Preparation method of 4-(acetoxy) phenyl-2-methyl-2-acrylate

Abstract

The invention discloses a preparation method of 4-(acetoxy) phenyl-2-methyl-2-acrylate, which takes mild DMAP as a reaction catalyst, produced phenolic ester is not easy to hydrolyze due to weak alkalinity, and the dripping speed and the reaction temperature are controlled at the same time, so that simultaneous esterification of two hydroxyls of hydroquinone can be effectively avoided, and the yield of 4-(acetoxy) phenyl-2-methyl-2-acrylate is improved. And generation of by-products can be reduced. According to the method, the ethyl acetate and petroleum ether mixed solvent with the ratio of 1: 2 is adopted for recrystallization, hot filtration operation is carried out, insoluble substances are by-products, solids separated out after filtrate is cooled are target products, operation is simple, high-yield target product powder solids can be directly obtained, and the purity can reach 80% or above. The method is simple and rapid in process, short in production period, low in production cost, high in total yield of target products and suitable for industrial production.

Description

Technical Field

[0001] The invention belongs to the technical field of synthesis of important photoresist intermediates, and particularly relates to a method for preparing 4-(acetoxy)phenyl-2-methyl-2-acrylate. Background Art

[0002] Photoresist, also known as photoresist or photoresist, is a light-sensitive mixed liquid. It is widely used in the manufacturing process of chip design, manufacturing, packaging and testing, and is a core material necessary for the photolithography process in the chip manufacturing process. As an important component of photoresist, the research of methacrylate monomers will help to promote the improvement of the resolution, sensitivity, thermal stability, etc. of photoresist. Through in-depth research on methacrylate monomers, it is possible to discover new and lower-cost synthesis methods, thereby reducing the production cost of photoresist. At the same time, the new monomer structure may also bring about an increase in production efficiency, further promoting the development of the photoresist industry. The research on hydroquinone methacrylate monomers is of great development significance.

[0003] Hydroquinone carboxylic acid esters are common and important chemical intermediates. The preparation of hydroquinone monocarboxylic acid esters is generally achieved by controlling the molar ratio of raw materials or reacting under harsh conditions. For example, the feed ratio of hydroquinone monoacetate can be strictly controlled, but it is still difficult to avoid the formation of diacetylated products. There are many methods for synthesizing hydroquinone monocarboxylic acid esters. K.Sapkota et al. directly monoacetylate hydroquinone in pyridine (120-130 ° C). K.Michigami selected hydrogen fluoride-pyridine system, but such reactions generally have problems such as poor selectivity, severe conditions, and low yield. CN105753697A selects equivalent amounts of hydroquinone and its dicarboxylic acid ester as substrates, adds equivalent amounts of acid binding agent, and reacts in a polar aprotic solvent at room temperature to obtain hydroquinone monoacetate product, but the purification of the product still requires the use of column chromatography method, which is cumbersome to operate and difficult to industrialize. CN1219531A mentions that ketoisophorone and an acylating agent can be used to prepare a dicarboxylic acid ester compound of hydroquinone, but what it selects is acid as catalyst. This method has the problem that the product is hydrolyzed under a strong acid environment to a certain extent, resulting in a low product yield. AR Hajipour selects to use a catalyst such as N-methylimidazole sulfate, which can increase the yield to more than 89%, but increases the cost of purchasing and recovering the catalyst. Xia Yingzi et al. synthesized hydroquinone monoacetate using D001 resin as a catalyst, but the yield is low, and toluene is used as a solvent in the reaction, and the aftertreatment is more complicated. Therefore, the current phenol acylation method generally has a lower conversion rate, poor atom economy, and cannot simply construct a monoacylated product that overcomes steric hindrance using a chemical method. In view of the fact that hydroquinone carboxylic acid ester has a very wide application in the field of pharmaceutical and chemical engineering, it is necessary to develop a chemical method for synthesizing hydroquinone carboxylic acid ester with high atom economy. Summary of the Invention

[0004] Purpose of the invention: The technical problem to be solved by the present invention is to provide a new synthesis process for 4-(acetoxy)phenyl-2-methyl-2-acrylate. By selecting mild DMAP as a catalyst, optimal process conditions are explored, which can effectively reduce the yield of by-products. At the same time, the product is extracted by a mixed solvent recrystallization method, the purification process is optimized, the cost is reduced, and the yield is increased. This is of great significance for further improving the synthesis efficiency of 4-(acetoxy)phenyl-2-methyl-2-acrylate.

