CN114805041B - Synthesis method of 2-chloro-3-fluoro-4- (trifluoromethyl) benzaldehyde - Google Patents
Synthesis method of 2-chloro-3-fluoro-4- (trifluoromethyl) benzaldehyde Download PDFInfo
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- CN114805041B CN114805041B CN202110079084.2A CN202110079084A CN114805041B CN 114805041 B CN114805041 B CN 114805041B CN 202110079084 A CN202110079084 A CN 202110079084A CN 114805041 B CN114805041 B CN 114805041B
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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
- 238000001308 synthesis method Methods 0.000 title claims description 6
- 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 18
- 238000006243 chemical reaction Methods 0.000 claims description 18
- 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 18
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 claims description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 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
- 238000003756 stirring Methods 0.000 claims description 16
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 15
- 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
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 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
- 230000002194 synthesizing effect Effects 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 238000002156 mixing Methods 0.000 claims description 4
- 239000000126 substance Substances 0.000 claims description 2
- 238000010189 synthetic method Methods 0.000 abstract description 7
- 230000015572 biosynthetic process Effects 0.000 abstract description 6
- 239000002994 raw material Substances 0.000 abstract description 6
- 238000003786 synthesis reaction Methods 0.000 abstract description 6
- 239000000575 pesticide Substances 0.000 abstract description 5
- 239000000543 intermediate Substances 0.000 abstract description 4
- 238000006193 diazotization reaction Methods 0.000 abstract description 2
- 238000005658 halogenation reaction Methods 0.000 abstract description 2
- 239000004009 herbicide Substances 0.000 abstract description 2
- 238000005984 hydrogenation reaction Methods 0.000 abstract description 2
- 238000006722 reduction 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
- 239000000203 mixture Substances 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
- 239000000463 material 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
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- 239000012847 fine chemical Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 229940127554 medical product Drugs 0.000 description 1
Classifications
-
- 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
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 invention takes the compound A as a basic raw material to obtain the 2-chloro-3-fluoro-4- (trifluoromethyl) benzaldehyde through halogenation reaction, hydrogenation reduction, diazotization reaction and nucleophilic substitution. The 2-chloro-3-fluoro-4- (trifluoromethyl) benzaldehyde disclosed by the invention can be widely applied to the pesticide synthesis process, such as the synthesis of pesticides such as herbicides, and the like, and has the advantages of higher synthesis yield and higher 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 an important fine chemical intermediate, can be applied to pesticides and medical products, and becomes a hot spot product in the field of fine chemical intermediates. However, no document reports about 2-chloro-3-fluoro-4- (trifluoromethyl) benzaldehyde and a synthetic method thereof exist at present. Therefore, a synthetic method which has the advantages of easily available raw materials, convenient operation, easy control of reaction and proper overall yield and is suitable for industrial production needs to be developed.
Disclosure of Invention
The invention aims to solve the technical problems that: in view of the above problems, a method for synthesizing 2-chloro-3-fluoro-4- (trifluoromethyl) benzaldehyde is provided.
In order to solve the technical problems, the invention adopts the following technical proposal:
a synthesis method of 2-chloro-3-fluoro-4- (trifluoromethyl) benzaldehyde, which 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 for reaction 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 with hydrochloric acid with the mass fraction of 10% at the temperature of 0-2 ℃, then dripping sodium nitrite solution with the mass fraction of 10% for stirring reaction, then adding hypophosphorous acid solution with the mass fraction of 50%, heating, and reacting to obtain a compound D;
(4) Dissolving the compound D in tetrahydrofuran, and carrying out nucleophilic substitution with dimethylformamide at-80 to-70 ℃ under the action of lithium diisopropylamide to obtain a compound E, namely 2-chloro-3-fluoro-4- (trifluoromethyl) benzaldehyde.
In the step (1), the mass ratio of the compound A to the ferric trichloride to the chlorosuccinimide is 1:0.2-0.5:1-2.
The addition 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.
In the step (4), the molar ratio of the lithium diisopropylamide to the compound D to the dimethylformamide is 1-3:1:3-6.
Compared with other methods, the invention has the beneficial technical effects that:
the invention takes the compound A as a basic raw material to obtain 2-chloro-3-fluoro-4- (trifluoromethyl) benzaldehyde through halogenation reaction, hydrogenation reduction, diazotization reaction and nucleophilic substitution;
the 2-chloro-3-fluoro-4- (trifluoromethyl) benzaldehyde disclosed by the invention can be widely applied to the pesticide synthesis process, such as the synthesis of pesticides such as herbicides, and the like, and has the advantages of higher synthesis yield and higher purity.
