Synthesis method of P-(1-ethoxyethoxy) styrene

Abstract

The invention discloses a synthesis method of P-(1-ethoxyethoxy) styrene, which comprises the following steps: S1, reacting 4-acetoxystyrene with alkaline metal salt in an organic solvent system under the protection of inert gas, the reaction time in the S1 is 1-3 hours, the molar ratio of the 4-acetoxystyrene to the alkaline metal salt is 1: (2.2-2.8), and the reaction time in the S2 is 1-3 hours; adjusting the pH value of the reaction liquid, concentrating under reduced pressure, extracting and drying to obtain an intermediate p-hydroxystyrene; s2, in a mixed solvent system of dichloromethane containing a polymerization inhibitor and lower alcohol, p-hydroxystyrene and ethyl vinyl ether react under the catalytic action of pyridinium toluenesulfonate to obtain P-(1-ethyoxyl ethyoxyl) styrene; according to the present invention, the first step reaction is researched, the reaction condition is mild, the energy and the production cost are saved, the reaction time is short, the reaction process is simple, and the yield of the step is improved to be close to 100% so as to improve the total yield of the product.

Description

Technical Field

[0001] This invention belongs to the field of photoresist technology and relates to a method for preparing a photoresist main resin monomer, particularly a method for synthesizing p-(1-ethoxyethoxy)styrene. Background Technology

[0002] P-(1-Ethoxyethoxy)styrene, also known as 4-ethoxyethoxystyrene, is a colorless to pale yellow liquid at room temperature and has a wide range of applications in the chemical industry. It can be used as a raw material in coatings, adhesives, and plastic additives; it can also be used as a monomer in the synthesis of polymers such as polylactic acid and polyvinylidene fluoride. Because its structure contains acid-instable groups, namely acetal structures, it can undergo chemical reactions under acidic conditions, thus changing its solubility from insoluble in developer to soluble. Therefore, it is also a common raw material in the photoresist field, used to synthesize the main resin polymer of photoresists, and applied in the field of electronic chemistry.

[0003] Regarding the synthesis method of p-(1-ethoxyethoxy)styrene, Chinese invention patent No. 202211741584.9, entitled "A Synthetic Method of 1-(1-ethoxyethoxy)-4-vinylbenzene," discloses a method for preparing an intermediate, p-hydroxystyrene, then adding p-hydroxystyrene, a sulfonate pyridine salt catalyst, and a first polymerization inhibitor to an organic solution, followed by the addition of ethyl vinyl ether for acetalization. The resulting reaction solution is purified to obtain the target product. In the second step of this paper, a sulfonate pyridine salt catalyst is used, avoiding the degradation of raw materials and products by the acidity of p-toluenesulfonic acid, thus improving product purity and yield. However, in the first reaction step of this literature, the preparation of p-hydroxystyrene involves the decarboxylation of p-hydroxycinnamic acid in N,N-dimethylformamide containing a polymerization inhibitor and potassium acetate. This step achieves a relatively high yield of 94.8%, with a reaction temperature of 120°C. The reaction process requires an initial 6-hour reaction time, followed by online monitoring and TLC analysis of the raw material content every half hour. After the reaction is complete, the mixture must be cooled to room temperature overnight before proceeding to subsequent processes. This results in an excessively long first-step reaction process, reducing the production efficiency of the product. Summary of the Invention

[0004] The purpose of this invention is to prepare P-(1-ethoxyethoxy)styrene that meets the application requirements in the field of electronic chemistry. Based on the existing technology, this invention optimizes the synthetic route, develops the synthetic route for the first step reaction, simplifies the preparation process, shortens the production time, improves the yield of each step, and reduces the production cost.

