CN109851479B - Chemical synthesis process of antibacterial agent spice carvacrol - Google Patents
Chemical synthesis process of antibacterial agent spice carvacrol Download PDFInfo
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- CN109851479B CN109851479B CN201910042135.7A CN201910042135A CN109851479B CN 109851479 B CN109851479 B CN 109851479B CN 201910042135 A CN201910042135 A CN 201910042135A CN 109851479 B CN109851479 B CN 109851479B
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Abstract
The invention relates to a chemical synthesis process of antibacterial carvacrol. The synthesis process adopts o-methyl phenol and isopropanol as raw materials, and compounds such as dichloromethane or n-hexane or petroleum ether and the like as reaction solvents, and the carvacrol is prepared by alkylation reaction, liquid-liquid extraction, atmospheric and vacuum concentration and vacuum distillation. The synthesis process has the characteristics of simple process, low production cost, high yield, excellent product quality and the like, and is easy for industrial production.
Description
Technical Field
The invention relates to a chemical synthesis process of an antibacterial agent spice carvacrol.
Background
Carvacrol is a phenol compound with a bactericidal effect and mainly exists in thymus plant essential oil in nature. One of the main antibacterial components in natural origanum oil, mountain pepper oil and other products is carvacrol. Because of broad antibacterial spectrum, safety and extremely low residual quantity in animal bodies, the antibacterial agent is applied to the aspects of treating dysentery, coccidiosis and the like of animals such as chickens, piglets and the like.
U.S. Patent No. 2286953 discloses a method for preparing carvacrol by condensation reaction of 2-chloropropane with o-cresol as raw material and anhydrous aluminium trichloride as catalyst. The invention patent CN 1488615A also introduces a method for preparing carvacrol by condensation reaction of o-cresol as raw material and anhydrous aluminium trichloride as catalyst with 2-chloropropane, but the method has the defects of high toxicity of alkylation material 2-chloropropane, low boiling point, difficult transportation and storage, higher price and the like.
The use of Zr-Al-SiO has been reported2The composite catalyst catalyzes the reaction of isopropanol and o-methylphenol to synthesize carvacrol (journal of chemical technology yand biotechnology,2009,84, 1499-.
The invention provides a chemical synthesis method of carvacrol, which not only avoids a plurality of defects caused by using 2-chloropropane as an alkylation material, improves the production safety, but also overcomes a series of defects caused by using isopropanol as the alkylation material and needing high-temperature reaction in the aspects of equipment, energy consumption, operation and the like.
The method is mainly characterized in that isopropanol is used as o-cresol for alkylation synthesis to obtain a carvacrol material, anhydrous aluminum trichloride or anhydrous ferric trichloride is used as a catalyst, dichloromethane, n-hexane or petroleum ether and the like are used as reaction solvents, so that o-cresol and isopropanol are subjected to alkylation condensation reaction, and then extracted by dichloromethane, n-hexane or petroleum ether and other solvents, and concentrated and rectified under reduced pressure to obtain a high-content carvacrol product meeting the use requirement.
Disclosure of Invention
Adding dichloromethane or n-hexane or petroleum ether serving as a solvent required by a reaction system into a reaction kettle with a stirring and refrigerating device, adding anhydrous aluminum trichloride or anhydrous ferric trichloride serving as a catalyst, stirring and cooling to 0 +/-5 ℃, slowly adding o-methylphenol, dropwise adding isopropanol when the temperature of the reaction system reaches 0 +/-5 ℃, reacting for 4 hours at 0 +/-5 ℃, and finishing the reaction. Slowly adding the reaction product into a reaction kettle filled with measured crushed ice at room temperature, stirring until the ice is completely melted, standing, separating an oil layer, extracting the water layer twice by using dichloromethane or normal hexane or petroleum ether, combining the separated oil layers, concentrating at 55-70 ℃ under normal pressure until no dichloromethane or normal hexane or petroleum ether solvent is evaporated to obtain a carvacrol crude product, and measuring the carvacrol content by using HPLC (high performance liquid chromatography) to be more than or equal to 65%. Vacuum distilling, vacuum degree of 100Pa, collecting distillate at 115 + -1 deg.C to obtain light yellow carvacrol refined product.
The specific process conditions of the invention are as follows:
(1) alkylation reaction C7H8O + C3H7OH → C10H14O
The material weight ratio of o-cresol and isopropanol is 1.3 +/-0.1: 1, the weight ratio of the catalyst to the o-cresol is 3.3 +/-0.1: 1, the volume ratio of dichloromethane or n-hexane or petroleum ether as a reaction system solvent to the o-cresol is 5.5 +/-0.5: 1, the reaction temperature is 0 +/-5 ℃, and the reaction time is 4 hours.
