Preparation process of perillyl alcohol

Abstract

The invention provides a preparation process of perillyl alcohol, and belongs to the technical field of perillyl alcohol preparation. The preparation process comprises the following steps: preparing the novel macroporous weak acid cationic resin; 2, preparation of the 10-epoxy pinane; and preparing the perillyl alcohol. The synthetic method comprises the following steps: dropwise adding synthesized 2, 10-epoxy pinane under an acidic condition, carrying out a ring-opening reaction and a nucleophilic substitution reaction to generate p-# imgabs0 #-1-alkene-8-acetoxyl-7-alcohol and a small amount of perillyl acetate and perillyl alcohol, and carrying out high-temperature cracking to obtain perillyl acetate, perillyl alcohol and other byproducts. And finally, saponification reaction, extraction, desolvation and reduced pressure distillation are carried out to obtain perillyl alcohol, the reaction temperature in the whole synthesis process is mild, medium corrosivity is small, waste generated in the synthesis process is relatively few, the extracted organic phase can be recycled after treatment, emission of organic matters is reduced, generation of waste water and waste residues is reduced, and the method is suitable for industrial production. The pollution to the environment is reduced, and the synthesized perillyl alcohol has relatively high purity and yield.

Description

Technical Field

[0001] The present invention relates to the technical field of perillyl alcohol preparation, and particularly relates to a preparation process of perillyl alcohol. Background Art

[0002] Perillyl alcohol is an important natural compound with various biological activities such as antibacterial, antiviral, and anti-inflammatory effects, and has broad application prospects in industries such as medicine, cosmetics, and food. Perillyl alcohol mainly exists in various plants such as perilla leaves, seeds, and roots, and can also be obtained by chemical synthesis methods.

[0003] Traditional plant extraction methods often have low extraction efficiency, and a large amount of plant raw materials are required to obtain a small amount of perillyl alcohol. A large amount of organic solvents are used in the extraction process, which not only increases the cost but also may cause environmental pollution. Moreover, due to the seasonal and regional differences of plant raw materials, the quality of the perillyl alcohol product obtained by extraction is unstable.

[0004] There are mainly two categories of known methods for preparing perillyl alcohol from 2,10-epoxypinane in chemical synthesis: one is the two-step method of hydration-dehydration; the other is the catalytic isomerization method. Both of these methods consume a large amount of highly toxic mercury salts and involve sulfuric acid solutions with strong corrosiveness, seriously affecting the environment.

[0005] Therefore, we have proposed a preparation process of perillyl alcohol with low medium corrosiveness, high purity, and high yield. Summary of the Invention

[0006] Aiming at the deficiencies existing in the prior art, the purpose of the present invention is to provide a preparation process of perillyl alcohol.

[0007] A preparation process of perillyl alcohol includes the following steps:

[0008] S1: Preparation of a novel macroporous weak acid cation resin

[0009] After washing and drying the macroporous cross-linked polystyrene resin, it is mixed and reacted with diethanolamine and isopropanol to obtain a novel macroporous weak acid cation resin;

[0010] S2: Preparation of 2,10-epoxypinane

[0011] Using β-pinene as a raw material, acetonitrile-water as a solvent, acetone as a catalyst, and hydrogen peroxide as an oxidant, 2,10-epoxypinane is synthesized through an epoxidation reaction;

[0012] S3: Preparation of perillyl alcohol

[0013] Under acidic conditions, 2,10-epoxypinane is added dropwise, and a ring-opening reaction and a nucleophilic substitution reaction occur to generate p- -1-ene-8-acetoxy-7-alcohol, a small amount of perillacetate and perilla alcohol, and then pyrolyzed at high temperature to obtain perillacetate, perilla alcohol and other by-products. Finally, saponification reaction, extraction, desolvation and vacuum distillation are carried out to obtain perilla alcohol.

