4-butoxybenzene propenone as well as preparation method and application of 4-butoxybenzene propenone
Through the replacement response of hydroxyl phenylthoetone and sulfonic acid orthodoxyl ester and a complication of polyetal formaldehyde, a high-purity 4-butado oxygenone ketone was successfully prepared to solve the problem of degradation of hydrochloric acid hydrochloride. It improves the scientific nature of drug quality control and the safety of medication.
Patent Information
- Application Number
- CN202411485281.4
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-10-23
- Publication Date
- 2025-01-24
AI Technical Summary
Dacronin hydrochloride will degrade under long-term storage or high temperature conditions, resulting in the impurity 4-butoxystyrene, which affects the quality of the drug and may cause side effects. There is currently a lack of mature synthesis technology.
Use the replacement reaction under alkaline conditions to the hydroxytherazone and sulfonic acid, generate 4-butadoxyhylthoone intermediates, and then react with polyetal formaldehyde under the action of alkali or organic salt. Get 4-butadoxylthonone.
The preparation of the 4-butadoxyrene ketone with high purity and high revenue is achieved, which provides an impurities control product for the qualitative and quantitative analysis of the impurity hydrochloride and its preparation. Sexual and medicinal safety.
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Figure CN119350150A_ABST
Abstract
Description
Technical Field
[0001] The present application relates to the field of biomedicine technology, and in particular to 4-butoxyphenylpropenone and a preparation method and application thereof. Background Art
[0002] Dyclonine is a local anesthetic with rapid onset, long duration of action, few adverse reactions and high safety. The dosage forms of dyclonine hydrochloride that have been marketed or reported in China mainly include ointments, creams, liniments, solutions, gels and emulsion-type slurries. The main component of dyclonine is dyclonine hydrochloride, with the chemical name of 1-(4-butoxyphenyl)-3-(1-piperidinyl)-1-propanone hydrochloride, which is white or almost white crystals or crystalline powder, with the CAS number of 536-43-6 and the molecular formula as follows: Studies have found that dyclonine hydrochloride will degrade during long-term storage, especially under high temperature conditions, to produce the impurity 4-butoxyphenylpropenone, which will affect the quality of the drug and produce side effects. Therefore, in order to ensure that the impurity content of dyclonine hydrochloride can always be controlled within the specified range during the entire shelf life and meet relevant safety requirements, it is extremely important to strictly control the impurity content in dyclonine hydrochloride and the initial preparation products.
[0003] At present, regarding the impurity 4-butoxyphenylpropenone, there is only literature reporting that an intermediate 4-butoxyphenylpropenone is formed during the preparation of 4-butoxyphenyl-1-(3-chloropropyl)-1-one, but the literature does not separate and purify 4-butoxyphenylpropenone to obtain a pure product.
[0004] Therefore, there is currently no mature synthesis process for 4-butoxyphenylpropenone, so there is an urgent need to provide a simple and efficient synthesis method for 4-butoxyphenylpropenone, so as to obtain high-purity 4-butoxyphenylpropenone, so as to prepare impurity reference substances for qualitative and quantitative analysis of impurities in the production of dyclonine and its preparations, and to achieve quality evaluation and control of dyclonine drugs. Summary of the invention
[0005] In order to achieve qualitative and quantitative analysis of the impurity 4-butoxyphenylpropenone in dyclonine drugs, the present application provides 4-butoxyphenylpropenone and a preparation method and application thereof.
[0006] In the first aspect, the present application provides a method for preparing 4-butoxyphenylpropenone, using the following technical solution: A method for preparing 4-butoxyphenylpropenone comprises the following steps: (1) dissolving p-hydroxyacetophenone and n-butyl sulfonate in solvent I, adding an alkaline reagent, heating the mixture for reaction, and performing post-treatment to obtain a 4-butoxyacetophenone intermediate; the molar ratio of p-hydroxyacetophenone to n-butyl sulfonate is 1:(1-2); (2) Dissolving the 4-butoxyacetophenone intermediate and polyformaldehyde in solvent II, adding a catalyst, heating the reaction, and performing post-treatment to obtain 4-butoxyphenylpropenone; the molar ratio of the 4-butoxyacetophenone intermediate to the polyformaldehyde is 1:(1-5).
