CN110922293A - Green production method of 1- (2, 3-dimethylphenyl) -1-chloroethane - Google Patents
Green production method of 1- (2, 3-dimethylphenyl) -1-chloroethane Download PDFInfo
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- CN110922293A CN110922293A CN201911226040.7A CN201911226040A CN110922293A CN 110922293 A CN110922293 A CN 110922293A CN 201911226040 A CN201911226040 A CN 201911226040A CN 110922293 A CN110922293 A CN 110922293A
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- C07C17/093—Preparation of halogenated hydrocarbons by replacement by halogens
- C07C17/16—Preparation of halogenated hydrocarbons by replacement by halogens of hydroxyl groups
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Abstract
The invention relates to a green production method of 1- (2, 3-dimethylphenyl) -1-chloroethane, which comprises the following steps: introducing hydrogen chloride into a reaction kettle filled with 1- (2, 3-dimethylphenyl) -1-ethanol for reaction, sending hydrogen chloride tail gas to the bottom of an absorption tower from the top of the reaction kettle, introducing an alkaline aqueous solution into the top of the absorption tower to absorb hydrogen chloride gas, and discharging reaction liquid from the bottom of the reaction kettle to obtain the 1- (2, 3-dimethylphenyl) -1-chloroethane. The process effectively absorbs the hydrogen chloride generated in the production process of the 1- (2, 3-dimethylphenyl) -1-chloroethane, so that the process is more environment-friendly. The yield of the reaction product 1- (2, 3-dimethylphenyl) -1-chloroethane obtained at the same time is more than 85 percent.
Description
Technical Field
The invention belongs to the field of pharmacy, and particularly relates to a method for producing 1- (2, 3-dimethylphenyl) -1-chloroethane by using 1- (2, 3-dimethylphenyl) -1-ethanol and hydrogen chloride, and relates to a preparation technology of 1- (2, 3-dimethylphenyl) -1-chloroethane in the field of pharmacy.
Background
Dexmedetomidine hydrochloride (dexmedetomidine hydrochloride) is the active dextro-isomer of medetomidine, a novel α 2-adrenoceptor agonist (sedative hypnotic) developed by Orion pharma/Abott, having sympatholytic, sedative and analgesic effects, having 8 times higher affinity for adrenoceptors than clonidine, short half-life, low effective dose, and being suitable for the start of intubation and sedation of ventilator patients during intensive care therapy, improving the stability of hemodynamics during surgery and reducing the incidence of myocardial ischemia.
1- (2, 3-dimethylphenyl) -1-chloroethane is an important intermediate in the synthesis process of dexmedetomidine. At present, a plurality of methods for producing 1- (2, 3-dimethylphenyl) -1-chloroethane are available, and the method is mainly a 1- (2, 3-dimethylphenyl) -1-ethanol method which is a chlorination reaction by taking 1- (2, 3-dimethylphenyl) -1-ethanol and hydrogen chloride as raw materials. However, the method has very obvious defects, namely, the post-treatment of a large amount of hydrogen chloride gas introduced into the system in the reaction process brings great disadvantages to environmental protection, and if the hydrogen chloride gas is directly discharged, the method can cause serious pollution to the environment. The hydrogen chloride is particularly necessary to be subjected to post-treatment at present when the green and environment-friendly process is advocated.
Disclosure of Invention
The technical purpose of the invention is to provide a method for producing 1- (2, 3-dimethylphenyl) -1-chloroethane from 1- (2, 3-dimethylphenyl) -1-ethanol and hydrogen chloride, wherein the process enables the hydrogen chloride generated in the production process of the 1- (2, 3-dimethylphenyl) -1-chloroethane to be effectively absorbed, the process is more environment-friendly, and the conversion rate of the 1- (2, 3-dimethylphenyl) -1-chloroethane in the obtained reaction product is more than 85%.
In order to realize the technical purpose of the invention, the technical scheme of the invention is as follows:
a green production method of 1- (2, 3-dimethylphenyl) -1-chloroethane, comprising the following steps:
introducing hydrogen chloride into a reaction kettle filled with 1- (2, 3-dimethylphenyl) -1-ethanol for reaction, sending the hydrogen chloride tail gas after the reaction into the bottom of an absorption tower from the top of the reaction kettle, and introducing an alkaline aqueous solution into the top of the absorption tower to absorb hydrogen chloride gas; and discharging the reaction liquid from the bottom of the reaction kettle to obtain the 1- (2, 3-dimethylphenyl) -1-chloroethane.
Preferably, the molar ratio of the 1- (2, 3-dimethylphenyl) -1-ethanol to the amount of hydrogen chloride introduced into the reaction kettle per hour is 1: 1-1: 10;
preferably, the reaction temperature is 10-70 ℃.
Preferably, the reaction time is 1-10 h.
