CN110437056B - Method for industrially preparing 2,3,4, 5-tetrafluorobenzoic acid - Google Patents
Method for industrially preparing 2,3,4, 5-tetrafluorobenzoic acid Download PDFInfo
- Publication number
- CN110437056B CN110437056B CN201910645352.5A CN201910645352A CN110437056B CN 110437056 B CN110437056 B CN 110437056B CN 201910645352 A CN201910645352 A CN 201910645352A CN 110437056 B CN110437056 B CN 110437056B
- Authority
- CN
- China
- Prior art keywords
- water
- sulfolane
- acid
- tetrafluorobenzoic acid
- tubular reactor
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- SFKRXQKJTIYUAG-UHFFFAOYSA-N 2,3,4,5-tetrafluorobenzoic acid Chemical compound OC(=O)C1=CC(F)=C(F)C(F)=C1F SFKRXQKJTIYUAG-UHFFFAOYSA-N 0.000 title claims abstract description 61
- 238000000034 method Methods 0.000 title claims abstract description 33
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 91
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 claims abstract description 60
- 239000000243 solution Substances 0.000 claims abstract description 32
- YJLVXRPNNDKMMO-UHFFFAOYSA-N 3,4,5,6-tetrafluorophthalic acid Chemical compound OC(=O)C1=C(F)C(F)=C(F)C(F)=C1C(O)=O YJLVXRPNNDKMMO-UHFFFAOYSA-N 0.000 claims abstract description 30
- 239000000463 material Substances 0.000 claims abstract description 24
- 239000012074 organic phase Substances 0.000 claims abstract description 24
- 239000003960 organic solvent Substances 0.000 claims abstract description 14
- 238000000605 extraction Methods 0.000 claims abstract description 10
- 239000003054 catalyst Substances 0.000 claims abstract description 7
- 239000011259 mixed solution Substances 0.000 claims abstract description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 54
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 46
- 229910000365 copper sulfate Inorganic materials 0.000 claims description 25
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical group [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 claims description 25
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 claims description 23
- 229930003268 Vitamin C Natural products 0.000 claims description 23
- 238000006243 chemical reaction Methods 0.000 claims description 23
- 235000019154 vitamin C Nutrition 0.000 claims description 23
- 239000011718 vitamin C Substances 0.000 claims description 23
- WMOVHXAZOJBABW-UHFFFAOYSA-N tert-butyl acetate Chemical group CC(=O)OC(C)(C)C WMOVHXAZOJBABW-UHFFFAOYSA-N 0.000 claims description 22
- 238000004821 distillation Methods 0.000 claims description 12
- 238000009776 industrial production Methods 0.000 claims description 3
- 239000008346 aqueous phase Substances 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims description 2
- 238000003889 chemical engineering Methods 0.000 abstract description 3
- 239000003814 drug Substances 0.000 abstract description 3
- 239000000543 intermediate Substances 0.000 abstract description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 17
- 239000012452 mother liquor Substances 0.000 description 16
- 238000004064 recycling Methods 0.000 description 8
- 238000007792 addition Methods 0.000 description 5
- 238000006114 decarboxylation reaction Methods 0.000 description 5
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 239000003153 chemical reaction reagent 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
- -1 tertiary amine compounds Chemical class 0.000 description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000011368 organic material Substances 0.000 description 1
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
- FZEHCVMJFTXUCY-UHFFFAOYSA-N tributylazanium;trifluoromethanesulfonate Chemical compound [O-]S(=O)(=O)C(F)(F)F.CCCC[NH+](CCCC)CCCC FZEHCVMJFTXUCY-UHFFFAOYSA-N 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
Images
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/22—Organic complexes
- B01J31/2204—Organic complexes the ligands containing oxygen or sulfur as complexing atoms
- B01J31/2208—Oxygen, e.g. acetylacetonates
-
- 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
- C07C51/377—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by splitting-off hydrogen or functional groups; by hydrogenolysis of functional groups
- C07C51/38—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by splitting-off hydrogen or functional groups; by hydrogenolysis of functional groups by decarboxylation
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/10—Complexes comprising metals of Group I (IA or IB) as the central metal
- B01J2531/16—Copper
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Inorganic Chemistry (AREA)
- Materials Engineering (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention belongs to the field of medicine, chemical engineering and material intermediates, and particularly relates to a method for industrially preparing 2,3,4, 5-tetrafluorobenzoic acid. Injecting a mixed solution containing 2,3,4, 5-tetrafluorophthalic acid, a catalyst, water and sulfolane into a tubular reactor by a pump, reacting for 3-8 minutes at the temperature of 180-250 ℃, allowing the mixed solution to flow out of an outlet of the tubular reactor to obtain a sulfolane solution of 2,3,4, 5-tetrafluorobenzoic acid, adding water and an organic solvent immiscible with water into the sulfolane solution for extraction, standing for layering, and distilling an upper organic phase to obtain the 2,3,4, 5-tetrafluorobenzoic acid. The method is environment-friendly, and the 2,3,4, 5-tetrafluorobenzoic acid has good selectivity and high yield.
