CN114057686A - Preparation method of bromo-pyrazole carboxylic ester compound - Google Patents
Preparation method of bromo-pyrazole carboxylic ester compound Download PDFInfo
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- 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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- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/06—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/06—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D231/08—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with oxygen or sulfur atoms directly attached to ring carbon atoms
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Abstract
The invention belongs to the field of organic synthesis, and particularly relates to a preparation method of a bromo-pyrazole carboxylic ester compound. The reaction formula is as follows,
Description
Technical Field
The invention belongs to the field of organic synthesis, and particularly relates to a preparation method of a bromo-pyrazole carboxylic ester compound.
Background
The benzamide compound is a novel pesticide with high efficiency and safety. Among them, 3-bromo-N- (2-methyl-4-chloro-6- (methionyl) phenyl) -1- (3-chloro-2-pyridyl) -1H-pyrazole-5-carboxamide (common name is tetrachloro-cyantraniliprole), 3-bromo-N- (2-methyl-4-cyano-6- (methionyl) phenyl) -1- (3-chloro-2-pyridyl) -1H-pyrazole-5-carboxamide (common name is cyantraniliprole) is a pesticide having a higher pesticidal activity by dupont. The bisamide-based compound 3-bromo-N- (2-chloro-4-bromo-6- ((1-cyclopropylethyl) acyl) phenyl) -1- (3-chloro-2-pyridinyl) -1H-pyrazole-5-carboxamide (commonly known as cyclic bromodiamide), which is being developed by shigaku corporation, has a broad spectrum of insecticidal activity. Shenyang chemical research institute found that 3-bromo-N- (2, 4-dichloro-6- (methionyl) phenyl) -1- (3, 5-dichloro-2-pyridinyl) -1H-pyrazole-5-carboxamide, which has high pesticidal activity, has also been developed as a pesticide, commonly known as tetrachlorantraniliprole.
The 3-bromo-1H-pyrazole-5-carboxylic ester is a key intermediate for synthesizing chlorantraniliprole, cyantraniliprole, cyromantraniliprole and tetrachloro-traniliprole. WO2003015518 discloses a synthesis method of 3-bromo-1- (pyridin-2-yl) -3-pyrazole-5-carboxylate, which comprises reacting 1- (pyridin-2-yl) -3-pyrazolidinone-5-carboxylate with tribromophosphine oxide or pentabrominated phosphine to obtain bromopyrazole carboxylate. The use of tribromophosphine oxide or penta-phosphine bromide can generate a large amount of phosphorus-containing and bromine-containing wastewater, and the environmental pollution is serious. The reaction formula is as follows:
CN101607957A also discloses a method for synthesizing 3-bromo-1- (pyridine-2-yl) -3-pyrazole-5-carboxylic ester, wherein 1- (pyridine-2-yl) -3-pyrazolidone-5-carboxylic ester reacts with p-toluenesulfonyl chloride, and then reacts with hydrogen bromide to prepare bromo-pyrazole carboxylic ester. Hydrogen bromide gas or an acetic acid solution of hydrogen bromide may be used as the brominating reagent during the bromination reaction. If hydrogen bromide gas is used as the brominating reagent, it is necessary to carry out the reaction in dibromomethane, which is a specific solvent, and 3-bromo-1- (pyridin-2-yl) -3-pyrazole-5-carboxylic ester can be prepared in high yield. If a hydrogen bromide acetic acid solution is used as a brominating reagent, 3-bromo-1- (pyridin-2-yl) -3-pyrazole-5-carboxylic ester can also be produced, but the yield is less than 10% of hydrogen bromide gas. The reaction formula is as follows:
although the methods can be used for preparing corresponding compounds, technical personnel are continuously updated along with market demands, and are dedicated to continuously researching and developing new, more advanced and reasonable preparation methods of bromo-pyrazole carboxylic ester compounds so as to obtain benzamide insecticides with better quality and lower price.
Disclosure of Invention
The invention aims to provide a method for preparing a pyrazole carboxylic ester compound with more simplicity and more high efficiency.
