A kind of efficient synthesis process of p-hydroxypropiophenone
By using anisole and an appropriate catalyst to react under specific reaction conditions, the problems of low yield of para-hydroxyphenyl acetone synthesis in the prior art are solved, and efficient and simple industrial production is achieved.
Patent Information
- Application Number
- CN202411797856.6
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-12-09
- Publication Date
- 2025-04-04
AI Technical Summary
The existing synthesis methods of parahydroxyphenyl acetone have low yields, complex operations and are not suitable for industrial production.
Amyle is used as raw material, combined with suitable catalysts (aluminum trichloride and zinc powder, etc.) and reaction conditions to prepare para-hydroxyphenyl acetone through one-step reaction.
It achieves high yield (up to 90%) and high purity (up to 99%) of parahydroxyphenyl acetone, which is easy to operate and is suitable for industrial production.
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Figure CN119751230A_ABST
Abstract
Description
Technical Field
[0001] The invention relates to the technical field of chemical synthesis, and in particular to a high-efficiency synthesis process of p-hydroxypropiophenone. Background Art
[0002] 4-Hydroxypropiophenone, also known as 4-hydroxypropiophenone, has a CAS number of 70-70-2. It is an important intermediate in chemical production and has a wide range of uses in chemical production such as medicines and pesticides. It is a necessary intermediate for drugs such as ritodrine and naorone.
[0003] At present, the synthesis methods of p-hydroxypropiophenone mainly include: 1. Using phenol and propionyl chloride as raw materials, and generating p-hydroxypropiophenone through Friedel-Crafts reaction. Although this method can obtain the target product in one step, the yield is relatively low, only 50%, and the amount of aluminum chloride used is relatively high; 2. Using phenol and propionic acid as raw materials, generating 4-hydroxypropiophenone through Nencki reaction, but the reaction activity of propionic acid is relatively low; 3. Using phenyl propionate as raw material, and using aluminum chloride as catalyst to perform Fries rearrangement to generate p-hydroxypropiophenone, but the yield in the literature is only 34-39%, and nitrobenzene with high toxicity is used as solvent.
[0004] In summary, most of the reported synthesis methods of p-hydroxypropiophenone have low yields, are not suitable for production, and are relatively complicated to operate; therefore, it is urgent to find a simple and efficient process for synthesizing p-hydroxypropiophenone. Summary of the invention
[0005] Based on the technical problems existing in the background technology, the present invention proposes an efficient synthesis process of p-hydroxypropiophenone. The present invention can prepare p-hydroxypropiophenone in one step, and the operation is simple and suitable for industrial production; and the yield and purity of p-hydroxypropiophenone are high.
[0006] The invention provides an efficient synthesis process of p-hydroxypropiophenone, comprising the following steps: mixing anisole, an organic solvent, a catalyst 1 and a catalyst 2, adding a substance A, reacting to obtain p-hydroxypropiophenone;
[0007] Wherein, substance A is one or more of propionyl chloride and propionyl bromide.
[0008] Preferably, catalyst 1 is aluminum trichloride.
[0009] Preferably, catalyst 1 is aluminum trichloride supported in sulfonated porous silica.
[0010] Preferably, in the process of preparing the catalyst 1, the sulfonated porous silica and the aluminum chloride aqueous solution are mixed, reacted at 80-85°C for 6-7h, and the solid-liquid separation, washing, and drying are performed to obtain the catalyst 1.
[0011] Preferably, the weight ratio of sulfonated porous silica to aluminum chloride is 1:0.6-0.65.
[0012] In the present invention, catalyst 1 is preferably aluminum chloride supported on sulfonated porous silica. The above-mentioned sulfonated porous silica can be purchased from the market. The good loading property of sulfonated porous silica for aluminum chloride can make the aluminum chloride evenly distributed and fixed on the porous silica, further improving its catalytic activity.
[0013] Preferably, the catalyst 2 is one or more of tin tetrachloride, iron powder, and zinc powder; more preferably, the catalyst 2 is zinc powder.
[0014] The present invention uses anisole as a raw material, selects suitable catalysts 1 and 2 to cooperate with each other, and combines suitable reaction conditions to prepare p-hydroxypropiophenone in one step, which can greatly improve the yield and product purity.
[0015] Preferably, the usage ratio of anisole and catalyst 1 is 1mmol:0.3-0.5g.
[0016] Preferably, the molar ratio of anisole to catalyst 2 is 1:0.02-0.08.
[0017] By selecting catalyst 1 and catalyst 2 to cooperate with each other, p-hydroxypropiophenone can be prepared in one step with high yield and high purity.
[0018] The molar ratio of anisole to substance A can be 1:0.9-1.1, preferably 1:1.
[0019] Preferably, the temperature is controlled to be between -5 and 30°C and substance A is added.
