CN114805041A - Synthetic method of 2-chloro-3-fluoro-4- (trifluoromethyl) benzaldehyde - Google Patents
Synthetic method of 2-chloro-3-fluoro-4- (trifluoromethyl) benzaldehyde Download PDFInfo
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- CN114805041A CN114805041A CN202110079084.2A CN202110079084A CN114805041A CN 114805041 A CN114805041 A CN 114805041A CN 202110079084 A CN202110079084 A CN 202110079084A CN 114805041 A CN114805041 A CN 114805041A
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- KOWIUODHHWBCOX-UHFFFAOYSA-N ClC1=C(C=O)C=CC(=C1F)C(F)(F)F Chemical compound ClC1=C(C=O)C=CC(=C1F)C(F)(F)F KOWIUODHHWBCOX-UHFFFAOYSA-N 0.000 title claims abstract description 27
- 238000010189 synthetic method Methods 0.000 title claims abstract description 10
- 238000000034 method Methods 0.000 claims abstract description 8
- 229940126062 Compound A Drugs 0.000 claims abstract description 7
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 claims abstract description 7
- 238000010534 nucleophilic substitution reaction Methods 0.000 claims abstract description 4
- 150000001875 compounds Chemical class 0.000 claims description 28
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical group CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 24
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 22
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 19
- LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 claims description 19
- 238000003756 stirring Methods 0.000 claims description 19
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 claims description 18
- 238000006243 chemical reaction Methods 0.000 claims description 17
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 claims description 16
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 claims description 16
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 15
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 11
- 239000003054 catalyst Substances 0.000 claims description 10
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 claims description 10
- 235000010288 sodium nitrite Nutrition 0.000 claims description 9
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 claims description 8
- ACVYVLVWPXVTIT-UHFFFAOYSA-N phosphinic acid Chemical compound O[PH2]=O ACVYVLVWPXVTIT-UHFFFAOYSA-N 0.000 claims description 8
- 238000010438 heat treatment Methods 0.000 claims description 7
- JNGZXGGOCLZBFB-IVCQMTBJSA-N compound E Chemical compound N([C@@H](C)C(=O)N[C@@H]1C(N(C)C2=CC=CC=C2C(C=2C=CC=CC=2)=N1)=O)C(=O)CC1=CC(F)=CC(F)=C1 JNGZXGGOCLZBFB-IVCQMTBJSA-N 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 5
- 238000001308 synthesis method Methods 0.000 claims description 5
- 238000002156 mixing Methods 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims description 2
- 230000002194 synthesizing effect Effects 0.000 claims 4
- 239000002994 raw material Substances 0.000 abstract description 6
- 239000000575 pesticide Substances 0.000 abstract description 5
- 230000015572 biosynthetic process Effects 0.000 abstract description 4
- 239000000543 intermediate Substances 0.000 abstract description 4
- 238000003786 synthesis reaction Methods 0.000 abstract description 4
- 238000006193 diazotization reaction Methods 0.000 abstract description 2
- 238000005658 halogenation reaction Methods 0.000 abstract description 2
- 230000002363 herbicidal effect Effects 0.000 abstract description 2
- 239000004009 herbicide Substances 0.000 abstract description 2
- 238000005984 hydrogenation reaction Methods 0.000 abstract description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- 239000012074 organic phase Substances 0.000 description 7
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- 238000005406 washing Methods 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 150000002431 hydrogen Chemical class 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 229910052763 palladium Inorganic materials 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- 101150041968 CDC13 gene Proteins 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 239000012847 fine chemical Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000026030 halogenation Effects 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229940127554 medical product Drugs 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/51—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition
- C07C45/516—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition involving transformation of nitrogen-containing compounds to >C = O groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C17/00—Preparation of halogenated hydrocarbons
- C07C17/35—Preparation of halogenated hydrocarbons by reactions not affecting the number of carbon or of halogen atoms in the reaction
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
- C07C201/06—Preparation of nitro compounds
- C07C201/12—Preparation of nitro compounds by reactions not involving the formation of nitro groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
- C07C209/30—Preparation of compounds containing amino groups bound to a carbon skeleton by reduction of nitrogen-to-oxygen or nitrogen-to-nitrogen bonds
- C07C209/32—Preparation of compounds containing amino groups bound to a carbon skeleton by reduction of nitrogen-to-oxygen or nitrogen-to-nitrogen bonds by reduction of nitro groups
- C07C209/36—Preparation of compounds containing amino groups bound to a carbon skeleton by reduction of nitrogen-to-oxygen or nitrogen-to-nitrogen bonds by reduction of nitro groups by reduction of nitro groups bound to carbon atoms of six-membered aromatic rings in presence of hydrogen-containing gases and a catalyst
- C07C209/365—Preparation of compounds containing amino groups bound to a carbon skeleton by reduction of nitrogen-to-oxygen or nitrogen-to-nitrogen bonds by reduction of nitro groups by reduction of nitro groups bound to carbon atoms of six-membered aromatic rings in presence of hydrogen-containing gases and a catalyst by reduction with preservation of halogen-atoms in compounds containing nitro groups and halogen atoms bound to the same carbon skeleton
-
- 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
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention belongs to the technical field of medical intermediates, and particularly relates to a synthetic method of 2-chloro-3-fluoro-4- (trifluoromethyl) benzaldehyde. The compound A is used as a basic raw material to obtain the 2-chloro-3-fluoro-4- (trifluoromethyl) benzaldehyde through a halogenation reaction, a hydrogenation reduction, a diazotization reaction and a nucleophilic substitution. 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 medical intermediates, and particularly relates to a synthetic method of 2-chloro-3-fluoro-4- (trifluoromethyl) benzaldehyde.
