CN109748864A - A kind of preparation method of 2- amino -5- bromopyridine - Google Patents
A kind of preparation method of 2- amino -5- bromopyridine Download PDFInfo
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- CN109748864A CN109748864A CN201711082543.2A CN201711082543A CN109748864A CN 109748864 A CN109748864 A CN 109748864A CN 201711082543 A CN201711082543 A CN 201711082543A CN 109748864 A CN109748864 A CN 109748864A
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- Prior art keywords
- aminopyridine
- amino
- preparation
- phenyltrimethyl
- bromopyridine
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Abstract
The invention belongs to technical field of organic synthesis, more particularly to a kind of preparation method of 2- amino -5- bromopyridine, reaction step is as follows: using 2-aminopyridine as raw material, using methylene chloride or chloroform as solvent, with phenyltrimethyl-ammonium tribromide 20-50 DEG C at a temperature of react 1-3 hours, the molar ratio of the 2-aminopyridine and phenyltrimethyl-ammonium tribromide is 0.7-1.4.It is using the beneficial effect of technical solution of the present invention: (1) avoids the generation of a large amount of 3 by-products in traditional preparation methods, reduces the load that the waste of raw material is separated with the later period；(2) raw material 2-aminopyridine is easy to get, at low cost, this route reaction condition is mild, high income, and whole process is generated without 3 by-products, has industrial prospect.
Description
Technical field
The invention belongs to technical field of organic synthesis, and in particular to a kind of preparation method of 2- amino -5- pyridine.
Background technique
Pyridine and its derivatives are widely distributed in nature.All contain in the structure of many plant components such as alkaloid
Pyridine cycle compound, they are the bases for producing many important compounds, are medicine, pesticide, dyestuff, surfactant, rubber
Indispensable raw material in the production such as auxiliary agent, feed addictive, food additives, adhesive.- 5 bromopyridine of 2- amino is a kind of
Important medicine intermediate can be used for synthesizing PI3Kinase inhibitor, haloperidid derivative and thiazolyl thiourea compound, ammonia
Pyridine derivative selective dopamine D3Receptor stimulating agent synthesizes imidazo [1,2-a] pyridine compounds VEGFR-2 inhibitor
Equal drugs, are also used to treat autoimmune disease, diseases associated with inflammation, cardiovascular disease, nerve and move back shape disease, allergy etc.
A variety of diseases.
Currently, common method, using bromine as bromating agent, is usually dissolved in bromine using 2-aminopyridine as raw material
Water, chloroform use in carbon tetrachloride equal solvent, but bromine has very big volatility and toxic, and operation, storage, transport are all
Inconvenience, and single bromination product is hardly resulted in for active aromatic compound, developing new bromine always for a long time
Agent replaces bromine.Phosphorus tribromide, NBS are solid brominated doses more early used, but also have the shortcomings that it is more, as NBS compared with
Valuableness, preparation are also inconvenient.Phosphorus tribromide has strong sharp aroma, is corrosive, and is dissolved in soluble after water.
Summary of the invention
The purpose of the present invention is overcoming in the prior art, bromating agent is expensive, is corrosive, the technologies such as more than 3 by-products
Deficiency provides a kind of preparation method of new 2- amino -5- bromopyridine.
In order to solve the above technical problems, The technical solution adopted by the invention is as follows:
A kind of preparation method of 2- amino -5- bromopyridine, reaction step are as follows:
Using 2-aminopyridine as raw material, using methylene chloride or chloroform as solvent, with phenyltrimethyl-ammonium tribromide
20-50 DEG C at a temperature of react 1-3 hour, the molar ratio of the 2-aminopyridine and phenyltrimethyl-ammonium tribromide is 0.7-
1.4。
Further, the dosage of the solvent is every gram of 2-aminopyridine 20-35ml.
Further, the dosage of the solvent is every gram of 2-aminopyridine 30ml.
Further, the temperature is preferably 30 DEG C.
Further, the 2-aminopyridine and phenyltrimethyl-ammonium tribromide molar ratio are 0.9-1.3.
It is using the beneficial effect of technical solution of the present invention:
(1) generation for avoiding a large amount of 3 by-products in traditional preparation methods reduces the waste and later period separation of raw material
Load；
(2) raw material 2-aminopyridine is easy to get, at low cost, this route reaction condition is mild, high income, and whole process is without 3
By-product generates, and has industrial prospect.
Specific embodiment
Below by embodiment, the present invention is further described, is not intended to limit scope of the presently claimed invention.
