CN116332758A - Method for synthesizing gallic acid ester by esterification reaction of gallic acid and glycol - Google Patents
Method for synthesizing gallic acid ester by esterification reaction of gallic acid and glycol Download PDFInfo
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- CN116332758A CN116332758A CN202310189064.XA CN202310189064A CN116332758A CN 116332758 A CN116332758 A CN 116332758A CN 202310189064 A CN202310189064 A CN 202310189064A CN 116332758 A CN116332758 A CN 116332758A
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- C07C67/00—Preparation of carboxylic acid esters
- C07C67/08—Preparation of carboxylic acid esters by reacting carboxylic acids or symmetrical anhydrides with the hydroxy or O-metal group of organic compounds
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- C07—ORGANIC CHEMISTRY
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- C07C67/00—Preparation of carboxylic acid esters
- C07C67/48—Separation; Purification; Stabilisation; Use of additives
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/48—Separation; Purification; Stabilisation; Use of additives
- C07C67/52—Separation; Purification; Stabilisation; Use of additives by change in the physical state, e.g. crystallisation
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- C—CHEMISTRY; METALLURGY
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/48—Separation; Purification; Stabilisation; Use of additives
- C07C67/58—Separation; Purification; Stabilisation; Use of additives by liquid-liquid treatment
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Abstract
The invention discloses a method for synthesizing gallic acid ester by esterification reaction of gallic acid and glycol, which comprises the steps of taking p-toluenesulfonic acid as a catalyst, heating and refluxing in an organic solvent for reaction for 5-20 hours, and carrying out post-treatment on reaction liquid after the reaction is finished to obtain a gallic acid ester compound. The gallic acid ester compound obtained by the invention can be used in the field of molecular biology. The method has the advantages of simple operation, low cost and easy acquisition of raw materials, simple purification and high purity of the obtained product, and is suitable for large-scale production.
Description
Technical Field
The invention relates to a method for synthesizing gallic acid ester by esterification reaction of gallic acid and glycol.
Background
Gallic acid is an important derivative of Chinese characteristic Chinese herbal medicine gallnut, has higher antioxidant activity, but has poor fat solubility; the fat solubility of gallic acid can be increased when its carboxyl group reacts with alcohol to form an esterified product. The gallic acid ester has 3 phenolic hydroxyl groups at ortho positions, is a proton donor, shows active reducibility, has good oxidation resistance, and is superior to the common synthetic antioxidants of tert-butyl p-hydroxy anisole (BHA) and 2, 6-di-tert-butyl p-cresol (BHT). The gallic acid ester compound is mainly used for antioxidation of oil or oil-based food, and fresh-keeping of fruits and vegetables. The product also has wide application in the fields of medicines, cosmetics, feeds, photosensitive thermosensitive materials and the like. Can also be used for resisting oxidation of fat and cream substances. The gallic acid ester compound has remarkable free radical elimination capability and biological activity, can be used as an antioxidant stabilizer or an anti-aging agent for biodiesel and certain materials, and can be approved as an antioxidant for oil or fat-rich foods by the United states Food and Drug Administration (FDA), the United states grain and agricultural organization (FAO) and the World Health Organization (WHO) after Propyl Gallate (PG) is used for antioxidant of fried foods. The gallate compound also has pharmacological activity, can be used for resisting platelet aggregation, enhancing fibrin and thrombolysis, dilating blood vessel, increasing coronary blood flow, etc., and has certain curative effects on cardiovascular and cerebrovascular diseases, viral diseases, bacterial infectious diseases, gastric ulcer, viral hepatitis, etc. The pharmaceutical product of propyl gallate is named as 'Tongmai ester'. Therefore, the synthesis of gallic acid ester compounds and the research on the application performance of the products are more and more paid attention to. Gallic acid dodecanol ester is an effective platelet aggregation inhibitor, and has been collected in the United states, british and other pharmacopoeias. In addition, it has bactericidal, bacteriostatic and antiseptic effects, and is a food antioxidant approved by WTO.
