CN108084004B - Method for synthesizing emodin anthrone - Google Patents

Method for synthesizing emodin anthrone Download PDF

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CN108084004B
CN108084004B CN201711290649.1A CN201711290649A CN108084004B CN 108084004 B CN108084004 B CN 108084004B CN 201711290649 A CN201711290649 A CN 201711290649A CN 108084004 B CN108084004 B CN 108084004B
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emodin
palladium
carbon catalyst
anthrone
mixture
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CN108084004A (en
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郭文华
肖金霞
赵景辉
张瑜
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Shaanxi Jiahe Pharmaceutical Co ltd
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/78—Separation; Purification; Stabilisation; Use of additives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
    • C07C45/65—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by splitting-off hydrogen atoms or functional groups; by hydrogenolysis of functional groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/78—Separation; Purification; Stabilisation; Use of additives
    • C07C45/80—Separation; Purification; Stabilisation; Use of additives by liquid-liquid treatment
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/78—Separation; Purification; Stabilisation; Use of additives
    • C07C45/81—Separation; Purification; Stabilisation; Use of additives by change in the physical state, e.g. crystallisation
    • 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
    • Y02P20/584—Recycling of catalysts

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Abstract

The invention provides a method for synthesizing emodin anthrone, which solves the problems that the traditional process causes serious harm to the environment and large-scale production cannot be carried out at present. The synthesis method takes emodin as an initial material, obtains high-purity emodin anthrone by reduction of a palladium-carbon catalyst and an ammonium formate system, has the advantages of simple process route, high yield, repeated application of raw materials, easy recovery, greatly reduced production cost, environmental friendliness and suitability for industrial production.

