A method for synthesizing p-hydroxyacetophenone
By using anhydrous hydrogen fluoride catalyst and phenyl acetate for rearrangement reaction under specific conditions, the problems of complex synthesis process and high energy consumption of p-hydroxyacetophenone in the prior art have been solved, and a highly selective and efficient synthesis effect has been achieved.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- CHIZHOU TINCI HIGH TECH MATERIALS CO LTD
- Filing Date
- 2024-11-26
- Publication Date
- 2026-05-26
AI Technical Summary
Existing methods for synthesizing p-hydroxyacetophenone are complex, energy-intensive, and have low selectivity, resulting in high production costs and numerous byproducts.
Anhydrous hydrogen fluoride was used as a catalyst to carry out a rearrangement reaction with phenyl acetate under specific temperature and pressure. The reaction conditions were optimized by using the polar solvent o-dichlorobenzene to improve the selectivity and conversion rate of p-hydroxyacetophenone.
It significantly improves the selectivity and synthesis efficiency of p-hydroxyacetophenone, reduces equipment investment and energy consumption, and reduces the generation of waste. The catalyst is also easy to recycle.
Smart Images
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Abstract
Description
Technical Field
[0001] This invention belongs to the field of p-hydroxyacetophenone synthesis technology, and specifically relates to a method for synthesizing p-hydroxyacetophenone. Background Technology
[0002] p-Hydroxyacetophenone has applications in engineering plastics additives, pharmaceuticals, and cosmetics. As a multifunctional cosmetic ingredient, it was recognized as an environmentally friendly cleaning ingredient by the U.S. Environmental Protection Agency in 2014. It not only has antioxidant, soothing, and emulsion-stabilizing effects, but also antiseptic and antibacterial properties. Its safety, gentleness, and low sensitization / irritation have led to its increasing use in high-end cosmetics, especially in children's skincare products and face masks. In the pharmaceutical field, p-hydroxyacetophenone and its derivatives have choleretic and litholytic effects, reducing cholesterol levels in bile and can be used as an adjunct treatment for cholecystitis and acute and chronic jaundice hepatitis. It is also a synthetic intermediate for many drugs, such as acetaminophen, salbutamol (an antiasthmatic), and butylphenylcarboxylic acid (an anti-inflammatory drug). In the field of engineering plastics additives, p-hydroxyacetophenone oxime, the product generated by the ammonium oxime reaction, can be used to prepare new materials with information storage functions and can also be applied in the field of photography; the Schiff base obtained by the reaction of p-hydroxyacetophenone with amine has fluorescence and can also be used to prepare luminescent materials, liquid crystal materials, synthetic resins, and to determine trace metals in food samples.
[0003] Currently, the main method for industrial production of p-hydroxyacetophenone is chemical synthesis, with two main process routes: one is to use anisole as raw material and prepare it through Friedel-Crafts reaction, desaturation, and other steps, but this process is costly, energy-intensive, time-consuming, and has low yield; the other is to use phenol as raw material and prepare it through esterification, transposition, and other steps. Although this process produces p-hydroxyacetophenone with shorter reaction steps and lower production costs, it generates a large amount of the byproduct o-hydroxyacetophenone and has low product selectivity.
[0004] Therefore, there is an urgent need to develop a synthetic method that is simple, low-cost, mild, and can improve the selectivity of p-hydroxyacetophenone. Summary of the Invention
[0005] This invention provides a method for synthesizing p-hydroxyacetophenone, which solves the problems of complex process, high energy consumption and low selectivity of p-hydroxyacetophenone in the prior art.
[0006] This invention provides a method for synthesizing p-hydroxyacetophenone, comprising the following steps: introducing a solution containing anhydrous hydrogen fluoride into a reaction vessel containing phenyl acetate to carry out a rearrangement reaction, wherein the rearrangement reaction is carried out at a temperature of 80-140°C and a pressure of 1-2 MPa, to obtain crude p-hydroxyacetophenone.
[0007] Optionally, the reaction time for the rearrangement reaction is 2 to 3 hours.
