Process for the preparation of 4-isopropenylphenol

Abstract

The application discloses a preparation method of 4-isopropenyl phenol, and comprises the following steps: S1, acylating reaction is carried out by using alpha-methyl styrene to obtain a first reaction mixture containing 4-isopropenyl phenylethanone intermediate; S2, the first reaction mixture containing 4-isopropenyl phenylethanone intermediate is directly added with composite additives and oxidants to obtain a second reaction mixture containing 4-isopropenyl phenyl acetate, and 4-isopropenyl phenyl acetate is obtained through post-treatment; and S3, hydrolysis reaction is carried out by using the 4-isopropenyl phenyl acetate to obtain the 4-isopropenyl phenol. The application is convenient to synthesize, high in reaction efficiency, and friendly to the environment.

Description

Technical Field

[0001] This application relates to the field of chemical synthesis, and in particular to a method for preparing 4-isopropenol. Background Technology

[0002] 4-Isopropenol (CAS No.: 4286-23-1, also known as p-isopropenylphenol or 4-hydroxy-α-methylstyrene) is a core intermediate in fine chemicals with both high reactivity and high application value. Its molecular structure contains both a nucleophilic phenolic hydroxyl group and an isopropenyl double bond capable of free radical polymerization. It can be widely used in phenolic resin modification, specialty polycarbonates, benzoxazine resins, and the synthesis of pharmaceutical intermediates. Furthermore, it is a key monomer for high-performance polymer resins used in photoresists for 248nm and below processes. With the rapid development of the semiconductor and high-end polymer materials industries, the market demand for high-purity 4-isopropenol continues to rise.

[0003] However, 4-isopropenol is chemically reactive and highly sensitive to heat, light, and oxygen. The isopropenyl double bond is prone to self-polymerization, and the phenolic hydroxyl group is easily oxidized, resulting in poor product storage stability and difficulty in controlling side reactions during synthesis. Furthermore, high-end applications such as semiconductor photoresists require extremely high product purity (typically ≥99.5%), imposing stringent requirements on the selectivity of the synthesis process, the mildness of reaction conditions, and purification efficiency. Summary of the Invention

[0004] To address at least one of the aforementioned problems, this application discloses a method for preparing 4-isopropenol. The method involves acylation, oxidative rearrangement, and hydrolysis of the starting material α-methylstyrene to obtain high-purity 4-isopropenol. The entire synthesis process is simple to operate and has high conversion efficiency.

[0005] The method for preparing 4-isopropenol provided in this application includes the following steps: S1: acylation reaction using α-methylstyrene to obtain a first reaction mixture containing 4-isopropenyl acetophenone intermediate; S2: the first reaction mixture containing 4-isopropenyl acetophenone intermediate is directly heated with a composite auxiliary agent and an oxidizing agent without separation and purification to obtain a second reaction mixture containing 4-isopropenyl phenyl acetate, and then post-treated to obtain pure 4-isopropenyl phenyl acetate; S3: hydrolysis reaction using the pure 4-isopropenyl phenyl acetate to obtain 4-isopropenol.

[0006] According to some embodiments of this application, obtaining a first reaction mixture containing the 4-isopropenyl acetophenone intermediate includes: performing an acylation reaction of α-methylstyrene with an acylation agent in an inert organic solvent in the presence of a catalyst to obtain a first reaction mixture containing the 4-isopropenyl acetophenone intermediate.

[0007] According to some embodiments of this application, the acylation agent is selected from at least one of acetyl chloride, acetyl bromide, acetic anhydride, or acetyl fluoride; the inert organic solvent is selected from at least one of dichloromethane, 1,2-dichloroethane, or chloroform; and the catalyst is selected from at least one of aluminum trichloride, ferric chloride, zinc chloride, boron trifluoride ether, sulfuric acid, methanesulfonic acid, trifluoromethanesulfonic acid, p-toluenesulfonic acid, β-zeolite, or sulfonic acid resin.

[0008] According to some embodiments of this application, obtaining a second reaction mixture containing the 4-isopropenylphenylacetate comprises: directly heating a composite auxiliary agent and an oxidant without separation and purification of a first reaction mixture containing the 4-isopropenylacetophenone intermediate to cause the 4-isopropenylacetophenone intermediate to undergo an oxidative rearrangement reaction, thereby obtaining a second reaction mixture containing the 4-isopropenylphenylacetate.

[0009] According to some embodiments of this application, the composite additive is selected from at least two of sodium carbonate, sodium bicarbonate, sodium dihydrogen phosphate, or sodium citrate; the oxidant is selected from at least one of m-chloroperoxybenzoic acid, peracetic acid, aqueous hydrogen peroxide solution, or tert-butyl hydroperoxide.

[0010] According to some embodiments of this application, obtaining the 4-isopropenol includes: hydrolyzing and purifying the pure 4-isopropenylphenyl acetate using an alkaline reagent to obtain the 4-isopropenol.

[0011] According to some embodiments of this application, the alkaline reagent is selected from at least one of sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium tert-butoxide, sodium tert-butoxide, ammonia, isopropylamine, trimethane, diethylamine, triethylamine, pyridine, or N,N-diisopropylethylamine.

[0012] According to some embodiments of this application, the hydrolysis reaction is carried out in a water-soluble organic solvent; the water-soluble organic solvent is selected from at least one of methanol, ethanol, isopropanol or tetrahydrofuran.

[0013] According to some embodiments of this application, the post-processing includes quenching, extraction, drying and concentration, and distillation, and the purification includes filtration, concentration, washing, crystallization, and drying.

[0014] According to some embodiments of this application, at least one of the acylation reaction, the oxidative rearrangement reaction, and the hydrolysis reaction is carried out in the presence of a polymerization inhibitor; the polymerization inhibitor is selected from hydroquinone, p-hydroxyanisole, 2,6-di-tert-butyl-p-cresol, and phenothiazine.

[0015] The method for preparing 4-isopropenol provided in this application does not require stringent reaction conditions and does not require the use of high-cost and high-risk reagents. The entire preparation process is convenient, safe, and economical, while also exhibiting high conversion rate and environmental friendliness.