Detailed Description
A synthetic method of 2-chloro-3-fluoro-4- (trifluoromethyl) benzaldehyde, which comprises the following steps:
(1) Taking materials according to the mass ratio of the compound A to the ferric trichloride to the chlorosuccinimide of 1:0.2-0.5:1-2, sequentially adding the raw materials A, the ferric trichloride, the chlorosuccinimide and the acetonitrile into a reaction bottle, heating to 80-85 ℃, carrying out reflux reaction for 3-5 h, adding the dichloromethane and 10% sodium carbonate solution, stirring until the mixture is dissolved, separating the solution, washing the solution, and concentrating the organic phase under reduced pressure until the organic phase is dried to obtain the compound B;
(2) Adding a compound B into a reaction bottle, adding 3-6% of palladium-carbon catalyst (the palladium-carbon catalyst contains 5% of palladium by weight) by the mass of the compound B, pressurizing to 2-3 MPa by using hydrogen, setting the temperature to 20-30 ℃, stirring and reacting 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 1:5 of the compound C and the mass ratio of 1:5-8 of the 10% sodium nitrite solution, wherein the mass ratio of the compound C and the 50% hypophosphorous acid solution is 1:10, adding the compound C into the 10% hydrochloric acid, dropwise adding the 10% sodium nitrite solution and the sodium nitrite solution, stirring and reacting for 1-2 h, adding the 50% hypophosphorous acid solution and reacting for 20-26 h at 20-25 ℃, extracting with dichloromethane, washing with water, and concentrating under reduced pressure to dryness to obtain the compound D;
(4) Taking materials according to the mole ratio of lithium diisopropylamide, compound D and dimethylformamide being 1-3:1:3-6, dissolving compound D in 20mL tetrahydrofuran, placing the tetrahydrofuran into a reactor, setting the temperature to be-80-70 ℃, dropwise adding a tetrahydrofuran solution containing lithium diisopropylamide, keeping the temperature to be-80-70 ℃, stirring for 1-2 h, dropwise adding dimethylformamide, keeping the temperature, continuously stirring for 1h, adding dilute hydrochloric acid and ethyl acetate, layering, concentrating an organic phase, and obtaining the compound E, namely the 2-chloro-3-fluoro-4-trifluoromethyl benzaldehyde.
Example 1
A synthetic method of 2-chloro-3-fluoro-4- (trifluoromethyl) benzaldehyde, which comprises the following steps:
(1) Sequentially adding 1g of raw material A, 0.2g of ferric trichloride, 1g of chlorosuccinimide and acetonitrile into a reaction bottle, heating to 80 ℃, carrying out reflux reaction for 3 hours, adding dichloromethane and 10% sodium carbonate solution, stirring until the mixture is clear, separating liquid, washing with water, and concentrating an organic phase under reduced pressure until the mixture is dry to obtain 1.1g of compound B, wherein the yield is 94.4%, and the purity is 96.8%;
(2) Adding 1g of compound B into a reaction bottle, adding 3% palladium-carbon catalyst (the palladium-carbon catalyst contains 5% weight of palladium) by the mass of the compound B, using hydrogen to raise the pressure to 2MPa, setting the temperature to 20 ℃, stirring and reacting for 2 hours, filtering, concentrating the filtrate to dryness to obtain 0.82g of compound C, wherein the yield is 93.5%, and the purity is 97.2%;
(3) 2g of compound C is added into 10g of hydrochloric acid with the mass fraction of 10%, 10g of sodium nitrite solution is dripped into the mixture, the mixture is stirred for reaction for 1h, 20g of hypophosphorous acid solution with the mass fraction of 50% is added into the mixture for reaction for 20h at the temperature of 20 ℃, dichloromethane is used for extraction, water is used for washing, and the mixture is concentrated to dryness under reduced pressure, so that 1.7g of compound D is obtained, the yield is 91.4%, and the purity is 98.1%;
(4) 2g of compound D is dissolved in 20mL of tetrahydrofuran, the solution is put into a reactor, the temperature is set at minus 80 ℃, 30mL of tetrahydrofuran solution containing 1.8g of lithium diisopropylamide is dropwise added, the temperature is kept at minus 80 ℃, the solution is stirred for 1h, 3g of dimethylformamide is dropwise added, the solution is kept at the temperature and is continuously stirred for 1h, dilute hydrochloric acid and ethyl acetate are added, layering and organic phase concentration are carried out, and then the compound E is obtained, namely 2.2g of 2-chloro-3-fluoro-4-trifluoromethyl benzaldehyde with the yield of 96.4% and the purity of 98.6%.
