Preparation method of ethyl p-methoxycinnamate
The method for synthesizing ethyl acetate using a sodium ethoxide catalyst simplifies the synthesis steps of ethyl p-methoxycinnamate, improves the yield and purity, solves the problems of high cost and environmental pollution in the prior art, and is suitable for industrial production.
Patent Information
- Application Number
- CN202510985523.4
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-07-17
- Publication Date
- 2025-10-21
AI Technical Summary
The prior art synthesis of ethyl p-methoxycinnamate involves many steps, takes a long time, and is costly. Furthermore, the catalysts used are toxic or pollute the environment, making it difficult to achieve efficient and low-cost synthesis.
Ethyl p-methoxycinnamate was synthesized in a one-pot process using sodium ethoxide as a catalyst and ethyl acetate and p-methoxybenzaldehyde as raw materials. The process was simplified and the yield was improved by dropwise addition at low temperature and reaction at medium temperature, combined with water extraction and ethanol crystallization.
The yield of ethyl p-methoxycinnamate is as high as over 90%, the purity can reach over 99.0%, and the reaction time is as short as 3-6 hours, which reduces process costs and environmental pollution and is suitable for industrial production.
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Figure CN120817855A_ABST
Abstract
Description
Technical Field
[0001] The invention relates to the technical field of chemical synthesis, and in particular to a method for preparing ethyl p-methoxycinnamate. Background Art
[0002] Ethyl p-methoxycinnamate can be extracted from the traditional Chinese medicine Kaempferia galanga. It has strong absorption of UV rays in the 280-320nm range, is non-irritating to the skin, and has minimal skin absorption, avoiding toxic side effects. It is an ideal sunscreen and is widely used in sunscreen products. It also has antibacterial activity and is used in antiseptic applications. It also has pharmacological activity, and many studies have shown significant inhibitory activity against tumor cells.
[0003] The most common preparation method is chemical synthesis. Jin Jishu's method is conventional, using p-methoxycinnamaldehyde as the raw material and pyridine as the catalyst to react with malonic acid in a Knoevenagel reaction to synthesize the intermediate p-methoxycinnamic acid. The intermediate then undergoes an esterification reaction with ethanol using sulfuric acid as a catalyst to synthesize ethyl p-methoxycinnamate. Zhang Hong et al. improved the toxic and environmentally polluting catalyst by replacing pyridine with ammonium acetate and sulfuric acid with p-toluenesulfonic acid. However, the problems of multiple reaction steps, low yield, and high price of malonic acid still exist. Zeng Qingyou et al. used a one-pot method to synthesize ethyl p-methoxycinnamate, which reduced the number of reaction steps but required large amounts of salt and catalyst, a long process time, and high cost. Zhang Chao et al. used p-methoxycinnamic acid and diethyl malonate as raw materials to synthesize ethyl p-methoxycinnamate in a one-pot method. This greatly simplified the reaction steps, but the catalyst KF / γAl2O3 was cumbersome to prepare and required large amounts. Although it can be recycled, its efficiency decreases after several uses, resulting in a relatively high overall cost.
[0004] How to synthesize ethyl p-methoxycinnamate through fewer steps and in a shorter time is a technical problem that needs to be solved in the prior art. Summary of the Invention
[0005] The purpose of the present invention is to overcome the above technical deficiencies, provide a method for preparing ethyl p-methoxycinnamate, and solve the technical problem of how to synthesize ethyl p-methoxycinnamate in a shorter time through fewer steps in the prior art.
[0006] To achieve the above technical objectives, the technical solution of the present invention provides a method for preparing ethyl p-methoxycinnamate, comprising the following steps: mixing ethyl acetate and an ethanol solution of sodium ethoxide, then dropwise adding p-methoxybenzaldehyde at 5-10°C, and then reacting at 30-50°C to obtain the ethyl p-methoxycinnamate.
[0007] In any embodiment, the ethyl acetate and the ethanol solution of sodium ethoxide are mixed at 2-10°C.
[0008] In any embodiment, the mass concentration of sodium ethoxide in the ethanol solution of sodium ethoxide is 30-35%.
[0009] In any embodiment, the reaction time at 30-50° C. is 3-6 hours.
[0010] In any embodiment, the molar ratio of sodium ethoxide to p-anisaldehyde in the ethanol solution of sodium ethoxide is (0.3-1.5):1.
[0011] In any embodiment, the molar ratio of ethanol to p-anisaldehyde in the ethanol solution of sodium ethoxide is (1-1.5):1 In any embodiment, the molar ratio of the ethyl acetate to the p-anisaldehyde is (2-5):1.