In order to achieve the purpose, the invention adopts the technical scheme that:
a preparation method of bromo-pyrazole carboxylic ester compounds has the following reaction formula:
in the formula: r1Selected from alkyl, haloalkyl, optionally 1-3 selected from alkyl-substituted phenyl, halogen-substituted phenyl, nitro-substituted phenyl; r2Is selected from C1-C6Alkyl radical, C2-C4Alkenyl radical, C2-C4Alkynyl, C3-C6Cycloalkyl, benzyl, halogen-substituted benzyl or substituted by up to 6C1-C4Alkyl-substituted benzyl of (a); r3Selected from H and chlorine.
Adding 3-substituted sulfonyloxy pyrazole carboxylate (II) into a proper organic solvent, and adding a brominating reagent to prepare a bromo pyrazole carboxylate compound (I); the brominating reagent is one or more of inorganic bromine salts.
The inorganic bromine salt is one or more of sodium bromide, potassium bromide, lithium bromide, ammonium bromide, magnesium bromide, calcium bromide, zinc bromide, barium bromide, ferric bromide, copper bromide and nickel bromide; the amount of the compound is 0.5 to 3 times of the molar amount of the compound represented by the general formula (II).
The reaction temperature is 0-130 ℃, and the reaction is carried out for 0.5-24 hours.
Further, the 3-substituted sulfonyloxy pyrazole carboxylate (II) is added into a proper organic solvent, a brominating reagent with the molar weight of 0.7-2 times of that of the compound shown in the general formula (II) is added, and the reaction is carried out for 1-18 hours at the temperature of 20-110 ℃ to obtain the bromo pyrazole carboxylate compound (I).
Further, the 3-substituted sulfonyloxy pyrazole carboxylate (II) is added into a proper organic solvent, a brominating reagent with the molar weight 1-1.5 times of that of the compound shown in the general formula (II) is added, and the reaction is carried out for 2-12 hours at the temperature of 40-90 ℃ to obtain the bromo pyrazole carboxylate compound (I).
The inorganic bromine salt is selected from sodium bromide, magnesium bromide, calcium bromide, zinc bromide or copper bromide.
The organic solvent is selected from diethyl ether, methyl butyl ether, tetrahydrofuran, dioxane, dimethoxyethane, toluene, xylene, chlorobenzene, dichlorobenzene, pentane, hexane, cyclohexane, heptane, dichloromethane, dichloroethane, chloroform, methyl acetate, ethyl acetate, butyl acetate, acetone, methyl ethyl ketone, cyclohexanone, acetonitrile, propionitrile, N-dimethylformamide, N-dimethylacetamide, dimethyl sulfoxide or N-methylpyrrolidone.
The suitable solvent is selected from tetrahydrofuran, toluene, xylene, chlorobenzene, methylethylketone, acetonitrile or N, N-dimethylformamide.
In the synthesis given above and in the definition of the radicals in the compounds of the formulae, the terms used are generally defined as follows:
alkyl means straight or branched chain forms, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl and the like. Cycloalkyl is meant to include cyclic chain forms such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, methylcyclopropyl, cyclopropylcyclopropyl and the like. Alkenyl means straight or branched chain alkenyl groups such as 1-propenyl, 2-propenyl, and the various butenyl groups and the like. Alkynyl means straight or branched alkynes such as 1-propynyl, 2-propynyl and the various butynyl groups and the like.
The invention has the characteristics that: the invention adopts inorganic bromine salt with low price as a brominating reagent for synthesizing the bromo-pyrazole carboxylate, and the bromo-pyrazole carboxylate with high yield is obtained through the substitution reaction of the 3-substituted sulfonyloxy pyrazole carboxylate and the inorganic bromine salt, thereby completing the invention. Compared with other bromination reagents, namely tribromophosphine oxide, the inorganic bromine salt avoids the generation of a large amount of phosphine-containing wastewater and reduces the environmental pollution. Compared with hydrogen bromide gas, the method has the advantages of cost advantage, easier operation and use in the reaction process, and higher safety and reliability, so the method is easier for industrial production.
