CN111574385B - Synthesis method of 2- (2, 4, 6-trichlorophenoxy) ethyl propylamine - Google Patents
Synthesis method of 2- (2, 4, 6-trichlorophenoxy) ethyl propylamine Download PDFInfo
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- CN111574385B CN111574385B CN202010460050.3A CN202010460050A CN111574385B CN 111574385 B CN111574385 B CN 111574385B CN 202010460050 A CN202010460050 A CN 202010460050A CN 111574385 B CN111574385 B CN 111574385B
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- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C213/06—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton from hydroxy amines by reactions involving the etherification or esterification of hydroxy groups
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- C07C213/08—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions not involving the formation of amino groups, hydroxy groups or etherified or esterified hydroxy groups
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Abstract
The invention discloses a method for synthesizing 2- (2, 4, 6-trichlorophenoxy) ethyl propylamine, which comprises the following steps: reacting 2,4, 6-trichlorophenol with ethylamine under the catalysis of boron trifluoride diethyl etherate, and then salifying with hydrochloric acid to obtain a compound A; the compound A is catalyzed by cesium hydroxide monohydrate, and reacts with 1-bromopropane by taking sodium carbonate as an acid-binding agent to obtain the 2- (2, 4, 6-trichlorophenoxy) ethylpropylamine. The method has simple operation steps, cheap and easily-obtained reaction raw materials, 94.18 percent of total molar yield, over 98.0 percent of purity of the produced 2- (2, 4, 6-trichlorophenoxy) ethyl propylamine and better quality of products, and is suitable for industrial production.
Description
Technical Field
The invention belongs to the technical field of synthesis of pesticide intermediates, and particularly relates to a synthesis method of 2- (2, 4, 6-trichlorophenoxy) ethylpropylamine.
Background
2- (2, 4, 6-trichlorophenoxy) ethyl propylamine is an important fine chemical intermediate and is a key intermediate for synthesizing pesticide prochloraz.
The synthesis of 2- (2, 4, 6-trichlorophenoxy) ethylpropylamine has mainly the following two routes:
(1) Chinese patent (CN 101402608) reports that 2,4,6-trichlorophenol is used as a substrate, and reacts with dichloroethane and liquid alkali to obtain an etherate, and then reacts with n-propylamine to obtain 2- (2,4,6-trichlorophenoxy) ethyl propylamine, wherein the reaction is shown as follows:
in the first step of the method, in the presence of liquid alkali, the obtained etherate is easy to have elimination reaction, and in addition, the reaction with n-propylamine requires high temperature and high pressure, the reaction conditions are harsh, the reaction is not easy to control, the requirement on equipment is high, and the investment is large.
(2) Wearangxia et al (N-N-propyl-N-2- (2, 4, 6-trichlorophenoxy) ethylamine, shanxi chemical, 1999) reported that starting from 2-phenoxyethanol, 2- (2, 4, 6-trichlorophenoxy) ethanol was first obtained by reaction with chlorine, and then with thionyl chloride to obtain 2- (2, 4, 6-trichlorophenoxy) ethyl chloride, which was then reacted with N-propylamine under high pressure to obtain 2- (2, 4, 6-trichlorophenoxy) ethyl-propylamine. The method also avoids the disadvantages of harsh reaction conditions, difficult control of the reaction, high requirements on reaction equipment and large investment, and the reaction is as follows:
in summary, the existing synthesis method of 2- (2, 4, 6-trichlorophenoxy) ethylpropylamine generally has the defects of harsh reaction conditions, difficult reaction control, high requirement on equipment and large investment, and no satisfactory result is obtained in domestic research on synthesis of 2- (2, 4, 6-trichlorophenoxy) ethylpropylamine at present. Therefore, the development of a synthetic route of the 2- (2, 4, 6-trichlorophenoxy) ethylpropylamine which has mild reaction conditions and safe operation and is suitable for industrial production is significant.
Disclosure of Invention
The invention aims to provide a synthesis method of 2- (2, 4, 6-trichlorophenoxy) ethyl propylamine, which has mild reaction conditions, safe operation and high yield and is suitable for industrial production, so as to solve the problems in the background technology.
