CN114573494B - Preparation method of chlorfenapyr - Google Patents

Preparation method of chlorfenapyr Download PDF

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CN114573494B
CN114573494B CN202210389911.2A CN202210389911A CN114573494B CN 114573494 B CN114573494 B CN 114573494B CN 202210389911 A CN202210389911 A CN 202210389911A CN 114573494 B CN114573494 B CN 114573494B
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reaction
chlorophenyl
chlorfenapyr
carbonitrile
tetrahydrofuran
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CN114573494A (en
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刘新乐
王建昌
王锡峰
薛宏斌
罗瑞生
王振江
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Shandong Weifang Shuangxing Pesticide Co ltd
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
    • C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The invention relates to a method for preparing chlorfenapyr. In a mixed solvent, in the presence of a catalyst and an acid-binding agent, carrying out bromination reaction on 2-p-chlorophenyl-5-trifluoromethyl pyrrole-3-nitrile and bromine to prepare an intermediate 4-bromo-2-p-chlorophenyl-5-trifluoromethyl pyrrole-3-nitrile; and then the intermediate is respectively reacted with bromochloromethane and sodium ethoxide under the action of alkali, and the target product chlorfenapyr is obtained through post-treatment. The method has the advantages of simple reaction steps, mild reaction conditions, higher reaction yield and purity, and good industrial application value.

Description

Preparation method of chlorfenapyr
Technical Field
The invention relates to a preparation method of chlorfenapyr.
Background
Chlorfenapyr (chlorfenapyr), trade name: removing, chemical name: the 4-bromo-2- (4-chlorophenyl) -1-ethoxymethyl-5- (trifluoromethyl) pyrrole-3-carbonitrile (m.p. 100 ℃ C. To 101 ℃ C.) is a novel phenylpyrrole insecticidal acaricide, and the action point is mitochondria in insect cells, which is different from the current commonly used insecticide. The product has the characteristics of broad insecticidal spectrum, high activity, long lasting period, safety to beneficial organisms, environmental friendliness and the like, and has the effects of contact killing and stomach toxicity.
The synthetic method of the chlorfenapyr is more, wherein 2-p-chlorophenyl-5-trifluoromethyl-3-cyano pyrrole is a key intermediate for synthesizing the chlorfenapyr, and the intermediate is subjected to bromination reaction and then substitution reaction with chloromethyl ethyl ether to obtain the chlorfenapyr. However, since the pyrrole ring of the 2-p-chlorophenyl-5-trifluoromethyl-3-cyanopyrrole contains chlorophenyl, trifluoromethyl and cyano, the groups are all electron withdrawing groups, so that the activity of the intermediate in the bromination reaction is lower, and the prepared product and purity are not high.
Pasteur company (CN 110382462A) found that the use of DIPEA instead of triethylamine as an acid-binding agent can increase the yield of the bromination reaction. And the post-treatment is simpler and more convenient, and the alkali DIPEA is easy to recycle. The yield of the A3 bromination step in the patent example was 88.2%. Comparative example B3 had only 75.3% yield in the bromination step with triethylamine as the base.
During the synthesis of 4-bromo-2- (4-chlorophenyl) -5-trifluoromethyl pyrrole-3-carbonitrile, mixed solvent of chloroform and DMF, liquid bromine as brominating reagent and catalyst M are adopted to perform bromination reaction, and the purity of the product is up to 93.6% and the yield is up to 99%. The waste water containing more than 15% of HBr is produced, and chlorine can be introduced for oxidation to recover bromine. Although the yield of this reaction is high, the specific composition of M is not disclosed, and the purity of the product is not high.
Bai Refei (CN 102746208A) 2- (4-chlorophenyl) -5-trifluoromethylpyrrole-3-carbonitrile and an oxidizing agent are added to a polar solvent, and after uniform mixing, bromine is added, and after completion of the reaction, 4-bromo-2- (4-chlorophenyl) -5-trifluoromethylpyrrole-3-carbonitrile is obtained by post-treatment in a yield of 92% -96%.
Liu Yuan et al (CN 109369498A) disclose that 2-p-chlorophenyl-5-trifluoromethylpyrrole-3-carbonitrile solution and bromine solution are simultaneously and continuously introduced into a microreactor to react, and the obtained mixed solution flows through two or more reaction modules in the microreactor to react with hydrogen peroxide solution introduced into the microreactor and distilled to obtain 4-bromo-2-p-chlorophenyl-5-trifluoromethylpyrrole-3-carbonitrile.