Detailed Description
The present invention will be described in more detail with reference to examples, but the present invention is not limited to these examples.
Example 1
Synthesis of 3-bromo-1- (3-chloropyridin-2-yl) -3-pyrazolidinone-5-carboxylic acid ethyl ester
500mL of toluene, ethyl pyrazolecarboxylate (85.1g, 98% and 0.24mol) and sodium bromide (27.4g, 99% and 0.264mol) are sequentially added into a 1000mL reaction bottle, the temperature is raised to 90 ℃, the temperature is maintained at 90 ℃ for reaction for 4 hours, the temperature is lowered to room temperature of 25 ℃, the filtration is carried out, and the toluene is evaporated from the filtrate under reduced pressure to obtain 78.1g of a product. The content of the product is 98.1% by external standard method quantitative analysis, and the yield is 95.9%.1H-NMR(600MHz，CDCl3):δ＝3.25-3.45(m,2H),δ＝5.28(t，1H)，δ＝6.88(t，1H)，δ＝7.67(d，1H)，δ＝8.10(d，1H)，δ＝1.20(t，3H)，δ＝4.18(q,2H)。
Example 2
Synthesis of 3-bromo-1- (3-chloropyridin-2-yl) -3-pyrazolidinone-5-carboxylic acid ethyl ester
500mL of toluene, ethyl pyrazolecarboxylate (85.1g, 98% and 0.24mol) and potassium bromide (31.7g, 99% and 0.264mol) are sequentially added into a 1000mL reaction bottle, the temperature is raised to 90 ℃, the temperature is maintained at 90 ℃ for reaction for 4 hours, the temperature is lowered to room temperature of 25 ℃, the filtration is carried out, and the toluene is evaporated from the filtrate under reduced pressure, so that 78.41g of the product is obtained. The content of the product is 97.6% by external standard method quantitative analysis, and the yield is 95.9%.1H-NMR(600MHz，CDCl3):δ＝3.25-3.45(m,2H),δ＝5.28(t，1H)，δ＝6.88(t，1H)，δ＝7.67(d，1H)，δ＝8.10(d，1H)，δ＝1.20(t，3H)，δ＝4.18(q,2H)。
Example 3
Synthesis of 3-bromo-1- (3-chloropyridin-2-yl) -3-pyrazolidinone-5-carboxylic acid ethyl ester
500mL of xylene, ethyl pyrazolecarboxylate (100.3g, 98%, 0.24mol) and potassium bromide (31.7g, 99%, 0.264mol) are sequentially added into a 1000mL reaction bottle, the temperature is raised to 100 ℃, the temperature is maintained at 100 ℃ for reaction for 3 hours, the temperature is lowered to room temperature of 25 ℃, the filtration is carried out, and the xylene is evaporated from the filtrate under reduced pressure to obtain 77.7g of a product. The content of the product is 97.6% by external standard method quantitative analysis, and the yield is 95%.1H-NMR(600MHz，CDCl3):δ＝3.25-3.45(m,2H),δ＝5.28(t，1H)，δ＝6.88(t，1H)，δ＝7.67(d，1H)，δ＝8.10(d，1H)，δ＝1.20(t，3H)，δ＝4.18(q,2H)。
Example 4
Into a 1000mL reaction flask were added 500mL of xylene, ethyl pyrazolecarboxylate (103.7g, 98%, 0.24mol), nickel bromide (58.2g, 99%, 0.264mol) in that order, andheating to 80 ℃, keeping the temperature at 80 ℃ for reaction for 5 hours, cooling to room temperature of 25 ℃, filtering, and evaporating xylene from the filtrate under reduced pressure to obtain 78g of a product. The content of the product is 97% by external standard method quantitative analysis, and the yield is 94.8%.1H-NMR(600MHz，CDCl3):δ＝3.25-3.45(m,2H),δ＝5.28(t，1H)，δ＝6.88(t，1H)，δ＝7.67(d，1H)，δ＝8.10(d，1H)，δ＝1.20(t，3H)，δ＝4.18(q,2H)。
Example 5
Adding 500mL of xylene, ethyl pyrazolecarboxylate (93.5g, 98% and 0.2mol) and calcium bromide (48g, 99% and 0.24mol) into a 1000mL reaction bottle in sequence, heating to 80 ℃, keeping the temperature at 80 ℃ for reaction for 5 hours, cooling to room temperature of 25 ℃, filtering, and evaporating xylene from the filtrate under reduced pressure to obtain 71.92g of a product. The content of the product is 98% by external standard method quantitative analysis, and the yield is 96%.1H-NMR(600MHz，CDCl3):δ＝3.25-3.45(m,2H),δ＝5.28(t，1H)，δ＝6.88(t，1H)，δ＝7.67(d，1H)，δ＝8.10(d，1H)，δ＝1.20(t，3H)，δ＝4.18(q,2H)。
