CN110437056A - The method of preparation of industrialization 2,3,4,5 tetra fluoro benzoic acid - Google Patents
The method of preparation of industrialization 2,3,4,5 tetra fluoro benzoic acid Download PDFInfo
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- CN110437056A CN110437056A CN201910645352.5A CN201910645352A CN110437056A CN 110437056 A CN110437056 A CN 110437056A CN 201910645352 A CN201910645352 A CN 201910645352A CN 110437056 A CN110437056 A CN 110437056A
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- water
- sulfolane
- industrialization
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- tubular reactor
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- 238000000034 method Methods 0.000 title claims abstract description 35
- 238000002360 preparation method Methods 0.000 title claims abstract description 27
- 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 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 81
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 claims abstract description 59
- 239000000463 material Substances 0.000 claims abstract description 37
- 239000000243 solution Substances 0.000 claims abstract description 34
- 238000006243 chemical reaction Methods 0.000 claims abstract description 29
- 239000012074 organic phase Substances 0.000 claims abstract description 24
- 229920001343 polytetrafluoroethylene Polymers 0.000 claims abstract description 14
- 239000003960 organic solvent Substances 0.000 claims abstract description 12
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 claims abstract description 9
- 239000003054 catalyst Substances 0.000 claims abstract description 6
- 239000011259 mixed solution Substances 0.000 claims abstract description 5
- 238000013517 stratification Methods 0.000 claims abstract description 5
- 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 40
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 27
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical group [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 claims description 24
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 claims description 20
- 229930003268 Vitamin C Natural products 0.000 claims description 20
- WMOVHXAZOJBABW-UHFFFAOYSA-N tert-butyl acetate Chemical group CC(=O)OC(C)(C)C WMOVHXAZOJBABW-UHFFFAOYSA-N 0.000 claims description 20
- 235000019154 vitamin C Nutrition 0.000 claims description 20
- 239000011718 vitamin C Substances 0.000 claims description 20
- 239000002253 acid Substances 0.000 claims description 19
- 238000004064 recycling Methods 0.000 claims description 17
- 238000004821 distillation Methods 0.000 claims description 4
- 150000003457 sulfones Chemical class 0.000 claims description 3
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 229910052802 copper Inorganic materials 0.000 claims description 2
- 239000010949 copper Substances 0.000 claims description 2
- 230000006837 decompression Effects 0.000 claims description 2
- XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical compound OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 claims 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims 1
- 239000005864 Sulphur Substances 0.000 claims 1
- 239000002904 solvent Substances 0.000 claims 1
- ISXSCDLOGDJUNJ-UHFFFAOYSA-N tert-butyl prop-2-enoate Chemical compound CC(C)(C)OC(=O)C=C ISXSCDLOGDJUNJ-UHFFFAOYSA-N 0.000 claims 1
- 239000000126 substance Substances 0.000 abstract description 3
- 239000003814 drug Substances 0.000 abstract description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 17
- 238000005292 vacuum distillation Methods 0.000 description 17
- 239000007788 liquid Substances 0.000 description 16
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
- 238000000605 extraction Methods 0.000 description 11
- 238000003810 ethyl acetate extraction Methods 0.000 description 5
- 125000005498 phthalate group Chemical class 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 238000006114 decarboxylation reaction Methods 0.000 description 3
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 239000005416 organic matter 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
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 206010054949 Metaplasia Diseases 0.000 description 1
- 238000007792 addition Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 235000010233 benzoic acid Nutrition 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
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 230000015689 metaplastic ossification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 230000001681 protective effect Effects 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
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- -1 tertiary amine compounds Chemical class 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
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
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)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Inorganic Chemistry (AREA)
- Materials Engineering (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention belongs to medicine, chemical industry, material intermediate fields, and in particular to a kind of method of 2,3,4,5- tetrafluorobenzoic aid of preparation of industrialization.It is will to contain 2,3,4,5- ptfe phthalate, catalyst, water and sulfolane mixed solution pump be injected into tubular reactor, reaction is 3~8 minutes between 180-250 DEG C, and tubular reactor outlet is flowed out up to 2, the sulfolane solution of 3,4,5- tetrafluorobenzoic aids, water is added in the sulfolane solution and is extracted with the immiscible organic solvent of water, after stratification, 2,3 are obtained after taking upper organic phase to distill, 4,5- tetrafluorobenzoic aids.The present invention is environmentally friendly, and 2, the selectivity of 3,4,5- tetrafluorobenzoic aids is good, high income.
