CN115057844A - Preparation method of chlorantraniliprole - Google Patents
Preparation method of chlorantraniliprole Download PDFInfo
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- CN115057844A CN115057844A CN202210796334.9A CN202210796334A CN115057844A CN 115057844 A CN115057844 A CN 115057844A CN 202210796334 A CN202210796334 A CN 202210796334A CN 115057844 A CN115057844 A CN 115057844A
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- chloro
- pyrazole
- bromo
- pyridyl
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- 239000005886 Chlorantraniliprole Substances 0.000 title claims abstract description 52
- PSOVNZZNOMJUBI-UHFFFAOYSA-N chlorantraniliprole Chemical compound CNC(=O)C1=CC(Cl)=CC(C)=C1NC(=O)C1=CC(Br)=NN1C1=NC=CC=C1Cl PSOVNZZNOMJUBI-UHFFFAOYSA-N 0.000 title claims abstract description 52
- 238000002360 preparation method Methods 0.000 title claims abstract description 17
- -1 3-chloro-2-pyridyl Chemical group 0.000 claims abstract description 60
- WOBVZGBINMTNKL-UHFFFAOYSA-N 2-amino-5-chloro-n,3-dimethylbenzamide Chemical compound CNC(=O)C1=CC(Cl)=CC(C)=C1N WOBVZGBINMTNKL-UHFFFAOYSA-N 0.000 claims abstract description 28
- 125000002252 acyl group Chemical group 0.000 claims abstract description 24
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 20
- 238000000034 method Methods 0.000 claims abstract description 19
- 230000031709 bromination Effects 0.000 claims abstract 2
- 238000005893 bromination reaction Methods 0.000 claims abstract 2
- 238000006243 chemical reaction Methods 0.000 claims description 83
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 54
- 239000002904 solvent Substances 0.000 claims description 42
- CKWPCHVZHFJDDA-UHFFFAOYSA-N 5-bromo-2-(3-chloropyridin-2-yl)-3,4-dihydropyrazole-3-carboxylic acid Chemical compound OC(=O)C1CC(Br)=NN1C1=NC=CC=C1Cl CKWPCHVZHFJDDA-UHFFFAOYSA-N 0.000 claims description 37
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 25
- 238000004321 preservation Methods 0.000 claims description 17
- 230000035484 reaction time Effects 0.000 claims description 13
- 238000009835 boiling Methods 0.000 claims description 8
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims description 8
- HFRXJVQOXRXOPP-UHFFFAOYSA-N thionyl bromide Chemical compound BrS(Br)=O HFRXJVQOXRXOPP-UHFFFAOYSA-N 0.000 claims description 7
- 238000001816 cooling Methods 0.000 claims description 6
- 238000001035 drying Methods 0.000 claims description 6
- 238000001914 filtration Methods 0.000 claims description 6
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims description 4
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 4
- 239000008096 xylene Substances 0.000 claims description 4
- OGFAWKRXZLGJSK-UHFFFAOYSA-N 1-(2,4-dihydroxyphenyl)-2-(4-nitrophenyl)ethanone Chemical compound OC1=CC(O)=CC=C1C(=O)CC1=CC=C([N+]([O-])=O)C=C1 OGFAWKRXZLGJSK-UHFFFAOYSA-N 0.000 claims description 3
- PHSPJQZRQAJPPF-UHFFFAOYSA-N N-alpha-Methylhistamine Chemical compound CNCCC1=CN=CN1 PHSPJQZRQAJPPF-UHFFFAOYSA-N 0.000 claims description 3
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 2
- 238000001704 evaporation Methods 0.000 claims 1
- 239000012535 impurity Substances 0.000 abstract description 22
- 238000009776 industrial production Methods 0.000 abstract description 3
- 238000004519 manufacturing process Methods 0.000 abstract description 2
- 230000003647 oxidation Effects 0.000 abstract description 2
- 238000007254 oxidation reaction Methods 0.000 abstract description 2
- 239000002994 raw material Substances 0.000 abstract description 2
- RZTQNNQCTBBNTK-UHFFFAOYSA-N 5-bromo-2-pyridin-2-yl-3,4-dihydropyrazole-3-carboxylic acid Chemical compound C1C(N(N=C1Br)C2=CC=CC=N2)C(=O)O RZTQNNQCTBBNTK-UHFFFAOYSA-N 0.000 abstract 1
- 150000001262 acyl bromides Chemical class 0.000 abstract 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 14
- 238000004821 distillation Methods 0.000 description 8
- 238000010992 reflux Methods 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- 239000007810 chemical reaction solvent Substances 0.000 description 6
- 238000001514 detection method Methods 0.000 description 6
- 239000012467 final product Substances 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 4
- 230000000052 comparative effect Effects 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- 238000011010 flushing procedure Methods 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 3
