A method for preparing p-hydroxystyrene

Abstract

The present invention provides a method for preparing p-hydroxystyrene, the method comprising reacting p-hydroxybenzaldehyde in an organic solvent with dimethylacetamide in a reactor under the catalysis of an alkaline catalyst to produce p-hydroxystyrene, wherein the method does not involve reacting p-hydroxybenzaldehyde with malonic acid to produce p-hydroxystyrene.

Description

Technical Field

[0001] This invention relates to the field of organic compound preparation technology, and specifically to a method for preparing p-hydroxystyrene. Background Technology

[0002] p-hydroxystyrene is an important organic compound with key applications and high value in chemical and pharmaceutical fields. In emerging photoresist technology, positive chemical amplification resists typically use derivatives of p-hydroxystyrene as acid-sensitive resins. P-hydroxystyrene-based polymeric photoresists have become a key technology for photolithography of 0.11μm linewidth chips, playing an indispensable role in the high-precision manufacturing of semiconductor chips. The importance of p-hydroxystyrene in the photoresist field is mentioned in related patents such as CN108658731B, as it can affect the performance of photoresists, thereby affecting the precision and quality of chip manufacturing.

[0003] p-Hydroxystyrene is also widely used in the synthesis of various polymer materials. It can participate in polymerization reactions as a monomer, endowing polymers with special properties. For example, its derivatives can be used to prepare polymer materials with specific functions, which have important applications in electronics, automotive, aerospace, and other fields. In the research and development of some high-performance materials, the structural characteristics of p-hydroxystyrene can bring good stability, heat resistance, and chemical resistance to the materials.

[0004] In pharmaceutical synthesis, p-hydroxystyrene is an important intermediate. Through further chemical reactions, it can introduce different functional groups to synthesize pharmacologically active compounds. Many drug synthesis routes involve the transformation of p-hydroxystyrene or its derivatives. For example, in the synthesis of some lipid-lowering drugs such as ciprofibrate, p-hydroxystyrene is a key starting material or intermediate, acting as a bridge to the final drug synthesis and providing an important foundation for pharmaceutical research and production.

[0005] Currently, the preparation of p-hydroxystyrene generally involves reacting p-hydroxybenzaldehyde with malonic acid under the catalysis of an alkaline catalyst.

[0006] Chinese invention patent application CN114751808A discloses a process for preparing p-hydroxystyrene from p-hydroxybenzaldehyde, wherein the reactants include p-hydroxybenzaldehyde, malonic acid, an alkaline catalyst (such as various amines such as monomethylamine and ethylenediamine, and alkalis such as sodium hydroxide), and a polymerization inhibitor (such as p-hydroxyanisole and hydroquinone). The reaction conditions are under an inert gas atmosphere, at 105℃-150℃ for 3-8 hours (or at 110℃-140℃ for 3-4 hours). Examples show that the yield of the reaction product p-hydroxystyrene is 73%-86%.

[0007] Chinese invention patent CN109336741B discloses a process for preparing p-hydroxystyrene from p-hydroxybenzaldehyde, wherein the reactants include p-hydroxybenzaldehyde, malonic acid, an ionic liquid (such as 1-methyl-3-propylimidazolium chloride), and sodium hydroxide. The reaction conditions are: first reacting at 20-60°C, then heating to 80-180°C, and finally cooling to room temperature after the reaction is complete. Example 1 shows a yield of 99.1% for the reaction product, p-hydroxystyrene.

[0008] Chinese invention patent CN109438191B discloses a process for preparing p-hydroxystyrene from p-hydroxybenzaldehyde, wherein the reactants include p-hydroxybenzaldehyde, malonic acid, an ionic liquid (such as N-ethylpyridine bromide), and sodium hydroxide. The reaction conditions are as follows: first, the reaction is carried out at 20-80°C, then heated to 100-180°C, and then cooled to room temperature. Example 1 shows that the yield of the reaction product p-hydroxystyrene is 99.5%.

[0009] Chinese invention patent CN109485550B discloses a process for preparing p-hydroxystyrene from p-hydroxybenzaldehyde, wherein the reactants include p-hydroxybenzaldehyde, malonic acid, an ionic liquid (such as N-butyl-N-methylpiperidine bromide chloride), and sodium hydroxide. The reaction conditions are: first reacting at 10-60°C, then heating to 80-200°C, and finally cooling to room temperature. Example 1 shows a yield of 99.3% for the reaction product p-hydroxystyrene.

