CN101709051A - Preparation method of 2-amino-3-chloro-5-(trifluoromethyl) pyridine - Google Patents
Preparation method of 2-amino-3-chloro-5-(trifluoromethyl) pyridine Download PDFInfo
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- CN101709051A CN101709051A CN200910234324A CN200910234324A CN101709051A CN 101709051 A CN101709051 A CN 101709051A CN 200910234324 A CN200910234324 A CN 200910234324A CN 200910234324 A CN200910234324 A CN 200910234324A CN 101709051 A CN101709051 A CN 101709051A
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- flumethiazine
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Abstract
The invention discloses a preparation method of 2-amino-3-chloro-5-(trifluoromethyl) pyridine, which comprises the steps of: adding sodium amide powder into a solvent which contains or does not contain a phase transfer catalyst, and then, adding 2-halogen-3-chloro-5-(trifluoromethyl) pyridine for reaction at 10-220 DEG C to prepare the 2-amino-3-chloro-5-(trifluoromethyl) pyridine. In the invention, the sodium amide is used as a reagent to react with the 2-halogen-3-chloro-5-(trifluoromethyl) pyridine under the catalytic condition of the phase transfer catalyst at normal pressure to prepare the 2-amino-3-chloro-5-(trifluoromethyl) pyridine. The invention has moderate reaction and simple post treatment.
Description
Technical field
The invention belongs to the fine chemistry field, be specifically related to the synthetic method of a kind of 2-amino-3-chloro-5-5-flumethiazine.
Background technology
Fluazinam is the exploitation of the former industry of Japanese stone company, is protectiveness phenyl amines sterilant, and fungicidal spectrum is wide, and the lasting period is long, and 2-amino-3-chloro-5-5-flumethiazine is the important intermediate of fluazinam.EP0031218 has announced its synthetic method, makes reagent with ammoniacal liquor, under 125 ℃, 2 normal atmosphere, and reaction 24h, yield 25%.CN101081833A has improved the reaction of EP0031218, makes reagent with liquefied ammonia, reacts 8h, yield 90% under 130 ℃ of high temperature, high pressure 3.5MPa condition.This two kinds of methods or yield is low, or use high temperature high voltage resistant equipment, the working condition harshness.
Summary of the invention
The objective of the invention is to overcome the problems referred to above, the method for preparing 2-amino-3-chloro-5-5-flumethiazine that a kind of cost is low, simple to operate, be suitable for suitability for industrialized production is provided.
Purpose of the present invention can reach by following measure:
The preparation method of a kind of 2-amino-3-chloro-5-5-flumethiazine, the sodium amide powder joined contain or do not contain in the solvent of phase-transfer catalyst, add 2-halogen-3-chloro-5-5-flumethiazine then and under 10～220 ℃, react, preparation 2-amino-3-chloro-5-5-flumethiazine; Reaction equation is as follows:
Wherein, X is a halogen, is preferably F or Cl.
The mol ratio of sodium amide and 2-halogen in the above-mentioned reaction-3-chloro-5-5-flumethiazine is 1～3: 1, the mol ratio of phase-transfer catalyst and 2-halogen-3-chloro-5-5-flumethiazine is 0～1.5: 1, and solvent load is 1～3 times of 2-halogen-3-chloro-5-5-flumethiazine quality.
Reaction of the present invention can not reacted under phase-transfer catalyst, but because the insoluble of sodium amide powder, add phase-transfer catalyst in the reaction process and can play the effect that improves reaction efficiency, catalyzed reaction process, therefore preferably in reaction, add phase-transfer catalyst.Phase-transfer catalyst among the present invention is selected quaternary ammonium salt, crown ether, aromatic amine or hydramine for use, concrete as tetraethylammonium bromide, etamon chloride, bromination tetrapropyl ammonium, hydrogen sulfate TBuA, phenyl trimethyl ammonium chloride, methyltributylammonichloride chloride, crown ether, aniline, N, accelerine, monomethylaniline, thanomin, Propanolamine, butanolamine or diethanolamine etc., be preferably methyltributylammonichloride chloride, N, accelerine or thanomin.The mol ratio of phase-transfer catalyst and 2-halogen-3-chloro-5-5-flumethiazine is preferably 0.1～0.8: 1.
