Method for synthesizing anise camphor

Abstract

The invention discloses an anethole synthesis method, and relates to the technical field of fine chemical engineering, and the anethole synthesis method comprises the following steps: 1, taking 4-n-propyl anisole as an initial raw material, and oxidizing the reaction by using air under a solvent-free condition to obtain p-methoxypropiophenone; 2, reducing the p-methoxypropiophenone into 1-(4-methoxyphenyl)-1-propanol by taking aluminum isopropoxide as a catalyst and isopropanol as a reducing agent; and 3, by taking concentrated sulfuric acid as a dehydrating agent, removing hydroxyl of the 1-(4-methoxyphenyl)-1-propanol to obtain anethole. The method has the beneficial effects that air is used for oxidation in the first step, no solvent is used, reaction conditions are simple, post-treatment is convenient, and the reaction conversion rate is high; in the second step, Meerwein-Ponndorf-Verley reduction reaction is used for the first time, dangerous processes such as hydrogenation reduction or hydroboration reduction are avoided, reaction conditions are mild, aftertreatment is simple, and the reaction conversion rate is high.

Description

Technical Field

[0001] This invention relates to the field of fine chemical technology, and in particular to a method for synthesizing anethole. Background Technology

[0002] Anethole, also known as anethole, is chemically named 1-methoxy-4-(1-propenyl)-benzene. It is widely used in the food, daily chemical, and pharmaceutical industries.

[0003] Natural anethole is mainly extracted by distillation from natural fennel oil, cumin oil, and star anise oil. Large-scale industrial synthesis of anethole is obtained by reacting anethole (methoxybenzene) with propionic acid derivatives or propionaldehyde.

[0004] The German company H&R used anisole to condense with propionaldehyde under an acid catalyst, followed by hydrolysis at 100°C–300°C to obtain anethole. This method has poor selectivity and produces a considerable amount of ortho-anethole (US4026951, 1975).

[0005] Huai'an Wanbang Fragrance Company uses anisole and propionyl chloride as starting materials, which undergo Friedel-Crafts acylation, followed by reduction with sodium borohydride, acid-catalyzed dehydration, and finally distillation to obtain the finished product, anethole. This route generates a significant amount of waste, and the use of sodium borohydride releases hydrogen gas, making the reaction hazardous (CN103058835, 2013).

[0006] BASF uses p-propyl anisole to prepare anethole under acidic conditions via thermal decomposition. This method uses a tubular reactor with reaction temperatures ranging from 320°C to 550°C, resulting in harsh reaction conditions and low yields (CN106103398, 2016).

[0007] Suqian Kesi uses acidic alumina to dehydrate methoxyphenylpropanol to produce anethole at 100℃~150℃. However, the raw material cannot be obtained from large-scale chemical raw materials and needs to be synthesized (CN108440257, 2018).

[0008] Another literature report (JOC, 2006, 71, 1480-1492) describes reacting p-methoxybenzaldehyde with an ethyl Grignard reagent, followed by heating and dehydration to obtain anethole. However, this method has a low yield, approximately 50%.

[0009] As can be seen from the above literature, the current methods for synthesizing anethole have disadvantages such as complex reactions, harsh reaction conditions, low product yield, expensive raw materials, special reaction equipment, and high industrial production costs. Summary of the Invention

[0010] To address the shortcomings of existing technologies, this invention provides a method for synthesizing anethole, which features simple and mild reaction conditions, straightforward post-processing, and high yield.

[0011] In order to achieve the objective of this invention, the following solution is proposed: A method for synthesizing anethole includes the following steps: Step 1: Using 4-n-propyl anisole as the starting material, the reaction is oxidized with air under solvent-free conditions to obtain p-methoxyacetone. The reaction temperature range is 150℃~200℃, and the reaction pressure is 10MPa~15MPa.

[0012] Step 2: The Meerwein-Ponndorf-Verley reduction reaction is carried out using aluminum isopropoxide as a catalyst and isopropanol as a reducing agent to reduce p-methoxyphenylacetone to 1-(4-methoxyphenyl)-1-propanol. The amount of aluminum isopropoxide used is 15%–35% of the amount of p-methoxyphenylacetone; the amount of isopropanol used is 2.5 to 4.5 times the amount of p-methoxyphenylacetone; the reaction solvent is either toluene or xylene; and the reaction temperature is 40℃–80℃.

