CN113956226A - Method for synthesizing carvachin - Google Patents
Method for synthesizing carvachin Download PDFInfo
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- CN113956226A CN113956226A CN202111401350.5A CN202111401350A CN113956226A CN 113956226 A CN113956226 A CN 113956226A CN 202111401350 A CN202111401350 A CN 202111401350A CN 113956226 A CN113956226 A CN 113956226A
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- 230000002194 synthesizing effect Effects 0.000 title claims abstract description 28
- 238000000034 method Methods 0.000 title claims abstract description 21
- 238000006243 chemical reaction Methods 0.000 claims abstract description 20
- 239000002904 solvent Substances 0.000 claims abstract description 19
- KGFYDIZALLKOLQ-UHFFFAOYSA-N 1-(2-Hydroxy-4,6-dimethoxy-phenyl)-3-(4-methoxy-phenyl)-propan-1-on Natural products C1=CC(OC)=CC=C1CCC(=O)C1=C(O)C=C(OC)C=C1OC KGFYDIZALLKOLQ-UHFFFAOYSA-N 0.000 claims abstract description 14
- BIVPXTSQQZIUFJ-UHFFFAOYSA-N 2'-hydroxy-4,4',6'-trimethoxychalcone Natural products C1=CC(OC)=CC=C1C(=O)C=CC1=C(O)C=C(OC)C=C1OC BIVPXTSQQZIUFJ-UHFFFAOYSA-N 0.000 claims abstract description 14
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims abstract description 14
- CGIBCVBDFUTMPT-RMKNXTFCSA-N Flavokawain A Chemical compound C1=CC(OC)=CC=C1\C=C\C(=O)C1=C(O)C=C(OC)C=C1OC CGIBCVBDFUTMPT-RMKNXTFCSA-N 0.000 claims abstract description 14
- CGIBCVBDFUTMPT-UHFFFAOYSA-N flavokawain A Natural products C1=CC(OC)=CC=C1C=CC(=O)C1=C(O)C=C(OC)C=C1OC CGIBCVBDFUTMPT-UHFFFAOYSA-N 0.000 claims abstract description 14
- ZXJJBDHPUHUUHD-UHFFFAOYSA-N 4',5,7-Trimethoxyflavone Chemical compound C1=CC(OC)=CC=C1C1=CC(=O)C2=C(OC)C=C(OC)C=C2O1 ZXJJBDHPUHUUHD-UHFFFAOYSA-N 0.000 claims abstract description 13
- KPZWHZSIXZXDMW-UHFFFAOYSA-N 1-(2,4,6-trimethoxyphenyl)ethanone Chemical compound COC1=CC(OC)=C(C(C)=O)C(OC)=C1 KPZWHZSIXZXDMW-UHFFFAOYSA-N 0.000 claims abstract description 12
- HHTWOMMSBMNRKP-UHFFFAOYSA-N carvacrol Natural products CC(=C)C1=CC=C(C)C(O)=C1 HHTWOMMSBMNRKP-UHFFFAOYSA-N 0.000 claims abstract description 12
- RECUKUPTGUEGMW-UHFFFAOYSA-N carvacrol Chemical compound CC(C)C1=CC=C(C)C(O)=C1 RECUKUPTGUEGMW-UHFFFAOYSA-N 0.000 claims abstract description 12
- 235000007746 carvacrol Nutrition 0.000 claims abstract description 12
- WYXXLXHHWYNKJF-UHFFFAOYSA-N isocarvacrol Natural products CC(C)C1=CC=C(O)C(C)=C1 WYXXLXHHWYNKJF-UHFFFAOYSA-N 0.000 claims abstract description 12
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- KZNIFHPLKGYRTM-UHFFFAOYSA-N apigenin Chemical compound C1=CC(O)=CC=C1C1=CC(=O)C2=C(O)C=C(O)C=C2O1 KZNIFHPLKGYRTM-UHFFFAOYSA-N 0.000 claims abstract description 10
- 239000002994 raw material Substances 0.000 claims abstract description 10
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 8
- 238000010520 demethylation reaction Methods 0.000 claims abstract description 7
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 6
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims abstract description 5
- 238000005917 acylation reaction Methods 0.000 claims abstract description 5
- 230000017858 demethylation Effects 0.000 claims abstract description 5
- FAQYAMRNWDIXMY-UHFFFAOYSA-N trichloroborane Chemical group ClB(Cl)Cl FAQYAMRNWDIXMY-UHFFFAOYSA-N 0.000 claims abstract description 5
- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 claims description 22
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 12
- JQNMAEHFTQBROH-JXMROGBWSA-N (e)-3-(4-methoxyphenyl)-1-(2,4,6-trimethoxyphenyl)prop-2-en-1-one Chemical compound C1=CC(OC)=CC=C1\C=C\C(=O)C1=C(OC)C=C(OC)C=C1OC JQNMAEHFTQBROH-JXMROGBWSA-N 0.000 claims description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 8