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- MOXMPWAWQLBNGS-UHFFFAOYSA-N 5-bromo-2-(3-chloropyridin-2-yl)pyrazole-3-carbonyl chloride Chemical compound ClC(=O)C1=CC(Br)=NN1C1=NC=CC=C1Cl MOXMPWAWQLBNGS-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 2
- 241000607479 Yersinia pestis Species 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- 238000005260 corrosion Methods 0.000 description 2
- 230000007797 corrosion Effects 0.000 description 2
- 230000002195 synergetic effect Effects 0.000 description 2
- 241000255777 Lepidoptera Species 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- 230000006837 decompression Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000002917 insecticide Substances 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 230000000974 larvacidal effect Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000002688 persistence Effects 0.000 description 1
- 230000000361 pesticidal effect Effects 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
The invention discloses a preparation method of chlorantraniliprole, which takes 3-bromo-1- (pyridyl) -4, 5-dihydro-1H-pyrazole-5-carboxylic acid (I) as a raw material, and is subjected to acyl bromination and oxidation with an acyl bromide reagent to prepare 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-formyl bromide shown in (II), and the 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-formyl bromide (II) reacts with 2-amino-5-chloro-N, 3-dimethyl benzamide (III) to obtain high-content chlorantraniliprole (IV), wherein the method is simple, convenient and safe to operate, Little damage to equipment, high yield, and no production of specific impurity (VI), and is suitable for industrial production.
Description
Technical Field
The invention relates to the field of pesticides, in particular to a preparation method of chlorantraniliprole.
Background
Chlorantraniliprole (chlorantraniliprole-pole) is a novel efficient, highly active and safe insecticide with the chemical name of 3-bromo-N- { 4-chloro-2-methyl-6- [ (methylamino) carbonyl ] phenyl } -1- (3-chloro-2-pyridyl) -1H-pyrazole-5-carboxamide, can effectively control almost all lepidoptera pests and partial other pests, and has excellent crop protection effect due to efficient larvicidal activity and pesticide effect persistence.
The synthesis of chlorantraniliprole reported in the current patent adopts thionyl chloride as an oxidation acyl chlorination reagent, and the generation process of the impurity (VI) is shown as the following reaction:
this reaction produces an intermediate (V) in which the bromine atom is replaced by a chlorine atom, which is further converted to an impurity (VI) which is a critical impurity in the chlorantraniliprole product. In order to inhibit the generation of the impurity (VI), patent CN110028489A discloses a method for preparing chlorantraniliprole by a reduced pressure method, which rapidly removes hydrogen chloride generated in the reaction by the reduced pressure method, reduces the probability of bromine atom being replaced by chlorine atom, when the reaction is in hectogram scale, the content of the impurity (VI) can be controlled between 0.3 wt% and 0.4 wt%, and if the scheme is not adopted, the content of the impurity (VI) is between 7.1 wt% and 13.3 wt%. However, it was found experimentally that the following problems exist with this method: firstly, a vacuum pump and other equipment for providing negative pressure can be seriously corroded due to the generation of a large amount of hydrogen chloride and sulfur dioxide in the reaction; secondly, when the reaction is amplified to a kilogram level, the content of the impurity (VI) still seriously exceeds the standard (more than 1.5wt percent, and the product requirement is less than 0.3wt percent) along with the increase of the generated hydrogen chloride; thirdly, the negative pressure reaction system is easy to generate bumping and has the safety risk of material flushing.
Based on the above problems, there is a need to develop a synthesis method with better selectivity, safety and economy, and chlorantraniliprole with impurity (VI) content meeting the product requirement can be produced under normal pressure.
Disclosure of Invention
The invention aims to provide a method for preparing chlorantraniliprole, thereby reducing impurities in a final product
The content of (a).
