CN102977008A - Synthetic method of 2-chloro-5-methylpyridine - Google Patents
Synthetic method of 2-chloro-5-methylpyridine Download PDFInfo
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- CN102977008A CN102977008A CN2012104432448A CN201210443244A CN102977008A CN 102977008 A CN102977008 A CN 102977008A CN 2012104432448 A CN2012104432448 A CN 2012104432448A CN 201210443244 A CN201210443244 A CN 201210443244A CN 102977008 A CN102977008 A CN 102977008A
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Abstract
The present invention discloses a synthetic method of 2-chloro-5-methylpyridine, comprising the following steps: diluting a raw material of a 3-methylpyridin oxide with a solvent, reacting with an electrophilic reagent and an organic nitrogen base under -60-100 DEG C to obtain an intermediate product, and then reacting with a chlorinating agent under the conditions of 40-200 DEG C to get the compound of 2-chloro-5-methylpyridine. The synthetic method is simple in production process, and high in yield. The yield can reach about 80% through calculating the 3-methylpyridin oxide.
Description
Technical field
The invention belongs to technical field of pesticide, be specifically related to a kind of preparation method of CMP compound.
Background technology
CMP is a kind of important " three medicines " intermediate, can be used for the anabasine insecticides such as imidacloprid synthesis, pyrrole worm be clear, the advantage such as this insecticides has interior suction, wide spectrum, colleges and universities, low toxicity, consumption is few, the cycle that continues is long, security good, resistance is strong.In addition, CMP is also for the synthesis of weedicides such as fluazifop, haloxyfops.
The synthetic route of CMP is mainly the cyclisation method, diazotization method, 3-picoline oxidation style, an one-step chlorination method etc.Wherein cyclisation method reactions steps is longer, and productive rate is low, and raw material is various, and production cost is higher; Diazotization method processing requirement is strict, and is seriously polluted, and production cost is higher; One one-step chlorination method exist the catalyzer cost high, reclaim difficulty, the characteristics such as can not recycle.
3-picoline oxidation style is simple to operate, investment cost is low, process is easy to control, production cost is lower, is the production line that China most manufacturer adopts, and the subject matter of this route is to select suitable chlorizating agent, reduce the isomer by product, improve the yield of major product.
At present, many chlorizating agents have been developed use, and select suitable multiple electrophilic reagent and chlorizating agent to use with, can act synergistically, and then improve chlorination yield, and this path has no report.
Summary of the invention
The purpose of this invention is to provide a kind of preparation method of CMP compound, and overcome yield problem on the low side in the existing synthetic technology.
The present invention adopts following technical scheme to achieve these goals:
The preparation method of CMP (I) compound comprises the steps:
（Ⅰ）
(1) first formula II compound 3-oxide of mathylpyridine is joined in the thinner, after the cooling, drip at a slow speed first electrophilic reagent, then be organic nitrogen(ous) base, adding fashionablely should have stirring, and 3-oxide of mathylpyridine and electrophilic reagent and organic nitrogen(ous) base are with the ratio reaction of mol ratio 1:1.5-5:1.5-5, thinner and electrophilic reagent mol ratio are 1:1-10, under-60-100 ℃ condition, react, obtain the formula III compound
（Ⅱ） （Ⅲ）
In the formula III, X represents the electrophilic reagent of dechlorination or the corresponding group of decarboxylation;
(2) with formula III compound and chlorizating agent the ratio take mol ratio as 1:0.1-20 as reactant, take thinner or in addition excessive chlorizating agent as solvent, at normal pressure or high pressure, react under the 40-200 ℃ of condition, obtain formula I compound CMP.
Described electrophilic reagent is one or more in acyl chlorides, acid anhydrides, phosphorus oxidation compound, phosphoryl chloride or the cyanato-chlorine.
Described electrophilic reagent is Acetyl Chloride 98Min., propionyl chloride, trichoroacetic chloride, diacetyl oxide, propionic anhydride, Benzoyl chloride, benzene sulfonyl chloride, C
1-C
4In alkyl substituted benzene SULPHURYL CHLORIDE, phosphorus trichloride, phosphorus pentachloride, sulfurous acid, cyanuryl chloride or the sulfuryl chloride one or more.
Described electrophilic reagent is the complex reagent that phosphorus oxychloride forms take mol ratio as 1:0.1-2 with electrophilic reagents such as Benzoyl chloride, phosphorus pentachloride, phosphorus trichloride and phthalyl chlorides respectively.