[0005] Technical solution: In order to solve the above technical problems, the present invention provides a method for preparing 4-(acetoxy)phenyl-2-methyl-2-acrylate, comprising the following steps:

[0006] 1) Preparation of Intermediate A Hydroquinone Monoacetate: A mixed solution of acetic anhydride and 4,4-dimethylaminopyridine in 1,4-dioxane was dropwise added to a solution of hydroquinone in 1,4-dioxane. After the addition was complete, the mixture was stirred thoroughly to react to obtain a mixed solution of intermediate A hydroquinone monoacetate, which was then treated to obtain a solid hydroquinone monoacetate.

[0007] 2) Preparation of 4-(acetoxy)phenyl-2-methyl-2-acrylate: The solid intermediate A, hydroquinone monoacetate, was added to 1,4-dioxane and heated to dissolve. The reaction solution was kept fully stirred to obtain a 1,4-dioxane solution of hydroquinone monoacetate. A 1,4-dioxane solution of methacrylic anhydride and DMAP was added dropwise to the 1,4-dioxane solution of hydroquinone monoacetate. After the dropwise addition was complete, the reaction solution was heated and fully stirred to obtain a mixed solution of 4-(acetoxy)phenyl-2-methyl-2-acrylate. The solution was extracted, concentrated, and then recrystallized from a mixed solvent of ethyl acetate and petroleum ether to obtain a solid 4-(acetoxy)phenyl-2-methyl-2-acrylate.

[0008] The 1,4-dioxane solution of hydroquinone in step 1) is prepared by adding 1,4-dioxane to hydroquinone and stirring and heating to 60-90° C. to dissolve the solution. The amount of 1,4-dioxane used is 2-4 times the mass of the hydroquinone.

[0009] Wherein, the molar ratio of hydroquinone, acetic anhydride and 4,4-dimethylaminopyridine in step 1) is 1:1-1.07:0.005-0.01.

[0010] Wherein, the dropping time in step 1) is 1 to 1.5 hours.

[0011] The reaction temperature in step 1) is 60° C. to 90° C., and the reaction time is 2 h to 4 h. If the reaction temperature is too low, the solubility of the raw materials is poor, and if the reaction temperature is too high, the phenolic ester obtained will decompose.

[0012] The treatment step in step 1) is as follows: adding water to the hydroquinone monoacetate mixed solution, adjusting the pH value to neutral with a weak base, extracting with dichloromethane organic solvent, drying the organic phase, and concentrating the organic solvent to obtain a hydroquinone monoacetate solid.

[0013] Wherein, the weak base is one or more of sodium bicarbonate, sodium carbonate or potassium carbonate, and a strong base will cause the product to decompose and reduce the yield.

[0014] Wherein, in step 2), the volume ratio of ethyl acetate to petroleum ether is 0.5 to 3:1.

[0015] Preferably, the volume ratio of ethyl acetate:petroleum ether is 1:2 to 1:3.

[0016] Wherein, step 2) further includes a hot filtration step after recrystallization, the hot filtration temperature is 50-60° C., the insoluble matter is a by-product, and the solid precipitated after cooling is the target product.

[0017] Beneficial effects: Compared with the prior art, the present invention has the following advantages:

[0018] (1) The present invention creatively develops a synthetic route for 4-(acetoxy)phenyl-2-methyl-2-acrylate. In the prior art, p-toluenesulfonic acid is mostly used as a catalyst to generate phenolic esters by reacting hydroquinone with acetic anhydride. However, phenolic esters are susceptible to ester hydrolysis under the action of strong acids and bases. The strong acidity of p-toluenesulfonic acid leads to an increase in by-products and difficulty in product purification. The present invention uses mild DMAP as a reaction catalyst. Due to its weak alkalinity, the produced phenolic ester is not easily hydrolyzed. Simultaneously, controlling the dropwise addition rate and reaction temperature can effectively avoid the simultaneous esterification of the two hydroxyl groups of hydroquinone, thereby reducing the generation of by-products. The present invention utilizes a mixed solvent for recrystallization during the purification process to purify the product, avoiding the commonly used purification method of column chromatography, greatly improving the efficiency of the operation, reducing costs, and being more suitable for industrial scale-up production.

