CN109705030A - A kind of new synthetic method of 2- amino -3- picoline - Google Patents
A kind of new synthetic method of 2- amino -3- picoline Download PDFInfo
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- CN109705030A CN109705030A CN201711016134.2A CN201711016134A CN109705030A CN 109705030 A CN109705030 A CN 109705030A CN 201711016134 A CN201711016134 A CN 201711016134A CN 109705030 A CN109705030 A CN 109705030A
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- picoline
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Abstract
The invention belongs to organic synthesis fields, and in particular to a kind of new synthetic method of 2- amino -3- picoline.2- cyano -3- picoline is not exclusively hydrolyzed to form 3- methyl -2- pyridine carboxamide under the conditions of diluted alkaline using hydrogen peroxide as oxidant by the new synthetic method, then with freshly prepd sodium hypobromite carry out Hofmann degradation to get.The present invention uses new preparation method, not only reduces cost, protects environment, and easy to operate, convenient post-treatment.High income, synthesis is simple, is suitble to industrialized production.
Description
Technical field
The invention belongs to organic synthesis fields, and in particular to a kind of new synthetic method of 2- amino -3- picoline.
Background technique
2- amino -3- picoline is important organic intermediate, can be used for synthesizing antasthmatic, antimicrobial, analgesic
Agent, AIDS resisting medicine and nitric oxide synthase inhibitor activity also have been reported that the compound is to be conducive to dissolution carbon nanotube recently
The excellent solubilizer of material.
The preparation of 2- amino -3- picoline is usually that 3- picoline and Sodamide are carried out aminating reaction, this reaction
Condition is harsh, and reaction reagent is rare, and by-product is more, and yield is low；Also have and carry out first by starting material of 2-aminopyridine
Base, but complex steps, route is long, and only 50 %, industrial application value be not high for total recovery.
Therefore, the new synthetic method for researching and developing a kind of 2- amino -3- picoline is current urgent problem to be solved.
Summary of the invention
The purpose of the present invention is to provide the new synthetic method of 2- amino -3- picoline, this method high income, synthesis letters
It is single, it is suitble to industrialized production.
To achieve the goals above, the present invention adopts the following technical scheme:
A kind of new synthetic method of 2- amino -3- picoline, which is characterized in that the new synthetic method is oxidation with hydrogen peroxide
2- cyano -3- picoline is not exclusively hydrolyzed to form 3- methyl -2- pyridine carboxamide under the conditions of diluted alkaline, then by agent
With freshly prepd sodium hypobromite carry out Hofmann degradation to get.
The new synthetic method includes the following steps:
Step 1: 2- cyano -3- picoline being added to the in the mixed solvent of NaOH aqueous solution and acetone, 15 under stirring
H is added dropwise in min2O2, 50 DEG C are warming up to, continues to be stirred to react 3. 5 h, stops reaction, acetone is evaporated off in 50 DEG C or less,
Freezing filters, and drying obtains white solid 3- methyl -2- pyridine carboxamide；
Step 2: by NaOH aqueous solution be cooled to 0~5 DEG C with brine ice, be slowly added dropwise bromine, drip 0. 5 h of Bi Baowen
, sodium hypobromite solution is made；White solid made from upper step is put into NaOH aqueous solution, freshly prepared secondary bromine is added dropwise in 0 DEG C of when
Acid sodium solution is added dropwise, and white solid gradually dissolves, and is warming up to 60 DEG C of 0. 5 h of reaction, stops reaction, reaction solution
It is cooling, it is extracted with ethyl acetate, organic phase is washed with water, and it is dry, it is concentrated to give red liquid, crude product vacuum distillation is received
107~108. 5 DEG C of collection, 2.67 kPa fractions are down to room temperature, obtain white final product.
The concentration of NaOH aqueous solution is 5% in step 1.
H in step 12O2The concentration of aqueous solution is 10%.
The concentration of NaOH aqueous solution is 12% in step 1.
Compared with prior art, effect of the invention is that: the present invention use new preparation method, not only reduce into
This, protects environment, and easy to operate, convenient post-treatment.High income, synthesis is simple, is suitble to industrialized production.
Specific embodiment
Embodiment 1
A kind of new synthetic method of 2- amino -3- picoline, includes the following steps:
Step 1: the mixing of NaOH aqueous solution and acetone that 50g 2- cyano -3- picoline is added to 5% mass fraction is molten
In agent 650ml, the H of 10% mass fraction is added dropwise under stirring in 15 min2O2125ml is warming up to 50 DEG C, continues to stir
3. 5 h are reacted, stops reaction, acetone is evaporated off in 50 DEG C or less, are freezed, are filtered, drying obtains white solid 3- first
Base -2- pyridine carboxamide 47g, yield 85.3%；
Step 2: 12% NaOH aqueous solution 320ml being cooled to 0~5 DEG C with brine ice, bromine 25ml is slowly added dropwise, is dripped
Sodium hypobromite solution is made in Bi Baowen 0.5h；White solid made from upper step is put into 12% NaOH aqueous solution 250ml
, 0 DEG C of when is added dropwise freshly prepared sodium hypobromite solution, is added dropwise, white solid gradually dissolves, and is warming up to 60 DEG C of reactions
0. 5 h stop reaction, and reaction solution is cooling, are extracted 3 times with 250ml ethyl acetate, organic phase with 50ml water washing 2 times,
It is dry, it is concentrated to give red liquid, crude product vacuum distillation collects 107~108. 5 DEG C, 2.67 kPa fractions are down to room temperature
, obtain white final product 35g, yield 88.5%.
