CN115057844B - A kind of preparation method of chlorantraniliprole - Google Patents
A kind of preparation method of chlorantraniliprole Download PDFInfo
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- CN115057844B CN115057844B CN202210796334.9A CN202210796334A CN115057844B CN 115057844 B CN115057844 B CN 115057844B CN 202210796334 A CN202210796334 A CN 202210796334A CN 115057844 B CN115057844 B CN 115057844B
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- pyrazole
- bromo
- pyridyl
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- 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 description 50
- 239000005886 Chlorantraniliprole Substances 0.000 title claims description 48
- 238000002360 preparation method Methods 0.000 title claims description 14
- 238000006243 chemical reaction Methods 0.000 claims abstract description 86
- -1 3-chloro-2-pyridyl Chemical group 0.000 claims abstract description 57
- 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 29
- 238000000034 method Methods 0.000 claims abstract description 19
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 16
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 60
- 239000002904 solvent Substances 0.000 claims description 41
- 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
- 125000002252 acyl group Chemical group 0.000 claims description 19
- 230000035484 reaction time Effects 0.000 claims description 12
- 238000009835 boiling Methods 0.000 claims description 9
- 239000003795 chemical substances by application Substances 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 group BrS(Br)=O HFRXJVQOXRXOPP-UHFFFAOYSA-N 0.000 claims description 7
- 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
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 2
- 230000031709 bromination Effects 0.000 claims 6
- 238000005893 bromination reaction Methods 0.000 claims 6
- 239000012535 impurity Substances 0.000 abstract description 22
- 150000001262 acyl bromides Chemical class 0.000 abstract description 3
- 238000009776 industrial production Methods 0.000 abstract description 3
- 238000004519 manufacturing process Methods 0.000 abstract description 3
- 239000002994 raw material Substances 0.000 abstract description 2
- CWFOCCVIPCEQCK-UHFFFAOYSA-N chlorfenapyr Chemical compound BrC1=C(C(F)(F)F)N(COCC)C(C=2C=CC(Cl)=CC=2)=C1C#N CWFOCCVIPCEQCK-UHFFFAOYSA-N 0.000 abstract 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
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 13
- 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
- 238000004321 preservation Methods 0.000 description 6
- 238000001816 cooling Methods 0.000 description 5
- 238000001035 drying Methods 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 239000012467 final product Substances 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 230000000052 comparative effect Effects 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- ALGLHCFROQVWRL-UHFFFAOYSA-N 5-bromo-2-(3-chloropyridin-2-yl)pyrazole-3-carboxamide Chemical compound NC(=O)C1=CC(Br)=NN1C1=NC=CC=C1Cl ALGLHCFROQVWRL-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- 230000006837 decompression Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000011010 flushing procedure 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
- 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 description 2
- 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
- PHSPJQZRQAJPPF-UHFFFAOYSA-N N-alpha-Methylhistamine Chemical compound CNCCC1=CN=CN1 PHSPJQZRQAJPPF-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
- 230000015572 biosynthetic process Effects 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
- 239000000463 material Substances 0.000 description 2
- 239000000575 pesticide Substances 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000002195 synergetic effect Effects 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 150000001263 acyl chlorides Chemical class 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000002267 larvicidal agent Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 230000002688 persistence Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000010189 synthetic method 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 present invention discloses a method for preparing chlorfenapyr, which uses 3-bromo-1- (pyridyl) -4,5-dihydro-1H-pyrazole-5-formic acid (I) as raw material, and oxidizes it simultaneously with an acyl bromide reagent to obtain 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-formyl bromide as shown in (II), 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-formyl bromide (II) and 2-amino-5-chloro-N, 3-dimethylbenzamide (III). The reaction yields high levels of Chlorfenapyr (IV), which is easy and safe to operate, causes minimal damage to equipment, has a high yield, and avoids the production of specific impurities (VI), making it suitable for industrial production.
Description
Technical Field
The invention relates to the field of pesticide, in particular to a preparation method of chlorantraniliprole.
Background
Chlorantraniliprole (chlorantranili-pole) is a novel efficient, high-activity and safe pesticide 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, which can effectively control almost all lepidopteran pests and some other pests, and its efficient larvicide activity and efficacy persistence provide outstanding crop protection effects.