[0013] Step 3: A dehydration reaction is carried out using concentrated sulfuric acid as the dehydrating agent to remove the hydroxyl groups of 1-(4-methoxyphenyl)-1-propanol, yielding anethole. The amount of concentrated sulfuric acid used is 1% to 5% of the amount of 1-(4-methoxyphenyl)-1-propanol; the reaction solvent is either toluene or xylene; and the reaction temperature is 60℃ to 100℃.

[0014] The advantages of this invention are as follows: the first step uses air for oxidation without any solvent, the reaction conditions are simple, the post-processing is convenient, and the reaction conversion rate is high; the second step is the first to use the Meerwein-Ponndorf-Verley reduction reaction, avoiding dangerous processes such as hydrogenation reduction or borohydride reduction, the reaction conditions are mild, the post-processing is simple, and the reaction conversion rate is high. Detailed Implementation

[0015] Example 1 Step 1: Add 150g of 4-n-propyl anisole to a stainless steel high-pressure reactor, introduce air, raise the reaction temperature to 180℃, pressurize the air to 12MPa, react for 15h, monitor the GC to ensure the remaining raw material is less than 5%, cool down, depressurize, and transfer the resulting reaction liquid to a distillation vessel for distillation to obtain 146g of p-methoxyacetone, with a yield of 89%.

[0016] Step 2: Add 82g of p-methoxyphenylacetone, 400g of toluene, 20.4g of aluminum isopropoxide, and 300g of isopropanol to the reactor and stir until homogeneous. Raise the temperature of the reactor to 50℃ and keep it at that temperature for 15h. GC monitoring shows that the reaction of the raw materials is complete. Cool to room temperature and add 1M dilute hydrochloric acid solution for quenching. Allow to stand and separate into layers to obtain the organic phase. Concentrate under reduced pressure to remove the toluene solvent. Distill the crude product to obtain 79g of 1-(4-methoxyphenyl)-1-propanol, with a yield of 95%.

[0017] Step 3: Add 55g of 1-(4-methoxyphenyl)-1-propanol, 120g of toluene, and 0.55g of concentrated sulfuric acid to the reactor. Raise the temperature of the reactor to 80℃ and keep it at that temperature for 7 hours. GC monitoring shows that the reaction of the raw materials is complete. Cool the reactor to room temperature and add a small amount of sodium bicarbonate solid for neutralization. Concentrate the organic phase under reduced pressure to remove the toluene solvent. Distill the crude product to obtain 45g of anethole, with a yield of 92%.

[0018] Example 2 Step 1: Add 300g of 4-n-propyl aniline to a stainless steel high-pressure reactor, introduce air, raise the reaction temperature to 160℃, pressurize the air to 13MPa, react for 20h, monitor the GC to ensure the remaining raw material is less than 5%, cool down, depressurize, and transfer the resulting reaction liquid to a distillation vessel for distillation to obtain 280g of p-methoxyacetone, with a yield of 85%.

[0019] Step 2: Add 164g of p-methoxyphenylacetone, 800g of xylene, 30.6g of aluminum isopropoxide, and 450g of isopropanol to the reactor and stir until homogeneous. Raise the temperature of the reactor to 70℃ and maintain the temperature for 12h. GC monitoring shows that the reaction of the raw materials is complete. Cool to room temperature and add 1M dilute hydrochloric acid solution for quenching. Allow to stand and separate into layers to obtain the organic phase. Concentrate under reduced pressure to remove xylene solvent. Distill the crude product to obtain 156g of 1-(4-methoxyphenyl)-1-propanol, with a yield of 94%.

[0020] Step 3: Add 100g of 1-(4-methoxyphenyl)-1-propanol, 200g of toluene, and 2g of concentrated sulfuric acid to the reactor. Raise the temperature of the reactor to 100℃ and keep it at that temperature for 5 hours. GC monitoring shows that the reaction of the raw materials is complete. Cool the reactor to room temperature and add a small amount of sodium bicarbonate solid for neutralization. Concentrate the organic phase under reduced pressure to remove the toluene solvent. Distill the crude product to obtain 83g of anethole, with a yield of 93%.

[0021] Example 3 Step 1: Add 300g of 4-n-propyl anisole to a stainless steel high-pressure reactor, introduce air, raise the reaction temperature to 195℃, pressurize the air to 14MPa, react for 20h, monitor the GC to ensure the remaining raw material is less than 5%, cool down, depressurize, and transfer the resulting reaction liquid to a distillation vessel for distillation to obtain 285g of p-methoxyacetone, with a yield of 87%.