Description
Technical Field
The invention belongs to the field of medicine, chemical engineering and material intermediates, and particularly relates to a method for industrially preparing 2,3,4, 5-tetrafluorobenzoic acid.
Background
2,3,4, 5-tetrafluorobenzoic acid is an important fine chemical product and is widely applied to the fields of quinolone drug synthesis, chemical engineering, materials and the like. However, since a large amount of organic materials are used in large-scale industrial production and the environment is seriously polluted, it is required to develop a new method for preparing 2,3,4, 5-tetrafluorobenzoic acid, both from the economical point of view and from the point of view of environmental protection and sustainable development.
The classical decarboxylation of 2,3,4, 5-tetrafluorophthalic acid to prepare 2,3,4, 5-tetrafluorobenzoic acid is carried out under the action of tertiary amine compounds such as tri-n-butylamine, and the like, so that the defects of using a large amount of toxic organic matters and causing great pollution exist, meanwhile, the decarboxylation reaction selectivity under the reaction condition is poor, and the yield of the 2,3,4, 5-tetrafluorobenzoic acid is low.
CN201910101903 utilizes a microchannel reactor with a static mixer to perform decarboxylation reaction on the aqueous solution of 2,3,4, 5-tetrafluorophthalic acid under the pressure of 30-80 Mpa to obtain the 2,3,4, 5-tetrafluorobenzoic acid. The reaction condition is simple, an organic solvent is not needed, the method is green and environment-friendly, the selectivity is good, and the yield is high. However, the method is carried out under high pressure (30-80 Mpa), and potential safety hazards exist in industrial production.
CN201610992872 uses 2,3,4, 5-tetrafluorophthalic acid to generate calcium salt and decarboxylate, thereby avoiding application of organic substances and reducing pollution. However, the method has the disadvantages of complicated operation process and low production efficiency.
CN201210213503 uses tri-n-butylamine trifluoromethanesulfonate to catalyze decarboxylation, but this method needs to be carried out under high pressure, and carbon dioxide is generated during the reaction process, so that the pressure of the reaction kettle is difficult to control.
In recent years, the demand of 2,3,4, 5-tetrafluorobenzoic acid is increasing, and a simple, safe and environment-friendly method for preparing 2,3,4, 5-tetrafluorobenzoic acid is also very important.
Disclosure of Invention
The invention aims to solve the problems and provide a method for industrially preparing 2,3,4, 5-tetrafluorobenzoic acid.
In order to achieve the purpose, the invention adopts the following technical scheme:
a method for industrially preparing 2,3,4, 5-tetrafluorobenzoic acid comprises the steps of injecting a mixed solution containing 2,3,4, 5-tetrafluorophthalic acid, a catalyst, water and sulfolane into a tubular reactor by a pump, reacting for 3-8 minutes at the temperature of 180 ℃ and 250 ℃, allowing an outlet of the tubular reactor to flow out to obtain a sulfolane solution of the 2,3,4, 5-tetrafluorobenzoic acid, adding water and an organic solvent immiscible with water into the sulfolane solution for extraction, standing for layering, and distilling an upper organic phase to obtain the 2,3,4, 5-tetrafluorobenzoic acid.
In the above method for industrially preparing 2,3,4, 5-tetrafluorobenzoic acid, the catalyst is copper sulfate and vitamin C. Copper sulfate and sodium sulfite can also be used as the catalyst, but can cause off-flavor in the product.
