CN115772146B - Method for preparing cannabidiol and cannabidiol - Google Patents
Method for preparing cannabidiol and cannabidiol Download PDFInfo
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- CN115772146B CN115772146B CN202211528056.5A CN202211528056A CN115772146B CN 115772146 B CN115772146 B CN 115772146B CN 202211528056 A CN202211528056 A CN 202211528056A CN 115772146 B CN115772146 B CN 115772146B
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- 229950011318 cannabidiol Drugs 0.000 title claims abstract description 158
- QHMBSVQNZZTUGM-UHFFFAOYSA-N Trans-Cannabidiol Natural products OC1=CC(CCCCC)=CC(O)=C1C1C(C(C)=C)CCC(C)=C1 QHMBSVQNZZTUGM-UHFFFAOYSA-N 0.000 title claims abstract description 157
- ZTGXAWYVTLUPDT-UHFFFAOYSA-N cannabidiol Natural products OC1=CC(CCCCC)=CC(O)=C1C1C(C(C)=C)CC=C(C)C1 ZTGXAWYVTLUPDT-UHFFFAOYSA-N 0.000 title claims abstract description 157
- PCXRACLQFPRCBB-ZWKOTPCHSA-N dihydrocannabidiol Natural products OC1=CC(CCCCC)=CC(O)=C1[C@H]1[C@H](C(C)C)CCC(C)=C1 PCXRACLQFPRCBB-ZWKOTPCHSA-N 0.000 title claims abstract description 157
- QHMBSVQNZZTUGM-ZWKOTPCHSA-N cannabidiol Chemical compound OC1=CC(CCCCC)=CC(O)=C1[C@H]1[C@H](C(C)=C)CCC(C)=C1 QHMBSVQNZZTUGM-ZWKOTPCHSA-N 0.000 title claims abstract description 156
- 238000000034 method Methods 0.000 title claims abstract description 30
- JOOXCMJARBKPKM-UHFFFAOYSA-N 4-oxopentanoic acid Chemical compound CC(=O)CCC(O)=O JOOXCMJARBKPKM-UHFFFAOYSA-N 0.000 claims abstract description 60
- 238000006243 chemical reaction Methods 0.000 claims abstract description 43
- 238000009835 boiling Methods 0.000 claims abstract description 31
- 239000013078 crystal Substances 0.000 claims abstract description 31
- 229940040102 levulinic acid Drugs 0.000 claims abstract description 30
- 238000010438 heat treatment Methods 0.000 claims abstract description 29
- 239000007788 liquid Substances 0.000 claims abstract description 22
- 239000003960 organic solvent Substances 0.000 claims abstract description 22
- 239000011259 mixed solution Substances 0.000 claims abstract description 20
- 238000002425 crystallisation Methods 0.000 claims abstract description 10
- 230000008025 crystallization Effects 0.000 claims abstract description 8
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 21
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 20
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical group O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 claims description 14
- 239000007787 solid Substances 0.000 claims description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 12
- 238000000926 separation method Methods 0.000 claims description 11
- 238000004808 supercritical fluid chromatography Methods 0.000 claims description 10
- 238000001816 cooling Methods 0.000 claims description 8
- 229910002092 carbon dioxide Inorganic materials 0.000 claims description 7
- 239000001569 carbon dioxide Substances 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 230000035484 reaction time Effects 0.000 claims description 4
- 238000001704 evaporation Methods 0.000 claims description 3
- 230000008020 evaporation Effects 0.000 claims description 3
- 238000001953 recrystallisation Methods 0.000 claims description 3
- 239000012752 auxiliary agent Substances 0.000 claims description 2
- 241000218236 Cannabis Species 0.000 abstract description 24
- 229930003827 cannabinoid Natural products 0.000 abstract description 14
- 239000003557 cannabinoid Substances 0.000 abstract description 14
- 238000002360 preparation method Methods 0.000 abstract description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 abstract description 4
- 238000005886 esterification reaction Methods 0.000 abstract description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract description 3
- 230000002378 acidificating effect Effects 0.000 abstract description 2
- 239000000284 extract Substances 0.000 abstract 1
- 125000000623 heterocyclic group Chemical group 0.000 abstract 1
- 230000000052 comparative effect Effects 0.000 description 18
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- 239000000243 solution Substances 0.000 description 10
- QXACEHWTBCFNSA-SFQUDFHCSA-N cannabigerol Chemical compound CCCCCC1=CC(O)=C(C\C=C(/C)CCC=C(C)C)C(O)=C1 QXACEHWTBCFNSA-SFQUDFHCSA-N 0.000 description 7