[0008] Optionally, the water content of the phenyl acetate is not higher than 400 ppm.
[0009] Optionally, the mass ratio of phenyl acetate to anhydrous hydrogen fluoride is 1:(1-2).
[0010] Optionally, the solution containing anhydrous hydrogen fluoride may further include a polar solvent.
[0011] Optionally, the polar solvent includes o-dichlorobenzene; the mass ratio of the anhydrous hydrogen fluoride to the o-dichlorobenzene is 1:(0.97-7.79).
[0012] Optionally, the solution containing anhydrous hydrogen fluoride is prepared by the following steps: dissolving anhydrous hydrogen fluoride in pure o-dichlorobenzene solution at -20 to 10°C to obtain the solution containing anhydrous hydrogen fluoride.
[0013] Optionally, the method further includes: subjecting the crude p-hydroxyacetophenone product to steam elution to obtain the p-hydroxyacetophenone product.
[0014] Optionally, the phenyl acetate is prepared by the following steps: heating and melting phenol, mixing it with acetic anhydride, and then performing esterification and condensation treatment in sequence to obtain the phenyl acetate.
[0015] Optionally, the esterification treatment is carried out at a temperature of 140–160°C for 3–12 hours; and / or the mass ratio of phenol to acetic anhydride is 1:(1–1.2).
[0016] The method for synthesizing p-hydroxyacetophenone provided by this invention uses anhydrous hydrogen fluoride as a catalyst to carry out a rearrangement reaction with phenyl acetate under specific temperature and pressure. This method can significantly increase the conversion rate of raw materials, the selectivity of p-hydroxyacetophenone, and improve the efficiency of the synthesis reaction. Furthermore, it has low equipment investment, low energy consumption, and low generation of waste. The anhydrous hydrogen fluoride catalyst is also easy to recover and reuse. Detailed Implementation
[0017] To make the objectives, technical solutions, and advantages of this invention clearer, the technical solutions in the embodiments of this invention will be clearly and completely described below in conjunction with the embodiments of this invention. Obviously, the described embodiments are only some embodiments of this invention, not all embodiments. Based on the embodiments of this invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this invention.
[0018] On one hand, the present invention provides a method for synthesizing p-hydroxyacetophenone, comprising the following steps: passing a solution containing anhydrous hydrogen fluoride into a reaction vessel containing phenyl acetate to carry out a rearrangement reaction, wherein the temperature of the rearrangement reaction is 80-140°C and the pressure is 1-2 MPa, to obtain crude p-hydroxyacetophenone.
[0019] In existing technologies, aluminum trichloride is typically used as a catalyst for the rearrangement reaction of phenyl acetate. However, the p-hydroxyacetophenone produced after the reaction has low selectivity and generates a large amount of o-hydroxyacetophenone, resulting in a low yield of the synthesis method.
[0020] This invention employs a method of introducing a solution containing anhydrous hydrogen fluoride into a reaction vessel containing phenyl acetate, using anhydrous hydrogen fluoride (AHF) as a catalyst to carry out a rearrangement reaction with phenyl acetate at 80-140℃ and 1-2 MPa. This significantly improves the selectivity of p-hydroxyacetophenone and greatly increases the yield of the synthesis reaction. The rearrangement reaction in this invention is shown in formula (1):
[0021]
[0022] Therefore, after phenyl acetate undergoes a rearrangement reaction with a solution containing anhydrous hydrogen fluoride, the crude p-hydroxyacetophenone product obtained includes p-hydroxyacetophenone, o-hydroxyacetophenone, and a small amount of dissolved hydrogen fluoride. The remaining overflowing hydrogen fluoride gas can be directly recycled by passing it into water.