Background
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 technical problems to be solved by the invention are as follows: aiming at the problems, the synthesis method of the 2-chloro-3-fluoro-4- (trifluoromethyl) benzaldehyde is provided.
In order to solve the technical problems, the invention adopts the following technical scheme:
a synthetic method of 2-chloro-3-fluoro-4- (trifluoromethyl) benzaldehyde has the following chemical formula:
the synthesis method comprises the following steps:
(1) mixing the compound A, ferric trichloride and chlorosuccinimide, dissolving in acetonitrile, and heating to react to obtain a compound B;
(2) under the action of a palladium-carbon catalyst, stirring the compound B in a hydrogen atmosphere for reaction to obtain a compound C;
(3) mixing the compound C and hydrochloric acid with the mass fraction of 10% at 0-2 ℃, then dropwise adding a sodium nitrite solution with the mass fraction of 10%, stirring for reaction, then adding a hypophosphorous acid solution with the mass fraction of 50%, heating, and reacting to obtain a compound D;
(4) and dissolving the compound D in tetrahydrofuran, and carrying out nucleophilic substitution with dimethylformamide at the temperature of-80 to-70 ℃ under the action of lithium diisopropylamide to obtain a compound E, namely 2-chloro-3-fluoro-4- (trifluoromethyl) benzaldehyde.
The mass ratio of the compound A, ferric trichloride and chlorosuccinimide in the step (1) is 1: 0.2-0.5: 1-2.
The adding amount of the palladium-carbon catalyst in the step (2) is 3-6% of the mass of the compound B.
In the step (3), the mass ratio of the compound C to the 10% hydrochloric acid is 1:5, the mass ratio of the compound C to the 10% sodium nitrite solution is 1: 5-8, and the mass ratio of the compound C to the 50% hypophosphorous acid solution is 1: 10.
The molar ratio of lithium diisopropylamide to the compound D to dimethylformamide in the step (4) is 1-3: 1: 3-6.