[0019] (2) Purification of the intermediate of the present invention: A certain amount of water is added to the reaction solution, and the pH value is adjusted to neutral with a weak base. The organic phase is extracted with dichloromethane and dried. The organic solvent is concentrated to obtain a solid product of hydroquinone monoacetate. The intermediate with a purity of 95% can be obtained.

[0020] (3) Through the creative development of purification processes for intermediates and products by the present invention, both intermediates and products can be purified through simple extraction and recrystallization operations, effectively reducing production cycles and production costs, and further improving reaction efficiency. The present invention uses a mixed solvent of ethyl acetate and petroleum ether with a volume ratio of 1:2 for recrystallization and performs a hot filtration operation. The insoluble matter is a by-product, and the solid precipitated after the filtrate is cooled is the target product. The operation is simple, and a powder solid of the target product can be directly obtained with a purity of over 80%.

[0021] (4) The synthesis process of the present invention is simple and rapid, and both hydroquinone monoacetate and 4-(acetoxy)phenyl-2-methyl-2-acrylate are purified by recrystallization, resulting in a short production cycle, low production cost, high total yield of the target product, and suitable for industrial production. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 The synthetic route of the present invention;

[0023] Figure 2This is the NMR characterization result of intermediate A;

[0024] Figure 3 This is the NMR characterization result of the by-product of the final product B;

[0025] Figure 4 NMR characterization results of final product B. DETAILED DESCRIPTION

[0026] Example 1 Preparation of 4-(acetoxy)phenyl-2-methyl-2-acrylate

[0027] Weigh 11 g (0.1 mol) of hydroquinone and place it in a 100 mL dry three-necked flask. Add 40 mL of 1,4-dioxane, start magnetic stirring and raise the temperature to 60°C. After the hydroquinone is completely dissolved, dissolve 10.29 g (0.1 mol) of acetic anhydride and 0.0122 g (0.001 mol) of 4,4-dimethylaminopyridine (DMAP) in 10 mL of 1,4-dioxane solvent and place the mixture in a dropping funnel. , slowly add dropwise to the above hydroquinone reaction solution for 1 hour. After the addition is complete, heat to 80°C and maintain the temperature for 4 hours. After the reaction is complete, add 20mL of water to the mixed solution, add sodium bicarbonate to adjust the pH to alkaline, extract with dichloromethane (40mL×3), separate the liquids with a separatory funnel, combine the lower organic phases, dry over anhydrous sodium sulfate, and concentrate the solvent to obtain 12.24g of crude intermediate A, namely 4-acetoxyphenol, with a crude yield of approximately 80.56%. The purity of intermediate A is 95.5%, and its NMR characterization is as follows Figure 2 As shown, the specific results of its nuclear magnetic characterization are as follows: 1H NMR (500 MHz, DMSO) δ7.17 ppm (s, 1H), δ6.83 ppm (d, 2H), δ6.67 ppm (d, 2H), δ2.28 ppm (s, 3H).

[0028] 1.52g (0.01mol) of crude intermediate A 4-acetoxyphenol, 1.54g (0.01mol) of methacrylic anhydride, and 0.00122g (0.0001mol) of 4,4-dimethylaminopyridine (DMAP) were placed in a dry 100mL single-necked flask. 40mL of 1,4-dioxane was added. Magnetic stirring was started, a condenser was installed, and the temperature was raised to 80°C in a water bath and maintained for 4 hours. The reaction was monitored by a plate. After the reaction of the raw materials was completed, the solvent was removed by rotary evaporation. The product was recrystallized with a mixed solvent of ethyl acetate and petroleum ether (volume ratio = 1:2) and filtered hot. The insoluble matter was a by-product. The solid precipitated after cooling was the target product. The crude target product obtained by recrystallization had a purity of 85.0%, a yield of 1.72g, and a yield of about 78.18%. The NMR characterization of the by-product is as follows: Figure 3 As shown, the NMR characterization results are as follows: 1H NMR (500MHz, DMSO) δ9.47ppm (s, 1H), δ6.95ppm (d, 2H), δ6.78ppm (d, 2H), δ6.24ppm (s, 1H), δ5.85ppm (s, 1H), δ1.99ppm (s, 3H). The NMR characterization of the target product is as follows Figure 4 As shown, the NMR characterization results are as follows: 1 H NMR (500MHz, DMSO) δ7.25ppm(d,2H), δ7.18ppm(d,2H), δ6.29ppm(s,1H), δ5.92ppm(s,1H), δ2.28ppm(s,3H), δ2.01ppm(s,3H).