Embodiment 1
By 9.4g 2-aminopyridine (0.1mol), 37.6g phenyltrimethyl-ammonium tribromide (0.1mol) and 300ml chloroform
It is added in 1L there-necked flask, mechanical stirring, thermometer and condensing reflux pipe is inserted in there-necked flask, start stirring and be allowed to mixing
It is even, it stirs 2 hours, is washed with the saturated sodium chloride solution that 40ml is prepared in advance, water phase is on upper layer, and organic phase is under at 30 DEG C
Layer, is layered with separatory funnel, and organic phase uses 20ml water washing 2-3 times again, and layering is dried, filtered, organic phase with anhydrous sodium sulfate
Rotary evaporation removes solvent chloroform, obtains grease, and ice water is cooling, adds elutriation to go out solid, obtains crude product, is recrystallized with benzene, filters,
Drying, obtains yellow solid 10g, yield 81%.
Embodiment 2
By 9.4g 2-aminopyridine (0.1mol), 37.6g phenyltrimethyl-ammonium tribromide (0.1mol) and 300ml chloroform
It is added in 1L there-necked flask, mechanical stirring, thermometer and condensing reflux pipe is inserted in there-necked flask, start stirring and be allowed to mixing
It is even, it stirs 2 hours, is washed with the saturated sodium chloride solution that 40ml is prepared in advance, water phase is on upper layer, and organic phase is under at 25 DEG C
Layer, is layered with separatory funnel, and organic phase uses 20ml water washing 2-3 times again, and layering is dried, filtered, organic phase with anhydrous sodium sulfate
Rotary evaporation removes solvent chloroform, obtains grease, and ice water is cooling, adds elutriation to go out solid, obtains crude product, is recrystallized with benzene, filters,
Drying, obtains yellow solid 8.43g, yield 78%.
The present embodiment is preferred forms.
Embodiment 3
By 9.4g 2-aminopyridine (0.1mol), 37.6g (phenyltrimethyl-ammonium tribromide 0.1mol) and 300ml dichloro
Methane is added in 1L there-necked flask, and mechanical stirring, thermometer and condensing reflux pipe are inserted in there-necked flask, stirring is started and is allowed to mix
Uniformly, it stirs 2 hours, is washed with the saturated sodium chloride solution that 40ml is prepared in advance, water phase is on upper layer, and organic phase is under at 30 DEG C
Layer, is layered with separatory funnel, and organic phase uses 20ml water washing 2-3 times again, and layering is dried, filtered, organic phase with anhydrous sodium sulfate
Rotary evaporation removes solvent chloroform, obtains grease, and ice water is cooling, adds elutriation to go out solid, obtains crude product, is recrystallized with benzene, filters,
Drying, obtains yellow solid 8.1g, yield 75%.
Claims (5)
1. a kind of preparation method of 2- amino -5- bromopyridine, it is characterised in that reaction step is as follows: being original with 2-aminopyridine
Material, using methylene chloride or chloroform as solvent, with phenyltrimethyl-ammonium tribromide 20-50 DEG C at a temperature of react 1-3
Hour, the molar ratio of the 2-aminopyridine and phenyltrimethyl-ammonium tribromide is 0.7-1.4.
2. a kind of preparation method of 2- amino -5- bromopyridine according to claim 1, it is characterised in that: the solvent
Dosage is every gram of 2-aminopyridine 20-35ml.
3. a kind of preparation method of 2- amino -5- bromopyridine according to claim 4, it is characterised in that: the solvent
Dosage is every gram of 2-aminopyridine 30ml.
4. a kind of preparation method of 2- amino -5- bromopyridine according to claim 1, it is characterised in that: the temperature is excellent
It is selected as 30 DEG C.
5. a kind of preparation method of 2- amino -5- bromopyridine according to claim 1, it is characterised in that: the 2- amino
Pyridine and phenyltrimethyl-ammonium tribromide molar ratio are 0.9-1.3.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711082543.2A CN109748864A (en) | 2017-11-07 | 2017-11-07 | A kind of preparation method of 2- amino -5- bromopyridine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711082543.2A CN109748864A (en) | 2017-11-07 | 2017-11-07 | A kind of preparation method of 2- amino -5- bromopyridine |
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| Publication Number | Publication Date |
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| CN109748864A true CN109748864A (en) | 2019-05-14 |
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| CN201711082543.2A Withdrawn CN109748864A (en) | 2017-11-07 | 2017-11-07 | A kind of preparation method of 2- amino -5- bromopyridine |
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2017
- 2017-11-07 CN CN201711082543.2A patent/CN109748864A/en not_active Withdrawn
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Application publication date: 20190514 |