[0016] Additional aspects and advantages of the invention will be set forth in part in the description which follows, and in part will be obvious from the description, or may be learned by practice of the invention. Attached Figure Description

[0017] The disclosure of this application will become more readily understood with reference to the accompanying drawings. It will be readily understood by those skilled in the art that these drawings are for illustrative purposes only and are not intended to limit the scope of protection of this application. Furthermore, similar numbers in the drawings are used to denote similar components, wherein: Figure 1 This is an exemplary flowchart of a method for preparing 4-isopropenol according to some embodiments of this application; Figure 2 The 1H NMR spectrum of 4-isopropenol obtained according to the preparation method shown in some embodiments of this application; Figure 3 The liquid chromatography of 4-isopropenol obtained according to the preparation method shown in some embodiments of this application; Figure 4 This is another liquid chromatogram of 4-isopropenol obtained according to the preparation method shown in some embodiments of this application; Figure 5 This is another liquid chromatogram of 4-isopropenol obtained according to the preparation method shown in some embodiments of this application. Detailed Implementation

[0018] To make the above-mentioned objectives, features, and advantages of this application more apparent and understandable, the specific embodiments of this application are described in detail below. Many specific details are set forth in the following description to provide a thorough understanding of this application. However, this application can be implemented in many other ways different from those described herein, and those skilled in the art can make similar modifications without departing from the spirit of this application. Therefore, this application is not limited to the specific embodiments disclosed below.

[0019] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the application. The terms “comprising” or “including” as used herein mean that an element or object preceding the word encompasses the elements or objects listed following the word and their equivalents, without excluding other elements or objects. The terms “and / or” or “and / or” as used herein include any and all combinations of one or more of the associated listed items. The terms “optionally” or “preferredly” as used herein may refer to embodiments that provide certain beneficial effects in certain circumstances, but this does not limit the scope to embodiments that have inferior technical effects or are unavailable, nor is it intended to exclude or limit the embodiments related to this application.

[0020] The numerical range disclosed in this application should be considered continuous, encompassing any value between the maximum and minimum values ​​defining the range. The maximum and / or minimum values ​​may or may not be included within the numerical range. Unless otherwise stated, the numerical range AB may include any combination of real numbers from A to B, as well as any subrange consisting of any two real numbers. For example, the numerical range 0-5 may include, but is not limited to, 1-4, 2-3, 2.3-2.8, etc.

[0021] Currently, existing synthetic routes for 4-isopropenol can be categorized as follows. The first is the bisphenol A high-temperature pyrolysis method. Using bisphenol A as a raw material, 4-isopropenol is prepared by pyrolysis under high temperature and high vacuum conditions in the presence of alkaline catalysts such as sodium hydroxide and potassium hydroxide. This method has several significant disadvantages. First, the reaction conditions are extreme, resulting in poor industrial applicability. The pyrolysis reaction requires a high temperature and high vacuum environment above 200℃, leading to extremely high equipment investment and energy consumption. It also places stringent requirements on equipment sealing and high-temperature resistance. During continuous production, the catalyst is prone to scaling and clogging the reactor, resulting in extremely poor production stability. Second, the selectivity and purity are insufficient. The raw material mother liquor has a complex composition, containing a large amount of unreacted phenol, bisphenol A isomers, and chromium / indene byproducts. The pyrolysis selectivity is less than 70%, and the variety of byproducts makes it difficult to obtain high-purity photoresist-grade products through simple purification. Third, the product is prone to deterioration, limiting the yield. Under high-temperature conditions, the isopropenyl double bond of the target product is highly susceptible to self-polymerization, leading to reduced product yield and decreased storage stability. This necessitates the addition of polymerization inhibitors, further increasing purification difficulty and cost. The second method is the hydroxyl protection-Wittig reaction. Using p-hydroxyacetophenone as a raw material, it is first reacted with 3,4-dihydropyran (DHP) under acid catalysis to protect the phenolic hydroxyl group, preparing 1-(4-tetrahydropyran-2-oxyphenyl)acetophenone. Then, it reacts with methyltriphenylphosphine bromide and potassium tert-butoxide to prepare a phosphorus ylide reagent, which then undergoes a Wittig reaction with the above intermediate, introducing an isopropenyl group at the carbonyl position to obtain 2-(4-(1-propen-2-yl)phenoxy)tetrahydro-2H-pyran. Finally, the tetrahydropyran protecting group is removed under acidic conditions to obtain 4-isopropenol. This method also has significant disadvantages: it is not only lengthy and inefficient, but it also generates a large amount of triphenylphosphine oxide hazardous waste, resulting in high solid waste treatment costs. Furthermore, the deprotected acidic environment exacerbates the self-polymerization of the product, leading to a decrease in product purity and making it difficult to meet the requirements of high-end applications. The third method is the Grignard reagent addition method, which prepares 4-isopropenol by adding p-hydroxyacetophenone to an alkyl magnesium halide Grignard reagent, followed by acetylation protection with acetic anhydride and deacetylation. This method all utilizes Grignard reagents, which pose safety risks, and requires an anhydrous and oxygen-free environment, placing extremely high demands on the moisture content of raw materials and the airtightness of equipment. Grignard reagents are prone to combustion and explosion upon contact with water and oxygen, making safety control during industrial-scale production extremely difficult. Moreover, the reaction generates large amounts of magnesium salt wastewater and residue, resulting in high costs for waste treatment and significant environmental pressure, hindering large-scale production.

[0022] Therefore, existing preparation methods generally suffer from problems such as lengthy synthetic routes, harsh reaction conditions, poor atom economy, high costs of waste treatment, and difficulty in industrial scale-up, making it difficult to simultaneously meet the industry's demands for high purity, low cost, green production, and large-scale production. Based on this, this application provides a method for preparing 4-isopropenol, using α-methylstyrene as a raw material, and efficiently preparing high-purity 4-isopropenol through three core reactions: acylation, oxidative rearrangement, and alkaline hydrolysis. This preparation process avoids the harsh reaction temperatures, vacuum pressures, and product polymerization problems caused by high-temperature pyrolysis methods, and also avoids the use of high-cost, low-efficiency phosphorus ylide reagents and high-reaction-risk Grignard reagents, possessing significant advantages such as high-efficiency conversion, convenient operation, safety, economy, and environmental friendliness.

[0023] The following describes some preferred embodiments of this application. It should be noted that the following description is for illustrative purposes only and is not intended to limit the scope of protection of this application. The steps involved in this application may be performed precisely in sequence, or various steps may be processed in reverse order or simultaneously. Furthermore, other operations may be added to these processes, or one or more steps may be removed from these processes.

[0024] refer to Figure 1 The illustrated flowchart shows an exemplary process for preparing 4-isopropenol according to some embodiments of this application. The preparation method may include the following steps: S1: acylation reaction using α-methylstyrene to obtain a first reaction mixture containing a 4-isopropenol acetophenone intermediate; S2: without separation and purification, the first reaction mixture containing the 4-isopropenol acetophenone intermediate is directly reacted with a composite auxiliary agent and an oxidant to obtain a second reaction mixture containing 4-isopropenol phenyl acetate, and post-processed to obtain pure 4-isopropenol phenyl acetate; and S3: hydrolysis reaction using the 4-isopropenol phenyl acetate to obtain the 4-isopropenol.