At present, gallic acid ester compounds can be synthesized by chemical or biochemical methods, and the chemical synthesis is mainly carried out by esterification reaction of gallic acid and alcohol under reflux, and the adopted catalyst comprises concentrated sulfuric acid, dry hydrogen chloride, magnetic nano solid superacid and the like, but the synthesis methods have the defects of high reaction temperature, long reaction time, low conversion rate, difficult separation of products, high cost and the like. The biochemical method mainly adopts enzymology and enzyme engineering, and tannase or immobilized enzyme thereof generated by fermenting microorganisms such as Aspergillus niger is known to hydrolyze ester bond of gallotannin, and is used for producing gallic acid. Tannase can also catalyze the reverse reaction of hydrolysis reaction for synthesizing gallate, but the disadvantage is obvious that the enzyme is easy to be deactivated by the influence of organic solvent, and the recycling rate of the enzyme is lower. CN10158575769a adopts a microwave reactor to carry out esterification reaction, has high requirements on equipment and high production cost, and is not suitable for industrial production.
Disclosure of Invention
The invention aims to solve the technical problem of overcoming the defects of the prior art and providing the synthesis method of the gallate with simple operation, short reaction time and high yield. According to the invention, from a direct esterification method, through intensive and careful researches on conditions such as a catalyst, a solvent, a reaction temperature and the like required by the reaction, gallic acid and glycol are adopted as raw materials to directly carry out the esterification reaction, the target product gallic acid ester is obtained with high yield and purity, and the yield is 90% after recrystallization, and the purity reaches 99%. The method provides a process route for synthesizing the gallate, which has the advantages of easily obtained raw materials, mild reaction conditions, simple experimental operation, low experimental cost and easy mass production, and provides possibility for mass industrialized production and large-scale application of the gallate.
In order to achieve the above purpose, the technical scheme adopted by the invention is as follows:
a method for synthesizing gallic acid ester by esterification reaction of gallic acid and glycol comprises the following steps:
gallic acid and a diol compound shown in a formula I take p-toluenesulfonic acid as a catalyst, and are heated and refluxed in an organic solvent for reaction for 5-20 hours, and after the reaction is finished, the reaction liquid is subjected to aftertreatment to obtain a gallic acid ester compound shown in a formula II;
in the formula I or the formula II, R is a C2-C8 methylene group or a C2-C8 methylene group containing an oxygen atom in a carbon chain.
Further, the diol compound is preferably ethylene glycol, 1, 3-propanediol, 1, 4-butanediol, 1, 5-pentanediol, diethylene glycol, triethylene glycol or tetraethylene glycol.
The ratio of the amounts of the gallic acid and the glycol compound is 1:2 to 1:12, preferably 1:10 to 12.
In the method, the catalyst is p-toluenesulfonic acid, and has the advantages of less reaction byproducts and high yield.
The ratio of the amount of gallic acid to the amount of p-toluenesulfonic acid is 1:0.05-0.5, preferably 1:0.1.
the organic solvent is one or more of 1, 4-dioxane, dimethyl sulfoxide, dimethylformamide, toluene, chloroform, acetone, tetrahydrofuran and acetonitrile, preferably 1, 4-dioxane, and the advantage of using 1, 4-dioxane is that the reaction byproducts are less, the yield is high, the boiling point is low, and the post-treatment is simple.
The volume amount of the organic solvent is preferably 0.5 to 2L/mol based on the amount of gallic acid.
In the present invention, the reaction time is preferably 10 to 11 hours.
The post-treatment method of the reaction liquid is preferably as follows: after the reaction is finished, the reaction solution is cooled to room temperature, petroleum ether is added for extraction, the petroleum ether phase at the upper layer is removed after layering, water is added to the organic phase at the lower layer, dichloromethane is added for extraction, the solvent is removed by evaporation of the organic phase at the lower layer, pure water is used for recrystallization, and white solid is obtained, namely the gallic acid ester compound shown in the formula II.
The invention has the beneficial effects that: according to the invention, diol raw materials are adopted to carry out esterification reaction of gallic acid, the polymer byproducts are inhibited from being produced in the reaction by controlling the equivalent of the catalyst and the reaction raw materials, the reaction temperature and the reaction time, and finally the monoesterified gallic acid ester is obtained with high selectivity, the product yield is 80% -90%, and the purity is high. In the post-treatment, the petroleum ether is creatively adopted as the extractant, and the petroleum ether can extract impurities and redundant equivalent diols in the reaction liquid, so that the organic phase only contains the target product gallic acid ester, and the subsequent purification is simpler and more convenient, thereby being beneficial to being applied to large-scale production. And the diol enriched in the petroleum ether can be recycled.
In the post-treatment method in the prior art, the excessive equivalent weight of alcohol and the product are generally extracted together into an organic phase, and then the product and the alcohol raw material are separated by secondary extraction, so that the subsequent product purification is complex, the yield is reduced, and the excessive alcohol raw material is difficult to recycle.