- 230000001335 demethylating effect Effects 0.000 claims description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- LPACBRAWRCXZGB-UHFFFAOYSA-N 3-methyl-2-phenylchromen-4-one Chemical compound O1C2=CC=CC=C2C(=O)C(C)=C1C1=CC=CC=C1 LPACBRAWRCXZGB-UHFFFAOYSA-N 0.000 claims description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical group CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 6
- -1 2' -hydroxy-4, 4', 6' -trimethoxychalcone 2',4,4',6 '-tetramethoxychalcone Chemical compound 0.000 claims description 5
- GAMYVSCDDLXAQW-AOIWZFSPSA-N Thermopsosid Natural products O(C)c1c(O)ccc(C=2Oc3c(c(O)cc(O[C@H]4[C@H](O)[C@@H](O)[C@H](O)[C@H](CO)O4)c3)C(=O)C=2)c1 GAMYVSCDDLXAQW-AOIWZFSPSA-N 0.000 claims description 5
- 229930003944 flavone Natural products 0.000 claims description 5
- 235000011949 flavones Nutrition 0.000 claims description 5
- 235000013824 polyphenols Nutrition 0.000 claims description 5
- VHBFFQKBGNRLFZ-UHFFFAOYSA-N vitamin p Natural products O1C2=CC=CC=C2C(=O)C=C1C1=CC=CC=C1 VHBFFQKBGNRLFZ-UHFFFAOYSA-N 0.000 claims description 5
- DQFBYFPFKXHELB-UHFFFAOYSA-N Chalcone Natural products C=1C=CC=CC=1C(=O)C=CC1=CC=CC=C1 DQFBYFPFKXHELB-UHFFFAOYSA-N 0.000 claims description 4
- 235000005513 chalcones Nutrition 0.000 claims description 4
- 239000003153 chemical reaction reagent Substances 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- ZRSNZINYAWTAHE-UHFFFAOYSA-N p-methoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C=C1 ZRSNZINYAWTAHE-UHFFFAOYSA-N 0.000 claims description 4
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 238000007363 ring formation reaction Methods 0.000 claims description 4
- DQFBYFPFKXHELB-VAWYXSNFSA-N trans-chalcone Chemical compound C=1C=CC=CC=1C(=O)\C=C\C1=CC=CC=C1 DQFBYFPFKXHELB-VAWYXSNFSA-N 0.000 claims description 4
- 238000005882 aldol condensation reaction Methods 0.000 claims description 3
- 239000012649 demethylating agent Substances 0.000 claims description 3
- 150000002212 flavone derivatives Chemical class 0.000 claims description 3
- 230000035484 reaction time Effects 0.000 claims description 3
- 238000006798 ring closing metathesis reaction Methods 0.000 claims description 2
- ULDHMXUKGWMISQ-UHFFFAOYSA-N carvone Chemical compound CC(=C)C1CC=C(C)C(=O)C1 ULDHMXUKGWMISQ-UHFFFAOYSA-N 0.000 claims 4
- 239000005973 Carvone Substances 0.000 claims 2
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- 231100000086 high toxicity Toxicity 0.000 abstract description 3
- 210000004027 cell Anatomy 0.000 description 4
- QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- GMVJKSNPLYBFSO-UHFFFAOYSA-N 1,2,3-tribromobenzene Chemical compound BrC1=CC=CC(Br)=C1Br GMVJKSNPLYBFSO-UHFFFAOYSA-N 0.000 description 1
- YWDUZLFWHVQCHY-UHFFFAOYSA-N 1,3,5-tribromobenzene Chemical compound BrC1=CC(Br)=CC(Br)=C1 YWDUZLFWHVQCHY-UHFFFAOYSA-N 0.000 description 1
- LKUDPHPHKOZXCD-UHFFFAOYSA-N 1,3,5-trimethoxybenzene Chemical compound COC1=CC(OC)=CC(OC)=C1 LKUDPHPHKOZXCD-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
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- 238000012404 In vitro experiment Methods 0.000 description 1
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- 244000046052 Phaseolus vulgaris Species 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
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- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- 244000269722 Thea sinensis Species 0.000 description 1
- 238000007792 addition Methods 0.000 description 1
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
