CN100497310C - Preparation method of 2-chlorin-5-trifluoro picoline - Google Patents
Preparation method of 2-chlorin-5-trifluoro picoline Download PDFInfo
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- CN100497310C CN100497310C CNB2006100445975A CN200610044597A CN100497310C CN 100497310 C CN100497310 C CN 100497310C CN B2006100445975 A CNB2006100445975 A CN B2006100445975A CN 200610044597 A CN200610044597 A CN 200610044597A CN 100497310 C CN100497310 C CN 100497310C
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- flumethiazine
- amino
- organic solvent
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- chloro
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Abstract
The process of preparing 2-amino-5-trifluoromethylpyridine as one new type of medicine intermediate includes the following steps: aminolysis of 2-chloro-5-trifluoromethyl pyridine in refluxing organic solvent at 120-135 deg.c and 2.0-3.5 MPa, eliminating organic solvent, water washing, letting stand, separating and rectifying. The process of the present invention is simple, easy to operate, favorable to industrial production and environment friendly, and the obtained product has purity not lower than 98 %, yield of 85 % and low production cost.
Description
Technical field
The present invention relates to the preparation method of medicine intermediate 2-amino-5-5-flumethiazine.
Background technology
2-amino-5-5-flumethiazine is the key intermediate of synthetic medicine (medicines of treatment cardiovascular and cerebrovascular disease), good effect, and instant effect is free from side effects, and is the indispensable Medicine of cardiovascular and cerebrovascular patient.Be in great demand very much in the world market.
2-amino-5-5-flumethiazine is not only as novel medicine, pesticide intermediate, also of many uses in organic synthesis and dye field, in recent years, it is found that and introduce the lipotropy that trifluoromethyl can improve compound on the heterocycle, thereby raising drug effect, the electron attractivity of raising during to the perviousness of organism film and tissue and organism reaction strengthens the physiologically active of compound.2-amino-5-5-flumethiazine has been widely used in fields such as medicine, agricultural chemicals, dyestuff at present.
Prior art is main raw material by the 2-amino-5-5-flumethiazine of Japanese a company exploitation with the 3-5-flumethiazine, carries out the restore nitrification reaction, generates this product and has only 60%, spent acid is many, and waste water is many, and environmental issue is difficult to solve, product purity is low, has only 96% content.
Summary of the invention
Technical problem to be solved by this invention provides the preparation method of a kind of 2-ammonia-5-5-flumethiazine, and technology is simple, easy to operate, does not produce waste water, spent acid, product purity height, yield height.
The preparation method of 2-ammonia of the present invention-5-5-flumethiazine is characterized in that comprising the steps:
(1) in the presence of organic solvent, feed liquefied ammonia in the 2-chloro-5-5-flumethiazine under 120-135 ℃, pressure 2.0-3.5Mpa, ammonolysis reaction 8-16 hour, the mol ratio of 2-chloro-5-5-flumethiazine and liquefied ammonia was 1:12-18.
(2) reaction solution removes organic solvent by distillation, washes static separation, obtains the amino substance crude product.
(3) the amino substance crude product carries out rectifying.
The described organic solvent of step (1) can adopt methyl alcohol, ethanol, Virahol, ether etc., and the quality of 2-chloro-5-5-flumethiazine and organic solvent turns to material 1:1.3-2.
The reaction solution that obtains behind the ammonolysis reaction can remove organic solvent by the distillation normal pressure.
Step (3) is for the amino substance of purifying (2-ammonia-5-5-flumethiazine) crude product, adopts common decompression distillation mode.Smart gold-plating condition is: 90-140 ℃ of temperature, and pressure-0.086--0.96Mpa.
Advantage of the present invention:
Technology is simple, and is easy to operate, is beneficial to suitability for industrialized production, no environmental protection problem.The product purity height that obtains, purity 〉=99%, yield are about 88%, and production cost is low.
The physico-chemical property of 2-ammonia-5-5-flumethiazine is:
Molecular formula: C
6H
5F
3N
2
Molecular weight: 162
Boiling point: 91 ℃/16mmHg
Fusing point: 42.5 ℃
Embodiment:
Describe the present invention in detail below in conjunction with embodiment, but do not limit the present invention.
Embodiment 1:
(1), ammonia is separated
Suction raw material 2-chloro-5-5-flumethiazine 1300g, methyl alcohol 1700g, liquefied ammonia 1462g in the autoclave of 5L open to stir and heat up, 120-135 ℃ of control temperature in the kettle, pressure 2.0-3.5Mpa., keep reaction 16 hours, be cooled to 60 ℃, slowly row pressure is to 0.0Mpa.Bubbling air catch up with gas more than 2 hours to NH
3Till not having.With reaction solution suction methyl alcohol still kettle, normal pressure steam to remove methyl alcohol, when methanol content in the amino substance less than 10% the time, stop distillation, be cooled to 50 ℃, a large amount of water of suction in still, wash, static, separate, the amino substance crude product, put into the 5000ml beaker.