Description
Technical field
The invention belongs to medicine, chemical industry, material intermediate fields, and in particular to a kind of 2,3,4,5- tetrafluoro of preparation of industrialization
The method of benzoic acid.
Background technique
2,3,4,5- tetrafluorobenzoic aids are a kind of important fine chemical products, are widely used in the conjunction of quinolone druge
At and the fields such as chemical industry, material.But large amount of organic matter is used in large-scale industrial production, it has seriously polluted the environment, because
No matter this is from economic angle, or from the perspective of protection environment and sustainable development, requires to develop new preparation 2,
The method of 3,4,5- tetrafluorobenzoic aid.
It is in tri-n-butylamine etc. that classical 2,3,4,5- ptfe phthalate decarboxylation, which prepares 2,3,4,5 tetra fluoro benzoic acid,
The lower progress of tertiary amine compounds effect, exist using a large amount of toxic organic compounds and heavy-polluted disadvantage, while the reaction condition
Under decarboxylic reaction it is selectively poor, the yield of 2,3,4,5- tetrafluorobenzoic aids is low.
CN201910101903 utilizes the micro passage reaction equipped with static mixer, 2,3,4,5- ptfe phthalates
Aqueous solution carry out decarboxylic reaction at 30~80Mpa and obtain 2,3,4,5 tetra fluoro benzoic acid.The reaction condition is simple, does not need
Organic solvent, environmentally protective, good, the high income of selectivity.But this method is carried out at high pressure (30~80Mpa), industrial metaplasia
There are security risks when production.
The method that CN201610992872 first generates calcium salt decarboxylation again using 2,3,4,5- ptfe phthalates, avoids
The application of organic matter reduces pollution.But this method operating process is cumbersome, and production efficiency is low.
CN201210213503 is reacted using trifluoromethanesulfonic acid tri-n-butylamine salt catalytic decarboxylation, but this method need to be in high-pressure section
It is carried out under part, and carbon dioxide is generated in reaction process makes the pressure of reaction kettle be difficult to control.
In recent years, 2, the demand of 3,4,5- tetrafluorobenzoic aids increasingly carrys out big, simple, safe and environmental-friendly preparation
The method of 2,3,4,5 tetra fluoro benzoic acid or extremely important.
Summary of the invention
Regarding the issue above, the present invention provides a kind of side of 2,3,4,5- tetrafluorobenzoic aid of preparation of industrialization
Method.
In order to achieve the above objectives, present invention employs following technical proposals:
A kind of method of 2,3,4,5- tetrafluorobenzoic aid of preparation of industrialization, will contain 2,3,4,5- ptfe phthalates,
The mixed solution pump of catalyst, water and sulfolane is injected into tubular reactor, and reaction is 3~8 points between 180-250 DEG C
Clock, tubular reactor outlet are flowed out the sulfolane solution up to 2,3,4,5- tetrafluorobenzoic aids, are added in the sulfolane solution
It water and is extracted with the immiscible organic solvent of water, after stratification, obtains 2,3,4,5- tetra- after taking upper organic phase to distill
Fluobenzoic acid.
In the method for above-mentioned 2,3,4,5- tetrafluorobenzoic aid of preparation of industrialization, the catalyst is copper sulphate and dimension
Raw element C.Catalyst can also use copper sulphate and sodium sulfite, but will cause and generate peculiar smell in product.
In the method for above-mentioned 2,3,4,5- tetrafluorobenzoic aid of preparation of industrialization, the additional amount of the copper sulphate is 2,
The 1-5% of 3,4,5- ptfe phthalate quality, the ascorbic additional amount are 2,3,4,5- ptfe phthalates
The 3-8% of quality.
In the method for above-mentioned 2,3,4,5- tetrafluorobenzoic aid of preparation of industrialization, the additional amount of the sulfolane is 2,
The 300-1000% of 3,4,5- ptfe phthalate quality, the additional amount of water is sulfolane quality in the mixed solution
5-20%.