[0014] Further, step S1: Preparation of a novel macroporous weak acid cation resin, which specifically includes the following steps:

[0015] S1.1: Wash the macroporous crosslinked chloromethyl polystyrene resin with tap water 6 - 8 times, then wash it with deionized water 1 - 2 times, put it into a vacuum drying oven, and dry it to constant weight at 100 - 110 °C to obtain the dried macroporous crosslinked polystyrene resin;

[0016] S1.2: Mix 10 - 20 parts by weight of the dried macroporous crosslinked polystyrene resin and 30 - 50 parts by weight of diethanolamine with a mass fraction of 98.5%, then add 20 - 30 parts by weight of isopropanol, and react at 70 - 75 °C for 6 - 8 h. After the reaction ends, obtain the reaction product;

[0017] S1.3: Obtain the separated product by vacuum filtration of the reaction product, wash the separated product with tap water 6 - 8 times, then wash it with deionized water 1 - 2 times, and then put it into a vacuum drying oven and dry it to constant weight at 100 - 110 °C to obtain the novel macroporous weak acid cation resin.

[0018] Further, step S2: Preparation of 2,10-epoxypinane, which specifically includes the following steps:

[0019] S2.1: Add 3.4 - 54.4 parts by weight of β-pinene, 80 - 1280 parts by weight of acetonitrile, 20 - 320 parts by weight of water, 3 - 48 parts by weight of acetone and 10.5 - 168 parts by weight of sodium bicarbonate to the reaction flask, dropwise add 14.17 - 226.72 parts by weight of 25% hydrogen peroxide at 23 - 25 °C, after the dropping is completed, raise the temperature to 40 - 42 °C, keep the temperature for reaction for 10 - 12 h, after the reaction ends, carry out suction filtration to obtain a solution;

[0020] S2.2: Add dichloromethane to the solution for extraction, extract 3 - 5 times, mix the extracted organic phases, add saturated sodium hydroxide for washing 2 - 3 times, add anhydrous sodium sulfate to the washed organic phase for drying, and then carry out suction filtration, desolvation and vacuum distillation to obtain 2,10-epoxypinane.

[0021] Further, step S3: Preparation of perilla alcohol, which specifically includes the following steps:

[0022] S3.1: Charge 2 - 15 parts by weight of a novel macroporous weak acid cation resin, 120 - 1308 parts by weight of glacial acetic acid, and 20 - 218 parts by weight of anhydrous sodium acetate into a reaction flask. Start heating. When the temperature reaches 60 - 70 °C, add dropwise 20 - 218 parts by weight of 2,10 - epoxy - pinane. After the addition is complete, carry out a temperature - rising reaction. After the reaction ends, cool down and filter to obtain a reaction solution;

[0023] S3.2: Wash the reaction solution with glacial acetic acid 2 - 3 times to obtain an organic phase. Combine the organic phases and then distill off acetic acid. Then add methyl tert - butyl ether for extraction and filtration. After filtration, wash the solid with methyl tert - butyl ether again. Combine the organic phases and carry out desolvation to obtain the desolvated organic phase;

[0024] S3.3: Pyrolyze the desolvated organic phase at high temperature. Then mix the organic phase, absolute ethanol, sodium hydroxide, and water and carry out a saponification reaction. After cooling, add dichloromethane for extraction 2 - 3 times. After removing dichloromethane, carry out vacuum distillation and collect the product in the distillation fraction of 118 - 121 °C, which is perillyl alcohol.

[0025] Further, in step S1.2, the diethanolamine is specifically diethanolamine with a mass fraction of 98.5%.

[0026] Further, in step S2.1, the hydrogen peroxide is specifically hydrogen peroxide with a mass fraction of 25%.

[0027] Further, in step S3.1, the temperature of the temperature - rising reaction is 75 - 76 °C, and the reaction time is 2 - 2.5 h.

[0028] Further, in step S3.3, the temperature of the high - temperature pyrolysis is 165 - 170 °C, and the pyrolysis time is 10 - 12 h.

[0029] Further, in step S3.3, the ratio of the organic phase, absolute ethanol, sodium hydroxide, and water is 3:1:1:2.

[0030] Further, in step S3.3, the saponification reaction temperature is 78 - 80 °C, and the reaction time is 2 - 3 h.