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- 230000002401 inhibitory effect Effects 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
- C07D311/26—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3
- C07D311/28—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 2 only
- C07D311/30—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 2 only not hydrogenated in the hetero ring, e.g. flavones
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a method for synthesizing carvacrol, which comprises the following steps: s01: synthesizing 2-hydroxy-4, 6-dimethoxyacetophenone, preparing 2,4, 6-trimethoxyacetophenone by acylation reaction of aniline, wherein a solvent is boron trichloride, and dichloroethane is subjected to selective demethylation under the condition of 0 ℃ to obtain 2-hydroxy-4, 6-dimethoxyacetophenone; s02: synthesizing 2' -hydroxy-4, 4',6 ' -trimethoxychalcone; s03: synthesis of 4',5, 7-trimethoxyflavone, S04: synthesizing 4',5, 7-trihydroxyflavone; the method has the advantages of easily available raw materials, mild reaction conditions and good yield, and solves the problems that the traditional method has low extraction rate, high energy consumption and high cost, is difficult to meet the increasing market demand, uses a solvent with high toxicity and high price, is easy to cause environmental pollution and causes high production cost, and simultaneously has complicated steps, long time consumption and low yield.
Description
Technical Field
The invention belongs to the technical field of carvacrol extraction, and particularly relates to a synthesis method of carvacrol.
Background
Carvachin, also known as 4',5, 7-trihydroxyflavone, carvachin is a natural polyphenol flavone compound, has estrogen-like action, is widely present in various fruits, vegetables, beans and tea leaves, wherein the carvachin has the highest content and various pharmacological actions, and has a wide anticancer range, in vitro experiments show that the carvachin has an inhibitory action on various tumor cells, such as liver cancer cells, stomach cancer cells, breast cancer cells, prostate cancer cells and the like, and has a wide application prospect, and because the content of the carvachin in medicinal materials is very low, the carvachin is usually prepared by a method of directly extracting from plants, the production of the carvachin can be improved by a chemical synthesis method, and the quality of the medicine can be greatly improved, so the carvachin is valued by researchers;
there are two main methods reported for synthesizing carvachin, one is obtained by some simple reactions using other readily available natural compounds, generally called semi-synthesis, and the second is synthesized by multi-step reactions using readily available chemical raw materials, called total synthesis;
at present, the traditional method for producing the carvacrol has low extraction rate, high energy consumption and high cost, is difficult to meet the increasing market demand, uses a solvent with higher toxicity and high price, is easy to cause environmental pollution and causes higher production cost, and has the disadvantages of complicated steps, long time consumption and low yield.
Disclosure of Invention
The invention aims to provide a method for synthesizing carvacrol, which mainly solves the following technical problems:
the traditional method has the advantages of low extraction rate, high energy consumption, high cost, difficulty in meeting the increasing market demand, use of a solvent with high toxicity and high price, easiness in causing environmental pollution and high production cost, complex steps, long time consumption and low yield.
