CN115010574B - Synthesis method of 1-bromo-2-chloro-4-fluoro-2-iodobenzene - Google Patents
Synthesis method of 1-bromo-2-chloro-4-fluoro-2-iodobenzene Download PDFInfo
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- CN115010574B CN115010574B CN202210631023.7A CN202210631023A CN115010574B CN 115010574 B CN115010574 B CN 115010574B CN 202210631023 A CN202210631023 A CN 202210631023A CN 115010574 B CN115010574 B CN 115010574B
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- RSODKRWMIINXMR-UHFFFAOYSA-N FC(C=CC1Br)=CC1(Cl)I Chemical compound FC(C=CC1Br)=CC1(Cl)I RSODKRWMIINXMR-UHFFFAOYSA-N 0.000 title claims abstract description 18
- 238000001308 synthesis method Methods 0.000 title claims description 7
- 238000006243 chemical reaction Methods 0.000 claims abstract description 38
- LEFQPBAWVJEIJS-UHFFFAOYSA-N 1-bromo-2-chloro-4-fluorobenzene Chemical compound FC1=CC=C(Br)C(Cl)=C1 LEFQPBAWVJEIJS-UHFFFAOYSA-N 0.000 claims abstract description 13
- 239000003513 alkali Substances 0.000 claims abstract description 8
- 239000003960 organic solvent Substances 0.000 claims abstract description 6
- 238000001816 cooling Methods 0.000 claims abstract description 3
- 238000010438 heat treatment Methods 0.000 claims abstract description 3
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims abstract description 3
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 32
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims description 25
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 22
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 claims description 18
- 239000012074 organic phase Substances 0.000 claims description 14
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 claims description 14
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 11
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 9
- 239000011630 iodine Substances 0.000 claims description 9
- 229910052740 iodine Inorganic materials 0.000 claims description 9
- 238000001035 drying Methods 0.000 claims description 8
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 7
- 230000035484 reaction time Effects 0.000 claims description 7
- 229910052938 sodium sulfate Inorganic materials 0.000 claims description 7
- 235000011152 sodium sulphate Nutrition 0.000 claims description 7
- 235000010265 sodium sulphite Nutrition 0.000 claims description 7
- 238000010791 quenching Methods 0.000 claims description 6
- 230000000171 quenching effect Effects 0.000 claims description 6
- 238000005406 washing Methods 0.000 claims description 6
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 claims description 5
- 238000000926 separation method Methods 0.000 claims description 4
- 238000010189 synthetic method Methods 0.000 claims description 4
- 239000002585 base Substances 0.000 claims description 2
- 238000000605 extraction Methods 0.000 claims description 2
- 239000007788 liquid Substances 0.000 claims description 2
- 238000000746 purification Methods 0.000 claims description 2
- 239000007787 solid Substances 0.000 claims description 2
- 239000003054 catalyst Substances 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 9
- 238000000034 method Methods 0.000 abstract description 5
- 230000002194 synthesizing effect Effects 0.000 abstract description 2
- 239000000243 solution Substances 0.000 description 13
- 238000002360 preparation method Methods 0.000 description 8
- RRXVVVHKJRXELS-UHFFFAOYSA-N 1-bromo-2-chloro-4-fluoro-3-iodobenzene Chemical compound Fc1ccc(Br)c(Cl)c1I RRXVVVHKJRXELS-UHFFFAOYSA-N 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 238000002425 crystallisation Methods 0.000 description 5
- 230000008025 crystallization Effects 0.000 description 5
- 238000001914 filtration Methods 0.000 description 4
- -1 polycyclic aromatic compounds Chemical class 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- 238000010268 HPLC based assay Methods 0.000 description 2
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
- MWPLVEDNUUSJAV-UHFFFAOYSA-N anthracene Chemical compound C1=CC=CC2=CC3=CC=CC=C3C=C21 MWPLVEDNUUSJAV-UHFFFAOYSA-N 0.000 description 2
- 238000004020 luminiscence type Methods 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 230000005855 radiation Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 150000001491 aromatic compounds Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000005281 excited state Effects 0.000 description 1
- 230000005283 ground state Effects 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 1
- BNHFWQQYLUPDOG-UHFFFAOYSA-N lithium;1,2,2,3-tetramethylpiperidine Chemical compound [Li].CC1CCCN(C)C1(C)C BNHFWQQYLUPDOG-UHFFFAOYSA-N 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C17/00—Preparation of halogenated hydrocarbons
- C07C17/093—Preparation of halogenated hydrocarbons by replacement by halogens
- C07C17/10—Preparation of halogenated hydrocarbons by replacement by halogens of hydrogen atoms
- C07C17/12—Preparation of halogenated hydrocarbons by replacement by halogens of hydrogen atoms in the ring of aromatic compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C17/00—Preparation of halogenated hydrocarbons
- C07C17/38—Separation; Purification; Stabilisation; Use of additives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C17/00—Preparation of halogenated hydrocarbons
- C07C17/38—Separation; Purification; Stabilisation; Use of additives
- C07C17/392—Separation; Purification; Stabilisation; Use of additives by crystallisation; Purification or separation of the crystals
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Analytical Chemistry (AREA)
- Crystallography & Structural Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention provides a method for synthesizing a key intermediate 1-bromo-2-chloro-4-fluoro-2-iodobenzene of an organic luminescent compound, which comprises the steps of dissolving 1-bromo-2-chloro-4-fluorobenzene in an organic solvent, cooling to a temperature of between-45 and-80 ℃ and then adding alkali for reaction; and adding iodine, heating to 15-35 ℃ for reaction, and thus the method has the advantages of high reaction yield, simple steps, low cost and popularization and application value.
