A process for the preparation of o-phenylphenol ethyl alcohol

Abstract

The application relates to a method for preparing o-phenylphenoxyethanol, which comprises the following steps: S1, mixing o-phenylphenol with a catalyst and feeding into a reaction kettle for nitrogen replacement, introducing ethylene oxide for reaction at a reaction temperature to obtain a crude o-phenylphenoxyethanol solution; S2, adding a neutralizing agent to the crude o-phenylphenoxyethanol solution for neutralization to a pH value of 6-8; and S3, adding a mixed solvent to the neutralized crude o-phenylphenoxyethanol solution for recrystallization treatment to obtain o-phenylphenoxyethanol; wherein the mixed solvent is water and an alcohol. The prepared o-phenylphenoxyethanol has high reaction yield, high purity, excellent color and luster, and the preparation method is simple in equipment, low in cost, green and environment-friendly, and suitable for industrial large-scale production.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, and specifically relates to a method for preparing o-phenylphenoxyethanol. Background Technology

[0002] o-Phenoxyethanol, as an important aromatic ether alcohol fine chemical raw material and intermediate, is often used in the fields of medicine, pesticides, dyes, polymer materials and optics.

[0003] Currently, there are two main routes for the preparation of o-phenylphenoxyethanol: one is the ethylene oxide method, which uses o-phenylphenol (OPP) and ethylene oxide (EO) as raw materials, reacting them under the action of a catalyst to prepare o-phenylphenoxyethanol. The other is the ethylene carbonate method, which uses o-phenylphenol and ethylene carbonate as raw materials, reacting them under the action of a catalyst to generate the target product. Although this method avoids the use of ethylene oxide, the raw materials are safe and there is no high-pressure risk, but the reaction temperature is high, there are many byproducts (such as carbon dioxide and ethylene glycol), purification is difficult, and industrial application is not yet mature.

[0004] Several industrialization solutions have been proposed for the ethylene oxide method. Chinese invention patent (publication number: CN102070415B) discloses a method for preparing o-phenylphenoxyethanol, in which o-phenylphenol and an alkaline catalyst are added to a reaction vessel, and ethylene oxide is introduced to react and obtain a crude product. The crude product is then obtained through recrystallization, alkaline washing, water washing, and drying to obtain the final product. The yield of this final product is 84.9%, which still has room for improvement, and the post-processing steps, including recrystallization, alkaline washing, water washing, and drying, are still relatively cumbersome. In response to this method, Chinese invention patent (publication number: CN115710163B) discloses a continuous flow method for producing o-phenylphenoxyethanol. In this method, a mixture of o-phenylphenol and a catalyst, along with ethylene oxide, are separated into two streams and introduced into a microchannel reactor for reaction. The resulting o-phenylphenoxyethanol reaction solution is then crystallized using a benzene solvent at 0°C to obtain the final product. This method significantly improves the yield, reaching over 93%. However, the benzene-based solvents used in the post-processing of this scheme are highly toxic, easily causing environmental pollution and resulting in poor environmental friendliness. Furthermore, the microchannel reactor equipment requires a large investment and has high production costs, making it difficult to apply industrially.

[0005] Therefore, there is a need to further improve the industrial method for preparing o-phenylphenoxyethanol. Summary of the Invention

[0006] Based on the above-mentioned technical problems, this application provides a method for preparing o-phenylphenoxyethanol. By neutralizing the crude product solution and recrystallizing it with an alcohol-containing mixed solvent, the yield and color of o-phenylphenoxyethanol product are improved under the condition of using a conventional reaction vessel. Moreover, the method is green and environmentally friendly, has low production cost, and is suitable for large-scale production.

[0007] According to a first aspect of the present invention, a method for preparing o-phenylphenoxyethanol is provided, the method comprising: S1, mixing o-phenylphenol with a catalyst and adding the mixture into a reaction vessel and purging it with nitrogen, and then introducing ethylene oxide at a reaction temperature to react and obtain a crude o-phenylphenoxyethanol solution; S2, adding a neutralizing agent to the crude o-phenylphenoxyethanol solution to neutralize it to a pH value of 6-8; S3, adding a mixed solvent to the neutralized crude o-phenylphenoxyethanol solution and recrystallizing it to obtain o-phenylphenoxyethanol, wherein the mixed solvent comprises water and an alcohol.

[0008] According to some embodiments, the neutralizing agent is selected from one or more of hydrochloric acid, phosphoric acid, glacial acetic acid, sulfuric acid, or lactic acid.

[0009] According to some embodiments, in the mixed solvent, the mass ratio of water to alcohol is (0.5~1.5):1.