[0029] Example 2 Preparation of 4-(acetoxy)phenyl-2-methyl-2-acrylate

[0030] Weigh 11.00 g (0.1 mol) of hydroquinone and place it in a 100 mL dry three-necked flask, add 40 mL of 1,4-dioxane, start magnetic stirring and heat to 60 ° C. After the hydroquinone is completely dissolved, 11.01 g (0.107 mol) of acetic anhydride, 0.0122 g (0.001 mol) of 4,4-dimethylaminopyridine (DMAP) and 10 mL of 1,4-dioxane are mixed and placed in a dropping funnel and slowly added dropwise to the reaction solution for 1.5 hours. After the addition is complete, the reaction solution is heated to 90 ° C and maintained at this temperature for 2 hours. After the reaction is completed, 15 mL of water is added to the mixed solution, potassium carbonate is added to adjust the pH to alkaline, and the mixture is extracted with dichloromethane (20 mL × 3). The lower organic phase is separated and combined with a separatory funnel and dried over anhydrous sodium sulfate, and the solvent is concentrated to obtain intermediate A. The crude product of 4-acetoxyphenol was 12.17 g, with a crude yield of about 80.01%. The purity of intermediate A was 95.2%, and the NMR characterization results were the same as those in Example 1.

[0031] 1.52 g (0.01 mol) of crude intermediate A 4-acetoxyphenol, 1.54 g (0.01 mol) of methacrylic anhydride, and 0.00122 g (0.0001 mol) of 4,4-dimethylaminopyridine (DMAP) were placed in a dry 50 mL single-necked flask. 30 mL of 1,4-dioxane was added, and the mixture was stirred magnetically with a condenser. The temperature was raised to 90°C in a water bath and maintained for 2 hours with a plate monitor. After the reaction was complete, the solvent was removed by rotary evaporation. The mixture was recrystallized from a mixture of ethyl acetate and petroleum ether (volume ratio = 1:2) and filtered hot. The insoluble matter was the byproduct, and the solid precipitated after cooling was the target product. The crude target product obtained by recrystallization had a purity of 85.2% and a yield of 1.66 g, for a yield of approximately 75.18%. The NMR characterization results of the byproduct and target product were the same as those in Example 1.

[0032] Example 3 Preparation of 4-(acetoxy)phenyl-2-methyl-2-acrylate

[0033] 11.00 g (0.01 mol) of hydroquinone was weighed and placed in a 100 mL dry three-necked flask, 40 mL of 1,4-dioxane was added, magnetic stirring was started and the temperature was raised to 60°C. After the hydroquinone was completely dissolved, 10.8 g (0.105 mol) of acetic anhydride, 0.0061 g (0.0005 mol) of 4,4-dimethylaminopyridine (DMAP) and 15 mL of 1,4-dioxane were mixed and placed in a dropping funnel and slowly added dropwise to the reaction solution for 1.5 hours. After the addition was complete, the temperature was raised to 60°C and maintained at this temperature for 3 hours. After the reaction was completed, 20 ml of water was added to the mixed solution, sodium carbonate was added to adjust the pH to alkaline, and the mixture was extracted with dichloromethane (40 mL×3). The lower organic phase was separated and combined using a separatory funnel and dried over anhydrous sodium sulfate, and the solvent was concentrated to obtain intermediate A. The crude product of 4-acetoxyphenol was 12.17 g, with a crude yield of about 80.01%. The purity of intermediate A was 96.1%, and the NMR characterization results were the same as those in Example 1.

[0034] 1.52 g (0.01 mol) of crude intermediate A 4-acetoxyphenol, 1.54 g (0.01 mol) of methacrylic anhydride, and 0.00122 g (0.0001 mol) of 4,4-dimethylaminopyridine (DMAP) were placed in a dry 100 mL single-necked flask. 20 mL of 1,4-dioxane was added, and the mixture was stirred magnetically with a condenser. The temperature was raised to 60°C in a water bath and the reaction was maintained for 3 hours with a plate monitoring. After the reaction was complete, the solvent was removed by rotary evaporation. The mixture was recrystallized from a mixture of ethyl acetate and petroleum ether (volume ratio = 1:2) and filtered hot. The insoluble matter was the byproduct, and the solid precipitated after cooling was the target product. The crude target product obtained by recrystallization had a purity of 84.5% and a yield of 1.61 g, for a yield of approximately 73.18%. The NMR characterization results of the byproduct and target product were the same as those in Example 1.