In the method for industrially preparing the 2,3,4, 5-tetrafluorobenzoic acid, the addition amount of the copper sulfate is 1-5% of the mass of the 2,3,4, 5-tetrafluorophthalic acid, and the addition amount of the vitamin C is 3-8% of the mass of the 2,3,4, 5-tetrafluorophthalic acid.
In the above method for industrially preparing 2,3,4, 5-tetrafluorobenzoic acid, the addition amount of sulfolane is 300-1000% of the mass of 2,3,4, 5-tetrafluorophthalic acid, and the addition amount of water in the mixed solution is 5-20% of the mass of sulfolane.
In the method for industrially preparing the 2,3,4, 5-tetrafluorobenzoic acid, the ratio of water to the organic solvent immiscible with water is 4:1-3:1, and the amount of water added into the sulfolane solution is 3-4 times of the mass of the sulfolane.
In the above method for industrially preparing 2,3,4, 5-tetrafluorobenzoic acid, the sulfolane solution is added with water and an organic solvent immiscible with water in a ratio of 3:1, wherein the organic solvent immiscible with water is tert-butyl acetate or ethyl acetate.
In the above method for industrially preparing 2,3,4, 5-tetrafluorobenzoic acid, the organic solvent immiscible with water is tert-butyl acetate.
In the above-mentioned industrial preparation method of 2,3,4, 5-tetrafluorobenzoic acid, the amount of the organic solvent added is 900-3000% of the mass of 2,3,4, 5-tetrafluorophthalic acid.
A method for industrially preparing 2,3,4, 5-tetrafluorobenzoic acid comprises the steps of injecting a solution containing 100kg of 2,3,4, 5-tetrafluorophthalic acid, 5kg of copper sulfate, 8kg of vitamin C, 20kg of water and 1000kg of sulfolane into a tubular reactor by a pump, reacting the materials in the tubular reactor at 250 ℃ for 8 minutes, allowing the materials to flow out of an outlet of the tubular reactor to obtain a sulfolane solution of the 2,3,4, 5-tetrafluorobenzoic acid, adding 3000kg of water and 1000kg of tert-butyl acetate into the sulfolane solution for extraction, standing for layering, and distilling an upper organic phase to obtain the 2,3,4, 5-tetrafluorobenzoic acid.
In the method for industrially preparing the 2,3,4, 5-tetrafluorobenzoic acid, the upper organic phase is distilled under normal pressure and then distilled under reduced pressure, the vacuum degree is not more than-0.09 MPa in the reduced pressure process, and the lower aqueous phase is distilled under reduced pressure to remove water and recover sulfolane.
Compared with the prior art, the invention has the advantages that:
under the catalysis of active copper generated by in-situ reaction of copper sulfate and vitamin C, 2,3,4, 5-tetrafluorophthalic acid undergoes decarboxylation reaction at high temperature to generate 2,3,4, 5-tetrafluorobenzoic acid; the method is environment-friendly, and the 2,3,4, 5-tetrafluorobenzoic acid has good selectivity and high yield.
Those skilled in the art will appreciate that sulfolane decomposes at temperatures below 220 c at relatively slow rates, but over 220 c, the decomposition rate increases dramatically with increasing temperature. However, the applicant unexpectedly found that the purity and yield of the 2,3,4, 5-tetrafluorobenzoic acid product obtained by the tubular reactor reaction are highest at 250 ℃ under the condition that copper sulfate and vitamins are used as catalysts.
Drawings
FIG. 1 is an HPLC chart of the product 2,3,4, 5-tetrafluorobenzoic acid in example 16.
Detailed Description
The reagents used in the following examples, unless otherwise specified, were purchased from conventional biochemical reagent stores.