Solvent of the present invention can be selected for use and be alkane, aromatic hydrocarbons or aprotic polar solvent, concrete as C8～C12 alkane, perhydronaphthalene, naphthane, biphenyl ether, chlorobenzene, dimethylbenzene, DMF, DMAC or DMSO, be preferably C8～C12 alkane, naphthane, dimethylbenzene or DMF.
Temperature of reaction in the reaction is preferably 120～180 ℃, and the reaction times is generally 0.5～24h, is reflected under rare gas element such as the protection of nitrogen gas to carry out.Reaction filters out the generation sodium halide after finishing, and precipitation promptly gets 2-amino-3-chloro-5-5-flumethiazine.
Beneficial effect of the present invention:
The present invention makes reagent with sodium amide, under the phase-transfer catalyst catalytic condition with 2-halogen-3-chloro-5-5-flumethiazine normal pressure under reaction make 2-amino-3-chlorine 5-5-flumethiazine.The present invention, reaction temperature and, aftertreatment is simple.
Embodiment
The preparation of embodiment 1,2-amino-3-chloro-5-5-flumethiazine
4.7g 0.12mol NaNH
2Pulverizing joins among the 60gDMF, and nitrogen protection is heated with stirring to backflow; in reaction solution, drip 21.6g 0.1mol 2,3-two chloro-5-5-flumethiazines, nitrogen protection again; stirring heating refluxes, and middle control raw material reaction is complete, finishes reaction; filter filtrate decompression precipitation, washing; dry; promptly get 2-amino-3-chloro-5-5-flumethiazine 16.8g, purity 98%, yield 83.7%.
The preparation of embodiment 2,2-amino-3-chloro-5-5-flumethiazine
4.7g 0.12mol NaNH
2Pulverizing joins in the 60g dimethylbenzene together with 1.5g 0.025mol thanomin, and nitrogen protection is heated with stirring to backflow; in reaction solution, drip 20.0g 0.1mol 2-fluoro-3-chloro-5-5-flumethiazine again, nitrogen protection, stirring heating refluxes; middle control raw material reaction is complete, finishes reaction, filters; the filtrate decompression precipitation; washing, drying promptly gets 2-amino-3-chloro-5-5-flumethiazine 19.1g; purity 96%, yield 93.4%.
The preparation of embodiment 3,2-amino-3-chloro-5-5-flumethiazine
5.5g 0.14mol NaNH
2Pulverizing joins in the 60g decane together with 6.7g 0.03mol methyltributylammonichloride chloride, and nitrogen protection is heated with stirring to backflow; in reaction solution, drip 20.0g 0.1mol 2-fluoro-3-chloro-5-5-flumethiazine again, nitrogen protection, stirring heating refluxes; middle control raw material reaction is complete, finishes reaction, filters; the filtrate decompression precipitation; washing, drying promptly gets 2-amino-3-chloro-5-5-flumethiazine 19.0g; purity 95%, yield 92.1%.
The preparation of embodiment 4,2-amino-3-chloro-5-5-flumethiazine
7.9g 0.2mol NaNH
2Pulverizing is together with 2.5g 0.02mol N, and accelerine joins in the 55g naphthane, nitrogen protection; be heated with stirring to backflow, in reaction solution, drip 20.0g 0.1mol 2-fluoro-3-chloro-5-5-flumethiazine again, nitrogen protection; stirring heating refluxes, and middle control raw material reaction is complete, finishes reaction; filter filtrate decompression precipitation, washing; dry; promptly get 2-amino-3-chloro-5-5-flumethiazine 19.2g, purity 97%, yield 94.7%.
Claims (8)
1. the preparation method of 2-amino-3-chloro-5-5-flumethiazine, it is characterized in that the sodium amide powder joined contains or does not contain in the solvent of phase-transfer catalyst, add 2-halogen-3-chloro-5-5-flumethiazine then and under 10～220 ℃, react, preparation 2-amino-3-chloro-5-5-flumethiazine; Reaction equation is as follows:
Wherein, X is a halogen.