Description
Technical Field
The invention belongs to the field of compound synthesis, and particularly relates to a synthesis method of 1-bromo-2-chloro-4-fluoro-2-iodobenzene.
Background
Along with the development of scientific technology, society is moving into information age, and luminescent materials are widely applied to high and new technical fields such as communication, radar, satellite, display, recording, optical computers, biomolecular probes and the like, so that research on organic luminescent materials is getting more attention. Luminescence is usually the intrinsic unbalanced radiation of excited ions, atoms, molecules or substances composed of them. The luminescence of the organic substance is a radiation transition phenomenon generated by the return of the molecule from the excited state to the ground state.
At present, research on light emission of simple aromatic compounds such as anthracene, naphthalene and derivatives thereof and polycyclic aromatic compounds and derivatives thereof as organic molecules is relatively wide, patent application CN113166126a discloses a series of organic light-emitting compounds and organic light-emitting devices containing the same, and the disclosed compounds are used as subjects of red light-emitting layers, so that the driving voltage, light-emitting efficiency and service life characteristics of the organic light-emitting devices can be improved. In the preparation of these compounds, 1-bromo-2-chloro-4-fluoro-2-iodobenzene is a key intermediate.
However, 1-bromo-2-chloro-4-fluoro-2-iodobenzene is a key intermediate for synthesizing organic luminescent materials, and is relatively expensive, so that the wide application of the excellent organic luminescent compounds is limited, and no report on a synthetic method of 1-bromo-2-chloro-4-fluoro-2-iodobenzene is currently seen.
Disclosure of Invention
The invention aims to provide a method for preparing a key intermediate 1-bromo-2-chloro-4-fluoro-2-iodobenzene of an organic light-emitting compound by taking low-cost 1-bromo-2-chloro-4-fluorobenzene as a raw material.
The invention provides a synthesis method of 1-bromo-2-chloro-4-fluoro-2-iodobenzene, which comprises the following steps:
(1) Dissolving 1-bromo-2-chloro-4-fluorobenzene in an organic solvent, cooling to-45 ℃ to-80 ℃ and then adding alkali for reaction;
(2) Adding iodine, heating to 15-35 ℃ for reaction to obtain the product;
the reaction formula is as follows:
further, the molar ratio of the 1-bromo-2-chloro-4-fluorobenzene, the alkali and the iodine is as follows: 1 (1-1.5) and 1-1.2).
Further, the molar ratio of the 1-bromo-2-chloro-4-fluorobenzene, the alkali and the iodine is as follows: 1:1.1:1.04.
Further, the alkali in the step (1) is lithium diisopropylamide, lithium tetramethylpiperidine, lithium bis (trimethylsilyl) amide, sodium bis (trimethylsilyl) amide, potassium bis (trimethylsilyl) amide;
the organic solvent is tetrahydrofuran, 2-methyltetrahydrofuran, methyl tertiary butyl ether, n-hexane, n-heptane, benzene, diethyl ether and isopropyl ether.
Further, the base in the step (1) is lithium diisopropylamide, and the organic solvent in the step (2) is tetrahydrofuran or 2-methyltetrahydrofuran.
Further, the temperature of the reaction in the step (1) is between 50 ℃ below zero and 78 ℃ below zero, and the reaction time is between 1 and 3 hours;
and/or the temperature of the reaction in the step (2) is 20-30 ℃, and the reaction time is 8-15 hours.
Further, the reaction temperature in the step (1) is-78 ℃ and the reaction time is 2 hours; and/or the temperature of the reaction in the step (2) is 25 ℃, and the reaction time is 12 hours.
Further, the method further comprises the following separation and purification steps:
(3) Adding the solution obtained after the reaction in the step (2) into concentrated hydrochloric acid for quenching, and adding n-heptane for extraction and liquid separation to obtain an organic phase;
(4) The organic phase is washed, dried, concentrated, crystallized by adding n-heptane and filtered to obtain a solid.