[0023] The mechanism of the rearrangement reaction is not yet fully understood; it may sometimes be an intramolecular reaction and sometimes an intermolecular reaction. The inventors speculate that phenyl acetate first needs to undergo protonation and carbon-oxygen bond breaking before it can undergo an intramolecular or intermolecular rearrangement reaction. Anhydrous hydrogen fluoride significantly affects the protonation process of phenyl acetate, and since the intermediate is an ion pair, anhydrous hydrogen fluoride can improve the stability of the intermediate, which is beneficial to the conversion of the substrate and the formation of the product. Furthermore, by using anhydrous hydrogen fluoride as a catalyst to carry out the rearrangement reaction with phenyl acetate under specific temperature and pressure conditions, the selectivity of p-hydroxyacetophenone can be significantly increased, thereby improving the efficiency of the synthesis reaction.
[0024] The method for synthesizing p-hydroxyacetophenone provided by this invention uses anhydrous hydrogen fluoride as a catalyst to carry out a rearrangement reaction with phenyl acetate under specific temperature and pressure. This method can significantly increase the conversion rate of raw materials, the selectivity of p-hydroxyacetophenone, and improve the efficiency of the synthesis reaction. Furthermore, it has low equipment investment, low energy consumption, and low generation of waste. The anhydrous hydrogen fluoride catalyst is also easy to recover and reuse.
[0025] Furthermore, the reaction time for the rearrangement reaction is 2–3 hours.
[0026] When anhydrous hydrogen fluoride and phenyl acetate undergo a rearrangement reaction at 80-140°C and 1-2 MPa, the inventors discovered that when the reaction time is 2-3 hours, the conversion rate of the raw materials can be further improved, and the selectivity of p-hydroxyacetophenone can be further improved. In one specific embodiment, the content of phenyl acetate in the reactants can be detected by ion chromatography. When the content of phenyl acetate is not higher than 0%, the rearrangement reaction can usually be judged to be complete.
[0027] In one specific embodiment, the water content of phenyl acetate is not higher than 400 ppm.
[0028] It is understandable that controlling the water content of phenyl acetate feedstock can further reduce the occurrence of side reactions, improve the conversion rate of feedstock, improve reaction efficiency, and further improve the selectivity of p-hydroxyacetophenone.
[0029] Optionally, the mass ratio of phenyl acetate to anhydrous hydrogen fluoride is 1:(1-2).
[0030] By further limiting the mass ratio of phenyl acetate to anhydrous hydrogen fluoride, the selectivity of p-hydroxyacetophenone can be further improved, and the pressure requirement can be further reduced, ensuring the safety of the reaction.
[0031] In one specific embodiment, the solution containing anhydrous hydrogen fluoride further includes a polar solvent.
[0032] Since the polarity of the solvent significantly affects the protonation process of phenyl acetate, and when the intermediate is an ion pair, increasing the solvent polarity can further improve the stability of the intermediate, thereby further improving the conversion rate of phenyl acetate and the selectivity of p-hydroxyacetophenone.
[0033] Specifically, the polar solvent includes o-dichlorobenzene; the mass ratio of anhydrous hydrogen fluoride to o-dichlorobenzene can be 1.0:(0.97 to 7.79).
[0034] The inventors discovered that by using o-dichlorobenzene as a solvent to dissolve anhydrous hydrogen fluoride and further limiting the mass ratio of the two, the conversion rate of phenyl acetate and the selectivity of p-hydroxyacetophenone can be further improved.
[0035] In one specific embodiment, the liner of the reactor is made of Hastelloy.
[0036] This invention does not limit the specific preparation method of the solution containing anhydrous hydrogen fluoride. Optionally, the solution containing anhydrous hydrogen fluoride is obtained by the following steps: dissolving anhydrous hydrogen fluoride in a pure o-dichlorobenzene solution at -20 to 10°C to obtain the solution containing anhydrous hydrogen fluoride. By further limiting the temperature of the o-dichlorobenzene pure solution, the solubility of anhydrous hydrogen fluoride can be further improved, and the conversion rate of phenyl acetate and the selectivity of p-hydroxyacetophenone can be further improved.