[0010] Chinese invention patent CN108658731B discloses a process for preparing p-hydroxystyrene from p-hydroxybenzaldehyde, wherein the reaction raw materials include p-hydroxybenzaldehyde, malonic acid, and a metal ion catalyst (cation such as Cu). 2+ Ni 2+ Organic or inorganic bases are used. The reaction is carried out in a distillation column at the reflux temperature of the reaction system, with a packing height equivalent to 3-30 theoretical plates. Examples 1-5 show that the two-stage reaction uses a metal ion catalyst and a base catalyst respectively, at a reaction temperature of 120°C or 140°C, and the yield of the reaction product p-hydroxystyrene is 91.3-95.1%, for example, 94.0% in Example 1.

[0011] Chinese invention patent CN106928047B discloses a process for preparing p-hydroxystyrene from p-hydroxybenzaldehyde, wherein the reaction raw materials include p-hydroxybenzaldehyde, malonic acid, and a base (triethylamine, etc.). The reaction conditions are a reflux reaction at 150°C.

[0012] Examples 1-5 show that the yield of p-hydroxystyrene is 92.1%-94.6%.

[0013] Chinese invention patent CN105175250B discloses a process for preparing p-hydroxystyrene from p-hydroxybenzaldehyde, wherein the reactants include p-hydroxybenzaldehyde, malonic acid, and a basic catalyst (such as triethylamine or pyrrolidine). The reaction conditions are 150°C for 6 hours. Examples show that the yield of the reaction product p-hydroxystyrene is 93%-98%.

[0014] Chinese invention patent application CN103709030A discloses a process for preparing p-hydroxystyrene from p-hydroxybenzaldehyde, wherein the reactants include p-hydroxybenzaldehyde, malonic acid, and a basic catalyst (piperidine, etc.). The reaction conditions are 100-120°C for 8-12 hours. Examples show that the yield of the reaction product p-hydroxystyrene is 83% or 84.1%.

[0015] Chinese invention patent CN102001918B discloses a process for preparing p-hydroxystyrene from p-hydroxybenzaldehyde. The reactants include p-hydroxybenzaldehyde, malonic acid, 4-methylpyridine, and piperidine (for the preparation of p-hydroxycinnamic acid), and p-hydroxycinnamic acid, DMF, and potassium acetate (for the preparation of p-hydroxystyrene). The reaction conditions are as follows: first, p-hydroxycinnamic acid is prepared by reacting at 80-95°C for 1.5 hours, and then p-hydroxycinnamic acid is reacted at 130-150°C for 1.5 hours to prepare p-hydroxystyrene. Examples show that the yield of the reaction product, p-hydroxystyrene, is approximately 98%.

[0016] Chinese invention patent CN100360486C discloses a process for preparing p-hydroxystyrene from p-hydroxybenzaldehyde, wherein the reactants include p-hydroxybenzaldehyde, malonic acid, and triethylamine as a catalyst. The reaction conditions are 150-160℃ (or initially at 80-100℃ for 2-5 hours and then increased to 150-160℃), with continuous stirring and temperature control for 5-8 hours. The reaction process is protected with an inert gas, and azeotropic dehydration is performed. Examples show a yield of 69%-78% for the p-hydroxystyrene product.

[0017] The various methods described above for preparing p-hydroxystyrene from p-hydroxybenzaldehyde and malonic acid under alkaline catalyst catalysis generally suffer from drawbacks such as high reaction costs (e.g., requiring expensive raw material malonic acid, with a market price of approximately 29,700 yuan / ton (manufacturer quote shown on the chemicalbook website on December 27, 2024); requiring high reaction temperatures; requiring inert gas protection; requiring the participation of ionic liquids; requiring distillation columns; requiring staged reactions; etc.). Therefore, there is a need in the art for an improved method for preparing p-hydroxystyrene to overcome these drawbacks. Summary of the Invention

[0018] This invention satisfies the needs of the art by providing a novel method for preparing p-hydroxystyrene.

[0019] Surprisingly, this invention discovers that the innovative use of dimethylacetamide (market price approximately 5300 RMB / ton, manufacturer's quote shown on the Chemicalbook website on December 27, 2024) instead of malonic acid as a raw material allows for the reaction with p-hydroxybenzaldehyde under alkaline catalyst to prepare p-hydroxystyrene. This avoids the use of expensive malonic acid while maintaining a high yield and achieving lower reaction costs, resulting in a 15% reduction in raw material costs. This invention also optimizes relevant reaction parameters and catalysts to achieve higher yields.

