CN112552231B - Synthetic method of 2- (3-chloro-5- (trifluoromethyl) pyridine-2-yl) ethylamine - Google Patents
Synthetic method of 2- (3-chloro-5- (trifluoromethyl) pyridine-2-yl) ethylamine Download PDFInfo
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- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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Abstract
The invention relates to the technical field of pesticide organic synthesis, and provides a synthetic method of 2- (3-chloro-5- (trifluoromethyl) pyridine-2-yl) ethylamine, which comprises the following steps: (1) under the protection of inert gas, cooling a borane solution to-10-0 ℃, slowly adding 2-cyano-3-chloro-5-trifluoromethylpyridine, after dropwise adding, continuing stirring for 30-60 min, then heating to 30-35 ℃, stirring for reaction for 1-3 h, cooling to 0-5 ℃ after the reaction is finished, dropwise adding a certain proportion of methanol, and then stirring for 6-8 h at room temperature; (2) distilling the reaction solution under reduced pressure, adding a certain proportion of water into the obtained concentrated solution, standing to separate out a solid, filtering, washing and drying. Which solves the problems of harsh reaction conditions, complex operation and low yield of the existing synthesis of 2- (3-chloro-5- (trifluoromethyl) pyridine-2-yl) ethylamine.
Description
Technical Field
The invention relates to the technical field of pesticide organic synthesis, in particular to a synthetic method of 2- (3-chloro-5- (trifluoromethyl) pyridine-2-yl) ethylamine.
Background
Succinate dehydrogenase inhibitors (SDHIs) are bactericides which act on pathogenic bacteria succinate dehydrogenase to inhibit the respiration of the pathogenic bacteria succinate dehydrogenase, and the bactericides have the advantages of specific action, strong drug effect, lasting effect and obvious yield increasing effect.
Fluopyram developed by Bayer crop science is one of representatives of SDHIs bactericides, can be used for preventing and controlling alternaria leaf spot, gray mold, powdery mildew, sclerotinia, early blight and the like on vegetables such as grapes, pear trees, bananas, apples, cucumbers, tomatoes and the like and field crops, and can also be used for preventing and controlling various nematodes, thereby being an efficient, green and low-toxicity nematicide. Fluopyram (Fluopyram), molecular formula: c16H11ClF6N2O, chemical name: n- {2- [ 3-chloro-5- (trifluoromethyl) -2-pyridinyl]Ethyl } -alpha, alpha-o-trifluoromethylbenzamide. Fluopyram is prepared from 2- (3-chloro-5- (trifluoromethyl) pyridin-2-yl) ethylamine and 2-The compound is obtained by reacting trifluoromethyl benzoyl chloride, wherein 2- (3-chloro-5- (trifluoromethyl) pyridine-2-yl) ethylamine is a key intermediate for synthesizing fluopyram. The most reported synthetic routes for 2- (3-chloro-5- (trifluoromethyl) pyridin-2-yl) ethylamine are prepared by high pressure hydrogenation reduction of 2-cyano-3-chloro-5-trifluoromethylpyridine using noble metal catalysts in about 80% yield. The reaction conditions are harsh and the operation is complicated.
Disclosure of Invention
Therefore, in view of the above, the present invention provides a method for synthesizing 2- (3-chloro-5- (trifluoromethyl) pyridin-2-yl) ethylamine, which solves the problems of harsh reaction conditions, complicated operation and low yield of the existing synthesis of 2- (3-chloro-5- (trifluoromethyl) pyridin-2-yl) ethylamine.
In order to achieve the purpose, the invention is realized by the following technical scheme:
a method for synthesizing 2- (3-chloro-5- (trifluoromethyl) pyridin-2-yl) ethylamine, comprising the steps of:
(1) under the protection of inert gas, cooling a borane solution to-10-0 ℃, slowly adding 2-cyano-3-chloro-5-trifluoromethylpyridine, after dropwise adding, continuing stirring for 30-60 min, then heating to 30-35 ℃, stirring for reaction for 1-3 h, cooling to 0-5 ℃ after the reaction is finished, dropwise adding a certain proportion of methanol, and then stirring for 6-8 h at room temperature;
(2) and (2) distilling the reaction liquid under reduced pressure, adding a certain proportion of water into the obtained concentrated solution, standing, precipitating a solid, filtering, washing and drying to obtain the 2- (3-chloro-5- (trifluoromethyl) pyridin-2-yl) ethylamine.
The further improvement is that: the addition amount of the methanol is 20-30 wt% of the 2-cyano-3-chloro-5-trifluoromethylpyridine.
The further improvement is that: the addition amount of the water is 60-80 wt% of the 2-cyano-3-chloro-5-trifluoromethylpyridine.
The further improvement is that: the borane solution is borane dimethyl sulfide solution or borane tetrahydrofuran solution.