- 229940065144 cannabinoids Drugs 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- QXACEHWTBCFNSA-UHFFFAOYSA-N cannabigerol Natural products CCCCCC1=CC(O)=C(CC=C(C)CCC=C(C)C)C(O)=C1 QXACEHWTBCFNSA-UHFFFAOYSA-N 0.000 description 6
- QZHPTGXQGDFGEN-UHFFFAOYSA-N chromene Chemical compound C1=CC=C2C=C[CH]OC2=C1 QZHPTGXQGDFGEN-UHFFFAOYSA-N 0.000 description 6
- 238000002156 mixing Methods 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 244000025254 Cannabis sativa Species 0.000 description 5
- 235000012766 Cannabis sativa ssp. sativa var. sativa Nutrition 0.000 description 5
- 235000012765 Cannabis sativa ssp. sativa var. spontanea Nutrition 0.000 description 5
- 235000009120 camo Nutrition 0.000 description 5
- 235000005607 chanvre indien Nutrition 0.000 description 5
- 239000011487 hemp Substances 0.000 description 5
- 230000001376 precipitating effect Effects 0.000 description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- 239000012535 impurity Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- 206010006187 Breast cancer Diseases 0.000 description 2
- 208000026310 Breast neoplasm Diseases 0.000 description 2
- -1 Cannabidiol (CBD) Natural products 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- CYQFCXCEBYINGO-UHFFFAOYSA-N THC Natural products C1=C(C)CCC2C(C)(C)OC3=CC(CCCCC)=CC(O)=C3C21 CYQFCXCEBYINGO-UHFFFAOYSA-N 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 125000002843 carboxylic acid group Chemical group 0.000 description 2
- CYQFCXCEBYINGO-IAGOWNOFSA-N delta1-THC Chemical compound C1=C(C)CC[C@H]2C(C)(C)OC3=CC(CCCCC)=CC(O)=C3[C@@H]21 CYQFCXCEBYINGO-IAGOWNOFSA-N 0.000 description 2
- 229960004242 dronabinol Drugs 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 241000218235 Cannabaceae Species 0.000 description 1
- WVOLTBSCXRRQFR-SJORKVTESA-N Cannabidiolic acid Natural products OC1=C(C(O)=O)C(CCCCC)=CC(O)=C1[C@@H]1[C@@H](C(C)=C)CCC(C)=C1 WVOLTBSCXRRQFR-SJORKVTESA-N 0.000 description 1
- VBGLYOIFKLUMQG-UHFFFAOYSA-N Cannabinol Chemical compound C1=C(C)C=C2C3=C(O)C=C(CCCCC)C=C3OC(C)(C)C2=C1 VBGLYOIFKLUMQG-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000001430 anti-depressive effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
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- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
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- 201000011510 cancer Diseases 0.000 description 1
- 230000008094 contradictory effect Effects 0.000 description 1
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- 230000001737 promoting effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
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Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/54—Improvements relating to the production of bulk chemicals using solvents, e.g. supercritical solvents or ionic liquids
Abstract
The invention discloses a method for preparing cannabidiol into cannabidiol and cannabidiol, belonging to the field of industrial cannabis processing. According to the invention, liquid cannabidiol is dissolved in an organic solvent, levulinic acid is added to obtain a mixed solution, the mixed solution is heated to a boiling state for reaction, after the reaction is finished, crystallization is carried out to obtain crystals, and the crystals are dissolved and separated to obtain cannabidene. The reaction principle is as follows: the cannabidiol has polyhydroxy groups, is alkaline, and the levulinic acid has carboxyl groups, is acidic, and under the condition of heating and boiling, the hydroxy groups on the heterocycle of the cannabidiol and the carboxyl groups on the levulinic acid are subjected to esterification reaction to obtain the cannabidimenyl. The preparation method disclosed by the invention is simple in preparation process, and the obtained cannabine is high in purity and yield, so that the technical problem that the yield of the cannabine is low when the industrial cannabis extracts the cannabinoid can be solved.
Description
Technical Field
The invention relates to the field of cannabinoids, in particular to a method for preparing cannabidiol from cannabidiol and cannabidiol.