[0035] Example 4 Preparation of 4-(acetoxy)phenyl-2-methyl-2-acrylate

[0036] Weigh 11 g (0.1 mol) of hydroquinone and place it in a 100 mL dry three-necked flask. Add 40 mL of 1,4-dioxane, start magnetic stirring and raise the temperature to 60°C. After the hydroquinone is completely dissolved, dissolve 10.29 g (0.1 mol) of acetic anhydride and 0.0122 g (0.001 mol) of 4,4-dimethylaminopyridine (DMAP) in 10 mL of 1,4-dioxane solvent and place the mixture in a dropping funnel. , slowly add dropwise to the above hydroquinone reaction solution for 1 hour. After the addition is complete, heat to 80°C and maintain this temperature for 4 hours. After the reaction is complete, add 20mL of water to the mixed solution, add sodium bicarbonate to adjust the pH to alkaline, extract with dichloromethane (40mL×3), separate the liquids with a separatory funnel, combine the lower organic phases, dry over anhydrous sodium sulfate, and concentrate the solvent to obtain 12.24g of crude intermediate A, namely 4-acetoxyphenol, with a crude yield of approximately 80.56%. The purity of intermediate A is 95.5%, and the NMR characterization is as follows Figure 2 As shown, the specific results of its NMR characterization are as follows: 1 H NMR (500MHz, DMSO) δ7.17ppm (s, 1H), δ6.83ppm (d, 2H), δ6.67ppm (d, 2H), δ2.28ppm (s, 3H).

[0037] 1.52g (0.01mol) of crude intermediate A 4-acetoxyphenol, 1.54g (0.01mol) of methacrylic anhydride, and 0.00122g (0.0001mol) of 4,4-dimethylaminopyridine (DMAP) were placed in a dry 100mL single-necked flask. 40mL of 1,4-dioxane was added. Magnetic stirring was started, a condenser was installed, and the temperature was raised to 80°C in a water bath and maintained for 4 hours. The reaction was monitored by plate monitoring. After the reaction of the raw materials was completed, the solvent was removed by rotary evaporation. The product was recrystallized with a mixed solvent of ethyl acetate and petroleum ether (volume ratio = 1:3) and filtered hot. The insoluble matter was a by-product. The solid precipitated after cooling was the target product. The crude target product obtained by recrystallization had a purity of 83.6%, a yield of 1.64g, and a yield of about 74.54%. The NMR characterization of the by-product is as follows Figure 3 As shown, the NMR characterization results are as follows: 1 H NMR (500MHz, DMSO) δ9.47ppm (s, 1H), δ6.95ppm (d, 2H), δ6.78ppm (d, 2H), δ6.24ppm (s, 1H), δ5.85ppm (s, 1H), δ1.99ppm (s, 3H). The NMR characterization of the target product is as follows Figure 4 As shown, the NMR characterization results are as follows: 1H NMR (500MHz, DMSO) δ7.25ppm(d,2H), δ7.18ppm(d,2H), δ6.29ppm(s,1H), δ5.92ppm(s,1H), δ2.28ppm(s,3H), δ2.01ppm(s,3H).

[0038] Comparative Example 1 Preparation of 4-(acetoxy)phenyl-2-methyl-2-acrylate

[0039] 11.00 g (0.1 mol) of hydroquinone was weighed and placed in a 100 mL dry three-necked flask, 40 mL of 1,4-dioxane was added, magnetic stirring was started and the temperature was raised to 60°C. After the hydroquinone was completely dissolved, 10.29 g (0.1 mol) of acetic anhydride, 0.26 g of p-toluenesulfonic acid (2% by mass of hydroquinone) and 10 mL of 1,4-dioxane were mixed and placed in a dropping funnel. The mixture was slowly added dropwise to the reaction solution for 1 hour. After the addition was complete, the reaction solution was heated to 80°C and maintained at this temperature for 3.5 hours. After the reaction was completed, 20 mL of water was added to the mixed solution, sodium bicarbonate was added to adjust the pH to alkaline, and the mixture was extracted with dichloromethane (40 mL×3). The lower organic phase was separated and combined using a separatory funnel and dried over anhydrous sodium sulfate, and the solvent was concentrated to obtain intermediate A. The purity of the crude 4-acetoxyphenol was 85.2%, the yield was 9.88 g, and the crude yield was about 65.12%.

