CN111057000A - Preparation method of 2-amino-5-bromopyridine - Google Patents
Preparation method of 2-amino-5-bromopyridine Download PDFInfo
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- CN111057000A CN111057000A CN201911175480.4A CN201911175480A CN111057000A CN 111057000 A CN111057000 A CN 111057000A CN 201911175480 A CN201911175480 A CN 201911175480A CN 111057000 A CN111057000 A CN 111057000A
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- aminopyridine
- amino
- bromopyridine
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- phenyltrimethylammonium tribromide
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D213/72—Nitrogen atoms
- C07D213/73—Unsubstituted amino or imino radicals
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- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention belongs to the technical field of organic synthesis, and particularly relates to a preparation method of 2-amino-5-bromopyridine, which comprises the following reaction steps: the method comprises the following steps of reacting 2-aminopyridine serving as a raw material with phenyltrimethylammonium tribromide at a temperature of between 20 and 50 ℃ for 1 to 3 hours by using dichloromethane or chloroform as a solvent, wherein the molar ratio of the 2-aminopyridine to the phenyltrimethylammonium tribromide is between 0.7 and 1.4. The technical scheme adopted by the invention has the beneficial effects that: (1) the generation of a large amount of 3-bit byproducts in the traditional preparation method is avoided, and the waste of raw materials and the load of later separation are reduced; (2) the raw material 2-aminopyridine is easy to obtain, the cost is low, the reaction condition of the route is mild, the yield is high, no 3-bit by-product is generated in the whole process, and the method has an industrial prospect.
Description
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to a preparation method of 2-amino-5-pyridine.
Background
Pyridine and its derivatives are widely distributed in nature. Many plant components such as alkaloids contain pyridine ring compounds in their structures, which are the basis for the production of many important compounds, which are essential raw materials for the production of pharmaceuticals, pesticides, dyes, surfactants, rubber aids, feed additives, food additives, adhesives, etc. 2-amino-5-bromopyridine is an important medical intermediate and can be used for synthesizing PI3Kinase inhibitors, halopyridine derivatives and thiazolyl thiourea compounds, aminopyridine derivative selective dopamine D3Receptor agonists, synthetic imidazo [1, 2-a]Pyridine compounds VEGFR-2 inhibitors and the like are also used for treating various diseases such as autoimmune diseases, inflammatory diseases, cardiovascular diseases, neurodegenerative diseases, anaphylaxis and the like.
At present, the commonly used method is to use 2-aminopyridine as a raw material, liquid bromine is used as a brominating agent, and the bromine is usually dissolved in solvents such as water, chloroform, carbon tetrachloride and the like for use, but the liquid bromine has great volatility and toxicity, is inconvenient to operate, store and transport, and is difficult to obtain a monobromo product for active aromatic compounds, and a new brominating agent is developed for a long time to replace the liquid bromine. Phosphorus tribromide and NBS are earlier used solid brominating agents, but have more disadvantages, such as more expensive NBS and inconvenient preparation. Phosphorus tribromide has strong pungent smell and is corrosive and easy to dissolve after being dissolved in water.
Disclosure of Invention
The invention aims to overcome the technical defects of high price, corrosivity, more 3-bit byproducts and the like of a brominating agent in the prior art and provide a novel preparation method of 2-amino-5-bromopyridine.
In order to solve the technical problems, the technical scheme adopted by the invention is as follows:
a preparation method of 2-amino-5-bromopyridine comprises the following reaction steps:
the method comprises the following steps of reacting 2-aminopyridine serving as a raw material with phenyltrimethylammonium tribromide at a temperature of between 20 and 50 ℃ for 1 to 3 hours by using dichloromethane or chloroform as a solvent, wherein the molar ratio of the 2-aminopyridine to the phenyltrimethylammonium tribromide is between 0.7 and 1.4.
Furthermore, the dosage of the solvent is 20-35ml for each gram of 2-aminopyridine.
Further, the solvent is used in an amount of 30ml per gram of 2-aminopyridine.
Further, the temperature is preferably 30 ℃.
Further, the molar ratio of the 2-aminopyridine to the phenyltrimethylammonium tribromide is 0.9-1.3.
The technical scheme adopted by the invention has the beneficial effects that:
(1) the generation of a large amount of 3-bit byproducts in the traditional preparation method is avoided, and the waste of raw materials and the load of later separation are reduced;
(2) the raw material 2-aminopyridine is easy to obtain, the cost is low, the reaction condition of the route is mild, the yield is high, no 3-bit by-product is generated in the whole process, and the method has an industrial prospect.
Detailed Description
The invention is further illustrated by the following examples, which are not intended to limit the scope of the claims.