In order to solve the technical problems, the invention adopts the following technical scheme:
the invention provides a preparation method of chlorantraniliprole, which comprises the following steps: reacting 3-bromo-1- (3-chloro-2-pyridyl) -4, 5-dihydro-1H-pyrazole-5-carboxylic acid with an acyl brominating reagent at normal pressure to obtain 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-formyl bromide, and reacting the 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-formyl bromide with 2-amino-5-chloro-N, 3-dimethylbenzamide to obtain the chlorantraniliprole.
Preferably, the acyl brominating reagent is one or more of dibromosulfoxide, phosphorus tribromide or phosphorus pentabromide,
further preferably, the acyl brominating reagent is dibromosulfoxide, so as to avoid generation
Meanwhile, the reaction yield and purity of the 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-formyl bromide are ensured.
Preferably, the feeding molar ratio of the 3-bromo-1- (3-chloro-2-pyridyl) -4, 5-dihydro-1H-pyrazole-5-carboxylic acid to the acyl brominating agent is 1:2 to 5.
Preferably, the 3-bromo-1- (3-chloro-2-pyridinyl) -4, 5-dihydro-1H-pyrazole-5-carboxylic acid is reacted with the acyl brominating reagent in the presence of a solvent, the temperature of the reaction being controlled to a temperature between 0 ℃ and the boiling point of the solvent.
Preferably, the reaction time of the 3-bromo-1- (3-chloro-2-pyridyl) -4, 5-dihydro-1H-pyrazole-5-carboxylic acid with the acyl brominating agent is controlled to be 1 to 10 hours.
Under the synergistic effect of the reaction parameters, the preparation yield of the 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-formyl bromide is improved.
Further preferably, the temperature of the reaction of the 3-bromo-1- (3-chloro-2-pyridinyl) -4, 5-dihydro-1H-pyrazole-5-carboxylic acid with the acyl brominating reagent is controlled to a temperature between 30 ℃ and the boiling point of the solvent.
Further preferably, the reaction time of the 3-bromo-1- (3-chloro-2-pyridyl) -4, 5-dihydro-1H-pyrazole-5-carboxylic acid with the acyl brominating agent is controlled to be 2 to 5 hours.
Still more preferably, the reaction time of the 3-bromo-1- (3-chloro-2-pyridyl) -4, 5-dihydro-1H-pyrazole-5-carboxylic acid with the acyl brominating agent is controlled to be 2 to 3 hours.
Further preferably, the reaction solvent of the 3-bromo-1- (3-chloro-2-pyridyl) -4, 5-dihydro-1H-pyrazole-5-carboxylic acid and the acyl brominating reagent is one or more of acetonitrile, toluene, chlorobenzene, dichloroethane and xylene.
More preferably, the feeding mass ratio of the 3-bromo-1- (3-chloro-2-pyridyl) -4, 5-dihydro-1H-pyrazole-5-carboxylic acid to the solvent is 1: 1-10.
More preferably, the feeding mass ratio of the 3-bromo-1- (3-chloro-2-pyridyl) -4, 5-dihydro-1H-pyrazole-5-carboxylic acid to the solvent is 1: 2-5.
The reaction of the 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-formyl bromide has better selectivity and the reaction time and the selection of the solvent are controlled by controlling the reaction temperature, the feeding molar ratio of the 3-bromo-1- (3-chloro-2-pyridyl) -4, 5-dihydro-1H-pyrazole-5-carboxylic acid to the acyl brominating reagent, the feeding mass ratio of the 3-bromo-1- (3-chloro-2-pyridyl) -4, 5-dihydro-1H-pyrazole-5-carboxylic acid to the solvent, the reaction time and the selection of the solvent, so that the reaction of the 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-formyl bromide is further improved The reaction yield of (1).
Preferably, the 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-carboxylic acid bromide is reacted with the 2-amino-5-chloro-N, 3-dimethylbenzamide in the presence of a solvent, the temperature of the reaction being controlled to be between 0 ℃ and the boiling point of the solvent.
Preferably, the reaction time of the 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-carboxylic acid bromide and the 2-amino-5-chloro-N, 3-dimethylbenzamide is controlled to be 0.5 to 10 hours.
Under the synergistic effect of the reaction parameters, the preparation yield of the chlorantraniliprole is improved.