[0010] According to some embodiments, the alcohol is selected from one or more alkyl alcohols containing 1-6 carbon atoms, preferably from one or more of methanol, ethanol or isopropanol.

[0011] According to some embodiments, the mass ratio of the neutralized crude o-phenylphenoxyethanol solution to the mixed solvent is 1:(0.2~3.0).

[0012] According to some embodiments, after S3, the method further includes: S4, filtering to obtain a filter cake and drying the filter cake to obtain the o-phenylphenoxyethanol.

[0013] According to some embodiments, in S4, the filtrate obtained from filtration is reused as at least a portion of the mixed solvent in S3.

[0014] According to some implementations, in S1, the reaction satisfies at least one of the following: The molar ratio of o-phenylphenol to ethylene oxide is 1:(0.98~1.05). Based on the total mass of the o-phenylphenol and ethylene oxide, the percentage of the catalyst added is 0.2-0.5%; The catalyst is selected from one or more of sodium hydroxide, potassium hydroxide, potassium carbonate, sodium carbonate, sodium sesquicarbonate, triphenylphosphine, tripropylamine, triethanolamine, and triethylamine. The reaction temperature is 110~150℃; The reaction time is 1 to 5 hours.

[0015] According to some embodiments, S1 further includes maintaining the reaction temperature and reaction pressure for 0.5 to 2.0 h after the reaction is completed to age until the pressure is constant; and in S2, cooling the crude o-phenylphenoxyethanol solution to 80 to 100°C before adding the neutralizing agent.

[0016] Beneficial technical effects of the present invention: This invention improves the reaction yield by performing a neutralization reaction after the reaction is completed and then recrystallizing using a mixed solvent including water and alcohols. On the other hand, it obtains a high-purity product with good color without using toxic solvents.

[0017] Furthermore, the preparation method of this invention uses simple equipment and has low cost. Subsequent processing steps eliminate the need for alkali washing and water washing, further simplifying the process. The filtrate obtained after recrystallization can be recycled as a mixed solvent, further reducing costs and minimizing waste emissions. Attached Figure Description

[0018] Figure 1 The high-performance liquid chromatogram of o-phenylphenoxyethanol prepared according to Example 1; Figure 2 The high-performance liquid chromatogram of o-phenylphenoxyethanol prepared according to Example 3; Figure 3 The high performance liquid chromatogram of o-phenylphenoxyethanol prepared according to Comparative Example 7 is shown. Detailed Implementation The present invention will be further described in detail below through specific embodiments, but the scope of protection of the present invention is not limited thereto.

[0019] This invention provides a method for preparing o-phenylphenoxyethanol, the method comprising: S1, mixing o-phenylphenol and a catalyst and adding them into a reaction vessel for nitrogen purging, and then introducing ethylene oxide at a reaction temperature to obtain a crude o-phenylphenoxyethanol solution; S2, adding a neutralizing agent to the crude o-phenylphenoxyethanol solution to neutralize it to a pH of 6-8; S3, adding a mixed solvent to the neutralized crude o-phenylphenoxyethanol solution for recrystallization to obtain o-phenylphenoxyethanol, wherein the mixed solvent comprises water and an alcohol.

[0020] This invention uses o-phenylphenol and ethylene oxide as reactants. Under the action of a catalyst, an ethoxylation reaction is carried out to obtain a crude o-phenylphenoxyethanol solution, which is then post-treated to obtain o-phenylphenoxyethanol. In the post-treatment, this invention innovatively adds a neutralizing agent and an alkaline catalyst to the crude o-phenylphenoxyethanol solution to neutralize it to a pH of 6-8. This significantly reduces the risk of discoloration caused by unreacted o-phenylphenol in the crude o-phenylphenoxyethanol under alkaline conditions, and significantly improves the color of the product. Recrystallization is then performed in a mixed solvent of water and alcohol to improve the yield and purity of the product.

[0021] In the post-processing recrystallization process, this invention uses a mixed solvent of water and alcohol, with water as a poor solvent and alcohol as a good solvent. By utilizing the difference in solubility of o-phenylphenoxyethanol in the two solvents, the purity and yield of the product can be improved simultaneously, while avoiding the use of toxic solvents, thus combining the advantages of environmental protection and safety.

[0022] According to one embodiment, the neutralizing agent is selected from one or more of hydrochloric acid, phosphoric acid, glacial acetic acid, sulfuric acid or lactic acid, and is added after the reaction to carry out the neutralization reaction and improve the color of the product.