Described organic nitrogen(ous) base is three (C
1-C
4Alkyl) amine, N, N-two (C
1-C
4Alkyl) benzylamine, N, N-two (C
1-C
4Alkyl) amine, N, N-two (C
1-C
4Alkyl) hexahydroaniline, C1-C4 alkyl replace or without in the pyridine that replaces one or more.
Described organic nitrogen(ous) base is Trimethylamine 99, triethylamine, tripropyl amine, Tributylamine, Diisopropylamine, N, N-dimethyl benzylamine, N, N-diethyl benzylamine, pyridine or C
1-C
4In the alkyl substituted pyridines one or more.
Described chlorizating agent is one or more in phosphorus trichloride, phosphorus oxychloride, phosphorus pentachloride, thionyl chloride, sulfuryl chloride, cyanuryl chloride, phosgene, trichloromethylchloroformate or the solid phosgene.
Described chlorizating agent is the complex reagent that phosphorus oxychloride forms take mol ratio as 1:0.1-2 with electrophilic reagents such as Benzoyl chloride, phosphorus pentachloride, phosphorus trichloride and phthalyl chlorides respectively.
Described thinner is aliphatics or aromatic series halohydrocarbon.
Described thinner is one or more in methylene dichloride, ethylene dichloride, chloroform, tetracol phenixin, chlorobenzene or the dichlorobenzene.
The preparation method of CMP compound, the preferable reaction temperature of step (1) be-40-10 ℃, and preferred diluent is methylene dichloride, 3-oxide of mathylpyridine and electrophilic reagent and organic nitrogen(ous) base are with the ratio reaction of mol ratio 1:1.5-5:1.5-5; The preferable reaction temperature of step (2) is 100-140 ℃, and preferred diluent is chlorobenzene, the ratio reaction take mol ratio as 1:0.2-5 of formula III compound and chlorizating agent.
The formula III compound can be separated from reaction system with intermediate forms among the present invention, also can not separate, and directly carries out next step chlorination reaction.Optimal way is that this rough intermediate is directly used in the second step reaction.
Can obtain the formula I compound CMP of higher yields according to the present invention, therefore, represent the valuable improvement of prior art according to the inventive method.
If use phosphorus oxychloride and phosphorus pentachloride compound system as the chlorizating agent of electrophilic reagent and second step, take Diisopropylamine as organic nitrogen(ous) base, then reaction equation can be as shown in the formula expression:
Using with of multiple electrophilic reagent and chlorizating agent acts synergistically, and then improves chlorination yield, is the novel method that consists of theme of the present invention.
Beneficial effect of the present invention:
Production technique of the present invention is convenient, and yield is high, can reach about 80% with 3-oxide of mathylpyridine calculated yield.
Embodiment
For a better understanding of the present invention, describe by following instance:
Embodiment 1:
With 50g, 0.4587mol the 3-oxide of mathylpyridine joins in the 600g methylene dichloride, the mixture cooling down slowly drips 82.05g to-30 ℃, 0.5351mol phosphorus oxychloride, 37.61g, 0.2676mol Benzoyl chloride and 92.65g, 0.9174mol Diisopropylamine, after dropwising, in stirring at room 1 hour, suction filtration, methylene dichloride is removed in distillation.Add the 500mL chlorobenzene, slowly drip 27.97g, 0.1824mol phosphorus oxychloride and 12.82g, the 0.0912mol Benzoyl chloride is warming up to back flow reaction, and the time is 9h altogether.Hydrolysis after reaction finishes, the liquid caustic soda neutralization, steam distillation obtains the formula I compound, yield 75.2%.
Embodiment 2:
With 50g, 0.4587mol the 3-oxide of mathylpyridine joins in the 600g methylene dichloride, the mixture cooling down slowly drips 102.56g to-30 ℃, 0.6689mol phosphorus oxychloride, 27.85g, 0.1338mol phosphorus pentachloride (phosphorus pentachloride is dissolved in the 60 g methylene dichloride) and 92.65g, 0.9174mol Diisopropylamine, after dropwising, in stirring at room 1 hour, suction filtration, methylene dichloride is removed in distillation.Add the 500mL chlorobenzene, slowly drip 34.86g, 0.2271mol phosphorus oxychloride and 9.51g, 0.0456mol phosphorus pentachloride (phosphorus pentachloride is dissolved in the 20 g chlorobenzenes) is warming up to back flow reaction, and the time is 9h altogether.Hydrolysis after reaction finishes, the liquid caustic soda neutralization, steam distillation obtains the formula I compound, yield 80.3%.