The synthesis of chlorantraniliprole reported in the current patent adopts thionyl chloride as an acyl chloride oxidizing reagent, and the production process of the impurity (VI) is shown in the following reaction:
This reaction will produce an intermediate (V) in which the bromine atom is replaced by a chlorine atom, which intermediate is further converted into an impurity (VI) which is a tightly controlled impurity in the chlorantraniliprole product. In order to inhibit the generation of impurities (VI), patent CN110028489A discloses a method for preparing chlorantraniliprole by a decompression method, which rapidly removes hydrogen chloride generated in the reaction by the decompression method, reduces the probability of substituting bromine atoms by chlorine atoms, and when the reaction is in a hundred gram scale, the content of the impurities (VI) can be controlled to be 0.3-0.4 wt%, and if the scheme is not adopted, the content of the impurities (VI) is 7.1-13.3 wt%. However, the experiment shows that the method has the following problems that firstly, a vacuum pump and other equipment for providing negative pressure can be severely corroded due to the fact that a large amount of hydrogen chloride and sulfur dioxide are generated by the reaction, secondly, when the reaction is amplified to the kilogram level, the content of impurities (VI) still can be seriously out of standard (more than 1.5wt% and the product requirement is less than 0.3 wt%) as the generated hydrogen chloride is increased, thirdly, the negative pressure reaction system is easy to be subjected to bumping, and the safety risk of flushing materials is caused.
Based on the above problems, there is a need to develop a synthetic method with better selectivity, safer and more economical, and the chlorantraniliprole with the impurity (VI) content meeting the product requirement can be produced and prepared under normal pressure.
Disclosure of Invention
The invention aims to provide a preparation method of chlorantraniliprole, thereby reducing impurities in a final productIs contained in the composition.
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 steps of 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 the chlorantraniliprole.
Preferably, the acyl bromide reagent is one or more of dibromosulfoxide, phosphorus tribromide or phosphorus pentabromide,
Further preferably, the acyl bromide reagent is dibromosulfoxide, in order to avoid formation ofMeanwhile, 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 reagent is 1:2-5.
Preferably, the 3-bromo-1- (3-chloro-2-pyridinyl) -4, 5-dihydro-1H-pyrazole-5-carboxylic acid is reacted with the acyl brominating agent 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-pyridinyl) -4, 5-dihydro-1H-pyrazole-5-carboxylic acid and the acyl brominating agent is controlled to be 1-10 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.
It is further preferred that 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 agent is controlled to be a temperature between 30 ℃ and the boiling point of the solvent.
Further preferably, the reaction time of the 3-bromo-1- (3-chloro-2-pyridinyl) -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-pyridinyl) -4, 5-dihydro-1H-pyrazole-5-carboxylic acid with the acylbrominating agent is controlled to be 2 to 3 hours.
Further preferably, the reaction solvent of the 3-bromo-1- (3-chloro-2-pyridinyl) -4, 5-dihydro-1H-pyrazole-5-carboxylic acid and the acyl brominating reagent is one or more of acetonitrile, toluene, chlorobenzene, dichloroethane, xylene.
Further preferably, the 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.
Still more preferably, the 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 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-formylbromide has better selectivity and the reaction yield of 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-formylbromide is further improved by controlling the reaction temperature, the feeding mole ratio of 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 3-bromo-1- (3-chloro-2-pyridyl) -4, 5-dihydro-1H-pyrazole-5-carboxylic acid to the solvent and the reaction time and solvent selection.
Preferably, the 3-bromo-1- (3-chloro-2-pyridinyl) -1H-pyrazole-5-carbonyl bromide is reacted with the 2-amino-5-chloro-N, 3-dimethylbenzamide in the presence of a solvent, and the temperature of the reaction is 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-formyl bromide and the 2-amino-5-chloro-N, 3-dimethylbenzamide is controlled to be 0.5-10 hours.
Under the synergistic effect of the reaction parameters, the preparation yield of the chlorantraniliprole is improved.
It is further preferred that the temperature of the reaction of the 3-bromo-1- (3-chloro-2-pyridinyl) -1H-pyrazole-5-carboxamide with the 2-amino-5-chloro-N, 3-dimethylbenzamide is controlled to be between 50 ℃ and the boiling point of the solvent.
Further preferably, the reaction time of the 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-carboxamide and 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-pyridinyl) -1H-pyrazole-5-carboxamide and 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-formyl bromide and the 2-amino-5-chloro-N, 3-dimethylbenzamide is one or more of acetonitrile, toluene, chlorobenzene, dichloroethane, xylene and cyclohexane.
Further preferably, the mass ratio of the 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-formyl bromide to the solvent is 1:1-5.