In the method for above-mentioned 2,3,4,5- tetrafluorobenzoic aid of preparation of industrialization, water is added in the sulfolane solution
Be 4:1-3:1 with the immiscible organic solvent ratio of water, the amount that water is added in sulfolane solution is 3-4 times of sulfolane quality.
In the method for above-mentioned 2,3,4,5- tetrafluorobenzoic aid of preparation of industrialization, water is added in the sulfolane solution
Be 3:1 with the immiscible organic solvent ratio of water, described is tert-butyl acetate or acetic acid second with the immiscible organic solvent of water
Ester.
It is described immiscible organic molten with water in the method for above-mentioned 2,3,4,5- tetrafluorobenzoic aid of preparation of industrialization
Agent is tert-butyl acetate.
In the method for above-mentioned 2,3,4,5- tetrafluorobenzoic aid of preparation of industrialization, the additional amount of the organic solvent is
The 900-3000% of 2,3,4,5- ptfe phthalate quality.
A kind of method of 2,3,4,5- tetrafluorobenzoic aid of preparation of industrialization, will contain 100kg2,3,4,5- tetrafluoro neighbour benzene two
Formic acid, 5kg copper sulphate, 8kg vitamin C, 20kg water and 1000kg sulfolane solution pump be injected into tubular reactor, object
Material is 8 minutes in 250 DEG C of reactions in tubular reactor, and tubular reactor outlet outflow obtains 2,3,4,5- tetrafluorobenzoic aids
Sulfolane solution is added 3000kg water in the sulfolane solution and 1000kg tert-butyl acetate is extracted, after stratification,
2,3,4,5 tetra fluoro benzoic acid is obtained after taking upper organic phase to distill.
In the method for above-mentioned 2,3,4,5- tetrafluorobenzoic aid of preparation of industrialization, upper organic phase is steamed by first normal pressure
It evaporates and is evaporated under reduced pressure again, in decompression process, vacuum degree is no more than -0.09MPa, and lower water is mutually evaporated under reduced pressure water removal recycling ring fourth
Sulfone.
Compared with prior art, the present invention has the advantages that
Under the active copper catalysis that copper sulphate and vitamin C reaction in-situ generate, 2,3,4,5- ptfe phthalates exist
Decarboxylic reaction occurs under hot conditions and generates 2,3,4,5 tetra fluoro benzoic acid；The present invention is environmentally friendly, and 2, and 3,4,5- tetra-
The selectivity of fluobenzoic acid is good, high income.
As known to those skilled in the art, for sulfolane at 220 DEG C or less, decomposition rate is slow, but when more than 220 DEG C
It waits, as the temperature rises, decomposition rate steeply rises.But applicant is found surprisingly that, is reacted by tubular reactor, In
Copper sulphate and vitamin are as under catalysts conditions, at 250 DEG C, 2,3,4, the 5- tetrafluorobenzoic aid of product that reacts it is pure
Degree and the equal highest of yield.
Figure of description
The HPLC of product 2,3,4,5 tetra fluoro benzoic acid in the embodiment 16 of Fig. 1 schemes.
Specific embodiment
Reagent as used in the following examples can be commercially available unless otherwise specified from routine biochemistry reagent shop.
Embodiment 1
Keeping tubular reactor temperature is 180 DEG C, prepared in advance to contain 100kg2,3,4,5- tetrafluoro O-phthalics
The solution pump of acid, 1kg copper sulphate, 3kg vitamin C, 50kg water and 300kg sulfolane is continuously injected into tubular reactor, material
Remaining time is 3 minutes in tubular reactor.Reaction terminates, and flows out and 900kg water, 300kg tert-butyl acetate are added in material
Extraction, for sulfolane mother liquid recycle to lower batch, the vacuum degree of vacuum distillation is -0.09MPa after lower aqueous layer vacuum distillation water removal, on
Layer organic phase elder generation air-distillation, then be evaporated under reduced pressure, when distillation to no distillate, complete for distillation, distill heating temperature and are no more than
140 DEG C, upper organic phase obtains 2,3,4,5- tetrafluorobenzoic aid 66.8kg, yield 82% after recycling tert-butyl acetate, and purity is
98% (HPLC).