[0031] Compared with the prior art, the present invention has at least the following beneficial effects:

[0032] 1. In the present invention, by adding dropwise the synthesized 2,10 - epoxy - pinane under acidic conditions, ring - opening reaction and nucleophilic substitution reaction occur to generate p - -1-ene-8-acetoxy-7-alcohol, a small amount of perillacetate and perillyl alcohol, and then pyrolyzed at high temperature to obtain perillacetate, perillyl alcohol and other by-products. Finally, saponification reaction, extraction, desolvation and vacuum distillation are carried out to obtain perillyl alcohol. The synthesized perillyl alcohol has high purity and yield. The medium has little corrosion during the whole synthesis process, and the waste generated during the synthesis process is relatively small. The organic phase after extraction can be recycled after treatment, reducing the emission of organic substances. At the same time, through washing and separation operations, the generation of waste water and waste residues is reduced, and the environmental pollution is reduced.

[0033] 2. The present invention uses β-pinene as a raw material to catalytically synthesize 2,10-epoxypinane. Using acetonitrile, water and acetone as a mixed solvent system, through the synergistic effect of the three solvents, the polarity of the mixed solvent system can be adjusted to meet the requirements of the 2,10-epoxypinane synthesis reaction, which is conducive to the smooth progress of the reaction. At the same time, through relatively mild and precise temperature control, it is conducive to the stable progress of the reaction, reducing the occurrence of side reactions caused by excessive temperature fluctuations, improving the selectivity of the reaction and the purity of 2,10-epoxypinane. The higher purity of 2,10-epoxypinane is more conducive to the subsequent synthesis of perillyl alcohol.

[0034] 3. The present invention prepares a novel macroporous weak acid cation resin. During the preparation process of perillyl alcohol, the novel macroporous weak acid cation resin shows high catalytic activity, greatly shortening the reaction time and improving the production efficiency. In the synthesis of perillyl alcohol, it can effectively promote the reaction of 2,10-epoxypinane with other reactants without causing excessive generation of by-products, ensuring the purity and yield of perillyl alcohol. Moreover, the resin catalyst with a macroporous structure is easy to separate from the reaction system by simple filtration operation after the reaction, which not only simplifies the process flow, reduces the operation difficulty, but also reduces the loss of the catalyst and saves costs. BRIEF DESCRIPTION OF THE DRAWINGS

[0035] The drawings incorporated herein and constituting a part of the specification illustrate embodiments of the present disclosure and, together with the specification, are further used to explain the principles of the present disclosure and enable those skilled in the relevant art to implement and use the present disclosure.

[0036] Figure 1 It is a process flow chart of the preparation of perillyl alcohol adopted in the embodiment of the present invention. DETAILED DESCRIPTION OF THE EMBODIMENTS

[0037] The following describes in detail a process for preparing perillyl alcohol provided by the present invention with reference to the drawings and specific embodiments.

[0038] Example 1

[0039] A process for preparing perillyl alcohol, as Figure 1 shown, includes the following steps:

[0040] S1: Preparation of novel macroporous weak acid cation resin

[0041] S1.1: Wash the macroporous crosslinked chloromethyl polystyrene resin 6 times with tap water, then wash it once with deionized water, put it into a vacuum drying oven, and dry it to constant weight at 100 °C to obtain dry macroporous crosslinked polystyrene resin;

[0042] S1.2: Mix 10 parts by weight of dry macroporous crosslinked polystyrene resin and 30 parts by weight of diethanolamine with a mass fraction of 98.5%, then add 20 parts by weight of isopropanol, and react at 70 °C for 6 h. After the reaction ends, obtain the reaction product;

[0043] S1.3: Obtain the separated product by vacuum filtration of the reaction product, wash the separated product 6 times with tap water, then wash it once with deionized water, and then put it into a vacuum drying oven and dry it to constant weight at 100 °C to obtain the novel macroporous weak acid cation resin;