[0020] Therefore, in one aspect, the present invention provides a method for preparing p-hydroxystyrene, the method comprising reacting p-hydroxybenzaldehyde in an organic solvent with dimethylacetamide in a reactor under the catalysis of an alkaline catalyst to produce p-hydroxystyrene, wherein the method does not include reacting p-hydroxybenzaldehyde with malonic acid to produce p-hydroxystyrene.

[0021] In some embodiments, the molar ratio of the raw material p-hydroxybenzaldehyde to the raw material dimethylacetamide is selected from 1:1 to 1:5 or any subrange or point value therein, for example, but not limited to, 1:1, 1:2, 1:3, 1:4, 1:5, 1:2-1:3; preferably 1:2. The present invention has particularly found that a molar ratio of 1:2 can achieve better reaction equilibrium and higher yield. This molar ratio is selected based on a comprehensive consideration of reaction kinetics and thermodynamics; at this ratio, the interaction between reactants and the conversion efficiency can reach an optimal state, which is beneficial to increasing the yield of the target product p-hydroxystyrene.

[0022] In some embodiments, the reaction of p-hydroxybenzaldehyde with dimethylacetamide in an organic solvent under the catalysis of an alkaline catalyst is carried out in a first stage and a subsequent second stage. The first stage is a reaction at a first temperature for a first time period, and the second stage is a reaction at a second temperature for a second time period, wherein the first temperature is lower than the second temperature. This two-stage temperature-variable reaction is based on in-depth research into the reaction mechanism. At the lower temperature of the first stage, the reactants can undergo preliminary activation and reaction under suitable temperature conditions for the synthesis of the key intermediate, fully generating the key intermediate and providing favorable conditions for further reaction at the higher temperature of the second stage. Through this segmented control of temperature and time, the reaction rate and selectivity can be effectively controlled, improving the yield of the final product, p-hydroxystyrene. However, when a single high-temperature reaction is used, the yield may be lower than that of the two-stage temperature-variable reaction. This may be because the high-temperature conditions are not as suitable for the synthesis of the key intermediate as the lower temperature conditions of the first stage, and / or the prolonged high-temperature reaction leads to excessive byproducts, reducing the overall reaction yield. For example, Example 1 of the present invention achieved a yield of 70.8% under a two-stage temperature-variable reaction, while Comparative Example 3 achieved a yield of 61.2% under a single high-temperature reaction.

[0023] In some embodiments, the first temperature is selected from 60-110°C or any sub-range or point value therein, for example, but not limited to, 60°C, 65°C, 70°C, 75°C, 80°C, 85°C, 90°C, 95°C, 100°C, 105°C, 110°C, 70-110°C, 80-100°C; preferably 60-110°C, more preferably 80-100°C, and most preferably 80°C. Through a series of experimental studies (Examples 1 and 2-9), the present invention found that when the first stage temperature is 40-50°C, the reaction starts relatively slowly and the yield is low. As the temperature rises to 60°C, the reaction rate gradually increases and the side reactions are better controlled, with the yield exceeding 80%. When the temperature rises to 80°C, the reaction yield reaches its highest level, and thereafter, the reaction yield decreases with increasing temperature.

[0024] In some embodiments, the second temperature is selected from 120-180°C or any sub-range or point value thereof, for example, but not limited to, 120°C, 125°C, 130°C, 135°C, 140°C, 145°C, 150°C, 155°C, 160°C, 165°C, 170°C, 175°C, 180°C, 130-180°C, 140-150°C; preferably 120-130°C, more preferably 120°C. Through a series of experimental studies (Examples 1 and 10-13), the present invention found that the second-stage reaction temperature of 150°C may be too high for DMAC to participate in the reaction, inhibiting the reaction process. After lowering the reaction temperature, the reaction yield increased, reaching its maximum at 120°C, and then decreasing thereafter. This indicates that 120°C may be more suitable for the DMAC to prepare p-hydroxystyrene reaction than 150°C, which is suitable for the reaction of malonic acid to p-hydroxystyrene.

[0025] In some implementations, the first time period is 2-4 hours or any subrange or point value thereof, for example, but not limited to, 2 hours, 3 hours, 4 hours, 2-3 hours; preferably 3 hours to achieve a higher yield.

[0026] In some implementations, the second time period is 3-8 hours or any subrange or point value thereof, for example, but not limited to, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 5-6 hours; preferably 5 hours to achieve a higher yield.

[0027] In some embodiments, the organic solvent is selected from dimethylformamide, dimethylacetamide, methylpyrrolidone, dimethyl sulfoxide, and toluene, with dimethylacetamide being preferred. When dimethylacetamide is chosen as the organic solvent, it is the same substance as the starting material dimethylacetamide, but it is not included in the amount of the starting material dimethylacetamide and is calculated separately. Choosing dimethylacetamide as the solvent can further simplify the reaction system and process, avoiding the use of additional substances (such as additional solvent types) and potential interference.

