CN105198800B - A kind of preparation method of the picoline of 2,3 dichloro of pesticide intermediate 5 - Google Patents
A kind of preparation method of the picoline of 2,3 dichloro of pesticide intermediate 5 Download PDFInfo
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- CN105198800B CN105198800B CN201410295228.8A CN201410295228A CN105198800B CN 105198800 B CN105198800 B CN 105198800B CN 201410295228 A CN201410295228 A CN 201410295228A CN 105198800 B CN105198800 B CN 105198800B
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Abstract
The invention belongs to the technical field of organic chemical industry, it is related to the important intermediate 2 of halogen pyridines organic compound, the preparation method of the picoline of 3 dichloro 5, more specifically, it is related to one kind with (1H) ketone of 5 methyl, 3,4 dihydropyridine 2 and chlorine for initiation material, has catalyzed and synthesized 2, the picoline of 3 dichloro 5, total recovery are stable more than 75%.The features of the present invention employs lewis acid and ligand combination as catalyst system and catalyzing so that reaction is with higher selectivity, production cost is low, equipment investment is few and production environment safety and environmental protection.
Description
Technical field
The invention belongs to the technical field of organic chemical industry, it is related to the important intermediate 2,3- of halogen pyridines organic compound
The preparation method of two chloro-5-methypyridines, more particularly, to one kind with the (letter of 5- methyl -3,4- dihydropyridine -2 (1H) -one
Claim：Pyridone) and chlorine be initiation material, catalyzed and synthesized the chloro-5-methypyridines of 2,3- bis-, total recovery it is stable 75% with
On.The features of the present invention employs lewis acid and ligand combination as catalyst system and catalyzing so that reaction with higher selectivity,
Production cost is low, equipment investment is few and production environment safety and environmental protection.
Background technology
Raw material pyridone, it is to be prepared with the propionic aldehyde morpholine method technique described in US4612377 patents, specifically synthesizes road
Line is described as follows：Propionic aldehyde and morpholine are prepared for morpholinyl methacrylaldehyde under alkaline matter catalysis, through Pintsch process, then with acrylic acid
Methyl esters reaction has synthesized ester intermediate, is then reacted with ammonium acetate, pyridone is prepared.
2,3- bis- chloro-5-methypyridines are a kind of organic intermediates for having very much application value, can further be fluorinated system
It is standby to obtain the chloro-5-trifluoromethylpyridines of 2,3- bis-, it is widely used to the fields such as agricultural chemicals, medicine, fine chemistry industry.
The chloro-5-trifluoromethylpyridines of 2,3- bis- are that efficient pesticides pyridine worm is grand, highy potent herbicide pyrrole for production in terms of agricultural chemicals
The key intermediate of the kind such as the spirit of fluorine chlorine standing grain and efficient germicide fluazinam.Above-mentioned three big kind has evolved into international market
Key product, have an extensive market prospects, but a domestic Recent Progresses In The Development to above-mentioned kind and unhappy, wherein, the fluorine of high quality
Change raw material 2, the preparation of the chloro-5-methypyridines of 3- bis-, turn into the major technology bottleneck in the field.
At present, the document of the open report synthesis chloro-5-methypyridines of 2,3- bis- is less, Pews R.G (Pews R.G,
Lysenko Z.Synthesis of halogenated pyridine[J].Org.Chem,1985,50(25):5115-
5119) chloro-5-methypyridines of 2,3- bis-, but two chloroacetonitriles in reaction have directly been synthesized using two chloroacetonitriles and methacrolein cyclisation
Conversion ratio there was only 60% or so, the utilization rate of raw material is low, and production cost is high.Although in without catalyst chlorination process, pyridine
Ketone can also generate a small amount of chloro-5-methypyridines of 2,3- bis-, but yield is but less than 20%.
Therefore, patent of the present invention creatively employs lewis acid and part using pyridone and chlorine as initiation material
Combination catalyst system and catalyzing, be prepared for important intermediate 2, the chloro-5-methypyridines of 3- bis-, there is following advantage：
(1) combination catalyst of lewis acid and part, there is preferable solubility in system, compared to without ligand system,
The reaction selectivity of the chloro-5-methypyridines of 2,3- bis- can be increased substantially, its highest proportion can reach 85%；
(2) POCl3 and solvent of recovery, can directly be applied mechanically, greatly save cost；
(3) synthesis technique of a chloro-5-methypyridine of 2,3- bis- is proposed, with cost is low, product purity is high into producing
The advantages that.