[0012] In any embodiment, after the reaction at 30-50° C., the method further comprises: further extracting with water to quench the reaction and washing the sodium ethoxide, then separating the layers and removing the aqueous phase, evaporating the p-anisaldehyde in the organic phase, and crystallizing the product with ethanol.
[0013] In any embodiment, the ethyl p-methoxycinnamate is obtained by reacting at 40° C. for 4 hours.
[0014] In any embodiment, the molar ratio of p-anisaldehyde, ethyl acetate and sodium ethoxide in the ethanol solution of sodium ethoxide is 1:3:1.2.
[0015] Compared with the prior art, the present invention has the following beneficial effects: the preparation method of ethyl p-methoxycinnamate proposed by the present invention comprises the following steps: mixing ethyl acetate and an ethanol solution of sodium ethoxide as a catalyst, then dropwise adding p-methoxybenzaldehyde at 5-10° C., and then reacting at 30-50° C. to obtain the ethyl p-methoxycinnamate, wherein the yield of ethyl p-methoxycinnamate can be as high as over 90%, the purity can reach over 99.0%, and the reaction time is as short as 3-6 hours. The synthetic process route is simpler than the traditional process, the raw materials used are simple and easily available, and the environmental pollution is small. The unreacted raw materials p-methoxybenzaldehyde and ethyl acetate can be recycled and reused, no high-temperature reaction is required, energy consumption is reduced, the overall process cost is low, and the method is suitable for industrial production. BRIEF DESCRIPTION OF THE DRAWINGS
[0016] Figure 1 The HPLC spectrum of ethyl p-methoxycinnamate prepared in Example 1 of the present invention is shown.
[0017] Figure 2 This is a photograph of ethyl p-methoxycinnamate obtained by the third repetition of the experiment in Example 4 of the present invention.
[0018] Figure 3This is the HPLC spectrum of ethyl p-methoxycinnamate obtained by repeating the experiment for the third time in Example 4 of the present invention. DETAILED DESCRIPTION
[0019] The "range" disclosed in this application is defined in the form of a lower limit and an upper limit. A given range is defined by selecting a lower limit and an upper limit, and the selected lower limit and upper limit define the boundaries of a particular range. The range defined in this way can be inclusive or exclusive of the end values, and can be arbitrarily combined, i.e., any lower limit can be combined with any upper limit to form a range. For example, if a range of 60 to 120 and 80 to 110 is listed for a particular parameter, it is understood that a range of 60 to 110 and 80 to 120 is also expected. In addition, if the minimum range values listed are 1 and 2, and if the maximum range values listed are 3, 4, and 5, then the following ranges can all be expected: 1 to 3, 1 to 4, 1 to 5, 2 to 3, 2 to 4, and 2 to 5. In this application, unless otherwise specified, the numerical range "a to b" represents an abbreviation of any real number combination between a and b, wherein a and b are both real numbers. For example, a numerical range of "0-5" indicates that all real numbers between "0-5" are listed herein, and "0-5" is simply an abbreviation for these numerical combinations. Furthermore, stating that a parameter is an integer ≥ 2 is equivalent to disclosing that the parameter is, for example, an integer of 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, etc.
[0020] Unless otherwise specified, the terms "include" and "comprising" used in this application may be open-ended or closed-ended. For example, "include" and "comprising" may mean that other components not listed may also be included or that only the listed components are included.
[0021] Unless otherwise specified, the term "or" is used in this application to be inclusive. For example, the phrase "A or B" means "A, B, or both A and B." More specifically, the condition "A or B" is satisfied if any of the following conditions are met: A is true (or exists) and B is false (or does not exist); A is false (or does not exist) and B is true (or exists); or both A and B are true (or exist).
[0022] This specific embodiment provides a preparation method of ethyl p-methoxycinnamate, comprising the following steps: mixing ethyl acetate and an ethanol solution of sodium ethoxide at 2-10° C., then dropwise adding p-methoxybenzaldehyde at 5-10° C., then reacting at 30-50° C. for 3-6 hours, then further extracting with water to quench the reaction and washing the sodium ethoxide, then standing and stratifying to remove the aqueous phase, evaporating the p-methoxybenzaldehyde in the organic phase, crystallizing the product with ethanol, centrifuging and vacuum drying to obtain off-white solid ethyl p-methoxycinnamate; the mass concentration of sodium ethoxide in the ethanol solution of sodium ethoxide is 30-35%.
[0023] In some embodiments, the molar ratio of sodium ethoxide to p-anisaldehyde in the ethanol solution of sodium ethoxide is (0.3-1.5):1; in some embodiments, the molar ratio of ethanol to p-anisaldehyde in the ethanol solution of sodium ethoxide is preferably (1-1.5):1.