[0028] In some embodiments, the weight ratio of the organic solvent to the raw material p-hydroxybenzaldehyde is 2-20:1. The weight of the organic solvent should be sufficient to fully dissolve the raw material. Too little solvent results in poor reactant dissolution and a significantly reduced reaction rate; too much solvent, while ensuring sufficient reactant dissolution, increases solvent recovery costs and reaction system volume, which is detrimental to industrial production. A ratio of 2-20:1 ensures sufficient reactant dissolution and a suitable reaction system condition, taking into account factors such as cost and ease of operation. The total volume of the reactants plus the organic solvent should ideally be 1 / 3 to 1 / 2 of the reaction vessel. This ratio ensures thorough mixing of materials during the reaction and avoids problems such as uneven heat transfer and reduced reaction efficiency caused by excessively large or small volumes.

[0029] In some embodiments, the molar ratio of the alkaline catalyst to the feedstock p-hydroxybenzaldehyde is selected from 1:5 to 1:20 or any sub-range or point value therein, for example, but not limited to, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:11, 1:12, 1:13, 1:14, 1:15, 1:16, 1:17, 1:18, 1:19, 1:20, 1:8 to 1:12; preferably 1:8 to 1:12, more preferably 1:10. When the molar ratio is too low, the catalyst dosage is insufficient, the reaction rate is slow, and the yield is low; when the molar ratio is too high, excess catalyst may lead to increased side reactions and increased costs. Within the range of 1:8 to 1:12, the reaction can proceed well, wherein when the molar ratio is 1:10, while ensuring a high yield, costs and side reactions can be effectively controlled.

[0030] In some embodiments, the alkaline catalyst is selected from hydroxides, organic bases, carbonates, and acetates.

[0031] In some embodiments, the hydroxide is selected from sodium hydroxide, potassium hydroxide, magnesium hydroxide, aluminum hydroxide, and ammonium hydroxide.

[0032] In some embodiments, the organic base is selected from monomethylamine, monopropylamine, 2-propenylamine, ethylenediamine, dipropylamine, cyclopropylamine, isopropylamine, diisopropylamine, di-n-butylamine, isobutylamine, diisobutylamine, triethylamine, n-butylamine, sec-butylamine, hexylamine, hexamethylenediamine, 1,2-dimethylpropylamine, 1,2-propanediamine, 1,5-dimethylhexylamine, 2-ethylhexylamine; cyclohexylamine, adamantane, piperidine, tetrahydropyrrole, 4-methylpiperidine, morpholine, cyclopentylamine and its derivatives.

[0033] In some embodiments, the carbonate is selected from potassium carbonate and sodium carbonate.

[0034] In some embodiments, the acetate is selected from potassium acetate and sodium acetate.

[0035] In some embodiments, the alkaline catalyst comprises sodium hydroxide and triethylamine.

[0036] Data from the embodiments of this invention show that sodium hydroxide-based alkaline catalysts can achieve higher reaction yields in this reaction compared to organic bases and carbonate-based alkaline catalysts. Surprisingly, this invention reveals that the combination of sodium hydroxide and triethylamine achieves a synergistic effect, resulting in yields higher than those achieved by using equimolar amounts of sodium hydroxide or triethylamine alone.

[0037] Without being limited by theory, the inventors speculate that this synergistic effect may be due to the following reasons:

[0038] Sodium hydroxide is a strong inorganic base that completely ionizes in aqueous solution, providing a large amount of hydroxide ions (OH-). While theoretically advantageous, this strong basicity may be beneficial for rapidly initiating reactions, especially in initial steps requiring a strong base to activate reactants (such as the carbonyl activation of p-hydroxybenzaldehyde). However, in organic solvent systems, the solubility of sodium hydroxide may be limited, potentially affecting its uniform distribution and thus the catalytic effect. Triethylamine, an organic base, is basic due to the lone pair of electrons on its nitrogen atom. Its relatively weak basicity may not promote reactions as effectively as sodium hydroxide for steps with lower reactivity or those sensitive to base strength. Triethylamine exhibits good solubility in many organic solvents, allowing for better mixing with reactants in organic synthesis reactions. In organic reaction systems like p-hydroxybenzaldehyde and dimethylacetamide, triethylamine may be more uniformly dispersed, facilitating contact between reactant molecules and the catalyst, thereby promoting the reaction.