[0005] The present invention provides a method for synthesizing p-(1-ethoxyethoxy)styrene. This method is a two-step process. Step S1 involves preparing p-hydroxystyrene from 4-acetoxystyrene, and Step S2 involves preparing p-(1-ethoxyethoxy)styrene from p-hydroxystyrene and ethyl vinyl ether. The key difference lies in the following: Step S1 involves reacting 4-acetoxystyrene with an alkaline metal salt in an organic solvent system under inert gas protection. The reaction time in Step S1 is 1-3 hours, and the molar ratio of 4-acetoxystyrene to the alkaline metal salt is 1:2.2-2.8. The pH of the reaction solution is adjusted and the solution is concentrated under reduced pressure. After extraction and drying, the intermediate p-hydroxystyrene is obtained. Step S2 involves reacting p-hydroxystyrene with ethyl vinyl ether in a mixed solvent system containing a polymerization inhibitor (dichloromethane) and a lower alcohol, catalyzed by pyridine toluenesulfonate, to obtain p-(1-ethoxyethoxy)styrene.

[0006] Furthermore, the organic solvent system in step S1 above is tetrahydrofuran, and the basic metal salt is either sodium hydroxide or potassium hydroxide. The basic metal salt needs to be prepared into an aqueous solution before the reaction.

[0007] Specifically, the process of step S1 above is as follows:

[0008] Organic solvent and 4-acetoxystyrene were added to a reactor, stirred, and the air inside the reactor was replaced with nitrogen. The temperature was lowered to -10℃ to 0℃, and under nitrogen protection, an aqueous solution of an alkaline metal salt with a volume of 1 to 1.2 times that of the organic solution was added dropwise. After the addition was complete, the temperature was raised to carry out the reaction. After the reaction was completed, the pH was adjusted to 7 to 8, and the mixture was allowed to stand for phase separation. The organic phase was concentrated under reduced pressure, and the aqueous phase was extracted with dichloromethane. The organic phase and the dichloromethane extract were combined, washed with saturated brine, and dried to obtain the above-mentioned p-hydroxystyrene.

[0009] It should be noted that the purity of the above-mentioned p-hydroxystyrene is not less than 98.0%.

[0010] Preferably, the reaction temperature in step S1 above is 15°C to 25°C.

[0011] Furthermore, the lower alcohol in the above-mentioned mixed solvent system is any one of methanol, ethanol, and isopropanol, and the volume ratio of dichloromethane to the lower alcohol is 15 to 25:1.

[0012] Specifically, the process of step S2 above is as follows:

[0013] The above-mentioned mixed solvent system was added to the reactor, along with the above-mentioned p-hydroxystyrene. The mixture was stirred, and then p-toluenesulfonic acid pyridine salt and a polymerization inhibitor were added. Ethyl vinyl ether was added dropwise at 15℃~25℃. After the addition was complete, the temperature was maintained and the reaction continued. After the reaction was completed, the reaction solution was concentrated once, extracted with an extraction solvent, decolorized with activated carbon, and concentrated a second time with a polymerization inhibitor. The second concentrated solution was dissolved in the extraction solvent, washed with sodium hydroxide aqueous solution and saturated brine, dried, and then concentrated a third time under reduced pressure with a polymerization inhibitor to obtain crude P-(1-ethoxyethoxy)styrene. The crude product was then distilled under reduced pressure with a polymerization inhibitor to obtain the finished P-(1-ethoxyethoxy)styrene product.

[0014] Preferably, the extraction solvent is n-hexane.

[0015] Furthermore, the aforementioned polymerization inhibitor is phenothiazine or a mixture of phenothiazine and 4-alkoxy-2,2,6,6-tetramethylpiperidine nitroxide radicals, wherein the mass ratio of phenothiazine to 4-alkoxy-2,2,6,6-tetramethylpiperidine nitroxide radicals in the aforementioned mixture is 1:0.01 to 0.05.

[0016] Compared with the prior art, the present invention has the following advantages:

[0017] This invention studies a method for synthesizing p-(1-ethoxyethoxy)styrene, with particular emphasis on the first step reaction. The first step reaction of this invention is carried out under mild conditions, requiring no special heating, which not only saves energy and production costs, but also has a short reaction time and a simple reaction process. More importantly, the yield of this step reaction is very high, increasing the yield of the prior art from 95% to nearly 100%, thereby improving the overall yield of the product.

[0018] In the study of the second step reaction, the present invention found that using an organic solvent consisting of a mixture of dichloromethane and lower alcohols as the reaction system also helps to improve the yield of this step to some extent.

