阅读说明：本技术 一种百里醌制备方法 (Preparation method of thymoquinone ) 是由 刘义恩 于 2018-07-27 设计创作，主要内容包括：本发明公开了一种百里醌制备方法,该制备方法,以百里酚为底物,以浓硫酸为磺化剂,二氧化锰为氧化剂,水为溶剂,经蒸馏、过滤、干燥,得到百里醌；其中,百里酚与浓硫酸的摩尔比为1：3～3.5；浓硫酸与二氧化锰的摩尔比为1:1～1.5；(1)在1500L的反应釜中加入90kg百里酚,600L溶剂油,开启搅拌,升温到60～65℃；(2)抽取186Kg浓硫酸到高位槽中,缓慢滴加到反应釜中,滴加放热,控制滴加温度在70-85℃；该发明,通过改变反应路线或优化合成方法,形成便于产业化的合成生产工艺,操作简便,过程控制严谨可靠,收率高,三废少,污染环境轻,对生产者劳动保护有利；并且百里醌mp：45.8～46.6℃,纯度(HPLC)：98.5～99％,转化率：96.8～97％,收率85％-90％。(The invention discloses a preparation method of thymoquinone, which comprises the steps of distilling, filtering and drying thymol serving as a substrate, concentrated sulfuric acid serving as a sulfonating agent, manganese dioxide serving as an oxidant and water serving as a solvent to obtain thymoquinone; wherein the molar ratio of thymol to concentrated sulfuric acid is 1:3 to 3.5; the molar ratio of concentrated sulfuric acid to manganese dioxide is 1: 1-1.5; (1) adding 90kg of thymol and 600L of solvent oil into a 1500L reaction kettle, starting stirring, and heating to 60-65 ℃; (2) pumping 186Kg of concentrated sulfuric acid into a head tank, slowly dripping into a reaction kettle, dripping to release heat, and controlling the dripping temperature to be 70-85 ℃; according to the invention, a synthesis production process convenient for industrialization is formed by changing a reaction route or optimizing a synthesis method, the operation is simple, the process control is precise and reliable, the yield is high, the three wastes are less, the environment pollution is light, and the method is beneficial to labor protection of producers; and thymoquinone mp: 45.8-46.6 ℃, purity (HPLC): 98.5-99%, conversion: 96.8-97% and 85% -90% of yield.)

1. A preparation method of thymoquinone is characterized by comprising the following steps: the preparation method comprises the steps of distilling, filtering and drying thymol serving as a substrate, concentrated sulfuric acid serving as a sulfonating agent, manganese dioxide serving as an oxidant and water serving as a solvent to obtain thymoquinone;

wherein the molar ratio of thymol to concentrated sulfuric acid is 1:3 to 3.5; the molar ratio of concentrated sulfuric acid to manganese dioxide is 1: 1-1.5.

The method mainly comprises the following steps:

(1) adding 90kg of thymol and 600L of solvent oil into a 1500L reaction kettle, starting stirring, and heating to 60-65 ℃;

(2) pumping 186Kg of concentrated sulfuric acid into a head tank, slowly dripping into a reaction kettle, dripping to release heat, and controlling the dripping temperature to be 70-85 ℃;

(3) reacting for 2-3h after the dropwise adding is finished, cooling to below 40 ℃, slowly adding 450Kg of water for dissolving, stirring for 0.5-1h after the completion, and standing to separate out a water phase;

(4) adding 1500Kg of water and 270Kg of 60-70% manganese dioxide into a 2000L reaction kettle, heating to 100 ℃, stirring again, extracting the water phase obtained in the step 3 into a head tank, dropwise adding for about 12-15 hours, keeping the dropwise adding temperature at 100 ℃, and distilling the product produced by the reaction;

(5) filtering the product obtained by distillation in the step 4 through cotton cloth, and drying the product for 3.5 to 4 hours at room temperature under the negative pressure of-0.09 MPa to obtain a thymoquinone product;

(6) pumping the filtrate obtained by filtering in the step 5 into a reaction kettle, and adding 30-50L of solvent oil for extraction; filtering the separated organic phase to remove impurities, and then evaporating the solvent oil to dryness under reduced pressure at the temperature of 30-35 ℃ for 5-7 hours to obtain the thymoquinone product.

2. The method for preparing thymoquinone according to claim 1, wherein: the dropping time is controlled to be 6-7 h.

3. The method for preparing thymoquinone according to claim 1, wherein: the molar ratio of the thymol to the concentrated sulfuric acid is 1: 3.2.

4. The method for preparing thymoquinone according to claim 1, wherein: the molar ratio of the concentrated sulfuric acid to the manganese dioxide is 1: 1.1.

5. The method for preparing thymoquinone according to claim 1, wherein: the solvent oil is refined No. 6 solvent oil.

6. The method for preparing thymoquinone according to claim 1, wherein: the stirring speed of the reaction kettle is 60-90 r/min.

7. The method for preparing thymoquinone according to claim 1, wherein: during the distillation, the temperature was controlled at 100 ℃.

