CN112624911A - 2-chloro-3-fluoro-4- (trifluoromethyl) benzaldehyde and synthetic method thereof - Google Patents
2-chloro-3-fluoro-4- (trifluoromethyl) benzaldehyde and synthetic method thereof Download PDFInfo
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Abstract
The invention belongs to the technical field of pesticide intermediates, and particularly relates to 2-chloro-3-fluoro-4- (trifluoromethyl) benzaldehyde. The invention discloses 2-chloro-3-fluoro-4- (trifluoromethyl) benzaldehyde and a synthetic method thereof; the 2-chloro-3-fluoro-4- (trifluoromethyl) benzaldehyde provided by the invention reacts at normal pressure to form a product in the synthetic process, the process is simple, the industrial application is convenient, the reaction condition is mild, the operation is simple, and the industrial production requirement is met; the 2-chloro-3-fluoro-4- (trifluoromethyl) benzaldehyde can be widely applied to the synthesis process of pesticides, such as herbicide and other pesticides, and has high synthesis yield and high purity.
Description
Technical Field
The invention belongs to the technical field of pesticide intermediates, and particularly relates to 2-chloro-3-fluoro-4- (trifluoromethyl) benzaldehyde and a synthetic method thereof.
Background
Because fluorine atoms have strong electronegativity and small atomic radius, the fluorine-containing compound has a plurality of unique properties and has important application value in the fields of biochemistry, medicines, pesticides, functional materials, dyes and the like. Many products currently contain at least one fluorine atom in agrochemicals and pharmaceuticals. Among these compounds, the trifluoromethyl compound accounts for a considerable proportion. Because of the special structure of trifluoromethyl group, the substrate has strong polarity, stability and lipophilicity, so that the medicine, pesticide and dye synthesized by the trifluoromethyl group have stronger activity than that of some traditional organic intermediates, and are concerned at home and abroad, at present, the trifluoromethyl benzene product becomes a group of important organic intermediates, and the trifluoromethyl benzene product has the advantages of serialization of varieties, excellent performance and high functional efficiency, and has become a research and development hotspot in the field of organic intermediates.
The 2-chloro-3-fluoro-4- (trifluoromethyl) benzaldehyde product is used as an important fine chemical intermediate, can be applied to pesticides and medical products, and becomes a hotspot product in the field of fine chemical intermediates. However, no literature report is available on 2-chloro-3-fluoro-4- (trifluoromethyl) benzaldehyde and its synthesis method. Therefore, it is necessary to develop a synthesis method which has easily available raw materials, convenient operation, easy control of reaction, proper overall yield and suitability for industrial production.
Disclosure of Invention
The invention aims to solve the problems and provides 2-chloro-3-fluoro-4- (trifluoromethyl) benzaldehyde and a synthesis method thereof.
In order to solve the technical problems, the invention adopts the following technical scheme:
the structural formula of the 2-chloro-3-fluoro-4- (trifluoromethyl) benzaldehyde is as follows:
the invention also provides a synthetic method of the 2-chloro-3-fluoro-4- (trifluoromethyl) benzaldehyde, which comprises the following steps: dissolving a compound F in an organic solvent, and carrying out nucleophilic substitution with dimethylformamide at-80 to-70 ℃ under the action of lithium diisopropylamide to obtain 2-chloro-3-fluoro-4- (trifluoromethyl) benzaldehyde; the structural formula of the compound F is
Preferably, the organic solvent is any one of tetrahydrofuran and ethylene glycol dimethyl ether; the molar ratio of the lithium diisopropylamide to the compound F to the dimethylformamide is 1-3: 1: 3-6.
Preferably, the synthesis method of the compound F is to perform diazotization reaction on the hydrochloric acid solution of the compound E and sodium nitrite, and then decompose the hydrochloric acid solution of hot cuprous chloride to form the compound F; the compound E has the structure
Preferably, the molar ratio of the compound E, the sodium nitrite and the cuprous chloride is 1: 1-5.
Preferably, the compound C is dissolved in tetrahydrofuran solution, ammonolysis reaction is carried out on the tetrahydrofuran solution and ammonia water to form a compound D, the compound D is dissolved in ethanol, and then Hofmann degradation is carried out on the ethanol, sodium hydroxide and sodium hypochlorite to synthesize a compound E;
the structural formula of the compound C is
The structural formula of the compound D is
Preferably, the mass ratio of the compound C to ammonia water is 1: 3-10, and the molar ratio of the compound D to sodium hydroxide to sodium hypochlorite is 1: 3-6: 1-3.