[0039] When sodium hydroxide and triethylamine are used in combination, the strong alkalinity of sodium hydroxide can rapidly initiate the reaction and activate the key functional groups of the reactants, while triethylamine, with its good solubility in organic systems and relatively mild alkalinity, can regulate the reaction environment and stabilize reaction intermediates during the reaction process. The synergistic effect of these two substances may reduce side reactions and improve reaction selectivity, resulting in a higher yield than when using sodium hydroxide or triethylamine alone.

[0040] In some embodiments, the alkaline catalyst comprises sodium hydroxide and triethylamine in a molar ratio of 3:1 to 1:3 or any subrange or point value thereof, for example, but not limited to, 3:1, 2.5:1, 2:1, 1.5:1, 1:1, 1:1.5, 1:2, 1:2.5, 1:3, 2:1 to 1:1, preferably a molar ratio of 2:1. Experimental data of the present invention demonstrate that when the molar ratio of sodium hydroxide to triethylamine is 3:1, the yield is higher than when only sodium hydroxide is used; when the molar ratio is 1:3, the yield is higher than when only triethylamine is used. Within the range of 3:1 to 1:3, the selectivity of the reaction gradually increases with the increase of the proportion of triethylamine. When the molar ratio is 2:1, it can ensure that sodium hydroxide provides sufficient alkalinity to initiate the reaction, and can also give full play to the role of triethylamine in regulating the reaction environment and stabilizing intermediates, thus achieving the maximum yield.

[0041] In some embodiments, the method further includes adding a polymerization inhibitor to the reaction. In some embodiments, the polymerization inhibitor is selected from p-hydroxyanisole and phenothiazine. During the reaction of p-hydroxybenzaldehyde with dimethylacetamide to produce p-hydroxystyrene, the system exhibits a certain tendency to polymerize. Experimental data from this invention demonstrate that adding specific polymerization inhibitors such as p-hydroxyanisole or phenothiazine can improve the yield, but not any polymerization inhibitor can achieve this effect.

[0042] In some embodiments, the method is carried out at atmospheric pressure.

[0043] In some embodiments, the method further includes removing the reaction solution from the reactor, adjusting the pH to weakly acidic with dilute hydrochloric acid in an ice-water bath, washing with pure water, then extracting with an organic extractant, washing the organic phase with a saturated sodium bicarbonate aqueous solution, drying with anhydrous sodium sulfate, and then transferring the dried organic phase to a rotary evaporator for vacuum distillation and concentration to obtain a colorless oily substance, which is p-hydroxystyrene.

[0044] In some embodiments, the method includes adjusting the pH to 4-6, preferably 4, using dilute hydrochloric acid in an ice-water bath.

[0045] In some embodiments, the organic extractant is selected from ethyl acetate, dichloromethane, or chloroform.

[0046] In some embodiments, the method further includes protecting the reaction with an inert gas.

[0047] In some embodiments, the inert gas is selected from nitrogen and argon. Detailed Implementation

[0048] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to embodiments.

[0049] Example 1

[0050] At room temperature and atmospheric pressure, the weights of p-hydroxybenzaldehyde (industrial grade; commercially available), dimethylacetamide (DMAC) (industrial grade; commercially available), and basic catalyst NaOH (industrial grade; commercially available) shown in Table 1 were added to a 150 ml round-bottom flask. A magnetic stir bar was added, and the mixture was continuously stirred at 150 rpm on a magnetically heated stirrer while simultaneously heating to 40 °C and maintaining the temperature for 3 hours. The temperature was then raised to 150 °C and maintained for 5 hours. After the reaction was complete, the reaction solution was removed from the round-bottom flask, and the pH was adjusted to 4 with 1 mol / L dilute hydrochloric acid in an ice-water bath. The mixture was washed with pure water and then extracted three times with 500 ml of ethyl acetate. After extraction, the organic phase was washed twice with a saturated sodium bicarbonate aqueous solution and dried with anhydrous sodium sulfate. The dried organic phase was then transferred to a rotary evaporator and concentrated by vacuum distillation at 35 °C to obtain a colorless oily substance, which was p-hydroxystyrene. The yield (in g) was measured, and the yield (%) was calculated. The yields are shown in Table 4 below. The yield was calculated by dividing the yield (g) of pure p-hydroxystyrene obtained in (A) by the percentage of the weight (12.01g) of p-hydroxystyrene obtained from the p-hydroxybenzaldehyde feedstock shown in Table 1, assuming a 1:1 complete conversion.