[0022] Step 2: Add 164g of p-methoxyphenylacetone, 800g of toluene, 50g of aluminum isopropoxide, and 500g of isopropanol to the reactor and stir until homogeneous. Raise the temperature of the reactor to 80℃ and maintain the temperature for 10h. GC monitoring shows that the reaction of the raw materials is complete. Cool to room temperature and add 1M dilute hydrochloric acid solution for quenching. Allow to stand and separate into layers to obtain the organic phase. Concentrate under reduced pressure to remove the toluene solvent. Distill the crude product to obtain 151g of 1-(4-methoxyphenyl)-1-propanol, with a yield of 91%.

[0023] Step 3: Add 130g of 1-(4-methoxyphenyl)-1-propanol, 250g of xylene, and 5g of concentrated sulfuric acid to the reactor. Raise the temperature of the reactor to 100℃ and keep it at that temperature for 5 hours. GC monitoring shows that the reaction of the raw materials is complete. Cool the reactor to room temperature and add a small amount of sodium bicarbonate solid for neutralization. Concentrate the organic phase under reduced pressure to remove xylene solvent. Distill the crude product to obtain 110g of anethole, with a yield of 95%.

[0024] Comparative Example 1 The effect of temperature on the reaction was investigated by comparing it with the first step of Example 1. The specific results are as follows: 150g of 4-n-propyl aniline was added to a stainless steel high-pressure reactor, air was introduced, the reaction temperature was raised to 120℃, the air pressure was increased to 12MPa, and the reaction was carried out for 30h. GC monitoring showed that the remaining raw material was about 30%. The temperature was lowered, the pressure was released, and the resulting reaction solution was transferred to a distillation vessel for distillation to obtain 84g of p-methoxyacetone, with a yield of 51%.

[0025] 150g of 4-n-propyl aniline was added to a stainless steel high-pressure reactor, air was introduced, the reaction temperature was raised to 220℃, the air pressure was increased to 12MPa, the reaction was carried out for 15h, and GC monitoring showed that the remaining raw material was less than 5%. The temperature was lowered, the pressure was released, and the resulting reaction solution was transferred to a distillation vessel for distillation to obtain 62g of p-methoxyacetone, with a yield of 38%.

[0026] Note: The optimal reaction temperature range for the first step is 150℃~200℃. Lowering the reaction temperature will significantly reduce the reaction yield, result in more raw material residue, and prolong the reaction time; raising the reaction temperature will cause side reactions and reduce the product yield.

[0027] Comparative Example 2 The effect of pressure on the reaction was investigated by comparing it with the first step of Example 1. The specific results are as follows: 150g of 4-n-propyl aniline was added to a stainless steel high-pressure reactor, air was introduced, the reaction temperature was raised to 180℃, the air pressure was increased to 8MPa, and the reaction was carried out for 32h. GC monitoring showed that the remaining raw material was about 21%. The temperature was lowered, the pressure was released, and the resulting reaction solution was transferred to a distillation vessel for distillation to obtain 102g of p-methoxyacetone, with a yield of 62%.

[0028] Note: The optimal reaction pressure range for the first step is 10MPa to 15MPa. Lowering the pressure will significantly reduce the reaction yield, resulting in the remaining raw materials. Since the stainless steel high-pressure reactor used in the experiment can only withstand a maximum pressure of 16MPa, experiments with reaction pressures exceeding 15MPa were not conducted.

[0029] Comparative Example 3 The effect of aluminum isopropoxide dosage on the reaction was investigated by comparing it with the second step of Example 1. The specific results are as follows: 82g of p-methoxyphenylacetone, 400g of toluene, 8.2g of aluminum isopropoxide, and 300g of isopropanol were added to the reactor and stirred until homogeneous. The reactor temperature was raised to 50℃ and the reaction was maintained for 24h. GC monitoring showed that 27% of the raw material remained. The mixture was cooled to room temperature and quenched with 1M dilute hydrochloric acid solution. After standing and separating into layers, the organic phase was obtained. The toluene solvent was removed by vacuum concentration. The crude product was then distilled to obtain 53g of 1-(4-methoxyphenyl)-1-propanol, with a yield of 64%.

[0030] 82g of p-methoxyphenylacetone, 400g of toluene, 32.8g of aluminum isopropoxide, and 300g of isopropanol were added to the reactor and stirred until homogeneous. The reactor temperature was raised to 50℃ and the reaction was maintained at this temperature for 15h. GC monitoring showed that 27% of the raw material remained. The mixture was then cooled to room temperature, and 1M dilute hydrochloric acid solution was added for quenching. After standing and separating into layers, the organic phase was obtained. The toluene solvent was removed by vacuum concentration. The crude product was then distilled to obtain 79g of 1-(4-methoxyphenyl)-1-propanol, with a yield of 95%.