Further preferably, the temperature of the reaction of said 3-bromo-1- (3-chloro-2-pyridinyl) -1H-pyrazole-5-carboxylic acid bromide with said 2-amino-5-chloro-N, 3-dimethylbenzamide is controlled to a temperature between 50 ℃ and the boiling point of said solvent.
Further preferably, the reaction time of the 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-carboxylic acid bromide with the 2-amino-5-chloro-N, 3-dimethylbenzamide is controlled to be 1 to 2 hours.
Still more preferably, the reaction time of the 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-carboxylic acid bromide with the 2-amino-5-chloro-N, 3-dimethylbenzamide is controlled to be 1 to 1.5 hours.
Further preferably, the reaction solvent of the 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-carboxylic acid bromide and the 2-amino-5-chloro-N, 3-dimethylbenzamide is one or more of acetonitrile, toluene, chlorobenzene, dichloroethane, xylene and cyclohexane.
More preferably, the feeding mass ratio of the 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-formyl bromide to the solvent is 1: 1-5.
Wherein, the 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-carboxylic acid bromide and the 2-amino-5-chloro-N, 3-dimethylbenzamide can be simultaneously put into a solvent for reaction; alternatively, the 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-carbonyl bromide may be added to a solvent to prepare a 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-carbonyl bromide solution, the 2-amino-5-chloro-N, 3-dimethylbenzamide may be added to a solvent to prepare a 2-amino-5-chloro-N, 3-dimethylbenzamide solution, and the 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-carbonyl bromide solution and 2-amino-5-chloro-N, and mixing the 3-dimethyl benzamide solution and reacting.
Still more preferably, when preparing the 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-carboxylic acid bromide solution, the feeding mass ratio of the 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-carboxylic acid bromide to the solvent is 1:1 to 2.
The reaction yield of the chlorantraniliprole is further improved by controlling the reaction temperature, the feeding molar ratio of the 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-formyl bromide to the 2-amino-5-chloro-N, 3-dimethyl benzamide, the feeding mass ratio of the 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-formyl bromide to the solvent, the reaction time and the selection of the solvent.
Wherein the reaction solvent of the 3-bromo-1- (3-chloro-2-pyridyl) -4, 5-dihydro-1H-pyrazole-5-carboxylic acid and the acyl brominating reagent and the reaction solvent of the 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-carboxylic acid bromide and the 2-amino-5-chloro-N, 3-dimethylbenzamide may be the same or different. Preferably, the reaction solvent of said 3-bromo-1- (3-chloro-2-pyridyl) -4, 5-dihydro-1H-pyrazole-5-carboxylic acid with said acyl brominating reagent is the same as the reaction solvent of said 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-carboxylic acid bromide with said 2-amino-5-chloro-N, 3-dimethylbenzamide.
The preparation method of the chlorantraniliprole comprises the following steps:
adding the 3-bromo-1- (3-chloro-2-pyridyl) -4, 5-dihydro-1H-pyrazole-5-formic acid and a solvent into a reactor, dropwise adding the acyl brominating reagent at the reaction temperature, and continuing the heat preservation reaction after the dropwise adding is finished. After the reaction is finished, the solvent is evaporated by a reduced pressure distillation method to obtain the 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-formyl bromide. Dissolving the 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-formyl bromide in a solvent to obtain a solution of 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-formyl bromide.
Adding the 2-amino-5-chloro-N, 3-dimethylbenzamide and a solvent into a reactor, dropwise adding the 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-formyl bromide solution at the reaction temperature, and continuing to perform heat preservation reaction after dropwise adding is finished. After the reaction is finished, cooling, filtering, rinsing and drying to obtain the chlorantraniliprole;
wherein the feeding molar ratio of the 3-bromo-1- (3-chloro-2-pyridyl) -4, 5-dihydro-1H-pyrazole-5-carboxylic acid to the acyl brominating reagent is controlled to be 1: 2-10, and controlling the feeding molar ratio of the 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-formyl bromide to the 2-amino-5-chloro-N, 3-dimethylbenzamide to be 1: 0.8-1.2.
Compared with the prior art, the invention has the following advantages:
the preparation method of chlorantraniliprole provided by the invention avoids impurities
The production of chlorantraniliprole leads the product quality of chlorantraniliprole to be higher. Meanwhile, the process does not need decompression operation, reduces equipment corrosion, eliminates the risk of material flushing, ensures that the preparation process of the chlorantraniliprole is safer and more environment-friendly, and is suitable for large-scale industrial production.
