CN101108823A - Method for preparing 3-picoline amido derivant - Google Patents
Method for preparing 3-picoline amido derivant Download PDFInfo
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- CN101108823A CN101108823A CNA200710070432XA CN200710070432A CN101108823A CN 101108823 A CN101108823 A CN 101108823A CN A200710070432X A CNA200710070432X A CN A200710070432XA CN 200710070432 A CN200710070432 A CN 200710070432A CN 101108823 A CN101108823 A CN 101108823A
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Abstract
The invention discloses a preparation method of the amino derivatives of the 3-methylpyridine. The alkane of the C7 to C8 and / or the dutrex of the C7 to C8 are used as the organic solvent and the aromatic amine of the C7 to C9 and / or the aliphatic alcohol amine are used as the phase transfer catalyst. The amino sodium salt of the 3-methylpyridine is produced by reacting under the temperature of 110 DEG C. to 165 DEG C., pressure of 0.1MPa to 5.0MPa and the ammonia partial pressure of 0MPa to 0.5MPa and the amino derivatives-2-amino-3-methylpyridine and 2-amino-5-methylpyridine of the 3-methylpyridine are gained through the Chichibabin reaction between the 3-methylpyridine and the amino salt of the alkali metal. The invention has easily gained raw materials, short process route, little side reaction, obviously high selectivity between the 2-amino-3-methylpyridine or 2-amino-5-methylpyridine and higher total yield.
Description
(1) technical field
The present invention relates to a kind of preparation method of an aminoderivative of 3-picoline, is raw material with the 3-picoline especially, the industrialized process for preparing of preparation 2-amino-3-picoline and 2-amino-5-picoline.
(2) technical background
One amination derivative of 3-picoline mainly is 2-amino-3-picoline and 2-amino-5-picoline.2-amino-3-picoline is important organic intermediate, it both can be used for synthetic antibacterial drug (referring to document Pharma.Chem.J., 2003,229), can be used for synthetic pain killer Fenbid again (referring to document Eur.JMed.Chem., 2003,513), synthetic (referring to document J.Med.Chem., 2002,5410) that also can be used for the anti-AIDS poison.2-amino-5-picoline also is a kind of important intermediate, and it not only is used for synthetic (referring to the U.S. Pat Pat.3974281) of medicine, and can be used for synthesize (referring to document JACS, 1968,4361) of agricultural chemicals.
The preparation method of one aminoderivative of 3-picoline has multiple.It is raw material that document (JACS, 1973,4453) has proposed with the 2-aminopyridine, prepares the method for 2-amino-3-picoline successively through chlorination, methylation reaction; Total recovery is less than 50%, and industrial value is not high; Document (heterocyclic chemistry, 2006,258) has been reported with the diaza azoles through the open loop cracking technology of cyclization Synthetic 2-amino-3-picoline again again, but there are shortcomings such as raw material sources are few, side reaction is many, and yield is low in this technology.Document (Can.J.Chem., 1965,725, Adv.Heterocycl.Chem.1966,229 and Chem.﹠amp; Ind., 1964,659) reported that respectively with the 3-picoline be raw material, prepare the operational path of an amination derivative of 3-picoline through Chichibabin reaction, but its yield has remained all further to be improved.
(3) summary of the invention
The objective of the invention is to propose a kind of is the operational path of feedstock production 2-amino-3-picoline and 2-amino-5-picoline with the 3-picoline, and yield is higher, to overcome the defective that prior art exists.
Design of the present invention is as follows:
Because the Chichibabin reaction between 3-picoline and the sodium amide, a large amount of cokings usually appear when carrying out under comparatively high temps, yield is lower, in order to improve this situation, the present invention adopts sodium amide-potassium amide mixture as the amination agent, and be that solvent, aromatic amine and/or hydramine are phase-transfer catalyst with the hydrocarbons, make temperature of reaction reduce, yield obviously improves.
