CN112250562A - Synthetic method of 2-bromo-5-methoxybenzoic acid - Google Patents
Synthetic method of 2-bromo-5-methoxybenzoic acid Download PDFInfo
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- CN112250562A CN112250562A CN202011137321.8A CN202011137321A CN112250562A CN 112250562 A CN112250562 A CN 112250562A CN 202011137321 A CN202011137321 A CN 202011137321A CN 112250562 A CN112250562 A CN 112250562A
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- methoxybenzoic acid
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- ODHJOROUCITYNF-UHFFFAOYSA-N 2-bromo-5-methoxybenzoic acid Chemical compound COC1=CC=C(Br)C(C(O)=O)=C1 ODHJOROUCITYNF-UHFFFAOYSA-N 0.000 title claims abstract description 41
- 238000010189 synthetic method Methods 0.000 title claims abstract description 15
- XHQZJYCNDZAGLW-UHFFFAOYSA-N 3-methoxybenzoic acid Chemical compound COC1=CC=CC(C(O)=O)=C1 XHQZJYCNDZAGLW-UHFFFAOYSA-N 0.000 claims abstract description 49
- 238000005893 bromination reaction Methods 0.000 claims abstract description 25
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims abstract description 23
- 239000002904 solvent Substances 0.000 claims abstract description 23
- 238000006243 chemical reaction Methods 0.000 claims abstract description 18
- 230000031709 bromination Effects 0.000 claims abstract description 17
- 150000008282 halocarbons Chemical class 0.000 claims abstract description 14
- 238000010791 quenching Methods 0.000 claims abstract description 14
- 230000000171 quenching effect Effects 0.000 claims abstract description 14
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 12
- 238000001308 synthesis method Methods 0.000 claims abstract description 11
- 239000003999 initiator Substances 0.000 claims abstract description 10
- 239000012295 chemical reaction liquid Substances 0.000 claims abstract description 9
- 239000005457 ice water Substances 0.000 claims abstract description 9
- 238000001914 filtration Methods 0.000 claims abstract description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 21
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 15
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 13
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 claims description 12
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 claims description 10
- 238000000034 method Methods 0.000 claims description 9
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 8
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical group [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims description 8
- MENYRYNFSIBDQN-UHFFFAOYSA-N 5,5-dibromoimidazolidine-2,4-dione Chemical compound BrC1(Br)NC(=O)NC1=O MENYRYNFSIBDQN-UHFFFAOYSA-N 0.000 claims description 6
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 6
- 229910052794 bromium Inorganic materials 0.000 claims description 6
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims description 5
- XWNSFEAWWGGSKJ-UHFFFAOYSA-N 4-acetyl-4-methylheptanedinitrile Chemical compound N#CCCC(C)(C(=O)C)CCC#N XWNSFEAWWGGSKJ-UHFFFAOYSA-N 0.000 claims description 5
- 239000004153 Potassium bromate Substances 0.000 claims description 5
- 230000015572 biosynthetic process Effects 0.000 claims description 5
- 229940094037 potassium bromate Drugs 0.000 claims description 5
- 235000019396 potassium bromate Nutrition 0.000 claims description 5
- 238000003786 synthesis reaction Methods 0.000 claims description 5
- 238000001953 recrystallisation Methods 0.000 claims description 3
- 239000002994 raw material Substances 0.000 description 9
- 239000000047 product Substances 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 5
- 239000012452 mother liquor Substances 0.000 description 5
- 230000000052 comparative effect Effects 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- RIUPLDUFZCXCHM-UHFFFAOYSA-N Urolithin A Chemical compound OC1=CC=C2C3=CC=C(O)C=C3OC(=O)C2=C1 RIUPLDUFZCXCHM-UHFFFAOYSA-N 0.000 description 2
- 238000003912 environmental pollution Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- 229930186301 urolithin Natural products 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 1
- PYKYMHQGRFAEBM-UHFFFAOYSA-N anthraquinone Natural products CCC(=O)c1c(O)c2C(=O)C3C(C=CC=C3O)C(=O)c2cc1CC(=O)OC PYKYMHQGRFAEBM-UHFFFAOYSA-N 0.000 description 1