Description

Method for synthesizing emodin anthrone
Technical Field
The invention belongs to the field of chemical synthesis, and particularly relates to a method for synthesizing emodin anthrone.
Background
Emodin anthrone with CAS number of 491-60-1 and molecular formula of C15H12O4Molecular weight 256.25, molecular structure:
Figure GDA0002671942430000011
the chemical name of emodin anthrone is 1, 3, 8-trihydroxy-6-methyl-10H-anthracene-9-one, which is an effective component in radix et rhizoma Rhei.
Emodin with CAS number of 518-82-1 and molecular formula of C15H10O5The chemical name is 1, 3, 8-trihydroxy-6-methylanthraquinone, which is derived from dried rhizome and root of Polygonum cuspidatum of Polygonaceae, and rhizome of Rheum palmatum, and is generally 50%, 80% and 98% of the plant type medicament.
The emodin and the derivatives thereof are easy to decompose in nature, have the advantages of environmental protection, no toxicity and harm to human, livestock, poultry, aquatic organisms and the like, good safety performance and better application prospect. The chemical components and pharmacological research of rhubarb begins in the middle of the 19 th century, and at present, many research reports about the chemical components and pharmacology of rheum plants are reported at home and abroad, and many pharmacological actions of rheum are the results of multi-target synergistic action of various chemical components contained in rheum officinale.
The rhubarb is the dried root and rhizome of Rheum palmatum L. Tanggute rhubarb R.tandutinum Maxim. ex Balf. or Rheum officinale R.offisile Baill. of Polygonaceae, has the effects of purging pathogenic accumulation, clearing heat and purging fire, cooling blood and removing toxicity, removing blood stasis and dredging channels, promoting diuresis and removing jaundice, and is a clinically common traditional Chinese medicine. Modern pharmacological research shows that the rhubarb has bacteriostasis component of free anthraquinone compound, purgative component of combined anthraquinone and dianthrone compound, anticoagulant component of flavone derivative-flavan-3-ol compound and astringent hemostatic component of tannin compound.
Through literature search, a process route suitable for large-scale production of emodin anthrone is not found, only some literatures mention that emodin is reduced by stannous chloride in a strong acid environment to obtain emodin anthrone, but the whole preparation process has large amounts of acid and stannous chloride, which causes serious harm to the environment.
Disclosure of Invention
The invention aims to solve the defects of the prior art and provide the method for synthesizing emodin anthrone, which has high yield, is suitable for industrial production and is environment-friendly.
In order to achieve the purpose, the technical solution provided by the invention is as follows:
the method for synthesizing emodin anthrone is characterized by comprising the following steps:
step 1) mixing emodin and acetic acid, adding ammonium formate and a palladium-carbon catalyst, heating and refluxing, stopping reaction after the liquid phase is monitored until the emodin content is lower than a set value, and performing suction filtration to obtain a mixture of emodin anthrone and the palladium-carbon catalyst after the reaction liquid is cooled to room temperature;
wherein the mass ratio of the emodin to the acetic acid to the ammonium formate to the palladium-carbon catalyst is 1: 4-6: 1.25: 0.125-0.25;
the emodin with liquid phase content of 98% can be used to generate emodin anthrone with high purity; the palladium-carbon catalyst is 10 percent of palladium-carbon catalyst, and the reaction speed is fastest and the reaction time is short by using the 10 percent of palladium-carbon catalyst; step 2) extracting the mixture of the obtained emodin anthrone and the palladium carbon catalyst with acetone for multiple times, dissolving the emodin anthrone in the acetone, and recycling the palladium carbon catalyst; vacuum concentrating acetone dissolved with emodin anthrone to small volume, standing, cooling for crystallization, and vacuum filtering to obtain high purity emodin anthrone.
Further, in the step 1), the emodin content set value is 1%.
Further, in the step 2), the obtained mixture of the emodin anthrone and the palladium carbon catalyst is extracted by acetone reflux three times.
Further, in order to fully dissolve the mixture and save the cost, the volume ratio of the mixture of the emodin anthrone and the catalyst obtained in the step 2) to acetone is 1: 30-40.
The invention has the advantages that:
the invention takes emodin as an initiator, and obtains high-purity emodin anthrone through reduction of a palladium-carbon catalyst and an ammonium formate system. The method has the advantages of simple process route, high yield, repeated use of raw materials, easy recovery, great reduction of production cost, environmental friendliness and suitability for industrial production.
Detailed Description
Emodin is taken as a starting material, dissolved in acetic acid and reduced into emodin anthrone in a reduction system of a 10% palladium-carbon catalyst and ammonium formate.
The synthesis mechanism of the invention is as follows:
Figure GDA0002671942430000031
the invention will now be described more fully hereinafter with reference to the accompanying specific embodiments:
example 1
20 g of emodin with the liquid phase content of 98%, 100ml of acetic acid, 25 g of ammonium formate and 2.5 g of 10% palladium-carbon catalyst are taken and placed in a 250 ml reaction bottle for stirring, the temperature is increased for reflux to react, the reaction is stopped when the liquid phase is monitored until the emodin content is lower than 1%, and the time is about 6 hours. Stopping heating, cooling the reaction liquid, and performing suction filtration to obtain a mixture of emodin anthrone and 10% palladium carbon catalyst.
Placing the mixture in a 1000 ml reaction bottle, adding 500 ml acetone for the first time, refluxing and extracting for 1 hour, and carrying out hot filtration to obtain a mixture of a palladium-carbon catalyst and a small amount of emodin anthrone; adding 200 ml of acetone into the mixture obtained in the first time for the second time, performing reflux extraction, and performing thermal filtration to obtain a palladium-carbon catalyst and a very small amount of emodin anthrone mixture; and adding 100ml of acetone into the mixture obtained in the second time for the third time, performing reflux extraction, and performing third heat filtration to obtain the palladium-carbon catalyst for recycling. And combining the three acetone solutions, concentrating under vacuum and reduced pressure to one fourth of the total volume, standing, cooling and crystallizing. After 8 hours, emodin anthrone is obtained by suction filtration and dried to obtain 17 g.