Compared with other methods, the method has the beneficial technical effects that:
the compound A is used as a basic raw material to obtain 2-chloro-3-fluoro-4- (trifluoromethyl) benzaldehyde through halogenation, hydrogenation reduction, diazotization and nucleophilic substitution;
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
A synthetic method of 2-chloro-3-fluoro-4- (trifluoromethyl) benzaldehyde comprises the following steps:
(1) taking materials according to the mass ratio of the compound A to ferric trichloride to chlorosuccinimide of 1: 0.2-0.5: 1-2, sequentially adding the raw materials A, ferric trichloride, chlorosuccinimide and acetonitrile into a reaction bottle, heating to 80-85 ℃, carrying out reflux reaction for 3-5 h, adding dichloromethane and 10% sodium carbonate solution, stirring until the mixture is clear, separating, washing, and concentrating organic phase under reduced pressure until the mixture is dry to obtain a compound B;
(2) adding the compound B into a reaction bottle, adding a palladium-carbon catalyst (5 wt% of palladium in the palladium-carbon catalyst) which is 3-6% of the mass of the compound B, boosting the pressure to 2-3 MPa by using hydrogen, setting the temperature to be 20-30 ℃, stirring for reaction for 2-3 h, filtering, and concentrating the filtrate to be dry to obtain a compound C;
(3) taking materials according to the mass ratio of a compound C to 10% hydrochloric acid of 1:5, the mass ratio of the compound C to 10% sodium nitrite solution of 1: 5-8 and the mass ratio of the compound C to 50% hypophosphorous acid solution of 1:10, adding the compound C to 10% hydrochloric acid at 0-2 ℃, dropwise adding 10% sodium nitrite solution and sodium nitrite solution, stirring and reacting for 1-2 h, adding 50% hypophosphorous acid solution of mass fraction, reacting for 20-26 h at 20-25 ℃, extracting with dichloromethane, washing with water, and concentrating under reduced pressure to dryness to obtain a compound D;
(4) taking materials according to the molar ratio of lithium diisopropylamide to compound D to dimethylformamide of 1-3: 1: 3-6, dissolving the compound D in 20mL of 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 h, dropwise adding dimethylformamide, keeping the temperature, continuously stirring for 1h, adding dilute hydrochloric acid and ethyl acetate, layering, and concentrating an organic phase to obtain a compound E, namely the 2-chloro-3-fluoro-4-trifluoromethylbenzaldehyde.
Example 1
A synthetic method of 2-chloro-3-fluoro-4- (trifluoromethyl) benzaldehyde comprises the following steps:
(1) adding 1g of raw material A, 0.2g of ferric trichloride, 1g of chlorosuccinimide and acetonitrile into a reaction bottle in sequence, heating to 80 ℃, carrying out reflux reaction for 3 hours, adding dichloromethane and 10% sodium carbonate solution, stirring until the solution is clear, separating the solution, washing with water, and concentrating the organic phase under reduced pressure until the organic phase is dried to obtain 1.1g of compound B, wherein the yield is 94.4% and the purity is 96.8%;
(2) adding 1g of the compound B into a reaction bottle, adding a palladium-carbon catalyst (5 wt% of palladium in the palladium-carbon catalyst) which is 3% of the mass of the compound B, boosting the pressure to 2MPa by using hydrogen, setting the temperature to be 20 ℃, stirring for reaction for 2 hours, filtering, and concentrating the filtrate to be dry to obtain 0.82g of the compound C, wherein the yield is 93.5%, and the purity is 97.2%;
(3) adding 2g of the compound C into 10g of hydrochloric acid with the mass fraction of 10% at 0 ℃, dropwise adding 10g of a sodium nitrite solution, stirring and reacting for 1h, adding 20g of a hypophosphorous acid solution with the mass fraction of 50%, reacting for 20h at 20 ℃, extracting with dichloromethane, washing with water, and concentrating under reduced pressure to dryness to obtain 1.7g of a compound D, wherein the yield is 91.4%, and the purity is 98.1%;
(4) dissolving 2g of the compound D in 20mL of tetrahydrofuran, putting the tetrahydrofuran into a reactor, setting the temperature to be 80 ℃ below zero, dropwise adding 30mL of a tetrahydrofuran solution containing 1.8g of lithium diisopropylamide, keeping the temperature to be 80 ℃ below zero, stirring for 1h, dropwise adding 3g of dimethylformamide, keeping the temperature, continuing stirring for 1h, adding dilute hydrochloric acid, ethyl acetate, layering, and concentrating an organic phase to obtain a compound E, namely obtaining 2.2g of 2-chloro-3-fluoro-4-trifluoromethylbenzaldehyde, wherein the yield is 96.4% and the purity is 98.6%.
2-chloro-3-fluoro-4-trifluoromethylbenzaldehyde nuclear magnetic resonance: 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).