Xu Shangcheng et al (Nanjing university of agriculture journal 2004, 27 (2): 105-108) disclose bromination of 2-p-chlorophenyl-5-trifluoromethylpyrrole-3-carbonitrile solution with bromine in sodium bicarbonate as an acid-binding agent in a yield of 91.6%.
Liu Yang et al (modern pesticides 2007,6 (2): 22-25 and 28) disclose substitution of 2-p-chlorophenyl-5- (trifluoromethyl) pyrrole-3-carbonitrile with bromine in chlorobenzene to give 2-p-chlorophenyl-4-bromo-5- (trifluoromethyl) pyrrole-3-carbonitrile in a reaction without the addition of an acid-binding agent with a yield of 90.7%.
In the process of preparing the chlorfenapyr in the prior art, a great deal of research is carried out in order to improve the yield and purity of the bromination reaction, however, the yield and purity of the obtained product still need to be improved, and the production cost needs to be reduced. Therefore, the development of a new method for preparing the chlorfenapyr still has huge market prospect and social benefit.
Disclosure of Invention
The technical problems to be solved by the invention are as follows: the preparation method of the chlorfenapyr has the advantages of high product purity, high yield, mild reaction conditions and simple post-treatment.
In order to solve the technical problem, the invention provides a method for preparing chlorfenapyr, which comprises the following steps:
1) In a mixed solvent, in the presence of a catalyst and an acid-binding agent, carrying out bromination reaction on 2-p-chlorophenyl-5-trifluoromethyl pyrrole-3-nitrile and bromine to prepare an intermediate 4-bromo-2-p-chlorophenyl-5-trifluoromethyl pyrrole-3-nitrile;
2) Reacting 4-bromo-2-p-chlorophenyl-5-trifluoromethyl pyrrole-3-carbonitrile with bromochloromethane and sodium ethoxide under the action of alkali, and performing aftertreatment to obtain a target product, namely chlorfenapyr;
the specific reaction formula is as follows:
preferably, the mixed solvent in step 1) is a mixed solvent of tetrahydrofuran and another inert solvent.
Suitable inert solvents are aliphatic hydrocarbons, preferably aliphatic C 5 -C 16 Hydrocarbons, more preferably C 5 -C 16 Alkanes, or C 5 -C 16 Cycloalkanes, such as pentane, hexane, cyclohexane or petroleum ether; halogenated hydrocarbons, preferably halogenated aliphatic C 1 -C 6 Paraffin, or halogenSubstituted aromatic C 6 -C 10 Hydrocarbons, e.g. CH 2 Cl 2 、CHCl 3 、CCl 4 、CH 2 ClCH 2 Cl、CCl 3 CH 3 、CHCl 2 CH 2 Cl、CCl 2 CCl 2 Or chlorobenzene; ethers, preferably C 1 -C 6 Cycloalkyl ethers, C 1 -C 6 alkyl-C 1 -C 6 Alkyl ether, C 1 -C 6 alkyl-C 3 -C 6 Cycloalkyl ethers, C 1 -C 6 polyol-C 1 -C 6 Alkyl ether and C 1 -C 6 alkyl-C 6 -C 10 Aryl ethers, e.g. CH 3 CH 2 OCH 2 CH 3 、(CH 3 ) 2 CHOCH(CH 3 ) 2 、CH 3 OC(CH 3 ) 3 (MTBE)、CH 3 OCH 3 (DME)、CH 3 OCH 2 CH 2 OCH 3 、CH 3 OC(CH 3 ) 2 CH 2 CH 3 And diethylene glycol; esters, preferably aliphatic C 1 -C 6 Alcohols and aliphatic C 1 -C 6 Esters of carboxylic acids, aromatic C 6 -C 10 Alcohols and aromatic C 6 -C 10 Esters of carboxylic acids, omega-hydroxy-C 1 -C 6 Cyclic esters of carboxylic acids, e.g. CH3C (O) OCH 2 CH 3 、CH 3 C(O)OCH 3 、CH 3 C(O)OCH 2 CH 2 CH 2 CH 3 、CH 3 C(O)OCH(CH 3 )CH 2 CH 3 、CH 3 C(O)OC(CH 3 )、CH 3 CH 2 CH 2 C(O)OCH 2 CH 3 、CH 3 CH(OH)C(O)OCH 2 CH 3 、CH 3 CH(OH)C(O)OCH 3 、CH 3 C(O)OCH 2 CH(CH 3 ) 2 、CH 3 C(O)OCH(CH 3 ) 2 、CH 3 CH 2 C(O)OCH 3 Benzyl benzoate and gamma-butyrolactone; carbonates, e.g. ethylene carbonate, propylene