Detailed Description
The present invention will be further described with reference to the following examples. However, the present invention is not limited to the following examples. The implementation conditions adopted in the embodiments can be further adjusted according to different requirements of specific use, and the implementation conditions not mentioned are conventional conditions in the industry. The technical features of the embodiments of the present invention may be combined with each other as long as they do not conflict with each other.
Reacting 3-bromo-1- (3-chloro-2-pyridyl) -4, 5-dihydro-1H-pyrazole-5-carboxylic acid with an acyl brominating reagent under normal pressure to obtain 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-formyl bromide, and reacting the 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-formyl bromide with 2-amino-5-chloro-N, 3-dimethylbenzamide to obtain chlorantraniliprole. Through the reaction design, impurities in the final product are obtained
The content of (A) is controlled. The reaction is only carried out under normal pressure, and the equipment is not required to be subjected to reduced pressure operation, so that the corrosion of the equipment is reduced, the risk of material flushing is eliminated, and the preparation process of the chlorantraniliprole is safer and more environment-friendly.
The following examples are given to illustrate the embodiments of the present invention:
example 1
In a 1000 ml reaction flask was added 3-bromo-1- (3-chloro-2-pyridinyl) -4, 5-dihydro-1H-pyrazole-5-carboxylic acid (94.2 g, 97%, 0.3 mol), 282.6 g acetonitrile. Dibromo sulfoxide (249.4 g, 1.2 mol) is slowly dropped at 30 ℃, after dropping, the reaction is continued for 2 hours under heat preservation, and the acetonitrile solvent is evaporated by reduced pressure distillation to obtain 115 g of reddish brown oily 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-formyl bromide. 3-bromo-1- (3-chloro-2-pyridinyl) -1H-pyrazole-5-carbonyl bromide was dissolved in 120 g of acetonitrile and used directly in the next reaction.
In a 1000 ml reaction flask, 2-amino-5-chloro-N, 3-dimethylbenzamide (60.0 g, 96%, 0.29 mol) and 180 g acetonitrile were added and the temperature was raised to reflux. Slowly dripping the acetonitrile solution of the 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-formyl bromide into a reaction bottle, and continuing to perform heat preservation reaction for 1 hour after the dripping is finished. Then cooled to room temperature, filtered, rinsed and dried to obtain 125.7 g of white solid chlorantraniliprole. Impurities
No detection was found, the quantitative content of chlorantraniliprole was 96.5%, and the yield in the above two steps was 83.6% (based on 3-bromo-1- (3-chloro-2-pyridyl) -4, 5-dihydro-1H-pyrazole-5-carboxylic acid).
Example 2
In a 1000 ml reaction flask, 3-bromo-1- (3-chloro-2-pyridinyl) -4, 5-dihydro-1H-pyrazole-5-carboxylic acid (79.3 g, 96%, 0.25 mol), 237.9 g toluene were added. Dibromo sulfoxide (259.8 g, 1.25 mol) was slowly dropped at 50 ℃, after dropping, the reaction was continued for 2 hours with heat preservation, and the toluene solvent was evaporated by reduced pressure distillation to obtain 97 g of 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-formyl bromide as a reddish brown oil. 3-bromo-1- (3-chloro-2-pyridinyl) -1H-pyrazole-5-carboxylic acid bromide was dissolved in 100 g of toluene and used directly in the next reaction.
In a 1000 ml reaction flask, 2-amino-5-chloro-N, 3-dimethylbenzamide (55.9 g, 96%, 0.27 mol) and 112 g of toluene were added, and the temperature was raised to reflux. Slowly dripping the toluene solution of the 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-formyl bromide into a reaction bottle, and continuing to perform heat preservation reaction for 1 hour after dripping is finished. Then cooling to room temperature, filtering, rinsing and drying to obtain white solid chlorantraniliprole 106.9 g and impurities
No detection, the quantitative content of chlorantraniliprole is 96.0%, and the yield of the two steps is 85.0% (based on 3-bromo-1- (3-chloro-2-pyridyl) -4, 5-dihydro-1H-pyrazole-5-formic acid).