Example 2
A synthetic method of 2-chloro-3-fluoro-4- (trifluoromethyl) benzaldehyde comprises the following steps:
(1) adding 1g of raw material A, 0.2g of ferric trichloride, 1g of chlorosuccinimide and acetonitrile into a reaction bottle in sequence, heating to 85 ℃, carrying out reflux reaction for 5 hours, adding dichloromethane and 10% sodium carbonate solution, stirring until the solution is clear, separating liquid, washing with water, and concentrating organic phase under reduced pressure until the solution is dry to obtain 1.12g of compound B, wherein the yield is 96% and the purity is 95.6%;
(2) adding 1g of the compound B into a reaction bottle, adding a palladium-carbon catalyst (5 wt% of palladium in the palladium-carbon catalyst) which is 3% of the mass of the compound B, boosting the pressure to 3MPa by using hydrogen, setting the temperature to be 30 ℃, stirring for reaction for 3 hours, filtering, and concentrating the filtrate to be dry to obtain 0.8g of a compound C, wherein the yield is 91.2%, and the purity is 95.3%;
(3) adding 2g of compound C into 10g of hydrochloric acid with the mass fraction of 10% at the temperature of 2 ℃, dropwise adding 10g of sodium nitrite solution, stirring and reacting for 2 hours, adding 20g of hypophosphorous acid solution with the mass fraction of 50%, reacting for 26 hours at the temperature of 25 ℃, extracting with dichloromethane, washing with water, and concentrating under reduced pressure until the mixture is dry to obtain 1.8g of compound D, wherein the yield is 96.8%, and the purity is 98.3%;
(4) dissolving 2g of the compound D in 20mL of tetrahydrofuran, putting the tetrahydrofuran into a reactor, setting the temperature to be-70 ℃, dropwise adding 30mL of a tetrahydrofuran solution containing 1.8g of lithium diisopropylamide, keeping the temperature to be-70 ℃, stirring for 2h, dropwise adding 3g of dimethylformamide, keeping the temperature, continuously stirring for 1h, adding dilute hydrochloric acid, ethyl acetate, layering, and concentrating an organic phase to obtain a compound E, namely obtaining 2.1g of 2-chloro-3-fluoro-4-trifluoromethylbenzaldehyde, wherein the yield is 92% and the purity is 98.9%.
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).
Claims (5)
1. A synthetic method of 2-chloro-3-fluoro-4- (trifluoromethyl) benzaldehyde is characterized in that the chemical formula of the synthetic method is as follows:
the synthesis method comprises the following steps:
(1) mixing the compound A, ferric trichloride and chlorosuccinimide, dissolving in acetonitrile, and heating to react to obtain a compound B;
(2) under the action of a palladium-carbon catalyst, stirring the compound B in a hydrogen atmosphere for reaction to obtain a compound C;
(3) mixing the compound C and hydrochloric acid with the mass fraction of 10% at 0-2 ℃, then dropwise adding a sodium nitrite solution with the mass fraction of 10%, stirring for reaction, then adding a hypophosphorous acid solution with the mass fraction of 50%, heating, and reacting to obtain a compound D;
(4) and dissolving the compound D in tetrahydrofuran, and carrying out nucleophilic substitution with dimethylformamide at the temperature of-80 to-70 ℃ under the action of lithium diisopropylamide to obtain a compound E, namely 2-chloro-3-fluoro-4- (trifluoromethyl) benzaldehyde.
2. The method for synthesizing 2-chloro-3-fluoro-4- (trifluoromethyl) benzaldehyde according to claim 1, wherein the mass ratio of the compound A, ferric trichloride and chlorosuccinimide in the step (1) is 1: 0.2-0.5: 1-2.
3. The method for synthesizing 2-chloro-3-fluoro-4- (trifluoromethyl) benzaldehyde according to claim 1, wherein the amount of the palladium-carbon catalyst added in step (2) is 3-6% by mass of the compound B.
4. The method for synthesizing 2-chloro-3-fluoro-4- (trifluoromethyl) benzaldehyde according to claim 1, wherein the mass ratio of the compound C to 10% hydrochloric acid in the step (3) is 1:5, the mass ratio of the compound C to 10% sodium nitrite solution is 1: 5-8, and the mass ratio of the compound C to 50% hypophosphorous acid solution is 1: 10.
5. The method for synthesizing 2-chloro-3-fluoro-4- (trifluoromethyl) benzaldehyde according to claim 1, wherein the molar ratio of lithium diisopropylamide to compound D to dimethylformamide in step (4) is 1-3: 1: 3-6.
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| US20110144334A1 (en) * | 2005-09-02 | 2011-06-16 | Nissan Chemical Industries, Ltd. | Isoxazoline-substituted benzamide compound and pesticide |
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| CN106905104A (en) * | 2017-01-03 | 2017-06-30 | 浙江巍华化工有限公司 | A kind of synthetic method of the fluoride trifluoro toluene of 2 bromine 5 |
| CN112110804A (en) * | 2020-09-28 | 2020-12-22 | 台州臻挚生物科技有限公司 | Preparation method of 3, 5-dihalo-trifluoro-acetophenone and derivatives thereof |
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| Title |
|---|
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