CN111056999A - Preparation method of 2-chloro-4-aminopyridine - Google Patents
Preparation method of 2-chloro-4-aminopyridine Download PDFInfo
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- CN111056999A CN111056999A CN201911175434.4A CN201911175434A CN111056999A CN 111056999 A CN111056999 A CN 111056999A CN 201911175434 A CN201911175434 A CN 201911175434A CN 111056999 A CN111056999 A CN 111056999A
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- chloropyridine
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- aminopyridine
- nitropyridine
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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)
- Pyridine Compounds (AREA)
Abstract
The invention belongs to the field of organic synthesis, and particularly relates to a preparation method of 2-chloro-4-aminopyridine, which comprises the following steps: (1) 2-chloropyridine is used as a raw material, chloroform is used as a solvent, and 2-chloropyridine oxide is generated under the action of m-chloroperoxybenzoic acid; (2) 2-chloropyridine oxide reacts with mixed acid consisting of concentrated nitric acid and concentrated sulfuric acid to generate 2-chloro-4-nitropyridine oxynitride; (3) 2-chloro-4-nitropyridine nitrogen oxide is reduced into 2-chloro-4-aminopyridine. The beneficial effects of the invention are as follows: the reaction condition is mild, the operation is easy, the post-treatment is simple, the scale-up production is easy, and the method is very suitable for industrial production; the catalytic effect is good, and the yield is high; the raw materials are cheap, and the production cost is low.
Description
Technical Field
The invention belongs to the field of organic synthesis, and particularly relates to a preparation method of 2-chloro-4-aminopyridine.
Background
2-chloro-4-aminopyridine is an important organic synthesis intermediate, and can be used for synthesizing novel N- (2-chloro-4-pyridyl) urea plant growth regulator, which belongs to the cytohormone activity plant regulator, has the functions of promoting cell growth and differentiation, can prevent plant aging, and can promote seedling formation and fruit hypertrophy. The compound preparation also has the effect on tuber plants such as potatoes, can improve the harvest of the potatoes, has little toxicity and great application to agricultural production, has commodities on the market abroad, and the 2-chloro-4-aminopyridine is a key intermediate for synthesizing the plant regulator.
The synthesis method of 2-chloro-4-aminopyridine reported in the current data has the disadvantages of harsh reaction conditions, complex process and high cost.
Disclosure of Invention
The invention aims to: overcomes the technical defects of high cost, low yield and the like in the prior art, and provides a preparation method of 2-chloro-4-aminopyridine, which has low cost and high yield and is suitable for industrial production.
In order to solve the technical problems, the technical scheme adopted by the invention is as follows:
a preparation method of 2-chloro-4-aminopyridine comprises the following steps:
(1) 2-chloropyridine is used as a raw material, chloroform is used as a solvent, and 2-chloropyridine oxynitride is generated under the action of m-chloroperoxybenzoic acid;
(2) 2-chloropyridine nitrogen oxide reacts with mixed acid consisting of concentrated nitric acid and concentrated sulfuric acid to generate 2-chloro-4-nitropyridine nitrogen oxide;
(3) 2-chloro-4-nitropyridine nitrogen oxide is reduced into 2-chloro-4-aminopyridine.
Further, the molar ratio of the 2-chloropyridine to the m-chloroperoxybenzoic acid in the step (1) is 1: 2-3.
Further, the volume ratio of the concentrated nitric acid to the concentrated sulfuric acid in the mixed acid in the step (2) is 1: 1.6-2.
Further, the reduction reaction in the step (3) is catalyzed by iron powder and concentrated hydrochloric acid, and ethanol and water are used as solvents.
Furthermore, the molar ratio of the 2-chloro-4-nitropyridine nitrogen oxide to the iron powder is 1: 5.
Further, the volume ratio of the ethanol to the water is 3: 1.
The reaction equation of the present invention is as follows:
the beneficial effects of the invention are as follows: the reaction condition is mild, the operation is easy, the post-treatment is simple, the scale-up production is easy, and the method is very suitable for industrial production; the catalytic effect is good, and the yield is high; the raw materials are cheap, and the production cost is low.
Detailed Description
The invention is further described with reference to specific embodiments, which are not intended to limit the scope of the claims.
Example 1
(1) Adding 2-chloropyridine (11.3g, 0.1mol), chloroform (100ml) and m-chloroperoxybenzoic acid (34.5g,0.2mol) into a 250ml three-neck flask, reacting for 10 hours at 25 ℃, monitoring the reaction by TLC, pouring the reaction solution into saturated sodium thiosulfate aqueous solution in an ice-water bath after the reaction is completed, stirring, detecting the complete destruction of the m-chloroperoxybenzoic acid by starch potassium iodide test paper, adjusting the pH of the reaction solution to be alkaline, extracting by DCM, merging organic layers, drying and concentrating to obtain 2-chloropyridine oxynitride with the molar yield of 68 percent;
(2) concentrated H was added to a 250ml three-necked flask2SO4(16ml), cooling ice water to 0 ℃, dropwise adding concentrated nitric acid (10ml) to form mixed acid, adding 2-chloropyridine oxynitride (6.4g, 0.05mol) in batches at 0 ℃, stirring for 20min at 0-10 ℃, heating to 100 ℃, stirring for reaction, monitoring by TLC (thin layer chromatography) until the reaction is complete, quenching by ice water after the reaction is finished, and performing suction filtration to obtain the 2-chloro-4-nitropyridine oxynitride with the molar yield of 65%;
(3) adding 2-chloro-4-nitropyridine nitrogen oxide (7.9g, 0.05mol), iron powder (14g, 0.25mol), ethanol 150ml, water 50ml and concentrated hydrochloric acid 5ml into a 500ml three-necked bottle, heating to reflux, monitoring by TLC until the reaction is complete, adding ethyl acetate 30ml after the reaction is complete, stirring, standing, carrying out suction filtration, layering, drying by anhydrous sodium sulfate, and concentrating to obtain the product 2-chloro-4-aminopyridine, wherein the molar yield is 85%.