[0019] Furthermore, in the purification process of the crude product, this invention employs a three-stage concentration combined with a single distillation, adding a certain amount of polymerization inhibitor during each concentration or distillation process. According to existing technology, phenothiazine belongs to the amine class of polymerization inhibitors, and 4-alkoxy-2,2,6,6-tetramethylpiperidine nitroxide radical belongs to the nitroxide radical class of polymerization inhibitors. Phenothiazine, an amine class of polymerization inhibitor, is commonly used in existing processes. This invention discovers that using a mixture of amine and nitroxide radical polymerization inhibitors in a certain proportion results in a more significant polymerization inhibition effect than using amine inhibitors alone, and also reduces the total amount of polymerization inhibitor used to some extent. Attached Figure Description

[0020] Figure 1This is the NMR spectrum of sample 1 prepared in this invention.

[0021] Figure 2 This is the gas chromatogram of sample 1 prepared according to the present invention. Detailed Implementation

[0022] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only a part of the embodiments of the present invention, and not all of them. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present invention.

[0023] Unless otherwise specified in the examples, the procedures can be followed according to conventional conditions; unless the manufacturers of the reagents or instruments used are specified, they are all conventional products that can be purchased commercially.

[0024] Example 1

[0025] P-(1-ethoxyethoxy)styrene, the specific steps are as follows:

[0026] S1. Synthesis of p-hydroxystyrene:

[0027] S1-1. Add 200L of tetrahydrofuran and 50kg of 4-acetoxystyrene to the reactor, start stirring and replace the air in the reactor with nitrogen;

[0028] S1-2. Cool the reactor to -5℃ and add 200L of sodium hydroxide aqueous solution under nitrogen protection. The solution contains 30.8kg of sodium hydroxide and the molar ratio of 4-acetoxystyrene to sodium hydroxide is 1:2.5. After the addition is complete, heat the reactor to 20℃ and react for 2.5h. After the reaction is complete, adjust the pH to 7.5 and let it stand for phase separation.

[0029] S1-3. The organic phase is concentrated under reduced pressure, and the aqueous phase is extracted with dichloromethane. The organic phase and the dichloromethane extract are combined, washed with saturated brine, and dried to prepare the p-hydroxystyrene intermediate 1.

[0030] Synthesis of S2, P-(1-ethoxyethoxy)styrene:

[0031] S2-1. Add 180L of a mixed organic solvent of dichloromethane and methanol (volume ratio of dichloromethane to lower alcohol is 20:1) to the reactor, add 35kg of p-hydroxystyrene, stir, add 7.5kg of p-toluenesulfonic acid pyridine salt and 118g of polymerization inhibitor. In this embodiment, the polymerization inhibitor is phenothiazine (including subsequent processes in this embodiment). Add about 16.6kg of ethyl vinyl ether dropwise at 20°C. After the dropwise addition is complete, maintain the temperature at 20°C and continue the reaction. During the reaction, use GC to detect the content of the target product. When the product content does not increase, it indicates that the reaction is complete.

[0032] S2-2. After the reaction is complete, the reaction solution is concentrated once to remove the solvent, resulting in a viscous substance. Hexane is added to the viscous substance and stirred. A brown substance precipitates in the lower layer. After separation, the lower layer is discarded to obtain a yellow solution. Activated carbon is added to the obtained yellow solution for decolorization to obtain an eluent. 2.36g of polymerization inhibitor is added to the eluent for a second concentration. The second concentrate is dissolved in the extraction solvent hexane, washed with 5% sodium hydroxide aqueous solution and saturated brine, dried, and then 7.08g of polymerization inhibitor is added for a third concentration under reduced pressure to obtain crude P-(1-ethoxyethoxy)styrene.

[0033] S2-3. Add 1.18g of polymerization inhibitor to crude P-(1-ethoxyethoxy)styrene, collect a small amount of the fore fraction by vacuum distillation, and collect the fraction at 55℃~60℃ as P-(1-ethoxyethoxy)styrene finished product sample 1.