Wherein, 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-formyl bromide and 2-amino-5-chloro-N, 3-dimethylbenzamide are simultaneously added into a solvent for reaction, or 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-formyl bromide is added into a solvent for preparing a 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-formyl bromide solution, and then 2-amino-5-chloro-N, 3-dimethylbenzamide is added into a solvent for preparing a 2-amino-5-chloro-N, 3-dimethylbenzamide solution, and 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-formyl bromide solution and 2-amino-5-chloro-N, 3-dimethylbenzamide solution are mixed for reaction.
Still more preferably, when preparing the 3-bromo-1- (3-chloro-2-pyridinyl) -1H-pyrazole-5-formyl bromide solution, the mass ratio of the 3-bromo-1- (3-chloro-2-pyridinyl) -1H-pyrazole-5-formyl bromide to the solvent is 1:1-2.
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-dimethylbenzamide, 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 solvent selection are controlled, so that the reaction yield of the chlorantraniliprole is further improved.
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-formyl bromide and the 2-amino-5-chloro-N, 3-dimethylbenzamide may be the same or different. Preferably, the reaction solvent of the 3-bromo-1- (3-chloro-2-pyridinyl) -4, 5-dihydro-1H-pyrazole-5-carboxylic acid and the acyl brominating reagent is the same as the reaction solvent of the 3-bromo-1- (3-chloro-2-pyridinyl) -1H-pyrazole-5-carbonyl bromide and the 2-amino-5-chloro-N, 3-dimethylbenzamide.
The preparation method of chlorantraniliprole specifically comprises the following steps:
Adding the 3-bromo-1- (3-chloro-2-pyridyl) -4, 5-dihydro-1H-pyrazole-5-carboxylic acid and a solvent into a reactor, dropwise adding the acyl brominating reagent at the reaction temperature, and continuing to perform heat preservation reaction after the dropwise adding is finished. After the reaction is finished, evaporating the solvent by a reduced pressure distillation method to obtain the 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-formyl bromide. The 3-bromo-1- (3-chloro-2-pyridinyl) -1H-pyrazole-5-carbonyl bromide is dissolved in a solvent to obtain a 3-bromo-1- (3-chloro-2-pyridinyl) -1H-pyrazole-5-carbonyl 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-formylbromide solution at the reaction temperature, and continuing to perform heat preservation reaction after the 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 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 is controlled 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 the chlorantraniliprole has higher product quality. Meanwhile, the process does not need to be subjected to decompression operation, equipment corrosion is reduced, the material flushing risk is eliminated, and the preparation process of chlorantraniliprole is safer and more environment-friendly and is suitable for large-scale industrial production.
Detailed Description
The invention is further described below with reference to examples. 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 which are not noted are conventional conditions in the industry. The technical features of the various embodiments of the present invention may be combined with each other as long as they do not collide with each other.
3-Bromo-1- (3-chloro-2-pyridyl) -4, 5-dihydro-1H-pyrazole-5-carboxylic acid is reacted with an acyl brominating reagent at 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 chlorantraniliprole. By the reaction design, the impurities in the final productThe content of (2) is controlled. The reaction is only carried out under normal pressure, the equipment is not required to be decompressed, the corrosion of the equipment is reduced, the risk of flushing is eliminated, and the preparation process of chlorantraniliprole is safer and more environment-friendly.
The following describes the embodiments of the present invention in detail with reference to examples:
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. Dibromosulfoxide (249.4 g, 1.2 mol) was slowly added dropwise at 30 ℃, and after the completion of the dropwise addition, the reaction was continued under heat preservation for 2 hours, and the acetonitrile solvent was evaporated by distillation under reduced pressure to give 115 g of 3-bromo-1- (3-chloro-2-pyridinyl) -1H-pyrazole-5-carbonyl bromide as a reddish brown oil. 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 mixture was heated to reflux. Slowly dropwise adding the acetonitrile solution of the 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-formyl bromide into the reaction bottle, and continuously preserving the heat for reaction for 1 hour after the dropwise adding is finished. Then cooled to room temperature, filtered, rinsed and dried to obtain 125.7 g of off-white solid chlorantraniliprole. Impurity(s)The quantitative content of chlorantraniliprole was 96.5% and the yield in the above two steps was 83.6% (calculated as 3-bromo-1- (3-chloro-2-pyridinyl) -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) was added, 237.9 g toluene. Dibromosulfoxide (259.8 g, 1.25 mol) was slowly added dropwise at 50 ℃, and after the completion of the addition, the reaction was continued under heat preservation for 2 hours, and the toluene solvent was evaporated by distillation under reduced pressure to give 97 g of 3-bromo-1- (3-chloro-2-pyridinyl) -1H-pyrazole-5-carbonyl bromide as a reddish brown oil. 3-bromo-1- (3-chloro-2-pyridinyl) -1H-pyrazole-5-carbonyl 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 toluene were added, and the mixture was warmed to reflux. Slowly dropwise adding the toluene solution of the 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-formyl bromide into the reaction bottle, and continuously preserving the heat for reaction for 1 hour after the dropwise adding is finished. Then cooling to room temperature, filtering, rinsing and drying to obtain 106.9 g of off-white solid chlorantraniliprole and impuritiesThe quantitative content of chlorantraniliprole was not detected and was 96.0% with a yield of 85.0% in the two steps (calculated as 3-bromo-1- (3-chloro-2-pyridinyl) -4, 5-dihydro-1H-pyrazole-5-carboxylic acid).