Preparation method of the present invention comprises following two steps:
(1) be raw material with 3-picoline and alkali-metal amide, at C
7～C
18Aliphatic alkanes and/or C
7～C
18In the aromatic hydrocarbon organic solvent, with C
7～C
9Aromatic amine and/or C
2～C
6Aliphatic hydramine be phase-transfer catalyst, be 110～165 ℃ in temperature, pressure is 0.1～5.0MPa, wherein the ammonia dividing potential drop is that reaction makes the disodium iminodiacetic (I) of 3-picoline under 0～0.5MPa condition;
(2) product (I) that step (1) is made adds entry at 30～80 ℃, and stirring reaction 1～2 hour filters, and with the distillation of gained filtrate decompression, collects cut 2-amino-3-picoline (II) and 2-amino-5-picoline (III) respectively.
Particularly; above-mentioned step (1) is: add alkali-metal amide, organic solvent and phase-transfer catalyst in reactor after; under nitrogen protection, be warming up to 110～165 ℃; slowly add the 3-picoline, Controlling System stagnation pressure 0.1～5.0MPa, wherein the ammonia dividing potential drop is 0～0.5MPa; stirring reaction 4～10 hours; when treating invariably to coagulate gas and emitting, stopped reaction, the disodium iminodiacetic (I) of 3-picoline.
Described alkali-metal amide is sodium amide-potassium amide mixture, and the mol ratio of sodium amide and potassium amide is 1: 0.1～1.0 in the described mixture.
Described organic solvent is the mixing of following one or both or two or more arbitrary proportions: heptane, octane, decane, dodecane, toluene, p-Xylol, m-xylene, 2,4,6-trimethylbenzene, dodecylbenzene, naphthane, perhydronaphthalene.
Described phase-transfer catalyst is the mixing of following one or both or two or more arbitrary proportions: to monomethylaniline, 3, and 5-xylidine, N, accelerine, thanomin, diethanolamine, trolamine, butanolamine.
Described alkali-metal amide total amount and the 3-picoline amount of substance ratio that feeds intake that feeds intake is 1.1～3.8: 1; The mass ratio that feeds intake of described 3-picoline, organic solvent and phase-transfer catalyst is 1: 1～3.5: 0.001～0.1, and the weight that described step (2) adds entry is 1～4 times of 3-picoline weight.
The underpressure distillation step of described step (2) is as follows: be decompressed to 20KPa earlier and remove organic solvent and phase-transfer catalyst, continue decompression again, under 106～109 ℃/2.01～2.14kPa and 109～121 ℃/2.01～2.14kPa condition, collect cut 2-amino-3-picoline (II) and 2-amino-5-picoline (III) respectively.
Further, total charging capacity of described alkali-metal amide is preferably 1.2～3.0: 1 with the amount of substance ratio that feeds intake of 3-picoline; The mass ratio that feeds intake of described 3-picoline, organic solvent and phase-transfer catalyst is preferably 1: 1.5～and 3.0: 0.015～0.04.
The temperature of reaction of described step (1) is preferably 130～155 ℃.
Concrete recommendation is described preparation method comprise the steps:
(1) in reactor, add alkali-metal amide, organic solvent and phase-transfer catalyst after, under nitrogen protection, be warming up to 130～155 ℃, slowly add the 3-picoline, Controlling System stagnation pressure 0.1～10MPa, ammonia dividing potential drop 0～0.5MPa, stirring reaction 4～10 hours is when treating that coagulating gas invariably emits, stopped reaction, the disodium iminodiacetic (I) of 3-picoline; Described organic solvent is C
7～C
18Aliphatic alkanes and/or C
7～C
18Aromatic hydrocarbon; Described phase-transfer catalyst is C
7～C
9Aromatic amine and/or C
2～C
6Aliphatic hydramine; Total mole dosage of described alkali-metal amide is 1.2～3.0 times of 3-picoline; The mass ratio that feeds intake of described 3-picoline, organic solvent and phase-transfer catalyst is 1: 1.5～3.0: 0.015～0.04;
(2) step (1) products therefrom (I) is cooled to 30～80 ℃ after, slowly add entry under the normal pressure, the add-on of described water is 1～4 times of 3-picoline weight, stirring reaction 1～2 hour, filtered while hot, filtrate decompression is distilled, be decompressed to 20KPa earlier and remove organic solvent and phase-transfer catalyst, continue decompression again, under 106～109 ℃/2.01～2.14kPa and 109～121 ℃/2.01～2.14kPa condition, collect cut 2-amino-3-picoline (II) and 2-amino-5-picoline (III) respectively.