[0025] For step S1, the acylation reaction can be carried out in an inert organic solvent. Any existing suitable inert organic solvent can be used in this application, including but not limited to aliphatic alkane solvents (e.g., n-pentane, n-hexane, isooctane, petroleum ether, methylcyclohexane, etc.), aromatic hydrocarbon solvents (e.g., benzene, toluene, xylene, cumene, biphenyl, naphthalene, etc.), halogenated hydrocarbon solvents (e.g., dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane, bromoethane, chlorobenzene, dichlorobenzene, etc.), ether solvents (e.g., diethyl ether, isopropyl ether, methyl tert-butyl ether, diphenyl ether, etc.), ester solvents (e.g., ethyl acetate, n-propyl acetate, ethyl propionate, ethyl benzoate, etc.), fluorinated solvents (e.g., trichlorotoluene, perfluoroethane, 1,1,1-trifluoroethane, etc.), etc., or other inert organic solvents suitable for high-temperature reactions such as diphenyl ether, liquid paraffin, methyl silicone oil, etc. Optionally or preferably, the inert organic solvent may be selected from at least one of dichloromethane, 1,2-dichloroethane, or chloroform. The acylation reaction can be carried out in the presence of a catalyst using α-methylstyrene and an acylation reagent in the inert organic solvent to obtain a first reaction mixture containing a 4-isopropenyl acetophenone intermediate. The acylation reagent can undergo a Friedel-Crafts acetylation reaction with α-methylstyrene to introduce an acetyl group at the para-position of the isopropenyl group. Exemplary acylation reagents may be at least one of acetyl chloride, acetic anhydride, acetyl bromide, acetyl fluoride, ketene, or a mixed acetic acid-trifluoroacetic acid anhydride. For example, the acylation reagent may be selected from at least one of acetyl chloride, acetyl bromide, acetic anhydride, or acetyl fluoride. The catalyst can be used to activate the acelation reagent to generate an acyl cation, thereby attacking the aromatic ring to complete the substitution. At least one of the following can be used as the catalyst: boron trifluoride ether, zinc chloride, tin tetrachloride, ferric chloride, aluminum trichloride, aluminum tribromide, titanium tetrachloride, methanesulfonic acid, trifluoromethanesulfonic acid, p-toluenesulfonic acid, sulfuric acid, metal salts of trifluoromethanesulfonic acid, rare earth chlorides, sulfonic acid type ion exchange resins, β-zeolite, modified molecular sieves, etc.

[0026] In the above acylation reaction, based on the amount of α-methylstyrene, the molar ratio of the acylation reagent to α-methylstyrene can be (0.9-2.0):1. For example, the molar ratio of the acylation reagent to α-methylstyrene can be 0.9:1, 1.1:1, 1.3:1, 1.5:1, 1.8:1, 2.0:1, etc., or any increase or decrease of the above molar ratios. Optionally or preferably, the molar ratio of the acylation reagent to α-methylstyrene is 1.1:1. The molar ratio of the catalyst used for catalysis to α-methylstyrene is (0.1-1.2):1. For example, the molar ratio of the catalyst to α-methylstyrene is 0.1:1, 0.3:1, 0.5:1, 0.7:1, 0.9:1, 1.2:1, etc., or any mass fraction of the above, or any decrease of the above. Optionally or preferably, the molar ratio of the catalyst to α-methylstyrene is 0.5:1. The volume of the inert organic solvent used to provide the reaction environment can be 1-20 times the weight of α-methylstyrene. For example, 6 times, 10 times, 15 times, etc.

[0027] In some embodiments, the above acylation reaction can be carried out at a reaction temperature of -10℃ to 30℃ for 1h to 10h. Optionally or preferably, the reaction temperature of the acylation reaction can be 0℃ to 25℃. Optionally or preferably, the reaction temperature of the acylation reaction can be -10℃, 0℃, 10℃, or 25℃. The reaction time of the acylation reaction can be 1h, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, etc. Optionally or preferably, the reaction time of the above acylation reaction is 3h or 4h.

[0028] For step S2, the composite auxiliary agent and the oxidant can be directly added to the first reaction mixture to undergo an oxidative rearrangement reaction with the 4-isopropenyl acetophenone intermediate, thereby obtaining a second reaction mixture containing 4-isopropenylphenyl acetate. This process does not require separation and purification of the first reaction mixture, but is carried out directly in the first reaction mixture. The generation of 4-isopropenylphenyl acetate from 4-isopropenyl acetophenone belongs to the Baeyer-Villiger reaction, also known as the Baeyer-Villiger oxidative rearrangement reaction. Any suitable oxidant, including but not limited to at least one of m-chloroperoxybenzoic acid m-CPBA, peracetic acid PAA, trifluoroperacetic acid TFPAA, perbenzoic acid, tert-butyl hydroperoxide TBHP, cumene peroxide, and aqueous hydrogen peroxide solution. The composite auxiliary agent adapted to the above is selected from at least two of sodium carbonate, sodium bicarbonate, sodium dihydrogen phosphate, or sodium citrate.

[0029] In the above oxidative rearrangement reaction, based on the amount of α-methylstyrene, the molar ratio of the oxidant to α-methylstyrene can be (1.0-2.0):1. For example, the molar ratio of the oxidant to α-methylstyrene can be 1.0:1, 1.2:1, 1.4:1, 1.5:1, 1.8:1, 2.0:1, or any increase or decrease of the above molar ratios. Optionally or preferably, the molar ratio of the oxidant to α-methylstyrene is 1.1:1 or 1.15:1. The composite additive used is a mixture of sodium carbonate or sodium bicarbonate with sodium dihydrogen phosphate or sodium citrate, such as a mixture of sodium carbonate and sodium dihydrogen phosphate, sodium carbonate and sodium citrate, sodium bicarbonate and sodium dihydrogen phosphate, or sodium bicarbonate and sodium citrate. Optionally or preferably, the molar ratio of sodium carbonate or sodium bicarbonate to sodium dihydrogen phosphate or sodium citrate is (2.0-3.0):1, for example, the molar ratio of sodium carbonate to sodium dihydrogen phosphate is 2.0:1, 2.2:1, 2.3:1, 2.4:1, 2.6:1, 2.8:1, 3.0:1, etc., or any increase or decrease of the above molar ratios. Other composite additive combinations follow the same principle; further, the molar ratio of sodium carbonate or sodium bicarbonate to the oxidant in the composite additive is 0.01:1, 0.03:1, 0.05:1, 0.07:1, 0.09:1, 0.1:1, etc., or any of the above mass fractions by weight or reduction, and the molar amounts of sodium dihydrogen phosphate and sodium citrate in the composite additive are determined by the molar ratio of sodium carbonate or sodium bicarbonate to sodium dihydrogen phosphate or sodium citrate. Optionally or preferably, in the composite additive, the molar ratio of sodium carbonate or sodium bicarbonate to the oxidant is 0.04:1, and the molar ratio of sodium carbonate or sodium bicarbonate to sodium dihydrogen phosphate or sodium citrate is 2.0:1.

