CN105503716A - Preparation method of 2,6-dicyanopyridine - Google Patents
Preparation method of 2,6-dicyanopyridine Download PDFInfo
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- CN105503716A CN105503716A CN201610063030.6A CN201610063030A CN105503716A CN 105503716 A CN105503716 A CN 105503716A CN 201610063030 A CN201610063030 A CN 201610063030A CN 105503716 A CN105503716 A CN 105503716A
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- preparation
- ammonia
- dicyanopyridine
- dicyanopyridines
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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
- C07D213/84—Nitriles
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pyridine Compounds (AREA)
Abstract
The invention belongs to the technical field of chemical synthesis, and particularly relates to a preparation method of 2,6-dicyanopyridine. According to the method, pyridine-2,6-dicarboxylic acid, ammonia and phosphorus pentachloride have a dehydration reaction in an organic solvent, and 2,6-dicyanopyridine is obtained. According to the method, raw materials are easy to get, steps are short, and the cost is low.
Description
Technical field
The invention belongs to chemosynthesis technical field, be specifically related to a kind of preparation method of 2,6-dicyanopyridine, this compound is the key intermediate of synthesis pybox class chiral catalyst.
Background technology
2,6-dicyanopyridine is the key intermediate synthesis of synthesis Pybox class chiral catalyst.
RoblouE etc. (SyntheticCommunications, 2004,34(20): 3743-3749) report with 2,6-lutidine is raw material and phenyl aldehyde pyrocondensation, ozonize rupture, with unsymmetrical dimethyl hydrazine condensation, obtained 2, the 6-dicyanopyridine of de-amine four-step reaction.This method step is long, and condition is harsh, raw material explosive.
Second method is with pyridine-2,6-dicarboxylic acid for raw material, and through esterification, aminolysis, Dehydration obtains 2,6-dicyanopyridine.This method of this method must through 3 steps reaction carry out, three-step reaction can adopt different dewatering agent to carry out, as trifluoroacetic anhydride (
organometallics 2009,
28, 3928-3940), diphenyl phosphorus chloride and DBU(
tetrahedron:Asymmetry 2010,
21, 1221-1225) but these two kinds of dewatering agents are expensive, or use comparatively phosphorus oxychloride (
chemistry & Industry 1974, (15), 617) but single step yield is only 57%.
The third method uses high-temperature metallic oxide catalysis 2,6-lutidine directly to prepare 2,6-dicyanopyridine in ammonia gas react.This law part is harsh, and yield is only 25%, and impurity is many.
Summary of the invention
The invention provides a kind of preparation method of 2,6-lutidine, be suitable for industrial production.
As implied above, the present invention's pyridine-2,6-dicarboxylic acid one step chemical reaction under ammonia and phosphorus pentachloride exist both obtained target product 2,6-dicyanopyridine, and the solvent that reaction uses is C
1-C
4halo or alkyl polyhalides hydrocarbon, C
1-C
4alkyl symmetrical ether or cyclic ethers, acetonitrile, dimethyl sulfoxide (DMSO),
n,Nthe common solvent such as-dimethyl formamide or above-mentioned solvent are with the mixed solvent of arbitrary proportion mixing composition.Ammonia can use and stores easily arbitrarily or use form, as liquefied ammonia, and ammonia, ammoniacal liquor, or the solution of ammonia in above-mentioned reaction solvent.Reaction can be carried out under-50-50 DEG C of temperature condition.Raw material of the present invention is easy to get, and mild condition is easy and simple to handle, and yield can reach more than 70%, is suitable for scale operation.
Preferably, reacting the solvent that uses is methylene dichloride, methyl tertiary butyl ether, acetonitrile, the mixed solvent of any one or above-mentioned solvent arbitrary proportion composition in DMF.
Preferably, reaction can be carried out under-33-30 DEG C of temperature condition.
Embodiment
Following instance is the explanation to embodiments of the present invention, but the invention is not restricted to following examples.
Embodiment 1
By pyridine-2,6-dicarboxylic acid (1.67g) be dissolved in methylene dichloride (20mL), add phosphorus pentachloride (4g), slowly pass into ammonia about 2 hours under stirring in 0 DEG C, reaction is finished, and slowly adds frozen water, separate organic phase, be washed till neutrality with saturated sodium bicarbonate, anhydrous magnesium sulfate drying, filter, concentrated, residuum vacuum-sublimation, obtains white crystal 2,6-dicyanopyridine (1.08g).Yield 83%.
Embodiment 2
Pyridine-2,6-dicarboxylic acid (1.67g) and 25% strong aqua (2mL) are dissolved in tetrahydrofuran (THF) (40mL), add phosphorus pentachloride (6g) in-20 DEG C in batches, finish, slowly rise to stirring at room temperature 3 hours, reaction is finished, slowly add frozen water, with dichloromethane extraction, be washed till neutrality with saturated sodium bicarbonate, anhydrous magnesium sulfate drying, filter, concentrated, residuum vacuum-sublimation, obtain white crystal 2,6-dicyanopyridine (0.99g).Yield 77%.