[0051] Table 1

[0052]

[0053] Comparative Example 1

[0054] At room temperature and normal pressure, the weights of p-hydroxybenzaldehyde (industrial grade; commercially available), malonic acid (industrial grade; commercially available), dimethylacetamide (DMAC) (industrial grade; commercially available), and basic catalyst NaOH (industrial grade; commercially available) shown in Table 2 were added to a 150 ml round-bottom flask. A magnetic stir bar was added, and the mixture was continuously stirred at 150 rpm on a magnetically heated stirrer while simultaneously heating to 40 °C and maintaining the temperature for 3 hours to carry out the reaction. Then, the temperature was raised to 150 °C and maintained for 5 hours to carry out the reaction. After the reaction was complete, the reaction solution was removed from the round-bottom flask and the pH was adjusted to 4 with 1 mol / L dilute hydrochloric acid in an ice-water bath. The mixture was washed with pure water and then extracted three times with 500 ml of ethyl acetate. After extraction, the organic phase was washed twice with a saturated sodium bicarbonate aqueous solution and dried with anhydrous sodium sulfate. The dried organic phase was then transferred to a rotary evaporator and concentrated by vacuum distillation at 35 °C to obtain a colorless oily substance, which was p-hydroxystyrene. The yield (in g) was measured and the percentage was calculated. The yields are shown in Table 4 below.

[0055] Table 2

[0056] Molecular weight (g / mol) mole (mol) molar equivalent ratio Feed amount (g) p-Hydroxybenzaldehyde 122.12 0.1 1 12.21 malonic acid 104.06 0.2 2 20.81 dimethylacetamide 87.12 0.54 5.4 47.04(50ml) NaOH 40.00 0.01 0.1 0.40

[0057] Comparative Example 2

[0058] At room temperature and normal pressure, the weights of p-hydroxybenzaldehyde (industrial grade; commercially available) shown in Table 3, the weights of malonic acid (industrial grade; commercially available) shown in Table 3, the weights of toluene (industrial grade; commercially available) shown in Table 3, and the weights of alkaline catalyst NaOH (industrial grade; commercially available) shown in Table 3 were added to a 150 ml round-bottom flask. A magnetic stir bar was added, and the mixture was continuously stirred at 150 rpm on a magnetically heated stirrer while simultaneously heating to 40 °C and maintaining the temperature for 3 hours to carry out the reaction. Then, the temperature was raised to 150 °C and maintained for 5 hours to carry out the reaction. After the reaction was complete, the reaction solution was removed from the round-bottom flask and the pH was adjusted to 4 with 1 mol / L dilute hydrochloric acid in an ice-water bath. The mixture was washed with pure water and then extracted three times with 500 ml of ethyl acetate. After extraction, the organic phase was washed twice with a saturated sodium bicarbonate aqueous solution and dried with anhydrous sodium sulfate. The dried organic phase was then transferred to a rotary evaporator and concentrated by vacuum distillation at 35 °C to obtain a colorless oily substance, which was p-hydroxystyrene. The yield (in g) was measured and the percentage was calculated. The yields are shown in Table 4 below.

[0059] Table 3

[0060] Molecular weight (g / mol) mole (mol) molar equivalent ratio Feed amount (g) p-Hydroxybenzaldehyde 122.12 0.1 1 12.21 malonic acid 104.06 0.2 2 20.81 Toluene 92.14 0.472 4.72 43.49(50ml) NaOH 40.00 0.01 0.1 0.40

[0061] Summarize:

[0062] Table 4

[0063] Yield (%) Example 1 70.8 Comparative Example 1 75.4 Comparative Example 2 74.2

[0064] Example 1, in conjunction with Comparative Examples 1 and 2, investigated the preparation of p-hydroxystyrene using dimethylacetamide instead of malonic acid.

[0065] In designing the experiment, considering that DMAC might act as both a reactant and a solvent, the amount of DMAC added in Example 1 was approximately 0.2 mol DMAC (corresponding to the molar amount of 0.2 mol malonic acid acting as a reactant in Comparative Examples 1 and 2) plus 50 ml DMAC (corresponding to the volume of 50 ml toluene acting as a solvent in Comparative Example 2), totaling 0.74 mol. Given that 0.2 mol DMAC is already a significant excess relative to p-hydroxybenzaldehyde, similar to 0.2 mol malonic acid, the effect of the additional DMAC in Example 1 on the reaction is likely insignificant or negligible, similar to the effect of toluene as a solvent in Comparative Example 2.

[0066] Table 4 shows that the yields of Comparative Example 1 and Comparative Example 2 are comparable, indicating that when the toluene solvent, which does not participate in the reaction, is replaced with DMAC, the yield remains basically unchanged. This may be because malonic acid is already in great excess relative to p-hydroxybenzaldehyde, so regardless of whether DMAC can react with p-hydroxybenzaldehyde, it is difficult to further promote the reaction.