[0030] In some embodiments, the above oxidative rearrangement reaction can be carried out at a reaction temperature of 0℃-50℃. Optionally or preferably, the reaction temperature of the oxidative rearrangement reaction can be 10℃-40℃. Optionally or preferably, the reaction temperature of the oxidative rearrangement reaction can be 20℃-30℃. Optionally or preferably, the reaction temperature of the oxidative rearrangement reaction can be -10℃ or 25℃. The reaction time of the oxidative rearrangement reaction can be 1h-10h. For example, 1h, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, etc. Optionally or preferably, the reaction time of the above oxidative rearrangement reaction is 2h.

[0031] Before step S3, the second reaction mixture can be post-treated to obtain pure 4-isopropenylphenylacetate. Exemplarily, the post-treatment may include quenching, extraction, drying and concentration, and distillation. The quenching can be used to terminate the oxidative rearrangement reaction in step S2 and to adjust the pH of the second reaction mixture to prevent ester hydrolysis. Exemplarily, the quenching can be performed using at least one of ice water, a saturated aqueous solution of sodium bicarbonate, a saturated aqueous solution of sodium carbonate, a saturated aqueous solution of sodium bisulfite, or a saturated aqueous solution of sodium thiosulfate. For example, ice water is used to cool the mixture to 0°C-10°C to control the temperature and prevent thermal side reactions. Subsequently, a saturated aqueous solution of sodium bicarbonate is added with slow stirring to adjust the pH, followed by the addition of an extraction solvent for extraction and separation. The extraction is used to separate the 4-isopropenylphenylacetate obtained from the reaction mixture. Exemplarily, the extraction can be performed using organic solvents such as dichloromethane or ethyl acetate. After quenching, an extraction solvent such as dichloromethane is added, and then the mixture is transferred to a separatory funnel and allowed to stand for separation. After separating the lower organic phase, wash 1-2 times with deionized water, then 1-2 times with saturated brine to remove organic acids and trace amounts of water. At this point, the 4-isopropenylphenyl acetate obtained in step S2 is dissolved in the organic solvent used for extraction. The drying and concentration are used for further dehydration and solvent removal. For example, anhydrous sodium sulfate, anhydrous magnesium sulfate, or other drying agents can be added to the organic solvent, and the mixture is stirred and allowed to stand for a sufficient time, such as 30 minutes, to fully dehydrate. Subsequently, vacuum concentration is performed, for example, by low-temperature vacuum distillation using a rotary evaporator to remove dichloromethane, yielding crude 4-isopropenylphenyl acetate. The distillation can be used to purify the crude product, removing unreacted reactants and reducing byproducts and impurities. For example, the distillation can be vacuum distillation, with a distillation pressure of 1-100 mbar, for example, 1 mbar, and a distillation temperature of 40℃-120℃, for example, 80℃. Finally, pure 4-isopropenylphenyl acetate is obtained.

[0032] For step S3, the pure 4-isopropenylphenyl acetate can be hydrolyzed and purified using an alkaline reagent to finally obtain 4-isopropenol. In some embodiments, the hydrolysis of 4-isopropenylphenyl acetate can be carried out with a water-soluble organic solvent. The water-soluble organic solvent may be selected from at least one of methanol, ethanol, n-propanol, isopropanol, n-butanol, ethylene glycol, propylene glycol, glycerol, tetrahydrofuran, 1,4-dioxane, acetone, butanone, acetonitrile, dimethyl sulfoxide, N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, tetramethylurea, and hexamethylphosphoric triamine. Optionally or preferably, the water-soluble organic solvent may be selected from at least one of methanol, ethanol, isopropanol, or tetrahydrofuran. The basic reagent used to initiate hydrolysis by nucleophilic attack to cause addition-elimination of 4-isopropenylphenyl acetate to break the ester bond can be selected from at least one of the following: inorganic bases (e.g., sodium hydroxide, potassium hydroxide, lithium hydroxide, calcium hydroxide, barium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, trisodium phosphate, disodium hydrogen phosphate, sodium sulfate, sodium sulfite, ammonia, etc.), alkoxide bases (e.g., sodium methoxide, sodium ethoxide, sodium isopropoxide, sodium tert-butoxide, potassium tert-butoxide, sodium benzyl alcohol, etc.), organic amine bases (e.g., diethylamine, triethylamine, diisopropylethylamine, isopropylamine, pyridine, 4,4-dimethylaminopyridine, piperidine, morpholine, DBU, DBN, dicyclohexylamine, N,N-diisopropylethylamine, tetramethylethylenediamine, N-methylmorpholine, etc.), and quaternary ammonium strong bases (e.g., tetramethylammonium hydroxide, tetraethylammonium hydroxide, tetrabutylammonium hydroxide, benzyltrimethylammonium hydroxide, etc.). Optionally or preferably, the alkaline reagent may be selected from at least one of sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium tert-butoxide, sodium tert-butoxide, ammonia, isopropylamine, trimethane, diethylamine, triethylamine, pyridine, or N,N-diisopropylethylamine.

[0033] In the above hydrolysis reaction, still based on the amount of α-methylstyrene, the molar ratio of the basic reagent to α-methylstyrene can be (0.1-3.0):1. For example, the molar ratio of the oxidizing reagent to α-methylstyrene can be 0.1:1, 0.5:1, 1.0:1, 1.5:1, 2.0:1, 2.5:1, 3.0:1, or any increase or decrease in the above molar ratios. Optionally or preferably, the molar ratio of the basic reagent to α-methylstyrene is 0.78:1 or 0.82. The volume of the water-soluble organic solvent used to provide the hydrolysis reaction environment can be 2-20 times the weight of α-methylstyrene. For example, 6 times, 10 times, 15 times, 20 times, etc.