(2) And (3) performing ice-dissolving extraction, namely slowly adding a reaction product into a reaction kettle filled with the measured crushed ice at room temperature after the reaction is finished, and stirring until the ice is completely melted. Separating oil layer with crushed ice amount 2-3 times of solvent amount, extracting water layer with 1/4-1/3 fresh solvent for 2-3 times, and mixing separated oil layers.
(3) Evaporating the solvent at the normal pressure of 55-70 ℃ and concentrating until no solvent flows out.
(4) Vacuum distilling, vacuum degree of 100Pa, and collecting the fraction at 115 deg.C and at l deg.C.
The catalyst in the invention is anhydrous aluminum trichloride or anhydrous ferric trichloride, and the aqueous phase after liquid-liquid extraction is an aluminum trichloride or ferric trichloride aqueous solution which can be recovered by a concentration dehydration mode.
By adopting the method, the yield of carvacrol is more than 70 percent and the content is more than 65 percent without reduced pressure distillation.
Description of the drawings:
figure 1 is a chemical synthesis process of the antibacterial agent carvacrol of the invention.
The invention has the advantages that the alkylation material used in the traditional process is a low-boiling-point compound 2-chloropropane which is toxic and difficult to transport and store and has higher price, and the alkylation material used in the whole process of the invention overcomes the defects of the traditional process and achieves safety, environmental protection and low price.
The specific implementation mode is as follows:
the details of the process examples are as follows
Example 1
Weighing 500L of dichloromethane, adding the dichloromethane into a 1000L reaction kettle with a stirring and cooling device, adding 300kg of catalyst anhydrous aluminum trichloride, stirring and cooling to-5 ℃, slowly adding 100kg of o-cresol, dropwise adding 72kg of isopropanol after the temperature of a reaction system reaches-5 ℃, and reacting for 4 hours at-5 ℃ to finish the reaction. Slowly adding the reaction product into a reaction kettle which is provided with a stirrer and is filled with 1200kg of crushed ice at room temperature, stirring and freezing until the ice is completely melted, standing, separating an oil layer, washing the water layer with 150L of dichloromethane twice, combining the separated oil layers, concentrating at 55 ℃ under normal pressure until no dichloromethane solvent is evaporated, and obtaining 122.2 kg of carvacrol crude product and 65.6 percent of carvacrol (measured by HPLC). Vacuum rectification is carried out under 100Pa, and fractions at 114-116 ℃ are collected to obtain 75.6 kg of light yellow carvacrol with the content of 98.8 percent.
Example 2
Weighing 500L of n-hexane, adding the n-hexane into a 1000L reaction kettle with a stirring and cooling device, adding 300kg of catalyst anhydrous aluminum trichloride, stirring and cooling to-5 ℃, slowly adding 100kg of o-cresol, dropwise adding 72kg of isopropyl alcohol after the temperature of a reaction system reaches-5 ℃, and reacting for 4 hours at-5 ℃ to finish the reaction. Slowly adding the reaction product into a reaction kettle which is provided with a stirrer and is filled with 1200kg of crushed ice at room temperature, stirring and freezing until the ice is completely melted, standing, separating an oil layer, washing the water layer with 150L of dichloromethane twice, combining the separated oil layers, concentrating at 70 ℃ under normal pressure until no n-hexane solvent is evaporated out, and obtaining 121.6 kg of carvacrol crude product and 65.4 percent of carvacrol (measured by HPLC). Vacuum rectification is carried out under 100Pa, fractions at 114-116 ℃ are collected to obtain 74.8 kg of light yellow carvacrol with the content of 98.6 percent.
Example 3
Weighing 500L of dichloromethane, adding the dichloromethane into 1000L of reaction kettle with a stirring and cooling device, adding 300.0kg of catalyst anhydrous ferric trichloride, stirring and cooling to-5 ℃, slowly adding 100kg of o-cresol, and dropwise adding the o-cresol when the temperature of a reaction system reaches-5 DEG C
72kg of isopropanol, and reacting at-5 ℃ for 4 hours to finish the reaction. Slowly adding the reaction product into a reaction kettle which is provided with a stirrer and is filled with 1200kg of crushed ice at room temperature, stirring and freezing until the ice is completely melted, standing, separating an oil layer, washing the water layer with 150L of dichloromethane twice, combining the separated oil layers, concentrating at 55 ℃ under normal pressure until no dichloromethane solvent is evaporated, and obtaining 121.4 kg of carvacrol crude product with the carvacrol content of 65.4 percent (measured by HPLC). Vacuum rectification is carried out under 100Pa, fractions at 114-116 ℃ are collected to obtain 74.6 kg of light yellow carvacrol with the content of 98.8 percent.