[0023] According to one embodiment, in the recrystallization process, the mass ratio of water to the alcohol is (0.5~1.5):1, preferably (0.8~1.2):1. Exemplary examples include mass ratios of 0.5:1, 0.6:1, 0.7:1, 0.8:1, 0.9:1, 1.0:1, 1.1:1, 1.2:1, 1.3:1, 1.4:1, or 1.5:1. When the mass ratio of water to the alcohol is within the above ranges, both product purity and yield can be improved.

[0024] According to one embodiment, the alcohol is selected from one or more alkyl alcohols containing 1-6 carbon atoms, preferably from one or more of methanol, ethanol or isopropanol, especially isopropanol.

[0025] The mass ratio of the neutralized crude o-phenylphenoxyethanol solution to the mixed solvent is 1:(0.2~3.0), preferably 1:(1.0~2.5). Exemplarily, the mass ratio of the neutralized crude o-phenylphenoxyethanol solution to the mixed solvent can be 1:0.2, 1:0.3, 1:0.4, 1:0.5, 1:0.6, 1:0.7, 1:0.8, 1:0.9, 1:1.0, 1:1.1, 1:1.2, 1:1.3, 1:1.4, 1:1.5, 1:1.6, 1:1.7, 1:1.8, 1:1.9, 1:2.0, 1:2.1, 1:2.2, 1:2.3, 1:2.4, 1:2.5, 1:2.6, 1:2.7, 1:2.8, 1:2.9, or 1:3.0. Add a mixed solvent at the mass ratio within the above range and perform recrystallization to further improve the product yield and purity.

[0026] According to one embodiment, after S3, the method further includes: S4, filtering to obtain a filter cake and drying the filter cake to obtain the o-phenylphenoxyethanol. In S4, the filtrate obtained from the filtration is reused as at least a portion of the mixed solvent in S3.

[0027] The above drying process is carried out under vacuum conditions, with a vacuum pressure ≤ -0.09 MPa and a drying temperature of 90~120℃, such as 90℃, 100℃, 110℃, or 120℃. The drying time can be adjusted according to different temperatures, such as 1~3 hours, for example 1 hour, 2 hours, or 3 hours. Vacuum drying can remove the recrystallization solvent remaining on the surface of o-phenylphenoxyethanol, improving the purity of the product.

[0028] According to one embodiment, in S1, the reaction satisfies at least one of the following: the molar ratio of o-phenylphenol to ethylene oxide is 1:(0.98~1.05), for example, it can be 1:0.98, 1:0.99, 1:1.0, 1:1.01, 1:1.02, 1:1.03, 1:1.04, or 1:1.05. By controlling the ratio, the target product (o-phenylphenoxyethanol) can be accurately obtained, while all by-products and raw material residues are controlled within acceptable limits.

[0029] According to one embodiment, based on the total mass of o-phenylphenol and ethylene oxide, the mass percentage of the catalyst is 0.2% to 0.5%, for example, 0.2%, 0.3%, 0.4%, or 0.5%. The catalyst is selected from one or more of sodium hydroxide, potassium hydroxide, potassium carbonate, sodium carbonate, and triethylamine.

[0030] In this invention, by limiting the mass percentage of the catalyst to 0.2-0.5%, the reaction rate can be controlled, ensuring product purity and color while also considering cost. The catalyst is selected from one or more of sodium hydroxide, potassium hydroxide, potassium carbonate, sodium carbonate, sodium sesquicarbonate, triphenylphosphine, tripropylamine, triethanolamine, or triethylamine, with sodium carbonate being preferred.

[0031] According to one embodiment, the reaction is carried out at a temperature of 110~150°C and a pressure of ≤0.5MPa for 1~5 hours. The reaction temperature can be 110°C, 115°C, 120°C, 125°C, 130°C, 135°C, 140°C, 145°C or 150°C.

[0032] According to one embodiment, S1 further includes maintaining the reaction temperature and reaction pressure for 0.5 to 2.0 hours after the reaction is completed to age the mixture until the pressure is constant.

[0033] According to one embodiment, in S2, the crude o-phenylphenoxyethanol solution is cooled to 80-100°C before adding the neutralizing agent, in order to prevent unreacted o-phenylphenol from being oxidized and discolored at high temperatures, reduce safety risks, and ensure product quality.

[0034] 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. These embodiments are merely some examples of the invention, not all examples. Other embodiments obtained without creative effort are all within the scope of protection of this invention.

[0035] Example Unless otherwise specified, all reagents used below are commercially available.