Background
Cannabidiol (CBC) has a high economic value without any mental activity, i.e. it is not fanciful and can affect the activity of other cannabinoids. The economic value of CBC is prominent in medical applications, e.g., it has been shown that CBC can prevent further deterioration of breast cancer, because CBC can leave ANANDAMDIDE (an endogenous cannabinoid known in humans to be able to combat cancer) in the blood for a long period of time, and CBC also shows combat against breast cancer when CBC and THC and other cannabinoids work together. In addition, CBC has anti-inflammatory, antidepressant and brain cell neogenesis promoting effects.
Industrial hemp refers to hemp with tetrahydrocannabinol content lower than 0.3%, china refers to industrial hemp as hemp (hemp), and is annual herb of Cannabiaceae (Cannabinaceae) Cannabis (Cannabis). The desired cannabinoids are generally proposed from industrial cannabis, such as cannabidiol (CBC), cannabidiol (CBD), cannabidiol (CBDA), cannabinol (CBN), cannabigerol (CBG), cannabigerol acid (CBGA) and the like.
Cannabidiol (CBC) is distributed throughout industrial cannabis plants, and in some industrial cannabis plants, the content of cannabidiol (CBC) is higher than that of other cannabinoids such as Cannabidiol (CBD), however, since cannabidiol (CBC) is not the main cannabinoid, the cannabidiol (CBC) belongs to a by-product and is produced in lower yield when the cannabinoid is extracted from industrial cannabis. And Cannabidiol (CBD) is a main product of industrial cannabis, so that the conversion of Cannabidiol (CBD) into cannabidiol (CBC) can be considered, and the method has research significance in improving the utilization value of industrial cannabis in the field of medicines.
Disclosure of Invention
The invention mainly aims to provide a method for preparing cannabigerol from cannabidiol and the cannabigerol, and aims to solve the technical problem that the yield of cannabigerol (CBC) is low when the cannabinoids in industrial cannabis are extracted in the prior art.
To achieve the above object, the present invention provides a method for preparing cannabidiol from cannabidiol.
The method for preparing cannabidiol into cannabidiol comprises the following steps:
s10, dissolving liquid cannabidiol into an organic solvent, adding levulinic acid to obtain a mixed solution, and heating the mixed solution to a boiling state for reaction; ;
and S20, after the reaction in the step S10 is finished, crystallizing to obtain crystals, dissolving the crystals and separating to obtain the cannabidene.
Optionally, the organic solvent includes at least one of ethanol, methanol, or acetone.
Optionally, the molar ratio of cannabidiol to levulinic acid is 1: (1-4).
Further alternatively, the molar ratio of cannabidiol to levulinic acid is 1:2.
Optionally, the weight ratio of cannabidiol to organic solvent is 1: (0.1-0.2).
Optionally, the heating to boiling conditions is carried out at a boiling temperature of 180 ℃ to 220 ℃.
Optionally, the reaction time is 30-40 min.
Alternatively, the cannabidiol is isolated by supercritical chromatography.
Optionally, the crystallization method includes any one of cooling crystallization, recrystallization, and evaporation crystallization.
Optionally, the yield of the cannabidiol is 28% -40% based on the input weight of the cannabidiol.
The invention also provides cannabis chromene, which is prepared by the method, and the purity of the cannabis chromene is more than or equal to 90 percent.
The invention has the beneficial effects that:
The invention provides a method for preparing cannabidiol, which utilizes the cannabidiol which is a high-yield product of industrial cannabis to prepare low-yield cannabidiol, improves the yield of the cannabidiol in the process of extracting the cannabinoid from industrial cannabis, and the obtained cannabidiol also has high purity of more than 90 percent and the yield reaches 28-40 percent.
The principle of the invention is as follows: cannabidiol has a polyhydroxy structure, is alkaline, and levulinic acid has a carboxylic acid group and is acidic. The invention utilizes hydroxyl on cannabidiol heterocycle and carboxyl on levulinic acid to carry out esterification reaction in boiling state to obtain cannabine. The method has simple operation and shorter process flow, and can save resources.
Drawings
For a clearer description of embodiments of the invention or of solutions in the prior art, the following brief description of the drawings is given for the purpose of illustrating the embodiments or the solutions in the prior art, it being obvious that the drawings in the following description are only some embodiments of the invention, and that other drawings may be obtained from the structures shown in these drawings without the need for inventive effort for a person skilled in the art.