[0031] Note: In the second step, the optimal range for aluminum isopropoxide dosage is 15%-35% of the p-methoxyacetone dosage. Reducing the aluminum isopropoxide dosage will significantly decrease the reaction yield, indicating incomplete reaction of the starting materials. Increasing the aluminum isopropoxide dosage has no significant effect on the reaction; considering material costs, adding extra dosage is unnecessary. Aluminum isopropoxide is a dedicated catalyst for the Meerwein-Ponndorf-Verley reduction reaction; replacing aluminum isopropoxide with magnesium isopropoxide, sodium isopropoxide, aluminum ethoxide, aluminum tert-butoxide, etc., will not yield the target product.

[0032] Comparative Example 4 The effect of isopropanol dosage on the reaction was investigated by comparing it with the second step of Example 1. The specific results are as follows: 82g of p-methoxyphenylacetone, 400g of toluene, 20.4g of aluminum isopropoxide, and 164g of isopropanol were added to the reactor and stirred until homogeneous. The reactor temperature was raised to 50℃ and the reaction was maintained at this temperature for 24h. GC monitoring showed that approximately 17% of the raw material remained. The mixture was cooled to room temperature and quenched with 1M dilute hydrochloric acid solution. After standing and separating into layers, the organic phase was obtained. The toluene solvent was removed by vacuum concentration. The crude product was then distilled to obtain 61g of 1-(4-methoxyphenyl)-1-propanol, with a yield of 74%.

[0033] 82g of p-methoxyphenylacetone, 400g of toluene, 32.8g of aluminum isopropoxide, and 410g of isopropanol were added to the reactor and stirred until homogeneous. The reactor temperature was raised to 50℃ and the reaction was maintained for 15h. GC monitoring showed that there was basically no raw material remaining. The mixture was cooled to room temperature and quenched with 1M dilute hydrochloric acid solution. After standing and separating into layers, the organic phase was obtained. The toluene solvent was removed by vacuum concentration. The crude product was then distilled to obtain 79g of 1-(4-methoxyphenyl)-1-propanol, with a yield of 95%.

[0034] Note: In the second step, the optimal amount of isopropanol is 2.5-4.5 times that of p-methoxyphenylacetone. Reducing the amount of isopropanol will decrease the reaction yield, indicating that the starting materials have not reacted completely. Increasing the amount of isopropanol has no significant effect on the reaction; considering material costs, increasing the amount further is unnecessary.

[0035] It should also be noted that isopropanol is the specific reducing agent for the Meerwein-Ponndorf-Verley reduction reaction, and replacing isopropanol with n-propanol, methanol, ethanol, tert-butanol, etc., will not yield the target product.

[0036] It should also be noted that toluene or xylene mainly serves to dissolve raw materials and perform post-processing extraction in the reaction system. Replacing them with other solvents such as ethyl acetate or methanol will produce side reactions in the reaction.

[0037] Comparative Example 5 The effect of temperature on the reaction was investigated by comparing it with the second step of Example 1. The specific results are as follows: 82g of p-methoxyacetone, 400g of toluene, 20.4g of aluminum isopropoxide, and 300g of isopropanol were added to the reactor and stirred until homogeneous. The reactor temperature was raised to 30°C and the reaction was maintained for 15 hours. GC monitoring showed that about 86% of the raw materials remained, indicating a large amount of residual raw materials that were difficult to process.

[0038] Note: The optimal reaction temperature for the second step is 40℃~80℃. When the temperature is below 40℃, the reaction rate slows down and a large amount of raw materials remain. When the temperature is above 80℃, isopropanol will boil out of the reaction system, and further heating will result in explosive boiling.

[0039] Comparative Example 6 Compared with step 3 of Example 1, the effect of concentrated sulfuric acid dosage on the reaction was investigated, and the specific results are as follows: 55g of 1-(4-methoxyphenyl)-1-propanol, 120g of toluene, and 0.28g of concentrated sulfuric acid were added to the reactor. The reactor temperature was raised to 80℃ and the reaction was maintained for 7 hours. GC monitoring showed that about 32% of the raw material remained. The mixture was cooled to room temperature, and a small amount of sodium bicarbonate solid was added for neutralization. The organic phase was concentrated under reduced pressure to remove the toluene solvent. The crude product was then distilled to obtain 32g of anethole, with a yield of 65%.