Embodiment 3:
With 50g, 0.4587mol the 3-oxide of mathylpyridine joins in the 600g methylene dichloride, the mixture cooling down slowly drips 63.34g to-30 ℃, 0.4460mol phosphorus oxychloride, 48.76g, 0.3567 phosphorus trichloride and 92.65g, 0.9174mol Diisopropylamine, after dropwising, in stirring at room 1 hour, suction filtration, methylene dichloride is removed in distillation.Add the 500mL chlorobenzene, slowly drip 23.34g, 0.1520mol phosphorus oxychloride and 16.72g, the 0.1216mol phosphorus trichloride is warming up to back flow reaction, and the time is 9h altogether.Hydrolysis after reaction finishes, the liquid caustic soda neutralization, steam distillation obtains the formula I compound, yield 78.2%.
Embodiment 4:
With 50g, 0.4587mol the 3-oxide of mathylpyridine joins in the 600g methylene dichloride, the mixture cooling down slowly drips 87.86g to-30 ℃, 0.5734mol phosphorus oxychloride, 46.53g, 0.2293 phthalyl chloride and 92.65g, 0.9174mol Diisopropylamine, after dropwising, in stirring at room 1 hour, suction filtration, methylene dichloride is removed in distillation.Add the 500mL chlorobenzene, slowly drip 30.00g, 0.1954mol phosphorus oxychloride and 15.89g, the 0.0782mol phthalyl chloride is warming up to back flow reaction, and the time is 9h altogether.Hydrolysis after reaction finishes, the liquid caustic soda neutralization, steam distillation obtains the formula I compound, yield 76.7%.
Claims (10)
1. the preparation method of a CMP (I) compound is characterized in that comprising the steps:
（Ⅰ）
(1) first formula II compound 3-oxide of mathylpyridine is joined in the thinner, after the cooling, drip at a slow speed first electrophilic reagent, then be organic nitrogen(ous) base, adding fashionablely should have stirring, and 3-oxide of mathylpyridine and electrophilic reagent and organic nitrogen(ous) base are with the ratio reaction of mol ratio 1:1.5-5:1.5-5, thinner and electrophilic reagent mol ratio are 1:1-10, under-60-100 ℃ condition, react, obtain the formula III compound
（Ⅱ） （Ⅲ）
In the formula III, X represents the electrophilic reagent of dechlorination or the corresponding group of decarboxylation;
(2) with formula III compound and chlorizating agent the ratio take mol ratio as 1:0.1-20 as reactant, take thinner or in addition excessive chlorizating agent as solvent, at normal pressure or high pressure, react under the 40-200 ℃ of condition, obtain formula I compound CMP.
2. the preparation method of CMP compound according to claim 1, it is characterized in that: described electrophilic reagent is one or more in acyl chlorides, acid anhydrides, phosphorus oxidation compound, phosphoryl chloride or the cyanato-chlorine.
3. the preparation method of CMP compound according to claim 2, it is characterized in that: described electrophilic reagent is Acetyl Chloride 98Min., propionyl chloride, trichoroacetic chloride, diacetyl oxide, propionic anhydride, Benzoyl chloride, benzene sulfonyl chloride, C
1-C
4In alkyl substituted benzene SULPHURYL CHLORIDE, phosphorus trichloride, phosphorus pentachloride, sulfurous acid, cyanuryl chloride or the sulfuryl chloride one or more.
4. the preparation method of CMP compound according to claim 3 is characterized in that: described electrophilic reagent is the complex reagent that phosphorus oxychloride forms take mol ratio as 1:0.1-2 with one of electrophilic reagents such as Benzoyl chloride, phosphorus pentachloride, phosphorus trichloride and phthalyl chloride respectively.
5. the preparation method of CMP compound according to claim 1, it is characterized in that: described organic nitrogen(ous) base is three (C
1-C
4Alkyl) amine, N, N-two (C
1-C
4Alkyl) benzylamine, N, N-two (C
1-C
4Alkyl) amine, N, N-two (C
1-C
4Alkyl) hexahydroaniline, C1-C4 alkyl replace or without in the pyridine that replaces one or more.