[0034] In some embodiments, the above hydrolysis reaction can be carried out at a reaction temperature of 0℃-30℃. Optionally or preferably, the reaction temperature of the hydrolysis reaction can be 10℃-20℃. Optionally or preferably, the reaction temperature of the oxidative rearrangement reaction can be 0℃ or 25℃. The reaction time of the hydrolysis reaction can be 2h-10h. For example, 2h, 3h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, etc. Optionally or preferably, the reaction time of the above oxidative rearrangement reaction is 3h or 4h.

[0035] After the hydrolysis reaction is completed, purification operations including filtration, concentration, washing, crystallization, and drying can be performed. Filtration removes unhydrolyzed reactants and various impurities. For example, filtration can be performed using vacuum filtration or atmospheric pressure filtration. During filtration, the filtrate is collected and combined, and the filter cake can be washed with pure water, with the washings incorporated into the filtrate. Concentration removes the water-soluble organic solvents used. Similarly, concentration can be performed under reduced pressure at low temperature to remove the water-soluble organic solvents, yielding crude 4-isopropenol. Washing removes water-soluble impurities from the crude product. For example, washing 2-3 times with ultrapure water. The organic phase is collected and then dried and concentrated (e.g., by adding a desiccant such as anhydrous sodium sulfate to remove water followed by vacuum concentration) before crystallization. The crystallization solvent used can be selected from at least one of ethyl acetate, dichloromethane, dichloroethane, tetrahydrofuran, acetonitrile, methanol, ethanol, methyl tert-butyl ether, ethylene glycol dimethyl ether, n-hexane, cyclohexane, n-heptane, methylcyclohexane, petroleum ether, toluene, or isopropyl ether. After the dried and concentrated organic phase is dissolved in the crystallization solvent, the temperature is adjusted to the crystallization temperature (e.g., -10°C to 20°C, such as 0°C), and crystallization is performed 2 to 3 times to obtain a high-purity wet product of 4-isopropenol. This wet product is then dried to obtain the final product. The drying can be performed using vacuum drying or a forced-air oven drying. The drying temperature can be 30°C-40°C, and the drying time can be 2 hours to 6 hours. For example, the above wet product can be dried at 40°C for 4 hours.

[0036] In steps S1 to S3 above, at least one step is carried out in the presence of a polymerization inhibitor. For example, in the acylation reaction in step S1, since the reactant is α-methylstyrene containing vinyl carbon-carbon double bonds, a polymerization inhibitor needs to be added to prevent the self-polymerization and cross-linking oligomerization of the double bond cationic bonds, thereby generating viscous resinous byproducts. The polymerization inhibitor can capture free radicals to cleave the free radical polymerization of the double bond. It can also inhibit cationic polymerization and passivate the activity of the double bond to prevent self-polymerization. Examples of polymerization inhibitors include phenolic inhibitors (e.g., hydroquinone, tert-butylhydroquinone, 2,6-di-tert-butyl-p-cresol, p-methoxyphenol, p-hydroxyanisole (i.e., 4-methoxyphenol), phenol, etc.), phenothiazine inhibitors (e.g., phenothiazine, N-methylphenothiazine, etc.), quinone inhibitors (e.g., 1,4-benzoquinone, 1,4-naphthoquinone, anthraquinone, etc.), aromatic amine inhibitors (e.g., N-phenyl-β-naphthylamine, N,N-diphenyl-p-phenylenediamine, diisopropylaniline, dicyclohexylamine, etc.), sulfur-containing inhibitors (e.g., thiourea, dimethyl sulfide, etc.), nitro inhibitors (e.g., TEMPO, nitrobenzene, m-dinitrobenzene, isoamyl nitrite, etc.), or other inhibitors such as triphenylphosphine, isoprene inhibitors, copper acetate, etc. Optionally or preferably, the polymerization inhibitor is selected from at least one of hydroquinone, p-hydroxyanisole, 2,6-di-tert-butyl-p-cresol, and phenothiazine. The mass of the added polymerization inhibitor may be 0.005%-0.1% of the mass of α-methylstyrene. For example, 0.1%.

[0037] The present application will be further described in detail below with reference to the embodiments. It should be noted that the following embodiments are for illustrative purposes only and are not intended to limit the scope of protection claimed in this application. Unless otherwise specified, the reagents, materials and instruments used are all commercially available products and can be obtained by purchase.

[0038] Examples 1-4: Synthesis and Preparation of Isopropylphenol Step 1: Acylation reaction In a 1L dry three-necked flask, aluminum trichloride (33.85g, 253.85mmol), 1,2-dichloroethane (360mL), and acetyl chloride (43.84g, 558.47mmol) were added sequentially under a nitrogen atmosphere. After mixing thoroughly, the mixture was cooled to 0℃ and reacted for 30 minutes. The temperature was controlled at -10℃, and 2,6-di-tert-butyl-p-cresol (111mg, 507.7umol) was added. Then, a 1,2-dichloroethane solution (120mL) containing the starting material α-methylstyrene (60g, 507.7mmol) was added dropwise. The mixture was heated to room temperature and reacted for 3 hours. After the reaction was completed, a reaction mixture containing the intermediate 4-isopropenyl acetophenone was obtained.

[0039] Step 2: Oxidative rearrangement reaction At a controlled temperature of -10℃, sodium carbonate (2.47 g, 23.37 mmol) and sodium citrate (2.53 g, 11.68 mmol) were slowly added to the reaction mixture, followed by dropwise addition of tert-butyl hydroperoxide (75.21 g, 584.21 mmol). The temperature was then raised to room temperature and reacted for 2 hours. After the reaction was completed, a reaction mixture containing 4-isopropenylphenyl acetate was obtained. The reaction mixture was quenched by adding ice water (100 mL) and saturated sodium bisulfite aqueous solution (200 mL) to the above reaction mixture at 0℃. The aqueous phase was extracted twice with dichloromethane (200 mL). The organic phase was dried and concentrated to obtain a crude product containing 4-isopropenylphenylacetate. The crude product was heated to 80℃ and distilled under reduced pressure of 1 mbar to obtain 73.5 g of the target 4-isopropenylphenylacetate intermediate product, with a yield of 82%. Intermediate NMR: 1 H NMR (400 MHz, Chloroform-d) δ 7.50 (d, J = 8.7 Hz, 2H), 7.08 (d, J = 8.7 Hz, 2H), 5.37 (t, J = 1.1 Hz, 1H), 5.11 (t, J = 1.5 Hz, 1H), 2.33 (s, 3H), 2.17 (s, 3H).