The substantive progressive following aspect that is embodied in of the present invention:
1, adopting sodium amide-potassium amide mixture is the amination agent, C
7～C
10Aromatic amine and/or C
2～C
6Aliphatic hydramine be phase-transfer catalyst, the Chichibabin reaction that makes the 3-picoline is when reducing temperature of reaction, the total recovery of target product obviously improves;
2, adopt the technology of Controlling System stagnation pressure and ammonia dividing potential drop, in temperature is 110～165 ℃, pressure is 0.1～5.0MPa, wherein the ammonia dividing potential drop is the disodium iminodiacetic of prepared in reaction 3-picoline under 0～0.5MPa condition, make the selectivity of 2-amino-3-picoline in the above-mentioned reaction product or 2-amino-5-picoline obviously improve, reduced the product separation costs.
(4) concrete implementation
Further set forth technical scheme of the present invention with specific embodiment below, but protection scope of the present invention is not limited thereto.
Embodiment 1
After sodium amide (19.5g) and potassium amide (11g) pulverizing; with perhydronaphthalene (90g) and monomethylaniline (1.54g) is joined in the four-hole boiling flask of 500ml; normal pressure also is heated with stirring to 140 ℃ under nitrogen protection; in 1 hour, drip 3-picoline 46.5g; reacted about 4 hours; close nitrogen valve; after no non-condensable gas is emitted in check and the affirmation system; be cooled to 60 ℃, slowly add the 65.0g deionized water, continued stirring reaction 1 hour; filtered while hot; remove a small amount of insolubles (0.2g), filtrate is cooled to room temperature, use the separating funnel phase-splitting; with the organic phase underpressure distillation; under rough vacuum, remove earlier and desolvate and phase-transfer catalyst, then respectively under 106～108 ℃/2.01kPa and 109～120 ℃/2.01kPa condition, collect cut (II) 39.4g and (III) 3.78g.Survey its boiling point and be respectively 221～222 ℃ (2-amino-3-picoline) and 227～228 ℃ (2-amino-5-picoline), with gas-chromatography above-mentioned two cuts are analyzed, its purity is respectively 99.6% and 99.1%, overall yield of reaction is 79.9%, above-mentioned two cuts are carried out ultimate analysis, and the ultimate analysis value of actual measurement and the comparing result of theoretical value are as follows:
Theoretical value: C, 66.67%; H, 7.40%; N, 25.93%
Measured value:
(II)?C，66.62％；H，7.47％；N，25.91％
(III)C，66.60％；H，7.41％；N，25.99％
Embodiment 2
After sodium amide (15.6g) and potassium amide (11g) pulverizing; with dimethylbenzene (90g) and N; accelerine (1.62g) joins in the four-hole boiling flask of 500ml together; normal pressure also is heated with stirring to 155 ℃ under nitrogen protection; in 1 hour, drip 3-picoline 46.5g; reacted about 5 hours; close nitrogen valve, after no non-condensable gas is emitted in check and the affirmation system, be cooled to 70 ℃; slowly add the 85.0g deionized water; continued stirring reaction 1 hour, filtered while hot is removed a small amount of insolubles (0.16g); filtrate is cooled to room temperature; use the separating funnel phase-splitting,, under rough vacuum, remove earlier and desolvate and phase-transfer catalyst the organic phase underpressure distillation; then respectively under 106～108 ℃/2.10kPa and 109～120 ℃/2.10kPa condition, collect cut (II) 39.8g and (III) 2.81g.Survey its boiling point and be respectively 221.5～222.5 ℃ (2-amino-3-picoline) and 226.5～228 ℃ (2-amino-5-picoline), with gas-chromatography above-mentioned two cuts are analyzed, its purity is respectively 99.4% and 99.0%, overall yield of reaction is 78.4%, above-mentioned two cuts are carried out ultimate analysis, and the ultimate analysis value of actual measurement and the comparing result of theoretical value are as follows:
Theoretical value: C, 66.67%; H, 7.40%; N, 25.93%
Measured value:
(II)?C，66.60％；H，7.46％；N，25.94％
(III)C，66.65％；H7.41％；N，25.94％
Embodiment 3
After sodium amide (19.5g) and potassium amide (27.5g) pulverizing; with naphthane (90g) and N; accelerine (1.62g) joins in the four-hole boiling flask of 500ml together; normal pressure also is heated with stirring to 130 ℃ under nitrogen protection; in 1 hour, drip 3-picoline 46.5g; reacted about 10 hours; close nitrogen valve; after no non-condensable gas is emitted in check and the affirmation system; be cooled to 80 ℃; slowly add the 185.0g deionized water; continued stirring reaction 1 hour; filtered while hot; remove a small amount of insolubles (0.26g); filtrate is cooled to room temperature; use the separating funnel phase-splitting; with the organic phase underpressure distillation; under rough vacuum, remove earlier and desolvate and phase-transfer catalyst; then respectively under 106～108 ℃/2.10kPa and 109～120 ℃/2.10kPa condition; collect cut (II) 32.8g and (III) 3.77g survey its boiling point and be respectively 221.5～222.5 ℃ (2-amino-3-picoline) and 226.5～228 ℃ (2-amino-5-picoline); with gas-chromatography above-mentioned two cuts are analyzed; its purity is respectively 99.6% and 99.5%; overall yield of reaction is 67.4%; above-mentioned two cuts are carried out ultimate analysis, and the ultimate analysis value of actual measurement and the comparing result of theoretical value are as follows:
Theoretical value: C, 66.67%; H, 7.40%; N, 25.93%
Measured value:
(II)?C，66.63％；H，7.42％；N，25.95％
(III)C，66.65％；H，7.39％；N，25.96％
Embodiment 4
After sodium amide (23.5g) and potassium amide (13.8g) pulverizing, join in the autoclave of 300ml with dodecylbenzene (140g) and trolamine (1.74g), feed nitrogen with air displacement clean after, feed ammonia again to 0.15MPa, slowly be heated to 140 ℃ while stirring, in 1 hour, drip 3-picoline (46.5g), and then feed nitrogen to stagnation pressure 1.2MPa, constant temperature and pressure reaction about 4 hours, be cooled to 60 ℃, be decompressed to normal pressure, slowly add the 82.0g deionized water, continued stirring reaction 1 hour, filtered while hot, remove a small amount of insolubles (0.2g), filtrate is cooled to room temperature, use the separating funnel phase-splitting, with the organic phase underpressure distillation, under rough vacuum, remove earlier and desolvate and phase-transfer catalyst, then respectively under 106～108 ℃/2.01kPa and 109～120 ℃/2.01kPa condition, collect cut (II) 9.4g and (III) 31.8g.Survey its boiling point and be respectively 221～222 ℃ (2-amino-3-picoline) and 227～228 ℃ (2-amino-5-picoline), with gas-chromatography above-mentioned two cuts are analyzed, its purity is respectively 99.1% and 99.3%, overall yield of reaction is 75.5%, above-mentioned two cuts are carried out ultimate analysis, and the ultimate analysis value of actual measurement and the comparing result of theoretical value are as follows:
Theoretical value: C, 66.67%; H, 7.40%; N, 25.93%
Measured value:
(II)?C，66.63％；H，7.38％；N，25.99％
(III)C，66.61％；H，7.45％；N，25.94％
Embodiment 5