- 150000004056 anthraquinones Chemical class 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 230000004900 autophagic degradation Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 230000002438 mitochondrial effect Effects 0.000 description 1
- 230000004898 mitochondrial function Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000007670 refining Methods 0.000 description 1
- 230000009758 senescence Effects 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/347—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups
- C07C51/363—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by introduction of halogen; by substitution of halogen atoms by other halogen atoms
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention provides a synthetic method of 2-bromo-5-methoxybenzoic acid, which comprises the following steps: dissolving m-methoxybenzoic acid in a halogenated hydrocarbon solvent, and carrying out bromination reaction with a bromination reagent under the action of a bromination initiator, a cocatalyst and sulfuric acid to obtain a 2-bromo-5-methoxybenzoic acid reaction solution; and pouring the reaction liquid of the 2-bromo-5-methoxybenzoic acid into ice water for quenching, recovering the halogenated hydrocarbon solvent under reduced pressure, filtering, and recrystallizing by using the solvent to obtain a finished product of the 2-bromo-5-methoxybenzoic acid. The synthesis method of the 2-bromo-5-methoxybenzoic acid provided by the invention has the advantage that the yield of the prepared 2-bromo-5-methoxybenzoic acid is high.
Description
Technical Field
The invention relates to the technical field of biological pharmacy, in particular to a synthetic method of 2-bromo-5-methoxybenzoic acid.
Background
2-bromo-5-methoxybenzoic acid is a key intermediate in the synthesis of urolithin a, a potent intestinal metabolite that restores mitochondria and reverses muscle senescence, and oral administration of urolithin a can improve mitochondrial function by stimulating a process called mitochondrial autophagy. The urolithin A is also a raw material of anthraquinone drugs with good antitumor activity.
In the related technology, patent CN106831397A takes m-methoxybenzoic acid as raw material, glacial acetic acid as solvent, and reacts with bromine to generate 2-bromo-5-methoxybenzoic acid, when bromination is carried out, because of the common influence of carboxyl steric hindrance and electronic effect, bromination difficulty is large, long-time reaction is needed, and bromination directional selectivity is poor, C-2 substitution is accompanied by C-3 substitution, isomers are more, byproducts are more, purity is low, multiple refining is needed, and yield is only 72%; in the synthetic methods provided by the literature RSC Adv, 2017.7.17254-17263, the yield is 73%; the synthesis method provided by ChemMedChem,2011.6.2273-2286 is not high, but the yield is 82%.
Therefore, it is necessary to provide a novel 2-bromo-5-methoxybenzoic acid to solve the above problems.
Disclosure of Invention
The invention aims to overcome the technical problems and provide a method for synthesizing 2-bromo-5-methoxybenzoic acid with high yield.
In order to achieve the above object, the present invention provides a method for synthesizing 2-bromo-5-methoxybenzoic acid, comprising the following steps:
dissolving m-methoxybenzoic acid in a halogenated hydrocarbon solvent, and carrying out bromination reaction with a bromination reagent under the action of a bromination initiator, a cocatalyst and sulfuric acid to obtain a 2-bromo-5-methoxybenzoic acid reaction solution;
and pouring the reaction liquid of the 2-bromo-5-methoxybenzoic acid into ice water for quenching, recovering the halogenated hydrocarbon solvent under reduced pressure, filtering, and recrystallizing by using the solvent to obtain a finished product of the 2-bromo-5-methoxybenzoic acid.
Preferably, the halogenated hydrocarbon solvent comprises one or more of dichloromethane, chloroform and dichloroethane.
Preferably, the bromination initiator is red phosphorus; the cocatalyst is one or two of potassium bromide and potassium bromate; the brominating reagent comprises one or more of N-bromosuccinimide, dibromohydantoin and bromine.
Preferably, the mass ratio of the m-anisic acid to the halogenated hydrocarbon solvent is 1 (0.5-20).
