Preparation method of bisamide insecticide intermediate pyrazole ester

Abstract

The invention belongs to the technical field of preparation of chemical pesticide raw material medicines, and particularly relates to a preparation method of a bisamide pesticide intermediate pyrazole ester, and the intermediate pyrazole ester is prepared by a substitution reaction of a compound R-1 and a compound R-3 under alkaline conditions. In the formula (I), R1 is alkyl of C1-C4; x is halogen. According to the preparation method, the reaction conditions of each step are mild, the yield of each step is relatively high, the problem that the yield of a key step is too low in the prior art is solved, and the production cost of the intermediate pyrazole ester is greatly reduced; the preparation method has the advantages of few by-products in each step, less three wastes and green and clean process, and overcomes the problem of large wastewater amount in the prior art.

Description

Technical Field

[0001] The invention belongs to the technical field of manufacturing chemical pesticide raw materials, and particularly relates to a method for preparing pyrazolyl ester, an intermediate of a diamide insecticide. Background Art

[0002] Diamide insecticides are a new class of chemical insecticides that effectively activate the ryanodine receptors of pests, causing them to excessively release calcium ions from their intracellular calcium stores, leading to paralysis and death. Diamide insecticides are typically prepared from pyrazolyl esters, a diamide insecticide intermediate. The chemical structure of pyrazolyl esters is shown below:

[0003] Wherein, R1 is selected from an alkyl group having 1 to 4 carbon atoms.

[0004] This intermediate pyrazolyl can be further converted with other raw materials to obtain diamide compounds, which can be used as diamide insecticides, such as chlorantraniliprole, cyantraniliprole, cyclofenamic acid, and thiofenamic acid. Therefore, this intermediate pyrazolyl is an extremely important intermediate in the diamide insecticide industry.

[0005] According to the inventor's research, the following route is generally used to prepare this intermediate pyrazole ester:

[0006] This route involves reacting 2,3-dichloropyridine with hydrazine hydrate to produce hydrazine pyridine, which is then cyclized with diethyl maleate in the presence of sodium ethoxide. The reaction then proceeds to bromination with phosphorus oxybromide and oxidation with potassium persulfate to produce the pyrazole ester. The inventors have found that this route utilizes a large number of chemical reagents, which can easily generate three wastes (waste salt, wastewater, and waste acid), leading to high production costs. For example, the cyclization step with hydrazine pyridine and diethyl maleate yields a low yield. The bromination step with phosphorus oxybromide has a bromine utilization rate of only 50%, generating a large amount of phosphorus- and bromine-containing wastewater that is difficult to treat. Potassium persulfate is often used in conjunction with concentrated sulfuric acid for oxidation, which, due to the large amount of concentrated sulfuric acid used, produces a large amount of waste acid. Furthermore, product isolation requires additional water washing to remove the residual sulfuric acid from the target compound, generating a large amount of wastewater. This results in a cumbersome post-processing process and a high level of waste. Summary of the Invention

[0007] The purpose of the present invention is to provide a method for preparing pyrazolyl ester, an intermediate of a diamide insecticide, thereby overcoming the shortcomings of the prior art, providing a method for preparing the intermediate pyrazolyl ester, reducing the addition of chemical reagents, reducing the generation of waste, and realizing the green industrial production of the intermediate pyrazolyl ester.

[0008] In order to achieve the above object, the technical solution of the present invention is: The present invention provides a method for preparing pyrazolyl ester, an intermediate of a diamide insecticide. , prepared by a substitution reaction between compound R-1 and compound R-3 under alkaline conditions; 、

[0009] Wherein, R1 is a C1-C4 alkyl group; X is a halogen.

[0010] In the substitution reaction of compound R-3 of the present invention, the electron-withdrawing effect of the nitrogen atom of the pyridine ring significantly reduces the leaving ability of the halogen atom on the ring. The halogen atom, as an electron-withdrawing group, further weakens the electron density of the ring, making nucleophilic substitution difficult to occur. Secondly, there are no strong electron-withdrawing groups (such as nitro or cyano) on the pyridine ring to activate the ortho-para positions of the halogen atom, making it difficult for nucleophilic reagents to attack the halogen substitution site. Through experiments, the present invention unexpectedly discovered that when using compound R-3 and compound R-1 as raw materials, the intermediate pyrazole ester can be obtained in high yield under alkaline conditions. The main reason for this is that the ester substituent at the 3-position of compound R-1 can increase the formation of N - The stability of the ion is beneficial to improving its nucleophilicity, thereby increasing the nucleophilic reaction activity; at the same time, the ester group can enhance the fat solubility of compound R-1, allowing compound R-1 and compound R-3 to react in a homogeneous system, which is beneficial to the reaction and thus the intermediate pyrazole ester can be obtained in high yield.