[0007] The present application provides a method for preparing 4-butoxyphenylpropenone. The preparation method has the advantages of simple operation, high yield and purity of 4-butoxyphenylpropenone, etc. The 4-butoxyphenylpropenone prepared by the method can be used as an impurity reference substance for qualitative and quantitative analysis of impurities in dyclonine hydrochloride raw materials and related preparations, so as to strengthen the quality control of dyclonine hydrochloride and related preparations, thereby improving the product quality of dyclonine hydrochloride and related preparations.
[0008] In the present application, by controlling the molar ratio of p-hydroxyacetophenone to n-butyl sulfonate in step (1) within the range of 1:(1-2), the yield of the obtained 4-butoxyacetophenone intermediate is above 87% and the purity is above 98%.
[0009] In the preparation method of 4-butoxyphenylpropenone provided in the present application, firstly, p-hydroxyacetophenone is used as a starting material, and a substitution reaction is carried out with n-butyl sulfonate under the action of a base to obtain a 4-butoxyacetophenone intermediate, and then a condensation reaction is carried out under the action of a base or an organic salt to generate 4-butoxyphenylpropenone. The synthetic route is as follows: p-Hydroxyacetophenone 4-butoxyacetophenone intermediate 4-butoxyphenylpropenone Optionally, the molar ratio of p-hydroxyacetophenone to n-butyl sulfonate is 1:(1-1.5); the molar ratio of the 4-butoxyacetophenone intermediate to paraformaldehyde is 1:(3-5).
[0010] In some embodiments, the molar ratio of parahydroxyacetophenone to n-butyl sulfonate can be 1:(1-1.2), 1:(1-1.5), 1:(1-1.8), 1:(1-2), 1:(1.2-1.5), 1:(1.2-1.8), 1:(1.2-2), 1:(1.5-1.8), 1:(1.5-2) or 1:(1.8-2).
[0011] In a specific embodiment, the molar ratio of p-hydroxyacetophenone to n-butyl sulfonate can also be 1:1, 1:1.2, 1:1.5, 1:1.8 or 1:2.
[0012] In some embodiments, the molar ratio of the 4-butoxyacetophenone intermediate to paraformaldehyde can be 1:(1-2), 1:(1-3), 1:(1-4), 1:(1-5), 1:(2-3), 1:(2-4), 1:(2-5), 1:(3-4), 1:(3-5) or 1:(4-5).
[0013] In a specific embodiment, the molar ratio of the 4-butoxyacetophenone intermediate to paraformaldehyde can also be 1:1, 1:2, 1:3, 1:4 or 1:5.
[0014] Optionally, the reaction temperature of step (1) is 50-100° C., and the reaction time with insulation and stirring is 5-10 h; the reaction temperature of step (2) is 60-100° C., and the reaction time with insulation and stirring is 5-10 h.
[0015] In some embodiments, the reaction temperature of step (1) can be 50-70°C, 50-80°C, 50-90°C, 50-100°C, 70-80°C, 70-90°C, 70-100°C, 80-90°C, 80-100°C or 90-100°C.
[0016] In a specific embodiment, the reaction temperature of step (1) can also be 50°C, 70°C, 80°C, 90°C or 100°C.
[0017] In some embodiments, the reaction temperature of step (2) can be 60-70°C, 60-80°C, 60-90°C, 60-100°C, 70-80°C, 70-90°C, 70-100°C, 80-90°C, 80-100°C or 90-100°C.
[0018] In a specific embodiment, the reaction temperature of step (2) can also be 60°C, 70°C, 80°C, 90°C or 100°C.