Example 1
The temperature of the tubular reactor was maintained at 180 ℃ and a pre-prepared solution containing 100kg of 2,3,4, 5-tetrafluorophthalic acid, 1kg of copper sulfate, 3kg of vitamin C, 50kg of water and 300kg of sulfolane was continuously pumped into the tubular reactor, the residence time of the material in the tubular reactor being 3 minutes. After the reaction is finished, adding 900kg of water into the effluent, extracting 300kg of tert-butyl acetate, distilling the lower water layer under reduced pressure to remove water, then mechanically using sulfolane mother liquor for the next batch, wherein the vacuum degree of reduced pressure distillation is-0.09 MPa, distilling the upper organic phase under normal pressure, then distilling under reduced pressure, completing distillation when no distillate is produced, heating the distillation at the temperature of not more than 140 ℃, and recovering tert-butyl acetate from the upper organic phase to obtain 66.8kg of 2,3,4, 5-tetrafluorobenzoic acid, wherein the yield is 82%, and the purity is 98% (HPLC).
Example 2
The temperature of the tubular reactor was maintained at 220 ℃ and a solution of 100kg of 2,3,4, 5-tetrafluorophthalic acid, 3kg of copper sulfate, 6kg of vitamin C, 50kg of water and 350kg of sulfolane, which had been prepared in advance, was continuously pumped into the tubular reactor, and the residence time of the material in the tubular reactor was 8 minutes. After the reaction is finished, adding 900kg of water into the effluent, extracting 225kg of tert-butyl acetate, and recycling the sulfolane mother liquor to the next batch after distilling the lower water layer under reduced pressure to remove water; the upper organic phase recovers tert-butyl acetate to obtain 72.5kg of 2,3,4, 5-tetrafluorobenzoic acid with 89% yield and 98.8% purity (HPLC).
Example 3
The temperature of the tubular reactor was maintained at 180 ℃ and the pre-prepared solution containing 100kg of 2,3,4, 5-tetrafluorophthalic acid, 5kg of copper sulfate, 8kg of vitamin C, 50kg of water and 600kg of sulfolane was continuously pumped into the tubular reactor, the residence time of the material in the tubular reactor being 5 minutes. After the reaction is finished, adding 2000kg of water into the effluent, extracting with 500kg of ethyl acetate, and recycling the sulfolane mother liquor to the next batch after distilling the lower water layer under reduced pressure to remove water; the ethyl acetate was recovered from the upper organic phase to yield 67.7kg of 2,3,4, 5-tetrafluorobenzoic acid in 83% yield and 98.5% purity (HPLC).
Example 4
The temperature of the tubular reactor was maintained at 220 ℃ and a solution prepared beforehand and containing 100kg of 2,3,4, 5-tetrafluorophthalic acid, 5kg of copper sulfate, 6kg of vitamin C, 200kg of water and 1000kg of sulfolane was continuously pumped into the tubular reactor, the residence time of the material in the tubular reactor being 4 minutes. After the reaction is finished, 3000kg of water and 1000kg of ethyl acetate are added into the effluent material for extraction, and the sulfolane mother liquor is reused in the next batch after the lower water layer is subjected to reduced pressure distillation and water removal; the ethyl acetate was recovered from the upper organic phase to yield 73.4kg of 2,3,4, 5-tetrafluorobenzoic acid in 90% yield and 99.1% purity (HPLC).
Example 5
The temperature of the tubular reactor was maintained at 250 ℃ and a pre-prepared solution containing 100kg of 2,3,4, 5-tetrafluorophthalic acid, 3kg of copper sulfate, 3kg of vitamin C, 50kg of water and 800kg of sulfolane was continuously pumped into the tubular reactor, the residence time of the material in the tubular reactor being 5 minutes. After the reaction is finished, adding 3000kg of water into the effluent, extracting with 940kg of ethyl acetate, and recycling the sulfolane mother liquor to the next batch after distilling the lower water layer under reduced pressure to remove water; the ethyl acetate was recovered from the upper organic phase to yield 78.3kg of 2,3,4, 5-tetrafluorobenzoic acid in 96% yield and 99.4% purity (HPLC).
Example 6
The temperature of the tubular reactor was maintained at 180 ℃ and a solution of 100kg2,3,4, 5-tetrafluorophthalic acid, 5kg copper sulfate, 6kg vitamin C, 20kg water and 300kg sulfolane, which had been prepared beforehand, was continuously pumped into the tubular reactor, the residence time of the material in the tubular reactor being 8 minutes. After the reaction is finished, 1000kg of water is added into the effluent, 350kg of tert-butyl acetate is used for extraction, and the sulfolane mother liquor is reused in the next batch after the lower water layer is subjected to reduced pressure distillation and water removal; the upper organic phase recovers tert-butyl acetate to obtain 65.2kg of 2,3,4, 5-tetrafluorobenzoic acid with yield of 80% and purity of 98.0% (HPLC).