The specific embodiment is as follows:
the following describes the technical scheme of the present invention with specific examples, but the scope of the present invention is not limited thereto.
The reagents used in the examples below were manufactured by the manufacturer and the specifications:
example 1: preparation of gallic acid-2-hydroxyethyl ester: gallic acid (17 g,0.1 mol) and ethylene glycol (62 g,1.0 mol) are reacted under the catalysis of p-toluenesulfonic acid (1.72 g,0.01 mol) in 100mL of 1, 4-dioxane solution for 10h, after TLC monitoring reaction is finished, the temperature is reduced to room temperature, 100mL of petroleum ether is added, layering is carried out, petroleum ether phase is removed, 100mL of water is added into the residual organic phase, 100mL of dichloromethane is added, extraction is carried out, water phase is removed, the organic phase is spin-dried, recrystallization operation is carried out by using pure water, suction filtration and drying are carried out, 19.3g of white solid is obtained, and the yield is 90%. Structural criteria of the product: nuclear magnetism: 1 HNMR(500MHz,DMSO-d6)δ9.27(s,2H),8.96(s,1H),6.97(s,2H),4.87(t,J＝5.3Hz,1H),4.22–4.07(m,2H),3.65(q,J＝4.6Hz,2H).ESI-MSm/z：215.2[M+H] +
example 2: preparation of gallic acid-2-diethylene glycol ester: gallic acid (17 g,0.1 mol) and diethylene glycol (106 g,1.0 mol) are reacted under reflux in 100ml of 1, 4-dioxane solution under the catalysis of p-toluenesulfonic acid (1.72 g,0.01 mol) for 10h, after the reaction, the temperature is reduced, 100ml of petroleum ether is added for extraction for 3 times, the petroleum ether phase is removed, water is added to the organic phase, dichloromethane extraction is carried out, spin drying is carried out, pure water is used for recrystallization, and 23.6g of white solid is obtained after drying, and the yield is 91%. Structural criteria of the product: nuclear magnetism: 1 HNMR(500MHz,DMSO-d6)δ9.33(s,2H),8.99(s,1H),7.03(s,2H),4.63(t,J＝7.1Hz,2H),4.29(t,J＝7.4Hz,1H),3.72(t,J＝7.1Hz,2H),3.68–3.62(m,2H),3.56(td,J＝7.2,1.2Hz,2H).ESI-MSm/z：259.2[M+H] +
example 3: preparation of gallic acid-2-triethylene glycol ester: gallic acid (17 g,0.1 mol) and triethylene glycol (150 g,1.0 mol) are reacted under the catalysis of p-toluenesulfonic acid (1.72 g,0.01 mol) in 100ml of 1, 4-dioxane solution for 10h, the temperature is reduced after the reaction, 100ml of petroleum ether is added for extraction for 3 times, the petroleum ether phase is removed, water is added to the organic phase, dichloromethane extraction and spin drying are carried out, pure water is used for recrystallization, and 27g of white solid is obtained after drying, and the yield is 90%. Structural criteria of the product: nuclear magnetism: 1 HNMR(500MHz,DMSO-d6)δ9.2(s,2H),8.96(s,1H),7.06–6.93(s,2H),4.69–4.57(t,J＝7.1Hz,2H),4.30–4.18(t,J＝7.5Hz,1H),3.74–3.69(t,J＝7.1Hz,2H),3.68–3.61(dtd,J＝7.5,6.4,1.2Hz,4H),3.61–3.56(m,4H),3.56–3.51(td,J＝7.0,0.9Hz,2H)。ESI-MSm/z：303.2[M+H] +
example 4: preparation of gallic acid-2-tetraethylene glycol tri-ester: gallic acid (17 g,0.1 mol) and tetraethylene glycol (194 g,1.0 mol) are reacted under reflux in 100ml of 1, 4-dioxane solution for 10 hours under the catalysis of p-toluenesulfonic acid (1.72 g,0.01 mol), after the reaction, the temperature is reduced, 100ml of petroleum ether is added for extraction for 3 times, the petroleum ether phase is removed, the organic phase is added with water, dichloromethane extraction, spin drying, recrystallization with pure water is carried out, and drying is carried out to obtain 30.6g of white solid with the yield of 90%. Structural criteria of the product: nuclear magnetism: 1 HNMR(500MHz,DMSO-d6)δ9.14(s,2H),8.8(s,1H),7.06-6.93(s,2H),4.69-4.57(t,J＝7.1Hz,2H),4.30–4.18(t,J＝7.5Hz,1H),3.74–3.69(t,J＝7.1Hz,2H),3.68–3.61(dtd,J＝7.5,6.4,1.2Hz,6H),3.61–3.56(m,4H),3.56–3.51(td,J＝7.0,0.9Hz,2H)。ESI-MSm/z：347[M+H] +
example 5 Effect of reaction solvent
The reaction solvent in example 1 was changed to tetrahydrofuran, and the yield of the final product was 40% under the same reaction conditions as in example 1.