In order to achieve the purpose, the invention provides the following technical scheme:
a synthetic method of 2- (2, 4, 6-trichlorophenoxy) ethyl propylamine sequentially comprises the following steps:
step (a): reacting 2,4, 6-trichlorophenol with ethylamine under the catalysis of boron trifluoride diethyl etherate, and then salifying with hydrochloric acid to obtain a compound A, wherein the reaction formula is as follows:
a step (b): reacting the compound A with 1-bromopropane under the catalysis of cesium hydroxide monohydrate by taking sodium carbonate as an acid-binding agent to obtain 2- (2, 4, 6-trichlorophenoxy) ethylpropylamine; the reaction formula is as follows:
as a further scheme of the invention: in the synthesis of the compound A in the step (a), the reaction solvent is toluene, and the weight of the reaction solvent is 4-8 times that of 2,4, 6-trichlorophenol.
As a further scheme of the invention: in the synthesis of the compound A in the step (a), the molar ratio of the 2,4, 6-trichlorophenol to the cyclic ethylamine is 1: 1.0-1.1.
As a further scheme of the invention: in the synthesis of the compound A in the step (a), the weight of boron trifluoride diethyl etherate is 4-6% of that of 2,4, 6-trichlorophenol.
As a further scheme of the invention: in the synthesis of the compound A in the step (a), the reaction temperature is 50-55 ℃, the time for dripping the cyclic ethylamine is 0.5-1.5 h, and the heat preservation time is 2-3 h after dripping.
As a further scheme of the invention: in the step (b), in the synthesis of the 2- (2, 4, 6-trichlorophenoxy) ethylpropylamine, the reaction solvent is N, N-dimethylformamide, and the weight of the N, N-dimethylformamide is 8-12 times that of the 2,4, 6-trichlorophenol.
As a further scheme of the invention: in the step (b) of synthesizing the 2- (2, 4, 6-trichlorophenoxy) ethylpropylamine, the molar ratio of the compound A to the 1-bromopropane to the sodium carbonate is 1: 1.0-1.1: 2.0-2.2.
As a further scheme of the invention: in the synthesis of 2- (2, 4, 6-trichlorophenoxy) ethylpropylamine in the step (b), the weight of the cesium hydroxide monohydrate is 4-6% of that of the compound A.
As a further scheme of the invention: in the step (b), in the synthesis of the 2- (2, 4, 6-trichlorophenoxy) ethylpropylamine, the reaction temperature is 30-35 ℃, the time for dripping the 1-bromopropane is 0.5-1.5 h, and the heat preservation time is 4-6 h after dripping is finished.
Compared with the prior art, the invention has the beneficial effects that: the 2- (2, 4, 6-trichlorophenoxy) ethyl propylamine prepared by the invention has the advantages of mild reaction conditions, safe operation and suitability for industrial production.
Detailed Description
The technical solution of the present patent will be described in further detail with reference to the following embodiments.
EXAMPLE 1 Synthesis of Compound A
2,4, 6-trichlorophenol (197.45g, 1.0mol), toluene (1184.70 g) and boron trifluoride ether (9.87 g) are put into a 2L four-mouth bottle, the temperature is raised to 50-55 ℃ by stirring, a peristaltic pump is used for dropwise adding ethylamine (45.22g, 1.05mol), the dropwise adding time is about 1h, the temperature is kept at 50-55 ℃ after dropwise adding is finished, the stirring reaction is carried out for 2.5h, HPLC (high performance liquid chromatography) detects that the residual amount of the 2,4, 6-trichlorophenol is less than 1%, and the reaction is finished.
Distilling toluene at normal pressure, cooling to 50-55 ℃ after about 620g of toluene is distilled out, dropwise adding 20% hydrochloric acid, adjusting the pH value to 4.0-5.0, installing a water separator, carrying out normal-pressure reflux until the moisture of the reaction solution is less than 0.5%, cooling to 0-5 ℃, carrying out suction filtration, and drying a filter cake to obtain 267.15g of compound A, wherein the molar yield is 96.45% and the HPLC purity is 99.23%.