[0011] In some embodiments, R1 is one of methyl, ethyl, propyl, and butyl; X is one of F, Cl, Br and I; Preferably, X is F or Cl. Studies have shown that when X is F or Cl, especially F, the yield of the intermediate pyrazole ester is higher.

[0012] The present invention is to prepare an intermediate pyrazole ester by substitution reaction of compound R-1 and compound R-3. The reaction conditions of the synthesis process are mild, and the product content and yield are high. At the same time, the raw materials used are simple and easy to obtain. Compound R-3 is an existing commercially available product. When R1 is a methyl group or an ethyl group, compound R-1 can use a commercially available product, thereby avoiding a complicated synthesis process. The synthesis method of the present invention avoids the problems of cumbersome operation steps and the need to use potassium persulfate for oxidation in the traditional synthesis process, and then the problem of using a large amount of concentrated sulfuric acid together and the generation of a large amount of wastewater in the subsequent treatment process.

[0013] In some embodiments, the base added in the substitution reaction includes but is not limited to alkali metal hydrides such as sodium hydride; or alkali metal alkoxides, such as sodium methoxide, sodium ethoxide; or alkali metal hydroxides, such as potassium hydroxide, sodium hydroxide; or alkali metal carbonates, phosphates, acetates, bicarbonates, such as lithium carbonate, sodium carbonate, potassium carbonate, cesium carbonate, sodium phosphate, potassium phosphate, sodium dihydrogen phosphate, disodium hydrogen phosphate, potassium dihydrogen phosphate, dipotassium hydrogen phosphate, sodium acetate, potassium acetate, sodium bicarbonate, potassium bicarbonate; or tertiary amines, such as triethylamine, diisopropylethylamine.

[0014] Specifically, the base is sodium hydroxide, potassium hydroxide, sodium bicarbonate, potassium bicarbonate, sodium carbonate, potassium carbonate, sodium methoxide and sodium ethoxide.

[0015] More specifically, the base is one or more of sodium carbonate, potassium carbonate, sodium methoxide and sodium ethoxide.

[0016] In the present invention, during the substitution reaction between compound R-1 and compound R-3, the addition of a base can neutralize the by-product acid and activate the nucleophilic reagent, thereby promoting the efficient substitution reaction of compound R-1 on compound R-3 and ensuring that the reaction proceeds efficiently and thoroughly.

[0017] Sodium ethoxide or sodium methoxide is usually dissolved in ethanol or methanol for use, and has good polarity matching with compound R-1 and compound R-3, forming a homogeneous reaction system, reducing mass transfer resistance, activating nucleophiles, and promoting the efficient substitution reaction of compound R-1 on compound R-3.

[0018] In some embodiments, the sodium ethoxide is an ethanol solution of sodium ethoxide, and the concentration of the ethanol solution of sodium ethoxide is 10-25 wt %.

[0019] Specifically, the concentration of the sodium ethoxide ethanol solution is 15-25wt%.

[0020] In some embodiments, the sodium methoxide is a methanol solution of sodium methoxide, and the concentration of the methanol solution of sodium methoxide is 10-35 wt %; Specifically, the concentration of the methanol solution of sodium methoxide is 15-30 wt %.

[0021] In some embodiments, the molar ratio of compound R-1, compound R-3, and base in the substitution reaction is 1:(0.8-1.2):(1-3). Within this dosage range, compound R-1 and compound R-3 react more thoroughly, resulting in a higher product content and yield.

[0022] Specifically, in the substitution reaction, the molar ratio of the compound R-1, the compound R-3 and the base is 1:(0.9-1.1):(1.5-2.5).

[0023] More specifically, in the substitution reaction, the molar ratio of the compound R-1, the compound R-3 and the base is 1:(1-1.05):(2-2.2).