[0037] More specifically, the preparation steps of the solution containing anhydrous hydrogen fluoride include: weighing a certain amount of o-dichlorobenzene pure solution using a tetrafluoroethylene receiving bottle and cooling it to -20 to 10°C in an ice machine; connecting the inlet of the tetrafluoroethylene receiving bottle cap to an anhydrous hydrogen fluoride cylinder, roughly judging the feed amount by weighing the mass change of the cylinder with a high-precision scale, closing the cylinder inlet after feeding, waiting for 60 minutes, and observing that there is no large amount of white smoke in the exhaust gas to confirm that the anhydrous hydrogen fluoride has dissolved in the o-dichlorobenzene pure solution; at this time, weighing the mass change of the tetrafluoroethylene receiving bottle can accurately measure the content of anhydrous hydrogen fluoride.
[0038] Furthermore, it also includes: subjecting crude p-hydroxyacetophenone to steam elution treatment to obtain p-hydroxyacetophenone product.
[0039] By subjecting crude hydroxyacetophenone, which includes p-hydroxyacetophenone, o-hydroxyacetophenone, and a small amount of hydrogen fluoride, to steam elution treatment, the o-hydroxyacetophenone and hydrogen fluoride dopants in p-hydroxyacetophenone can be removed, and the p-hydroxyacetophenone product can be obtained; optionally, the steam temperature of the steam elution treatment is 100-120°C.
[0040] The present invention does not limit the source of phenyl acetate; it can be obtained by purchase or by preparation methods commonly used in the prior art.
[0041] Optionally, phenyl acetate is prepared by the following steps: phenol is heated and melted, then mixed with acetic anhydride, and subsequently subjected to esterification and condensation treatment to obtain phenyl acetate.
[0042] When phenol and acetic anhydride are used as raw materials for esterification, the esterification reaction occurs as shown in formula (2):
[0043]
[0044] Specifically, a certain amount of phenol is heated to melt it and then placed in a three-necked flask. Acetic anhydride is added to the three-necked flask, and esterification and condensation are carried out in sequence. After washing with water and distillation, phenyl acetate is obtained.
[0045] By first heating and melting phenol, the preparation method can be further simplified, the esterification time can be shortened, and the preparation method does not introduce water, which can further improve the conversion rate of phenyl acetate and the selectivity of p-hydroxyacetophenone.
[0046] In one specific embodiment, the esterification treatment is carried out at a temperature of 140–160°C for 3–12 hours; the mass ratio of phenol to acetic anhydride is 1:(1–1.2).
[0047] By further defining the specific conditions of esterification and the ratio of raw materials for synthesizing phenyl acetate, the efficiency of esterification can be further improved, the conversion rate of raw materials can be increased, and the esterification time can be further shortened.
[0048] The following detailed description of a method for synthesizing p-hydroxyacetophenone provided by the present invention is provided through specific embodiments.
[0049] Example 1
[0050] (1) Take 400g of phenol, heat it to melt it and put it into a three-necked flask. Add 480g of acetic anhydride to the three-necked flask and perform esterification treatment at 140℃ for 5h. After condensing and refluxing, washing with water and distilling, phenyl acetate is obtained.
[0051] (2) Weigh 194g of o-dichlorobenzene pure solution and place it in a tetrafluoro receiving bottle. Cool it in an ice machine to -10 to -20℃, so that 100g of anhydrous hydrogen fluoride dissolves in the o-dichlorobenzene pure solution to obtain a solution containing anhydrous hydrogen fluoride.
[0052] (3) A rearrangement reaction was carried out by introducing a solution containing anhydrous hydrogen fluoride into a reaction vessel containing 100g of phenyl acetate. The rearrangement reaction was carried out at a temperature of 80℃ and a pressure of 1MPa to obtain crude p-hydroxyacetophenone.
[0053] Example 2
[0054] The difference between this embodiment and Embodiment 1 is that in step (1), the amount of acetic anhydride added is 400g.
[0055] Example 3
[0056] The difference between this embodiment and Embodiment 1 is that in step (1), the amount of acetic anhydride added is 600g.
[0057] Example 4
[0058] The difference between this embodiment and Embodiment 1 is that in step (1), the esterification temperature is 142°C.
[0059] Example 5
[0060] The difference between this embodiment and Embodiment 1 is that in step (1), the esterification temperature is 100°C.