The purpose of the invention can be realized by the following technical scheme:
the method for synthesizing the carvacrol comprises the following steps:
s01: synthesizing 2-hydroxy-4, 6-dimethoxyacetophenone, preparing 2,4, 6-trimethoxyacetophenone by acylation reaction of aniline, wherein a solvent is boron trichloride, and dichloroethane is subjected to selective demethylation under the condition of 0 ℃ to obtain 2-hydroxy-4, 6-dimethoxyacetophenone;
s02: synthesizing 2' -hydroxy-4, 4',6 ' -trimethoxychalcone, 2,4, 6-trimethoxyacetophenone and p-methoxybenzaldehyde are used as raw materials to obtain 2',4,4',6 ' -tetramethoxy chalcone through claisen-Schmidt reaction, then, selectively demethylating to obtain 2 '-hydroxy-4, 4',6 '-trimethoxychalcone, wherein the selective demethylating reaction time of the 2' -hydroxy-4, 4', 6' -trimethoxychalcone 2',4,4',6 '-tetramethoxychalcone is 2 hours, a solvent dichloromethane is added in the reaction process, and finally, the obtained 2' -hydroxy-4, 4', 6' -trimethoxychalcone is darker in color and needs to be recrystallized and decolored;
s03: synthesizing 4',5, 7-trimethoxy flavone, wherein chalcone in the previous step is subjected to ring closure reaction, and a ring closure reagent is DMF (dimethyl formamide), so as to obtain methylated flavone;
s04: the synthesis of 4',5, 7-trihydroxy flavone adopts pyridine hydrochloride to remove methyl of methyl flavone, the pyridine hydrochloride is used as a solvent and participates in chemical reaction, and after methyl is removed, a plurality of phenolic hydroxyl groups on a benzene ring are relatively active and are easy to oxidize, the whole reaction environment needs to be sealed, and nitrogen is used for replacing air in a system for protection.
As a further scheme of the invention: the selective demethylation in S01 adopts BC13As a selective demethylating agent, BC13The molar ratio of the 2,4, 6-trimethoxyacetophenone to the ethyl acetate is 1.2: 1.
As a further scheme of the invention: 2',4,4',6 ' -tetramethoxy chalcone in S02 and BC13In a molar ratio of 1: 1.2.
As a further scheme of the invention: the chemical reaction temperature in S04 was 120 degrees.
As a further scheme of the invention: the dosage of the pyridine hydrochloride in the S04 is 8 times of that of the methylflavone.
The invention has the beneficial effects that:
the method has the advantages of easily available raw materials, mild reaction conditions and good yield, and solves the problems that the traditional method has low extraction rate, high energy consumption and high cost, is difficult to meet the increasing market demand, uses a solvent with high toxicity and high price, easily causes environmental pollution and causes high production cost, and simultaneously has complicated steps, long time consumption and low yield.
Drawings
The invention will be further described with reference to the accompanying drawings.
FIG. 1 is a chemical structural formula of the carvacrol of the present invention;
FIG. 2 is a synthetic expression of 2-hydroxy-4, 6-dimethoxyacetophenone of the present invention;
FIG. 3 is a synthetic expression of 2' -hydroxy-4, 4',6 ' -trimethoxychalcone of the present invention;
FIG. 4 is a synthetic expression of 4',5, 7-trimethoxyflavone of the present invention;
fig. 5 is a synthetic expression of carvacrol of the present invention.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Example 1, as shown in fig. 1-5, a method for synthesizing carvacrol is provided, comprising the steps of:
s01: synthesizing 2-hydroxy-4, 6-dimethoxyacetophenone, and preparing 2,4, 6-trimethoxyacetophenone by acylation reaction of aniline: reacting 30g of aniline and 100g of hydrobromic acid in 100ml of hydrogen peroxide at room temperature for 6 hours to obtain 2,4, 6-tribromobenzene, wherein the yield can reach 96%, the obtained tribromobenzene uses sulfuric acid as an oxidant and ethanol as a solvent, slowly dropwise adding a sodium nitrite solution at room temperature, deaminating to obtain 2,4, 6-trimethoxybenzene, the yield reaches 85%, and then, selectively demethylating by adopting a solvent of boron trichloride and dichloroethane at 0-5 ℃ to obtain 2-hydroxy-4, 6-dimethoxyacetophenone;