[0020] Preferably, the reaction is first carried out at 0-30°C for 1-3 hours, and then the temperature is raised to 40-80°C and the reaction is carried out for 5-8 hours.
[0021] The invention selects suitable ratios and reaction conditions to further improve the yield and purity of p-hydroxypropiophenone.
[0022] Preferably, the organic solvent is one or more of toluene, chlorobenzene, xylene, dichloromethane, dichloroethane, chloroform, and carbon tetrachloride.
[0023] Preferably, after the reaction is completed, p-hydroxypropiophenone is purified.
[0024] Preferably, the specific purification steps include: after the reaction is completed, adding the reaction solution into water to cool it down, separating the solid from the liquid, and taking the solid for recrystallization to obtain p-hydroxypropiophenone.
[0025] Preferably, the solvent for recrystallization is one or more of dichloromethane, dichloroethane, chloroform, carbon tetrachloride, methanol, ethanol, and isopropanol.
[0026] The invention selects anisole as a starting raw material, abandons the traditional process in which phenol is used as a starting raw material and needs to be synthesized in steps, prepares p-hydroxypropiophenone in one step, is easy to operate, and has simple purification steps, so that the production is more efficient and more suitable for industrial production; and the yield and purity of p-hydroxypropiophenone prepared in one step are greatly improved, which is much higher than that of the existing method for preparing p-hydroxypropiophenone in one step, and has high industrial production value.
[0027] The yield of p-hydroxypropiophenone prepared by the process of the invention can reach 90%, and the purity can reach more than 99%. BRIEF DESCRIPTION OF THE DRAWINGS
[0028] Figure 1 The HPLC spectrum of p-hydroxypropiophenone obtained in Example 3.
[0029] Figure 2-4 The HPLC spectra of p-hydroxypropiophenone prepared in Comparative Examples 1-3 are shown in sequence. DETAILED DESCRIPTION
[0030] The technical solution of the present invention is described in detail below through specific embodiments.
[0031] Example 1
[0032] An efficient synthesis process of p-hydroxypropiophenone comprises the following steps:
[0033] Mix 10mmol of anisole and 30ml of dichloromethane, then add 3g of aluminum chloride and 0.5mmol of iron powder, mix well, adjust the temperature to -5℃, add 10mmol of propionyl chloride dropwise, after the addition is complete, first keep the temperature at 0℃ for 2h, then raise the temperature to reflux and keep the temperature for 6h.
[0034] After the reaction was completed, the reaction solution was added dropwise to 40 ml of water, cooled to room temperature, and filtered to obtain a crude product;
[0035] The crude product was dissolved in dichloromethane, heated to reflux °C and stirred for 1 h, cooled to room temperature, filtered, and dried to obtain p-hydroxypropiophenone.
[0036] Example 2
[0037] An efficient synthesis process of p-hydroxypropiophenone comprises the following steps:
[0038] The sulfonated porous silica and the aluminum chloride aqueous solution were mixed so that the weight ratio of the sulfonated porous silica to the aluminum chloride was 1:0.65, reacted at 85° C. for 6 h, filtered, washed with water until the washing liquid did not contain chloride ions, and dried to obtain a catalyst 1;
[0039] Mix 10 mmol of anisole and 30 ml of toluene, then add 4 g of catalyst 1 and 0.5 mmol of tin tetrachloride and mix well. Adjust the temperature to 0°C, and drop 10 mmol of propionyl bromide. After the addition is complete, heat at 10°C for 2 hours, then heat to 70°C and heat for 6 hours.
[0040] After the reaction was completed, the reaction solution was added dropwise to 40 ml of water, cooled to room temperature, and filtered to obtain a crude product;
[0041] The crude product was dissolved in toluene, heated to 60°C and stirred for 1 h, cooled to room temperature, filtered, and dried to obtain p-hydroxypropiophenone.
[0042] Example 3
[0043] An efficient synthesis process of p-hydroxypropiophenone comprises the following steps:
[0044] The sulfonated porous silica and the aluminum chloride aqueous solution were mixed so that the weight ratio of the sulfonated porous silica to the aluminum chloride was 1:0.6, reacted at 80° C. for 7 h, filtered, washed with water until the washing liquid did not contain chloride ions, and dried to obtain a catalyst 1;
[0045] Mix 10 mmol of anisole and 30 ml of dichloroethane, then add 5 g of catalyst 1 and 0.5 mmol of zinc powder and mix well. Adjust the temperature to 5 °C, and drop 10 mmol of propionyl chloride. After the addition is complete, heat at 30 °C for 2 hours, then heat to 75 °C and heat for 6 hours.
[0046] After the reaction was completed, the reaction solution was added dropwise to 40 ml of water, cooled to room temperature, and filtered to obtain a crude product;
[0047] The crude product was dissolved in ethanol, heated to 60°C and stirred for 1 hour, cooled to room temperature, filtered, and dried to obtain p-hydroxypropiophenone.