Example 7
The temperature of the tubular reactor was maintained at 220 ℃ and a solution prepared beforehand and containing 100kg of 2,3,4, 5-tetrafluorophthalic acid, 3kg of copper sulfate, 6kg of vitamin C, 40kg of water and 600kg of sulfolane was continuously pumped into the tubular reactor, the residence time of the material in the tubular reactor being 5 minutes. After the reaction is finished, adding 2000kg of water into the effluent, extracting with 500kg of tert-butyl acetate, and recycling the sulfolane mother liquor to the next batch after distilling the lower water layer under reduced pressure to remove water; the upper organic phase recovers tert-butyl acetate to obtain 70.9kg of 2,3,4, 5-tetrafluorobenzoic acid with yield 87% and purity 98.3% (HPLC).
Example 8
The temperature of the tubular reactor was maintained at 250 ℃ and a pre-prepared solution containing 100kg of 2,3,4, 5-tetrafluorophthalic acid, 5kg of copper sulfate, 3kg of vitamin C, 50kg of water and 600kg of sulfolane was continuously pumped into the tubular reactor, the residence time of the material in the tubular reactor being 3 minutes. After the reaction is finished, adding 2000kg of water into the effluent, extracting with tert-butyl acetate, and recycling sulfolane mother liquor to the next batch after the lower water layer is subjected to reduced pressure distillation and water removal; the upper organic phase recovers tert-butyl acetate to obtain 75.0kg of 2,3,4, 5-tetrafluorobenzoic acid with yield of 92% and purity of 98.8% (HPLC).
Example 9
The temperature of the tubular reactor was maintained at 180 ℃ and a solution of 100kg2,3,4, 5-tetrafluorophthalic acid, 3kg copper sulfate, 8kg vitamin C, 100kg water and 1000kg sulfolane, which had been prepared beforehand, was continuously pumped into the tubular reactor, and the residence time of the material in the tubular reactor was 3 minutes. After the reaction is finished, 3000kg of water and 1200kg of ethyl acetate are added into the effluent, the mixture is extracted, and sulfolane mother liquor is reused in the next batch after the lower water layer is subjected to reduced pressure distillation to remove water; the ethyl acetate was recovered from the upper organic phase to give 66.0kg of 2,3,4, 5-tetrafluorobenzoic acid in 81% yield and 98.8% purity (HPLC).
Example 10
The temperature of the tubular reactor was maintained at 230 ℃ and a solution of 100kg of 2,3,4, 5-tetrafluorophthalic acid, 1kg of copper sulfate, 3kg of vitamin C, 100kg of water and 1000kg of sulfolane, which had been prepared in advance, was continuously pumped into the tubular reactor, and the residence time of the material in the tubular reactor was 8 minutes. After the reaction is finished, 3000kg of water and 1300kg of ethyl acetate are added into the effluent material for extraction, and the sulfolane mother liquor is reused in the next batch after the lower water layer is subjected to reduced pressure distillation and water removal; the ethyl acetate was recovered from the upper organic phase to give 61.1kg of 2,3,4, 5-tetrafluorobenzoic acid in 75% yield and 96.9% purity (HPLC).
Example 11
The temperature of the tubular reactor was maintained at 220 ℃ and a solution prepared beforehand and containing 100kg of 2,3,4, 5-tetrafluorophthalic acid, 5kg of copper sulfate, 3kg of vitamin C, 20kg of water and 300kg of sulfolane was continuously pumped into the tubular reactor, the residence time of the material in the tubular reactor being 5 minutes. After the reaction is finished, 1000kg of water is added into the effluent, 280kg of ethyl acetate is used for extraction, and sulfolane mother liquor is reused in the next batch after the lower water layer is subjected to reduced pressure distillation and water removal; the ethyl acetate was recovered from the upper organic phase to yield 71.7kg of 2,3,4, 5-tetrafluorobenzoic acid in 88% yield and 98.6% purity (HPLC).