The content of the invention
The invention belongs to the technical field of organic chemical industry, it is related to the important intermediate 2,3- of halogen pyridines organic compound
The preparation method of two chloro-5-methypyridines, more particularly, to one kind using pyridone and chlorine as initiation material, catalyze and synthesize
2,3- bis- chloro-5-methypyridines, total recovery are stable more than 75%.The features of the present invention employs lewis acid and part is made
For catalyst system and catalyzing so that reaction has selectivity height, production cost is low, equipment investment is few.
The preparation method of one kind chloro-5-methypyridines of 2,3- bis-, comprises the following steps：
(1) solvent and pyridone are added in reactor, 10~50 DEG C of controlling reaction temperature, then passes to chlorine, reacted
Pyridone chlorine addition product is made；
(2) by lewis acid and ligand combination thing, it is added in pyridone chlorine addition product, is warming up to 10~100 DEG C, continues
Chlorine is passed through into reaction solution；
(3) by POCl3 and above-mentioned reaction solution, in 10~50 DEG C of temperature ranges, after being sufficiently mixed, then it is added drop-wise to
It is preinstalled with the reactor of solvent, 80~200 DEG C of 2~10h of reaction；
(4) after back flow reaction terminates, by the way of distillation, POCl3 and solvent are reclaimed, then high vacuum rectification, received
Collect the chloro-5-methypyridine products of 2,3- bis-；
(5) the recovery POCl3 to step (4) and the solvent recycled directly in step (3).
In above-mentioned steps (1), the organic media is chlorobenzene, dichloroethanes, o-dichlorohenzene, dimethylbenzene, toluene etc., and it is used
Measure as 3~7 times of pyridone weight.
In above-mentioned steps (2), the lewis acid is iron chloride, aluminium chloride, titanium tetrachloride, zinc chloride, boron chloride, five
Niobium chloride, Antimony pentachloride, stannic chloride, copper chloride, phosphotungstic acid, p-methyl benzenesulfonic acid, benzene sulfonic acid, hydrogen chloride etc. or its mixture, its
Dosage is 0.05~0.4 times of pyridone molal quantity.
In above-mentioned steps (2), the part is N, N, N', N, ' N "-five methyl diethylentriamine (PMDETA), second two
Amine tetraacethyl (EDTA), imidazoles, 2,2 '-bipyridyl, pyrazine, glycine, ethylenediamine, 8-hydroxyquinoline, N, N'- dimethyl second two
Amine (DMEDA), tetramethylethylenediamine (TMEDA) etc., its dosage are 0.1~3 times of pyridone molal quantity.
In above-mentioned steps (3), the POCl3 dosage is 1~5 times of pyridone weight.
A kind of the shortcomings that present invention is solved in the presence of existing synthetic method, it is proposed that easy to operate, reaction selectivity
High preparation method, it possesses advantages below：(1) the raw material pyridone of the chloro-5-methypyridines of 2,3- bis- is prepared, is domestic morpholine
The large chemical products of propionic aldehyde method manufacturer, steady sources, reliable in quality；(2) using lewis acid and the assembly of part
System is used as catalyst, is effectively increased the conversion ratio of pyridone, improves the selectivity of the chloro-5-methypyridines of 2,3- bis-, significantly
Ground improves reaction production capacity, meanwhile, it is easy to rectification and purification to obtain the product of high-purity；(3) it is the preparation chloro- 5- fluoroforms of 2,3- bis-
Yl pyridines provide the raw material of high quality, eliminate the closed loop in document report or the multiple troublesome operation work such as chlorination and fluorination
Skill, have the advantages that production cost is low, equipment investment is few；
Embodiment
The following examples are illustrated the present invention in more detail, rather than limitation of the invention further.Unless
It is otherwise noted, " % " therein is " quality % ".
Embodiment 1
500mL four-hole boiling flasks, 50.20g pyridones, 150.00g chlorobenzenes are added, temperature control is at 20 DEG C or so, then
20L/hr is passed through chlorine, after reacting 0.5 hour, can obtain 232.60g pyridone chlorine addition solution.
Embodiment 2
The pyridone chlorine addition liquid obtained using embodiment 1 adds 8.10g ferric trichlorides and 20.23gN, N, N' as raw material,
N, ' N "-five methyl diethylentriamine (PMDETA) parts as catalyst, control temperature continues 20L/hr and is passed through at 20 DEG C
Chlorine 0.5h.