2. method according to claim 1, the mol ratio that it is characterized in that sodium amide and 2-halogen-3-chloro-5-5-flumethiazine is 1～3: 1, the mol ratio of phase-transfer catalyst and 2-halogen-3-chloro-5-5-flumethiazine is 0～1.5: 1, and solvent load is 1～3 times of 2-halogen-3-chloro-5-5-flumethiazine quality.
3. method according to claim 1 and 2 is characterized in that described phase-transfer catalyst is quaternary ammonium salt, crown ether, aromatic amine or hydramine.
4. method according to claim 3, it is characterized in that described phase-transfer catalyst is tetraethylammonium bromide, etamon chloride, bromination tetrapropyl ammonium, hydrogen sulfate TBuA, phenyl trimethyl ammonium chloride, methyltributylammonichloride chloride, crown ether, aniline, N, accelerine, monomethylaniline, thanomin, Propanolamine, butanolamine or diethanolamine.
5. method according to claim 1 and 2 is characterized in that described solvent is alkane, aromatic hydrocarbons or aprotic polar solvent.
6. method according to claim 5 is characterized in that described solvent is C8～C12 alkane, perhydronaphthalene, naphthane, biphenyl ether, chlorobenzene, dimethylbenzene, DMF, DMAC or DMSO.
7. method according to claim 1 is characterized in that temperature of reaction is 120～180 ℃.
8. method according to claim 1 is characterized in that described X is F or Cl.
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106117131A (en) * | 2016-06-29 | 2016-11-16 | 天津市均凯化工科技有限公司 | A kind of method preparing 2 amino 3 chlorine 5 trifluoromethyl pyridines |
| CN110508161A (en) * | 2018-05-22 | 2019-11-29 | 江苏斯凯氟复合材料有限公司 | A kind of preparation method of hydrophilic polyfluortetraethylemicroporous microporous membrane |
| CN111205221A (en) * | 2020-01-20 | 2020-05-29 | 武汉工程大学 | Pyridine quaternary ammonium salt compound and preparation method and application thereof |
| CN113527194A (en) * | 2021-03-15 | 2021-10-22 | 武威广达科技有限公司 | Preparation method of 2-amino-3-chloro-5-trifluoromethylpyridine |
| CN115385852A (en) * | 2022-09-05 | 2022-11-25 | 湖南阿斯迪康药业有限公司 | Efficient synthesis method of 2-amino-4-trifluoromethylpyridine |
-
2009
- 2009-11-24 CN CN200910234324A patent/CN101709051A/en active Pending
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106117131A (en) * | 2016-06-29 | 2016-11-16 | 天津市均凯化工科技有限公司 | A kind of method preparing 2 amino 3 chlorine 5 trifluoromethyl pyridines |
| CN106117131B (en) * | 2016-06-29 | 2018-09-04 | 天津市均凯化工科技有限公司 | A method of preparing 2- amido-3-5-trifluoro picolines |
| CN110508161A (en) * | 2018-05-22 | 2019-11-29 | 江苏斯凯氟复合材料有限公司 | A kind of preparation method of hydrophilic polyfluortetraethylemicroporous microporous membrane |
| CN111205221A (en) * | 2020-01-20 | 2020-05-29 | 武汉工程大学 | Pyridine quaternary ammonium salt compound and preparation method and application thereof |
| CN111205221B (en) * | 2020-01-20 | 2021-11-12 | 武汉工程大学 | Pyridine quaternary ammonium salt compound and preparation method and application thereof |
| CN113527194A (en) * | 2021-03-15 | 2021-10-22 | 武威广达科技有限公司 | Preparation method of 2-amino-3-chloro-5-trifluoromethylpyridine |
| CN113527194B (en) * | 2021-03-15 | 2023-10-03 | 武威广达科技有限公司 | Preparation method of 2-amino-3-chloro-5-trifluoromethyl pyridine |
| CN115385852A (en) * | 2022-09-05 | 2022-11-25 | 湖南阿斯迪康药业有限公司 | Efficient synthesis method of 2-amino-4-trifluoromethylpyridine |
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