Example 12
The temperature of the tubular reactor was maintained at 250 ℃ and a pre-prepared solution containing 100kg of 2,3,4, 5-tetrafluorophthalic acid, 3kg of copper sulfate, 6kg of vitamin C, 20kg of water and 300kg of sulfolane was continuously pumped into the tubular reactor, the residence time of the material in the tubular reactor being 3 minutes. After the reaction is finished, adding 1000kg of water into the effluent, extracting with 300kg of ethyl acetate, and recycling the sulfolane mother liquor to the next batch after distilling the lower water layer under reduced pressure to remove water; the ethyl acetate was recovered from the upper organic phase to yield 74.2kg of 2,3,4, 5-tetrafluorobenzoic acid in 91% yield and 99.0% purity (HPLC).
Example 13
The temperature of the tubular reactor was maintained at 220 ℃ and a solution of 100kg of 2,3,4, 5-tetrafluorophthalic acid, 3kg of copper sulfate, 3kg of vitamin C, 30kg of water and 600kg of sulfolane, which had been prepared in advance, was continuously pumped into the tubular reactor, and the residence time of the material in the tubular reactor was 8 minutes. After the reaction is finished, adding 2000kg of water into the effluent, extracting with 500kg of ethyl acetate, and recycling the sulfolane mother liquor to the next batch after distilling the lower water layer under reduced pressure to remove water; the ethyl acetate was recovered from the upper organic phase to give 72.5kg of 2,3,4, 5-tetrafluorobenzoic acid in 89% yield and 98.3% purity (HPLC).
Example 14
The temperature of the tubular reactor was maintained at 220 ℃ and a pre-prepared solution containing 100kg of 2,3,4, 5-tetrafluorophthalic acid, 1kg of copper sulfate, 6kg of vitamin C, 20kg of water and 600kg of sulfolane was continuously pumped into the tubular reactor, the residence time of the material in the tubular reactor being 3 minutes. After the reaction is finished, adding 2000kg of water into the effluent, extracting 550kg of tert-butyl acetate, and mechanically applying sulfolane mother liquor to the next batch after distilling a lower water layer under reduced pressure to remove water; the upper organic phase recovers tert-butyl acetate to obtain 69.3kg of 2,3,4, 5-tetrafluorobenzoic acid with 85% yield and 97.9% purity (HPLC).
Example 15
The temperature of the tubular reactor was maintained at 180 ℃ and a solution of 100kg2,3,4, 5-tetrafluorophthalic acid, 5kg copper sulfate, 6kg vitamin C, 50kg water and 1000kg sulfolane, which had been prepared beforehand, was continuously pumped into the tubular reactor, and the residence time of the material in the tubular reactor was 5 minutes. After the reaction is finished, adding 3000kg of water into the effluent, extracting with tert-butyl acetate, and recycling sulfolane mother liquor to the next batch after the lower water layer is subjected to reduced pressure distillation and water removal; the upper organic phase recovers tert-butyl acetate to obtain 66.0kg of 2,3,4, 5-tetrafluorobenzoic acid with 81% yield and 97.5% purity (HPLC).
Example 16
The temperature of the tubular reactor was maintained at 250 ℃ and the pre-prepared solution containing 100kg of 2,3,4, 5-tetrafluorophthalic acid, 5kg of copper sulfate, 8kg of vitamin C, 200kg of water and 1000kg of sulfolane was continuously pumped into the tubular reactor, the residence time of the material in the tubular reactor being 8 minutes. After the reaction is finished, 3000kg of water is added into the effluent, 1000kg of tert-butyl acetate is used for extraction, and the sulfolane mother liquor is reused in the next batch after the lower water layer is subjected to reduced pressure distillation and water removal; the recovery of tert-butyl acetate from the upper organic phase yielded 80.7kg of 2,3,4, 5-tetrafluorobenzoic acid in 99% yield and 99.5% purity (HPLC).
The specific embodiments described herein are merely illustrative of the spirit of the invention and aid in the understanding of the invention, and are not to be construed as limiting the invention. In addition, the technical features described in the embodiments of the present invention may be combined with each other as long as they do not conflict with each other. Various modifications or additions may be made to the described embodiments or alternatives may be employed by those skilled in the art without departing from the spirit or ambit of the invention as defined in the appended claims.