[0044] S2: Preparation of 2,10-epoxypinane

[0045] S2.1: Add 3.4 parts by weight of β-pinene, 80 parts by weight of acetonitrile, 20 parts by weight of water, 3 parts by weight of acetone and 10.5 parts by weight of sodium bicarbonate to the reaction flask, dropwise add 14.17 parts by weight of hydrogen peroxide with a mass fraction of 25% at 23 °C, and after the addition is completed, raise the temperature to 40 °C and keep the temperature for reaction for 10 h. After the reaction ends, filter by suction to obtain a solution;

[0046] S2.2: Add dichloromethane to the solution for extraction for 3 times. After mixing the extracted organic phases, add saturated sodium hydroxide for washing 3 times. Add anhydrous sodium sulfate to the washed organic phase for drying, and then filter by suction and strip the solvent, and carry out vacuum distillation to obtain 2,10-epoxypinane;

[0047] S3: Preparation of perillyl alcohol

[0048] S3.1: Put 2 parts by weight of the novel macroporous weak acid cation resin, 120 parts by weight of glacial acetic acid, and 20 parts by weight of anhydrous sodium acetate into the reaction flask, start heating, and when the temperature reaches 60 °C, dropwise add 20 parts by weight of 2,10-epoxypinane. After the addition is completed, raise the temperature to 75 °C and keep the temperature for reaction for 2 h. After cooling and filtering, obtain the reaction solution;

[0049] S3.2: Wash the reaction solution 2 times with glacial acetic acid to obtain the organic phase. After combining the organic phases, strip acetic acid, then add methyl tert-butyl ether for extraction and filtration. After filtration, wash the solid with methyl tert-butyl ether again, and then combine the organic phases and strip the solvent to obtain the stripped organic phase;

[0050] S3.3: Heat the desolvated organic phase to 165 °C and pyrolyze it at high temperature for 10 h. Then, mix the organic phase, absolute ethanol, sodium hydroxide, and water in a ratio of 3:1:1:2, heat it to 78 °C, carry out saponification reaction for 2 h, cool it down, add dichloromethane for extraction twice, remove dichloromethane, and then carry out vacuum distillation. Collect the product in the fraction range of 118 - 121 °C, which is perillyl alcohol.

[0051] Example 2

[0052] A preparation process of perillyl alcohol, as Figure 1 shown, includes the following steps:

[0053] S1: Preparation of novel macroporous weak acid cation resin

[0054] S1.1: Wash the macroporous crosslinked chloromethyl polystyrene resin 8 times with tap water, then wash it 2 times with deionized water, put it into a vacuum drying oven, and dry it to constant weight at 110 °C to obtain dry macroporous crosslinked polystyrene resin;

[0055] S1.2: Mix 10 parts by weight of dry macroporous crosslinked polystyrene resin and 30 parts by weight of diethanolamine with a mass fraction of 98.5%, add 20 parts by weight of isopropanol, and react at 75 °C for 8 h. After the reaction, obtain the reaction product;

[0056] S1.3: Obtain the separated product by vacuum filtration of the reaction product. Wash the separated product 8 times with tap water, then wash it 2 times with deionized water, and then put it into a vacuum drying oven and dry it to constant weight at 110 °C to obtain the novel macroporous weak acid cation resin;

[0057] S2: Preparation of 2,10-epoxypinane

[0058] S2.1: Add 3.4 parts by weight of β-pinene, 80 parts by weight of acetonitrile, 20 parts by weight of water, 3 parts by weight of acetone, and 10.5 parts by weight of sodium bicarbonate to the reaction flask. Dropwise add 14.17 parts by weight of hydrogen peroxide with a mass fraction of 25% at 25 °C. After the addition is completed, raise the temperature to 42 °C and keep the temperature for reaction for 12 h. After the reaction, carry out suction filtration to obtain the solution;

[0059] S2.2: Add dichloromethane to the solution for extraction 5 times. Mix the extracted organic phases, add saturated sodium hydroxide for washing 3 times, add anhydrous sodium sulfate to the washed organic phase for drying, then carry out suction filtration and desolvation, and carry out vacuum distillation to obtain 2,10-epoxypinane;