[0024] The product content and yield generated within this dosage range are optimal.

[0025] In some embodiments, the solvent used in the substitution reaction includes, but is not limited to, C1-C4 alcohols, aliphatic ketones, acetates, aromatic solvents, heteroaromatic solvents, aliphatic solvents, halogenated solvents, nitriles, amides, sulfones, sulfoxides, and mixtures thereof.

[0026] Specifically, the solvent used in the substitution reaction is ethanol, acetone, or acetonitrile.

[0027] In some embodiments, the substitution reaction time is 8 to 12 h.

[0028] In some embodiments, the compound R-1 is prepared by bromination of compound R-2;

[0029] Wherein, R1 is a C1-C4 alkyl group.

[0030] When R1 of compound R-1 is methyl or ethyl, commercially available products can be used directly, or compound R-2 can be prepared by bromination. The process of preparing compound R-1 by bromination of compound R-2 is mild, simple to operate, and produces a high product content and yield.

[0031] Specifically, the brominating agent in the bromination reaction is HBr or an alkali metal bromide salt such as sodium bromide, potassium bromide or an alkaline earth metal bromide salt such as magnesium bromide, calcium bromide.

[0032] More specifically, the brominating agent is HBr.

[0033] More specifically, the concentration of the HBr solution is 20-50 wt %, preferably 30-50 wt %.

[0034] Specifically, sodium nitrite and cuprous bromide are also added into the bromination reaction.

[0035] More specifically, the molar ratio of the compound R-2, sodium nitrite and cuprous bromide is 1:(1-2):(1-3), preferably 1:(1-1.5):(1-2.5); more preferably 1:(1.3-1.5):(1.5-2.5).

[0036] Within this dosage range, the reaction of compound R-2, sodium nitrite and cuprous bromide is more thorough, and the content and yield of the generated product are higher.

[0037] Specifically, the solvent used in the bromination reaction includes, but is not limited to, one of acetonitrile, dichloroethane, dibromoethane, dichloromethane, benzene, xylene, toluene, tetrahydrofuran, dimethyl sulfoxide, N,N-dimethylformamide, and acetone.

[0038] More specifically, the solvent used in the bromination reaction is selected from one of dichloroethane, toluene and dichloromethane.

[0039] More specifically, the solvent used in the bromination reaction is ethylene dichloride.

[0040] Specifically, the temperature of the bromination reaction is 20-30 °C.

[0041] Specifically, the bromination reaction time is 4-6 h.

[0042] Specifically, compound R-2 and the brominating agent are mixed evenly, cooled to 0-5 ° C, sodium nitrite solution is added dropwise, heated to 20-30 ° C, mixed evenly, and then cuprous bromide is added and reacted for 4-6 h.

[0043] In some embodiments, the compound R-2 is prepared by a ring-closing reaction of compound 2 and hydrazine hydrate;

[0044] Wherein, R1 is a C1-C4 alkyl group.

[0045] Specifically, an acid is further added in the ring-closure reaction; the molar ratio of the compound 2, hydrazine hydrate and the acid is 1:(1.0-2.0):(0.9-1.8).

[0046] More specifically, the molar ratio of the compound 2, hydrazine hydrate and acid is 1:(1.0-1.5):(1.0-1.5).

[0047] More specifically, the molar ratio of compound 2, hydrazine hydrate, and acid is 1:(1.0-1.3):(1.2-1.4). Within this dosage range, the reaction of compound 2, hydrazine hydrate, and acid is more thorough, resulting in a higher product content and yield.

[0048] Specifically, the solvent used in the ring-closure reaction includes, but is not limited to, acetonitrile, dichloroethane, benzene, xylene, toluene, tetrahydrofuran, dimethyl sulfoxide, N,N-dimethylformamide, and acetone.

[0049] More specifically, the solvent used in the substitution reaction is selected from one of benzene, xylene and toluene.

[0050] More specifically, the solvent used in the substitution reaction is toluene.

[0051] Specifically, the conditions for the ring-closure reaction are: heating under reflux for 12 to 16 hours.

[0052] Specifically, acid and hydrazine hydrate are sequentially added dropwise to a solution of compound 2 at 0-5° C., and then the temperature is raised to reflux for reaction.