carbonate, CH 3 CH 2 OC(O)OCH 2 CH 3 And CH (CH) 3 OC(O)OCH 3 The method comprises the steps of carrying out a first treatment on the surface of the Nitriles, UOSelecting C 1 -C 6 Nitriles, e.g. ACN and CH 3 CH 2 A CN; alcohols, preferably C 1 -C 4 Alcohols and C 2 -C 4 Alkanediols, e.g. CH 3 OH、CH 3 CH 2 OH、CH 3 CH 2 CH 2 OH、CH 3 CH(OH)CH 3 、CH 3 (CH 2 ) 3 OH and C (CH) 3 ) 3 OH、CH 2 (OH)CH 2 (OH)、CH 3 CH(OH)CH 2 OH; amides and urea derivatives, preferably DMF, NMP, DMA, DMI, DMPU, HMPA; in addition, DMSO and sulfolane.
More preferably, the mixed solvent of step 1) is a mixed solvent of tetrahydrofuran and carbon tetrachloride; most preferably, in the mixed solvent, the volume ratio of tetrahydrofuran to carbon tetrachloride is 5:1-2.
Preferably, the catalyst in the step 1) is iron powder, manganese dioxide or ferric bromide; more preferably iron powder.
Preferably, the acid-binding agent of step 1) is selected from the group consisting of 4-dimethylaminopyridine, DIPEA, triethylamine, sodium bicarbonate, potassium bicarbonate, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate; most preferably, the acid binding agent is selected from 4-dimethylaminopyridine.
Preferably, the molar ratio of the 2-p-chlorophenyl-5-trifluoromethyl-pyrrole-3-carbonitrile, the bromine, the catalyst and the acid binding agent in the step 1) is 1:1.0-2.0:0.1-0.2:1.0-3.0, more preferably, the molar ratio is 1:1.0-1.2:0.1-0.15:1.0-1.5.
Preferably, the reaction temperature of step 1) is from 30 to 60 ℃, more preferably from 40 to 50 ℃;
preferably, the reaction time of step 1) is 2 to 10 hours, more preferably 3 to 5 hours.
The reaction mixture of step 1) may be worked up in a conventional manner, for example by mixing with water, separating the phases and, if appropriate, purifying the crude product in a conventional manner. Typically, after the reaction of step 1) is completed, the solvent is removed from the reaction mixture by distillation. Alternatively, after the completion of the reaction, water may be added to the mixture, a part of the solvent may be distilled off again, and then the aqueous layer may be removed and the organic layer containing the compound of formula III may be dried, for example, by adding a hygroscopic material. The product of step 1) may also be obtained by crystallization from an organic layer or by removal of an organic solvent.
Preferably, the post-treatment method of the step 1) is as follows: and (3) cooling the reaction liquid, adding water, stirring, distilling to remove the mixed solvent, precipitating a large amount of light yellow solid in the water phase, filtering, washing the filter cake with water for three times, collecting the filter cake, and drying to obtain the intermediate 4-bromo-2-p-chlorophenyl-5-trifluoromethyl pyrrole-3-nitrile.
The reaction process of step 2) may be carried out in a manner common in the art.
Preferably, the reaction process of step 2) is: dissolving 4-bromo-2-p-chlorophenyl-5-trifluoromethyl pyrrole-3-nitrile in tetrahydrofuran, slowly dropwise adding tetrahydrofuran containing sodium hydride, stirring for reaction, dropwise adding bromochloromethane, continuing the reaction, treating with tetrahydrofuran solution containing sodium ethoxide, detecting the reaction progress by TLC (thin layer chromatography), cooling, filtering, removing solvent, and recrystallizing with mixed solvent of n-hexane/ethyl acetate to obtain white solid chlorfenapyr.