[0060] S3: Preparation of perillyl alcohol

[0061] S3.1: Charge 2 parts by weight of a novel macroporous weak acid cation exchange resin, 120 parts by weight of glacial acetic acid, and 20 parts by weight of anhydrous sodium acetate into a reaction flask. Start heating. When the temperature reaches 70 °C, add dropwise 20 parts by weight of 2,10-epoxypinane. After the addition is complete, raise the temperature to 76 °C and hold for reaction for 2.5 h. After cooling and filtration, a reaction solution is obtained;

[0062] S3.2: Wash the reaction solution with glacial acetic acid three times to obtain an organic phase. Combine the organic phases and distill off acetic acid. Then add methyl tert-butyl ether for extraction and filtration. After filtration, wash the solid with methyl tert-butyl ether again. Combine the organic phases and carry out desolvation to obtain the desolvated organic phase;

[0063] S3.3: Heat the desolvated organic phase to 170 °C and carry out high-temperature pyrolysis for 12 h. Then mix the organic phase, absolute ethanol, sodium hydroxide, and water in a ratio of 3:1:1:2, heat to 80 °C, and carry out saponification reaction for 3 h. After cooling, extract three times with dichloromethane. After removing dichloromethane, carry out vacuum distillation and collect the product in the fraction range of 118 - 121 °C, which is perillyl alcohol.

[0064] Example 3 - 9

[0065] Repeat Example 1, only changing the amounts of β-pinene, acetonitrile, water, acetone, sodium bicarbonate, and hydrogen peroxide. The relevant amounts and reaction results are listed in Table 1.

[0066] Example 10 - 16

[0067] Repeat Example 1, only changing the amounts of 2,10-epoxypinane, the novel macroporous weak acid cation exchange resin, glacial acetic acid, and anhydrous sodium acetate. The relevant amounts and reaction results are listed in Table 2.

[0068] Table 1. Reaction results of 2,10-epoxypinane in Examples 1 - 9

[0069]

[0070] Table 2. Reaction results of perillyl alcohol in Examples 1 - 2, 10 - 16

[0071]

[0072] It can be seen from the data in Table 1 and Table 2 above that the present invention can successfully synthesize 2,10-epoxypinane and perillyl alcohol, and the synthesized perillyl alcohol has high purity and yield.

[0073] The above embodiments are only illustrative of the principles and effects of the present invention and are not intended to limit the present invention. Any person familiar with this technology can modify or change the above embodiments without departing from the spirit and scope of the present invention. Therefore, all equivalent modifications or changes made by those with ordinary knowledge in the technical field without departing from the spirit and technical idea disclosed by the present invention should still be covered by the claims of the present invention.

Claims

1. A process for preparing perillyl alcohol, characterized in that: The steps include: S1: Preparation of novel macroporous weak acid cation resin The macroporous cross-linked polystyrene resin is washed and dried, and then mixed with diethanolamine and isopropanol to react to obtain a novel macroporous weak acid cationic resin. S2: Preparation of 2,10-epoxypinane 2,10-epoxypinane was synthesized by epoxidation reaction using β-pinene as raw material, acetonitrile-water as solvent, acetone as catalyst and hydrogen peroxide as oxidant. S3: Preparation of Perillyl Alcohol Under acidic conditions, 2,10-epoxypinane is added dropwise to cause a ring-opening reaction and a nucleophilic substitution reaction to generate p-hydroxy-1-ene-8-acetoxy-7-ol and a small amount of perillyl acetate and perillyl alcohol, which are then cracked at high temperature to obtain perillyl acetate, perillyl alcohol and other by-products, and finally saponification reaction, extraction, desolventization and reduced pressure distillation are carried out to obtain perillyl alcohol.