[0053] In some embodiments, the compound 2 is prepared by condensing compound 1 with acetonitrile and sodium alkoxide;

[0054] Wherein, R1 is a C1-C4 alkyl group.

[0055] Specifically, the molar ratio of the compound 1, acetonitrile and sodium alkoxide is 1:(3-10):(2.0-3.5), preferably 1:(5-8):(2.0-3.0), and more preferably 1:(5.0-5.5):(2.0-2.3).

[0056] Specifically, the solvent used in the condensation reaction includes but is not limited to acetone, butanone, N,N-dimethylformamide, dimethyl sulfoxide, acetonitrile, benzene, toluene, xylene, 2-methyltetrahydrofuran, tetrahydrofuran, dichloroethane, dichloromethane, chloroform, preferably 2-methyltetrahydrofuran or tetrahydrofuran.

[0057] Specifically, the temperature of the condensation reaction is 15-25°C.

[0058] Specifically, the condensation reaction time is 10 to 14 h.

[0059] Specifically, sodium alkoxide is added to a mixed solution of compound 1 and acetonitrile at 0-5°C, and then the temperature is raised to 15-25°C and the reaction is carried out for 10-14 hours.

[0060] Beneficial effects of the present invention: (1) The present invention prepares the intermediate pyrazole ester by substitution reaction of compound R-1 and compound R-3. The reaction conditions of the synthesis process are mild, and the product content and yield are high. At the same time, the raw materials used are simple and easy to obtain. Compound R-3 is an existing commercial product. When R1 is methyl or ethyl, compound R-1 can also use a commercial product, thus avoiding a complicated synthesis process. The synthesis method of the present invention avoids the problems of the traditional synthesis process, such as the cumbersome operation steps and the need to use potassium persulfate for oxidation and then combine with a large amount of concentrated sulfuric acid, as well as the generation of a large amount of wastewater during the subsequent treatment process.

[0061] (2) The present invention provides a feasible new route for the synthesis of intermediate pyrazole esters. The reaction conditions of each step of the preparation method are mild and the yield of each step is high, which overcomes the problem of low yield of key steps in the prior art and greatly reduces the production cost of the intermediate pyrazole esters. In the preparation method, each step has few by-products and less three wastes, and the process is green and clean, which overcomes the problem of large amount of wastewater in the prior art. BRIEF DESCRIPTION OF THE DRAWINGS

[0062] The accompanying drawings, which constitute a part of the present invention, are used to provide a further understanding of the present invention. The exemplary embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute improper limitations on the present invention.

[0063] Figure 1 This is a liquid chromatogram of compound Ia prepared in Example 1 of the present invention; Figure 2 This is the mass spectrum of compound Ia prepared in Example 1 of the present invention. DETAILED DESCRIPTION

[0064] Those skilled in the art will appreciate that the following examples are intended to illustrate the present invention only and should not be construed as limiting the scope of the invention. Unless otherwise specified, the examples were performed under conventional conditions or manufacturer's recommended conditions. Components used without manufacturer's indication are commercially available conventional products.

[0065] As described in the background technology, the prior art for synthesizing the intermediate pyrazole ester uses many chemical reagents, which easily produces three wastes (waste salt, waste water, and waste acid) and has a high production cost. In order to solve the above technical problems, the present invention proposes a method for preparing the intermediate pyrazole ester.

[0066] A typical embodiment of the present invention provides a method for preparing an intermediate pyrazole ester, comprising the following synthetic route:

[0067] Wherein, R1 is selected from C1-C4 alkyl.

[0068] In order to enable those skilled in the art to more clearly understand the technical solution of the present invention, the technical solution of the present invention will be described in detail below with reference to specific embodiments.

[0069] Example 1 The synthesis steps of ethyl 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylate (Compound Ia) are as follows: Step 1: Condensation reaction To a 3 L round-bottom flask equipped with a stirrer and thermometer, add 200.0 g of diethyl oxalate (1.36 mol), 300.0 g (7.3 mol) of acetonitrile, and 1.5 L of tetrahydrofuran. The temperature was lowered to 0°C and 200.0 g (2.9 mol) of solid sodium ethoxide was added. After the addition was complete, the temperature was slowly raised to 20°C. The reaction was stirred for 12 h, filtered, and the filter cake was rinsed with 300.0 g of tetrahydrofuran to obtain 200 g of ethyl cyanoaceruvate sodium salt with a content of 97.6% and a yield of 88.0%.