Since the pyrrole ring of the 2-p-chlorophenyl-5-trifluoromethyl-3-cyanopyrrole contains chlorophenyl, trifluoromethyl and cyano, the groups are all electron withdrawing groups, so that the activity of the intermediate in the bromination reaction is lower. According to the method, the catalyst is introduced in the bromination step, so that the activation energy of bromination reaction can be effectively reduced, and the reaction is promoted to be carried out, and the reaction yield is improved.
In addition, hydrobromic acid is generated in the bromination reaction, and an acid binding agent is usually introduced in the prior art to neutralize the acid generated in the reaction, so that the reaction is promoted to move forward. The inventors of the present application have unexpectedly found that when 4-dimethylaminopyridine is used as an acid-binding agent in examining the influence of different acid-binding agents on the reaction yield and purity, the reaction yield can be significantly improved over conventional acid-binding agents such as triethylamine, DIPEA, sodium bicarbonate, etc.
Further, in the prior art, fei qing et al (agricultural chemicals, 2006, 45 (6): 385-386, 391) used a mixed solvent of chloroform as the main solvent (the purity of bromination reaction in this document is 95%, the yield is 98%, which is significantly higher than that reported in other documents), and the inventors examined the influence of different solvents on the yield and purity of the product, and found that the yield and purity were the best when tetrahydrofuran and carbon tetrachloride were used as the mixed solvent in the catalytic system of the present invention.
In another aspect of the present invention, there is provided a method for preparing a bromothalonil intermediate 4-bromo-2-p-chlorophenyl-5-trifluoromethylpyrrole-3-carbonitrile, comprising the steps of:
1) In a mixed solvent, in the presence of a catalyst and an acid-binding agent, carrying out bromination reaction on 2-p-chlorophenyl-5-trifluoromethyl pyrrole-3-nitrile and bromine to prepare an intermediate 4-bromo-2-p-chlorophenyl-5-trifluoromethyl pyrrole-3-nitrile;
the specific reaction formula is as follows:
preferably, the mixed solvent in step 1) is a mixed solvent of tetrahydrofuran and another inert solvent.
Suitable inert solvents are aliphatic hydrocarbons, preferably aliphatic C 5 -C 16 Hydrocarbons, more preferably C 5 -C 16 Alkanes, or C 5 -C 16 Cycloalkanes, such as pentane, hexane, cyclohexane or petroleum ether; halogenated hydrocarbons, preferably halogenated aliphatic C 1 -C 6 Alkanes, or halogenated aromatic C 6 -C 10 Hydrocarbons, e.g. CH 2 Cl 2 、CHCl 3 、CCl 4 、CH 2 ClCH 2 Cl、CCl 3 CH 3 、CHCl 2 CH 2 Cl、CCl 2 CCl 2 Or chlorobenzene; ethers, preferably C 1 -C 6 Cycloalkyl ethers, C 1 -C 6 alkyl-C 1 -C 6 Alkyl ether, C 1 -C 6 alkyl-C 3 -C 6 Cycloalkyl ethers, C 1 -C 6 polyol-C 1 -C 6 Alkyl ether and C 1 -C 6 alkyl-C 6 -C 10 Aryl ethers, e.g. CH 3 CH 2 OCH 2 CH 3 、(CH 3 ) 2 CHOCH(CH 3 ) 2 、CH 3 OC(CH 3 ) 3 (MTBE)、CH 3 OCH 3 (DME)、CH 3 OCH 2 CH 2 OCH 3 、CH 3 OC(CH 3 ) 2 CH 2 CH 3 And diethylene glycol; esters, preferably aliphatic C 1 -C 6 Alcohols and aliphatic C 1 -C 6 Esters of carboxylic acids, aromatic C 6 -C 10 Alcohols and aromatic C 6 -C 10 Esters of carboxylic acids, omega-hydroxy-C 1 -C 6 Cyclic esters of carboxylic acids, e.g. CH3C (O) OCH 2 CH 3 、CH 3 C(O)OCH 3 、CH 3 C(O)OCH 2 CH 2 CH 2 CH 3 、CH 3 C(O)OCH(CH 3 )CH 2 CH 3 、CH 3 C(O)OC(CH 3 )、CH 3 CH 2 CH 2 C(O)OCH 2 CH 3 、CH 3 CH(OH)C(O)OCH 2 CH 3 、CH 3 CH(OH)C(O)OCH 3 、CH 3 C(O)OCH 2 CH(CH 3 ) 2 、CH 3 