[0034] Example 2

[0035] P-(1-ethoxyethoxy)styrene, the specific steps are as follows:

[0036] S1. Synthesis of p-hydroxystyrene:

[0037] S1-1. Add 200L of tetrahydrofuran and 55kg of 4-acetoxystyrene to the reactor, start stirring and replace the air in the reactor with nitrogen;

[0038] S1-2. Cool the reactor to 0℃ and add 240L of potassium hydroxide aqueous solution under nitrogen protection. The solution contains 30.8kg of potassium hydroxide and the molar ratio of 4-acetoxystyrene to potassium hydroxide is 1:2.2. After the addition is complete, heat the reactor to 15℃ and react for 3 hours. After the reaction is complete, adjust the pH to 7.1 and let it stand for phase separation.

[0039] S1-3, the same as in Example 1, prepared the p-hydroxystyrene intermediate 2.

[0040] Synthesis of S2, P-(1-ethoxyethoxy)styrene:

[0041] S2-1. Add 200L of a mixed organic solvent of dichloromethane and ethanol (volume ratio of dichloromethane to ethanol is 15:1) to the reactor, add 35kg of p-hydroxystyrene, stir, add 7.2kg of p-toluenesulfonic acid pyridine salt and 80g of polymerization inhibitor. In this embodiment, the polymerization inhibitor is phenothiazine and 4-alkoxy-2,2,6,6-tetramethylpiperidine nitroxide radical (including subsequent processes in this embodiment) in a mass ratio of 1:0.02. Add 18.0kg of ethyl vinyl ether dropwise at 15°C. After the dropwise addition is complete, maintain the temperature at 15°C and continue the reaction. During the reaction, use GC to detect the content of the target product. When the product content does not increase, it indicates that the reaction is complete.

[0042] S2-2, the same step as in Example 1, except that the amount of polymerization inhibitor added in the second and third concentrations is 1.5g and 4.5g respectively, to obtain crude P-(1-ethoxyethoxy)styrene.

[0043] S2-3. Add 0.5g of polymerization inhibitor to the above crude P-(1-ethoxyethoxy)styrene, collect a small amount of the fore fraction by vacuum distillation, and collect the fraction at 55℃~60℃ as P-(1-ethoxyethoxy)styrene finished product sample 2.

[0044] Example 3

[0045] The synthesis method of 4-tert-butoxystyrene includes the following specific steps:

[0046] S1. Synthesis of p-hydroxystyrene:

[0047] S1-1. Add 200L of tetrahydrofuran and 52kg of 4-acetoxystyrene to the reactor, start stirring and replace the air in the reactor with nitrogen;

[0048] S1-2. Cool the reactor to -10℃ and add 220L of sodium hydroxide aqueous solution under nitrogen protection. The solution contains 35.9kg of sodium hydroxide and the molar ratio of 4-acetoxystyrene to sodium hydroxide is 1:2.8. After the addition is complete, heat the reactor to 25℃ and react for 1 hour. After the reaction is complete, adjust the pH to 7.9 and let it stand for phase separation.

[0049] S1-3, the same as in Example 1, prepared the p-hydroxystyrene intermediate 3.

[0050] Synthesis of S2, P-(1-ethoxyethoxy)styrene:

[0051] S2-1. Add 220L of a mixed organic solvent of dichloromethane and isopropanol (volume ratio of dichloromethane to isopropanol is 25:1) to the reactor, add 35kg of p-hydroxystyrene, stir, add 7.8kg of p-toluenesulfonic acid pyridine salt and 90g of polymerization inhibitor. In this embodiment, the polymerization inhibitor is phenothiazine and 4-alkoxy-2,2,6,6-tetramethylpiperidine nitroxide radical (including subsequent processes in this embodiment) in a mass ratio of 1:0.05. Add 20.0kg of ethyl vinyl ether dropwise at 25°C. After the dropwise addition is complete, maintain the temperature at 25°C and continue the reaction. During the reaction, use GC to detect the content of the target product. When the product content does not increase, it indicates that the reaction is complete.