The further improvement is that: the borane solution is prepared by reacting an alkali metal borohydride with an acid in an organic solvent.
The further improvement is that: the alkali metal borohydride is potassium borohydride or sodium borohydride.
The further improvement is that: the acid is one or the mixture of two or more of hydrochloric acid, sulfuric acid, phosphoric acid, acetic acid, trifluoroacetic acid and boron trifluoride diethyl etherate solution.
The further improvement is that: the organic solvent is one or a mixture of more than two of benzene, toluene, xylene, chlorobenzene, dichlorobenzene, 1, 4-dioxane, acetonitrile, ethyl acetate, N-dimethylformamide, N-dimethylacetamide, dimethyl sulfoxide and sulfolane.
The further improvement is that: the inert gas is nitrogen or argon.
By adopting the technical scheme, the invention has the beneficial effects that:
the invention has the advantages of mild synthesis conditions, simple operation and high product yield and purity. The used raw materials are easy to obtain, can be directly purchased or self-made in the market, the self-making process is simple, the cost is low, the preparation by using a noble metal catalyst through high-pressure hydrogenation reduction in the prior art is not needed, the production cost is greatly reduced, and the method is suitable for industrial production.
Detailed Description
The following detailed description will be provided for the embodiments of the present invention with reference to specific embodiments, so that how to apply the technical means to solve the technical problems and achieve the technical effects can be fully understood and implemented.
Unless otherwise indicated, the techniques employed in the examples are conventional and well known to those skilled in the art, and the reagents and products employed are also commercially available. The source, trade name and if necessary the constituents of the reagents used are indicated at the first appearance.
Example one
A method for synthesizing 2- (3-chloro-5- (trifluoromethyl) pyridin-2-yl) ethylamine, comprising the steps of:
(1) under the protection of nitrogen, cooling 50ml of borane tetrahydrofuran solution to 0 ℃, slowly adding 8g of 2-cyano-3-chloro-5-trifluoromethylpyridine, after the dropwise addition is finished, continuing stirring for 30min, then heating to 30 ℃, stirring for reaction for 1h, cooling to 5 ℃ after the reaction is finished, dropwise adding 1.6g of methanol, and then stirring for 6h at room temperature;
(2) the reaction solution was distilled under reduced pressure to obtain a concentrated solution, 5g of water was added to the concentrated solution, and the concentrated solution was allowed to stand to precipitate a solid, which was then filtered, washed and dried to obtain 7.8g of 2- (3-chloro-5- (trifluoromethyl) pyridin-2-yl) ethylamine. The yield is 89.7%, and the purity is 98.5%.
Example two
A method for synthesizing 2- (3-chloro-5- (trifluoromethyl) pyridin-2-yl) ethylamine, comprising the steps of:
(1) dissolving potassium borohydride in N, N-dimethylformamide, and then dropwise adding trifluoroacetic acid to enable the potassium borohydride raw material to be completely reacted, so as to obtain a borane solution;
(2) under the protection of nitrogen, taking 50ml of borane solution prepared in the step (1), cooling to 0 ℃, slowly adding 8g of 2-cyano-3-chloro-5-trifluoromethylpyridine, after the dropwise addition is finished, continuing stirring for 30min, then heating to 30 ℃, stirring for reaction for 1h, cooling to 5 ℃ after the reaction is finished, dropwise adding 1.6g of methanol, and then stirring for 6h at room temperature;
(3) the reaction solution was distilled under reduced pressure to obtain a concentrated solution, 5g of water was added to the concentrated solution, and the concentrated solution was allowed to stand to precipitate a solid, which was then filtered, washed and dried to obtain 8.0g of 2- (3-chloro-5- (trifluoromethyl) pyridin-2-yl) ethylamine. The yield is 92.0 percent, and the purity is 98.8 percent.
EXAMPLE III
A method for synthesizing 2- (3-chloro-5- (trifluoromethyl) pyridin-2-yl) ethylamine, comprising the steps of:
(1) dissolving potassium borohydride in toluene, and then dropwise adding hydrochloric acid to enable the potassium borohydride raw material to be completely reacted, so as to obtain a borane solution;
(2) under the protection of nitrogen, taking 50ml of borane solution prepared in the step (1), cooling to-5 ℃, slowly adding 8g of 2-cyano-3-chloro-5-trifluoromethylpyridine, after the dropwise addition is finished, continuing stirring for 45min, then heating to 32 ℃, stirring for reaction for 2h, cooling to 3 ℃ after the reaction is finished, dropwise adding 2g of methanol, and then stirring for 7h at room temperature;
(3) the reaction solution was distilled under reduced pressure to obtain a concentrated solution, 5.6g of water was added to the concentrated solution, and a solid was precipitated after standing, filtered, washed and dried to obtain 8.1g of 2- (3-chloro-5- (trifluoromethyl) pyridin-2-yl) ethylamine. The yield was 93.1% and the purity 98.1%.