Preferably, the molar ratio of the m-methoxybenzoic acid to the bromination initiator is 1 (0.01-0.2).
Preferably, the molar ratio of the m-anisic acid to the cocatalyst is 1 (0.01-0.2).
Preferably, the mass ratio of the m-anisic acid to the sulfuric acid is 1 (0.5-5).
Preferably, the molar ratio of the m-methoxybenzoic acid to the brominating reagent is 1 (0.6-3.0).
Preferably, the bromination reaction is carried out at the temperature of-10 ℃ to 80 ℃ for 1 to 24 hours.
Preferably, the solvent used for recrystallization comprises one or more of methanol, ethanol and isopropanol.
Compared with the related art, in the synthetic method of 2-bromo-5-methoxybenzoic acid, cheap and easily available m-methoxybenzoic acid is used as a raw material for synthesis, and the synthetic method has the characteristics of simplicity in operation, high purity, high yield and the like, and experimental results show that the yield of 2-bromo-5-methoxybenzoic acid obtained by the synthetic method is more than 92% and the purity is 98-99.6%; in the synthetic method, the bromine atom in the bromization reagent has high utilization rate, the using amount of sulfuric acid is small, three wastes are less, the product yield is high, the economic benefit is high, the environmental pollution can be reduced, the product production is clean and environment-friendly, and the method is suitable for mass production.
Detailed Description
The technical solutions in the embodiments of the present invention will be 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 invention provides a synthetic method of 2-bromo-5-methoxybenzoic acid, which comprises the following steps:
dissolving m-methoxybenzoic acid in a halogenated hydrocarbon solvent, and carrying out bromination reaction with a bromination reagent under the action of a bromination initiator, a cocatalyst and sulfuric acid to obtain a 2-bromo-5-methoxybenzoic acid reaction solution;
and pouring the reaction liquid of the 2-bromo-5-methoxybenzoic acid into ice water for quenching, recovering the halogenated hydrocarbon solvent under reduced pressure, filtering, and recrystallizing by using the solvent to obtain a finished product of the 2-bromo-5-methoxybenzoic acid.
Preferably, the halogenated hydrocarbon solvent comprises one or more of dichloromethane, chloroform and dichloroethane; the bromination initiator is red phosphorus; the cocatalyst is one or two of potassium bromide and potassium bromate; the brominating reagent comprises one or more of N-bromosuccinimide, dibromohydantoin and bromine; the mass ratio of the m-methoxybenzoic acid to the halogenated hydrocarbon solvent is 1 (0.5-20); the molar ratio of the m-methoxybenzoic acid to the bromination initiator is 1 (0.01-0.2); the molar ratio of the m-methoxybenzoic acid to the cocatalyst is 1 (0.01-0.2); the mass ratio of the m-anisic acid to the sulfuric acid is 1 (0.5-5); the molar ratio of the m-methoxybenzoic acid to the brominating reagent is 1 (0.6-3.0); the temperature of the bromination reaction is-10 ℃ to 80 ℃, and the time is 1 to 24 hours. The solvent used for recrystallization comprises one or more of methanol, ethanol and isopropanol.
Example one
Adding 75g of dichloromethane, 15.2g (0.1mol) of m-methoxybenzoic acid, 30mL of concentrated sulfuric acid, 1.19g (0.01mol) of potassium bromide and 1.23g (0.01mol) of red phosphorus into a 500mL four-neck flask in sequence, starting stirring, adding 26.7g (0.15mol) of N-bromosuccinimide at 25 ℃, controlling the reaction temperature to be 25-30 ℃, reacting for 3h, monitoring the reaction of raw materials by High Performance Liquid Chromatography (HPLC), pouring the reaction Liquid into 200g of ice water for quenching, decompressing and recovering dichloromethane after quenching, filtering mother liquor, and recrystallizing by using 65mL of ethanol to obtain 21.57g of 2-bromo-5-methoxybenzoic acid. The yield of 2-bromo-5-methoxybenzoic acid is 93.4%, and the purity is 99.1%.