FIG. 1 is a schematic flow chart of a process for preparing cannabidiol from cannabidiol in accordance with the present invention.
The achievement of the objects, functional features and advantages of the present invention will be further described with reference to the accompanying drawings, in conjunction with the embodiments.
Detailed Description
It should be understood that the specific embodiments described herein are for purposes of illustration only and are not intended to limit the scope of the invention.
The following description of the embodiments of the present invention will be made clearly and fully with reference to the accompanying drawings, in which it is evident that the embodiments described are only some, but not all embodiments of the invention. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
The description as it relates to "first", "second", etc. in the present invention is for descriptive purposes only and is not to be construed as indicating or implying a relative importance or implicitly indicating the number of technical features indicated. Thus, a feature defining "a first" or "a second" may explicitly or implicitly include at least one such feature. In addition, the technical solutions of the embodiments may be combined with each other, but it is necessary to base that the technical solutions can be realized by those skilled in the art, and when the technical solutions are contradictory or cannot be realized, the combination of the technical solutions should be considered to be absent and not within the scope of protection claimed in the present invention.
Cannabidiol (CBC) is distributed throughout industrial cannabis plants, and in some industrial cannabis plants, the content of cannabidiol (CBC) is higher than that of other cannabinoids such as Cannabidiol (CBD), however, since cannabidiol (CBC) is not the main cannabinoid, the cannabidiol (CBC) belongs to a by-product and is produced in lower yield when the cannabinoid is extracted from industrial cannabis. And Cannabidiol (CBD) is a major product of industrial cannabis, so conversion of Cannabidiol (CBD) into cannabidiol (CBC) can be considered to improve the utility value of industrial cannabis in the medical field.
In view of this, the present invention provides a process for preparing cannabidiol into cannabidiol, comprising the steps of:
S10, dissolving liquid cannabidiol into an organic solvent, adding levulinic acid to obtain a mixed solution, and heating the mixed solution to a boiling state for reaction;
and S20, after the reaction in the step S10 is finished, crystallizing to obtain crystals, dissolving the crystals and separating to obtain the cannabidene.
Wherein the cannabidiol of the present invention has the structural formula (1):
Levulinic acid has the structural formula (2):
cannabigerol has structural formula (3):
as is clear from the structural formula (1), cannabidiol has a polyhydroxy structure, exhibits basicity, and levulinic acid has a carboxylic acid group, and exhibits acidity. The invention utilizes hydroxyl on cannabidiol heterocycle and carboxyl of levulinic acid to carry out esterification reaction, thus obtaining cannabidiol.
The reaction in the step is carried out in a boiling state, so that the raw materials can be promoted to react more completely, and the synthesis of the cannabis chromene is accelerated.
In the step S10, because the solubility of the solid cannabidiol in the organic solvent is very low and only about 30%, the liquid cannabidiol is selected as the reaction raw material, and has very good solubility and dispersibility in the organic solvent, thereby being beneficial to improving the utilization rate of the cannabidiol and obtaining the cannabidene with higher yield.
The present invention is not limited to the process for preparing liquid cannabidiol, and in some embodiments, liquid cannabidiol may be formed by heating solid cannabidiol to a temperature of 40 ℃ to 50 ℃.
The present invention is not limited to the kind of the organic solvent in step S10, and in some embodiments, the organic solvent is preferably at least one of ethanol, methanol or acetone, more preferably ethanol, and may be medical alcohol with a purity of 99%.
Under the condition of normal temperature and normal pressure, the boiling point of the cannabidiol is up to 463.9 ℃, more resources are required to be consumed if the boiling reaction state is to be achieved, or higher-end instruments and equipment are used, the organic solvent has higher solubility for the cannabidiol, can improve the yield of the cannabidiol, can also play a role in reducing the azeotropic point of the whole reaction system, can control the reaction system to achieve the boiling state at a lower temperature, and saves resources.
In some embodiments, the boiling temperature in the reaction by heating to boiling is preferably 180 ℃ to 220 ℃.
The invention is not limited to the reaction time for the reaction by heating the mixture to boiling, and preferably, in some embodiments, the reaction time is 30min to 40min.
The invention is also not limited to the molar ratio of cannabidiol to levulinic acid, preferably the molar ratio of cannabidiol to levulinic acid prior to carrying out the reaction is 1: (1-4), more preferably 1:2. At the above molar ratio, a high yield of cannabidiol can be obtained.