Embodiment 3
In 500ml four-hole boiling flask, 100.52g chlorination benzene solvents are pre-installed, backflow are warming up to, then by embodiment 2
After reaction solution mixes with POCl3, it is added dropwise in four-hole boiling flask, is added dropwise, 120 DEG C of insulation reaction 4h, it is anti-obtains dark brown
Liquid, air-distillation recovery POCl3 and Benzene Chloride are answered, then, rectification under vacuum, obtains 54.67g2, the chloro- 5- methyl pyrroles of 3- bis-
Pyridine.
Gas spectrum normalizing content is 99.50%, and outward appearance is water white transparency solid, and 2,3- bis- chloro-5-methypyridines are to pyridone
Yield is 75%.
Embodiment 4-6
On the basis of embodiment 2, change the dosage of ferric trichloride, other conditions are constant.Acquired results are as shown in table 1.
Influence of the ferric trichloride dosage of table 1 to the chloro-5-methypyridine yields of 2,3- bis-
Embodiment 7-10
On the basis of embodiment 2, fixed ferric trichloride weight is 8.10g and is 20.00g with weight, changes part
Species, other conditions are constant.Acquired results are as shown in table 2.
Influence of the different ligands of table 2 to the chloro-5-methypyridine yields of 2,3- bis-
Embodiment 11-13
On the basis of embodiment 3, the POCl3 acidity chlorobenzene liquid of recovery is applied mechanically, wherein POCl3 is added to reaction
Required weight, other conditions are constant.Acquired results are as shown in table 3.
The difference of table 3 applies mechanically influence of the number to the chloro-5-methypyridine yields of 2,3- bis-
Claims (8)
1. one kind 2, the preparation method of the chloro-5-methypyridines of 3- bis-, it is characterised in that comprise the following steps：
(1) solvent and 5- methyl -3,4- dihydropyridine -2 (1H) -one are added in reactor, controlling reaction temperature is 10~50
DEG C, chlorine is then passed to, (1H) -one chlorine addition product of 5- methyl -3,4- dihydropyridine -2 is made in 0.3~3h of reaction；
(2) by lewis acid and ligand combination thing, it is added in 5- methyl -3,4- dihydropyridine -2 (1H) -one chlorine addition product, rises
Temperature continues to be passed through chlorine into reaction solution to preset temperature；
(3) after being sufficiently mixed POCl3 and above-mentioned reaction solution, then it is added drop-wise in the reactor for being preinstalled with solvent, backflow is anti-
Should；
(4) after back flow reaction terminates, by the way of distillation, POCl3 and solvent are reclaimed, then high vacuum rectification, collect 2,
The chloro-5-methypyridine products of 3- bis-；
(5) the recovery POCl3 to step (4) and the solvent recycled directly in step (3)；
In above-mentioned steps (2), the lewis acid is iron chloride, aluminium chloride, titanium tetrachloride, zinc chloride, boron chloride, phosphoric
Niobium, Antimony pentachloride, stannic chloride, copper chloride, phosphotungstic acid, p-methyl benzenesulfonic acid, benzene sulfonic acid, hydrogen chloride or its a variety of mixture, it is used
Measure as 0.05~0.4 times of (1H) the -one molal quantity of 5- methyl -3,4- dihydropyridines -2；The part is N, N, N', N, ' N "-five
Methyl diethylenetriamines (PMDETA), ethylenediamine tetra-acetic acid (EDTA), imidazoles, 2,2 '-bipyridyl, pyrazine, glycine, second two
Amine, 8-hydroxyquinoline, N, N'- dimethyl-ethylenediamines (DMEDA), tetramethylethylenediamine (TMEDA) or its a variety of mixture, it is used
Measure as 0.1~3 times of (1H) the -one molal quantity of 5- methyl -3,4- dihydropyridines -2.
2. the preparation method of the chloro-5-methypyridines of 2,3- bis- according to claim 1, it is characterised in that above-mentioned steps (1)
In, the solvent is chlorobenzene, dichloroethanes, o-dichlorohenzene, dimethylbenzene, toluene, and its dosage is 5- methyl -3,4- dihydropyridine -2
3~7 times of (1H) -one weight.
3. the preparation method of the chloro-5-methypyridines of 2,3- bis- according to claim 1, it is characterised in that above-mentioned steps (2)
In, the reaction temperature is 10~100 DEG C, and it is 1~3h to lead to the chlorine reaction time.