Preferably, the alkaline aqueous solution is an inorganic alkaline aqueous solution.
Preferably, the inorganic base is sodium hydroxide, potassium hydroxide, sodium carbonate, sodium bicarbonate or potassium carbonate.
Preferably, the flow rate of the alkaline aqueous solution introduced into the absorption tower is as follows: the molar flow rate of the inorganic base is 0.1-2.0 mol/h.
Preferably, the green production method of 1- (2, 3-dimethylphenyl) -1-chloroethane further comprises the step of distilling the reaction solution discharged from the bottom of the reaction kettle under normal pressure.
Drawings
FIG. 1 is a diagram of a process apparatus of the present invention.
Wherein: 1 is a hydrogen chloride storage tank, 2 is a stirrer, 3 is a pump, 4 is a kettle bottom discharge port, 5 is an absorption tower, and 6 is an alkaline aqueous solution storage tank.
Detailed Description
Example 1
And (3) carrying out qualitative and quantitative detection on the reaction product by adopting a high performance liquid chromatography: octadecylsilane chemically bonded silica is used as a filler (a chromatographic column with 4.6mm multiplied by 150mm and 5 mu m or equivalent efficiency) and 0.02mol/L disodium hydrogen phosphate solution (the pH value is adjusted to 6.3 by phosphoric acid) -acetonitrile (75:25) is used as a mobile phase; the detection wavelength was 220nm, and the amount of sample was 20. mu.l.
Introducing 1- (2, 3-dimethylphenyl) -1-ethanol and hydrogen chloride into a reaction kettle filled with 1- (2, 3-dimethylphenyl) -1-ethanol according to the molar ratio of the amount of the 1- (2, 3-dimethylphenyl) -1-ethanol to the hydrogen chloride in each hour of 1:10, heating to the reaction temperature of 70 ℃, strongly stirring for reaction for 5 hours, pumping the hydrogen chloride generated by the reaction out of the top of the reaction kettle, pumping the hydrogen chloride into the bottom of an absorption tower, and pumping potassium hydroxide solution into the tower top at the flow rate of 0.1 mol/hour to absorb the hydrogen chloride gas. The reaction solution was discharged from the bottom of the vessel and distilled at normal pressure to obtain high purity 1- (2, 3-dimethylphenyl) -1-chloroethane with a yield of 85.2%.
Example 2
The qualitative and quantitative detection method and operation of the reaction product are the same as those in example 1, and the implementation steps for changing the molar ratio of the reactants and the operation parameters are as follows:
introducing 1- (2, 3-dimethylphenyl) -1-ethanol and hydrogen chloride into a reaction kettle filled with 1- (2, 3-dimethylphenyl) -1-ethanol according to the molar ratio of the amount of the 1:7 introduced into the reaction kettle per hour, heating to the reaction temperature of 50 ℃, strongly stirring for reaction for 3 hours, pumping the hydrogen chloride generated by the reaction out of the top of the reaction kettle, pumping the hydrogen chloride into the bottom of an absorption tower, and pumping a sodium hydroxide solution into the top of the reaction tower at the flow rate of 2.0 mol/hour to absorb the hydrogen chloride gas. The reaction solution was discharged from the bottom of the vessel and distilled at normal pressure to obtain high purity 1- (2, 3-dimethylphenyl) -1-chloroethane with a yield of 87.6%.
Example 3
The qualitative and quantitative detection method and operation of the reaction product are the same as those in example 1, and the implementation steps for changing the molar ratio of the reactants and the operation parameters are as follows:
introducing 1- (2, 3-dimethylphenyl) -1-ethanol and hydrogen chloride into a reaction kettle filled with 1- (2, 3-dimethylphenyl) -1-ethanol according to the molar ratio of the amount of the 1:5 introduced into the reaction kettle per hour, heating to the reaction temperature of 30 ℃, strongly stirring for reaction for 1h, pumping the hydrogen chloride generated by the reaction out of the top of the reaction kettle, pumping the hydrogen chloride into the bottom of an absorption tower, and pumping potassium carbonate solution into the top of the reaction tower at the flow rate of 1.5mol/h to absorb the hydrogen chloride gas. The reaction solution was discharged from the bottom of the vessel and distilled at normal pressure to obtain high purity 1- (2, 3-dimethylphenyl) -1-chloroethane with a yield of 88.9%.