[0040] Step 3: Hydrolysis reaction The intermediate 4-isopropenylphenyl acetate (73 g, 414 mmol) was added to a 500 mL three-necked flask, followed by the addition of methanol (600 mL) and stirring until dissolved. The mixture was cooled to 0 °C, and sodium bicarbonate solid (34.8 g, 414 mmol) was added in batches. The mixture was then heated to room temperature and reacted for 4 h. After the reaction was complete, the insoluble solids were removed by filtration, and the filtrate was concentrated under reduced pressure. The concentrate was diluted and dissolved in ethyl acetate (300 mL), washed 2-3 times with ultrapure water (50 mL), and the organic phase was dried and concentrated to obtain the crude product. The crude product was dissolved in ethyl acetate (20 mL), methanol (5 mL), and cyclohexane (100 mL), and the mixture was cooled to 0 °C and crystallized twice. The solid product was collected by filtration and dried at 40 °C for 4 h to obtain 47.5 g of the target 4-isopropenylphenol, with a yield of 85%. The product was analyzed by gas chromatography and liquid chromatography (see details). Figure 3 The purity of the product was >99.9% and there was no phenol residue. The content of gold ions in the product was less than 50 ppb, as determined by inductively coupled plasma mass spectrometry. No polymer residue was determined by gel permeation chromatography. Product NMR: 1¹H NMR (400 MHz, DMSO-d⁶) δ 9.47 (s, 1H), 7.33 (d, J = 8.6 Hz, 2H), 6.73 (d, J = 8.7 Hz, 2H), 5.26 (d, J = 1.7 Hz, 1H), 4.92 (t, J = 1.6 Hz, 1H), 2.05 (s, 3H). See details... Figure 2 .

[0041] Example 2-4: Synthesis and Preparation of Isopropylphenol Step 1: Acylation reaction In a 1L dry three-necked flask, under a nitrogen atmosphere, boron trifluoride diethyl ether (36.03g, 253.85mmol), 1,2-dichloroethane (360mL), and acetic anhydride (57g, 558.47mmol) were added sequentially. After mixing thoroughly, the mixture was cooled to 0℃ and reacted for 30 minutes. The temperature was controlled at -10℃, and 2,6-di-tert-butyl-p-cresol (111mg, 507.7umol) was added. Then, a 1,2-dichloroethane solution (120mL) containing the starting material α-methylstyrene (60g, 507.7mmol) was added dropwise. The reaction was controlled at temperature for 4 hours. After the reaction was completed, a reaction mixture containing the intermediate 4-isopropenyl acetophenone was obtained.

[0042] Step 2: Oxidative rearrangement reaction The temperature was controlled at -10℃, and sodium bicarbonate (1.91 g, 22.47 mmol) and sodium dihydrogen phosphate (1.35 g, 11.23 mmol) were slowly added to the reaction mixture, followed by the dropwise addition of tert-butyl hydroperoxide (50.63 g, 561.74 mmol). The temperature was then raised to room temperature and reacted for 2 hours. After the reaction was completed, a reaction mixture containing 4-isopropenylphenyl acetate was obtained. At 0℃, ice water (100mL) and saturated sodium bisulfite aqueous solution (200mL) were added successively to the above reaction mixture to quench the reaction. The aqueous phase was extracted twice with dichloromethane (200mL). The organic phase was dried and concentrated to obtain a crude product containing 4-isopropenylphenylacetate. The crude product was heated to 80℃ and distilled under reduced pressure of 1mbar to obtain 70g of the target 4-isopropenylphenylacetate intermediate product, with a yield of 78%. Intermediate NMR: 1 H NMR (400 MHz, Chloroform-d) δ 7.50 (d, J = 8.7 Hz, 2H), 7.08 (d, J = 8.7 Hz, 2H), 5.37 (t, J = 1.1 Hz, 1H), 5.11 (t, J = 1.5 Hz, 1H), 2.33 (s, 3H), 2.17 (s, 3H).

[0043] Step 3: Hydrolysis reaction 70 g (397 mmol) of the intermediate 4-isopropenylphenyl acetate was added to a 500 mL three-necked flask, followed by 600 mL of methanol. The mixture was stirred until dissolved, cooled to 0 °C, and 42.10 g (397 mmol) of sodium carbonate solid was added in batches. The mixture was then heated to room temperature and reacted for 3 h. After the reaction was complete, the insoluble solids were removed by filtration, and the filtrate was concentrated under reduced pressure. The concentrate was diluted and dissolved in 300 mL of ethyl acetate, washed 2-3 times with 50 mL of ultrapure water, and the organic phase was dried and concentrated to obtain the crude product. The crude product was dissolved in 20 mL of ethyl acetate, 5 mL of methanol, and 100 mL of cyclohexane. The mixture was cooled to 0 °C and crystallized twice. The solid product was collected by filtration and dried at 40 °C for 4 h to obtain 46 g of the target 4-isopropenylphenol, with a yield of 86%. The product was analyzed by liquid chromatography (see details). Figure 4 The purity of the product was >99.9% and there was no phenol residue. The content of gold ions in the product was less than 50 ppb, as determined by inductively coupled plasma mass spectrometry. No polymer residue was determined by gel permeation chromatography.

[0044] Product NMR: 1 H NMR (400 MHz, DMSO-d6) δ 9.47 (s, 1H), 7.33 (d, J = 8.6Hz, 2H), 6.73 (d, J = 8.7 Hz, 2H), 5.26 (d, J = 1.7 Hz, 1H), 4.92 (t, J = 1.6Hz, 1H), 2.05 (s, 3H).

[0045] Example 3-4 Synthesis and Preparation of Isopropylphenol Step 1: Acylation reaction In a 1L dry three-necked flask, under a nitrogen atmosphere, boron trifluoride diethyl ether (36.03g, 253.85mmol), 1,2-dichloroethane (360mL), and acetic anhydride (57g, 558.47mmol) were added sequentially. After mixing thoroughly, the mixture was cooled to 0℃ and reacted for 30 minutes. The temperature was controlled at -10℃, and 2,6-di-tert-butyl-p-cresol (111mg, 507.7umol) was added. Then, a 1,2-dichloroethane solution (120mL) containing the starting material α-methylstyrene (60g, 507.7mmol) was added dropwise. The reaction was controlled at temperature for 4 hours. After the reaction was completed, a reaction mixture containing the intermediate 4-isopropenyl acetophenone was obtained.