s02: the synthesis of 2' -hydroxy-4, 4',6 ' -trimethoxychalcone takes 2,4, 6-trimethoxyacetophenone and p-methoxybenzaldehyde as raw materials, and the molar ratio of the two is 1: 1.05, obtaining 2',4,4',6 ' -tetramethoxychalcone by claisen-Schmidt reaction, using aluminum trichloride as a catalyst, using carbon disulfide as a solvent, stirring for 4 hours at about 40 ℃, obtaining the yield of 86%, then selectively demethylating to obtain 2' -hydroxy-4, 4',6 ' -trimethoxychalcone, and obtaining the 2' -hydroxy-4, 4',6 ' -trimethoxychalcone 2',4,4',6 ' -tetramethoxychalcone, wherein the selective demethylation reaction time is 2 hours, adding dichloromethane as the solvent in the reaction process, and finally obtaining the 2' -hydroxy-4, 4',6 ' -trimethoxychalcone with darker color and needing recrystallization and decolorization, wherein the yield is 80%;
s03: synthesizing 4',5, 7-trimethoxy flavone by a cyclization reaction of chalcone in the previous step, wherein the cyclization reagent is DMF (dimethyl formamide), and the molar ratio of the chalcone to the DMF is 1: 1.1, reacting for 3 hours at room temperature to obtain methylated 4',5, 7-trimethoxy flavone;
s04: synthesizing 4',5, 7-trihydroxy flavone, removing methyl of methylflavone by pyridine hydrochloride, wherein the molar ratio of the two is 1: and 8, pyridine hydrochloride is used as a solvent and also participates in chemical reaction, and after methyl is removed, a plurality of phenolic hydroxyl groups on a benzene ring are relatively active and are easy to oxidize, the whole reaction environment needs to be sealed, and nitrogen is used for replacing air in a system for protection.
Example 2, as shown in fig. 1 to 5, the method for synthesizing carvacrol comprises the following steps:
s01: synthesizing 2-hydroxy-4, 6-dimethoxyacetophenone, preparing 2,4, 6-trimethoxyacetophenone by acylation reaction of aniline, selectively demethylating dichloroethane at 0 deg.C in the presence of boron trichloride to obtain 2-hydroxy-4, 6-dimethoxyacetophenone, and optionally preparing N-acetyl-D-methyl-L-methyl-N-ethyl-N-methyl-N-phenyl-N-methyl-N-ethyl-N-methyl-N-phenyl-N-methyl-N-phenyl-N-ethyl-N-methyl-ethyl-N-ethyl-phenyl-ethyl-phenyl with BC1 as solvent3As a selective demethylating agent, BC13The molar ratio of the 2,4, 6-trimethoxyacetophenone is 1.2:1, and the yield reaches about 90 percent;
s02: synthesizing 2' -hydroxy-4, 4',6 ' -trimethoxychalcone, using 2,4, 6-trimethoxyacetophenone and p-methoxybenzaldehyde as raw materials, obtaining 2',4,4',6 ' -tetramethoxychalcone by claisen-schmitt reaction, then selectively demethylating to obtain 2' -hydroxy-4, 4',6 ' -trimethoxychalcone, and 2',4,4',6 ' -tetramethoxychalcone, the selective demethylation reaction is quicker, the reaction only needs 2 hours, the molar ratio of the 2',4,4',6 ' -tetramethoxychalcone to BC13 is 1:1.2, and solvent dichloromethane is added in the reaction process, the finally obtained 2' -hydroxy-4, 4',6 ' -trimethoxy chalcone has darker color and needs to be recrystallized and decolored;
s03: the synthesis of 4',5, 7-trimethoxy flavone is a commonly used method for synthesizing flavone compounds at present, wherein a ring closing reagent selected is DMF (dimethyl formamide), methylated flavone is obtained, when the molar ratio of the iodine to the raw materials is 3:24, the yield can reach 87.6 percent at the highest, and the temperature is 120 ℃ at the best;
s04: the synthesis of 4',5, 7-trihydroxy carvachin is carried out by removing methyl of methylflavone with pyridine hydrochloride, wherein the pyridine hydrochloride is used as solvent and participates in chemical reaction at 120 ℃, the reaction temperature is 120 ℃, the benzene ring has a plurality of phenolic hydroxyl groups which are relatively active and easy to be oxidized after removing the methyl, the whole reaction environment needs to be sealed, and nitrogen is used for replacing air in a system for protection, experiments show that when the using amount of the pyridine hydrochloride is 8 times of that of the methylflavone, the raw materials are basically reacted completely, and the total yield from aniline raw materials to carvachin products reaches the maximum value of 39.3 percent through calculation.