[0070] Step 2: Ring closure reaction 800.0 g of toluene and 200.0 g (1.2 mol) of sodium cyanoacetone ethyl ester were added to a 2 L round-bottom flask equipped with a stirrer and a thermometer. The temperature was lowered to 0°C and 100.0 g (1.66 mol) of acetic acid was added dropwise. After the addition was complete, 80.0 g (1.28 mol) of 80% hydrazine hydrate was added dropwise at 0-5°C. After the addition was complete, the temperature was raised to reflux for 14 h. A water separator was used to separate water during the reflux process. After the reaction was completed, the solvent was removed by decompression and desolvation. 500 ml of water and 500 ml of toluene were added, the mixture was stirred and separated, and 500 ml of toluene was added for extraction twice. The organic phases were combined and desolvated under reduced pressure to obtain 133 g of ethyl 5-amino-1H-pyrazole-3-carboxylate, with a content of 98% and a yield of 70%.

[0071] Step 3: Bromination reaction To a 2L round-bottom flask equipped with a stirrer and a thermometer, 5-amino-1H-pyrazole-3-carboxylic acid ethyl ester (108 g, 0.682 mol) was added, 48% HBr 500 ml was added, the temperature was lowered to 0 ° C, and sodium nitrite (70 g, 1.0 mol) aqueous solution (150 ml) was slowly added dropwise. After the addition was complete, the temperature was raised to 25 ° C and stirred for 30 minutes. Cuprous bromide (200 g, 1.36 mol) was added and stirred at 25 ° C for 5 h. Saturated sodium bicarbonate aqueous solution was added to neutralize to pH = 6-7, and 500 ml of dichloroethane was added for extraction. The aqueous layer was extracted twice with 500 ml of dichloroethane. The dichloroethane layers were combined and desolvated under reduced pressure to give 122 g of 5-bromo-1H-3-pyrazolecarboxylic acid ethyl ester, content: 98%, yield 80%.

[0072] Step 4: Substitution Reaction In a 1L round-bottom flask equipped with a stirrer and a thermometer, 111.7g (0.5mol) of 5-bromo-1H-3-pyrazolecarboxylic acid ethyl ester and 75g (0.5mol) of 2,3-dichloropyridine were added, 500ml of acetone was added, and the mixture was stirred until clear. 140g (1mol) of potassium carbonate solid was added, the temperature was raised to reflux, and the reaction was kept at this temperature for 10h. The mixture was cooled to room temperature, filtered, and the filtrate was distilled under reduced pressure to remove the solvent to obtain 138g of 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic acid ethyl ester (Compound Ia), with a content of 95% and a yield of 79%. Figures 1 and 2 shown.

[0073] Example 2 The synthesis steps of 3-bromo-1-(3-chloro-2-pyridyl)-1H-pyrazole-5-carboxylic acid methyl ester are as follows: Step 1: Condensation reaction To a 3 L round-bottom flask equipped with a stirrer and thermometer, 162.2 g of dimethyl oxalate (1.36 mol), 300.0 g (7.3 mol) of acetonitrile, and 1.5 L of 2-methyltetrahydrofuran were added. The temperature was lowered to 0°C and 160.0 g (2.9 mol) of solid sodium methoxide was added. After the addition was complete, the temperature was slowly raised to 20°C. The reaction was stirred for 12 h, filtered, and the filter cake was rinsed with 300.0 g of 2-methyltetrahydrofuran to obtain 186.2 g of methyl cyanoaceruvate sodium salt, with a content of 98% and a yield of 90%.

[0074] Step 2: Ring closure reaction 800.0 g of toluene and 182.5 g (1.2 mol) of sodium cyanoacetonate were added to a 2 L round-bottom flask equipped with a stirrer and a thermometer. The temperature was lowered to 0°C and 100.0 g (1.66 mol) of acetic acid was added dropwise. After the addition was complete, 90.1 g (1.44 mol) of 80% hydrazine hydrate was added dropwise at 0-5°C. After the addition was complete, the temperature was raised to reflux for 14 h. A water separator was used to separate water during the reflux process. After the reaction was completed, the solvent was removed by decompression. 500 ml of water and 500 ml of toluene were added, the mixture was stirred and separated, and 500 ml of toluene was added for extraction twice. The organic phases were combined and decompressed to obtain 132.7 g of methyl 5-amino-1H-pyrazole-3-carboxylate, with a content of 97% and a yield of 76%.