Example two
70g of chloroform, 15.2g (0.1mol) of m-methoxybenzoic acid, 30mL of concentrated sulfuric acid, 1.67g (0.01mol) of potassium bromate and 1.48g (0.012mol) of red phosphorus are sequentially added into a 500mL four-neck flask, stirring is started, 21.36g (0.12mol) of N-bromosuccinimide is added at 25 ℃, the reaction temperature is controlled to be 25-30 ℃, the reaction is carried out for 3h, after the reaction of the raw materials is monitored by HPLC, the reaction liquid is poured into 200g of ice water for quenching, the chloroform is recovered under reduced pressure after quenching, mother liquor is filtered, and is recrystallized by 60mL of methanol, so that 21.41g of 2-bromo-5-methoxybenzoic acid is obtained. The yield of the 2-bromo-5-methoxybenzoic acid is 92.7%, and the purity is 99.2%.
EXAMPLE III
80g of dichloromethane, 15.2g (0.1mol) of m-methoxybenzoic acid, 25mL of concentrated sulfuric acid, 1.67g (0.01mol) of potassium bromate and 1.23g (0.01mol) of red phosphorus are sequentially added into a 500mL four-neck flask, stirring is started, 42.9g (0.15mol) of dibromohydantoin is added at 25 ℃, the reaction temperature is controlled to be 25-30 ℃, the reaction is carried out for 3h, after the raw materials are monitored by HPLC to be reacted, the reaction liquid is poured into 200g of ice water for quenching, dichloromethane is recovered under reduced pressure after quenching, mother liquor is filtered, and is recrystallized by 70mL of ethanol, so that 21.62g of 2-bromo-5-methoxybenzoic acid is obtained. The yield of 2-bromo-5-methoxybenzoic acid is 93.6%, and the purity is 99.4%.
Example four
75g of dichloroethane, 15.2g (0.1mol) of m-methoxybenzoic acid, 25mL of concentrated sulfuric acid, 1.78g (0.015mol) of potassium bromide and 0.98g (0.008mol) of red phosphorus are sequentially added into a 500mL four-neck flask, stirring is started, 37.18g (0.13mol) of dibromohydantoin is added at 25 ℃, the reaction temperature is controlled to be 25-30 ℃, the reaction is performed for 3h, after the reaction of raw materials is monitored by HPLC, the reaction liquid is poured into 200g of ice water for quenching, dichloroethane is recovered under reduced pressure after quenching, mother liquor is filtered, and is recrystallized by 75mL of methanol, so that 21.43g of 2-bromo-5-methoxybenzoic acid is obtained. The yield is 92.8 percent, and the purity is 99.5 percent.
EXAMPLE five
Adding 90g of chloroform, 15.2g (0.1mol) of m-methoxybenzoic acid, 25mL of concentrated sulfuric acid, 1.78g (0.015mol) of potassium bromide and 0.98g (0.008mol) of red phosphorus into a 500mL four-neck flask in sequence, starting stirring, adding 34.32g (0.12mol) of dibromohydantoin at 25 ℃, controlling the reaction temperature to be 25-30 ℃, reacting for 3h, after the reaction of raw materials is monitored by HPLC, pouring the reaction liquid into 200g of ice water for quenching, recovering chloroform under reduced pressure after quenching, filtering mother liquor, recrystallizing by using 85mL of isopropanol to obtain 21.43g of 2-bromo-5-methoxybenzoic acid. The yield of the 2-bromo-5-methoxybenzoic acid is 92.8 percent, and the purity is 99.5 percent.