Example 2
50 g of emodin with the liquid phase content of 98%, 280ml of acetic acid, 62.5 g of ammonium formate and 6.25 g of 10% palladium-carbon catalyst are taken and placed in a 1000 ml reaction bottle for stirring, the temperature is increased for reflux to carry out reaction, the reaction is stopped when the liquid phase is monitored until the emodin content is lower than 1%, and the time is about 6 hours. Stopping heating, cooling the reaction liquid, and performing suction filtration to obtain a mixture of emodin anthrone and 10% palladium carbon catalyst.
Placing the mixture into a 2000 ml reaction bottle, adding 1000 ml acetone for reflux extraction for 1 hour for the first time, carrying out heat filtration to obtain a mixture of the palladium-carbon catalyst and a small amount of emodin anthrone, adding 500 ml acetone into the mixture obtained in the first time for the second time, carrying out reflux extraction, carrying out heat filtration to obtain a mixture of the palladium-carbon catalyst and a small amount of emodin anthrone, adding 300 ml acetone into the mixture obtained in the second time for the third time, carrying out reflux extraction, and carrying out heat filtration for the third time to obtain the palladium-carbon catalyst for recycling. And combining the three acetone solutions, concentrating under vacuum and reduced pressure to one fourth of the total volume, standing, cooling and crystallizing. After 8 hours, emodin anthrone is obtained by suction filtration and dried to obtain 42 g.
Example 3
30 g of emodin with the liquid phase content of 98%, 115ml of acetic acid, 37.5 g of ammonium formate and 5.25 g of 10% palladium-carbon catalyst are taken and placed in a 250 ml reaction bottle for stirring, the temperature is increased and the reflux is carried out for reaction, the reaction is stopped when the liquid phase is monitored until the emodin content is lower than 1%, and the time is about 6 hours. Stopping heating, cooling the reaction liquid, and performing suction filtration to obtain a mixture of emodin anthrone and 10% palladium carbon catalyst.
Placing the mixture in a 1000 ml reaction bottle, adding 700 ml acetone for reflux extraction for 1 hour for the first time, carrying out heat filtration to obtain a mixture of the palladium-carbon catalyst and a small amount of emodin anthrone, adding 300 ml acetone into the mixture obtained in the first time for the second time, carrying out reflux extraction, carrying out heat filtration to obtain a mixture of the palladium-carbon catalyst and a small amount of emodin anthrone, adding 200 ml acetone into the mixture obtained in the second time for the third time, carrying out reflux extraction, and carrying out heat filtration for the third time to obtain the palladium-carbon catalyst for recycling. And combining the three acetone solutions, concentrating under vacuum and reduced pressure to one fourth of the total volume, standing, cooling and crystallizing. After 8 hours, emodin anthrone is obtained by suction filtration and is dried to obtain 25 g.
Example 4
5 kg of emodin with the liquid phase content of 98%, 25 l of acetic acid, 6.25 kg of ammonium formate and 1 kg of palladium-carbon catalyst with the liquid phase content of 10% are taken and placed in a 50 l reaction bottle for stirring, the temperature is increased for reflux to react, the reaction is stopped when the liquid phase is monitored until the emodin content is lower than 1%, and the time is about 6 hours. Stopping heating, cooling the reaction liquid, and performing suction filtration to obtain a mixture of emodin anthrone and 10% palladium carbon catalyst.
Placing the mixture in a 100-liter reaction kettle, adding 80 liters of acetone for reflux extraction for 1 hour for the first time, performing heat filtration to obtain a palladium-carbon catalyst and a small amount of emodin anthrone mixture, adding 60 liters of acetone into the mixture obtained in the first time for reflux extraction, performing heat filtration to obtain a palladium-carbon catalyst and a very small amount of emodin anthrone mixture, adding 30 liters of acetone into the mixture obtained in the second time for reflux extraction, and performing heat filtration for the third time to obtain the palladium-carbon catalyst for recycling. And combining the three acetone solutions, concentrating under vacuum and reduced pressure to one fourth of the total volume, standing, cooling and crystallizing. Filtering after 8 hours to obtain emodin anthrone, and drying to obtain 4.2 kg.
Example 5
100 kg of emodin with the liquid phase content of 98%, 570 l of acetic acid, 125 kg of ammonium formate and 25 kg of 10% palladium carbon catalyst are taken and placed in a 1000 l reaction kettle for stirring, the temperature is increased and the reflux is carried out for reaction, the liquid phase is monitored until the emodin content is lower than 1%, the reaction is stopped, and the time is about 6 hours. Stopping heating, cooling the reaction liquid, and performing suction filtration to obtain a mixture of emodin anthrone and 10% palladium carbon catalyst.
Placing the mixture in a 3000-liter reaction kettle, adding 2000 liters of acetone for reflux extraction for 1 hour for the first time, performing heat filtration to obtain a palladium-carbon catalyst and a small amount of emodin anthrone mixture, adding 1000 liters of acetone into the mixture obtained in the first time for reflux extraction, performing heat filtration to obtain a palladium-carbon catalyst and a very small amount of emodin anthrone mixture, adding 500 liters of acetone into the mixture obtained in the second time for reflux extraction, and performing heat filtration for the third time to obtain the palladium-carbon catalyst for recycling. And combining the three acetone solutions, concentrating under vacuum and reduced pressure to one fourth of the total volume, standing, cooling and crystallizing. After 8 hours, emodin anthrone is obtained by suction filtration and is dried to obtain 82 kg.
While the invention has been described with reference to specific embodiments, the invention is not limited thereto, and various equivalent modifications or substitutions can be easily made by those skilled in the art within the technical scope of the present disclosure.