6. the preparation method of CMP compound according to claim 5, it is characterized in that: described organic nitrogen(ous) base is Trimethylamine 99, triethylamine, tripropyl amine, Tributylamine, Diisopropylamine, N, N-dimethyl benzylamine, N, N-diethyl benzylamine, pyridine or C
1-C
4In the alkyl substituted pyridines one or more.
7. the preparation method of CMP compound according to claim 1, it is characterized in that: described chlorizating agent is one or more in phosphorus trichloride, phosphorus oxychloride, phosphorus pentachloride, thionyl chloride, sulfuryl chloride, cyanuryl chloride, phosgene, trichloromethylchloroformate or the solid phosgene.
8. the preparation method of CMP compound according to claim 7 is characterized in that: described chlorizating agent is the complex reagent that phosphorus oxychloride forms take mol ratio as 1:0.1-2 with electrophilic reagents such as Benzoyl chloride, phosphorus pentachloride, phosphorus trichloride and phthalyl chlorides respectively.
9. the preparation method of CMP compound according to claim 9, it is characterized in that: described thinner is one or more in methylene dichloride, ethylene dichloride, chloroform, tetracol phenixin, chlorobenzene or the dichlorobenzene.
10. the preparation method of CMP compound according to claim 1, it is characterized in that: the preferable reaction temperature of described step (1) is-40-10 ℃, preferred diluent is methylene dichloride, the preferable reaction temperature of step (2) is 100-140 ℃, preferred diluent is chlorobenzene, the ratio reaction take mol ratio as 1:0.2-5 of formula III compound and chlorizating agent.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104030976A (en) * | 2014-04-29 | 2014-09-10 | 安徽国星生物化学有限公司 | Preparation method of 2-chloro-5-methylpyridine compound |
| CN107721912A (en) * | 2017-11-17 | 2018-02-23 | 南京红太阳生物化学有限责任公司 | A kind of preparation method of the picoline of 2 chlorine 5 |
| CN115010657A (en) * | 2022-07-18 | 2022-09-06 | 江苏瑞祥化工有限公司 | Method for preparing 2-chloro-5-methylpyridine by continuous flow |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1075476A (en) * | 1992-02-19 | 1993-08-25 | 拜尔公司 | The preparation method of 2-chloro-5-picoline |
| CN101260076A (en) * | 2007-03-08 | 2008-09-10 | 南京第一农药集团有限公司 | Method for preparing 2-chloro-5-methylpyridine |
| CN102219732A (en) * | 2011-04-22 | 2011-10-19 | 安徽国星生物化学有限公司 | Preparation method for 2-chlorine-5-methylpyridine compound |
-
2012
- 2012-11-08 CN CN2012104432448A patent/CN102977008A/en active Pending
Patent Citations (3)
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|---|---|---|---|---|
| CN1075476A (en) * | 1992-02-19 | 1993-08-25 | 拜尔公司 | The preparation method of 2-chloro-5-picoline |
| CN101260076A (en) * | 2007-03-08 | 2008-09-10 | 南京第一农药集团有限公司 | Method for preparing 2-chloro-5-methylpyridine |
| CN102219732A (en) * | 2011-04-22 | 2011-10-19 | 安徽国星生物化学有限公司 | Preparation method for 2-chlorine-5-methylpyridine compound |
Non-Patent Citations (1)
| Title |
|---|
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104030976A (en) * | 2014-04-29 | 2014-09-10 | 安徽国星生物化学有限公司 | Preparation method of 2-chloro-5-methylpyridine compound |
| CN107721912A (en) * | 2017-11-17 | 2018-02-23 | 南京红太阳生物化学有限责任公司 | A kind of preparation method of the picoline of 2 chlorine 5 |
| CN107721912B (en) * | 2017-11-17 | 2020-10-30 | 南京红太阳生物化学有限责任公司 | Preparation method of 2-chloro-5-methylpyridine |
| CN115010657A (en) * | 2022-07-18 | 2022-09-06 | 江苏瑞祥化工有限公司 | Method for preparing 2-chloro-5-methylpyridine by continuous flow |
| CN115010657B (en) * | 2022-07-18 | 2024-01-23 | 江苏瑞祥化工有限公司 | Method for preparing 2-chloro-5-methylpyridine through continuous flow |
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Application publication date: 20130320 |