Comparative example 1 Synthesis of Compound A
2,4, 6-trichlorophenol (197.45g, 1.0 mol) and toluene (1184.70 g) are put into a 2L four-mouth bottle, stirred and heated to 50-55 ℃, a peristaltic pump is used for dropwise adding the cyclic ethylamine (45.22g, 1.05mol), the dropwise adding time is about 1h, the temperature is kept between 50 and 55 ℃ after dropwise adding, stirring reaction is carried out for 2.5h, HPLC (high performance liquid chromatography) detects that the residue of the 2,4, 6-trichlorophenol is 97.02 percent, the temperature is controlled between 50 and 55 ℃, stirring reaction is continuously carried out for 5h, HPLC detects that the residue of the 2,4, 6-trichlorophenol is 95.76 percent, and the residue is discarded.
Example 2 Synthesis of 2- (2, 4, 6-trichlorophenoxy) ethylpropylamine
Adding the compound A (138.49g, 0.50mol), N-dimethylformamide (1384.90 g), sodium carbonate (111.30g, 1.05mol) and cesium hydroxide monohydrate (6.92 g) into a 3L four-mouth bottle, controlling the temperature to be 30-35 ℃, dropwise adding 1-bromopropane (64.57g, 0.525 mol) by using a peristaltic pump, controlling the temperature to be 30-35 ℃ after dropwise adding, continuously stirring for 5 hours, detecting by HPLC that the residue of the compound A is less than 1%, and finishing the reaction.
Suction filtration, leaching a filter cake for 3 times by using N, N-dimethylformamide (138.49 g/time), combining filtrate and washing liquor, carrying out reduced pressure distillation to recover the N, N-dimethylformamide, adding toluene (415.47 g), dropwise adding 20% hydrochloric acid, adjusting the pH value to 3.0-4.0, installing a water separator, carrying out normal pressure reflux until the moisture content of a reaction solution is less than 0.5%, cooling to 0-5 ℃, suction filtration, putting the filter cake into another clean 1L four-mouth bottle, adding pure water (415.47 g), adjusting the pH value to 7.0-8.0 by using 10% sodium carbonate, transferring into a separating funnel, standing to separate an organic layer, controlling the temperature of the organic layer to be 80-90 ℃, carrying out reduced pressure distillation to remove residual moisture, stopping reduced pressure distillation when the moisture content is less than 0.3%, obtaining 137.97g of 2- (2, 4, 6-trichlorophenoxy) ethyl propylamine, wherein the molar yield is 97.65%, and the purity of HPLC is 98.65%.
COMPARATIVE EXAMPLE 2 Synthesis of 2- (2, 4, 6-Trichlorophenoxy) ethylpropylamine
Adding the compound A (138.49g, 0.50mol) into a 3L four-mouth bottle, adding N, N-dimethylformamide (1384.90 g), sodium carbonate (111.30g, 1.05mol) into the bottle, controlling the temperature to be 30-35 ℃, dropwise adding 1-bromopropane (64.57g, 0.525mol) by using a peristaltic pump for about 1h, controlling the temperature to be 30-35 ℃ and continuously stirring for 5h after dropwise adding is finished, detecting the residue of the compound A by HPLC to be 98.13 percent, heating to reflux, continuously stirring for 5h, detecting the residue of the compound A by HPLC, and discarding the compound A, wherein the residue of the compound A is 86.92 percent.
Although the preferred embodiments of the present patent have been described in detail, the present patent is not limited to the above embodiments, and various changes can be made without departing from the spirit of the present patent within the knowledge of those skilled in the art.
Claims (9)
1. A synthetic method of 2- (2, 4, 6-trichlorophenoxy) ethyl propylamine is characterized by sequentially comprising the following steps:
step (a): reacting 2,4, 6-trichlorophenol with ethylamine under the catalysis of boron trifluoride diethyl etherate, and then salifying with hydrochloric acid to obtain a compound A; the reaction formula is as follows:
step (b): under the catalysis of cesium hydroxide monohydrate, sodium carbonate is used as an acid-binding agent to react with 1-bromopropane to obtain 2- (2, 4, 6-trichlorophenoxy) ethylpropylamine, and the reaction formula is as follows:
2. the method for synthesizing 2- (2, 4, 6-trichlorophenoxy) ethylpropylamine according to claim 1, wherein in the synthesis of the compound A in the step (a), the reaction solvent is toluene, and the weight of the reaction solvent is 4-8 times that of 2,4, 6-trichlorophenol.