2-chloro-3-fluoro-4-trifluoromethylbenzaldehyde nuclear magnetic resonance: 1H NMR (400 MHz, CDC 13) 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, which comprises the following steps:
(1) Sequentially adding 1g of raw material A, 0.2g of ferric trichloride, 1g of chlorosuccinimide and acetonitrile into a reaction bottle, heating to 85 ℃, carrying out reflux reaction for 5 hours, adding dichloromethane and 10% sodium carbonate solution, stirring until the mixture is clear, separating liquid, washing with water, and concentrating an organic phase under reduced pressure until the mixture is dry to obtain 1.12g of compound B, wherein the yield is 96%, and the purity is 95.6%;
(2) Adding 1g of compound B into a reaction bottle, adding 3% palladium-carbon catalyst (the palladium-carbon catalyst contains 5% weight of palladium) by the mass of the compound B, using hydrogen to raise the pressure to 3MPa, setting the temperature to 30 ℃, stirring and reacting for 3 hours, filtering, concentrating the filtrate to dryness to obtain 0.8g of 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%, dropwise adding 10g of sodium nitrite solution, stirring and reacting for 2h, adding 20g of hypophosphorous acid solution with the mass fraction of 50%, reacting for 26h at 25 ℃, extracting with dichloromethane, washing with water, concentrating under reduced pressure to dryness to obtain 1.8g of compound D, wherein the yield is 96.8%, and the purity is 98.3%;
(4) 2g of compound D is dissolved in 20mL of tetrahydrofuran, the solution is put into a reactor, the temperature is set at-70 ℃, 30mL of tetrahydrofuran solution containing 1.8g of lithium diisopropylamide is dropwise added, the temperature is kept at-70 ℃, stirring is carried out for 2h, 3g of dimethylformamide is dropwise added, the stirring is continued for 1h at the maintained temperature, dilute hydrochloric acid and ethyl acetate are added, layering and concentration of an organic phase are carried out, thus obtaining compound E, namely 2.1g of 2-chloro-3-fluoro-4-trifluoromethyl benzaldehyde with the yield of 92% and the purity of 98.9%.
2-chloro-3-fluoro-4-trifluoromethylbenzaldehyde nuclear magnetic resonance: 1H NMR (400 MHz, CDC 13) 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 synthesis method of 2-chloro-3-fluoro-4- (trifluoromethyl) benzaldehyde, which is characterized by comprising 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 for reaction 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 with hydrochloric acid with the mass fraction of 10% at the temperature of 0-2 ℃, then dripping sodium nitrite solution with the mass fraction of 10% for stirring reaction, then adding hypophosphorous acid solution with the mass fraction of 50%, heating, and reacting to obtain a compound D;
(4) Dissolving the compound D in tetrahydrofuran, and carrying out nucleophilic substitution with dimethylformamide at-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 to the ferric trichloride to the 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 palladium-carbon catalyst in the step (2) is added in an amount of 3 to 6% by mass of the compound B.
4. The method for synthesizing 2-chloro-3-fluoro-4- (trifluoromethyl) benzaldehyde according to claim 1, wherein in the step (3), the mass ratio of compound C to 10% hydrochloric acid is 1:5, the mass ratio of compound C to 10% sodium nitrite solution is 1:5-8, and the mass ratio of 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, compound D and dimethylformamide in step (4) is 1-3:1:3-6.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106631811A (en) * | 2016-11-23 | 2017-05-10 | 山东友帮生化科技有限公司 | Preparation method of 3-chloro-4-fluoronitrobenzene |
| 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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| JP5293921B2 (en) * | 2005-09-02 | 2013-09-18 | 日産化学工業株式会社 | Isoxazoline-substituted benzamide compounds and pest control agents |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106631811A (en) * | 2016-11-23 | 2017-05-10 | 山东友帮生化科技有限公司 | Preparation method of 3-chloro-4-fluoronitrobenzene |
| 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 |
Non-Patent Citations (1)
| Title |
|---|
| Design and synthesis of fused bicyclic inhibitors targeting the L5 loop site of centromere-associated protein E;Takaharu Hirayama, et al.;Bioorganic & Medicinal Chemistry Letters;第26卷(第17期);第4296-4300页 * |
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