[0019] In some embodiments, the insulation time of step (2) can be 5-6h, 5-8h, 6-8h, 6-10h or 8-10h.
[0020] In a specific embodiment, the insulation time of step (2) can also be 5h, 6h, 8h or 10h.
[0021] Optionally, the solvent I is selected from one or more of 1,4-dioxane, N,N-dimethylformamide, acetonitrile and toluene; the solvent II is selected from one or more of 1,4-dioxane, tetrahydrofuran, toluene, acetonitrile, N,N-dimethylformamide and N-methylpyrrolidone.
[0022] Optionally, in step (1), the n-butyl sulfonate is n-butyl methanesulfonate or n-butyl p-toluenesulfonate; and the alkaline agent is selected from one or more of potassium carbonate, sodium carbonate, sodium hydroxide, sodium methoxide and potassium tert-butoxide.
[0023] Optionally, in step (2), the catalyst is selected from one or more of sodium hydroxide, potassium hydroxide, diisopropylamine trifluoroacetate, piperidine trifluoroacetate and morpholine trifluoroacetate.
[0024] Optionally, the post-treatment in step (2) comprises column chromatography, and the eluent used in the column chromatography is a mixture of n-hexane and ethyl acetate.
[0025] Optionally, the volume ratio of n-hexane to ethyl acetate is 30:1-5:1.
[0026] In some embodiments, the volume ratio of n-hexane to ethyl acetate can be 30:1-20:1, 30:1-15:1, 30:1-10:1, 30:1-5:1, 20:1-15:1, 20:1-10:1, 20:1-5:1, 15:1-10:1, 15:1-5:1 or 10:1-5:1.
[0027] In a specific embodiment, the volume ratio of n-hexane to ethyl acetate can also be 30:1, 20:1, 15:1, 10:1 or 5:1.
[0028] In a second aspect, the present application provides a 4-butoxyphenylpropenone, the structural formula of which is shown in Formula I:
[0029] In a third aspect, the present application provides an application of 4-butoxyphenylpropenone in the quality control of dyclonine hydrochloride and related preparations.
[0030] The 4-butoxyphenylpropenone prepared in the present application can be used as an impurity standard for the qualitative and quantitative analysis of impurities in dyclonine hydrochloride, and for scientifically evaluating the quality of dyclonine hydrochloride and its preparations, thereby improving the safety of dyclonine hydrochloride and its preparations.
[0031] In summary, this application has the following beneficial effects: 1. The present application uses hydroxyacetophenone as the starting material, and through a two-step reaction, a high-purity, high-yield 4-butoxyphenylpropenone is prepared. The 4-butoxyphenylpropenone prepared by the above-mentioned preparation method can be used as an impurity standard for the qualitative and quantitative analysis of impurities, and scientifically evaluates the quality of dyclonine hydrochloride and preparations, thereby improving the drug safety of dyclonine hydrochloride and preparations. In addition, the preparation method of 4-butoxyphenylpropenone provided in the present application also has the advantages of simple operation, mild reaction, short reaction route, low cost, etc., and can be industrialized.
[0032] 2. The present application further controls the molar ratio of p-hydroxyacetophenone to n-butyl sulfonate within the range of 1:(1-1.5), and the reaction temperature within the range of 70-90°C, and the yield of the obtained 4-butoxyacetophenone intermediate can reach more than 90.0%, and the purity reaches more than 99.00%.