Example 1
Adding 9.4g of 2-aminopyridine (0.1mol), 37.6g of phenyltrimethylammonium tribromide (0.1mol) and 300ml of chloroform into a 1L three-necked flask, inserting mechanical stirring, a thermometer and a condensation reflux pipe into the three-necked flask, starting stirring to mix the materials uniformly, stirring at 30 ℃ for 2 hours, washing with 40ml of prepared saturated sodium chloride solution, separating an aqueous phase from an upper layer and an organic phase from a lower layer by using a separating funnel, washing the organic phase with 20ml of water for 2-3 times, separating the layers, drying with anhydrous sodium sulfate, filtering, performing rotary evaporation on the organic phase to remove a solvent chloroform to obtain an oily substance, cooling with ice water, adding water to precipitate a solid to obtain a crude product, recrystallizing with benzene, filtering, and drying to obtain 10g of a yellow solid, wherein the yield is 81%.
Example 2
Adding 9.4g of 2-aminopyridine (0.1mol), 37.6g of phenyltrimethylammonium tribromide (0.1mol) and 300ml of chloroform into a 1L three-necked flask, inserting mechanical stirring, a thermometer and a condensation reflux pipe into the three-necked flask, starting stirring to mix the materials uniformly, stirring at 25 ℃ for 2 hours, washing with 40ml of prepared saturated sodium chloride solution, separating an aqueous phase from an upper layer and an organic phase from a lower layer by using a separating funnel, washing the organic phase with 20ml of water for 2-3 times, separating the layers, drying with anhydrous sodium sulfate, filtering, performing rotary evaporation on the organic phase to remove a solvent chloroform to obtain an oily substance, cooling with ice water, adding water to precipitate a solid to obtain a crude product, recrystallizing with benzene, filtering, and drying to obtain 8.43g of a yellow solid, wherein the yield is 78%.
This embodiment is the best mode.
Example 3
Adding 9.4g of 2-aminopyridine (0.1mol), 37.6g (0.1mol of phenyltrimethylammonium tribromide) and 300ml of dichloromethane into a 1L three-necked flask, inserting mechanical stirring, a thermometer and a condensation reflux pipe into the three-necked flask, starting stirring to mix the two materials uniformly, stirring at 30 ℃ for 2 hours, washing with 40ml of prepared saturated sodium chloride solution, separating an aqueous phase from an upper layer and an organic phase from a lower layer by using a separating funnel, washing the organic phase with 20ml of water for 2-3 times, separating the layers, drying with anhydrous sodium sulfate, filtering, performing rotary evaporation on the organic phase to remove a solvent chloroform to obtain an oily substance, cooling with ice water, adding water to precipitate a solid to obtain a crude product, recrystallizing with benzene, filtering, and drying to obtain 8.1g of a yellow solid, wherein the yield is 75%.
Claims (5)
1. A preparation method of 2-amino-5-bromopyridine is characterized by comprising the following reaction steps: the method comprises the following steps of reacting 2-aminopyridine serving as a raw material with phenyltrimethylammonium tribromide at a temperature of between 20 and 50 ℃ for 1 to 3 hours by using dichloromethane or chloroform as a solvent, wherein the molar ratio of the 2-aminopyridine to the phenyltrimethylammonium tribromide is between 0.7 and 1.4.
2. The process for preparing 2-amino-5-bromopyridine according to claim 1, wherein: the dosage of the solvent is 20-35ml for each gram of 2-aminopyridine.
3. The process according to claim 4, wherein the reaction is carried out in the presence of a 2-amino-5-bromopyridine: the amount of the solvent is 30ml per gram of 2-aminopyridine.
4. The process for preparing 2-amino-5-bromopyridine according to claim 1, wherein: the temperature is preferably 30 ℃.
5. The process for preparing 2-amino-5-bromopyridine according to claim 1, wherein: the molar ratio of the 2-aminopyridine to the phenyltrimethylammonium tribromide is 0.9-1.3.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911175480.4A CN111057000A (en) | 2019-11-26 | 2019-11-26 | Preparation method of 2-amino-5-bromopyridine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911175480.4A CN111057000A (en) | 2019-11-26 | 2019-11-26 | Preparation method of 2-amino-5-bromopyridine |
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| CN111057000A true CN111057000A (en) | 2020-04-24 |
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| CN201911175480.4A Pending CN111057000A (en) | 2019-11-26 | 2019-11-26 | Preparation method of 2-amino-5-bromopyridine |
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2019
- 2019-11-26 CN CN201911175480.4A patent/CN111057000A/en active Pending
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Application publication date: 20200424 |