Example 3
In a 1000 ml reaction flask was added 3-bromo-1- (3-chloro-2-pyridinyl) -4, 5-dihydro-1H-pyrazole-5-carboxylic acid (64.1 g, 95%, 0.20 mol), 320 g of 1, 2-dichloroethane. Dibromo sulfoxide (103.9 g, 0.5 mol) is slowly dropped at 40 ℃, after dropping, the reaction is continued for 2 hours under heat preservation, and the 1, 2-dichloroethane solvent is evaporated by reduced pressure distillation to obtain 80 g of red brown oily 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-formyl bromide. 3-bromo-1- (3-chloro-2-pyridinyl) -1H-pyrazole-5-carboxylic acid bromide was dissolved in 100 g of 1, 2-dichloroethane and used directly in the next reaction.
In a 1000 ml reaction flask, 2-amino-5-chloro-N, 3-dimethylbenzamide (51.8 g, 96%, 0.25 mol) and 120 g of 1, 2-dichloroethane were added and the temperature was raised to reflux. Slowly dripping the 1, 2-dichloroethane solution of the 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-formyl bromide into a reaction bottle, and continuing to perform heat preservation reaction for 1 hour after finishing dripping. Then cooling to room temperature, filtering, rinsing and drying to obtain 84.4 g of white solid chlorantraniliprole and impurities
No detection was found, the quantitative content of chlorantraniliprole was 96.7%, and the yield in the above two steps was 84.5% (based on 3-bromo-1- (3-chloro-2-pyridinyl) -4, 5-dihydro-1H-pyrazole-5-carboxylic acid).
Example 4
In a 500 ml reaction flask, 3-bromo-1- (3-chloro-2-pyridinyl) -4, 5-dihydro-1H-pyrazole-5-carboxylic acid (50 g, 97%, 0.16 mol), 150 g acetonitrile were added. Phosphorus tribromide (129.9 g, 0.48 mol) is slowly dropped at 50 ℃, after the dropping is finished, the reaction is continued for 2 hours under heat preservation, and acetonitrile solvent is evaporated by reduced pressure distillation to obtain 52 g of 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-formyl bromide in reddish brown oil. 3-bromo-1- (3-chloro-2-pyridinyl) -1H-pyrazole-5-carboxylic acid bromide was dissolved in 100 g of acetonitrile and used directly in the next reaction.
In a 500 ml reaction flask, 2-amino-5-chloro-N, 3-dimethylbenzamide (33.1 g, 96%, 0.16 mol) and 100 g were addedAcetonitrile, heating to reflux. Slowly dripping the acetonitrile solution of the 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-formyl bromide into a reaction bottle, and continuing to perform heat preservation reaction for 1 hour after the dripping is finished. Then cooled to room temperature, filtered, rinsed and dried to obtain 50.6 g of white solid chlorantraniliprole. Impurities
No detection was found, and the quantitative content of chlorantraniliprole was 93.1%, and the yield in the above two steps was 61% (based on 3-bromo-1- (3-chloro-2-pyridyl) -4, 5-dihydro-1H-pyrazole-5-carboxylic acid).
Example 5
In a 500 ml reaction flask, 3-bromo-1- (3-chloro-2-pyridinyl) -4, 5-dihydro-1H-pyrazole-5-carboxylic acid (50 g, 97%, 0.16 mol), 150 g of 1, 2-dichloroethane were added. Phosphorus pentabromide (137.7 g, 0.32 mol) is slowly dropped at 50 ℃, after the dropping is finished, the reaction is continued for 2 hours under heat preservation, and the 1, 2-dichloroethane solvent is evaporated by a reduced pressure distillation method to obtain 55 g of 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-formyl bromide in red brown oil. 3-bromo-1- (3-chloro-2-pyridinyl) -1H-pyrazole-5-carboxylic acid bromide was dissolved in 110 g of 1, 2-dichloroethane and used directly in the next reaction.
In a 500 ml reaction flask, 2-amino-5-chloro-N, 3-dimethylbenzamide (33.1 g, 96%, 0.16 mol) and 100 g of 1, 2-dichloroethane were added and the temperature was raised to reflux. Slowly dripping the acetonitrile solution of the 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-formyl bromide into a reaction bottle, and continuing to perform heat preservation reaction for 1 hour after the dripping is finished. Then cooled to room temperature, filtered, rinsed and dried to obtain 54.1 g of white solid chlorantraniliprole. Impurities
No detection was found, and the quantitative content of chlorantraniliprole was 94.3%, and the yield in the above two steps was 66% (based on 3-bromo-1- (3-chloro-2-pyridyl) -4, 5-dihydro-1H-pyrazole-5-carboxylic acid).