4. the preparation method of the chloro-5-methypyridines of 2,3- bis- according to claim 1, it is characterised in that above-mentioned steps (3)
In, the mixing temperature is 10~50 DEG C, and the reaction time is 0.2~1.5h.
5. the preparation method of the chloro-5-methypyridines of 2,3- bis- according to claim 1, it is characterised in that above-mentioned steps (3)
In, the back flow reaction temperature is 80~200 DEG C, and the reaction time is 2~8h.
6. the preparation method of the chloro-5-methypyridines of 2,3- bis- according to claim 1, it is characterised in that above-mentioned steps (3)
In, the POCl3 dosage is 1~5 times of 5- methyl -3,4- dihydropyridine -2 (1H) -one weight.
A kind of 7. preparation method of the chloro-5-methypyridines of 2,3- bis- according to claim 1, it is characterised in that 500mL tetra-
Mouthful flask adds (1H) -one of 50.20g 5- methyl -3,4- dihydropyridine -2,150.00g chlorobenzenes, temperature control at 20 DEG C or so,
Then 20L/hr is passed through chlorine, after reacting 0.5 hour, can obtain 232.60g5- methyl -3,4- dihydropyridine -2 (1H) -one chlorine
Addition solution, it is raw material by obtained 5- methyl -3,4- dihydropyridine -2 (1H) -one chlorine addition liquid, adds 8.10g ferric trichlorides
And 20.23gN, N, N', N, ' N "-five methyl diethylentriamine (PMDETA) parts as catalyst, control temperature at 20 DEG C,
Continue 20L/hr and be passed through chlorine 0.5h, in 500ml four-hole boiling flask, pre-install 100.52g chlorination benzene solvents, be warming up to backflow,
Then by reaction solution mixed with POCl3 after, be added dropwise in four-hole boiling flask, be added dropwise, 120 DEG C of insulation reaction 4h, obtain
Dark brown reaction solution, air-distillation recovery POCl3 and Benzene Chloride, then, rectification under vacuum, obtain 54.67g2, bis- chloro- 5- of 3-
Picoline.
A kind of 8. preparation method of the chloro-5-methypyridines of 2,3- bis- according to claim 7, it is characterised in that tri-chlorination
The dosage of iron is 15.32g.
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| CN201410295228.8A CN105198800B (en) | 2014-06-25 | 2014-06-25 | A kind of preparation method of the picoline of 2,3 dichloro of pesticide intermediate 5 |
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| CN105198800B true CN105198800B (en) | 2018-02-16 |
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| CN110078660B (en) * | 2019-05-16 | 2021-01-01 | 江苏扬农化工集团有限公司 | Preparation method of 2-chloro-5-methylpyridine |
| CN111333568B (en) * | 2020-04-16 | 2021-10-26 | 江苏扬农化工集团有限公司 | Selective synthesis method of 2-chloro-5-methylpyridine and 2, 3-dichloro-5-methylpyridine |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4420618A (en) * | 1980-03-07 | 1983-12-13 | Ishihara Sangyo Kaisha Ltd. | Process for producing 5-chloro-β-trifluoromethylpyridines |
| CN102058918A (en) * | 2000-02-10 | 2011-05-18 | 株式会社根本杏林堂 | Syringe tube and cylinder holder, syringe piston and piston holder and syringe |
| CN102757383A (en) * | 2012-07-11 | 2012-10-31 | 江苏扬农化工集团有限公司 | Industrial production method for preparing 2-chloro-5-picoline |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0512436A1 (en) * | 1991-05-02 | 1992-11-11 | Ishihara Sangyo Kaisha, Ltd. | Method for producing substituted pyridine derivatives |
| CN103508942B (en) * | 2013-08-08 | 2015-09-23 | 浙江工业大学 | A kind of synthetic method of 2,3-bis-chloro-5-methypyridine |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4420618A (en) * | 1980-03-07 | 1983-12-13 | Ishihara Sangyo Kaisha Ltd. | Process for producing 5-chloro-β-trifluoromethylpyridines |
| CN102058918A (en) * | 2000-02-10 | 2011-05-18 | 株式会社根本杏林堂 | Syringe tube and cylinder holder, syringe piston and piston holder and syringe |
| CN102757383A (en) * | 2012-07-11 | 2012-10-31 | 江苏扬农化工集团有限公司 | Industrial production method for preparing 2-chloro-5-picoline |
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