Example 2
(1) Adding 2-chloropyridine (11.3g, 0.1mol), chloroform (100ml) and m-chloroperoxybenzoic acid (43.1g,0.25mol) into a 250ml three-neck flask, reacting for 10 hours at 25 ℃, monitoring the reaction by TLC, pouring the reaction solution into saturated sodium thiosulfate aqueous solution in an ice-water bath after the reaction is completed, stirring, detecting the complete destruction of the m-chloroperoxybenzoic acid by starch potassium iodide test paper, adjusting the pH of the reaction solution to be alkaline, extracting by DCM, merging organic layers, drying and concentrating to obtain 2-chloropyridine oxynitride with the molar yield of 72 percent;
(2) concentrated H was added to a 250ml three-necked flask2SO4(18ml), cooling ice water to 0 ℃, dropwise adding concentrated nitric acid (10ml) to form mixed acid, adding 2-chloropyridine oxynitride (6.4g, 0.05mol) in batches at 0 ℃, stirring for 20min at 0-10 ℃, heating to 100 ℃, stirring for reaction, monitoring by TLC (thin layer chromatography) until the reaction is complete, quenching by ice water after the reaction is finished, and performing suction filtration to obtain the 2-chloro-4-nitropyridine oxynitride, wherein the molar yield is 70%;
(3) this step was carried out as in example 1.
This embodiment is the best mode.
Example 3
(1) Adding 2-chloropyridine (11.3g, 0.1mol), chloroform (100ml) and m-chloroperoxybenzoic acid (51.8g,0.3mol) into a 250ml three-neck flask, reacting for 10 hours at 25 ℃, monitoring the reaction by TLC, pouring the reaction solution into saturated sodium thiosulfate aqueous solution in an ice-water bath after the reaction is completed, stirring, detecting the complete destruction of the m-chloroperoxybenzoic acid by starch potassium iodide test paper, adjusting the pH of the reaction solution to be alkaline, extracting by DCM, merging organic layers, drying and concentrating to obtain 2-chloropyridine oxynitride, wherein the molar yield is 70%;
(2) concentrated H was added to a 250ml three-necked flask2SO4(20ml), cooling ice water to 0 ℃, dropwise adding concentrated nitric acid (10ml) to form mixed acid, adding 2-chloropyridine oxynitride (6.4g, 0.05mol) in batches at 0 ℃, stirring for 20min at 0-10 ℃, heating to 100 ℃, stirring for reaction, monitoring by TLC (thin layer chromatography) until the reaction is complete, quenching by ice water after the reaction is finished, and performing suction filtration to obtain the 2-chloro-4-nitropyridine oxynitride with the molar yield of 68%;
(3) this step was carried out as in example 1.
Claims (6)
1. A preparation method of 2-chloro-4-aminopyridine is characterized by comprising the following steps:
(1) 2-chloropyridine is used as a raw material, chloroform is used as a solvent, and 2-chloropyridine oxynitride is generated under the action of m-chloroperoxybenzoic acid;
(2) 2-chloropyridine nitrogen oxide reacts with mixed acid consisting of concentrated nitric acid and concentrated sulfuric acid to generate 2-chloro-4-nitropyridine nitrogen oxide;
(3) 2-chloro-4-nitropyridine nitrogen oxide is reduced into 2-chloro-4-aminopyridine.
2. The process according to claim 1, wherein the molar ratio of 2-chloropyridine to m-chloroperoxybenzoic acid in step (1) is 1: 2-3.
3. The method for preparing 2-chloro-4-aminopyridine according to claim 1, wherein the volume ratio of the concentrated nitric acid to the concentrated sulfuric acid in the mixed acid in the step (2) is 1: 1.6-2.
4. The process according to claim 1, wherein the reduction reaction in step (3) is catalyzed by iron powder and concentrated hydrochloric acid, and ethanol and water are used as solvents.
5. The method for preparing 2-chloro-4-aminopyridine according to claim 1, wherein the molar ratio of the 2-chloro-4-nitropyridine nitroxide to the iron powder is 1: 5.
6. The process according to claim 1, wherein the volume ratio of ethanol to water is 3: 1.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114751855A (en) * | 2022-05-23 | 2022-07-15 | 上海皓鸿生物医药科技有限公司 | Preparation method of 2-bromo-4-amino-5-methylpyridine |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114751855A (en) * | 2022-05-23 | 2022-07-15 | 上海皓鸿生物医药科技有限公司 | Preparation method of 2-bromo-4-amino-5-methylpyridine |
| CN114751855B (en) * | 2022-05-23 | 2024-05-07 | 上海皓鸿生物医药科技有限公司 | Preparation method of 2-bromo-4-amino-5-methylpyridine |
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Application publication date: 20200424 |