Preferably, the compound A is dissolved in tetrahydrofuran, nucleophilic substitution is carried out on the compound A and carbon dioxide under the action of lithium diisopropylamide to synthesize a compound B, and the compound B and thionyl chloride react to synthesize an acyl chloride compound C;
the structural formula of the compound A is
The structural formula of the compound B is
Preferably, the molar ratio of the compound A to the lithium diisopropylamide is 1: 1-1.5; the solid-liquid g/mL ratio of the compound A to tetrahydrofuran is 1: 10; the solid-liquid g/mL ratio of the compound B to the thionyl chloride is 1: 10.
Meanwhile, the chemical synthesis structural formula of the synthetic method of the 2-chloro-3-fluoro-4- (trifluoromethyl) benzaldehyde is as follows:
compared with other methods, the method has the beneficial technical effects that:
(1) the invention discloses 2-chloro-3-fluoro-4- (trifluoromethyl) benzaldehyde and a synthetic method thereof;
(2) in the synthesis process of the 2-chloro-3-fluoro-4- (trifluoromethyl) benzaldehyde provided by the invention, the reaction is carried out at normal pressure to form a product, the process is simple, the industrial application is convenient, the reaction condition is mild, the operation is simple, and the industrial production requirement is met;
(3) the 2-chloro-3-fluoro-4- (trifluoromethyl) benzaldehyde can be widely applied to the synthesis process of pesticides, such as herbicide and other pesticides, and has high synthesis yield and high purity.
Detailed Description
The technical solutions in the embodiments of the present invention are clearly and completely described below, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
The structural formula of the 2-chloro-3-fluoro-4- (trifluoromethyl) benzaldehyde is as follows:
the nuclear magnetic data of the compound by nuclear magnetic detection are 1H NMR (400 MHz, CDC13) δ =10.51 (d, J = 0.4 Hz, 1H), 7.84 (d, J = 8.0 Hz, 1H), 7.67 (m, 1H).
The synthesis process is as follows:
(1) a, according to the molar ratio of the compound A to lithium diisopropylamide of 1: 1-1.5; the solid-liquid g/mL ratio of the compound A to tetrahydrofuran is 1: 10; the preparation method of the tetrahydrofuran solution containing lithium diisopropylamide comprises the steps of mixing lithium diisopropylamide and tetrahydrofuran according to the solid-liquid g/mL ratio of 1:15 to obtain a solid-liquid g/mL ratio of 1: 10; taking materials, sequentially adding a compound A and tetrahydrofuran into a reactor in a nitrogen atmosphere, controlling the temperature to be minus 80 to minus 75 ℃, dropwise adding a tetrahydrofuran solution containing lithium diisopropylamide, maintaining the temperature to be minus 80 to minus 75 ℃, continuously stirring for 30 to 40min, introducing carbon dioxide into the reactor, maintaining the standard atmospheric pressure in the reactor by using the carbon dioxide, and stirring for 1 to 2h to obtain a compound B;
b. taking materials according to the solid-liquid g/mL ratio of the compound B to the thionyl chloride of 1:10, adding the compound B into the thionyl chloride, carrying out reflux reaction at 85-90 ℃, continuing to keep the temperature and stir for 3-5 h after the compound B is completely dissolved, and then carrying out reduced pressure concentration to dryness to obtain a compound C;
(2) c, taking materials according to the mass ratio of the compound C to 25% ammonia water of 1: 3-10, adding 25% ammonia water into a reactor, setting the temperature to be 0-2 ℃, dissolving the compound C in tetrahydrofuran, dripping the compound C into the reactor, stirring for 1-2 hours, carrying out suction filtration on the mixture in the reactor, washing a filter cake with water, and drying to obtain a compound D;
d. taking a material according to the mol ratio of the compound D to sodium hydroxide to sodium hypochlorite of 1: 3-6: 1-3, wherein the solid-liquid ratio of the compound D to ethanol g/mL is 1:10, adding the compound D and ethanol into a reaction bottle, stirring for dissolving, adding a sodium hydroxide solution with the mass fraction of 20%, stirring for 30-40 min, controlling the temperature to be 0 ℃, adding an aqueous solution containing sodium hypochlorite, stirring for 1h, heating to 80 ℃, keeping the temperature for 5h, cooling to room temperature, extracting with ethyl acetate, washing with water, drying with anhydrous sodium sulfate, and concentrating to obtain a compound E;