[0061] Example 6
[0062] The difference between this embodiment and Embodiment 1 is that in step (1), the esterification temperature is 160°C.
[0063] Example 7
[0064] The difference between this embodiment and Embodiment 1 is that in step (1), the esterification treatment time is 8 hours.
[0065] Example 8
[0066] The difference between this embodiment and embodiment 1 is that in step (2), the amount of anhydrous hydrogen fluoride added is 25g.
[0067] Example 9
[0068] The difference between this embodiment and embodiment 1 is that in step (2), the amount of anhydrous hydrogen fluoride added is 50g.
[0069] Example 10
[0070] The difference between this embodiment and embodiment 1 is that in step (2), the amount of anhydrous hydrogen fluoride added is 200g.
[0071] Example 11
[0072] The difference between this embodiment and embodiment 1 is that in step (2), the amount of o-dichlorobenzene pure solution added is 388g.
[0073] Example 12
[0074] The difference between this embodiment and embodiment 1 is that in step (2), the o-dichlorobenzene pure solution is cooled to -20°C.
[0075] Example 13
[0076] The difference between this embodiment and embodiment 1 is that in step (2), the o-dichlorobenzene pure solution is cooled to 0°C.
[0077] Example 14
[0078] The difference between this embodiment and embodiment 1 is that in step (2), the o-dichlorobenzene pure solution is cooled to 10°C.
[0079] Example 15
[0080] The difference between this embodiment and Embodiment 1 is that in step (3), the rearrangement reaction temperature is 80°C and the pressure is 1.5 MPa.
[0081] Example 16
[0082] The difference between this embodiment and Embodiment 1 is that in step (3), the rearrangement reaction temperature is 80°C and the pressure is 2MPa.
[0083] Example 17
[0084] The difference between this embodiment and Embodiment 1 is that in step (3), the rearrangement reaction temperature is 100°C.
[0085] Example 18
[0086] The difference between this embodiment and Embodiment 1 is that in step (3), the rearrangement reaction temperature is 120°C.
[0087] Comparative Example 1
[0088] The difference between this comparative example and Example 1 is that the rearrangement reaction temperature in step (3) is 25°C.
[0089] Comparative Example 2
[0090] The difference between this comparative example and Example 1 is that the rearrangement reaction temperature in step (3) is 60°C.
[0091] Comparative Example 3
[0092] The difference between this comparative example and Example 1 is that the pressure of the rearrangement reaction in step (3) is 0.5 MPa.
[0093] Comparative Example 4
[0094] The difference between this comparative example and Example 1 is that the rearrangement reaction temperature in step (3) is 145°C.
[0095] Comparative Example 5
[0096] The difference between this comparative example and Example 1 is that the pressure of the rearrangement reaction in step (3) is 0.2 MPa.
[0097] Test case
[0098] The crude p-hydroxyacetophenone obtained in the above embodiments and comparative examples was tested; the contents of p-hydroxyacetophenone and o-hydroxyacetophenone were detected by GC (gas chromatography detection), the contents of phenyl acetate in the reactants were measured by GC, and the conversion rate of phenyl acetate, the selectivity of p-hydroxyacetophenone and the selectivity of o-hydroxyacetophenone were calculated by comparison.
[0099] Conversion rate of phenyl acetate = Amount of phenyl acetate consumed after the reaction / Amount of phenyl acetate before the reaction.
[0100] The purity of phenyl acetate, the selectivity of p-hydroxyacetophenone, and the selectivity of o-hydroxyacetophenone can be obtained directly from GC (gas chromatography) data.
[0101] Phenol conversion rate = (mass of phenol consumed in the reaction / amount of phenol added) * 100%.
[0102] The test results are shown in Tables 1 and 2.