Comparative example
CN107531606A provides a synthesis method of 2-bromo-5-methoxybenzoic acid, which takes water as a solvent, uses bromine to carry out bromination reaction under the action of sodium hydroxide, and the yield of the 2-bromo-5-methoxybenzoic acid can reach 90.8 percent, and the synthesis method provided by the method is adopted for carrying out tests, and the specific process is as follows:
to a 500mL four-necked flask, 15.2g (0.1mol) of m-methoxybenzoic acid was added, and 80g of water was added and stirred to disperse the m-methoxybenzoic acid. Then 27.33g (0.205mol) of a 30% aqueous sodium hydroxide solution was added. Then, the liquid temperature was cooled to 0 ℃ and 16.78g (0.105mol) of bromine was added dropwise at a temperature of 0 to 5 ℃. After the dropwise addition, stirring is carried out for 1 hour at a liquid temperature of 0-5 ℃. After the reaction was completed, 0.128g of sodium sulfite was added, 10g of toluene was added, and the temperature was raised to 70 ℃. The organic phase was separated and removed, and 10.4g (0.1mol) of 35% hydrochloric acid was added dropwise to the aqueous phase, followed by stirring for 1 hour. The precipitated crystal is filtered and dried under reduced pressure to obtain 19.17g of 2-bromine-5-methoxybenzoic acid, which has poor product quality and more impurities. The actual yield of 2-bromo-5-methoxybenzoic acid was 83%, and the purity was 98.5%.
Compared with the comparative example, the yield of the first to fifth examples is obviously higher than the actual yield of the comparative example, and the purity is improved relative to the comparative example.
Compared with the related art, in the synthetic method of 2-bromo-5-methoxybenzoic acid, cheap and easily available m-methoxybenzoic acid is used as a raw material for synthesis, and the synthetic method has the characteristics of simplicity in operation, high purity, high yield and the like, and experimental results show that the yield of 2-bromo-5-methoxybenzoic acid obtained by the synthetic method is more than 92% and the purity is 98-99.6%; in the synthetic method, the bromine atom in the bromization reagent has high utilization rate, the using amount of sulfuric acid is small, three wastes are less, the product yield is high, the economic benefit is high, the environmental pollution can be reduced, the product production is clean and environment-friendly, and the method is suitable for mass production.
While the foregoing is directed to embodiments of the present invention, it will be understood by those skilled in the art that various changes may be made without departing from the spirit and scope of the invention.
Claims (10)
1. A synthetic method of 2-bromo-5-methoxybenzoic acid is characterized by comprising the following steps:
dissolving m-methoxybenzoic acid in a halogenated hydrocarbon solvent, and carrying out bromination reaction with a bromination reagent under the action of a bromination initiator, a cocatalyst and sulfuric acid to obtain a 2-bromo-5-methoxybenzoic acid reaction solution;
and pouring the reaction liquid of the 2-bromo-5-methoxybenzoic acid into ice water for quenching, recovering the halogenated hydrocarbon solvent under reduced pressure, filtering, and recrystallizing by using the solvent to obtain a finished product of the 2-bromo-5-methoxybenzoic acid.
2. The method of synthesis according to claim 1, wherein the halogenated hydrocarbon solvent comprises one or more of dichloromethane, chloroform, dichloroethane.
3. The method of synthesis of claim 1, wherein the bromination initiator is red phosphorus; the cocatalyst is one or two of potassium bromide and potassium bromate; the brominating reagent comprises one or more of N-bromosuccinimide, dibromohydantoin and bromine.
4. The synthesis method according to claim 1, wherein the mass ratio of the m-anisic acid to the halogenated hydrocarbon solvent is 1 (0.5-20).
5. The synthesis method of claim 1, wherein the molar ratio of the m-anisic acid to the bromination initiator is 1 (0.01-0.2).
6. The synthesis method of claim 1, wherein the molar ratio of the m-anisic acid to the cocatalyst is 1 (0.01-0.2).
7. The synthesis method of claim 1, wherein the mass ratio of the m-anisic acid to the sulfuric acid is 1 (0.5-5).
8. The synthesis method of claim 1, wherein the molar ratio of the m-anisic acid to the brominating reagent is 1 (0.6-3.0).
9. The synthesis method according to claim 1, wherein the bromination reaction is carried out at-10 ℃ to 80 ℃ for 1 hour to 24 hours.
10. The synthesis method according to claim 1, wherein the solvent used for recrystallization comprises one or more of methanol, ethanol and isopropanol.
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