[0075] Step 3: Bromination reaction To a 2L round-bottom flask equipped with a stirrer and a thermometer, 5-amino-1H-pyrazole-3-carboxylic acid methyl ester (99.2g, 0.682mol) was added, 40% HBr 500ml was added, the temperature was lowered to 0°C, and an aqueous solution of sodium nitrite (70g, 1.0mol) (150ml) was slowly added dropwise. After the addition was complete, the temperature was raised to 25°C and stirred for 30 minutes. Cuprous bromide (200g, 1.36mol) was added and stirred at 25°C for 5 hours. Saturated aqueous sodium bicarbonate solution was added to neutralize the pH to 6-7, and 500ml of dichloroethane was added for extraction. The aqueous layer was extracted twice with 500ml of dichloroethane. The dichloroethane layers were combined and desolvated under reduced pressure to give 116.7g of 5-bromo-1H-3-pyrazolecarboxylic acid methyl ester, with a content of 97% and a yield of 81%.

[0076] Step 4: Substitution Reaction In a 1 L round-bottom flask equipped with a stirrer and a thermometer, 105.7 g (0.5 mol) of 5-bromo-1H-3-pyrazolecarboxylic acid methyl ester and 75 g (0.5 mol) of 2,3-dichloropyridine were added, and 500 ml of methanol was added. The mixture was stirred until dissolved, and 106 g (1 mol) of sodium carbonate solid was added. The temperature was raised to reflux and the reaction was kept at this temperature for 10 h. The mixture was cooled to room temperature, filtered, and the filtrate was distilled under reduced pressure to remove the solvent to obtain 136.8 g of 3-bromo-1-(3-chloro-2-pyridyl)-1H-pyrazole-5-carboxylic acid methyl ester with a content of 96% and a yield of 83%.

[0077] Example 3 The synthesis steps of 3-bromo-1-(3-chloro-2-pyridyl)-1H-pyrazole-5-carboxylic acid methyl ester are as follows: Among them, steps 1 to 3 are the same as in Example 2, except that the substitution reaction in step 4 is different. The substitution reaction process in step 4 is as follows: Step 4: Substitution Reaction In a 1 L round-bottom flask equipped with a stirrer and a thermometer, 105.7 g (0.5 mol) of methyl 5-bromo-1H-3-pyrazolecarboxylate and 75 g (0.5 mol) of 2,3-dichloropyridine were added, and 500 ml of methanol was added. The mixture was stirred until dissolved. The reaction temperature was controlled at 25°C, and 108 g (0.6 mol) of a 30% sodium methoxide methanol solution was added dropwise. The reaction was kept warm for 8 h. Glacial acetic acid was added to adjust the pH to 6-7. The mixture was filtered, and the filtrate was distilled under reduced pressure to remove the solvent to obtain 141.6 g of methyl 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylate, with a content of 95% and a yield of 85%.

[0078] Example 4 The synthesis steps of 3-bromo-1-(3-chloro-2-pyridyl)-1H-pyrazole-5-carboxylic acid methyl ester are as follows: Among them, steps 1 to 3 are the same as in Example 2, except that the substitution reaction in step 4 is different. The substitution reaction process in step 4 is as follows: Step 4: Substitution Reaction In a 1 L round-bottom flask equipped with a stirrer and a thermometer, 105.7 g (0.5 mol) of methyl 5-bromo-1H-3-pyrazolecarboxylate and 75 g (0.5 mol) of 2,3-dichloropyridine were added, and 500 ml of acetonitrile was added. The mixture was stirred until dissolved. 107 g (1 mol) of solid sodium carbonate was added, and the temperature was raised to reflux. The reaction was kept at this temperature for 10 h, cooled to room temperature, filtered, and the filtrate was distilled under reduced pressure to remove the solvent to obtain 130.2 g of methyl 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylate, with a content of 96% and a yield of 79%.