[0033] 3. The present application further controls the molar ratio of the 4-butoxyacetophenone intermediate to polyformaldehyde in step (2) within the range of 1:(3-5), the reaction temperature within the range of 70-90°C, and the insulation time within the range of 5-8h. The yield and purity of the obtained 4-butoxyphenylacetophenone are higher, the yield can reach more than 88.0%, and the purity can reach more than 99.00%. BRIEF DESCRIPTION OF THE DRAWINGS
[0034] Figure 1 is the nuclear magnetic resonance spectrum of 4-butoxyphenylpropenone obtained in Example 5; Figure 2 This is a liquid chromatogram of 4-butoxyphenylpropenone obtained in Example 5. DETAILED DESCRIPTION
[0035] The present application provides a 4-butoxyphenylpropenone, and the preparation method thereof comprises the following steps: (1) dissolving p-hydroxyacetophenone and n-butyl sulfonate in solvent I, and adding an alkaline reagent; then heating to 50-100° C., stirring and reacting for 5-10 hours, monitoring by TLC (petroleum ether / ethyl acetate: 3 / 1), filtering to remove solids, concentrating the filtrate under reduced pressure, extracting with ethyl acetate, and drying over anhydrous sodium sulfate; and concentrating and drying the filtrate at 40-50° C. to obtain a 4-butoxyacetophenone intermediate.
[0036] Wherein, the molar ratio of p-hydroxyacetophenone to n-butyl sulfonate is 1:(1-2); the n-butyl sulfonate is n-butyl methanesulfonate or n-butyl p-toluenesulfonate; the alkaline agent is selected from one or more of potassium carbonate, sodium carbonate, sodium hydroxide, sodium methoxide and potassium tert-butoxide; the solvent I is selected from one or more of 1,4-dioxane, N,N-dimethylformamide, acetonitrile and toluene; (2) Dissolve the 4-butoxyacetophenone intermediate and polyformaldehyde in solvent II, and add a catalyst; then raise the temperature to 60-100° C., stir and react for 5-10 hours, monitor by TLC (n-hexane / ethyl acetate: 3 / 1), filter to remove salt, concentrate the filtrate under reduced pressure, dilute, filter to remove salt, concentrate the filtrate under reduced pressure, and perform column chromatography to obtain 4-butoxyacetophenone.
[0037] The molar ratio of the 4-butoxyacetophenone intermediate to the paraformaldehyde is 1:(1-5); the catalyst is selected from one or more of sodium hydroxide, potassium hydroxide, diisopropylamine trifluoroacetate, piperidine trifluoroacetate and morpholine trifluoroacetate; the solvent II is selected from one or more of 1,4-dioxane, tetrahydrofuran, toluene, acetonitrile, N,N-dimethylformamide and N-methylpyrrolidone. The eluent used in the column chromatography is a mixture of n-hexane and ethyl acetate, and the volume ratio of n-hexane to ethyl acetate is 30:1-5:1.
[0038] In the examples of the present application, the CAS number of p-hydroxyacetophenone is 99-93-4; the CAS number of n-butyl methanesulfonate is 1912-32-9; the CAS number of n-butyl p-toluenesulfonate is 778-28-9; the CAS number of paraformaldehyde is 30525-89-4; the CAS number of piperidine trifluoroacetate is 107326-30-7; the remaining raw materials, reagents, solvents, etc. of the present application can also be obtained commercially.
[0039] The present application is further described in detail below in combination with preparation examples, embodiments and detection experiments.
[0040] Preparation Example 1-5 Preparation Examples 1-5 respectively synthesize a 4-butoxyacetophenone.
[0041] The difference between the above preparation examples is that the molar ratio of p-hydroxyacetophenone to n-butyl sulfonate is shown in Table 1 below.
[0042] The preparation method of 4-butoxyacetophenone of Preparation Example 1-5 comprises the following steps: Dissolve p-hydroxyacetophenone and n-butyl methanesulfonate in acetonitrile (25 mL), add potassium carbonate (6.16 g, 44.56 mmol); after the addition is completed, heat to 80°C, keep warm and stir to react for 6 hours; monitor the reaction by TLC (petroleum ether / ethyl acetate: 3 / 1); after the reaction is completed, filter out the solid, concentrate the filtrate under reduced pressure, add ethyl acetate (100 mL), wash with purified water (50 mL×3), dry with sodium sulfate, filter out the sodium sulfate, and concentrate the filtrate under reduced pressure at 45°C to obtain 4-butoxyacetophenone.