(3) taking materials according to the molar ratio of the compound E to the sodium nitrite to the cuprous chloride of 1: 1-5, dissolving the compound E in a hydrochloric acid solution with the mass fraction of 10%, adding the hydrochloric acid solution into a reactor, controlling the temperature to be 0 ℃, dropwise adding the sodium nitrite solution with the mass fraction of 10%, stirring for 1-2 h to obtain a reaction solution, dropwise adding the reaction solution into a reaction bottle containing a cuprous chloride acid solution with the temperature of 95-98 ℃, maintaining the temperature to be 90-95 ℃ after dropwise adding, heating for 2-4 h, cooling to room temperature, extracting with ethyl acetate, washing with water, and concentrating to obtain a compound F1;
(4) according to the method, the organic solvent is any one of tetrahydrofuran and ethylene glycol dimethyl ether; the molar ratio of the lithium diisopropylamide to the compound F to the dimethylformamide is 1-3: 1: 3-6, taking materials, dissolving the compound F in tetrahydrofuran, putting the tetrahydrofuran into a reactor, setting the temperature to be-80 to-70 ℃, dropwise adding a tetrahydrofuran solution containing lithium diisopropylamide, keeping the temperature to be-80 to-70 ℃, stirring for 1-2 hours, dropwise adding the dimethylformamide, keeping the temperature, continuously stirring for 1 hour, adding dilute hydrochloric acid and ethyl acetate, layering, and concentrating an organic phase to obtain the 2-chloro-3-fluoro-4-trifluoromethylbenzaldehyde.
Example 1
The synthesis of the 2-chloro-3-fluoro-4- (trifluoromethyl) benzaldehyde of the invention is as follows:
(1) synthesis of Compound C:
a. under the atmosphere of nitrogen, 1.5g of compound A and 15mL of tetrahydrofuran are sequentially added into a reactor, the temperature is controlled to be-75 ℃, 10mL of tetrahydrofuran solution containing 1.1g of lithium diisopropylamide is dropwise added, the temperature is maintained to be-75 ℃, stirring is continued for 30min, carbon dioxide is introduced into the reactor, the standard atmospheric pressure in the reactor is maintained by utilizing the carbon dioxide, stirring is carried out for 1h, 15mL of dilute hydrochloric acid and 30mL of ethyl acetate are added into the reactor, stirring, standing, layering and organic phase concentration are carried out, so that 1.6g of compound B, namely 2-fluoro-3-trifluoromethylbenzoic acid is obtained, the yield is 84.1%, and the purity is 96.8%;
compound B nuclear magnetic: 1H NMR (400 MHz, CDC13) δ 13.70 (br, 1H), 8.18-8.14 (m, 1H), 8.02-7.98 (m, 1H), 7.50 (t, J = 8.0 Hz, 1H);
b. adding 1.5g of the compound B into 15mL of thionyl chloride, carrying out reflux reaction at 85 ℃, continuing to keep the temperature and stir for 3h after the compound B is completely dissolved, and then concentrating under reduced pressure until the compound B is dried to obtain 1.5g of a compound C, namely 2-fluoro-3-trifluoromethyl benzoyl chloride, wherein the yield is 91.9%, and the purity is 92.6%;
nuclear magnetism of compound C: 1H NMR (400 MHz, CDC13) δ = 8.29 (m, 1H), 7.92 (m, 1H), 7.44 (m, 1H).
The synthetic chemical formula of the compound C is as follows:
(2) synthesis of Compound E
c. Adding 15mL of 25% ammonia water by mass into a reactor, setting the temperature to be 0 ℃, dissolving 1.5g of the compound C in 20mL of tetrahydrofuran, dripping the mixture into the reactor, stirring for 1h, carrying out suction filtration on the mixture in the reactor, washing a filter cake with water, and drying to obtain 1.2g of a compound D, namely the 2-fluoro-3-trifluoromethyl benzamide, wherein the yield is 87.5% and the purity is 94.8%;
nuclear magnetism of compound D: 1H NMR (400 MHz, CDC13) δ = 8.32 (t, J =7.6 Hz, 1H), 7.78 (t, J = 7.2 Hz, 1H),7.39 (t, J = 8.0 Hz, 1H), 6.65 (br, 1H), 6.36 (br, 1H);
d. adding 1.2g of the compound D and 12mL of ethanol into a reaction bottle, stirring for dissolving, adding 5.0g of a sodium hydroxide solution with the mass fraction of 20%, stirring for 30min, controlling the temperature to be 0 ℃, adding 20mL of an aqueous solution containing 1.5g of sodium hypochlorite, stirring for 1h, heating to 80 ℃, preserving heat for 5h, cooling to room temperature, extracting with ethyl acetate, washing with water, drying with anhydrous sodium sulfate, and concentrating to obtain 0.93g of a compound E, namely the 2-fluoro-3-trifluoromethylaniline, wherein the yield is 89.6%, and the purity is 96.5%.