Further, the concentrated hydrochloric acid in the step (3) is 6N hydrochloric acid;
and/or step (4) of washing with an aqueous sodium sulfite solution; the drying is drying with sodium sulfate.
The invention has the beneficial effects that: the invention adopts the cheap 1-bromo-2-chloro-4-fluorobenzene as the raw material, successfully synthesizes the key intermediate 1-bromo-2-chloro-4-fluoro-2-iodobenzene of the organic light-emitting compound, has high yield, simple preparation steps and low cost, and has popularization and application values.
It should be apparent that, in light of the foregoing, various modifications, substitutions and alterations can be made herein without departing from the spirit and scope of the invention as defined by the appended claims.
The above-described aspects of the present invention will be described in further detail below with reference to specific embodiments in the form of examples. It should not be understood that the scope of the above subject matter of the present invention is limited to the following examples only. All techniques implemented based on the above description of the invention are within the scope of the invention.
Detailed Description
The raw materials and equipment used in the invention are all known products and are obtained by purchasing commercial products.
Example 1 preparation of 1-bromo-2-chloro-4-fluoro-2-iodobenzene
1-bromo-2-chloro-4-fluorobenzene (20.9 g,0.1 mol) is dissolved in 210mL of anhydrous tetrahydrofuran, cooled to-78 ℃, lithium Diisopropylamide (LDA) (110mL,1.0M in THF) is slowly added dropwise, and after the dropwise addition is finished, the reaction is continued for 2 hours with heat preservation; controlling the temperature to minus 78 ℃, dropwise adding iodine (26.5 g, dissolved in 60mL tetrahydrofuran), and after the dropwise adding is finished, returning the temperature to 25 ℃ for reacting for 12 hours; after the reaction is completed, quenching the reaction solution into 6N hydrochloric acid, adding 210mL of N-heptane, separating the solution, washing the organic phase to light yellow by using sodium sulfite aqueous solution, concentrating the organic phase sodium sulfate after drying, adding 30mL of N-heptane for crystallization, and filtering to obtain 28.1g of 1-bromo-2-chloro-4-fluoro-3-iodobenzene with a yield of 84%;
HNMR (400 m, dmso): δ=7.84-7.87 (dd, 1H), 7.21-7.25 (dd, 1H). HPLC assay purity 97.1%;
example 2 preparation of 1-bromo-2-chloro-4-fluoro-2-iodobenzene
1-bromo-2-chloro-4-fluorobenzene (20.9 g,0.1 mol) is dissolved in 210mL of anhydrous tetrahydrofuran, cooled to-50 ℃, LDA (110mL,1.0M in THF) is slowly added dropwise, and the reaction is continued for 2 hours after the dropwise addition is finished; iodine (26.5 g, dissolved in 60mL tetrahydrofuran) is added dropwise at the temperature of minus 50 ℃, and the temperature is returned to 25 ℃ for reaction for 12 hours after the addition is finished; after the reaction is completed, quenching the reaction solution into 6N hydrochloric acid, adding 210mL of N-heptane, separating the solution, washing the organic phase to light yellow by using sodium sulfite aqueous solution, concentrating the organic phase sodium sulfate after drying, adding 30mL of N-heptane for crystallization, and filtering to obtain 25.0g of 1-bromo-2-chloro-4-fluoro-3-iodobenzene with a yield of 75%;
HNMR (400 m, dmso): δ=7.84-7.87 (dd, 1H), 7.21-7.25 (dd, 1H). (HPLC detection purity 95.6%;
example 3 preparation of 1-bromo-2-chloro-4-fluoro-2-iodobenzene
1-bromo-2-chloro-4-fluorobenzene (20.9 g,0.1 mol) is dissolved in 210mL anhydrous 2-methyltetrahydrofuran, the temperature is reduced to-50 ℃, LDA (110mL,1.0M in THF) is slowly added dropwise, and the reaction is continued for 2 hours after the dropwise addition is finished; iodine (26.5 g, dissolved in 60mL tetrahydrofuran) is added dropwise at the temperature of minus 50 ℃, and the temperature is returned to 25 ℃ for reaction for 12 hours after the addition is finished; after the reaction is completed, quenching the reaction solution into 6N hydrochloric acid, adding 210mL of N-heptane, separating the solution, washing the organic phase to light yellow by using sodium sulfite aqueous solution, concentrating the organic phase sodium sulfate after drying, adding 30mL of N-heptane for crystallization, and filtering to obtain 25.0g of 1-bromo-2-chloro-4-fluoro-3-iodobenzene with a yield of 75%;
HNMR (400 m, dmso): δ=7.84-7.87 (dd, 1H), 7.21-7.25 (dd, 1H). HPLC assay purity 98.2%;