[0043] The yield, yield and purity of 4-butoxyacetophenone obtained in Preparation Example 1-5 are shown in Table 1.
[0044] Table 1 The molar ratio of p-hydroxyacetophenone to n-butyl methanesulfonate and the detection results of 4-butoxyacetophenone Preparation Example 6 Preparation Example 6 Synthesis of 4-butoxyacetophenone
[0045] The difference between the above Preparation Example and Preparation Example 2 is that n-butyl methanesulfonate is replaced by n-butyl p-toluenesulfonate (9.92 g, 43.47 mmol).
[0046] The yield of 4-butoxyacetophenone obtained in Preparation Example 6 was 6.0 g, the yield was 84.99%, and the purity was 99.02%.
[0047] Preparation Example 7 Preparation Example 7 Synthesis of 4-butoxyacetophenone.
[0048] The above Preparation Example is different from Preparation Example 2 in that acetonitrile is replaced by N,N-dimethylformamide, and potassium carbonate is replaced by potassium tert-butoxide (5.00 g, 44.56 mmol).
[0049] The yield of 4-butoxyacetophenone obtained in Preparation Example 7 was 6.3 g, the yield was 89.24%, and the purity was 99.21%.
[0050] Preparation Example 8-11 Preparation Example 7 Synthesis of 4-butoxyacetophenone.
[0051] The difference between the above preparation example and preparation example 2 is: reaction temperature, as shown in Table 2 below.
[0052] Table 2 Reaction temperature in Preparation Examples 8-11 and detection results of 4-butoxyacetophenone Preparation Example Reaction temperature (℃) Yield (%) purity(%) 2 80 92.6 99.45 8 50 87.3 98.24 9 70 90.1 99.11 10 90 91.7 99.27 11 100 89.5 98.58 Examples 1-5 Examples 1-5 synthesize a 4-butoxyphenylpropenone respectively.
[0053] The difference between the above embodiments is that the molar ratio of 4-butoxyacetophenone to paraformaldehyde is shown in Table 3 below.
[0054] The preparation method of 4-butoxyphenylpropenone of Example 1-5 comprises the following steps: (1) According to the method provided in Preparation Example 2, a 6-fold scale-up test was performed to synthesize 4-butoxyacetophenone (yield 93.4%, purity 99.47%); (2) Dissolve 4-butoxyacetophenone and paraformaldehyde in dioxane (5 mL), add piperidine trifluoroacetate (112 mg, 0.56 mmol); after the addition, heat to 80°C, keep warm and stir for 6 hours. Monitor the reaction by TLC (n-hexane / ethyl acetate: 3 / 1). After the reaction is completed, filter to remove the solid, concentrate the filtrate under reduced pressure, dilute with methyl tert-butyl ether (30 mL), filter to remove the salt, concentrate the filtrate under reduced pressure, dilute with methyl tert-butyl ether (30 mL), filter to remove the salt, concentrate the filtrate under reduced pressure, and use n-hexane / ethyl acetate (15:1) for column chromatography to obtain 4-butoxyphenylpropenone.
[0055] Table 3 Addition amount and molar ratio of 4-butoxyacetophenone and paraformaldehyde in Examples 1-5 Examples 6-12 Examples 6-12 respectively synthesize a 4-butoxyphenylpropenone.
[0056] The difference between the above embodiment and embodiment 5 is that the reaction temperature and the insulation time in step (2) are specifically shown in Table 4 below.
[0057] Table 4 Reaction temperature and insulation time in step (2) of Example 5 and Example 6-12 Examples 13-16 Examples 13-16 respectively synthesize a 4-butoxyphenylpropenone.
[0058] The difference between the above embodiment and embodiment 5 is that the ratio of the eluent used in column chromatography is shown in Table 5 below.