[0040] 1.52 g (0.01 mol) of crude intermediate A4-acetoxyphenol, 1.54 g (0.01 mol) of methacrylic anhydride, and 0.03 g of p-toluenesulfonic acid (2% by mass of hydroquinone) were placed in a dry 100 mL single-necked flask, 40 mL of 1,4-dioxane solvent was added, magnetic stirring was turned on, a condenser was configured, the water bath was heated to 80°C and the reaction was maintained for 4 hours, and the plate was monitored. After the reaction of the raw materials was completed, the solvent was removed by rotary evaporation, 20 ml of water was added, and sodium bicarbonate was added to adjust the temperature. The pH value was adjusted to neutral, and the aqueous phase was extracted with ethyl acetate (30 mL*3). 2 g of anhydrous sodium sulfate was weighed and the organic phase was dried. After the organic phase was partially concentrated, 15 mL of petroleum ether was added. A large amount of white solid precipitated. The solid was collected by filtration and recrystallized with 40 mL of a mixed solvent of ethyl acetate and petroleum ether (volume ratio of 1:2). The filtrate was cooled, crystallized, and filtered to obtain 1.232 g of solid 4-(acetoxy)phenyl-2-methyl-2-acrylate with a purity of 65.6% and a yield of about 56.00%.

[0041] Comparative Example 2 Preparation of 4-(acetoxy)phenyl-2-methyl-2-acrylate

[0042] Weigh 11.00 g (0.1 mol) of hydroquinone and place it in a 100 mL dry three-necked flask, add 40 mL of 1,4-dioxane, start magnetic stirring and raise the temperature to 60 ° C. After the hydroquinone is completely dissolved, mix 10.8 g (0.105 mol) of acetic anhydride, 0.0061 g (0.0005 mol) of 4,4-dimethylaminopyridine (DMAP) and 15 mL of 1,4-dioxane and place them in a dropping funnel and add the mixture to the reaction mixture. The reaction mixture was slowly added dropwise for 1.5 hours. After the addition was complete, the temperature was raised to 60°C and maintained at this temperature for 3 hours. After the reaction was completed, 20 mL of water was added to the mixed solution, and sodium carbonate was added to adjust the pH to alkaline. The mixture was extracted with dichloromethane (40 mL × 3). The lower organic phase was separated and combined using a separatory funnel, dried over anhydrous sodium sulfate, and the solvent was concentrated to obtain the intermediate A4-acetoxyphenol crude product with a purity of 95.0%, a yield of 12.17 g, and a crude yield of about 80.01%.

[0043] The crude intermediate A4-acetoxyphenol 1.52g (0.01mol), methacrylic anhydride 1.54g (0.01mol), 4,4-dimethylaminopyridine (DMAP) 0.00122g (0.0001mol) 0.03g were placed in a dry 100mL single-necked flask, 40mL of solvent 1,4-dioxane was added, magnetic stirring was turned on, a condenser was configured, the water bath was heated to 70℃ and the reaction was maintained for 4 hours, the plate was monitored, and after the reaction of the raw materials was completed, the solvent was removed by rotary evaporation, and 20ml of 1,4-dioxane was added. l of water and sodium bicarbonate was added to adjust the pH to neutral. The aqueous phase was extracted with ethyl acetate (30 mL*3). 2 g of anhydrous sodium sulfate was weighed and the organic phase was dried. The organic phase was partially concentrated and 15 mL of petroleum ether was added. A large amount of white solid precipitated. The solid was collected by filtration and recrystallized from 40 mL of a mixed solvent of ethyl acetate and petroleum ether (volume ratio of 1:2). The purity of the crude target product 4-(acetyloxy)phenyl-2-methyl-2-acrylate was 78.3%, the yield was 1.21 g, and the yield was about 55.45%.

[0044] Comparative Example 3

[0045] Weigh 11.00 g (0.1 mol) of hydroquinone and place it in a 100 ml dry three-necked flask, add 40 mL of 1,4-dioxane, start magnetic stirring and heat to 60 ° C. After the hydroquinone is completely dissolved, 10.29 g (0.1 mol) of acetic anhydride, 0.26 g of p-toluenesulfonic acid (2% by mass of hydroquinone) and 10 mL of 1,4-dioxane are mixed and placed in a dropping funnel. The mixture is slowly added dropwise to the reaction solution for 1 hour. After the addition is complete, the reaction solution is heated to 80 ° C. and maintained at this temperature for 3.5 hours. After the reaction is completed, 20 mL of water is added to the mixed solution, sodium bicarbonate is added to adjust the pH to alkaline, and the mixture is extracted with dichloromethane (40 mL × 3). The lower organic phase is separated and combined with a separatory funnel and dried over anhydrous sodium sulfate, and the solvent is concentrated to obtain intermediate A. The purity of the crude 4-acetoxyphenol was 70.2%, the yield was 9.88 g, and the crude yield was about 65.12%.