Example 6
In a 10L reactor, 3-bromo-1- (3-chloro-2-pyridinyl) -4, 5-dihydro-1H-pyrazole-5-carboxylic acid (942 g, 97%, 3 mol), 4710 g of 1, 2-dichloroethane were added. Dibromo sulfoxide (1870.8 g, 9 mol) is slowly dropped at 40 ℃, after dropping, the reaction is continued for 2 hours under heat preservation, and the 1, 2-dichloroethane solvent is evaporated by reduced pressure distillation to obtain 1106 g of 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-formyl bromide as a reddish brown oil. 3-bromo-1- (3-chloro-2-pyridinyl) -1H-pyrazole-5-carboxylic acid bromide was dissolved in 1200 g of 1, 2-dichloroethane and used directly in the next reaction.
In a 10l reactor, 2-amino-5-chloro-N, 3-dimethylbenzamide (620 g, 96%, 3 mol) and 1800 g of 1, 2-dichloroethane were added and the temperature was raised to reflux. Slowly dripping the 1, 2-dichloroethane solution of the 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-formyl bromide into a reaction bottle, and continuing to perform heat preservation reaction for 1 hour after finishing dripping. Then cooling to room temperature, filtering, rinsing and drying to obtain 1264.3 g of white solid chlorantraniliprole and impurities
No detection was found, and the quantitative content of chlorantraniliprole was 96.3%, and the yield in the above two steps was 84.0% (based on 3-bromo-1- (3-chloro-2-pyridyl) -4, 5-dihydro-1H-pyrazole-5-carboxylic acid).
Comparative example 1
In a 10L pilot reactor, 3-bromo-1- (3-chloro-2-pyridinyl) -4, 5-dihydro-1H-pyrazole-5-carboxylic acid (942 g, 97%, 3 mol), 2830 g acetonitrile were added. Slowly adding thionyl chloride (1428 g, 12 mol) dropwise at 30 ℃ under the reaction pressure of-0.05 Mpa, and heating to 50 ℃ after the dropwise addition is finished to react for 2 hours (in the heating process, the system is vigorously boiled). The acetonitrile solvent was evaporated by distillation under reduced pressure to give 1000 g of 3-bromo-1- (3-chloro-2-pyridinyl) -1H-pyrazole-5-carbonyl chloride as a reddish brown oil. 3-bromo-1- (3-chloro-2-pyridinyl) -1H-pyrazole-5-carbonyl chloride was dissolved in 1200 g of acetonitrile and used directly in the next reaction.
In a 10L reactor, 2-amino-5-chloro-N, 3-dimethylbenzamide (600 g, 96%, 2.9 mol) and 1800 g acetonitrile were added under-0.04 MPa, and the mixture was heated to reflux. Slowly dripping the 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-methyl into a reaction kettleAnd after dropwise adding, reacting for 1 hour under the condition of heat preservation, cooling to room temperature, filtering, rinsing and drying to obtain 1244 g of white solid chlorantraniliprole. Impurities
The content of (a) was 1.5% by weight, the quantitative content of chlorantraniliprole was 96.1%, and the yield of the above two steps was 82.5% (based on 3-bromo-1- (3-chloro-2-pyridyl) -4, 5-dihydro-1H-pyrazole-5-carboxylic acid).
Comparing the examples with the comparative examples, it can be seen that the impurities in the final product can be significantly reduced by using the reaction designed by the present invention
The content of (a). Wherein, as shown in comparative example 1, even if the conventional reaction was adopted in combination with the preparation method of reduced pressure, impurities in the final product were present when the reaction scale was enlarged
The content of (a) is still not effectively controlled. However, as shown in the examples, the impurities in the final product can be obtained by the designed reaction of the invention even in large-scale production of chlorantraniliprole
The content of (A) still meets the requirement, and is beneficial to industrial production. Moreover, the method adopted by the invention is safer compared with the method in comparative example 1. In addition, the purity and yield of chlorantraniliprole cannot be influenced by adopting the reaction designed by the invention because the reaction raw materials are changed compared with the traditional reaction mode, and the examples show that the purity and yield of the chlorantraniliprole can be equal to or even better than those of the traditional preparation method.