After sodium amide (39.3g) and potassium amide (15.4g) pulverizing, with 2,4,6-trimethylbenzene (100g), decane (40g), N, accelerine (1.1g) and butanolamine (0.8g) join in the autoclave of 300ml together, feed nitrogen with air displacement clean after, feed ammonia again to 0.25MPa, slowly be heated to 150 ℃, in 1 hour, drip 3-picoline (46.5g) while stir, and then feed nitrogen to stagnation pressure 3.8MPa, constant temperature and pressure reaction about 4 hours is cooled to 60 ℃, is decompressed to normal pressure, slowly add the 91.0g deionized water, continued stirring reaction 1 hour, filtered while hot is removed a small amount of insolubles (0.2g), filtrate is cooled to room temperature, use the separating funnel phase-splitting,, under rough vacuum, remove earlier and desolvate and phase-transfer catalyst the organic phase underpressure distillation, then respectively under 107～109 ℃/2.14kPa and 110～121 ℃/2.14kPa condition, collect cut (II) 7.4g and (III) 33.9g.Survey its boiling point and be respectively 221.5～222.5 ℃ (2-amino-3-picoline) and 227.8～229 ℃ (2-amino-5-picoline), with gas-chromatography above-mentioned two cuts are analyzed, its purity is respectively 99.4% and 99.2%, overall yield of reaction is 75.6%, above-mentioned two cuts are carried out ultimate analysis, and the ultimate analysis value of actual measurement and the comparing result of theoretical value are as follows:
Theoretical value: C, 66.67%; H, 7.40%; N, 25.93%
Measured value:
(II)?C，66.64％；H，7.37％；N，25.99％
(III)C，66.60％；H，7.43％；N，25.97％
Embodiment 6
After sodium amide (39.3g) and potassium amide (27.5g) pulverizing, with perhydronaphthalene (100g), decane (40g), N, accelerine (1.0g) and trolamine (0.8g) join in the autoclave of 300ml together, feed nitrogen with air displacement clean after, feed ammonia again to 0.35MPa, slowly be heated to 130 ℃ while stirring, in 1 hour, drip 3-picoline (46.5g), and then feeding nitrogen to stagnation pressure 1.0MPa, constant temperature and pressure reaction about 10 hours is cooled to 60 ℃, be decompressed to normal pressure, material is transferred in the 500ml there-necked flask, under 60 ℃, slowly adds the 176g deionized water, continued stirring reaction 1 hour, filtered while hot, remove a small amount of insolubles (0.25g), filtrate is cooled to room temperature, use the separating funnel phase-splitting, with the organic phase underpressure distillation, under rough vacuum, remove earlier and desolvate and phase-transfer catalyst, then respectively under 107～109 ℃/2.14kPa and 110～121 ℃/2.14kPa condition, collect cut (II) 8.4g and (III) 32.9g.Survey its boiling point and be respectively 221.8～222.7 ℃ (2-amino-3-picoline) and 228～229 ℃ (2-amino-5-picoline), with gas-chromatography above-mentioned two cuts are analyzed, its purity is respectively 99.4% and 99.2%, overall yield of reaction is 75.6%, above-mentioned two cuts are carried out ultimate analysis, and the ultimate analysis value of actual measurement and the comparing result of theoretical value are as follows:
Theoretical value: C, 66.67%; H, 7.40%; N, 25.93%
Measured value:
(II)?C，66.61％；H，7.41％；N，25.98％
(III)C，66.69％；H，7.40％；N，25.91％
Embodiment 7
After sodium amide (19.6g) and potassium amide (27.5g) pulverizing, with perhydronaphthalene (100g), decane (40g), N, accelerine (0.5g) and trolamine (0.2g) join in the autoclave of 300ml together, feed nitrogen with air displacement clean after, feed ammonia again to 0.35MPa, slowly be heated to 165 ℃ while stirring, in 1 hour, drip 3-picoline (46.5g), and then feeding nitrogen to stagnation pressure 5.0MPa, constant temperature and pressure reaction about 10 hours is cooled to 80 ℃, be decompressed to normal pressure, material is transferred in the 500ml there-necked flask, under 60G, slowly adds the 176g deionized water, continued stirring reaction 2 hours, filtered while hot, remove a small amount of insolubles (0.21g), filtrate is cooled to room temperature, use the separating funnel phase-splitting, with the organic phase underpressure distillation, under rough vacuum, remove earlier and desolvate and phase-transfer catalyst, then respectively under 107～109 ℃/2.14kPa and 110～121 ℃/2.14kPa condition, collect cut (II) 9.4g and (III) 30.8g.Survey its boiling point and be respectively 221.8～222.7 ℃ (2-amino-3-picoline) and 228～229 ℃ (2-amino-5-picoline), with gas-chromatography above-mentioned two cuts are analyzed, its purity is respectively 99.4% and 99.2%, overall yield of reaction is 73.9%, above-mentioned two cuts are carried out ultimate analysis, and the ultimate analysis value of actual measurement and the comparing result of theoretical value are as follows:
Theoretical value: C, 66.67%; H, 7.40%; N, 25.93%
Measured value:
(II)?C，66.65％；H，7.38％；N，25.97％
(III)C，66.61％；H，7.40％；N，25.99％。
Claims (10)
1. the preparation method of an aminoderivative of a 3-picoline is characterized in that described preparation method comprises the steps:
(1) be raw material with 3-picoline and alkali-metal amide, at C
7～C
18Aliphatic alkanes and/or C
7～C
18In the aromatic hydrocarbon organic solvent, with C
7～C
9Aromatic amine and/or C
2～C
6Aliphatic hydramine be phase-transfer catalyst, be 110～165 ℃ in temperature, pressure is 0.1～5.0MPa, wherein the ammonia dividing potential drop is that reaction makes the disodium iminodiacetic (I) of 3-picoline under 0～0.5MPa condition;
(2) product (I) that step (1) is made adds entry at 30～80 ℃, and stirring reaction 1～2 hour filters, and with the distillation of gained filtrate decompression, collects cut 2-amino-3-picoline (II) and 2-amino-5-picoline (III) respectively.
2. the preparation method of an aminoderivative of 3-picoline as claimed in claim 1; it is characterized in that described step (1) is: after in reactor, adding alkali-metal amide, organic solvent and phase-transfer catalyst; under nitrogen protection, be warming up to 110～165 ℃; slowly add the 3-picoline; Controlling System stagnation pressure 0.1～5.0MPa; wherein the ammonia dividing potential drop is 0～0.5MPa; stirring reaction 4～10 hours; when treating that coagulating gas invariably emits; stopped reaction, the disodium iminodiacetic (I) of 3-picoline.
3. the preparation method of an aminoderivative of 3-picoline as claimed in claim 1 is characterized in that described alkali-metal amide is sodium amide-potassium amide mixture, and the mol ratio of sodium amide and potassium amide is 1: 0.1～1.0 in the described mixture.
4. the preparation method of an aminoderivative of 3-picoline as claimed in claim 1, it is characterized in that described organic solvent is the mixing of following one or both or two or more arbitrary proportions: heptane, octane, decane, dodecane, toluene, p-Xylol, m-xylene, 2,4,6-trimethylbenzene, dodecylbenzene, naphthane, perhydronaphthalene.
5. the preparation method of an aminoderivative of 3-picoline as claimed in claim 1, it is characterized in that described phase-transfer catalyst is the mixing of following one or both or two or more arbitrary proportions: to monomethylaniline, 3,5-xylidine, N, accelerine, thanomin, diethanolamine, trolamine, butanolamine.
6. as the preparation method of an aminoderivative of the described 3-picoline of one of claim 1～5, it is characterized in that described alkali-metal amide total amount and the 3-picoline amount of substance ratio that feeds intake that feeds intake is 1.1～3.8: 1; The mass ratio that feeds intake of described 3-picoline, organic solvent and phase-transfer catalyst is 1: 1～3.5: 0.001～0.1, and the weight that described step (2) adds entry is 1～4 times of 3-picoline weight.
7. the preparation method of an aminoderivative of 3-picoline as claimed in claim 6, the underpressure distillation step that it is characterized in that described step (2) is as follows: be decompressed to 20KPa earlier and remove organic solvent and phase-transfer catalyst, continue decompression again, under 106～109 ℃/2.01～2.14kPa and 109～121 ℃/2.01～2.14kPa condition, collect cut 2-amino-3-picoline (II) and 2-amino-5-picoline (III) respectively.