C(O)OCH(CH 3 ) 2 、CH 3 CH 2 C(O)OCH 3 Benzyl benzoate and gamma-butyrolactone; carbonates, e.g. ethylene carbonate, propylene carbonate, CH 3 CH 2 OC(O)OCH 2 CH 3 And CH (CH) 3 OC(O)OCH 3 The method comprises the steps of carrying out a first treatment on the surface of the Nitriles, preferably C 1 -C 6 Nitriles, e.g. ACN and CH 3 CH 2 A CN; alcohols, preferably C 1 -C 4 Alcohols and C 2 -C 4 Alkanediols, e.g. CH 3 OH、CH 3 CH 2 OH、CH 3 CH 2 CH 2 OH、CH 3 CH(OH)CH 3 、CH 3 (CH 2 ) 3 OH and C (CH) 3 ) 3 OH、CH 2 (OH)CH 2 (OH)、CH 3 CH(OH)CH 2 OH; amides and urea derivatives, preferably DMF, NMP, DMA, DMI, DMPU, HMPA; in addition, DMSO and sulfolane.
More preferably, the mixed solvent of step 1) is a mixed solvent of tetrahydrofuran and carbon tetrachloride; most preferably, in the mixed solvent, the volume ratio of tetrahydrofuran to carbon tetrachloride is 5:1-2.
Preferably, the catalyst in the step 1) is iron powder, manganese dioxide or ferric bromide; more preferably iron powder.
Preferably, the acid-binding agent of step 1) is selected from the group consisting of 4-dimethylaminopyridine, DIPEA, triethylamine, sodium bicarbonate, potassium bicarbonate, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate; most preferably, the acid binding agent is selected from 4-dimethylaminopyridine.
Preferably, the molar ratio of the 2-p-chlorophenyl-5-trifluoromethyl-pyrrole-3-carbonitrile, the bromine, the catalyst and the acid binding agent in the step 1) is 1:1.0-2.0:0.1-0.2:1.0-3.0, more preferably, the molar ratio is 1:1.0-1.2:0.1-0.15:1.0-1.5.
Preferably, the reaction temperature of step 1) is from 30 to 60 ℃, more preferably from 40 to 50 ℃;
preferably, the reaction time of step 1) is 2 to 10 hours, more preferably 3 to 5 hours.
The reaction mixture of step 1) may be worked up in a conventional manner, for example by mixing with water, separating the phases and, if appropriate, purifying the crude product in a conventional manner. Typically, after the reaction of step 1) is completed, the solvent is removed from the reaction mixture by distillation. Alternatively, after the completion of the reaction, water may be added to the mixture, a part of the solvent may be distilled off again, and then the aqueous layer may be removed and the organic layer containing the compound of formula III may be dried, for example, by adding a hygroscopic material. The product of step 1) may also be obtained by crystallization from an organic layer or by removal of an organic solvent.
Preferably, the post-treatment method of the step 1) is as follows: and (3) cooling the reaction liquid, adding water, stirring, distilling to remove the mixed solvent, precipitating a large amount of light yellow solid in the water phase, filtering, washing the filter cake with water for three times, collecting the filter cake, and drying to obtain the intermediate 4-bromo-2-p-chlorophenyl-5-trifluoromethyl pyrrole-3-nitrile.
Compared with the prior art, the invention has the beneficial effects that:
(1) Compared with the method for preparing the chlorfenapyr in the prior art, the method has the advantages that the yield of the intermediate 4-bromo-2-p-chlorophenyl-5-trifluoromethyl pyrrole-3-nitrile is higher, and the reaction cost is reduced;
(2) The method has simple reaction steps and mild reaction conditions, and the reagents used in the reaction are cheap and easily available, so that the industrialization is easy to realize.
(3) The method has high product purity, and can realize the high-purity product by simple post-treatment, thereby saving the subsequent purification steps.