(2), smart gold-plating
The amino substance crude product is dropped in the decompression distillation still, opens vacuum, when vacuum tightness reach-during 0.086Mpa, smart gold-plating still begins heat temperature raising to 140 ℃, when cat head has backflow, and the control heating, kept total reflux 30 minutes, then by extraction: backflow=1:8, decompression distillation, the extraction cut enters the front-end volatiles receiving tank, took a sample once in 10 minutes, the chromatogram tracking analysis is when main distillate fraction content reaches more than 99%, extraction cut incision finished product receiving tank, at this moment control of reflux ratio is at 1:4, when the rising of still temperature, when tower top temperature descends to some extent, the accent reflux ratio is 1:8, took a sample once in 5 minutes, the chromatogram tracking analysis is when main distillate fraction content is lower than 98%, stop extraction, cooling, emptying is behind system's normal pressure, stop vacuum pump, the metering front-end volatiles, finished product, after cut gets the finished product packing warehouse-in.Product yield 85%.
Embodiment 2:
With the technological operation step of embodiment 1, different condition is:
The solvent that the ammonolysis reaction stage adopts is ethanol 1800g, 120-135 ℃ of temperature of reaction, and pressure 2.0Mpa, in 16 hours reaction times, product purity is more than 98%, yield 85%.
Embodiment 3
With the technological operation step of embodiment 1, different condition is:
The solvent that the ammonolysis reaction stage adopts is Virahol 2000g, 120-135 ℃ of temperature of reaction, and pressure 3.5Mpa, in 10 hours reaction times, product purity is more than 98%, yield 84%.
Embodiment 4
With the technological operation step of embodiment 1, different condition is:
The solvent that the ammonolysis reaction stage adopts is methyl alcohol 2000g, 120-135 ℃ of temperature of reaction, and pressure 3Mpa, in 20 hours reaction times, product purity is more than 98%, yield 83%.
Claims (3)
1, the preparation method of a kind of 2-amino-5-5-flumethiazine is characterized in that comprising the steps:
(1) in the presence of organic solvent, feed liquefied ammonia in the 2-chloro-5-5-flumethiazine under 120-135 ℃, pressure 2.0-3.5Mpa, ammonolysis reaction 8-16 hour, the mol ratio of 2-chloro-5-5-flumethiazine and liquefied ammonia was 1:12-18,
(2) reaction solution removes organic solvent by distillation, washes static separation, obtains the amino substance crude product.
(3) the amino substance crude product carries out rectifying.
2, the preparation method of 2-amino according to claim 1-5-5-flumethiazine, it is characterized in that the described organic solvent of step (1) is: methyl alcohol, ethanol, Virahol or ether, the mass ratio of 2-chloro-5-5-flumethiazine and organic solvent is 1:1.3-2.
3, the preparation method of 2-amino according to claim 1-5-5-flumethiazine is characterized in that the described rectifying condition of step (3) is: 90-140 ℃ of temperature, and pressure-0.086--0.96Mpa.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006100445975A CN100497310C (en) | 2006-05-29 | 2006-05-29 | Preparation method of 2-chlorin-5-trifluoro picoline |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006100445975A CN100497310C (en) | 2006-05-29 | 2006-05-29 | Preparation method of 2-chlorin-5-trifluoro picoline |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101081832A CN101081832A (en) | 2007-12-05 |
| CN100497310C true CN100497310C (en) | 2009-06-10 |
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| CNB2006100445975A Expired - Fee Related CN100497310C (en) | 2006-05-29 | 2006-05-29 | Preparation method of 2-chlorin-5-trifluoro picoline |
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Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN110143916B (en) * | 2019-05-12 | 2020-08-21 | 大连九信精细化工有限公司 | Synthesis process of fluazinam |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3681369A (en) * | 1970-04-20 | 1972-08-01 | George O P Doherty | 2,6-BIS (TRIFLUOROMETHYL)-1H-IMIDAZO{8 4,5-b{9 PYRIDINE |
| GB1417349A (en) * | 1972-10-10 | 1975-12-10 | Dow Chemical Co | Substituted aminohalopyridines |
| EP0031218A1 (en) * | 1979-12-24 | 1981-07-01 | Ishihara Sangyo Kaisha Ltd. | A 2-amino-trifluoromethyl-halogenopyridine compound and a process for producing the same |
| US4331670A (en) * | 1979-12-25 | 1982-05-25 | Ishihara Sangyo Kaisha, Ltd. | Pyridylanilines |
| US4349681A (en) * | 1979-12-24 | 1982-09-14 | Ishihara Sangyo Kaisha, Ltd. | 2-Amino-3-chloro-5-trifluoromethylpyridine |
-
2006
- 2006-05-29 CN CNB2006100445975A patent/CN100497310C/en not_active Expired - Fee Related
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3681369A (en) * | 1970-04-20 | 1972-08-01 | George O P Doherty | 2,6-BIS (TRIFLUOROMETHYL)-1H-IMIDAZO{8 4,5-b{9 PYRIDINE |
| GB1417349A (en) * | 1972-10-10 | 1975-12-10 | Dow Chemical Co | Substituted aminohalopyridines |
| EP0031218A1 (en) * | 1979-12-24 | 1981-07-01 | Ishihara Sangyo Kaisha Ltd. | A 2-amino-trifluoromethyl-halogenopyridine compound and a process for producing the same |
| US4349681A (en) * | 1979-12-24 | 1982-09-14 | Ishihara Sangyo Kaisha, Ltd. | 2-Amino-3-chloro-5-trifluoromethylpyridine |
| US4331670A (en) * | 1979-12-25 | 1982-05-25 | Ishihara Sangyo Kaisha, Ltd. | Pyridylanilines |
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| CN101081832A (en) | 2007-12-05 |
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Granted publication date: 20090610 Termination date: 20120529 |