8. the preparation method of an aminoderivative of 3-picoline as claimed in claim 6, the total charging capacity that it is characterized in that described alkali-metal amide is 1.2～3.0: 1 with the amount of substance ratio that feeds intake of 3-picoline; The mass ratio that feeds intake of described 3-picoline, organic solvent and phase-transfer catalyst is 1: 1.5～3.0: 0.015～0.04.
9. the preparation method of an aminoderivative of 3-picoline as claimed in claim 1, the temperature of reaction that it is characterized in that described step (1) is 130～155 ℃.
10. the preparation method of an aminoderivative of 3-picoline as claimed in claim 1 is characterized in that described preparation method comprises the steps:
(1) in reactor, add alkali-metal amide, organic solvent and phase-transfer catalyst after, under nitrogen protection, be warming up to 130～155 ℃, slowly add the 3-picoline, Controlling System stagnation pressure 0.1～5.0MPa, ammonia dividing potential drop 0～0.5MPa, stirring reaction 4～10 hours is when treating that coagulating gas invariably emits, stopped reaction, the disodium iminodiacetic (I) of 3-picoline; Described organic solvent is C
7～C
18Aliphatic alkanes and/or C
7～C
18Aromatic hydrocarbon; Described phase-transfer catalyst is C
7～C
9Aromatic amine and/or C
2～C
6Aliphatic hydramine; Total mole dosage of described alkali-metal amide is 1.2～3.0 times of 3-picoline; The mass ratio that feeds intake of described 3-picoline, organic solvent and phase-transfer catalyst is 1: 1.5～3.0: 0.015～0.04;
(2) step (1) products therefrom (I) is cooled to 30～80 ℃ after, slowly add entry under the normal pressure, the add-on of described water is 1～4 times of 3-picoline weight, stirring reaction 1～2 hour, filtered while hot, filtrate decompression is distilled, be decompressed to 20KPa earlier and remove organic solvent and phase-transfer catalyst, continue decompression again, respectively 106～109 ℃/2.01～2.14kPa and 109～121 ℃/2.01～～the 2.14kPa condition under, collect fraction 2-amino-3-picoline (II) and 2-amino-5-picoline (III).
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| CN104447523A (en) * | 2014-11-27 | 2015-03-25 | 安徽星宇化工有限公司 | Method for synthesizing aminopyridine with pyridine base mixture as well as separation and purification method of aminopyridine |
| CN104513195A (en) * | 2014-11-28 | 2015-04-15 | 南京红太阳生物化学有限责任公司 | Aminopyridine isomeride separation method |
| CN104529886A (en) * | 2014-11-29 | 2015-04-22 | 南京红太阳生物化学有限责任公司 | Method for separating mixed aminopyridine through crystallization and rectification coupling technology |
| CN108358834A (en) * | 2018-01-17 | 2018-08-03 | 兰州大学 | A kind of polysubstituted pyridine derivative and preparation method thereof |
| CN114409593A (en) * | 2022-01-20 | 2022-04-29 | 上海泾维化工科技有限公司 | Preparation method of 2-amino-5-methylpyridine |
-
2007
- 2007-08-01 CN CNA200710070432XA patent/CN101108823A/en active Pending
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104447523A (en) * | 2014-11-27 | 2015-03-25 | 安徽星宇化工有限公司 | Method for synthesizing aminopyridine with pyridine base mixture as well as separation and purification method of aminopyridine |
| CN104513195A (en) * | 2014-11-28 | 2015-04-15 | 南京红太阳生物化学有限责任公司 | Aminopyridine isomeride separation method |
| CN104529886A (en) * | 2014-11-29 | 2015-04-22 | 南京红太阳生物化学有限责任公司 | Method for separating mixed aminopyridine through crystallization and rectification coupling technology |
| CN108358834A (en) * | 2018-01-17 | 2018-08-03 | 兰州大学 | A kind of polysubstituted pyridine derivative and preparation method thereof |
| CN114409593A (en) * | 2022-01-20 | 2022-04-29 | 上海泾维化工科技有限公司 | Preparation method of 2-amino-5-methylpyridine |
| CN114409593B (en) * | 2022-01-20 | 2024-02-23 | 上海泾维化工科技有限公司 | Preparation method of 2-amino-5-methylpyridine |
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