It can be seen from the above examples that the present invention uses inexpensive inorganic bromine salt as a brominating agent for synthesizing bromopyrazole carboxylate, and the high yield of bromopyrazole carboxylate is obtained by substitution reaction of 3-substituted sulfonyloxy pyrazole carboxylate with inorganic bromine salt, thereby completing the present invention. Compared with other brominating reagents, namely tribromophosphine oxide and hydrogen bromide, the inorganic bromine salt avoids the generation of a large amount of phosphine-containing wastewater, reduces the environmental pollution, has cost advantage, is easier to operate and use in the reaction process, and is safer and more reliable. In addition, the method of the invention is simple and easy for post-treatment, and the high-content bromo-pyrazole carboxylate can be obtained in high yield only by filtering and concentrating.
Examples of the applications
Chlorantraniliprole
According to the reaction formula, the 3-p-toluenesulfonate-1-pyridylpyrazole-5-carboxyethyl ester prepared in the above example is subjected to bromination, hydrolysis, acylation and oxidation to prepare pyrazole acyl chloride, and then the pyrazole acyl chloride is reacted with 2-amino-3-methyl-5-chlorobenzoylmethylamine to prepare a commercial variety chlorantraniliprole (common name: chlorantraniliprole), wherein the content is 98%, and the total reaction yield is 73.8% (calculated by 3-p-toluenesulfonate-1-pyridylpyrazole-5-carboxyethyl ester).
It can be seen from the above application examples that the invention adopts inorganic bromine salt with low price as a bromination reagent for synthesizing bromopyrazole carboxylate, and the bromopyrazole carboxylate is obtained with high yield through the substitution reaction of 3-substituted sulfonyloxy pyrazole carboxylate and inorganic bromine salt, and meanwhile, the bromopyrazole carboxylate is further used as an intermediate for preparing bisamide insecticides, so that high-content commercial insecticide chlorantraniliprole can be prepared with high yield. The method improves the quality of the product, reduces the production cost, and simultaneously reduces the discharge of three wastes, so the method is easier for industrialized production.
Claims (8)
1. A preparation method of bromo-pyrazole carboxylic ester compounds has the following reaction formula:
adding 3-substituted sulfonyloxy pyrazole carboxylate (II) into a proper organic solvent, and adding a brominating reagent to prepare a bromo pyrazole carboxylate compound (I); the brominating reagent is one or more of inorganic bromine salts.
2. The process for preparing bromopyrazole carboxylic acid ester compounds according to claim 1, wherein: the inorganic bromine salt is one or more of sodium bromide, potassium bromide, lithium bromide, ammonium bromide, magnesium bromide, calcium bromide, zinc bromide, barium bromide, ferric bromide, copper bromide and nickel bromide; the amount of the compound is 0.5 to 3 times of the molar amount of the compound represented by the general formula (II).
3. The process for producing a bromopyrazole carboxylic acid ester compound according to claim 1 or 2, wherein: the reaction temperature is 0-130 ℃, and the reaction is carried out for 0.5-24 hours.