Example 4
Weighing 500L of n-hexane, adding the n-hexane into a 1000L reaction kettle with a stirring and cooling device, adding 300.0kg of catalyst anhydrous ferric trichloride, stirring and cooling to-5 ℃, slowly adding L00kg o-methylphenol, dropwise adding 72kg of isopropanol when the temperature of a reaction system reaches-5 ℃, reacting for 4 hours at-5 ℃ and finishing the reaction. Slowly adding the reaction product into a reaction kettle which is provided with a stirrer and is filled with 1200kg of crushed ice at room temperature, stirring and freezing until the ice is completely melted, standing, separating an oil layer, washing the water layer with 150L of dichloromethane twice, combining the separated oil layers, concentrating at 70 ℃ under normal pressure until no n-hexane solvent is evaporated out, and obtaining 122.1 kg of carvacrol crude product with 65.3 percent of carvacrol (determined by HPLC). Vacuum rectification is carried out under 100Pa, fractions at 114-116 ℃ are collected to obtain 75.2 kg of light yellow carvacrol with the content of 98.8 percent.
Claims (1)
1. A preparation method of an antibacterial agent spice carvacrol is characterized by comprising the following steps:
(1) adding a solvent dichloromethane required by a reaction system into a reaction kettle with a stirring and refrigerating device, adding catalyst anhydrous aluminum trichloride or anhydrous ferric trichloride, stirring and cooling to 0 +/-10 ℃, slowly adding o-cresol until the temperature of the reaction system reaches 0 +/-10 ℃, dropwise adding isopropanol, reacting for 4 hours at 0 +/-10 ℃, and finishing the reaction, wherein in the above reaction, the weight ratio of the materials of o-cresol and isopropanol is 1.3 +/-0.1: 1, the weight ratio of the dosages of the catalyst and the o-cresol is 3.3 +/-0.1: 1, the weight ratio of the dosages of dichloromethane or n-hexane or petroleum ether as a solvent of the reaction system to the dosages of the o-cresol is 5.5 +/-0.5: 1;
(2) after the reaction is finished, slowly adding the reaction product solution into a stirred reaction kettle with metered crushed ice at room temperature, fully stirring for ice decomposition, wherein the consumption of the crushed ice is 2-3 times of that of the solvent, standing, separating an oil layer, extracting a water layer for 2-3 times by using a fresh solvent with the reaction solvent amount of 1/4-1/3, combining the separated oil layers, concentrating in a distillation kettle at the normal pressure of 55 ℃ until no solvent is evaporated out to obtain a carvacrol crude product, and measuring the carvacrol content by using HPLC (high performance liquid chromatography) to be more than or equal to 65%;
(3) the crude product is subjected to reduced pressure distillation to collect distillate under the vacuum degree of 100Pa at the temperature of 115 +/-1 ℃, and the content of the light yellow carvacrol refined product is more than or equal to 98 percent.
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| CN112920022B (en) * | 2021-01-11 | 2023-09-01 | 福建中农牧生物科技有限公司 | Method for preparing carvacrol from o-cresol |
| CN113304743B (en) * | 2021-05-14 | 2022-01-04 | 安徽海华科技集团有限公司 | Method for preparing high-purity carvacrol by using o-cresol |
| CN113896617B (en) * | 2021-10-18 | 2022-04-05 | 安徽海华科技集团有限公司 | Chemical synthesis process of carvacrol |
Citations (3)
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| CN1488615A (en) * | 2003-09-08 | 2004-04-14 | 中国农业科学院饲料研究所 | Green synthesis process for carvacrol for fodder antibacterial agent |
| CN104649867A (en) * | 2013-11-21 | 2015-05-27 | 辽宁药联制药有限公司 | Preparation method of propofol |
| CN105523897A (en) * | 2015-12-30 | 2016-04-27 | 淮安万邦香料工业有限公司 | A synthetic method of carvacrol |
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|---|---|---|---|---|
| CN1488615A (en) * | 2003-09-08 | 2004-04-14 | 中国农业科学院饲料研究所 | Green synthesis process for carvacrol for fodder antibacterial agent |
| CN1244530C (en) * | 2003-09-08 | 2006-03-08 | 中国农业科学院饲料研究所 | Green synthesis process for carvacrol for fodder antibacterial agent |
| CN104649867A (en) * | 2013-11-21 | 2015-05-27 | 辽宁药联制药有限公司 | Preparation method of propofol |
| CN105523897A (en) * | 2015-12-30 | 2016-04-27 | 淮安万邦香料工业有限公司 | A synthetic method of carvacrol |
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| Alumina-Catalyzed Reactions of Hydroxyarenes and Hydroaromatic Ketones. 10. Reaction of Phenol with 2-Propanol;LeRoy H. Klemm and Dennis R. Taylor;《Journal of Organic Chemistry》;19801001;第45卷;4326-4329 * |
| Synthesis of carvacrol by Friedel–Crafts alkylation of o cresol with isopropanol using superacidic catalyst UDCaT-5;Ganapati D. Yadav and Shashikant B. Kamble;《Journal of Chemical Technology & Biotechnol》;20090609;第84卷;第1500页右栏第3段，第1501页右栏第3段,第1502页表1 * |
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