Detailed Description
The following is a detailed description of the present invention by way of examples. In the present invention, the following examples are provided for better illustration of the present invention and are not intended to limit the scope of the present invention. Materials, reagents and the like used in the examples described below are commercially available unless otherwise specified.
Example 1
In a 500mL reaction flask, 27.1g (about 0.1 mol) of 2-p-chlorophenyl-5-trifluoromethylpyrrole-3-carbonitrile was added, dissolved with 200mL of tetrahydrofuran and 50mL of carbon tetrachloride, and then 0.6g of iron powder, 14.7g (about 0.12 mol) of 4-dimethylaminopyridine was added and stirred for 30 minutes. Then 19.8g (about 0.11 mol) of bromine is slowly dripped into the solution, the temperature is controlled to be 40-50 ℃, and the reaction is carried out for 4 hours at room temperature after the dripping. After the reaction is finished, cooling the reaction liquid, adding water, stirring, distilling to remove the mixed solvent, precipitating a large amount of light yellow solid in the water phase, filtering, washing the filter cake with water for three times, collecting the filter cake, and drying to obtain 33.2g of light yellow and white solid 4-bromo-2-p-chlorophenyl-5-trifluoromethylpyrrole-3-carbonitrile, wherein the purity of the product detected by HPLC is 98.5%, and the yield is 95.0%.
Examples 2-5 effect of different solvents on reaction yield and product purity.
Example 2
The procedure is as in example 1 except that 250mL of tetrahydrofuran is used in place of 200mL of tetrahydrofuran and 50mL of carbon tetrachloride.
Example 3
The difference from example 1 is that 250mL of carbon tetrachloride is used instead of 200mL of tetrahydrofuran and 50mL of carbon tetrachloride, and the other conditions are the same as in example 1.
Example 4
The procedure is as in example 1 except that 200mL of carbon tetrachloride and 50mL of tetrahydrofuran are used instead of 200mL of tetrahydrofuran and 50mL of carbon tetrachloride.
Example 5
The procedure is as in example 1 except that 200mL of tetrahydrofuran and 50mL of carbon tetrachloride are replaced with 200mL of tetrahydrofuran and 50mL of chlorobenzene.
The yield and purity data for examples 2-5 are shown below:
examples numbering Purity (%) Yield (%)
Example 2 96.8 91.8
Example 3 95.7 92.5
Example 4 93.0 88.1
Example 5 93.8 82.3
As can be seen from examples 1-5, when tetrahydrofuran and carbon tetrachloride are used as the mixed solvent, the yield and purity of the product are greatly improved.
Examples 6-9 effect of different acid binding agents on reaction yield and product purity.
Example 6
The procedure is as in example 1 except that 14.7g of DIPEA is used instead of 14.7g of 4-dimethylaminopyridine.
Example 7
The procedure is as in example 1 except that 14.7g of triethylamine is used in place of 14.7g of 4-dimethylaminopyridine.
Example 8
The procedure is as in example 1 except that 14.7g of sodium bicarbonate is used instead of 14.7g of 4-dimethylaminopyridine.
Example 9
The procedure is as in example 1 except that 14.7g of sodium carbonate is used instead of 14.7g of 4-dimethylaminopyridine.
The yield and purity data for examples 6-9 are shown below:
examples numbering Purity (%) Yield (%)
Example 6 95.3 86.3
Example 7 93.6 82.7
Example 8 94.2 76.3
Example 9 92.6 79.8
As can be seen from examples 1 and 6-9, when 4-dimethylaminopyridine is used as an acid binding agent, the yield and purity of the product are greatly improved.
Examples 10-12 effect of different catalysts on reaction yield and product purity.
Example 10
The difference from example 1 is that 0.1mol of manganese dioxide is used instead of 0.1mol of iron powder, and the other conditions are the same as in example 1.
Example 11
The difference from example 1 is that 0.1mol of iron powder is replaced by 0.1mol of iron tribromide, and the other conditions are the same as in example 1.
Example 12
The difference from example 1 is that no catalyst is added and the other conditions are the same as in example 1.
The yield and purity data for examples 10-12 are shown below:
examples numbering Purity (%) Yield (%)
Example 10 94.5 88.7
Example 11 95.1 85.3
Example 12 93.2 74.7
As can be seen from examples 1 and 10-12, when iron powder is used as a catalyst, the yield and purity of the product are greatly improved.