Compound E nuclear magnetic: 1H NMR (400 MHz, CDC13) δ =7.03-6.92 (m, 3H), 3.88 (br, 2H).
The synthetic chemical formula of the compound E is as follows:
(3) and (2) synthesizing a compound F, namely dissolving 1.8g of the compound E in 10mL of hydrochloric acid solution with the mass fraction of 10%, adding the solution into a reactor, controlling the temperature to be 0 ℃, dropwise adding 10g of sodium nitrite solution with the mass fraction of 10%, stirring for 1h to obtain a reaction solution, dropwise adding the reaction solution into a reaction bottle containing 10g of cuprous chloride acid solution with the temperature of 95 ℃, maintaining the temperature to be 95 ℃ after dropwise adding, heating for 3h, cooling, extracting with ethyl acetate, washing with water, and concentrating to obtain 1.7g of the compound F, namely 2-fluoro-3-trifluoromethylchlorobenzene, wherein the yield is 85.2%, and the purity is 97.2%.
Nuclear magnetism of compound F: 1H NMR (400 MHz, CDC13) δ =7.63 (m, 1H), 7.53 (m, 1H), 7.22 (m, 1H).
Wherein the cuprous chloride hydrochloric acid solution is prepared by mixing 3g of cuprous chloride with 10g of hydrochloric acid solution with the mass fraction of 15% to obtain the cuprous chloride hydrochloric acid solution.
The synthetic chemical formula of the compound F is as follows:
(4) 2-chloro-3-fluoro-4- (trifluoromethyl) benzaldehyde is synthesized by dissolving 2g of compound F in 10mL of tetrahydrofuran, placing the mixture into a reactor, setting the temperature to be-78 ℃, dropwise adding 30mL of a tetrachlorofuran solution containing 1.8g of lithium diisopropylamide, keeping the temperature to be-78 ℃, stirring for 1h, dropwise adding 3g of dimethylformamide, keeping the temperature, continuously stirring for 1h, adding 30mL of diluted hydrochloric acid and 50mL of ethyl acetate, layering, and concentrating an organic phase to obtain 2.1g of 2-chloro-3-fluoro-4-trifluoromethylbenzaldehyde, wherein the yield is 92% and the purity is 95.8%.
2-chloro-3-fluoro-4-trifluoromethylbenzaldehyde nuclear magnetic: 1H NMR (400 MHz, CDC13) δ =10.51 (d, J = 0.4 Hz, 1H), 7.84 (d, J = 8.0 Hz, 1H), 7.67 (m, 1H).
The chemical formula of the synthesis is
Example 2
The synthesis of the 2-chloro-3-fluoro-4- (trifluoromethyl) benzaldehyde of the invention is as follows:
(1) synthesis of Compound C:
a. under the atmosphere of nitrogen, 1.5g of compound A and 15mL of tetrahydrofuran are sequentially added into a reactor, the temperature is controlled to be 80 ℃ below zero, 10mL of tetrahydrofuran solution containing 1.2g of lithium diisopropylamide is dropwise added, the temperature is maintained to be 80 ℃ below zero, stirring is continued for 40min, carbon dioxide is introduced into the reactor, the standard atmospheric pressure in the reactor is maintained by using the carbon dioxide, stirring is carried out for 2h, 15mL of dilute hydrochloric acid and 30mL of ethyl acetate are added into the reactor, stirring, standing, layering and organic phase concentration are carried out, so that 1.72g of compound B, namely 2-fluoro-3-trifluoromethylbenzoic acid is obtained, the yield is 90.4%, and the purity is 98.8%;
compound B nuclear magnetic: 1H NMR (400 MHz, CDC13) δ 13.70 (br, 1H), 8.18-8.14 (m, 1H), 8.02-7.98 (m, 1H), 7.50 (t, J = 8.0 Hz, 1H);
b. adding 1.5g of the compound B into 15mL of thionyl chloride, carrying out reflux reaction at 90 ℃, continuing to keep the temperature and stir for 5 hours after the compound B is completely dissolved, and then concentrating under reduced pressure until the compound B is dried to obtain 1.53g of a compound C, namely 2-fluoro-3-trifluoromethyl benzoyl chloride, wherein the yield is 93.7%, and the purity is 94.2%;
nuclear magnetism of compound C: 1H NMR (400 MHz, CDC13) δ = 8.29 (m, 1H), 7.92 (m, 1H), 7.44 (m, 1H).