[0036] Example 1 400g of o-phenylphenol and 1.52g of sodium carbonate catalyst were added to a reactor in a specific ratio. Nitrogen gas was introduced to replace the air in the reactor. After the pressure inside the reactor stabilized, the temperature was raised to 115℃, and 106.62g of ethylene oxide (EO) (molar ratio of o-phenylphenol to ethylene oxide 1:1.03) was introduced to carry out an ethoxylation reaction for 3 hours. After the reaction, the pressure was 0.45MPa. The reaction temperature was maintained until the pressure was constant, and the reaction was aged for 2 hours to obtain a crude o-phenylphenoxyethanol solution. The crude o-phenylphenoxyethanol was then cooled to 90℃ and phosphoric acid was added to neutralize the pH to 7. The neutralized reaction solution was transferred out of the reactor, and 254g of water and 254g of isopropanol were added as a mixed solvent for recrystallization. The mass ratio of the neutralized crude o-phenylphenoxyethanol solution to the mixed solvent was 1:1. The wet filter cake was obtained by suction filtration and then vacuum dried (vacuum pressure -0.098 MPa, drying temperature 95℃, drying time 2 h) to obtain a white o-phenylphenoxyethanol solid. The yield was 95%, the melting point was 74.2℃, and the purity was 99.66% as determined by HPLC. Its HPLC chromatogram is shown below. Figure 1 As shown.

[0037] Example 2 o-Phenoxyethanol was prepared according to the method of Example 1, the only difference from Example 1 being that the molar ratio of o-phenylphenol to ethylene oxide was 1:1.01, that is, 400g of o-phenylphenol, 1.51g of sodium carbonate, and 104.55g of ethylene oxide (EO).

[0038] Example 3 o-Phenylacetylethanol was prepared according to the method of Example 1, the only difference being that the molar ratio of o-phenylphenol to ethylene oxide was 1:1.05, i.e., 400 g of o-phenylphenol, 1.53 g of sodium carbonate, and 108.70 g of ethylene oxide (EO). The HPLC chromatogram of the prepared o-phenylphenoxyethanol is shown below. Figure 2 As shown.

[0039] Example 4 o-Phenoxyethanol was prepared according to the method of Example 1, the only difference being that the amount of sodium carbonate catalyst added was 2.53 g.

[0040] Example 5 o-Phenoxyethanol was prepared according to the method of Example 1, the only difference from Example 1 being that sodium hydroxide was added as the catalyst.

[0041] Example 6 o-Phenoxyethanol was prepared according to the method of Example 1, the only difference from Example 1 being that triethylamine was added as the catalyst.

[0042] Example 7 o-Phenoxyethanol was prepared according to the method of Example 1, the only difference from Example 1 being that the reaction temperature was 135°C.

[0043] Example 8 o-Phenoxyethanol was prepared according to the method of Example 1, the only difference from Example 1 being that the reaction time was 2 hours.

[0044] Example 9 o-Phenoxyethanol was prepared according to the method of Example 1, the only difference from Example 1 being that the neutralizing agent was sulfuric acid.

[0045] Example 10 o-Phenoxyethanol was prepared according to the method of Example 1, except that the recrystallization solvent was 254g of water and 254g of methanol.

[0046] Example 11 o-Phenoxyethanol was prepared according to the method of Example 1, the only difference being that the recovered filtrate was used for recrystallization in the post-treatment.

[0047] Example 12 o-Phenoxyethanol was prepared according to the method of Example 1, except that the recrystallization solvent was 305g of water and 203g of isopropanol, wherein the mass ratio of water to isopropanol was 1.5:1.

[0048] Example 13 o-Phenoxyethanol was prepared according to the method of Example 1, except that the recrystallization solvent was 169g of water and 339g of isopropanol, wherein the mass ratio of water to isopropanol was 0.5:1.

[0049] Comparative Example 1 o-Phenoxyethanol was prepared according to the method of Example 1, the only difference from Example 1 being that no phosphoric acid neutralizing agent was added for the neutralization reaction.

[0050] Comparative Example 2 o-Phenoxyethanol was prepared according to the method of Example 1, the only difference being that phosphoric acid was added as a neutralizing agent to neutralize the pH to 5.

[0051] Comparative Example 3 o-Phenoxyethanol was prepared according to the method of Example 1, the only difference being that phosphoric acid was added to neutralize the pH to 9.

[0052] Comparative Example 4 o-Phenoxyethanol was prepared according to the method of Example 1, the only difference from Example 1 being that recrystallization was performed using only isopropanol solvent.

[0053] Comparative Example 5 o-Phenoxyethanol was prepared according to the method of Example 1, except that the recrystallization solvent was a mixed solution of 218 g of water and 544 g of isopropanol, wherein the mass ratio of water to isopropanol was 0.4:1.