Example 6 Effect of diol equivalent
The amount of ethylene glycol used in example 1 was changed to 1.2mol, and the reaction conditions were the same as in example 1, whereby the yield of the final product was 85%.
The amount of ethylene glycol used in example 1 was changed to 0.8mol, and the yield of the final product was 61% under the same reaction conditions as in example 1.
The amount of ethylene glycol used in example 1 was changed to 0.5mol, and the yield of the final product was 42% under the same reaction conditions as in example 1.
It can be seen that the equivalent weight of ethylene glycol has a decisive influence on the yield of the product, and that this equivalent weight must be in large excess.
EXAMPLE 7 Effect of reaction temperature
The reaction temperature in example 1 was changed to 80℃and the other reaction conditions were the same as in example 1, whereby the yield of the final product was 60%.
Example 9 Effect of reaction time
The reaction time was changed to 6 hours in example 1, and the yield of the final product was 70% under the same reaction conditions as in example 1.
The reaction time was changed to 12 hours in example 1, and the yield of the final product was 82% under the same reaction conditions as in example 1.
Example 9 Effect of the post-treatment method
The post-treatment mode of the reaction liquid in the example 1 is changed to: water was added and the mixture was extracted with dichloromethane, the yield of the final product was 50%.
The post-treatment mode of the reaction liquid in the example 1 is changed to: ethyl acetate, then washed with water and saturated brine, and recrystallized from n-hexane, the yield of the final product was 40%.
Claims (10)
1. A method for synthesizing gallic acid ester by esterification reaction of gallic acid and glycol is characterized by comprising the following steps:
gallic acid and a diol compound shown in a formula I take p-toluenesulfonic acid as a catalyst, and are heated and refluxed in an organic solvent for reaction for 5-20 hours, and after the reaction is finished, the reaction liquid is subjected to aftertreatment to obtain a gallic acid ester compound shown in a formula II;
in the formula I or the formula II, R is a C2-C8 methylene group or a C2-C8 methylene group containing an oxygen atom in a carbon chain.
2. The method of claim 1, wherein the glycol compound is ethylene glycol, 1, 3-propanediol, 1, 4-butanediol, 1, 5-pentanediol, diethylene glycol, triethylene glycol, or tetraethylene glycol.
3. The method of claim 1, wherein the ratio of the amounts of gallic acid and glycol compound is 1:2 to 1:12.
4. A method according to claim 3, wherein the ratio of the amounts of gallic acid and glycol compound is 1:10 to 12.
5. The method according to claim 1, wherein the ratio of the amount of gallic acid to the amount of p-toluenesulfonic acid is 1:0.05-0.5.
6. The method of claim 5, wherein the ratio of the amount of gallic acid to the amount of p-toluenesulfonic acid material is 1:0.1.
7. the method of claim 1, wherein the organic solvent is one or more of 1, 4-dioxane, dimethyl sulfoxide, dimethylformamide, toluene, chloroform, acetone, tetrahydrofuran, and acetonitrile.
8. The method of claim 7, wherein the organic solvent is 1, 4-dioxane.
9. The method of claim 1, wherein the reaction time is from 10 to 11 hours.
10. The method according to claim 1, wherein the post-treatment method of the reaction liquid is as follows: after the reaction is finished, the reaction solution is cooled to room temperature, petroleum ether is added for extraction, the petroleum ether phase at the upper layer is removed after layering, water is added to the organic phase at the lower layer, dichloromethane is added for extraction, the solvent is removed by evaporation of the organic phase at the lower layer, pure water is used for recrystallization, and white solid is obtained, namely the gallic acid ester compound shown in the formula II.
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| CN109877768A (en) * | 2019-04-12 | 2019-06-14 | 国网福建省电力有限公司漳州供电公司 | A kind of conducting rod clamping device |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN109877768A (en) * | 2019-04-12 | 2019-06-14 | 国网福建省电力有限公司漳州供电公司 | A kind of conducting rod clamping device |
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