CN106187875B - A kind of synthesis 2, the method for dipicolimic acid 2 - Google Patents
A kind of synthesis 2, the method for dipicolimic acid 2 Download PDFInfo
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- CN106187875B CN106187875B CN201610603337.0A CN201610603337A CN106187875B CN 106187875 B CN106187875 B CN 106187875B CN 201610603337 A CN201610603337 A CN 201610603337A CN 106187875 B CN106187875 B CN 106187875B
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- Prior art keywords
- synthesis
- dipicolimic acid
- dichloropyridine
- dipicolimic
- acid
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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
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/79—Acids; Esters
-
- 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
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/79—Acids; Esters
- C07D213/803—Processes of preparation
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pyridine Compounds (AREA)
Abstract
The invention discloses a kind of synthesis 2, the methods of dipicolimic acid 2, using 2,6- dichloropyridine is raw material, in the case where completely cutting off air, using anhydrous ether or THF as solvent, it acts on obtaining grignard reagent with active metal under the action of initiator, after cooling, is passed through excessively dry carbon dioxide gas, acidified to obtain 2, dipicolimic acid 2, this method is using cheap 2,6 dichloropyridines are raw material, and at low cost, in addition synthesis technology route is simple, it is easy to control, is easy to industrial production.
Description
Technical field
The invention belongs to pesticide, medicine intermediate development field, in particular to a kind of synthesis 2, the side of dipicolimic acid 2
Method.
Background technique
2, dipicolimic acid 2 is the important pesticide of one kind, medicine intermediate, is largely present in the gemma of bacterium, at present
Biology extraction is mainly passed through for the acquisition of 2,6- pyridinedicarboxylic acid or is obtained using 2,6- dimethyl.No matter which kind of side
Method, cost is all higher, results in existing market 2, and dipicolimic acid 2 holds at high price.
Since domestic pyridine production capacity improves, increased simultaneously for the demand of chloro-pyridine, a large amount of pyridines are obtained through superchlorination
To different chlorization products, and the by-product that 2,6 dichloropyridines become chloropyridine product largely occurs, and has lower price excellent
Gesture becomes cheap raw material.
Summary of the invention
The present invention provide it is a kind of synthesis 2, the method for dipicolimic acid 2, with cheap 2,6 dichloropyridines be raw material,
At low cost, in addition synthesis technology route is simple, is easy to control, and is easy to industrial production.
To solve the above-mentioned problems, the technical solution adopted by the present invention is that it is such, a kind of synthesis 2, dipicolimic acid 2
Method, using 2,6- dichloropyridine be raw material, using anhydrous ether or THF as solvent, causing in the case where completely cutting off air
It acts on obtaining grignard reagent with magnesium metal under the action of agent, after cooling, is passed through excessively dry carbon dioxide gas, it is acidified to obtain
To 2, dipicolimic acid 2 is as follows when reacting:
Preferably, the magnesium metal dosage is 2~4 times of 2,6- dichloropyridine mole.
Preferably, the dosage of the solvent is 5~20 times of 2,6- dichloropyridine mole.
Preferably, the initiator is iodine or Bromofume.
Preferably, the dosage of the initiator is 2,6- dichloropyridine mole 0.1%~1%.
Preferably, 2,6- dichloropyridine and active metal operative temperature are 30~65 DEG C.
Preferably, 2,6- dichloropyridine and active metal action time are 4~12 hours.
Preferably, before carbon dioxide is passed through, Grignard Reagent is cooled to -20~-5 DEG C.
The invention has the following advantages that
1. the process line of selection of the invention is simple, it is easy to control, is easy to industrial production.
2. the low in raw material price that the present invention uses is general industry raw material, there is biggish cost advantage.
3. process line of the invention is environmentally friendly, environmental pollution is small.
Specific example
The present invention is further illustrated below with reference to example, but the scope of protection of the present invention is not limited thereto.
Embodiment 1
148g (1mol) 2,6- dichloropyridine is dissolved in 721g (10mol) tetrahydrofuran solution, and 60g (2.5mol) is added
Magnesium powder is passed through nitrogen isolation air, and heated solution causes 55 DEG C of (i.e. 2,6- dichloropyridine and active metal effects in the case where stirring
Temperature is 55 DEG C), the initiator Bromofume of 0.55g (0.005mol) is added, stirring carries out 6 hours (i.e. 2,6- dichloros of reaction
Pyridine and active metal action time are 6 hours), the solution after reaction is transparent；- 15 DEG C are cooled to, is slowly introducing excessive dry
Dry carbon dioxide gas determines to react, sentence when the carbon dioxide of entrance is identical as tail gas tolerance according to carbon dioxide flow
Fixed reaction terminates, after solution is acidified, filter, remove tetrahydrofuran, obtain 2, dipicolimic acid 2, yield is
94.5%, purity is 97% after extraction,
Embodiment 2
Before initiator is added, solution is heated to 30 DEG C, and (i.e. 2,6- dichloropyridine is with active metal operative temperature
30 DEG C) outside, remaining reaction condition is identical with embodiment 1, after reaction, obtains 2, and dipicolimic acid 2, yield is
92%, purity is 75.2% after extraction.
Embodiment 3
Before initiator is added, solution is heated to 60 DEG C, and (i.e. 2,6- dichloropyridine is with active metal operative temperature
60 DEG C) outside, remaining reaction condition is identical with embodiment 1, after reaction, obtains 2, and dipicolimic acid 2, yield is
93.8%, purity is 94.3% after extraction.