[0024] In some embodiments, the molar ratio of the ethyl acetate to the p-anisaldehyde is (2-5):1.
[0025] In some embodiments, the reaction is carried out at 40° C. for 4 hours to obtain the ethyl p-methoxycinnamate.
[0026] In some embodiments, the molar ratio of p-anisaldehyde, ethyl acetate, and sodium ethoxide in the ethanol solution of sodium ethoxide is 1:3:1.2.
[0027] To reduce production costs while maintaining safety and environmental protection, the present invention improves upon existing synthesis methods, synthesizing ethyl p-methoxycinnamate in a one-pot process using p-anisaldehyde and ethyl acetate as raw materials and sodium ethoxide as a catalyst. The materials used are inexpensive and readily available, and the process is environmentally friendly. The synthesis route of the present invention is as follows: In order to make the purpose, technical solutions and advantages of the present invention more clearly understood, the present invention will be further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the present invention.
[0028] In the present invention, references to “some embodiments”, “this embodiment”, examples, etc. describe a subset of all possible embodiments, but it can be understood that “some embodiments” may be the same subset or different subsets of all possible embodiments, and may be combined with each other without conflict.
[0029] If similar descriptions of "first / second" appear in the application documents, the following explanation is added. In the following description, the terms "first\second\third" are merely used to distinguish similar objects and do not represent a specific order for the objects. It is understandable that "first\second\third" can be interchanged with the specific order or sequence where permitted, so that the embodiments described herein can be implemented in an order other than that illustrated or described herein.
[0030] In this embodiment, the term "and / or" is merely a description of the association relationship between associated objects, indicating that three relationships may exist. For example, object A and / or object B may represent three situations: object A exists alone, object A and object B exist at the same time, and object B exists alone.
[0031] Below, the embodiment of the present application is described. The embodiment described below is exemplary and is only used to explain the present application, and is not to be construed as limiting the present application. Where specific techniques or conditions are not specified in the embodiments, the techniques or conditions described in the literature in this area or the product specifications are used. Reagents or instruments used that do not specify the manufacturer are conventional products that can be obtained commercially.
[0032] Reagents: p-anisaldehyde, ethyl acetate, sodium ethoxide, ethanol.
[0033] Instruments: Shanghai Lichen thermal constant temperature heating magnetic stirrer, electronic balance, refrigerator, melting point tester, vacuum oven, Agilent 1200 high performance liquid chromatograph, Fourier transform infrared spectrometer.
[0034] Example 1 This embodiment provides a preparation method of ethyl p-methoxycinnamate, comprising the following steps: adding 58 g of ethyl acetate to a three-necked reaction flask, maintaining moderate stirring, slowly adding 95 g of a 30% sodium ethoxide ethanol solution at 5° C. and mixing, then dropwise adding 30 g of p-methoxybenzaldehyde at 10° C., reacting at 45° C. for 4 hours after the dropwise addition is complete, then further extracting with water to quench the reaction and washing the sodium ethoxide, then allowing the mixture to stand for stratification and removing the aqueous phase, evaporating the p-methoxybenzaldehyde in the organic phase, crystallizing the product with ethanol, centrifuging, and vacuum drying to obtain ethyl p-methoxycinnamate as an off-white solid.
[0035] The melting point of the detected ethyl p-methoxycinnamate was 49.5°C, and high performance liquid chromatography analysis showed that the mass fraction of the target substance was 99.38%.
[0036] Example 2 The preparation method of ethyl p-methoxycinnamate in this example differs from that in Example 1 in that the molar ratio of sodium ethoxide to p-methoxybenzaldehyde is changed. The molar ratios of sodium ethoxide to p-methoxybenzaldehyde are 0.3:1, 0.6:1, 0.9:1, 1.2:1, and 1.5:1, respectively. Other reaction conditions and steps are the same as those in Example 1. The recovery rates are shown in Table 1.
[0037] Table 1: the impact of the consumption of sodium ethoxide on ethyl methoxycinnamate yield As can be seen from Table 1, the yield tends to increase with the increase in the amount of catalyst sodium ethoxide used, but it almost stops increasing when the ratio reaches 1.2:1.
[0038] Example 3 The preparation method of ethyl p-methoxycinnamate in this example differs from that in Example 1 in that the molar ratio of sodium ethoxide to p-anisaldehyde is 1:1, the reaction time at 45° C. is 5 h, the molar ratios of p-anisaldehyde to ethyl acetate are 2:1, 3:1, 4:1, and 5:1, respectively. Other reaction conditions and steps are the same as those in Example 1. The yields are shown in Table 2.