In the description herein, references to the description of "one embodiment," "an example," "a specific example" or the like are intended to mean that a particular feature, structure, material, or characteristic described in connection with the embodiment or example is included in at least one embodiment or example of the invention. In this specification, the schematic representations of the terms used above do not necessarily refer to the same embodiment or example. Furthermore, the particular features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments or examples.
The foregoing is merely exemplary and illustrative of the present invention and various modifications, additions and substitutions may be made by those skilled in the art to the specific embodiments described without departing from the scope of the invention as defined in the following claims.
Claims (5)
1. The method for synthesizing the carvacrol is characterized by comprising the following steps of:
s01: synthesizing 2-hydroxy-4, 6-dimethoxyacetophenone, preparing 2,4, 6-trimethoxyacetophenone by acylation reaction of aniline, wherein a solvent is boron trichloride, and dichloroethane is subjected to selective demethylation under the condition of 0-5 ℃ to obtain 2-hydroxy-4, 6-dimethoxyacetophenone;
s02: synthesizing 2' -hydroxy-4, 4',6 ' -trimethoxychalcone, 2,4, 6-trimethoxyacetophenone and p-methoxybenzaldehyde are used as raw materials to obtain 2',4,4',6 ' -tetramethoxy chalcone through claisen-Schmidt reaction, then, selectively demethylating to obtain 2 '-hydroxy-4, 4',6 '-trimethoxychalcone, wherein the selective demethylating reaction time of the 2' -hydroxy-4, 4', 6' -trimethoxychalcone 2',4,4',6 '-tetramethoxychalcone is 2 hours, a solvent dichloromethane is added in the reaction process, and finally, the obtained 2' -hydroxy-4, 4', 6' -trimethoxychalcone is darker in color and needs to be recrystallized and decolored;
s03: synthesizing 4',5, 7-trimethoxy flavone, wherein chalcone in the previous step is subjected to ring closure reaction, and a ring closure reagent is DMF (dimethyl formamide), so as to obtain methylated flavone;
s04: the synthesis of 4',5, 7-trihydroxy flavone adopts pyridine hydrochloride to remove methyl of methyl flavone, the pyridine hydrochloride is used as a solvent and participates in chemical reaction, and after methyl is removed, a plurality of phenolic hydroxyl groups on a benzene ring are relatively active and are easy to oxidize, the whole reaction environment needs to be sealed, and nitrogen is used for replacing air in a system for protection.
2. The method for synthesizing carvachin of claim 1, wherein the selective demethylation in S01 adopts BC13As a selective demethylating agent, BC13The molar ratio of the 2,4, 6-trimethoxyacetophenone to the ethyl acetate is 1.2: 1.
3. The method for synthesizing carvone according to claim 2, wherein 2',4,4',6 ' -tetramethoxychalcone and BC1 in S02 are used3In a molar ratio of 1: 1.2.
4. The method for synthesizing carvacrol according to claim 1, wherein the chemical reaction temperature in the S04 is 120 ℃.
5. The method for synthesizing carvone according to claim 1, wherein the dosage of pyridine hydrochloride in S04 is 8 times of that of methyl flavone.
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| CN102079737A (en) * | 2010-12-31 | 2011-06-01 | 昆明理工大学 | Method for preparing apigenin |
| CN104031016A (en) * | 2014-06-24 | 2014-09-10 | 陕西嘉禾植物化工有限责任公司 | Synthetic method of apigenin |
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| CN112824370A (en) * | 2019-11-20 | 2021-05-21 | 南京科技职业学院 | Method for synthesizing pentamethoxyl chalcone |
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| CN102079737A (en) * | 2010-12-31 | 2011-06-01 | 昆明理工大学 | Method for preparing apigenin |
| CN104031016A (en) * | 2014-06-24 | 2014-09-10 | 陕西嘉禾植物化工有限责任公司 | Synthetic method of apigenin |
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