In some embodiments, after dissolving the liquid cannabidiol in the organic solvent and adding levulinic acid, the mixture may be further stirred at a speed of 500rpm to 1000 rpm.
It will be appreciated that the above restrictions on the type of organic solvent, the temperature to which the heating is to be carried out, the time of the reaction, the weight ratio of cannabidiol to organic solvent, and the molar ratio of cannabidiol to levulinic acid may be satisfied either or both, and the reaction may be completed to obtain the cannabidene having higher yield and purity.
In step S20, the crystallization may include any one of cooling crystallization, recrystallization, and evaporation crystallization. The obtained crystals contain a large amount of cannabidiol and cannabidiol which do not participate in the reaction and other impurities, and the cannabidiol with better purity can be obtained through separation.
In some embodiments, the crystals are dissolved with an organic solvent, preferably at least one of ethanol, methanol, acetone, chloroform, diethyl ether, having good solubility for both cannabidiol and cannabidiol in the crystals.
After dissolution of the crystals, the present invention is not limited to the manner in which the cannabidiol is isolated therefrom, and in some embodiments, the isolation may be performed by supercritical chromatography, and high purity solid cannabidiol may be obtained.
In some embodiments, the mobile phase used in the supercritical chromatography is carbon dioxide, and organic solvents such as acetonitrile, methanol, isopropanol, ethyl acetate and the like are used as auxiliary agents, the separation temperature is preferably minus 100 ℃ to 160 ℃, the cannabidene and other impurities are in solid states at the temperature of minus 100 ℃ to 160 ℃, under the above separation conditions, the purification time of the cannabidene is shortened, the separation efficiency is improved, and the high-purity cannabidene is obtained.
The cannabidiol obtained by the method has high purity of more than 90 percent, and the yield of the cannabidiol is 28-40 percent based on the input weight of the cannabidiol.
The present invention provides a preferred embodiment of a process for preparing cannabidiol from cannabidiol, comprising the steps of:
S10, pouring solid cannabidiol into a beaker, heating to 40-50 ℃, and heating to obtain liquid cannabidiol, wherein the liquid cannabidiol is prepared by mixing cannabidiol with an organic solvent 1: (0.1-0.2) adding an organic solvent into liquid cannabidiol according to the weight ratio of the cannabidiol to the levulinic acid 1: adding levulinic acid into the reaction system according to the molar ratio of (1-4), stirring uniformly at the rotating speed of 500-1000 rpm to obtain mixed solution, heating the mixed solution to 180-220 ℃ to enable the reaction system to reach a boiling state, and continuously reacting for 30-40 min under the boiling state.
S20, crystallizing the reaction system to separate out crystals after the reaction in the step S10 is finished, crushing the crystals, dissolving the crystals into an organic solvent, and separating to obtain the cannabine.
The technical scheme of the present invention will be further described in detail with reference to the following specific examples, which are to be construed as merely illustrative, and not limitative of the remainder of the disclosure.
Example 1
Referring to fig. 1, fig. 1 is a schematic flow chart of an embodiment 1 of a method for preparing cannabidiol according to the present invention.
In this embodiment, the method for preparing cannabidiol from cannabidiol comprises the following steps:
S10, pouring 50g of cannabidiol into a beaker, heating to 40 ℃, obtaining liquid cannabidiol by heating, mixing the liquid cannabidiol with 7.5g of medical alcohol with the purity of 99%, adding 37g of levulinic acid, stirring uniformly at the speed of 500rpm to obtain a mixed solution, heating the mixed solution to 180 ℃, enabling a reaction system to reach a boiling state, and continuously reacting for 30min under the boiling state.
S20, after the reaction in the step S10 is finished, cooling to 25 ℃, precipitating crystals, crushing the crystals, dissolving the crystals into medical alcohol with the purity of 99%, then taking carbon dioxide as a mobile phase and ethyl acetate as an auxiliary phase, setting the separation temperature to be minus 100 ℃, and separating by a supercritical chromatography to obtain the solid cannabidene.
Example 2
Referring to fig. 1, fig. 1 is a schematic flow chart of an embodiment 1 of a method for preparing cannabidiol according to the present invention.