[0067] Table 4 shows that DMAC from Example 1 can react with p-hydroxybenzaldehyde to produce p-hydroxystyrene (reaction formula below) under the same conditions without the presence of malonic acid, acting as a reactant rather than just a solvent, and achieving a considerable yield. Although the yield decreased, it is still more cost-effective than the cost reduction achieved by replacing the raw materials. Assuming a market price of 240 yuan / kg for p-hydroxybenzaldehyde, the total cost of 0.1 mol p-hydroxybenzaldehyde + 0.2 mol DMAC is approximately 3.02 yuan, and the total cost of 0.1 mol p-hydroxybenzaldehyde + 0.2 mol malonic acid is approximately 3.55 yuan. Replacing malonic acid with DMAC reduces the cost of the raw materials by (3.55 - 3.02) / 3.55, or 15%, which is extremely significant in industrial production. Existing technologies (such as CN105175250B) only consider dimethylacetamide as a solvent in this reaction, but this invention proves that dimethylacetamide can participate in this reaction as a raw material, and achieves a considerable yield and a very significant cost reduction.

[0068]

[0069] Comparative Example 3: Single Reaction Temperature

[0070] Based on Example 1, the two-stage heating reaction was replaced with a single-stage reaction at 150°C for 8 hours, while all other aspects remained the same, to conduct Comparative Example 3. The yield was 61.2%.

[0071] Examples 2-9: First-stage reaction temperature

[0072] To improve the reaction yield, the reaction temperature was optimized. Based on Example 1, the second-stage reaction temperature was kept constant at 150°C, while the first-stage reaction temperature was adjusted to 40°C. All other parameters remained the same, and Examples 2-9 were performed. The reaction temperatures and yields of Examples 2-9 are shown in Table 5 below.

[0073] Table 5

[0074]

[0075] Table 5 shows that when the reaction temperature of the first stage is increased from 40℃, the reaction yield increases. When the temperature is increased to 60℃, the yield exceeds 80%. When the temperature is increased to 80℃, the reaction yield reaches its peak. Therefore, 80℃ is determined to be the optimal reaction temperature for the first stage.

[0076] Examples 10-13: Second-stage reaction temperature

[0077] To improve the reaction yield, the reaction temperature was optimized. Based on Example 1, the first-stage reaction temperature was kept constant at 40°C, and the second-stage reaction temperature was adjusted to 150°C, while all other parameters remained the same, resulting in Examples 10-13. The reaction temperatures and yields of Examples 10-13 are shown in Table 6 below.

[0078] Table 6

[0079]

[0080] Table 6 shows that 150℃ is not the optimal temperature for this reaction. When the temperature of the second stage reaction is lowered from 150℃, the reaction yield actually increases. The yield reaches its maximum value when the temperature is lowered to 120℃. When the temperature is lowered further, the yield drops sharply. Therefore, 120℃ is determined to be the optimal reaction temperature for the second stage.

[0081] Examples 14-17: Alkaline Catalysts

[0082] To improve the reaction yield, the catalyst was optimized. Based on Example 5, the basic catalyst NaOH was replaced with equimolar amounts of triethylamine (organic base), sodium carbonate (carbonate), or various combinations of basic catalysts, while all other aspects remained the same, for Examples 14-17. Triethylamine was chosen as the representative organic base because it has good solubility in organic solvents and a relatively mild alkalinity, which may have a positive impact on the reaction selectivity; sodium carbonate, as the representative carbonate, is low in cost and can provide a certain alkaline environment. The catalysts and yields of Examples 14-17 are shown in Table 7 below.

[0083] Table 7

[0084] alkaline catalyst Yield (%) Example 5 Sodium hydroxide (0.01 mol) 88.3 Example 14 Triethylamine (0.01 mol) 74.5 Example 15 Sodium carbonate (0.01 mol) 65.2 Example 16 Sodium hydroxide (0.005 mol) + triethylamine (0.005 mol) 92.4 Example 17 Sodium hydroxide (0.005 mol) + Sodium carbonate (0.005 mol) 76.4

[0085] Table 7 shows that sodium hydroxide-based alkaline catalysts can achieve higher reaction yields in this reaction compared to organic bases and carbonate-based alkaline catalysts. Surprisingly, this invention discovered that the combination of sodium hydroxide and triethylamine achieves a synergistic effect, resulting in higher yields than equimolar amounts of sodium hydroxide or triethylamine alone.