[0040] 55g of 1-(4-methoxyphenyl)-1-propanol, 120g of toluene, and 3.3g of concentrated sulfuric acid were added to the reactor. The reactor temperature was raised to 80℃ and kept at that temperature for 7h. The basic reaction of the raw materials was monitored by GC. The temperature was lowered to room temperature, and a small amount of sodium bicarbonate solid was added for neutralization. The organic phase was concentrated under reduced pressure to remove the toluene solvent. The crude product was then distilled to obtain 40g of anethole, with a yield of 81%.

[0041] Note: In the third step, the optimal range for the amount of concentrated sulfuric acid is 1% to 5% of the amount of 1-(4-methoxyphenyl)-1-propanol. When the amount of concentrated sulfuric acid is less than 1%, the reaction rate slows down and some raw materials remain. When the amount of concentrated sulfuric acid is more than 5%, although the raw materials react completely, the product will begin to undergo polymerization.

[0042] Comparative Example 7 The effect of temperature on the reaction was investigated by comparing it with step 3 of Example 1. The specific results are as follows: 55g of 1-(4-methoxyphenyl)-1-propanol, 120g of toluene, and 0.55g of concentrated sulfuric acid were added to the reactor. The reactor temperature was raised to 50°C and the reaction was maintained for 7 hours. GC monitoring showed that 73% of the raw materials remained, indicating a large amount of residual raw materials. The reactor was then discarded for further processing.

[0043] 55g of 1-(4-methoxyphenyl)-1-propanol, 120g of toluene, and 0.55g of concentrated sulfuric acid were added to the reactor. The reactor temperature was raised to 50℃ and kept at that temperature for 7 hours. GC monitoring showed that the reaction of the raw materials was complete. The mixture was then cooled to room temperature, and a small amount of sodium bicarbonate solid was added for neutralization. The organic phase was concentrated under reduced pressure to remove the toluene solvent. The crude product was then distilled to obtain 37g of anethole, with a yield of 76%.

[0044] Note: The optimal reaction temperature range for the third step is 60℃~100℃; when the temperature is below 60℃, the reaction rate slows down and a large amount of raw materials remain; when the temperature is above 100℃, the product will begin to polymerize, reducing the reaction yield.

[0045] It is also noted that the optimal reaction solvent for the third step is toluene or xylene. Using other solvents such as ethanol, acetonitrile, tetrahydrofuran, ethyl acetate, methyl tert-butyl ether, etc., will not effectively yield the target product.

[0046] The above embodiments are only used to illustrate the technical concept and features of the present invention, and are not intended to be unique or to limit the present invention. Those skilled in the art should understand that various changes or equivalent substitutions made to the present invention without departing from its scope are all within the protection scope of the present invention.

Claims

1. A method for synthesizing anethole, characterized in that, Includes the following steps: Step 1: Using 4-n-propyl anisole as the starting material, the reaction is oxidized with air under solvent-free conditions to obtain p-methoxyacetone; Step 2: Using aluminum isopropoxide as a catalyst and isopropanol as a reducing agent, p-methoxyphenylacetone is reduced to 1-(4-methoxyphenyl)-1-propanol. Step 3: Using concentrated sulfuric acid as a dehydrating agent, the hydroxyl groups of 1-(4-methoxyphenyl)-1-propanol are removed to obtain anethole.

2. The method for synthesizing anethole according to claim 1, characterized in that, In the first step, the reaction temperature range is 150℃~200℃.

3. The method for synthesizing anethole according to claim 1, characterized in that, In the first step, the reaction pressure is 10MPa to 15MPa.

4. The method for synthesizing anethole according to claim 1, characterized in that, In the second step, the amount of aluminum isopropoxide used is 15% to 35% of the amount of p-methoxyacetone used.

5. The method for synthesizing anethole according to claim 1, characterized in that, In the second step, the amount of isopropanol used is 2.5 to 4.5 times that of p-methoxyphenylacetone.

6. The method for synthesizing anethole according to claim 1, characterized in that, In the second step, the reaction temperature is 40℃~80℃.

7. The method for synthesizing anethole according to claim 1, characterized in that, In the third step, the amount of concentrated sulfuric acid used is 1% to 5% of the amount of 1-(4-methoxyphenyl)-1-propanol used.

8. The method for synthesizing anethole according to claim 1, characterized in that, In the third step, the reaction temperature is 60℃~100℃.

9. The method for synthesizing anethole according to claim 1, characterized in that, In the second and third steps, the reaction solvent is either toluene or xylene.

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