[0046] To the intermediate A hydroquinone monoacetate 0.152g (0.001mol), methacrylic anhydride 0.154g (0.001mol), 4,4-dimethylaminopyridine (DMAP) 0.0122g (0.0001mol), was added 10mL of 1,4-dioxane solvent, magnetic stirring was started, a condenser was provided, the temperature was raised to 80℃ in a water bath and the reaction was maintained for 4 hours, and the reaction was monitored by spot plate. After the reaction of the raw materials was completed, the solvent was removed by rotary evaporation. After the reaction of the raw materials was completed, the solvent was removed by rotary evaporation to obtain an oily substance. The oily substance was gently dissolved and recrystallized with 10ml of a mixed solvent of methanol and water (volume ratio of 1:2), hot dissolved and filtered, and the filtrate was cooled to obtain a white solid. TLC spot plate monitoring showed that no target product was generated. It was confirmed by nuclear magnetic resonance that the product was completely hydrolyzed into by-products.

[0047] Comparative Example 4

[0048] Weigh 11.00 g (0.1 mol) of hydroquinone and place it in a 100 mL dry three-necked flask, add 40 mL of 1,4-dioxane, start magnetic stirring and heat to 60 ° C. After the hydroquinone is completely dissolved, 10.29 g (0.1 mol) of acetic anhydride, 0.0122 g (0.001 mol) of 4,4-dimethylaminopyridine (DMAP) and 10 mL of 1,4-dioxane are mixed as solvents and placed in a dropping funnel. The mixture is slowly added dropwise to the reaction solution for 1 hour, monitored by TLC spot plate, and the temperature is raised to 80 ° C. and maintained at this temperature for 3.5 hours. After the reaction is completed, 20 mL of water is added to the mixed solution, sodium bicarbonate is added to adjust the pH to alkaline, and the mixture is extracted with dichloromethane (40 mL × 3). The lower organic phase is separated and combined with a separatory funnel and dried over anhydrous sodium sulfate, and the solvent is concentrated to obtain intermediate A. The purity of the crude 4-acetoxyphenol was 95.0%, the yield was 12.17 g, and the crude yield was about 80.01%.

[0049] To the intermediate A hydroquinone monoacetate 0.152g (0.001mol), methacrylic anhydride 0.154g (0.001mol), 4,4-dimethylaminopyridine (DMAP) 0.0122g (0.0001mol), was added 10mL of 1,4-dioxane solvent, magnetic stirring was started, a condenser was provided, and the temperature was raised to 80℃ in a water bath and kept for 4 hours. The reaction was monitored by TLC. After the reaction of the raw materials was completed, the solvent was removed by rotary evaporation. After the reaction of the raw materials was completed, the solvent was removed by rotary evaporation. After the reaction of the raw materials was completed, 5mL of water was added and the pH was adjusted to neutral with sodium bicarbonate. The aqueous phase was extracted with ethyl acetate (30mL*3). 2g of anhydrous sodium sulfate was weighed and the organic phase was dried. The organic phase was partially concentrated and 15mL of petroleum ether was added. A large amount of white solid precipitated. The solid was collected by filtration and hot dissolved and filtered with 5mL of a mixed solvent of methanol and water (volume ratio of 2:1). After the filtrate was cooled, TLC was monitored by TLC. No target product was produced and all the products were hydrolyzed to by-products.