1H NMR (CDCl3) δ (× 10-6):2.334 (s ,3H ,CH3 ) ,5.430 (b ,2H ,NH2) ,6.846
~8. 110 (m, 3H, pyridine H).
Embodiment 2
A kind of new synthetic method of 2- amino -3- picoline, includes the following steps:
Step 1: 48g 2- cyano -3- picoline is added to the NaOH aqueous solution of 5% mass fraction and the mixed solvent of acetone
In 650ml, the H of 10% mass fraction is added dropwise under stirring in 15 min2O2125ml is warming up to 50 DEG C, and it is anti-to continue stirring
3.5h is answered, stops reaction, acetone is evaporated off in 50 DEG C or less, is freezed, is filtered, drying obtains white solid 3- methyl -2-
Pyridine carboxamide 47g, yield 85.3%；
Step 2: 12% NaOH aqueous solution 320ml being cooled to 0~5 DEG C with brine ice, bromine 25ml is slowly added dropwise, is dripped
Sodium hypobromite solution is made in Bi Baowen 0.5h；White solid made from upper step is put into 12% NaOH aqueous solution 250ml
, 0 DEG C of when is added dropwise freshly prepared sodium hypobromite solution, is added dropwise, white solid gradually dissolves, and is warming up to 60 DEG C of reactions
0.5h stops reaction, and reaction solution is cooling, is extracted 3 times with 250ml ethyl acetate, and organic phase is done with 50ml water washing 2 times
It is dry, it is concentrated to give red liquid, crude product vacuum distillation collects 107~108. 5 DEG C, and 2.67 kPa fractions are down to room temperature,
Obtain white final product 33g, yield 87.8%.
Embodiment 3
Influence of the concentration of sodium hydroxide solution to yield in cyan-hydrolysis reaction
In the identical situation of sodium hydroxide concentration, change concentration of sodium hydroxide solution, as a result such as table 1:
For the hydrolysis of 2- amino -3- picoline when alkaline concentration is 5 %, product yield is higher it can be seen from table 1.Alkali
Liquid concentration is too low, and reaction carries out incomplete；Excessive concentration easily leads to amide product and continues to be hydrolyzed into acid, declines yield.
The foregoing is only a preferred embodiment of the present invention, is not intended to restrict the invention, for the skill of this field
For art personnel, the invention may be variously modified and varied.All within the spirits and principles of the present invention, made any to repair
Change, equivalent replacement, improvement etc., should all be included in the protection scope of the present invention.
Claims (5)
1. a kind of new synthetic method of 2- amino -3- picoline, which is characterized in that the new synthetic method is using hydrogen peroxide as oxygen
2- cyano -3- picoline is not exclusively hydrolyzed to form 3- methyl -2- pyridine carboxamide under the conditions of diluted alkaline, so by agent
Afterwards with freshly prepd sodium hypobromite carry out Hofmann degradation to get.
2. a kind of new synthetic method of 2- amino -3- picoline according to claim 1, which is characterized in that the synthesis
New method includes the following steps: step 1: 2- cyano -3- picoline is added to the mixed solvent of NaOH aqueous solution and acetone
In, H is added dropwise in 15 min under stirring2O2, 50 °C are warming up to, continues to be stirred to react 3.5 h, stops reaction, in 50 °C
Acetone is evaporated off below, freezes, filters, drying obtains white solid 3- methyl -2- pyridine carboxamide；Step 2: by
NaOH aqueous solution is cooled to 0~5 °C with brine ice, and bromine is slowly added dropwise, and drips 0. 5 h of Bi Baowen, and sodium hypobromite is made
Solution；White solid made from upper step is put into NaOH aqueous solution, freshly prepared sodium hypobromite solution is added dropwise in 0 °C of when, drips
Add complete, white solid gradually dissolves, and is warming up to 60 °C of 0. 5 h of reaction, stops reaction, and reaction solution is cooling, uses acetic acid
Ethyl ester extraction, organic phase are washed with water, dry, are concentrated to give red liquid, and crude product vacuum distillation collects 107~108.
5 DEG C, 2.67 kPa fractions are down to room temperature, obtain white final product.
3. a kind of new synthetic method of 2- amino -3- picoline according to claim 2, which is characterized in that in step 1
The concentration of NaOH aqueous solution is 5%.
4. a kind of new synthetic method of 2- amino -3- picoline according to claim 2, which is characterized in that in step 1
H2O2The concentration of aqueous solution is 10%.
5. a kind of new synthetic method of 2- amino -3- picoline according to claim 2, which is characterized in that in step 1
The concentration of NaOH aqueous solution is 12%.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111925333A (en) * | 2020-09-01 | 2020-11-13 | 济南悟通生物科技有限公司 | Preparation method, product and application of 2-amino-5-methylpyrazine |
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2017
- 2017-10-26 CN CN201711016134.2A patent/CN109705030A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111925333A (en) * | 2020-09-01 | 2020-11-13 | 济南悟通生物科技有限公司 | Preparation method, product and application of 2-amino-5-methylpyrazine |
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Application publication date: 20190503 |
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