Embodiment 4
Other than initiator used is iodine, remaining operation is identical with embodiment 1, after reaction, obtains 2,6-
Pyridinedicarboxylic acid, yield 91.2%, purity is 96.1% after extraction.
Embodiment 5
In addition to be stirred to react the time be 4 hours other than (i.e. 2,6- dichloropyridine and active metal action time be 4 hours),
Remaining operating procedure is identical with embodiment 1, obtains 2. after reaction, dipicolimic acid 2, yield 93.2%, purity
It is 95.8%.
Embodiment 6
Before being passed through in addition to carbon dioxide, grignard reagent is cooled to -5 DEG C, remaining reaction condition and the complete phase of embodiment 1
Together, after reaction, processing obtains 2, dipicolimic acid 2, yield 89.6%, purity 91%.
Embodiment 7
In addition to magnesium powder dosage is 4mol, before carbon dioxide is passed through, grignard reagent is cooled to -20 DEG C of outer, remaining reactions
Condition is identical with example 1, and after reaction, extraction obtains 2, dipicolimic acid 2, yield 93.2%, and purity is
94.7%.
The foregoing is merely illustrative of the preferred embodiments of the present invention, is not intended to limit the invention, all in essence of the invention
Within mind and principle, any modification, equivalent replacement, improvement and so on be should all be included in the protection scope of the present invention.
Claims (8)
1. a kind of synthesis 2, the method for dipicolimic acid 2, which is characterized in that using 2,6- dichloropyridine is raw material, empty in isolation
It in the case where gas, using anhydrous ether or THF as solvent, acts on obtaining grignard reagent with magnesium metal under the action of initiator, drop
Wen Hou, is passed through excessively dry carbon dioxide gas, acidified to obtain 2, dipicolimic acid 2, and reaction equation is as follows:
2. a kind of synthesis 2 according to claim 1, the method for dipicolimic acid 2, which is characterized in that the gold
Belong to 2~4 times that magnesium dosage is 2,6- dichloropyridine mole.
3. a kind of synthesis 2 according to claim 1, the method for dipicolimic acid 2, which is characterized in that described is molten
Agent dosage is 5~20 times of 2,6- dichloropyridine mole.
4. a kind of synthesis 2 according to claim 1, the method for dipicolimic acid 2, which is characterized in that described draws
Sending out agent is iodine or Bromofume.
5. according to claim 1 or 4 a kind of synthesis 2, the method for dipicolimic acid 2, which is characterized in that described
Initiator amount is 2,6- dichloropyridine mole 0.1%~1%.
6. a kind of synthesis 2 according to claim 1, the method for dipicolimic acid 2, which is characterized in that 2,6- dichloro pyrroles
Pyridine and magnesium metal operative temperature are 30~65 DEG C.
7. a kind of synthesis 2 according to claim 1, the method for dipicolimic acid 2, which is characterized in that 2,6- dichloro pyrroles
Pyridine and magnesium metal action time are 4~12 hours.
8. a kind of synthesis 2 according to claim 1, the method for dipicolimic acid 2, which is characterized in that carbon dioxide is logical
Before entering, Grignard Reagent is cooled to -20~-5 DEG C.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201610603337.0A CN106187875B (en) | 2016-07-28 | 2016-07-28 | A kind of synthesis 2, the method for dipicolimic acid 2 |
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| CN201610603337.0A CN106187875B (en) | 2016-07-28 | 2016-07-28 | A kind of synthesis 2, the method for dipicolimic acid 2 |
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| CN106187875A CN106187875A (en) | 2016-12-07 |
| CN106187875B true CN106187875B (en) | 2019-08-16 |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103497152A (en) * | 2013-10-11 | 2014-01-08 | 河北汇华药业有限公司 | Method for preparing pyridine-2,6-dicarboxylic acid via liquid phase catalytic oxidation |
| CN103664767A (en) * | 2013-12-06 | 2014-03-26 | 常熟市联创化学有限公司 | Method for preparing 2, 6-pyridinedicarboxylic acid |
| CN104513196A (en) * | 2015-01-15 | 2015-04-15 | 安润医药科技（苏州）有限公司 | Synthetic method for roflumilast |
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2016
- 2016-07-28 CN CN201610603337.0A patent/CN106187875B/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103497152A (en) * | 2013-10-11 | 2014-01-08 | 河北汇华药业有限公司 | Method for preparing pyridine-2,6-dicarboxylic acid via liquid phase catalytic oxidation |
| CN103664767A (en) * | 2013-12-06 | 2014-03-26 | 常熟市联创化学有限公司 | Method for preparing 2, 6-pyridinedicarboxylic acid |
| CN104513196A (en) * | 2015-01-15 | 2015-04-15 | 安润医药科技（苏州）有限公司 | Synthetic method for roflumilast |
Non-Patent Citations (2)
| Title |
|---|
| 2,6-吡啶二甲醛合成方法的改进;冯志君等;《阜阳师范学院学报（自然科学版）》;20070331;第24卷(第1期);29-30,66 |
| 格氏试剂制备性质及其在合成中应用;曾育才;《宁德师专学报（自然科学版）》;19990831;第11卷(第3期);170-176,182 |
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