Claims (9)
1. A method for industrially preparing 2,3,4, 5-tetrafluorobenzoic acid is characterized in that a mixed solution containing 2,3,4, 5-tetrafluorophthalic acid, a catalyst, water and sulfolane is injected into a tubular reactor by a pump, the reaction lasts for 3-8 minutes at the temperature of 180 ℃ and 250 ℃, a sulfolane solution of the 2,3,4, 5-tetrafluorobenzoic acid is obtained after the outflow of an outlet of the tubular reactor, water and an organic solvent immiscible with water are added into the sulfolane solution for extraction, and after standing and layering, an upper organic phase is taken for distillation to obtain the 2,3,4, 5-tetrafluorobenzoic acid;
the catalyst is copper sulfate and vitamin C.
2. The method for industrially producing 2,3,4, 5-tetrafluorobenzoic acid as claimed in claim 1, wherein the amount of copper sulfate added is 1 to 5% by mass of 2,3,4, 5-tetrafluorophthalic acid, and the amount of vitamin C added is 3 to 8% by mass of 2,3,4, 5-tetrafluorophthalic acid.
3. The method for industrially producing 2,3,4, 5-tetrafluorobenzoic acid according to claim 1, wherein the amount of sulfolane added is 300-1000% by mass of 2,3,4, 5-tetrafluorophthalic acid, and the amount of water added in the mixed solution is 5-20% by mass of sulfolane.
4. The method for industrially producing 2,3,4, 5-tetrafluorobenzoic acid according to claim 1, wherein the ratio of water to the water-immiscible organic solvent is 4:1 to 3:1, and the amount of water added to the sulfolane solution is 3 to 4 times the mass of sulfolane.
5. The method of claim 4, wherein the sulfolane solution is added with water and a water-immiscible organic solvent at a ratio of 3:1, wherein the water-immiscible organic solvent is t-butyl acetate or ethyl acetate.
6. The process for the industrial production of 2,3,4, 5-tetrafluorobenzoic acid according to claim 5, wherein the water-immiscible organic solvent is t-butyl acetate.
7. The method for industrially producing 2,3,4, 5-tetrafluorobenzoic acid as claimed in claim 1, wherein the amount of said organic solvent added is 900-3000% based on the mass of 2,3,4, 5-tetrafluorophthalic acid.
8. A method for industrially preparing 2,3,4, 5-tetrafluorobenzoic acid is characterized in that a solution containing 100kg of 2,3,4, 5-tetrafluorophthalic acid, 5kg of copper sulfate, 8kg of vitamin C, 20kg of water and 1000kg of sulfolane is injected into a tubular reactor by a pump, materials react in the tubular reactor at 250 ℃ for 8 minutes, a sulfolane solution of the 2,3,4, 5-tetrafluorobenzoic acid is obtained by outflow from an outlet of the tubular reactor, 3000kg of water and 1000kg of tert-butyl acetate are added into the sulfolane solution for extraction, and after standing and layering, an upper organic phase is taken to be distilled to obtain the 2,3,4, 5-tetrafluorobenzoic acid.