[0054] Comparative Example 6 o-Phenoxyethanol was prepared according to the method of Example 1, except that the recrystallization solvent was a mixed solution of 339 g of water and 169 g of isopropanol, wherein the mass ratio of water to isopropanol was 2:1.

[0055] Comparative Example 7 o-Phenylacetylethanol was prepared according to the method of Example 1, the only difference being that the recrystallization solvent was 508g of water. The HPLC chromatogram of the prepared o-phenylphenoxyethanol is shown below. Figure 3 As shown.

[0056] The index information of the o-phenylphenoxyethanol products prepared by the above embodiments and comparative examples is shown in Table 1.

[0057] Table 1

[0058] The above data test results show that when the neutralization reaction is carried out using a neutralizing agent and the pH value is neutralized to 7, compared with the results when no neutralizing agent is added (Comparative Example 1), the pH value is neutralized to 5 (Comparative Example 2), and the pH value is neutralized to 9 (Comparative Example 3), the o-phenylphenoxyethanol obtained is a white solid with higher purity. The products obtained in Comparative Examples 1 to 3 are light yellow and their purity is also reduced.

[0059] The preparation results of Examples 1, 12-13, and Comparative Examples 4 to 7 show that using the mixed solvent of water and alcohol as the recrystallization solvent, with a water-to-alcohol mass ratio in the range of (0.5~1.5):1, yields o-phenylphenoxyethanol with higher purity and higher yield. It is precisely because the recrystallization solvent used in the post-processing of this invention can achieve one-step impurity removal and crystallization purification of crude o-phenylphenoxyethanol, thereby improving the purity and yield of the product, that the yield of this method is generally above 90%, and the purity of the obtained o-phenylphenoxyethanol is above 99%.

[0060] The above embodiments fully demonstrate the effectiveness, superiority, and economy of the method of the present invention. The present invention is not limited to the above embodiments; any modifications, substitutions, and improvements made without departing from the principles and spirit of the present invention should fall within the protection scope of the present invention.

Claims

1. A method for preparing o-phenylphenoxyethanol, characterized in that, The method includes: S1, o-phenylphenol and catalyst are mixed and added into the reactor for nitrogen purging. Ethylene oxide is introduced at the reaction temperature to carry out the reaction and obtain crude o-phenylphenoxyethanol solution. S2, add a neutralizing agent to the crude o-phenylphenoxyethanol solution to neutralize it to a pH of 6-8; S3, add a mixed solvent to the neutralized crude o-phenylphenoxyethanol solution and recrystallize to obtain o-phenylphenoxyethanol, wherein the mixed solvent includes water and alcohols.

2. The method according to claim 1, wherein, The neutralizing agent is selected from one or more of hydrochloric acid, phosphoric acid, glacial acetic acid, sulfuric acid, or lactic acid.

3. The method according to claim 1, wherein, In the mixed solvent, the mass ratio of water to alcohol is (0.5~1.5):

1.

4. The method according to claim 1, wherein, The alcohols are selected from one or more alkyl alcohols containing 1-6 carbon atoms, and are preferably selected from one or more of methanol, ethanol or isopropanol.

5. The method according to claim 1, wherein, The mass ratio of the neutralized crude o-phenylphenoxyethanol solution to the mixed solvent is 1:(0.2~3.0).

6. The method according to claim 1, wherein, After S3, the method further includes: S4, filtering to obtain a filter cake and drying the filter cake to obtain the o-phenylphenoxyethanol.

7. The method according to claim 6, wherein, In S4, the filtrate obtained from filtration is reused as at least a portion of the mixed solvent in S3.

8. The method according to claim 1, wherein, In S1, the reaction satisfies at least one of the following conditions: The molar ratio of o-phenylphenol to ethylene oxide is 1:(0.98~1.05). Based on the total mass of o-phenylphenol and ethylene oxide, the mass percentage of the catalyst is 0.2-0.5%; the catalyst is selected from one or more of sodium hydroxide, potassium hydroxide, potassium carbonate, sodium carbonate, sodium sesquicarbonate, triphenylphosphine, tripropylamine, triethanolamine, and triethylamine. The reaction temperature is 110~150℃; The reaction time is 1 to 5 hours.

9. The method according to claim 1, wherein, S1 further includes maintaining the reaction temperature for 0.5~2.0h after the reaction is completed to age the mixture until the pressure is constant; and In S2, the crude o-phenylphenoxyethanol solution is cooled to 80-100°C before the neutralizing agent is added.

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