Example 3
In a 1000 ml reaction flask, 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 was added. Dibromosulfoxide (103.9 g, 0.5 mol) was slowly added dropwise at 40 ℃, and after completion of the dropwise addition, the reaction was continued under heat preservation for 2 hours, and the 1, 2-dichloroethane solvent was evaporated to dryness by distillation under reduced pressure to give 80 g of 3-bromo-1- (3-chloro-2-pyridinyl) -1H-pyrazole-5-carboxylic acid bromide as a reddish brown oil. 3-bromo-1- (3-chloro-2-pyridinyl) -1H-pyrazole-5-carbonyl 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 dropwise adding the 1, 2-dichloroethane solution of the 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-formyl bromide into the reaction bottle, and keeping the temperature for reaction for 1 hour after the dropwise adding is finished. Then cooling to room temperature, filtering, rinsing and drying to obtain 84.4 g of off-white solid chlorantraniliprole and impuritiesThe quantitative content of chlorantraniliprole was 96.7% and the yield of the above two steps was 84.5% (calculated as 3-bromo-1- (3-chloro-2-pyridinyl) -4, 5-dihydro-1H-pyrazole-5-carboxylic acid).
Example 4
In a 500ml reaction flask, 3-bromo-1- (3-chloro-2-pyridinyl) -4, 5-dihydro-1H-pyrazole-5-carboxylic acid (50 g, 97%,0.16 mol) was added, 150 g acetonitrile. Phosphorus tribromide (129.9 g, 0.48 mol) was slowly added dropwise at 50 ℃ and the reaction was continued at a constant temperature for 2 hours after completion of the addition, and the acetonitrile solvent was evaporated by distillation under reduced pressure to give 52 g of 3-bromo-1- (3-chloro-2-pyridinyl) -1H-pyrazole-5-carboxylic acid bromide as a reddish brown oil. 3-bromo-1- (3-chloro-2-pyridinyl) -1H-pyrazole-5-carbonyl 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 acetonitrile were added, and the mixture was heated to reflux. Slowly dropwise adding the acetonitrile solution of the 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-formyl bromide into the reaction bottle, and continuously preserving the heat for reaction for 1 hour after the dropwise adding is finished. Then cooled to room temperature, filtered, rinsed and dried to obtain 50.6 g of off-white solid chlorantraniliprole. Impurity(s)The quantitative content of chlorantraniliprole was 93.1% and the yield of the above two steps was 61% (calculated as 3-bromo-1- (3-chloro-2-pyridinyl) -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) was added, 150 g of 1, 2-dichloroethane. Phosphorus pentabromide (137.7 g, 0.32 mol) was slowly added dropwise at 50℃and the reaction was continued at a constant temperature for 2 hours after completion of the addition, and the 1, 2-dichloroethane solvent was evaporated to dryness by distillation under reduced pressure to give 55 g of 3-bromo-1- (3-chloro-2-pyridinyl) -1H-pyrazole-5-carboxylic acid bromide as a reddish brown oil. 3-bromo-1- (3-chloro-2-pyridinyl) -1H-pyrazole-5-carbonyl 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 dropwise adding the acetonitrile solution of the 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-formyl bromide into the reaction bottle, and continuously preserving the heat for reaction for 1 hour after the dropwise adding is finished. Then cooled to room temperature, filtered, rinsed and dried to obtain 54.1 g of off-white solid chlorantraniliprole. Impurity(s)The quantitative content of chlorantraniliprole was 94.3% and the yield of the above two steps was 66% (calculated as 3-bromo-1- (3-chloro-2-pyridinyl) -4, 5-dihydro-1H-pyrazole-5-carboxylic acid).