[0039] Table 2: the impact of the consumption of ethyl acetate on yield As can be seen from Table 2, when the molar ratio of p-anisaldehyde to ethyl acetate is 3:1, it has the best cost advantage.
[0040] Example 4 This embodiment provides a preparation method of ethyl p-methoxycinnamate, comprising the following steps: adding ethyl acetate to a three-necked reaction flask, maintaining moderate stirring, slowly adding an ethanol solution of sodium ethoxide having a mass concentration of 30% at 5° C. and mixing, then dropwise adding 30 g of p-methoxybenzaldehyde at 10° C., reacting at 40° C. for 4 hours after the dropwise addition is complete, wherein the molar ratio of p-methoxybenzaldehyde, ethyl acetate, and sodium ethoxide is 1:3:1.2, then further extracting with water to quench the reaction and washing the sodium ethoxide, then standing to separate and removing the aqueous phase, evaporating the p-methoxybenzaldehyde in the organic phase, crystallizing the product with ethanol, centrifuging, and vacuum drying to obtain ethyl p-methoxycinnamate as an off-white solid.
[0041] The experiment was repeated 5 times, and the experimental results are shown in Figure 3.
[0042] Table 3 As can be seen from Table 3, the yield of the five repeated experiments was stable and reproducible, with an average yield of 91.3%. Figure 2 and Figure 3 It can be seen that the prepared ethyl p-methoxycinnamate is a white solid with a purity of up to 99.8%.
[0043] The present invention uses sodium ethoxide as a catalyst and p-methoxybenzaldehyde and ethyl acetate as reaction raw materials to synthesize ethyl p-methoxycinnamate in a one-pot method. The preferred reaction conditions are: the material ratio n (p-methoxybenzaldehyde): n (ethyl acetate): n (sodium ethoxide) = 1:3:1.2, the sodium ethoxide and p-methoxybenzaldehyde are added at a low temperature, the reaction temperature is 40°C, the reaction time is 4 hours, the reaction yield can reach more than 90%, and the purity can reach more than 99.0%.
[0044] The synthetic process is simpler than the traditional process, the raw materials used are simple and easily available, and the environmental pollution is less. The unreacted raw materials p-anisaldehyde and ethyl acetate can be recycled and reused. There is no high-temperature reaction, which reduces energy consumption, has a low overall process cost, and is suitable for industrial production.
[0045] The specific embodiments of the present invention described above do not limit the scope of protection of the present invention. Any other corresponding changes and modifications made based on the technical concept of the present invention should be included in the scope of protection of the claims of the present invention.
Claims
1. A method for preparing ethyl p-methoxycinnamate, characterized in that: The method comprises the following steps: mixing ethyl acetate and an ethanol solution of sodium ethoxide, then dropwise adding p-methoxybenzaldehyde at 5-10 DEG C, and then reacting at 30-50 DEG C to obtain the p-methoxycinnamic acid ethyl ester.
2. The preparation method of ethyl p-methoxycinnamate according to claim 1, wherein The ethyl acetate and the ethanol solution of sodium ethoxide are mixed at 5-10°C.
3. The preparation method of ethyl p-methoxycinnamate according to claim 1, wherein The mass concentration of sodium ethoxide in the sodium ethoxide ethanol solution is 30-35%.
4. The preparation method of ethyl p-methoxycinnamate according to claim 1, wherein The reaction time is 3-6 hours at 30-50°C.
5. The preparation method of ethyl p-methoxycinnamate according to claim 1, wherein The molar ratio of sodium ethoxide to p-anisaldehyde in the sodium ethoxide ethanol solution is (0.3-1.5):
1.
6. The preparation method of ethyl p-methoxycinnamate according to claim 5, wherein The molar ratio of ethanol to p-anisaldehyde in the ethanol solution of sodium ethoxide is (1-1.5):1 The method for preparing ethyl p-methoxycinnamate according to claim 1, wherein the molar ratio of the ethyl acetate to the p-methoxybenzaldehyde is (2-5):
1.
7. The preparation method of ethyl p-methoxycinnamate according to claim 1, wherein After the reaction is carried out at 30-50° C., the method further comprises: further extracting with water to quench the reaction and washing the sodium ethoxide, then separating and removing the aqueous phase, evaporating the p-anisaldehyde in the organic phase, and using ethanol to crystallize the product.
8. The preparation method of ethyl p-methoxycinnamate according to claim 1, wherein The reaction was carried out at 40° C. for 4 hours to obtain the ethyl p-methoxycinnamate.
9. The method for preparing ethyl p-methoxycinnamate according to claim 1, wherein The molar ratio of p-anisaldehyde, ethyl acetate and sodium ethoxide in the ethanol solution of sodium ethoxide is 1:3:1.2.