[0052] S2-2, the same step as in Example 1, except that the amount of polymerization inhibitor added in the second and third concentrations is 1.6g and 4.6g respectively, to obtain crude P-(1-ethoxyethoxy)styrene.

[0053] S2-3. Add 0.7g of polymerization inhibitor to the above crude P-(1-ethoxyethoxy)styrene, collect a small amount of the fore fraction by vacuum distillation, and collect the fraction at 55℃~60℃ as P-(1-ethoxyethoxy)styrene finished product sample 3.

[0054] Example 4

[0055] The specific implementation process is the same as in Example 1, except that in the step "S2, Synthesis of P-(1-ethoxyethoxy)styrene", the polymerization inhibitor used is phenothiazine and 4-alkoxy-2,2,6,6-tetramethylpiperidine nitroxide free radical in a mass ratio of 1:0.01, and the finished P-(1-ethoxyethoxy)styrene sample 4.

[0056] Comparative Example 1

[0057] The specific implementation process is the same as in Example 1, except that in step "S2-1", 200L of dichloromethane is added to the reactor, and the subsequent process is the same as in Example 1, to prepare P-(1-ethoxyethoxy)styrene product reference standard 1.

[0058] Analysis and Testing

[0059] The samples prepared in this invention were analyzed by 1H NMR and HPLC-MS / MS, confirming that the structure of the obtained samples conforms to the characteristics of p-(1-ethoxyethoxy)styrene. Some of the analytical spectra are shown in the appendix. Figure 1 .

[0060] The purity and impurities such as polymerization inhibitors in the samples were determined using high-performance gas chromatography (HPLC). The results are shown in Tables 1 and 2, and some test chromatograms are attached. Figure 2 .

[0061] The intermediate and sample were weighed, and the yield was calculated using the following formula. The results are shown in Table 1.

[0062] The yield calculation formula is:

[0063] Intermediate yield = Actual weight of the intermediate obtained (g) / Theoretical p-hydroxystyrene (g) calculated based on the amount of 4-acetoxystyrene used × 100%;

[0064] Product yield = Actual weight of intermediate obtained (g) / Theoretical P-(1-ethoxyethoxy)styrene (g) calculated based on the amount of p-hydroxystyrene used × Intermediate yield × 100%.

[0065] Table 1: Summary of Sample and Reference Standard Yield and Purity Test Results

[0066]

[0067] As shown in Table 1, the yield of the first step reaction of this invention is very high, approaching 100%, significantly improving the overall yield of the process. The second step reaction, using a mixture of dichloromethane and lower alcohols as the reaction system, also contributes to improving the yield to some extent. This indicates that choosing a suitable solvent helps the reaction proceed in the forward direction, making the reaction more complete. Furthermore, phenothiazine belongs to the amine class of polymerization inhibitors, and 4-alkoxy-2,2,6,6-tetramethylpiperidine nitroxide radical belongs to the nitroxide radical class of polymerization inhibitors. In existing technologies for preparing the target product, phenothiazine, an amine class of polymerization inhibitor, is commonly used. However, this invention has found that using a mixture of amine and nitroxide radical polymerization inhibitors in a certain proportion results in a more significant polymerization inhibition effect than using only amine inhibitors, and it can also reduce the total amount of polymerization inhibitor used to some extent.

[0068] Table 2: Gas chromatogram peaks of sample 1

[0069]

[0070] As can be seen from the results in Table 2, the sample prepared by this invention has very few types of impurity peaks, with only two types of impurities.

[0071] Elemental analysis was performed on the product samples and reference standards. The test results are shown in Table 3.

[0072] Table 3: Summary of Elemental Analysis Results for Samples and Reference Standards

[0073]

[0074]

[0075] As can be seen from the results in Table 3, the elemental impurities in the samples prepared by this invention are very low, with a total of less than 20 ppb.

Claims

1. A method for synthesizing p-(1-ethoxyethoxy)styrene, wherein the synthesis method is a two-step process, comprising step S1, preparing p-hydroxystyrene from 4-acetoxystyrene, and step S2, preparing p-(1-ethoxyethoxy)styrene from p-hydroxystyrene and ethyl vinyl ether, characterized in that, Step S1 refers to the reaction of 4-acetoxystyrene with an alkaline metal salt in an organic solvent system under inert gas protection. The reaction time in step S1 is 1 to 3 hours, and the molar ratio of 4-acetoxystyrene to the alkaline metal salt is 1:2.2 to 2.