Claims (3)

1. A synthetic method of emodin anthrone is characterized by comprising the following steps:
step 1) mixing emodin and acetic acid, adding ammonium formate and palladium-carbon catalyst, heating and refluxing, stopping reaction when the content of emodin is lower than 1% by liquid phase monitoring, standing for 6 hours, and performing suction filtration to obtain a mixture of emodin anthrone and palladium-carbon catalyst after the reaction liquid is cooled to room temperature;
wherein the mass ratio of the emodin to the acetic acid to the ammonium formate to the palladium-carbon catalyst is 1: 4-6: 1.25: 0.125-0.25;
the emodin with liquid phase content of 98% is selected; the palladium-carbon catalyst is 10 percent palladium-carbon catalyst;
step 2) refluxing and extracting the mixture of the obtained emodin anthrone and the palladium carbon catalyst by using acetone, dissolving the emodin anthrone in the acetone, and recycling the palladium carbon catalyst; vacuum concentrating acetone dissolved with emodin anthrone under reduced pressure, standing, cooling for crystallization, and vacuum filtering to obtain emodin anthrone.
2. The method for synthesizing emodin anthrone according to claim 1, characterized in that: in the step 2), the mixture of emodin anthrone and palladium carbon catalyst is extracted by acetone reflux for three times.
3. The method for synthesizing emodin anthrone according to claim 2, characterized in that: the volume ratio of the mixture of emodin anthrone and palladium carbon catalyst obtained in the step 2) to acetone is 1: 30-40.
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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR0128107B1 (en) * 1994-08-12 1998-04-04 강박광 Process for benzanthrone
CN1827574A (en) * 2006-04-19 2006-09-06 中国农业科学院兰州畜牧与兽药研究所 Chemical synthesis process for hypericin and derivatives thereof

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR0128107B1 (en) * 1994-08-12 1998-04-04 강박광 Process for benzanthrone
CN1827574A (en) * 2006-04-19 2006-09-06 中国农业科学院兰州畜牧与兽药研究所 Chemical synthesis process for hypericin and derivatives thereof

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
Folding-Induced Selective Hydrogenation of Helical 9, 10-Anthraquinone Analogues;Hai-Yu Hu等;《ORGANIC LETTERS》;20081231;第10卷(第21期);补充信息 *
REDUCTION OF ALDEHYDES AND KETONES TO METHYLENE DERIVATIVES USING AMMONIUM FORMATE AS A CATALYTIC HYDROGEN TRANSFER AGENT;Siya Ram等;《Tetrahedron Letters》;19881231;第29卷(第31期);第3741-3744页 *

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