[0046] Step 2: Oxidative rearrangement reaction The temperature was controlled at -10℃, and sodium bicarbonate (1.91 g, 22.47 mmol) and sodium dihydrogen phosphate (1.35 g, 11.23 mmol) were slowly added to the reaction mixture, followed by the dropwise addition of tert-butyl hydroperoxide (50.63 g, 561.74 mmol). The temperature was then raised to room temperature and reacted for 2 hours. After the reaction was completed, a reaction mixture containing 4-isopropenylphenyl acetate was obtained. At 0℃, ice water (100mL) and saturated sodium bisulfite aqueous solution (200mL) were added successively to the above reaction mixture to quench the reaction. The aqueous phase was extracted twice with dichloromethane (200mL). The organic phase was dried and concentrated to obtain a crude product containing 4-isopropenylphenylacetate. The crude product was heated to 80℃ and distilled under reduced pressure of 1mbar to obtain 70g of the target 4-isopropenylphenylacetate intermediate product, with a yield of 78%. Intermediate NMR: 1 H NMR (400 MHz, Chloroform-d) δ 7.50 (d, J = 8.7 Hz, 2H), 7.08 (d, J = 8.7 Hz, 2H), 5.37 (t, J = 1.1 Hz, 1H), 5.11 (t, J = 1.5 Hz, 1H), 2.33 (s, 3H), 2.17 (s, 3H).

[0047] Step 3: Hydrolysis reaction The intermediate 4-isopropenylphenyl acetate (70 g, 397 mmol) was added to a 500 mL three-necked flask, followed by the addition of methanol (600 mL) and stirring until dissolved. The mixture was cooled to 0 °C, and 25% ammonia (32.4 g, 477 mmol) was added dropwise. The mixture was then heated to 40 °C and reacted for 3 h. After the reaction was completed, the mixture was concentrated under reduced pressure. The concentrate was diluted and dissolved in ethyl acetate (300 mL), washed 2-3 times with ultrapure water (50 mL), and the organic phase was dried and concentrated to obtain the crude product. The crude product was dissolved in ethyl acetate (20 mL), methanol (5 mL), and cyclohexane (100 mL), and the mixture was cooled to 0 °C and crystallized twice at low temperature. The solid product was collected by filtration and dried at 40 °C for 4 h to obtain 43 g of the target 4-isopropenylphenol, with a yield of 80%. The product was analyzed by liquid chromatography (see details). Figure 5 The purity of the product was >99.8% and there was no phenol residue. The content of gold ions in the product was less than 50 ppb, as determined by inductively coupled plasma mass spectrometry. No polymer residue was determined by gel permeation chromatography.

[0048] Product NMR: 1H NMR (400 MHz, DMSO-d6) δ 9.47 (s, 1H), 7.33 (d, J = 8.6Hz, 2H), 6.73 (d, J = 8.7 Hz, 2H), 5.26 (d, J = 1.7 Hz, 1H), 4.92 (t, J = 1.6Hz, 1H), 2.05 (s, 3H).

[0049] Synthesis and preparation of comparative example 1,4-isopropenylphenyl acetate intermediate Step 1: Acylation reaction In a 1L dry three-necked flask, aluminum trichloride (33.85g, 253.85mmol), 1,2-dichloroethane (360mL), and acetyl chloride (43.84g, 558.47mmol) were added sequentially under a nitrogen atmosphere. After mixing thoroughly, the mixture was cooled to 0℃ and reacted for 30 minutes. The temperature was controlled at -10℃, and 2,6-di-tert-butyl-p-cresol (111mg, 507.7umol) was added. Then, a 1,2-dichloroethane solution (120mL) containing the starting material α-methylstyrene (60g, 507.7mmol) was added dropwise. The mixture was heated to room temperature and reacted for 3 hours. After the reaction was completed, a reaction mixture containing the intermediate 4-isopropenyl acetophenone was obtained.

[0050] Step 2: Oxidative rearrangement reaction Sodium carbonate (2.47 g, 23.37 mmol) was slowly added to the reaction mixture at a controlled temperature of -10 °C, followed by dropwise addition of tert-butyl hydroperoxide (75.21 g, 584.21 mmol). The temperature was then raised to room temperature and reacted for 2 hours. After the reaction was completed, a reaction mixture containing 4-isopropenylphenyl acetate was obtained. At 0℃, ice water (100mL) and saturated sodium bisulfite aqueous solution (200mL) were added successively to the above reaction mixture to quench the reaction. The aqueous phase was extracted twice with dichloromethane (200mL). The organic phase was dried and concentrated to obtain a crude product containing 4-isopropenylphenylacetate. The crude product was heated to 80℃ and distilled under reduced pressure of 1mbar to obtain 62g of the target 4-isopropenylphenylacetate intermediate product, with a yield of 69%. Intermediate NMR: 1 H NMR (400 MHz, Chloroform-d) δ 7.50 (d, J = 8.7 Hz, 2H), 7.08 (d, J = 8.7 Hz, 2H), 5.37 (t, J = 1.1 Hz, 1H), 5.11 (t, J = 1.5 Hz, 1H), 2.33 (s, 3H), 2.17 (s, 3H).

[0051] Synthesis and preparation of comparative example 2,4-isopropenylphenyl acetate intermediate Step 1: Acylation reaction In a 1L dry three-necked flask, aluminum trichloride (33.85g, 253.85mmol), 1,2-dichloroethane (360mL), and acetyl chloride (43.84g, 558.47mmol) were added sequentially under a nitrogen atmosphere. After mixing thoroughly, the mixture was cooled to 0℃ and reacted for 30 minutes. The temperature was controlled at -10℃, and 2,6-di-tert-butyl-p-cresol (111mg, 507.7umol) was added. Then, a 1,2-dichloroethane solution (120mL) containing the starting material α-methylstyrene (60g, 507.7mmol) was added dropwise. The mixture was heated to room temperature and reacted for 3 hours. After the reaction was completed, a reaction mixture containing the intermediate 4-isopropenyl acetophenone was obtained.

[0052] Step 2: Oxidative rearrangement reaction Sodium citrate (2.53 g, 11.68 mmol) was slowly added to the reaction mixture at a controlled temperature of -10 °C, followed by dropwise addition of tert-butyl hydroperoxide (75.21 g, 584.21 mmol). The temperature was then raised to room temperature and reacted for 2 hours. After the reaction was completed, a reaction mixture containing 4-isopropenylphenyl acetate was obtained. At 0℃, ice water (100mL) and saturated sodium bisulfite aqueous solution (200mL) were added successively to the above reaction mixture to quench the reaction. The aqueous phase was extracted twice with dichloromethane (200mL). The organic phase was dried and concentrated to obtain a crude product containing 4-isopropenylphenylacetate. The crude product was heated to 80℃ and distilled under reduced pressure of 1mbar to obtain 50g of the target 4-isopropenylphenylacetate intermediate product, with a yield of 56%. Intermediate NMR: 1 H NMR (400 MHz, Chloroform-d) δ 7.50 (d, J = 8.7 Hz, 2H), 7.08 (d, J = 8.7 Hz, 2H), 5.37 (t, J = 1.1 Hz, 1H), 5.11 (t, J = 1.5 Hz, 1H), 2.33 (s, 3H), 2.17 (s, 3H).