9. The industrial preparation method of 2,3,4, 5-tetrafluorobenzoic acid according to any one of claims 1 to 8, characterized in that the upper organic phase is distilled under atmospheric pressure and then under reduced pressure, the vacuum degree does not exceed-0.09 MPa in the reduced pressure process, and the lower aqueous phase is distilled under reduced pressure to remove water and recover sulfolane.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910645352.5A CN110437056B (en) | 2019-07-17 | 2019-07-17 | Method for industrially preparing 2,3,4, 5-tetrafluorobenzoic acid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910645352.5A CN110437056B (en) | 2019-07-17 | 2019-07-17 | Method for industrially preparing 2,3,4, 5-tetrafluorobenzoic acid |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN110437056A CN110437056A (en) | 2019-11-12 |
| CN110437056B true CN110437056B (en) | 2022-05-06 |
Family
ID=68430650
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910645352.5A Active CN110437056B (en) | 2019-07-17 | 2019-07-17 | Method for industrially preparing 2,3,4, 5-tetrafluorobenzoic acid |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110437056B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111138356A (en) * | 2019-12-20 | 2020-05-12 | 南京金浩医药科技有限公司 | Preparation method of disperse yellow 64 |
| CN115417761B (en) * | 2022-08-31 | 2024-04-02 | 福建华药生物技术有限公司 | Industrial continuous production method of 2,3,4, 5-tetrafluorobenzoic acid |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6143130A (en) * | 1984-08-07 | 1986-03-01 | Nippon Shokubai Kagaku Kogyo Co Ltd | Production of 1,2,3,4-tetrafluorobenzene |
| JPH0525084A (en) * | 1991-07-24 | 1993-02-02 | Sds Biotech Kk | Production of 2,3,4,5-tetrafluorobenzoic acid |
| CN100560558C (en) * | 2005-10-13 | 2009-11-18 | 暨南大学 | A kind of 2,3,5, the preparation method of 6-tetrafluorobenzoic aid |
| CN102627553A (en) * | 2012-03-21 | 2012-08-08 | 浙江沙星医药化工有限公司 | Preparation method of 2,3,4,5-tetrafluorobenzoyl chloride |
| CN109879746A (en) * | 2019-01-31 | 2019-06-14 | 贵阳中精科技有限公司 | The method of 2,3,4,5 tetra fluoro benzoic acid is continuously synthesized with micro passage reaction |
-
2019
- 2019-07-17 CN CN201910645352.5A patent/CN110437056B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN110437056A (en) | 2019-11-12 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN110437056B (en) | Method for industrially preparing 2,3,4, 5-tetrafluorobenzoic acid | |
| CN113214051B (en) | Method for synthesizing 2, 6-dihydroxytoluene by using waste acid | |
| CN114920630A (en) | Continuous production process and equipment for ethylene glycol monovinyl ether | |
| CN106866399B (en) | Tetrachlorobenzoquinone and preparation method thereof | |
| CN114685253A (en) | Preparation method of prothioconazole intermediate 3, 5-dichloro-2-pentanone | |
| CN112661126B (en) | Preparation method of solid hydroxylamine hydrochloride | |
| CN113754528A (en) | Preparation method of cyclopentanecarboxylic acid | |
| CN110255632B (en) | Method for preparing ruthenium trichloride from ruthenium-containing waste | |
| CN109651327B (en) | Process method for preparing xanthone under catalyst-free condition | |
| CN112500295A (en) | Production process of 3, 5-dichloronitrobenzene | |
| CN111848686A (en) | Preparation method of isooctyl trithioacetate antimony | |
| CN108752246A (en) | A kind of industrialization production method of efficient 2- nitryl-4-thiamphenicol benzoic acids | |
| CN111333506A (en) | Method for synthesizing carbasalate calcium | |
| CN113666905B (en) | Preparation method of rosuvastatin calcium intermediate | |
| EP3896057A1 (en) | Method for continuously preparing 5-citalopram diol | |
| CN112300027B (en) | Preparation method of amino butyronitrile | |
| CN108715580A (en) | A kind of industrialized preparing process of 2- nitryl-4-thiamphenicol benzoic acids | |
| CN104230690B (en) | A kind of solid catalysis efficiently prepares the method for 9-Fluorenone | |
| CN113024425B (en) | Preparation method of clethodim | |
| CN114956996B (en) | Production method of methyl salicylate | |
| CN113354542B (en) | Preparation method of 2-fluoro-6-nitroaniline | |
| CN115806534B (en) | Preparation method of 5-hydroxymethylfurfural | |
| CN115093354B (en) | Method for synthesizing caprolactam through Beckmann rearrangement reaction | |
| CN113979965B (en) | Continuous production method of 4, 5-dichloro-2-octyl-4-isothiazolin-3-ketone | |
| CN112390744A (en) | Synthesis method of 6-methoxypyridine-3-methyl formate |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: Method for industrial preparation of 2,3,4,5-tetrafluorobenzoic acid Granted publication date: 20220506 Pledgee: China Minsheng Banking Corp Wenzhou branch Pledgor: ZHEJIANG HUAJI BIOTECHNOLOGY Co.,Ltd. Registration number: Y2024980003498 |
|
| PE01 | Entry into force of the registration of the contract for pledge of patent right |