EXAMPLE 13 Synthesis of chlorfenapyr
In a 300mL reaction flask, 17.5g (0.05 mol) of 4-bromo-2-p-chlorophenyl-5-trifluoromethylpyrrole-3-carbonitrile was added, followed by addition of 70mL of tetrahydrofuran, stirring and dissolution, and then, dropwise adding 3.0g (60%, 0.075 mol) of sodium hydride in 70mL of tetrahydrofuran, stirring and reacting, stirring at 30℃for 0.5h, then, dropwise adding 12.9g (0.10 mol) of bromochloromethane, reacting at 60℃for 6h, treating with a tetrahydrofuran solution containing 7.5g (0.12 mol) of sodium ethoxide, reacting at 60℃for 7h, cooling, filtering, removing the solvent, and recrystallizing with a mixed solvent of n-hexane/ethyl acetate to obtain 18.6g of white solid bromoxynil, the yield being 91.3%.
Although embodiments of the present invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made therein without departing from the principles and spirit of the invention, the scope of which is defined in the appended claims and their equivalents.

Claims (3)

1. A method for preparing chlorfenapyr, comprising the steps of:
1) In a 500mL reaction flask, 27.1g of 2-p-chlorophenyl-5-trifluoromethylpyrrole-3-carbonitrile was added, dissolved with 200mL of tetrahydrofuran and 50mL of carbon tetrachloride, then 0.6g of iron powder, 14.7g of 4-dimethylaminopyridine was added, and stirred for 30min; then slowly dripping 19.8g of liquid bromine, controlling the temperature to be 40-50 ℃, and reacting for 4 hours at room temperature after dripping; after the reaction is finished, adding water into the reaction solution, stirring, distilling to remove the mixed solvent, precipitating a large amount of light yellow solid in the water phase, filtering, washing the filter cake with water for three times, collecting the filter cake, and drying to obtain 33.2g of light yellow and white solid 4-bromo-2-p-chlorophenyl-5-trifluoromethylpyrrole-3-carbonitrile, wherein the purity of the product detected by HPLC is 98.5%, and the yield is 95.0%;
2) Reacting 4-bromo-2-p-chlorophenyl-5-trifluoromethyl pyrrole-3-carbonitrile with bromochloromethane and sodium ethoxide under the action of alkali, and performing aftertreatment to obtain a target product, namely chlorfenapyr;
the specific reaction formula is as follows:
2. the method for preparing the chlorfenapyr according to claim 1, wherein:
the reaction process of the step 2) is as follows: dissolving 4-bromo-2-p-chlorophenyl-5-trifluoromethyl pyrrole-3-nitrile in tetrahydrofuran, slowly dropwise adding tetrahydrofuran containing sodium hydride, stirring for reaction, dropwise adding bromochloromethane, continuing the reaction, treating with tetrahydrofuran solution containing sodium ethoxide, reacting for a period of time, detecting the reaction progress by TLC, cooling, filtering, removing solvent, and recrystallizing with mixed solvent of n-hexane/ethyl acetate to obtain white solid chlorfenapyr.
3. A process for preparing a chlorfenapyr intermediate 4-bromo-2-p-chlorophenyl-5-trifluoromethylpyrrole-3-carbonitrile comprising the steps of:
in a 500mL reaction flask, 27.1g of 2-p-chlorophenyl-5-trifluoromethylpyrrole-3-carbonitrile was added, dissolved with 200mL of tetrahydrofuran and 50mL of carbon tetrachloride, then 0.6g of iron powder, 14.7g of 4-dimethylaminopyridine was added, and stirred for 30min; then slowly dripping 19.8g of liquid bromine, controlling the temperature to be 40-50 ℃, and reacting for 4 hours at room temperature after dripping; after the reaction is finished, adding water into the reaction solution, stirring, distilling to remove the mixed solvent, precipitating a large amount of light yellow solid in the water phase, filtering, washing the filter cake with water for three times, collecting the filter cake, and drying to obtain 33.2g of light yellow and white solid 4-bromo-2-p-chlorophenyl-5-trifluoromethylpyrrole-3-carbonitrile, wherein the purity of the product detected by HPLC is 98.5%, and the yield is 95.0%;
the specific reaction formula is as follows:
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