[0059] Table 5 Ratios of eluents used in column chromatography in step (2) of Example 5 and Examples 13-16 Example Volume ratio of hexane to ethyl acetate 5 15：1 13 5：1 14 10：1 15 20：1 16 30：1 Performance testing (1) The nuclear magnetic resonance (NMR) spectrum of 4-butoxyphenylpropenone obtained in Example 5 was measured using a 400 MHz nuclear magnetic resonance spectrometer. The spectrum is as follows: Figure 1 The specific results are as follows: MS (ESI) [M + H] +=205; HNMR (400MHz, CD3Cl, ppm) δ7.94-7.96(m, 2H), 7.14-7.27(m, 1H), 6.94(d, J=0.9Hz, 2H), 6.39-6.45(m , 1H), 5.84-5.88 (m, 1H), 4.03 (t, J=6.5Hz, 2H), 1.76-1.83 (m, 2H), 1.46-1.55 (m, 2H), 0.98 (t, J=7.4Hz, 3H).
[0060] (2) 4-butoxyphenylpropenone was prepared according to the method provided in Example 1-16, the yield of 4-butoxyphenylpropenone was calculated (second step), and the purity of 4-butoxyphenylpropenone was detected by high performance liquid chromatography. The results are shown in Table 6 below.
[0061] The liquid chromatography test results of 4-butoxyphenylpropenone obtained in Example 5 are as follows: Figure 2 As shown by Figure 2 It can be seen that the purity of 4-butoxyphenylpropenone obtained in Example 5 is 99.19%.
[0062] Table 6 Yield and purity of 4-butoxyphenylpropenone obtained in Examples 1-16 According to the test results in Table 6, the yield of 4-butoxyphenylpropenone obtained by the preparation method provided in Examples 1-16 is 86.8-91.2%, and the purity is 98.24-99.22%. Therefore, it is shown that the preparation method of 4-butoxyphenylpropenone provided in Examples 1-16 of the present application can obtain 4-butoxyphenylpropenone with high yield and high purity.
[0063] The test results of Examples 1-5 show that with the increase in the amount of paraformaldehyde added, the yield of the obtained 4-butoxyphenylpropenone shows a trend of gradually increasing, while the purity shows a trend of first increasing and then decreasing; further comparison shows that the yield of 4-butoxyphenylpropenone obtained in Examples 3-5 is 88.7-90.4% (≥88.0%), and the purity is 99.08-99.22% (≥99.00%). Therefore, it is explained that the present application further controls the molar ratio of 4-butoxyphenylacetophenone and paraformaldehyde in the preparation method within the range of 1: (3-5), and the yield and purity of the obtained 4-butoxyphenylpropenone are higher.
[0064] The test results of Example 5 and Example 6-12 show that the yield of 4-butoxyphenylpropenone obtained in Example 6, Example 9, and Example 12 is 86.8-87.5%, and the purity is 98.24-98.96%; while the yield of 4-butoxyphenylpropenone obtained in Example 5, Example 7-8, and Example 10-11 is 88.6-90.4% (≥88.0%), and the purity is 99.04-99.19% (≥99.00%). Therefore, it is explained that the present application further controls the reaction temperature in step (2) of the preparation method to 70-90°C, and the insulation time to 5-8h, and the yield and purity of the obtained 4-butoxyphenylpropenone are higher.
[0065] The test results of Example 5 and Examples 13-16 show that the ratio of the eluent will affect the yield and purity of 4-butoxyphenylpropenone. As the content of n-hexane in the eluent increases, the yield of 4-butoxyphenylpropenone gradually decreases, while the purity gradually increases and then remains basically unchanged; among them, the purity of 4-butoxyphenylpropenone obtained in Example 13 is only 98.31%; the yield of 4-butoxyphenylpropenone obtained in Example 16 is only 88.4%; and the yield of 4-butoxyphenylpropenone obtained in Examples 5 and Examples 14-15 is 90.0-90.8% (≥90.0%), and the purity is 99.03-99.20% (≥99.00%). Therefore, it is explained that in step (2) of the preparation method of the present application, n-hexane and ethyl acetate with a volume ratio of 10:1-20:1 are further used as eluents, and the yield and purity of the obtained 4-butoxyphenylpropenone are higher.