Technical Field

The invention relates to the technical field of chemical industry, in particular to a preparation method of thymoquinone.

Background

Thymoquinone is used as a main effective monomer separated from nigella sativa seed oil, has potential cancer prevention and inhibition effects, and can inhibit the growth of various tumor cells such as breast cancer, pancreatic cancer, prostate cancer and the like; thymoquinone (2-isopropyl-5-methyl-1, 4-benzoquinone) can remarkably inhibit in-vitro EPCs tubule formation, inhibit in-vitro expression of VEGF in pancreatic cancer PANC-1 cells, remarkably inhibit pancreatic tumor growth in tumor-bearing nude mice, and down-regulate positive expression of Ki-67, CD34 and VEGF in pancreatic tumor tissues, can be used as a vascular inhibition drug for treating pancreatic cancer, can remarkably inhibit colorectal cancer growth and metastasis, inhibit in-vitro bladder cancer cell production, and induce apoptosis. However, the existing preparation method of thymoquinone is a nitration-catalytic hydrogenation-diazotization synthesis route, a sulfonation-oxidation synthesis route and a salen-Co II catalyst one-step synthesis route, and the preparation methods are relatively troublesome in the preparation process, relatively harsh in reaction conditions, relatively low in purity of the prepared finished product and relatively low in conversion rate, so that the preparation method of thymoquinone is necessary.

Disclosure of Invention

The invention aims to provide a preparation method of thymoquinone, which aims to solve the problems in the background technology.

In order to solve the technical problems, the invention provides the following technical scheme: a preparation method of thymoquinone comprises the steps of distilling, filtering and drying thymol serving as a substrate, concentrated sulfuric acid serving as a sulfonating agent, manganese dioxide serving as an oxidant and water serving as a solvent to obtain thymoquinone;

wherein the molar ratio of thymol to concentrated sulfuric acid is 1:3 to 3.5; the molar ratio of concentrated sulfuric acid to manganese dioxide is 1: 1-1.5.

The method mainly comprises the following steps:

(1) adding 90kg of thymol and 600L of solvent oil into a 1500L reaction kettle, starting stirring, and heating to 60-65 ℃;

(2) pumping 186Kg of concentrated sulfuric acid into a head tank, slowly dripping into a reaction kettle, dripping to release heat, and controlling the dripping temperature to be 70-85 ℃;

(3) reacting for 2-3h after the dropwise adding is finished, cooling to below 40 ℃, slowly adding 450Kg of water for dissolving, stirring for 0.5-1h after the completion, and standing to separate out a water phase;

(4) adding 1500Kg of water and 270Kg of 60-70% manganese dioxide into a 2000L reaction kettle, heating to 100 ℃, stirring again, extracting the water phase obtained in the step 3 into a head tank, dropwise adding for about 12-15 hours, keeping the dropwise adding temperature at 100 ℃, and distilling the product produced by the reaction;

(5) filtering the product obtained by distillation in the step 4 through cotton cloth, and drying the product for 3.5 to 4 hours at room temperature under the negative pressure of-0.09 MPa to obtain a thymoquinone product;

(6) pumping the filtrate obtained by filtering in the step 5 into a reaction kettle, and adding 30-50L of solvent oil for extraction; filtering the separated organic phase to remove impurities, and then evaporating the solvent oil to dryness under reduced pressure at the temperature of 30-35 ℃ for 5-7 hours to obtain the thymoquinone product.

According to the technical scheme, the dripping time is controlled to be 6-7 h.

According to the technical scheme, the molar ratio of the thymol to the concentrated sulfuric acid is 1: 3.2.

According to the technical scheme, the molar ratio of the concentrated sulfuric acid to the manganese dioxide is 1: 1.1.

According to the technical scheme, the solvent oil is refined No. 6 solvent oil.

According to the technical scheme, the stirring speed of the reaction kettle is 60-90 r/min.

According to the technical scheme, the temperature is controlled to be 100 ℃ in the distillation process.

Compared with the prior art, the invention has the following beneficial effects: according to the invention, the purity of thymoquinone is higher through distillation, filtration and drying, a synthetic production process convenient for industrialization is formed by changing a reaction route or optimizing a synthetic method, the operation is simple and convenient, the process control is precise and reliable, the yield is high, the cost is low, raw materials are easy to obtain, the reaction condition is mild, the product quality is stable, the three wastes are less, the environment pollution is light, and the method is beneficial to labor protection of producers; and thymoquinone mp: 45.8-46.6 ℃, purity (HPLC): 98.5-99%, conversion: 96.8-97% and 85% -90% of yield.

Drawings

The accompanying drawings, which are included to provide a further understanding of the invention and are incorporated in and constitute a part of this specification, illustrate embodiments of the invention and together with the description serve to explain the principles of the invention and not to limit the invention. In the drawings:

FIG. 1 is the principal chemical reaction scheme 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 drawings in 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.

Referring to fig. 1, the present invention provides a technical solution: a method for preparing thymoquinone;