3. The method for synthesizing 2- (2, 4, 6-trichlorophenoxy) ethylpropylamine according to claim 1, wherein in the synthesis of the compound A in the step (a), the molar ratio of 2,4, 6-trichlorophenol to the cyclic ethylamine is 1: 1.0-1.1.
4. The method for synthesizing 2- (2, 4, 6-trichlorophenoxy) ethylpropylamine according to claim 1, wherein the weight of boron trifluoride ethyl ether in the synthesis of compound A in step (a) is 4-6% of that of 2,4, 6-trichlorophenol.
5. The method for synthesizing 2- (2, 4, 6-trichlorophenoxy) ethylpropylamine according to claim 1, wherein in the synthesis of the compound A in the step (a), the reaction temperature is 50-55 ℃, the time for dripping the ethylamine is 0.5-1.5 h, and the holding time is 2-3 h after dripping.
6. The method for synthesizing 2- (2, 4, 6-trichlorophenoxy) ethylpropylamine according to claim 1, wherein in the step (b) for synthesizing 2- (2, 4, 6-trichlorophenoxy) ethylpropylamine, the reaction solvent is N, N-dimethylformamide, and the weight is 8-12 times of that of 2,4, 6-trichlorophenol.
7. The method for synthesizing 2- (2, 4, 6-trichlorophenoxy) ethylpropylamine according to claim 1, wherein in the step (b) for synthesizing the 2- (2, 4, 6-trichlorophenoxy) ethylpropylamine, the molar ratio of the compound A to the 1-bromopropane to the sodium carbonate is 1: 1.0-1.1: 2.0-2.2.
8. The method for synthesizing 2- (2, 4, 6-trichlorophenoxy) ethylpropylamine according to claim 1, wherein in the step (b) for synthesizing the 2- (2, 4, 6-trichlorophenoxy) ethylpropylamine, the weight of the cesium hydroxide monohydrate is 4-6% of that of the compound A.
9. The method for synthesizing 2- (2, 4, 6-trichlorophenoxy) ethylpropylamine according to claim 1, wherein in the synthesis of 2- (2, 4, 6-trichlorophenoxy) ethylpropylamine in the step (b), the reaction temperature is 30-35 ℃, the time for dripping 1-bromopropane is 0.5-1.5 h, and the holding time is 4-6 h after dripping.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0084236A2 (en) * | 1981-12-22 | 1983-07-27 | Fbc Limited | Fungicidal heterocyclic compounds and compositions containing them |
| WO2002057215A2 (en) * | 2001-01-16 | 2002-07-25 | Theravance, Inc. | Sodium channel modulators |
| CN101402608A (en) * | 2008-11-25 | 2009-04-08 | 乐斯化学有限公司 | Method for producing bactericide prochloraz |
| CN108727376A (en) * | 2018-05-21 | 2018-11-02 | 中国计量大学 | The rich iodine class compound of 9- azabicyclos [3.3.1] nonane coupling and its preparation method and purposes |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CA2579756C (en) * | 2004-06-19 | 2013-04-30 | Human Biomolecular Research Institute | Modulators of central nervous system neurotransmitters |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0084236A2 (en) * | 1981-12-22 | 1983-07-27 | Fbc Limited | Fungicidal heterocyclic compounds and compositions containing them |
| WO2002057215A2 (en) * | 2001-01-16 | 2002-07-25 | Theravance, Inc. | Sodium channel modulators |
| CN101402608A (en) * | 2008-11-25 | 2009-04-08 | 乐斯化学有限公司 | Method for producing bactericide prochloraz |
| CN108727376A (en) * | 2018-05-21 | 2018-11-02 | 中国计量大学 | The rich iodine class compound of 9- azabicyclos [3.3.1] nonane coupling and its preparation method and purposes |
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