Example 4
The qualitative and quantitative detection method and operation of the reaction product are the same as those in example 1, and the implementation steps for changing the molar ratio of the reactants and the operation parameters are as follows:
introducing 1- (2, 3-dimethylphenyl) -1-ethanol and hydrogen chloride into a reaction kettle filled with 1- (2, 3-dimethylphenyl) -1-ethanol according to the molar ratio of the amount of the 1:3 introduced into the reaction kettle per hour, heating to the reaction temperature of 10 ℃, strongly stirring for reaction for 10 hours, pumping the hydrogen chloride generated by the reaction out of the top of the reaction kettle, pumping the hydrogen chloride into the bottom of an absorption tower, and pumping the hydrogen carbonate solution into the top of the reaction kettle at the flow rate of 1.0 mol/hour to absorb the hydrogen chloride gas. The reaction solution was discharged from the bottom of the vessel and distilled at normal pressure to obtain 1- (2, 3-dimethylphenyl) -1-chloroethane of high purity in a yield of 89.1%.
Example 5
The qualitative and quantitative detection method and operation of the reaction product are the same as those in example 1, and the implementation steps for changing the molar ratio of the reactants and the operation parameters are as follows:
1- (2, 3-dimethylphenyl) -1-ethanol and hydrogen chloride are introduced into a reaction kettle filled with 1- (2, 3-dimethylphenyl) -1-ethanol according to the molar ratio of 1:1 of the amount introduced into the reaction kettle per hour, the reaction kettle is heated to the reaction temperature of 40 ℃, the mixture is stirred vigorously for reaction for 7 hours, the hydrogen chloride generated by the reaction is extracted from the top of the reaction kettle and is pumped into the bottom of an absorption tower, and a sodium carbonate solution is pumped into the top of the reaction kettle at the flow rate of 0.5 mol/hour to absorb the hydrogen chloride gas. The reaction solution was discharged from the bottom of the vessel and distilled at normal pressure to obtain high purity 1- (2, 3-dimethylphenyl) -1-chloroethane with a yield of 91.4%.
Claims (8)
1. A green production method of 1- (2, 3-dimethylphenyl) -1-chloroethane is characterized by comprising the following steps:
introducing hydrogen chloride into a reaction kettle filled with 1- (2, 3-dimethylphenyl) -1-ethanol for reaction, sending the hydrogen chloride tail gas after the reaction into the bottom of an absorption tower from the top of the reaction kettle, introducing an alkaline aqueous solution into the top of the absorption tower to absorb hydrogen chloride gas, and discharging reaction liquid from the bottom of the reaction kettle to obtain the 1- (2, 3-dimethylphenyl) -1-chloroethane.
2. The green production method of 1- (2, 3-dimethylphenyl) -1-chloroethane according to claim 1, characterized in that the molar ratio of 1- (2, 3-dimethylphenyl) -1-ethanol to the amount of hydrogen chloride introduced into the reaction kettle per hour is 1:1 to 1: 10.
3. The green production method of 1- (2, 3-dimethylphenyl) -1-chloroethane according to claim 1, characterized in that the temperature of the reaction is 10 to 70 ℃.
4. The green production method of 1- (2, 3-dimethylphenyl) -1-chloroethane according to claim 1, characterized in that the reaction time is 1-10 h.
5. The method for green production of 1- (2, 3-dimethylphenyl) -1-chloroethane according to claim 1, wherein the aqueous alkaline solution is an aqueous solution of an inorganic base.
6. A green process for the production of 1- (2, 3-dimethylphenyl) -1-chloroethane according to claim 5, wherein the inorganic base is sodium hydroxide, potassium hydroxide, sodium carbonate, sodium bicarbonate or potassium carbonate.
7. The process for the green production of 1- (2, 3-dimethylphenyl) -1-chloroethane according to claim 6, wherein the flow rate of the aqueous alkaline solution to the absorption column is: the molar flow rate of the inorganic base is 0.1-2.0 mol/h.
8. The method for green production of 1- (2, 3-dimethylphenyl) -1-chloroethane according to claim 1, further comprising the step of atmospheric distillation of the reaction solution discharged from the bottom of the reaction vessel.
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| CN103497177A (en) * | 2012-09-29 | 2014-01-08 | 天津滨江药物研发有限公司 | Amino heterocyclic aromatic compound serving as c-Met inhibitor, and preparation method thereof |
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2019
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| CN103694175A (en) * | 2013-12-18 | 2014-04-02 | 北京华禧联合科技发展有限公司 | New method for preparing dexmedetomidine hydrochloride |
| US20170050905A1 (en) * | 2015-08-19 | 2017-02-23 | Honeywell International, Inc. | Methods for Removing Acidic Impurities from Halogenated Propenes |
| CN107961646A (en) * | 2016-10-19 | 2018-04-27 | 中国石油化工股份有限公司 | A kind of processing method of chloride tail gas |
| CN206325366U (en) * | 2016-11-14 | 2017-07-14 | 重庆康普化学工业股份有限公司 | hydrogen chloride gas after-treatment device |
| CN109180418A (en) * | 2018-10-09 | 2019-01-11 | 江苏扬农化工集团有限公司 | A kind of propylene oxide co-production object resource utilization synthetic pesticide intermediate 2,4 dichloro benzene ethyl ketone method |
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