[0066] Although the present invention has been described in detail above with general descriptions and specific embodiments, it is obvious to those skilled in the art that some modifications or improvements may be made thereto based on the present invention. Therefore, these modifications or improvements made without departing from the spirit of the present invention all fall within the scope of protection claimed by the present invention.
Claims
1. A method for preparing 4-butoxyphenylpropenone, characterized in that: The following steps are involved: (1) dissolving p-hydroxyacetophenone and n-butyl sulfonate in solvent I, adding an alkaline reagent, heating the mixture for reaction, and performing post-treatment to obtain a 4-butoxyacetophenone intermediate; the molar ratio of p-hydroxyacetophenone to n-butyl sulfonate is 1:(1-2); (2) Dissolving the 4-butoxyacetophenone intermediate and polyformaldehyde in solvent II, adding a catalyst, heating the reaction, and performing post-treatment to obtain 4-butoxyphenylpropenone; the molar ratio of the 4-butoxyacetophenone intermediate to the polyformaldehyde is 1:(1-5).
2. The method for preparing 4-butoxyphenylpropenone according to claim 1, characterized in that: The molar ratio of p-hydroxyacetophenone to n-butyl sulfonate is 1:(1-1.5); the molar ratio of 4-butoxyacetophenone intermediate to paraformaldehyde is 1:(3-5).
3. The method for preparing 4-butoxyphenylpropenone according to claim 1, characterized in that: The reaction temperature of step (1) is 50-100° C., and the reaction time with heat preservation and stirring is 5-10 hours; the reaction temperature of step (2) is 60-100° C., and the reaction time with heat preservation and stirring is 5-10 hours.
4. The method for preparing 4-butoxyphenylpropenone according to claim 1, characterized in that: The solvent I is selected from one or more of 1,4-dioxane, N,N-dimethylformamide, acetonitrile and toluene; the solvent II is selected from one or more of 1,4-dioxane, tetrahydrofuran, toluene, acetonitrile, N,N-dimethylformamide and N-methylpyrrolidone.
5. The method for preparing 4-butoxyphenylpropenone according to claim 1, characterized in that: In the step (1), the n-butyl sulfonate is n-butyl methanesulfonate or n-butyl p-toluenesulfonate; and the alkaline agent is selected from one or more of potassium carbonate, sodium carbonate, sodium hydroxide, sodium methoxide and potassium tert-butoxide.
6. The method for preparing 4-butoxyphenylpropenone according to claim 1, characterized in that: In the step (2), the catalyst is selected from one or more of sodium hydroxide, potassium hydroxide, diisopropylamine trifluoroacetate, piperidine trifluoroacetate and morpholine trifluoroacetate.
7. The method for preparing 4-butoxyphenylpropenone according to any one of claims 1 to 6, characterized in that: The post-treatment in step (2) includes column chromatography, and the eluent used in the column chromatography is a mixture of n-hexane and ethyl acetate.
8. The method for preparing 4-butoxyphenylpropenone according to claim 7, characterized in that: The volume ratio of n-hexane to ethyl acetate is 30:1-5:
1.
9. 4-Butoxyphenylpropenone obtained by the preparation method of 4-butoxyphenylpropenone according to any one of claims 1 to 8, characterized in that: The structural formula of the 4-butoxyphenylpropenone is shown in Formula I:
10. Use of 4-butoxyphenylpropenone obtained by the preparation method of 4-butoxyphenylpropenone according to any one of claims 1 to 8 and 4-butoxyphenylpropenone according to claim 9 in the quality control of dyclonine hydrochloride and related preparations.