the weight of the 4-cumylphenol (1).

8. The highly selective preparation method of 4-(4-acetylcumyl)phenol ester compounds according to claim 7, characterized in that: The 4-cumylphenol (1) reacts with the first acylating agent at 15-20°C.

9. The highly selective preparation method of 4-(4-acetylcumyl)phenol ester compounds according to any one of claims 1, 7, or 8, characterized in that: The molar ratio of the 4-cumylphenol (1) to the first acylating agent is 1:1 to 1.

5.

10. The highly selective preparation method of 4-(4-acetylcumyl)phenol ester compounds according to claim 1, characterized in that: The molar ratio of the acid binding agent to the 4-cumylphenol (1) is 1 to 1.6:

1.

11. The highly selective preparation method of 4-(4-acetylcumyl)phenol ester compounds according to claim 5, characterized in that: The first quenching agent is water, and the amount of the water is 1-20 times the weight of the 4-cumylphenol (1).

12. The highly selective preparation method of 4-(4-acetylcumyl)phenol ester compounds according to claim 1, characterized in that: The molar ratio of the second acylating agent to the 4-cumylphenol ester (2) is 0.8 to 2:

1.

13. The highly selective preparation method of 4-(4-acetylcumyl)phenol ester compounds according to claim 6, characterized in that: The acylation catalyst is aluminum chloride, and the molar ratio of aluminum chloride to 4-cumylphenol ester (2) is 0.8-3:

1.

14. The highly selective preparation method of 4-(4-acetylcumyl)phenol ester compounds according to claim 13, characterized in that: The second quencher is a hydrochloric acid solution, the mass percentage concentration of the hydrochloric acid solution is 1% to 10%, and the mass ratio of the hydrochloric acid solution to the aluminum chloride is 2 to 5:

1.

15. The highly selective preparation method of 4-(4-acetylcumyl)phenol ester compounds according to claim 6, characterized in that: The acylation catalyst is aluminum chloride, and the contact reaction temperature of the mixture of the 4-cumylphenol ester (2), the acetyl chloride and the aluminum chloride is 0-30°C.

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