[0050] As can be seen from Examples 1-4 and Comparative Examples 1-4, in terms of catalyst selection, p-toluenesulfonic acid is a strong acid, and the phenolic hydroxyl groups in the reaction substrate are active groups, resulting in an increase in by-products. Compared to using DMAP, the esterification reaction can be completed quickly at a lower temperature with fewer side reactions, resulting in a lower yield. In the post-processing process for the target product, a mixed solvent of methanol and water is used, and under heating conditions, the phenolic ester is thermally decomposed into phenol and carboxylic acid, all of which become by-products. Therefore, the choice of mixed solvent for recrystallization is extremely important. The present invention uses mild DMAP as the starting catalyst in the first step of the synthesis. Due to its weak alkalinity, the produced phenolic ester is not easily hydrolyzed. Simultaneously, controlling the addition rate and reaction temperature effectively prevents the simultaneous esterification of the two hydroxyl groups of hydroquinone, thereby reducing the formation of by-products. In the intermediate purification, a certain amount of water is added to the reaction solution, the pH is adjusted to neutral with a weak base, and then the organic phase is extracted with dichloromethane and dried. The organic solvent is concentrated to obtain a solid product of hydroquinone monoacetate, resulting in an intermediate with a purity of 95%. In the purification of the target product, a mixed solvent of ethyl acetate and petroleum ether with a volume ratio of 1:2 is used for recrystallization and hot filtration is performed. The insoluble matter is a by-product, and the solid precipitated after the filtrate is cooled is the target product. The operation is simple and a powder solid of the target product with high yield and high purity can be directly obtained.

Claims

1. A method for preparing 4-(acetoxy)phenyl-2-methyl-2-acrylate, characterized in that: The following steps are involved: 1) Preparation of Intermediate A Hydroquinone Monoacetate: A mixed solution of acetic anhydride and 4,4-dimethylaminopyridine in 1,4-dioxane was dropwise added to a solution of hydroquinone in 1,4-dioxane. After the addition was complete, the mixture was stirred thoroughly to react to obtain a mixed solution of intermediate A hydroquinone monoacetate, which was then treated to obtain a solid hydroquinone monoacetate. 2) Preparation of 4-(acetoxy)phenyl-2-methyl-2-acrylate: The solid intermediate A, hydroquinone monoacetate, was added to 1,4-dioxane and heated to dissolve. The reaction solution was kept fully stirred to obtain a 1,4-dioxane solution of hydroquinone monoacetate. A 1,4-dioxane solution of methacrylic anhydride and DMAP was added dropwise to the 1,4-dioxane solution of hydroquinone monoacetate. After the addition was complete, the reaction solution was heated and fully stirred to obtain a mixed solution of 4-(acetoxy)phenyl-2-methyl-2-acrylate. The solution was extracted, concentrated, and then recrystallized from a mixed solvent of ethyl acetate and petroleum ether to obtain solid 4-(acetoxy)phenyl-2-methyl-2-acrylate.

2. The method for preparing 4-(acetoxy)phenyl-2-methyl-2-acrylate according to claim 1, characterized in that: The 1,4-dioxane solution of hydroquinone in step 1) is prepared by adding 1,4-dioxane to hydroquinone and stirring and heating to 60-90° C. to dissolve the solution. The amount of 1,4-dioxane used is 2-4 times the mass of the hydroquinone.

3. The method for preparing 4-(acetoxy)phenyl-2-methyl-2-acrylate according to claim 1, characterized in that: The molar ratio of hydroquinone, acetic anhydride and 4,4-dimethylaminopyridine in step 1) is 1:1-1.07:0.005-0.

01.

4. The method for preparing 4-(acetoxy)phenyl-2-methyl-2-acrylate according to claim 1, wherein The addition time in step 1) is 1 to 1.5 hours.

5. The method for preparing 4-(acetoxy)phenyl-2-methyl-2-acrylate according to claim 1, wherein: In step 1), the reaction temperature is 60°C to 90°C, and the reaction time is 2h to 4h.

6. The method for preparing 4-(acetoxy)phenyl-2-methyl-2-acrylate according to claim 1, characterized in that: The treatment step in step 1) is as follows: adding water to the hydroquinone monoacetate mixed solution, adjusting the pH value to neutral with a weak base, extracting with dichloromethane organic solvent, drying the organic phase, and concentrating the organic solvent to obtain a hydroquinone monoacetate solid.

7. The method for preparing 4-(acetoxy)phenyl-2-methyl-2-acrylate according to claim 6, characterized in that: The weak base is one or more of sodium bicarbonate, sodium carbonate or potassium carbonate.

8. The method for preparing 4-(acetoxy)phenyl-2-methyl-2-acrylate according to claim 1, characterized in that: In step 2), the volume ratio of ethyl acetate to petroleum ether is 0.5 to 3:

1.

9. The method for preparing 4-(acetoxy)phenyl-2-methyl-2-acrylate according to claim 1, wherein: Step 2) further includes a hot filtration step after recrystallization, the hot filtration temperature is 50-60°C, the insoluble matter is a by-product, and the solid precipitated after cooling is the target product.

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