4. The process for preparing bromopyrazole carboxylic acid esters according to claim 3, wherein: adding 3-substituted sulfonyloxy pyrazole carboxylate (II) into a proper organic solvent, adding a brominating agent with the molar weight of 0.7-2 times of that of the compound shown in the general formula (II), reacting for 1-18 hours at 20-110 ℃, and reacting to obtain the bromo pyrazole carboxylate compound (I).
5. The process for preparing bromopyrazole carboxylic acid esters according to claim 4, wherein: adding 3-substituted sulfonyloxy pyrazole carboxylate (II) into a proper organic solvent, adding a brominating agent with the molar weight 1-1.5 times that of the compound shown in the general formula (II), reacting for 2-12 hours at 40-90 ℃, and reacting to obtain the bromo pyrazole carboxylate compound (I).
6. The process for preparing bromopyrazole carboxylic acid ester compounds according to claim 2, wherein: the inorganic bromine salt is selected from sodium bromide, magnesium bromide, calcium bromide, zinc bromide or copper bromide.
7. The process for preparing bromopyrazole carboxylic acid ester compounds according to claim 1, wherein: the organic solvent is selected from diethyl ether, methyl butyl ether, tetrahydrofuran, dioxane, dimethoxyethane, toluene, xylene, chlorobenzene, dichlorobenzene, pentane, hexane, cyclohexane, heptane, dichloromethane, dichloroethane, chloroform, methyl acetate, ethyl acetate, butyl acetate, acetone, methyl ethyl ketone, cyclohexanone, acetonitrile, propionitrile, N-dimethylformamide, N-dimethylacetamide, dimethyl sulfoxide or N-methylpyrrolidone.
8. The process for preparing bromopyrazole carboxylic acid esters according to claim 7, wherein: the suitable solvent is selected from tetrahydrofuran, toluene, xylene, chlorobenzene, methylethylketone, acetonitrile or N, N-dimethylformamide.
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| CN202010777398.5A CN114057686A (en) | 2020-08-05 | 2020-08-05 | Preparation method of bromo-pyrazole carboxylic ester compound |
| PCT/CN2021/108021 WO2022028258A1 (en) | 2020-08-05 | 2021-07-23 | Preparation method for bromopyrazole carboxylate compound |
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| TW202342443A (en) * | 2022-01-31 | 2023-11-01 | 美商富曼西公司 | Methods for the preparation of ethyl 3-bromo-1-(3-chloropyridin-2-yl)-4,5-dihydro-1h-pyrazole-5-carboxylate |
| WO2024049748A1 (en) * | 2022-08-29 | 2024-03-07 | Fmc Corporation | A new and efficient process for preparing 3 -halo-4, 5-dihydro-1h-pyrazoles |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20050215798A1 (en) * | 2002-07-31 | 2005-09-29 | Annis Gary D | Method for preparing 3-halo-4,5-dihydro-1h-pyrazoles |
| CN1826332A (en) * | 2002-07-31 | 2006-08-30 | 纳幕尔杜邦公司 | Method for preparing 3-halo-4,5-dihydro-1H-pyrazoles |
| CN101558056A (en) * | 2006-12-15 | 2009-10-14 | 石原产业株式会社 | Process for production of anthranilamide compound |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US20050215798A1 (en) * | 2002-07-31 | 2005-09-29 | Annis Gary D | Method for preparing 3-halo-4,5-dihydro-1h-pyrazoles |
| CN1826332A (en) * | 2002-07-31 | 2006-08-30 | 纳幕尔杜邦公司 | Method for preparing 3-halo-4,5-dihydro-1H-pyrazoles |
| CN101558056A (en) * | 2006-12-15 | 2009-10-14 | 石原产业株式会社 | Process for production of anthranilamide compound |
Non-Patent Citations (1)
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| 吴永果等: "3-溴-1-(3-氯-2-吡啶基)-4,5-二氢-1H-吡唑-5-甲酸乙酯的合成研究", 《精细化工中间体》 * |
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