The synthetic chemical formula of the compound C is as follows:
(2) synthesis of Compound E
c. Adding 20mL of 25% ammonia water by mass into a reactor, setting the temperature to be 2 ℃, dissolving 1.5g of the compound C in 20mL of tetrahydrofuran, dripping the mixture into the reactor, stirring for 2 hours, carrying out suction filtration on the mixture in the reactor, washing a filter cake with water, and drying to obtain 1.26g of a compound D, namely the 2-fluoro-3-trifluoromethyl benzamide, wherein the yield is 91.9%, and the purity is 95.9%;
nuclear magnetism of compound D: 1H NMR (400 MHz, CDC13) δ = 8.32 (t, J =7.6 Hz, 1H), 7.78 (t, J = 7.2 Hz, 1H),7.39 (t, J = 8.0 Hz, 1H), 6.65 (br, 1H), 6.36 (br, 1H);
d. adding 1.2g of the compound D and 12mL of ethanol into a reaction bottle, stirring for dissolving, adding 5.0g of a sodium hydroxide solution with the mass fraction of 20%, stirring for 40min, controlling the temperature to be 0 ℃, adding 20mL of an aqueous solution containing 1.8g of sodium hypochlorite, stirring for 1h, heating to 80 ℃, preserving heat for 5h, cooling to room temperature, extracting with ethyl acetate, washing with water, drying with anhydrous sodium sulfate, and concentrating to obtain 1g of a compound E, namely the 2-fluoro-3-trifluoromethylaniline, wherein the yield is 96.4% and the purity is 97.2%.
Compound E nuclear magnetic: 1H NMR (400 MHz, CDC13) δ =7.03-6.92 (m, 3H), 3.88 (br, 2H).
The synthetic chemical formula of the compound E is as follows:
(3) and (2) synthesizing a compound F, namely dissolving 1.8g of the compound E in 10mL of hydrochloric acid solution with the mass fraction of 10%, adding the solution into a reactor, controlling the temperature to be 0 ℃, dropwise adding 12g of sodium nitrite solution with the mass fraction of 10%, stirring for 1h to obtain a reaction solution, dropwise adding the reaction solution into a reaction bottle containing 11g of cuprous chloride acid solution with the temperature of 98 ℃, maintaining the temperature to be 95 ℃ after dropwise adding, heating for 2h, cooling to room temperature, extracting with ethyl acetate, washing with water, and concentrating to obtain 1.82g of the compound F, namely 2-fluoro-3-trifluoromethylchlorobenzene, wherein the yield is 91.2%, and the purity is 98.1%.
Nuclear magnetism of compound F: 1H NMR (400 MHz, CDC13) δ =7.63 (m, 1H), 7.53 (m, 1H), 7.22 (m, 1H).
Wherein the cuprous chloride hydrochloric acid solution is prepared by mixing 4g of cuprous chloride with 10g of hydrochloric acid solution with the mass fraction of 15% to obtain the cuprous chloride hydrochloric acid solution.
The synthetic chemical formula of the compound F is as follows:
(4) 2-chloro-3-fluoro-4- (trifluoromethyl) benzaldehyde is synthesized by dissolving 2g of compound F in 10mL of tetrahydrofuran, placing the mixture into a reactor, setting the temperature to be-70 ℃, dropwise adding 30mL of a tetrachlorofuran solution containing 2.0g of lithium diisopropylamide, keeping the temperature to be-75 ℃, stirring for 1h, dropwise adding 3.1g of dimethylformamide, keeping the temperature, continuing stirring for 1h, adding 30mL of diluted hydrochloric acid and 50mL of ethyl acetate, layering, and concentrating an organic phase to obtain 2.2g of 2-chloro-3-fluoro-4-trifluoromethylbenzaldehyde, wherein the yield is 96.4% and the purity is 98.1%.
2-chloro-3-fluoro-4-trifluoromethylbenzaldehyde nuclear magnetic: 1H NMR (400 MHz, CDC13) δ =10.51 (d, J = 0.4 Hz, 1H), 7.84 (d, J = 8.0 Hz, 1H), 7.67 (m, 1H).