[0048] Comparative Example 1
[0049] Without adding zinc powder, p-hydroxypropiophenone was prepared according to the method of Example 3.
[0050] Comparative Example 2
[0051] Zinc powder was replaced with magnesium powder, and p-hydroxypropiophenone was prepared according to the method of Example 3.
[0052] Comparative Example 3
[0053] Zinc powder was replaced with zinc oxide, and p-hydroxypropiophenone was prepared according to the method of Example 3.
[0054] The purity of the p-hydroxypropiophenone obtained in Examples 1-3 and Comparative Examples 1-3 was tested, and the yield was statistically analyzed. The results are shown in Tables 1 and Figure 1-4 shown.
[0055] Figure 1 The HPLC spectrum of p-hydroxypropiophenone obtained in Example 3.
[0056] Figure 2-4 The HPLC spectra of p-hydroxypropiophenone prepared in Comparative Examples 1-3 are shown in sequence.
[0057] Table 1 Test results
[0058] Grouping Yield of p-hydroxypropiophenone (%) Purity of p-Hydroxypropiophenone (%) Example 1 89.6 99.9 Example 2 93.9 99.9 Example 3 99.5 99.9 Comparative Example 1 61.3 96.3 Comparative Example 2 71.2 95.3 Comparative Example 3 88.2 98.0
[0059] It can be seen from Table 1 that the present invention selects suitable catalysts 1 and 2 to cooperate with each other, and combines suitable reaction conditions to prepare p-hydroxypropiophenone in one step, and the p-hydroxypropiophenone prepared by the obtained process has high yield and high purity.
[0060] The above description is only a preferred specific implementation manner of the present invention, but the protection scope of the present invention is not limited thereto. Any technician familiar with the technical field can make equivalent replacements or changes according to the technical scheme and inventive concept of the present invention within the technical scope disclosed by the present invention, which should be covered by the protection scope of the present invention.
Claims
1. An efficient synthesis process for parahydroxypropiophenone, characterized in that: The method comprises the following steps: mixing anisole, an organic solvent, catalyst 1 and catalyst 2, adding substance A, and reacting to obtain p-hydroxypropiophenone; Wherein, substance A is one or more of propionyl chloride and propionyl bromide.
2. The efficient synthesis process of parahydroxypropiophenone according to claim 1, characterized in that: Catalyst 1 is aluminum chloride; Preferably, catalyst 1 is aluminum trichloride supported in sulfonated porous silica; Preferably, in the process of preparing the catalyst 1, the sulfonated porous silica and the aluminum chloride aqueous solution are mixed, reacted at 80-85° C. for 6-7 hours, and the solid-liquid separation is performed, washed, and dried to obtain the catalyst 1; Preferably, the weight ratio of sulfonated porous silica to aluminum chloride is 1:0.6-0.
65.
3. The efficient synthesis process of parahydroxypropiophenone according to claim 1 or 2, characterized in that: Catalyst 2 is one or more of tin tetrachloride, iron powder and zinc powder.
4. The efficient synthesis process of p-hydroxypropiophenone according to any one of claims 1 to 3, characterized in that: The usage ratio of anisole and catalyst 1 is 1mmol:0.3-0.5g.
5. The efficient synthesis process of p-hydroxypropiophenone according to any one of claims 1 to 4, characterized in that: The molar ratio of anisole to catalyst 2 is 1:0.02-0.
08.
6. The efficient synthesis process of p-hydroxypropiophenone according to any one of claims 1 to 5, characterized in that: The temperature was controlled between -5 and 30°C and substance A was added.
7. The efficient synthesis process of p-hydroxypropiophenone according to any one of claims 1 to 6, characterized in that: First, keep the temperature at 0-30℃ for 1-3h, then raise the temperature to 40-80℃ and keep the temperature for 5-8h.
8. The efficient synthesis process of p-hydroxypropiophenone according to any one of claims 1 to 7, characterized in that: The organic solvent is one or more of toluene, chlorobenzene, xylene, dichloromethane, dichloroethane, chloroform and carbon tetrachloride.
9. The efficient synthesis process of p-hydroxypropiophenone according to any one of claims 1 to 8, characterized in that: After the reaction is completed, p-hydroxypropiophenone is purified.
10. The efficient synthesis process of p-hydroxypropiophenone according to claim 9, characterized in that: The specific purification steps include: after the reaction is completed, adding the reaction solution into water to cool down, separating the solid and the liquid, taking the solid for recrystallization, and obtaining p-hydroxypropiophenone; preferably, the solvent for recrystallization is one or more of dichloromethane, dichloroethane, chloroform, carbon tetrachloride, methanol, ethanol, and isopropanol.