8. The pH of the reaction solution is adjusted and the solution is concentrated under reduced pressure. After extraction and drying, the intermediate p-hydroxystyrene is obtained. Step S2 refers to the reaction of p-hydroxystyrene with ethyl vinyl ether in a mixed solvent system containing dichloromethane and a lower alcohol, catalyzed by pyridine toluenesulfonate, to obtain p-(1-ethoxyethoxy)styrene.

2. The method for synthesizing p-(1-ethoxyethoxy)styrene according to claim 1, characterized in that, The organic solvent system in step S1 is tetrahydrofuran, and the basic metal salt is either sodium hydroxide or potassium hydroxide. The basic metal salt needs to be prepared into an aqueous solution before the reaction.

3. The method for synthesizing p-(1-ethoxyethoxy)styrene according to claim 2, characterized in that, The specific process of step S1 is as follows: Organic solvent and 4-acetoxystyrene were added to a reactor, stirred, and the air inside the reactor was replaced with nitrogen. The temperature was lowered to -10℃ to 0℃, and under nitrogen protection, an aqueous solution of an alkaline metal salt with a volume of 1 to 1.2 times that of the organic solution was added dropwise. After the addition was complete, the temperature was raised to carry out the reaction. After the reaction was completed, the pH was adjusted to 7 to 8, and the mixture was allowed to stand for phase separation. The organic phase was concentrated under reduced pressure, and the aqueous phase was extracted with dichloromethane. The organic phase and the dichloromethane extract were combined, washed with saturated brine, and dried to obtain the p-hydroxystyrene.

4. The method for synthesizing p-(1-ethoxyethoxy)styrene according to claim 1, characterized in that, The purity of the p-hydroxystyrene is not less than 98.0%.

5. The method for synthesizing p-(1-ethoxyethoxy)styrene according to claim 1, characterized in that, The reaction temperature in step S1 is 15℃~25℃.

6. The method for synthesizing p-(1-ethoxyethoxy)styrene according to claim 1, characterized in that, The lower alcohol in the mixed solvent system is any one of methanol, ethanol, and isopropanol, and the volume ratio of dichloromethane to the lower alcohol is 15-25:

1.

7. The method for synthesizing p-(1-ethoxyethoxy)styrene according to claim 6, characterized in that, The specific process of step S2 is as follows: The mixed solvent system described above is added to the reactor, along with p-hydroxystyrene. The mixture is stirred, and then p-toluenesulfonic acid pyridine salt and a polymerization inhibitor are added. Ethyl vinyl ether is added dropwise at 15°C to 25°C. After the addition is complete, the temperature is maintained and the reaction continues. After the reaction is complete, the reaction solution is concentrated once, extracted with an extraction solvent, decolorized with activated carbon, and concentrated a second time with a polymerization inhibitor. The second concentrated solution is dissolved in the extraction solvent, washed with sodium hydroxide aqueous solution and saturated brine, dried, and then concentrated a third time under reduced pressure with a polymerization inhibitor to obtain crude P-(1-ethoxyethoxy)styrene. A polymerization inhibitor is added to the crude product and the product is distilled under reduced pressure to obtain the finished P-(1-ethoxyethoxy)styrene.

8. The method for synthesizing p-(1-ethoxyethoxy)styrene according to claim 7, characterized in that, The extraction solvent is n-hexane.

9. The method for synthesizing p-(1-ethoxyethoxy)styrene according to claim 7, characterized in that, The polymerization inhibitor is phenothiazine or a mixture of phenothiazine and 4-alkoxy-2,2,6,6-tetramethylpiperidine nitroxide radicals, wherein the mass ratio of phenothiazine to 4-alkoxy-2,2,6,6-tetramethylpiperidine nitroxide radicals in the mixture is 1:0.01 to 0.05.

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