example 4 preparation of 1-bromo-2-chloro-4-fluoro-2-iodobenzene
1-bromo-2-chloro-4-fluorobenzene (20.9 g,0.1 mol) is dissolved in 210mL anhydrous 2-methyltetrahydrofuran, the temperature is reduced to minus 78 ℃, LDA (110mL,1.0M in THF) is slowly added dropwise, and the reaction is continued for 2 hours after the dropwise addition is finished; controlling the temperature to minus 78 ℃, dropwise adding iodine (26.5 g, dissolved in 60mL tetrahydrofuran), and after the dropwise adding is finished, returning the temperature to 25 ℃ for reacting for 12 hours; after the reaction is completed, quenching the reaction solution into 6N hydrochloric acid, adding 210mL of N-heptane, separating the solution, washing the organic phase to light yellow by using sodium sulfite aqueous solution, concentrating the organic phase sodium sulfate after drying, adding 30mL of N-heptane for crystallization, and filtering to obtain 28.1g of 1-bromo-2-chloro-4-fluoro-3-iodobenzene with a yield of 84%;
HNMR (400 m, dmso): δ=7.84-7.87 (dd, 1H), 7.21-7.25 (dd, 1H). HPLC purity 97.5%;
example 5 preparation of 1-bromo-2-chloro-4-fluoro-2-iodobenzene
1-bromo-2-chloro-4-fluorobenzene (20.9 g,0.1 mol) is dissolved in 210mL of anhydrous tetrahydrofuran, cooled to-10 ℃, LDA (110mL,1.0M in THF) is slowly added dropwise, and the reaction is continued for 2 hours after the dropwise addition is finished; iodine (26.5 g, dissolved in 60mL tetrahydrofuran) is added dropwise at-10deg.C, and the temperature is returned to 25deg.C after the addition is completed for reacting for 12 hours; after the reaction is completed, the reaction solution is quenched into 6N hydrochloric acid, 210mL of N-heptane is added, the solution is separated, the organic phase is washed to be light yellow by sodium sulfite aqueous solution, the organic phase sodium sulfate is concentrated after being dried, 30mL of N-heptane is added for crystallization, and the reaction solution is filtered to obtain 13.2g of 1-bromo-2-chloro-4-fluoro-3-iodobenzene with the yield of 47%;
HNMR (400 m, dmso): δ=7.84-7.87 (dd, 1H), 7.21-7.25 (dd, 1H). Purity by HPLC 92.1%.
It can be seen that the product 1-bromo-2-chloro-4-fluoro-2-iodobenzene can be successfully prepared at a reaction temperature of-10 ℃, but the yield is obviously reduced and the purity is also reduced. Whereas, the yields were higher when the reaction temperatures of examples 1 to 4 were in the range of-50℃to-78 ℃. Especially at-78 ℃.
In conclusion, the invention provides the synthesis method of the key intermediate 1-bromo-2-chloro-4-fluoro-2-iodobenzene of the organic light-emitting compound, which has the advantages of high yield, simple preparation steps, low cost and popularization and application values.
Claims (4)
1. The synthesis method of the 1-bromo-2-chloro-4-fluoro-2-iodobenzene is characterized by comprising the following steps:
(1) Dissolving 1-bromo-2-chloro-4-fluorobenzene in an organic solvent, cooling to-78 ℃ and adding alkali for reaction; the alkali is lithium diisopropylamide, and the organic solvent is tetrahydrofuran or 2-methyltetrahydrofuran; the reaction temperature is-78 ℃, and the reaction time is 1-3 hours;
(2) Adding iodine, heating to 20-30 ℃ for reaction to obtain the catalyst; the reaction time is 8-15 hours;
the reaction formula is as follows:
the molar ratio of the 1-bromine-2-chlorine-4-fluorobenzene to the alkali to the iodine is as follows: 1 (1-1.5), 1-1.2; the synthesis method also comprises the following separation and purification steps:
(3) Adding the solution obtained after the reaction in the step (2) into concentrated hydrochloric acid for quenching, and adding n-heptane for extraction and liquid separation to obtain an organic phase;
(4) The organic phase is washed, dried, concentrated, crystallized by adding n-heptane and filtered to obtain a solid.
2. The synthetic method according to claim 1, wherein the molar ratio of 1-bromo-2-chloro-4-fluorobenzene, base and iodine is: 1:1.1:1.04.
3. The synthetic method of claim 1 wherein the time of the reaction of step (1) is 2 hours; and/or the temperature of the reaction in the step (2) is 25 ℃, and the reaction time is 12 hours.
4. The synthetic method of claim 1 wherein the concentrated hydrochloric acid of step (3) is 6N hydrochloric acid;
and/or step (4) of washing with an aqueous sodium sulfite solution; the drying is drying with sodium sulfate.
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