[0079] Example 5 The synthesis steps of ethyl 3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylate (Compound Ia) are as follows: Among them, steps 1 to 3 are the same as in Example 1, except that the substitution reaction in step 4 is different. The substitution reaction process in step 4 is as follows: Step 4: Substitution Reaction In a 1 L round-bottom flask equipped with a stirrer and a thermometer, 111.7 g (0.5 mol) of ethyl 5-bromo-1H-3-pyrazolecarboxylate and 65.8 g (0.5 mol) of 2-fluoro-3-chloropyridine were added, and 500 ml of acetone was added. The mixture was stirred until dissolved. 140 g (1 mol) of solid potassium carbonate was added, and the temperature was raised to reflux. The reaction was kept at this temperature for 10 h, cooled to room temperature, filtered, and the filtrate was distilled under reduced pressure to remove the solvent to obtain 155 g of ethyl 3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylate with a content of 96% and a yield of 90%.

[0080] The foregoing description is merely a preferred embodiment of the present invention and is not intended to limit the present invention. Those skilled in the art will readily appreciate that various modifications and variations of the present invention are possible. Any modifications, equivalent substitutions, or improvements made within the spirit and principles of the present invention are intended to be within the scope of protection of the present invention.

Claims

1. A method for preparing pyrazole esters, an intermediate of a diamide insecticide, characterized in that: The intermediate pyrazole ester , prepared by a substitution reaction between compound R-1 and compound R-3 under alkaline conditions; 、 Wherein, R1 is a C1-C4 alkyl group; X is a halogen.

2. The method for preparing pyrazole ester, an intermediate of the diamide insecticide according to claim 1, wherein: The base added in the substitution reaction is selected from alkali metal hydrides, alkali metal alkoxides, alkali metal hydroxides, alkali metal carbonates, alkali metal phosphates, alkali metal acetates, alkali metal bicarbonates or tertiary amines.

3. The method according to claim 1, characterized in that The molar ratio of the compound R-1, the compound R-3 and the base is 1:(0.8-1.2):(1-3); Alternatively, the substitution reaction time is 8 to 12 h.

4. The method for preparing pyrazole ester, an intermediate of the diamide insecticide according to claim 1, wherein: The X is F or Cl.

5. The method for preparing pyrazole ester, an intermediate of the diamide insecticide according to claim 1, wherein: The compound R-1 is prepared by bromination reaction of compound R-2; Wherein, R1 is a C1-C4 alkyl group.

6. The method for preparing pyrazole ester, an intermediate of the diamide insecticide according to claim 5, characterized in that: The brominating agent in the bromination reaction is HBr, alkali metal bromide or alkaline earth metal bromide; Alternatively, sodium nitrite and cuprous bromide are further added to the bromination reaction; or, the molar ratio of the compound R-2, sodium nitrite and cuprous bromide is 1:(1-2):(1-3); Or, the temperature of the bromination reaction is 20-30 ° C; Alternatively, the bromination reaction time is 4-6 h.

7. The method for preparing pyrazole ester, an intermediate of the diamide insecticide according to claim 5, characterized in that: The compound R-2 is prepared by a ring-closing reaction of compound 2 and hydrazine hydrate; Wherein, R1 is a C1-C4 alkyl group.

8. The method for preparing pyrazole ester, an intermediate of the diamide insecticide according to claim 7, characterized in that: Acid is also added to the ring-closure reaction; the molar ratio of compound 2, hydrazine hydrate and acid is 1: (1.0-2.0): (0.9-1.8); Alternatively, the ring-closure reaction conditions are: heating under reflux for 12 to 16 hours; Alternatively, acid and hydrazine hydrate are sequentially added dropwise to a solution of compound 2 at 0-5°C, and then the temperature is raised to reflux for reaction.

9. The method for preparing pyrazole ester, an intermediate of the bisamide insecticide according to claim 7, characterized in that: The compound 2 is prepared by condensing the compound 1 with acetonitrile and sodium alkoxide; Wherein, R1 is a C1-C4 alkyl group.

10. The method for preparing pyrazole esters as a diamide insecticide intermediate according to claim 9, characterized in that: The molar ratio of the compound 1, acetonitrile and sodium alkoxide is 1:(3-10):(2.0-3.5); Alternatively, the condensation reaction temperature is 15-25°C; Alternatively, the condensation reaction time is 10 to 14 hours.

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