Example 6
Into a 10L reactor was charged 3-bromo-1- (3-chloro-2-pyridinyl) -4, 5-dihydro-1H-pyrazole-5-carboxylic acid (942 g, 97%,3 moles), 4710 g1, 2-dichloroethane. Dibromosulfoxide (1870.8 g,9 mol) was slowly added dropwise at 40 ℃, after the addition was completed, the reaction was continued at a constant temperature for 2 hours, and the 1, 2-dichloroethane solvent was evaporated off by distillation under reduced pressure to give 1106 g of 3-bromo-1- (3-chloro-2-pyridinyl) -1H-pyrazole-5-carbonyl bromide as a reddish brown oil. 3-bromo-1- (3-chloro-2-pyridinyl) -1H-pyrazole-5-carbonyl bromide was dissolved in 1200 g of 1, 2-dichloroethane and used directly in the next reaction.
2-Amino-5-chloro-N, 3-dimethylbenzamide (620 g, 96%,3 mol) and 1800 g of 1, 2-dichloroethane were added to a 10-liter reaction vessel, and the temperature was raised to reflux. Slowly dropwise adding the 1, 2-dichloroethane solution of the 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-formyl bromide into the reaction bottle, and keeping the temperature for reaction for 1 hour after the dropwise adding is finished. Cooling to room temperature, filtering, rinsing and drying to obtain white solid chlorantraniliprole 1264.3 g, impurityThe quantitative content of chlorantraniliprole was 96.3% and the yield of the above two steps was 84.0% (calculated as 3-bromo-1- (3-chloro-2-pyridinyl) -4, 5-dihydro-1H-pyrazole-5-carboxylic acid).
Comparative example 1
To a 10L pilot reactor was added 3-bromo-1- (3-chloro-2-pyridinyl) -4, 5-dihydro-1H-pyrazole-5-carboxylic acid (942 g, 97%,3 mol), 2830 g acetonitrile. Thionyl chloride (1428 g, 12 mol) is slowly added dropwise under the reaction pressure of-0.05 Mpa at 30 ℃, and the temperature is raised to 50 ℃ for 2 hours (the boiling of the system is severe in the heating process) after the addition. Acetonitrile solvent was evaporated by distillation under reduced pressure to give 1000 g of 3-bromo-1- (3-chloro-2-pyridinyl) -1H-pyrazole-5-carboxylic acid 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.
2-Amino-5-chloro-N, 3-dimethylbenzamide (600 g, 96%,2.9 mol) and 1800 g of acetonitrile were added to a 10L reactor, and the reaction pressure was-0.04 MPa, and the temperature was raised to reflux. Slowly dropwise adding the acetonitrile solution of the 3-bromo-1- (3-chloro-2-pyridyl) -1H-pyrazole-5-formyl chloride into the reaction kettle, carrying out heat preservation reaction for 1 hour after the dropwise adding is finished, cooling to room temperature, filtering, rinsing and drying to obtain 1244 g of off-white solid chlorantraniliprole. Impurity(s)The quantitative content of chlorantraniliprole was 96.1% with a yield of 82.5% in the two steps (calculated as 3-bromo-1- (3-chloro-2-pyridinyl) -4, 5-dihydro-1H-pyrazole-5-carboxylic acid).
As can be seen by comparing the examples with the comparative examples, the use of the reaction designed according to the invention allows a significant reduction in impurities in the final productIs contained in the composition. Wherein, as shown in comparative example 1, even if the conventional reaction-coupled pressure-reducing preparation method is adopted, when the reaction scale is enlarged, impurities in the final productThe content of (2) is still not effectively controlled. However, as shown in the examples, the reaction designed by the present invention is used to produce chlorantraniliprole in large scale, and impurities in the final productThe content of the product still meets the requirements, and is beneficial to industrial production. Also, the method employed in the present invention is safer than the method in comparative example 1. In addition, the reaction designed by the invention can not cause the influence on the purity and the yield of the chlorantraniliprole because of the change of the reaction raw materials compared with the traditional reaction mode, and the examples show that the purity and the yield of the chlorantraniliprole in the invention can be equal to or even better than those of the traditional preparation method.
The present invention has been described in detail with the purpose of enabling those skilled in the art to understand the contents of the present invention and to implement the same, but not to limit the scope of the present invention, and all equivalent changes or modifications made according to the spirit of the present invention should be included in the scope of the present invention.
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