In this embodiment, the method for preparing cannabidiol from cannabidiol comprises the following steps:
S10, pouring 50.00g of cannabidiol into a beaker, heating to 50 ℃, obtaining liquid cannabidiol by heating, mixing the liquid cannabidiol with 5.00g of methanol, adding 18.56g of levulinic acid, stirring uniformly at a speed of 800rpm, obtaining a mixed solution, heating the mixed solution to 200 ℃, enabling a reaction system to reach a boiling state, and continuously reacting for 35min under the boiling state.
S20, after the reaction in the step S10 is finished, cooling to 25 ℃, precipitating crystals, crushing the crystals, dissolving the crystals into a methanol solution, then taking carbon dioxide as a mobile phase and acetonitrile as an auxiliary phase, setting the separation temperature to be below 150 ℃, and separating by a supercritical chromatography to obtain the solid cannabidene.
Example 3
Referring to fig. 1, fig. 1 is a schematic flow chart of an embodiment 3 of a method for preparing cannabidiol according to the present invention.
In this embodiment, the method for preparing cannabidiol from cannabidiol comprises the following steps:
S10, pouring 50.00g of cannabidiol into a beaker, heating to 45 ℃, obtaining liquid cannabidiol by heating, mixing the liquid cannabidiol with 10.00g of acetone, adding 73.85g of levulinic acid, stirring uniformly at a rotating speed of 1000rpm, obtaining a mixed solution, heating the mixed solution to 220 ℃, enabling a reaction system to reach a boiling state, and continuously reacting for 40min under the boiling state.
S20, after the reaction in the step S10 is finished, cooling to 25 ℃, precipitating crystals, crushing the crystals, dissolving the crystals into an acetone solution, taking carbon dioxide as a mobile phase and ethyl acetate as an auxiliary phase, setting the separation temperature to be below 160 ℃, and separating by a supercritical chromatography to obtain the solid cannabidene.
Example 4
Referring to fig. 1, fig. 1 is a schematic flow chart of an embodiment 4 of a method for preparing cannabidiol according to the present invention.
In this embodiment, the method for preparing cannabidiol from cannabidiol comprises the following steps:
S10, pouring 50.00g of cannabidiol into a beaker, heating to 40 ℃, obtaining liquid cannabidiol by heating, mixing the liquid cannabidiol with 7.50g of medical alcohol with the purity of 99%, adding 55.39g of levulinic acid, stirring uniformly at the speed of 1000rpm to obtain a mixed solution, heating the mixed solution to 210 ℃, enabling a reaction system to reach a boiling state, and continuously reacting for 35min under the boiling state.
S20, after the reaction in the step S10 is finished, cooling to 25 ℃, precipitating crystals, crushing the crystals, dissolving the crystals into medical alcohol with the purity of 99%, taking carbon dioxide as a mobile phase and isopropanol as an auxiliary phase, setting the separation temperature to be minus 120 ℃, and separating by a supercritical chromatography to obtain the solid cannabidene.
Example 5
Referring to fig. 1, fig. 1 is a schematic flow chart of an embodiment 5 of a method for preparing cannabidiol according to the present invention.
In this embodiment, the method for preparing cannabidiol from cannabidiol comprises the following steps:
s10, pouring 50g of cannabidiol into a beaker, heating to 40 ℃, obtaining liquid cannabidiol by heating, mixing the liquid cannabidiol with 7.5g of ethanol solution, adding 46.16g of levulinic acid, stirring uniformly at a rotating speed of 500rpm, obtaining a mixed solution, heating the mixed solution to 180 ℃, enabling a reaction system to reach a boiling state, and continuously reacting for 40min under the boiling state.
S20, after the reaction in the step S10 is finished, cooling to 25 ℃, precipitating crystals, crushing the crystals, dissolving the crystals into an ethanol solution, taking carbon dioxide as a mobile phase and ethyl acetate as an auxiliary phase, setting the separation temperature to be below 160 ℃, and separating by a supercritical chromatography to obtain the solid cannabidene.
Comparative example 1
Comparative example 1 differs from the preparation method of example 1 in that the cannabidiol used in step S10 of comparative example 1 is a solid cannabidiol.
Comparative example 2
Comparative example 2 differs from the preparation of example 1 in that the molar ratio of cannabidiol to levulinic acid used in step S10 of comparative example 2 is 1:5.
Comparative example 3
Comparative example 3 differs from the preparation of example 1 in that the molar ratio of cannabidiol to levulinic acid used in step S10 of comparative example 3 is 1:0.5.