[0086] Examples 18-21: Composite Catalyst Ratio

[0087] To improve the reaction yield, the catalyst ratio in the catalyst combination was optimized. Based on Example 16, and keeping other conditions consistent and the total catalyst amount fixed at 0.01 mol, the molar ratio of sodium hydroxide to triethylamine was systematically changed to conduct Examples 18-21. The catalysts and yields of Examples 18-21 are shown in Table 8 below.

[0088] Table 8

[0089]

[0090] Table 8 shows that as the proportion of triethylamine increases, the reaction yield gradually increases. When the molar ratio is 2:1, the synergistic effect is strongest, and the reaction yield reaches its highest value. Further increasing the proportion of triethylamine will reduce the reaction yield.

[0091] Examples 22-25: Polymerization Inhibitors

[0092] Based on Example 19, 0.1 g of various polymerization inhibitors were further added to the reaction, while all other aspects remained the same, to carry out Examples 22-25. The catalysts and yields of Examples 22-25 are shown in Table 9 below.

[0093] Table 9

[0094] Polymerization inhibitor (0.1g) Yield (%) Example 19 none 95.2 Example 22 4-tert-butylcatechol 94.9 Example 23 p-hydroxyanisole 97.3 Example 24 phenothiazine 96.9 Example 25 hydroquinone 95.4

[0095] Table 9 shows that the polymerization inhibitors p-hydroxyanisole and phenothiazine have a certain effect on improving the yield, while 4-tert-butylcatechol and hydroquinone have not significantly improved the yield.

[0096] Although the present invention has been described in detail through the above preferred embodiments, its innovation lies in successfully replacing expensive malonic acid with dimethylacetamide as a raw material, and through systematic optimization of various aspects such as reaction temperature, time, catalyst type and ratio, significantly reducing production costs while ensuring high yield, thus overcoming many defects of the prior art. Reasonable improvements and modifications made by those skilled in the art, based on the core innovative ideas and principles of the present invention, should be covered within the scope of protection of the present invention.

Claims

1. A method for preparing p-hydroxystyrene, the method comprising reacting p-hydroxybenzaldehyde in an organic solvent with dimethylacetamide in a reactor under the catalysis of an alkaline catalyst to produce p-hydroxystyrene, wherein the method does not include reacting p-hydroxybenzaldehyde with malonic acid to produce p-hydroxystyrene. The reaction of p-hydroxybenzaldehyde in an organic solvent with dimethylacetamide under the catalysis of an alkaline catalyst is carried out in a first stage and a subsequent second stage, wherein the first stage is a reaction at a first temperature for a first time period, and the second stage is a reaction at a second temperature for a second time period, wherein the first temperature is lower than the second temperature; The first temperature is 60-110℃; The second temperature is 120-150℃.

2. The method according to claim 1, wherein the organic solvent is dimethylacetamide.

3. The method according to claim 1, wherein the molar ratio of the alkaline catalyst to the raw material p-hydroxybenzaldehyde is 1:5 to 1:

20.

4. The method according to claim 1, wherein the molar ratio of the alkaline catalyst to the raw material p-hydroxybenzaldehyde is 1:8 to 1:

12.

5. The method according to claim 1, wherein the molar ratio of the alkaline catalyst to the raw material p-hydroxybenzaldehyde is 1:

10.

6. The method according to claim 1, wherein the alkaline catalyst is selected from hydroxides, organic bases, and carbonates.

7. The method according to claim 6, wherein the hydroxide is selected from sodium hydroxide, potassium hydroxide, magnesium hydroxide, aluminum hydroxide, and ammonium hydroxide.

8. The method according to claim 6, wherein the organic base is selected from ethylenediamine, dipropylamine, isopropylamine, diisopropylamine, di-n-butylamine, isobutylamine, diisobutylamine, triethylamine, n-butylamine, sec-butylamine, and hexylamine.

9. The method according to claim 6, wherein the carbonate is selected from potassium carbonate and sodium carbonate.

10. The method of claim 6, wherein the alkaline catalyst comprises sodium hydroxide and triethylamine.

11. The method of claim 10, wherein the alkaline catalyst comprises sodium hydroxide and triethylamine in a molar ratio of 3:1 to 1:

3.

12. The method of claim 11, wherein the alkaline catalyst comprises sodium hydroxide and triethylamine in a molar ratio of 2:

1.

13. The method of claim 1, wherein the method further comprises adding a polymerization inhibitor during the reaction.

14. The method of claim 13, wherein the polymerization inhibitor is selected from p-hydroxyanisole and phenothiazine.

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