The present invention has been described in detail in order to enable those skilled in the art to understand the invention and to practice it, and it is not intended to limit the scope of the invention, and all equivalent changes and modifications made according to the spirit of the present invention should be covered by the present invention.
Claims (10)
1. The preparation method of chlorantraniliprole is characterized in that 3-bromo-1- (3-chloro-2-pyridyl) -4, 5-dihydro-1H-pyrazole-5-carboxylic acid is reacted with an acyl brominating reagent under normal pressure to obtain 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-formyl bromide, and the 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-formyl bromide is reacted with 2-amino-5-chloro-N, 3-dimethylbenzamide to obtain the chlorantraniliprole.
2. The method for preparing chlorantraniliprole according to claim 1, wherein the acyl bromination reagent is one or more of dibromosulfoxide, phosphorus tribromide or phosphorus pentabromide.
3. The preparation method of chlorantraniliprole according to claim 1, wherein the feeding molar ratio of the 3-bromo-1- (3-chloro-2-pyridyl) -4, 5-dihydro-1H-pyrazole-5-carboxylic acid to the acyl brominating reagent is 1:2 to 5.
4. The process for the preparation of chlorantraniliprole according to claim 1, wherein the 3-bromo-1- (3-chloro-2-pyridyl) -4, 5-dihydro-1H-pyrazole-5-carboxylic acid is reacted with the acyl brominating reagent in the presence of a solvent, the temperature of the reaction being controlled to be between 0 ℃ and the boiling point of the solvent; and/or controlling the reaction time to be 1-10 hours.
5. The method for preparing chlorantraniliprole according to claim 4, wherein the temperature of the reaction is controlled to be between 30 ℃ and the boiling point of the solvent; and/or controlling the reaction time to be 2-5 hours.
6. The preparation method of chlorantraniliprole according to claim 4, wherein the solvent is one or more of acetonitrile, toluene, chlorobenzene, dichloroethane and xylene; and/or the feeding mass ratio of the 3-bromo-1- (3-chloro-2-pyridyl) -4, 5-dihydro-1H-pyrazole-5-formic acid to the solvent is 1: 1-10.
7. The method for preparing chlorantraniliprole according to claim 1, wherein the 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-carboxylic acid bromide is reacted with the 2-amino-5-chloro-N, 3-dimethylbenzamide in the presence of a solvent, and the reaction temperature is controlled to be between 0 ℃ and the boiling point of the solvent; and/or controlling the reaction time to be 0.5-10 hours.
8. The method for preparing chlorantraniliprole according to claim 7, wherein the temperature of the reaction is controlled to be between 50 ℃ and the boiling point of the solvent; and/or controlling the reaction time to be 1-2 hours.
9. The method for preparing chlorantraniliprole according to claim 7, wherein the solvent is one or more of acetonitrile, toluene, chlorobenzene, dichloroethane, xylene and cyclohexane; and/or the feeding mass ratio of the 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-formyl bromide to the solvent is 1: 1-5.
10. The method for preparing chlorantraniliprole according to any one of claims 1 to 9, which is characterized by comprising the following steps:
adding the 3-bromo-1- (3-chloro-2-pyridyl) -4, 5-dihydro-1H-pyrazole-5-formic acid and a solvent into a reactor, dropwise adding the acyl brominating reagent at a reaction temperature, continuing to perform heat preservation reaction after dropwise adding is finished, and evaporating the solvent under reduced pressure after the reaction is finished to obtain the 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-formyl bromide; dissolving the 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-formyl bromide in a solvent to obtain a 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-formyl bromide solution;
adding the 2-amino-5-chloro-N, 3-dimethylbenzamide and a solvent into a reactor, dropwise adding the 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-formyl bromide solution at a reaction temperature, continuing to perform heat preservation reaction after dropwise adding is finished, and after the reaction is finished, cooling, filtering, rinsing and drying to obtain the chlorantraniliprole;
wherein the feeding molar ratio of the 3-bromo-1- (3-chloro-2-pyridyl) -4, 5-dihydro-1H-pyrazole-5-carboxylic acid to the acyl brominating reagent is controlled to be 1: 2-10, and controlling the feeding molar ratio of the 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-formyl bromide to the 2-amino-5-chloro-N, 3-dimethylbenzamide to be 1: 0.8-1.2.
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