Comparative example 4
Comparative example 3 is different from the preparation method of example 1 in that comparative example 4 is heated to 80 c in step S10, and the reaction system is controlled to perform the reaction in a non-boiling state.
Performance testing
The purity and yield of the cannabidiol obtained in examples 1 to 5 and comparative examples 1 to 4 were measured, and the results are shown in table 1.
Wherein the yield of cannabigerol is calculated by the following formula:
cannabis chromene yield (%) = (cannabis chromene weight/cannabidiol feed weight) ×100%.
Table 1 purity and yield of cannabidiol obtained in examples 1 to 5 and comparative examples 1 to 4
As can be seen from table 1: the cannabis chromene prepared by the method has the yield of 28-40% and the purity of more than 90%.
Comparative example 1 the reaction was carried out using solid cannabidiol, which resulted in incomplete reaction due to its very low solubility in alcohol, lower yield of cannabidiol, and only 65.4% of purity of cannabidiol was affected due to the more subsequent impurities, which was not ideal in separation effect.
Too much levulinic acid of comparative example 2 and too little levulinic acid of comparative example 3 may cause surplus of raw material cannabidiol or levulinic acid, which in turn affects yield and purity of cannabidiol.
The reaction in comparative example 4 was not carried out in a boiling state, and the reaction was incomplete, and the yield and purity of cannabidiol were also affected.
The foregoing description is only of the preferred embodiments of the present invention, and is not intended to limit the scope of the invention, but rather is intended to cover any equivalents of the structures or equivalent processes disclosed herein or in the alternative, which may be employed directly or indirectly in other related arts.
Claims (5)
1. A process for preparing cannabidiol from cannabidiol comprising the steps of:
dissolving liquid cannabidiol into an organic solvent, adding levulinic acid to obtain a mixed solution, and heating the mixed solution to a boiling state for reaction;
after the reaction is finished, crystallizing to obtain crystals, dissolving the crystals and separating to obtain cannabine;
the liquid cannabidiol is obtained by heating solid cannabidiol to 40-50deg.C;
The molar ratio of cannabidiol to levulinic acid is 1: (1-4);
the boiling temperature in the reaction after heating to a boiling state is 180-220 ℃;
separating to obtain cannabinene by supercritical chromatography, wherein the mobile phase used by the supercritical chromatography is carbon dioxide, and the separation temperature is minus 100-160 ℃ by taking an organic solvent as an auxiliary agent;
taking the input weight of the cannabidiol as a reference, the yield of the cannabidiol is 28% -40%;
the purity of the cannabidiol is more than or equal to 90 percent.
2. The method of preparing cannabidiol according to claim 1, wherein the organic solvent comprises at least one of ethanol, methanol or acetone.
3. The method for preparing cannabidiol according to claim 1, wherein the weight ratio of cannabidiol to the organic solvent is 1: (0.1-0.2).
4. The method for preparing cannabidiol according to claim 1, wherein the reaction time is 30-40 min.
5. The method for preparing cannabidiol according to claim 1, wherein the crystallization method for obtaining crystals comprises any one of cooling crystallization, recrystallization, and evaporation crystallization.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US9950976B1 (en) * | 2015-10-27 | 2018-04-24 | CLS Labs, Inc. | Cannabidiol extraction and conversion process |
| WO2021207605A1 (en) * | 2020-04-10 | 2021-10-14 | 3Bc, Llc | Methods for preparing cannabinoids and related instruments |
| CN115066238A (en) * | 2019-12-27 | 2022-09-16 | 海湾医学公司 | Preparation of cannabichromenes and related cannabinoids |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9950976B1 (en) * | 2015-10-27 | 2018-04-24 | CLS Labs, Inc. | Cannabidiol extraction and conversion process |
| CN115066238A (en) * | 2019-12-27 | 2022-09-16 | 海湾医学公司 | Preparation of cannabichromenes and related cannabinoids |
| WO2021207605A1 (en) * | 2020-04-10 | 2021-10-14 | 3Bc, Llc | Methods for preparing cannabinoids and related instruments |
Non-Patent Citations (1)
| Title |
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| Photochemistry of Cannabidiol (CBD) Revised. A Combined Preparative and Spectrometric Investigation;Paolo Seccamani et al.;J. Nat. Prod.;第84卷;第2858−2865页 * |
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