2. A process for preparing perillyl alcohol according to claim 1, characterized in that: Step S1: Preparation of a novel macroporous weakly acidic cationic resin, specifically comprising the following steps: S1.1: Wash the macroporous cross-linked chloromethyl polystyrene resin with tap water for 6-8 times, then wash it with deionized water for 1-2 times, put it into a vacuum drying oven, and dry it at 100-110° C. to constant weight to obtain a dry macroporous cross-linked polystyrene resin; S1.2: 10-20 parts by weight of dry macroporous cross-linked polystyrene resin and 30-50 parts by weight of 98.5% diethanolamine are mixed, and then 20-30 parts by weight of isopropanol are added, and the mixture is reacted at 70-75° C. for 6-8 hours. After the reaction is completed, a reaction product is obtained; S1.3: The reaction product is filtered under reduced pressure to obtain a separated product, the separated product is washed with tap water for 6-8 times, and then washed with deionized water for 1-2 times, and then placed in a vacuum drying oven, and dried at 100-110°C to constant weight to obtain a new macroporous weak acid cation resin.

3. A process for preparing perillyl alcohol according to claim 2, characterized in that: Step S2: Preparation of 2,10-epoxypinane, specifically comprising the following steps: S2.1: Add 3.4-54.4 parts by weight of β-pinene, 80-1280 parts by weight of acetonitrile, 20-320 parts by weight of water, 3-48 parts by weight of acetone and 10.5-168 parts by weight of sodium bicarbonate to a reaction bottle, and dropwise add 14.17-226.72 parts by weight of 25% hydrogen peroxide at 23-25°C. After the dropwise addition is completed, heat to 40-42°C, keep the temperature for reaction for 10-12 hours, and after the reaction is completed, filter to obtain a solution; S2.2: Add dichloromethane to the solution for extraction, extract 3-5 times, mix the extracted organic phases, add saturated sodium hydroxide to wash 2-3 times, add anhydrous sodium sulfate to dry the washed organic phase, then filter, desolventize, and distill under reduced pressure to obtain 2,10-epoxypinane.

4. A process for preparing perillyl alcohol according to claim 3, characterized in that: Step S3: Preparation of perillyl alcohol, specifically comprising the following steps: S3.1: Add 2-15 parts by weight of a novel macroporous weak acid cationic resin, 120-1308 parts by weight of glacial acetic acid, and 20-218 parts by weight of anhydrous sodium acetate into a reaction bottle, turn on the heating, and when heated to 60-70° C., dropwise add 20-218 parts by weight of 2,10-epoxypinene, and after the dropwise addition is completed, heat the reaction, cool the reaction, and filter the reaction solution after the reaction is completed; S3.2: The reaction solution is washed with glacial acetic acid for 2-3 times to obtain an organic phase, the organic phases are combined and then evaporated to remove acetic acid, and then methyl tert-butyl ether is added for extraction and filtration, and after filtration, the solid is washed with methyl tert-butyl ether, and the organic phases are combined and desolventized to obtain an organic phase after desolventization; S3.3: The organic phase after desolventizing is cracked at high temperature, and then the organic phase, anhydrous ethanol, sodium hydroxide and water are mixed and saponified. After cooling, dichloromethane is added to extract 2-3 times. After removing dichloromethane, vacuum distillation is performed to collect the product of the 118-121°C fraction, which is perillyl alcohol.

5. A process for preparing perillyl alcohol according to claim 2, characterized in that: The diethanolamine in step S1.2 is specifically diethanolamine with a mass fraction of 98.5%.

6. The process for preparing perillyl alcohol according to claim 3, characterized in that: The hydrogen peroxide in step S2.1 is specifically hydrogen peroxide with a mass fraction of 25%.

7. The process for preparing perillyl alcohol according to claim 4, characterized in that: The temperature of the temperature-raising reaction in step S3.1 is 75-76° C., and the reaction time is 2-2.5 h.

8. The process for preparing perillyl alcohol according to claim 4, characterized in that: The temperature of high temperature pyrolysis in step S3.3 is 165-170°C, and the pyrolysis time is 10-12h.

9. The process for preparing perillyl alcohol according to claim 4, characterized in that: The ratio of organic phase, anhydrous ethanol, sodium hydroxide and water in step S3.3 is 3:1:1:

2.

10. The process for preparing perillyl alcohol according to claim 4, characterized in that: In step S3.3, the saponification reaction temperature is 78-80°C and the reaction time is 2-3h.

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