The chemical formula of the synthesis is
Although the present invention has been described in detail with reference to the preferred embodiments, it will be understood by those skilled in the art that various changes may be made and equivalents may be substituted without departing from the spirit and scope of the invention as defined in the appended claims. The techniques, shapes, and configurations not described in detail in the present invention are all known techniques.
Claims (9)
2. a method of synthesizing 2-chloro-3-fluoro-4- (trifluoromethyl) benzaldehyde according to claim 1, comprising: dissolving a compound F in an organic solvent, and carrying out nucleophilic substitution with dimethylformamide at-80 to-70 ℃ under the action of lithium diisopropylamide to obtain 2-chloro-3-fluoro-4- (trifluoromethyl) benzaldehyde; the structural formula of the compound F is
3. The method for synthesizing 2-chloro-3-fluoro-4- (trifluoromethyl) benzaldehyde according to claim 2, wherein the organic solvent is any one of tetrahydrofuran and ethylene glycol dimethyl ether; the molar ratio of the lithium diisopropylamide to the compound F to the dimethylformamide is 1-3: 1: 3-6.
4. The method for synthesizing 2-chloro-3-fluoro-4- (trifluoromethyl) benzaldehyde according to any one of claims 2 to 3, wherein the compound F is synthesized by diazotizing a hydrochloric acid solution of the compound E with sodium nitrite, and decomposing the solution in a hot cuprous chloride hydrochloric acid solution to form the compound F; the compound E has the structure
5. The method for synthesizing 2-chloro-3-fluoro-4- (trifluoromethyl) benzaldehyde according to claim 4, wherein the molar ratio of the compound E to the sodium nitrite to the cuprous chloride is 1:1 to 5.
6. The method for synthesizing 2-chloro-3-fluoro-4- (trifluoromethyl) benzaldehyde according to claim 5, wherein the compound C is dissolved in a tetrahydrofuran solution, ammonolysis reaction is carried out on the tetrahydrofuran solution and ammonia water to form a compound D, the compound D is dissolved in ethanol, and Hofmann degradation is carried out on the ethanol, sodium hydroxide and sodium hypochlorite to synthesize a compound E;
the structural formula of the compound C is
The structural formula of the compound D is
7. The method for synthesizing 2-chloro-3-fluoro-4- (trifluoromethyl) benzaldehyde according to claim 6, wherein the mass ratio of the compound C to ammonia water is 1: 3-10, and the molar ratio of the compound D to sodium hydroxide to sodium hypochlorite is 1: 3-6: 1-3.
8. The method for synthesizing 2-chloro-3-fluoro-4- (trifluoromethyl) benzaldehyde according to claim 7, wherein the compound A is dissolved in tetrahydrofuran, nucleophilic substitution is performed with carbon dioxide under the action of lithium diisopropylamide to synthesize a compound B, and the compound B is reacted with thionyl chloride to synthesize an acyl chloride compound C;
the structural formula of the compound A is
The structural formula of the compound B is
9. The method for synthesizing 2-chloro-3-fluoro-4- (trifluoromethyl) benzaldehyde according to claim 8, wherein the molar ratio of the compound A to lithium diisopropylamide is 1:1 to 1.5; the solid-liquid g/mL ratio of the compound B to the thionyl chloride is 1: 10.
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CN114920655A (en) * | 2022-07-07 | 2022-08-19 | 南京正荣医药化学有限公司 | Preparation method of 2-fluoro-3-trifluoromethylaniline |
CN115010605A (en) * | 2022-04-28 | 2022-09-06 | 杭州励德生物科技有限公司 | Preparation method of 2-fluoro-3-trifluoromethylaniline |
CN115073299A (en) * | 2022-06-14 | 2022-09-20 | 爱斯特(成都)生物制药股份有限公司 | Method for preparing 2-fluoro-3-trifluoromethylaniline |
CN115141100A (en) * | 2022-08-04 | 2022-10-04 | 苏州永健生物医药有限公司 | Preparation method of 2-fluoro-3-trifluoromethylaniline |
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CN113773204A (en) * | 2021-10-20 | 2021-12-10 | 上海万溯药业有限公司 | Preparation method of fluoroaniline |
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CN115073299A (en) * | 2022-06-14 | 2022-09-20 | 爱斯特(成都)生物制药股份有限公司 | Method for preparing 2-fluoro-3-trifluoromethylaniline |
CN114920655A (en) * | 2022-07-07 | 2022-08-19 | 南京正荣医药化学有限公司 | Preparation method of 2-fluoro-3-trifluoromethylaniline |
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