[0053] The method for preparing 4-isopropenol disclosed in this application uses α-methylstyrene as a raw material and efficiently prepares high-purity 4-isopropenol through three core reactions: acylation, oxidative rearrangement, and alkaline hydrolysis. The step of preparing the 4-isopropenylphenyl acetate intermediate utilizes a composite auxiliary agent to effectively improve the reaction yield. The entire preparation process avoids the harsh reaction temperatures, vacuum pressures, and product polymerization problems associated with high-temperature pyrolysis methods, and also avoids the use of high-cost, low-efficiency phosphorus ylide reagents and high-reaction-risk Grignard reagents, thus possessing significant advantages such as high-efficiency conversion, convenient operation, safety, economy, and environmental friendliness.

[0054] Furthermore, the 4-isopropenol product obtained by the preparation method disclosed in this application has a liquid chromatography purity of ≥99.9%, with no phenol residue, no polymerization byproducts, and a metal ion impurity content of less than 50 ppb. The final product possesses excellent qualities of high purity, low impurities, low metal ions, and no residual monomers or polymers, fully meeting the stringent high-purity requirements for use in photoresist material monomers, electronic chemicals, pharmaceutical intermediates, and precision synthesis.

[0055] This application has described the basic concepts. Obviously, for those skilled in the art, the above detailed disclosure is merely illustrative and does not constitute a limitation of this application. Although not explicitly stated herein, those skilled in the art may make various modifications, improvements, and corrections to this application. Such modifications, improvements, and corrections are suggested in this application, and therefore such modifications, improvements, and corrections still fall within the spirit and scope of the exemplary embodiments of this application.

[0056] Furthermore, this application uses specific terms to describe its embodiments. For example, "an embodiment," "one embodiment," and / or "some embodiments" refer to a particular feature, structure, or characteristic related to at least one embodiment of this application. Therefore, it should be emphasized and noted that "an embodiment," "one embodiment," or "an alternative embodiment" mentioned twice or more in different locations in this application do not necessarily refer to the same embodiment. In addition, certain features, structures, or characteristics in one or more embodiments of this application can be appropriately combined.

[0057] Similarly, it should be noted that, in order to simplify the description of this application and thus aid in the understanding of one or more embodiments of the invention, the foregoing description of the embodiments of this application sometimes combines multiple features into one embodiment or its description. However, this disclosure method does not imply that the subject matter of this application requires more features than those mentioned in the claims. In fact, the embodiments have fewer features than all the features of the single embodiments disclosed above.

[0058] Finally, it should be understood that the embodiments described in this application are merely illustrative of the principles of the embodiments of this application. Other modifications may also fall within the scope of this application. Therefore, alternative configurations of the embodiments of this application are considered as examples and not limitations, and are regarded as consistent with the teachings of this application. Accordingly, the embodiments of this application are not limited to the embodiments explicitly described and illustrated in this application.

Claims

1. A method for preparing 4-isopropenol, characterized in that, The preparation method includes the following steps: S1: Acidification reaction of α-methylstyrene yields a first reaction mixture containing 4-isopropenyl acetophenone intermediate; S2: The first reaction mixture containing 4-isopropenyl acetophenone intermediate does not require separation and purification. It is directly reacted with composite auxiliaries and oxidants to obtain the second reaction mixture containing 4-isopropenyl phenyl acetate. After post-treatment, pure 4-isopropenyl phenyl acetate is obtained. S3: Hydrolyze the pure 4-isopropenylphenyl acetate to obtain 4-isopropenol.

2. The preparation method according to claim 1, characterized in that, The first reaction mixture containing the 4-isopropenyl acetophenone intermediate comprises: In the presence of a catalyst, α-methylstyrene is subjected to an acylation reaction with an acylation reagent in an inert organic solvent to obtain a first reaction mixture containing the 4-isopropenyl acetophenone intermediate.

3. The preparation method according to claim 2, characterized in that, The acylation reagent is selected from at least one of acetyl chloride, acetyl bromide, acetic anhydride, or acetyl fluoride; the inert organic solvent is selected from at least one of dichloromethane, 1,2-dichloroethane, or chloroform; and the catalyst is selected from at least one of aluminum trichloride, ferric chloride, zinc chloride, boron trifluoride ether, sulfuric acid, methanesulfonic acid, trifluoromethanesulfonic acid, p-toluenesulfonic acid, β-zeolite, or sulfonic acid resin.

4. The preparation method according to claim 2, characterized in that, The second reaction mixture containing the 4-isopropenylphenyl acetate comprises: The first reaction mixture containing 4-isopropenyl acetophenone does not require separation and purification. A composite auxiliary agent and an oxidant are directly added to cause the 4-isopropenyl acetophenone intermediate to undergo an oxidative rearrangement reaction, resulting in a second reaction mixture containing the 4-isopropenyl phenyl acetate.

5. The preparation method according to claim 4, characterized in that, The composite additive is selected from at least two of sodium carbonate, sodium bicarbonate, sodium dihydrogen phosphate, or sodium citrate; the oxidant is selected from at least one of m-chloroperoxybenzoic acid, peracetic acid, aqueous hydrogen peroxide solution, or tert-butyl hydroperoxide.

6. The preparation method according to claim 4, characterized in that, The 4-isopropenol is obtained by: The pure 4-isopropenylphenyl acetate was hydrolyzed and purified using an alkaline reagent to obtain 4-isopropenol.

7. The preparation method according to claim 6, characterized in that, The alkaline reagent is selected from at least one of sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium tert-butoxide, sodium tert-butoxide, ammonia, isopropylamine, trimethane, diethylamine, triethylamine, pyridine, or N,N-diisopropylethylamine.

8. The preparation method according to claim 6, characterized in that, The hydrolysis reaction is carried out in a water-soluble organic solvent; the water-soluble organic solvent is selected from at least one of methanol, ethanol, isopropanol or tetrahydrofuran.

9. The preparation method according to claim 6, characterized in that, The post-processing includes quenching, extraction, drying and concentration, and distillation, while the purification includes filtration, concentration, washing, crystallization, and drying.

10. The preparation method according to claim 1, characterized in that, At least one of the acylation reaction, the oxidative rearrangement reaction, and the hydrolysis reaction is carried out in the presence of a polymerization inhibitor; the polymerization inhibitor is selected from hydroquinone, p-hydroxyanisole, 2,6-di-tert-butyl-p-cresol, and phenothiazine.

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