[0103] Test results
[0104] Table 1
[0105] Serial Number Phenol conversion rate (%) Purity (%) of phenyl acetate Example 1 93.99 97.27 Example 2 94.26 97.34 Example 3 98.13 98.28 Example 4 99.74 99.05 Example 5 70.61 83.68 Example 6 99.74 99.09 Example 7 99.49 99.16
[0106] Data Analysis: Examples 1-7 investigated the amount of raw material (acetic anhydride) and the temperature of esterification in the preparation of phenyl acetate. Among them, the phenol conversion rate and phenyl acetate purity of Example 5 were slightly lower, while the phenol conversion rate and phenyl acetate purity of Examples 1-4, 6, and 7 were higher. This indicates that the esterification temperature of 140-160℃ helps to improve the phenol conversion rate and phenyl acetate purity.
[0107] Table 2
[0108]
[0109]
[0110] Data Analysis:
[0111] Analysis of Examples 15-17 and Comparative Examples 1-3 showed that the conversion rate of phenyl acetate and the selectivity of p-hydroxyacetophenone in Examples 15-17 were significantly better than those in Comparative Examples 1-3. It can be seen that controlling the temperature of the rearrangement reaction at 80-140℃ and the pressure at 1-2MPa helps to improve the conversion rate of phenyl acetate and the selectivity of p-hydroxyacetophenone.
[0112] In Examples 8-10, as the amount of anhydrous hydrogen fluoride gradually increased, the conversion rate of phenyl acetate also gradually increased. In Example 10, the mass ratio of phenyl acetate to anhydrous hydrogen fluoride was 1:2, and the conversion rate of phenyl acetate and the selectivity of p-hydroxyacetophenone were both high. Therefore, a mass ratio of phenyl acetate to anhydrous hydrogen fluoride of 1:(1-2) helps to improve the conversion rate of phenyl acetate and the selectivity of p-hydroxyacetophenone.
[0113] Examples 11-14 investigated the preparation process of solutions containing anhydrous hydrogen fluoride, and the results of Examples 11-14 were similar to those of Example 1.
[0114] The rearrangement reaction in Comparative Example 4 was carried out at a temperature higher than 140°C. This temperature may be because it could easily lead to equipment leakage, incomplete reaction, and a decrease in conversion rate.
[0115] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.
Claims
1. A method for synthesizing p-hydroxyacetophenone, characterized in that, Includes the following steps: A rearrangement reaction is carried out by introducing a solution containing anhydrous hydrogen fluoride into a reaction vessel containing phenyl acetate. The rearrangement reaction is carried out at a temperature of 80-140°C and a pressure of 1-2 MPa to obtain crude p-hydroxyacetophenone.
2. The synthesis method according to claim 1, characterized in that, The reaction time for the rearrangement reaction is 2 to 3 hours.
3. The synthesis method according to claim 1 or 2, characterized in that, The water content of the phenyl acetate is not higher than 400 ppm.
4. The synthesis method according to any one of claims 1-3, characterized in that, The mass ratio of phenyl acetate to anhydrous hydrogen fluoride is 1:(1-2).
5. The synthesis method according to any one of claims 1-4, characterized in that, The solution containing anhydrous hydrogen fluoride also includes a polar solvent.
6. The synthesis method according to claim 5, characterized in that, The polar solvent includes o-dichlorobenzene; the mass ratio of the anhydrous hydrogen fluoride to the o-dichlorobenzene is 1:(0.97-7.79).
7. The synthesis method according to claim 6, characterized in that, The solution containing anhydrous hydrogen fluoride is prepared by the following steps: Anhydrous hydrogen fluoride was dissolved in pure o-dichlorobenzene solution at -20 to 10°C to obtain the solution containing anhydrous hydrogen fluoride.
8. The synthesis method according to any one of claims 1-7, characterized in that, Also includes: The crude p-hydroxyacetophenone was subjected to steam elution to obtain the p-hydroxyacetophenone product.
9. The synthesis method according to any one of claims 1-8, characterized in that, The phenyl acetate is prepared by the following steps: Phenol is heated and melted, then mixed with acetic anhydride, and subsequently subjected to esterification and condensation treatments to obtain phenyl acetate.
10. The synthesis method according to claim 9, characterized in that, The esterification treatment is performed at a temperature of 140–160°C for a time of 3–12 hours; and / or, The mass ratio of phenol to acetic anhydride is 1:(1-1.2).