Embodiment 3
Liquefied ammonia (0.5mL) and acetonitrile (50mL) are placed in-40 DEG C of cryostats, add pyridine-2,6-dicarboxylic acid (1.67g), rise to 0 DEG C, add phosphorus pentachloride (4g) in batches, finish, stirring at room temperature 2 hours, reaction is finished, concentrating under reduced pressure, residuum methylene dichloride dissolves, and is washed till neutrality with saturated sodium bicarbonate, anhydrous magnesium sulfate drying, concentrated, separate out solid, gained solid recrystallisation from isopropanol, obtain white crystal 2,6-dicyanopyridine (1.13g).Yield 88%.
Claims (6)
1. the preparation method of a dicyanopyridine: pyridine-2,6-dicarboxylic acid and phosphorus pentachloride and ammonia act in organic solvent, obtain 2,6-dicyanopyridine.
2. the preparation method of 2,6-dicyanopyridines as claimed in claim 1, is characterized in that: the ammonia used be specially in ammonia, liquefied ammonia, ammoniacal liquor or ammonia solution in organic solvent any one.
3. the preparation method of 2,6-dicyanopyridines as described in claim 1 and 2, is characterized in that: the organic solvent used is C
1-C
4halo or alkyl polyhalides hydrocarbon, C
1-C
4alkyl symmetrical ether or cyclic ethers, acetonitrile, dimethyl sulfoxide (DMSO),
n,Nany one in-dimethyl formamide, or two or more in above-mentioned solvent are with mixed solvents of arbitrary proportion composition.
4. the preparation method of 2,6-dicyanopyridines as claimed in claim 1, is characterized in that, temperature of reaction is-50 ~ 50 DEG C.
5. the preparation method of 2,6-dicyanopyridines as claimed in claim 3, is characterized in that, the solvent used is methylene dichloride, methyl tertiary butyl ether, acetonitrile, the mixed solvent of any one or the above-mentioned solvent arbitrary proportion composition in DMF.
6. the preparation method of 2,6-dicyanopyridines as claimed in claim 4, is characterized in that, temperature of reaction is-33 ~ 30 DEG C.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610063030.6A CN105503716A (en) | 2016-01-30 | 2016-01-30 | Preparation method of 2,6-dicyanopyridine |
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| CN201610063030.6A CN105503716A (en) | 2016-01-30 | 2016-01-30 | Preparation method of 2,6-dicyanopyridine |
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| CN105503716A true CN105503716A (en) | 2016-04-20 |
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ID=55712087
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| CN201610063030.6A Pending CN105503716A (en) | 2016-01-30 | 2016-01-30 | Preparation method of 2,6-dicyanopyridine |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1332959C (en) * | 2001-02-21 | 2007-08-22 | Nps制药公司 | Heteropolycyclic compounds and their use as metabotropic glutamate receptor antagonists |
| CN103221047A (en) * | 2010-01-13 | 2013-07-24 | 坦颇罗制药股份有限公司 | Compounds and methods |
-
2016
- 2016-01-30 CN CN201610063030.6A patent/CN105503716A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1332959C (en) * | 2001-02-21 | 2007-08-22 | Nps制药公司 | Heteropolycyclic compounds and their use as metabotropic glutamate receptor antagonists |
| CN103221047A (en) * | 2010-01-13 | 2013-07-24 | 坦颇罗制药股份有限公司 | Compounds and methods |
Non-Patent Citations (5)
| Title |
|---|
| J. VELISCEK-CAROLAN ET AL: "Effective Am(III)/Eu(III) separations using 2,6-bis(1,2,4-triazin-3-yl)pyridine (BTP) functionalised titania particles and hierarchically porous beads", 《CHEMICAL COMMUNICATIONS》 * |
| MICHAELA JANSEN ET AL: "Variations of acidic functions at position 2 and substituents at positions 4, 5 and 6 of the indole moiety and their effect on NMDA-glycine site affinity", 《EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY》 * |
| TETSU TSUBOGO ET AL: "Synthesis of optically active, unnatural a-substituted glutamic acid derivatives by a chiral calcium-catalyzed 1,4-addition reaction", 《TETRAHEDRON: ASYMMETRY》 * |
| 胡知之 等: "对硝基苯甲酸的氰化条件的探讨", 《鞍山钢铁学院学报》 * |
| 韦长梅 等: "对氨基苯甲脒二盐酸盐合成工艺改进", 《化工时刊》 * |
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Application publication date: 20160420 |