Example four
A method for synthesizing 2- (3-chloro-5- (trifluoromethyl) pyridin-2-yl) ethylamine, comprising the steps of:
(1) dissolving potassium borohydride in 1, 4-dioxane, and then dropwise adding acetic acid to enable the potassium borohydride raw material to be completely reacted to obtain borane solution;
(2) under the protection of nitrogen, taking 50ml of borane solution prepared in the step (1), cooling to-10 ℃, slowly adding 8g of 2-cyano-3-chloro-5-trifluoromethylpyridine, after the dropwise addition is finished, continuing stirring for 60min, then heating to 35 ℃, stirring for reaction for 3h, cooling to 0 ℃ after the reaction is finished, dropwise adding 2.4g of methanol, and then stirring for 8h at room temperature;
(3) the reaction solution was distilled under reduced pressure to obtain a concentrated solution, 6.4g of water was added to the concentrated solution, and a solid was precipitated after standing, filtered, washed and dried to obtain 8.1g of 2- (3-chloro-5- (trifluoromethyl) pyridin-2-yl) ethylamine. The yield was 93.1% and the purity 98.7%.
The above description is only an embodiment utilizing the technical content of the present disclosure, and any modification and variation made by those skilled in the art can be covered by the claims of the present disclosure, and not limited to the embodiments disclosed.
Claims (4)
1. A synthetic method of 2- [ 3-chloro-5- (trifluoromethyl) pyridin-2-yl ] ethylamine is characterized in that: the method comprises the following steps:
(1) under the protection of inert gas, cooling a borane solution to-10-0 ℃, slowly adding 2- [ 3-chloro-5-trifluoromethyl-2-pyridyl ] -acetonitrile, continuously stirring for 30-60 min after the dropwise addition is finished, then heating to 30-35 ℃, stirring for reaction for 1-3 h, cooling to 0-5 ℃ after the reaction is finished, dropwise adding a certain proportion of methanol, and then stirring for 6-8 h at room temperature;
the addition amount of the methanol is 20-30 wt% of the 2- [ 3-chloro-5-trifluoromethyl-2-pyridyl ] -acetonitrile,
the borane solution is prepared by reacting alkali metal borohydride with acid in an organic solvent, wherein the alkali metal borohydride is potassium borohydride or sodium borohydride, and the acid is one or a mixture of two or more of hydrochloric acid, sulfuric acid, phosphoric acid, acetic acid, trifluoroacetic acid and boron trifluoride diethyl etherate solution;
(2) and (3) distilling the reaction liquid under reduced pressure, adding a certain proportion of water into the obtained concentrated solution, standing, precipitating a solid, filtering, washing and drying to obtain the 2- [ 3-chloro-5- (trifluoromethyl) pyridin-2-yl ] ethylamine.
2. The method of claim 1, wherein the method comprises the following steps: the addition amount of the water is 60-80 wt% of 2- [ 3-chloro-5-trifluoromethyl-2-pyridyl ] -acetonitrile.
3. The method of claim 1, wherein the method comprises the following steps: the organic solvent is one or a mixture of more than two of benzene, toluene, xylene, chlorobenzene, dichlorobenzene, 1, 4-dioxane, acetonitrile, ethyl acetate, N-dimethylformamide, N-dimethylacetamide, dimethyl sulfoxide and sulfolane.
4. The method of claim 1, wherein the method comprises the following steps: the inert gas is nitrogen or argon.
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| CN101080390A (en) * | 2004-12-21 | 2007-11-28 | 拜尔农科股份有限公司 | Process for the preparation of a 2-ethylaminopyridine derivative |
| CN105745194A (en) * | 2013-11-15 | 2016-07-06 | 拜耳作物科学股份公司 | Catalytic hydrogenation of nitriles |
| CN110291069A (en) * | 2016-12-21 | 2019-09-27 | 拜耳农作物科学股份公司 | Catalytic Hydrogenation of Nitriles |
| CN110698392A (en) * | 2019-09-09 | 2020-01-17 | 中国农业大学 | A kind of bisamide compound and its preparation method and application |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101080390A (en) * | 2004-12-21 | 2007-11-28 | 拜尔农科股份有限公司 | Process for the preparation of a 2-ethylaminopyridine derivative |
| CN105745194A (en) * | 2013-11-15 | 2016-07-06 | 拜耳作物科学股份公司 | Catalytic hydrogenation of nitriles |
| CN110291069A (en) * | 2016-12-21 | 2019-09-27 | 拜耳农作物科学股份公司 | Catalytic Hydrogenation of Nitriles |
| CN110698392A (en) * | 2019-09-09 | 2020-01-17 | 中国农业大学 | A kind of bisamide compound and its preparation method and application |
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