Embodiment 2
Keeping tubular reactor temperature is 220 DEG C, prepared in advance to contain 100kg2,3,4,5- tetrafluoro O-phthalics
The solution pump of acid, 3kg copper sulphate, 6kg vitamin C, 50kg water and 350kg sulfolane is continuously injected into tubular reactor, material
Remaining time is 8 minutes in tubular reactor.Reaction terminates, and flows out and 900kg water, 225kg tert-butyl acetate are added in material
Extraction, sulfolane mother liquid recycle is to lower batch after lower aqueous layer vacuum distillation water removal；Upper organic phase obtains after recycling tert-butyl acetate
2,3,4,5- tetrafluorobenzoic aid 72.5kg, yield 89%, purity are 98.8% (HPLC).
Embodiment 3
Keeping tubular reactor temperature is 180 DEG C, prepared in advance to contain 100kg2,3,4,5- tetrafluoro O-phthalics
The solution pump of acid, 5kg copper sulphate, 8kg vitamin C, 50kg water and 600kg sulfolane is continuously injected into tubular reactor, material
Remaining time is 5 minutes in tubular reactor.Reaction terminates, and flows out and 2000kg water is added in material, 500kg ethyl acetate extraction
It takes, sulfolane mother liquid recycle is to lower batch after lower aqueous layer vacuum distillation water removal；Upper organic phase obtains 2,3 after recycling ethyl acetate,
4,5- tetrafluorobenzoic aid 67.7kg, yield 83%, purity are 98.5% (HPLC).
Embodiment 4
Keeping tubular reactor temperature is 220 DEG C, prepared in advance to contain 100kg2,3,4,5- tetrafluoro O-phthalics
The solution pump of acid, 5kg copper sulphate, 6kg vitamin C, 200kg water and 1000kg sulfolane is continuously injected into tubular reactor, object
Material remaining time in tubular reactor is 4 minutes.Reaction terminates, and flows out and 3000kg water, 1000kg acetic acid second are added in material
Ester extraction, sulfolane mother liquid recycle is to lower batch after lower aqueous layer vacuum distillation water removal；Upper organic phase obtains after recycling ethyl acetate
2,3,4,5- tetrafluorobenzoic aid 73.4kg, yield 90%, purity are 99.1% (HPLC).
Embodiment 5
Keeping tubular reactor temperature is 250 DEG C, prepared in advance to contain 100kg2,3,4,5- tetrafluoro O-phthalics
The solution pump of acid, 3kg copper sulphate, 3kg vitamin C, 50kg water and 800kg sulfolane is continuously injected into tubular reactor, material
Remaining time is 5 minutes in tubular reactor.Reaction terminates, and flows out and 3000kg water is added in material, 940kg ethyl acetate extraction
It takes, sulfolane mother liquid recycle is to lower batch after lower aqueous layer vacuum distillation water removal；Upper organic phase obtains 2,3 after recycling ethyl acetate,
4,5- tetrafluorobenzoic aid 78.3kg, yield 96%, purity are 99.4% (HPLC).
Embodiment 6
Keeping tubular reactor temperature is 180 DEG C, prepared in advance to contain 100kg2,3,4,5- tetrafluoro O-phthalics
The solution pump of acid, 5kg copper sulphate, 6kg vitamin C, 20kg water and 300kg sulfolane is continuously injected into tubular reactor, material
Remaining time is 8 minutes in tubular reactor.Reaction terminates, and flows out and 1000kg water, 350kg tert-butyl acetate are added in material
Extraction, sulfolane mother liquid recycle is to lower batch after lower aqueous layer vacuum distillation water removal；Upper organic phase obtains after recycling tert-butyl acetate
2,3,4,5- tetrafluorobenzoic aid 65.2kg, yield 80%, purity are 98.0% (HPLC).
Embodiment 7
Keeping tubular reactor temperature is 220 DEG C, prepared in advance to contain 100kg2,3,4,5- tetrafluoro O-phthalics
The solution pump of acid, 3kg copper sulphate, 6kg vitamin C, 40kg water and 600kg sulfolane is continuously injected into tubular reactor, material
Remaining time is 5 minutes in tubular reactor.Reaction terminates, and flows out and 2000kg water, 500kg tert-butyl acetate are added in material
Extraction, sulfolane mother liquid recycle is to lower batch after lower aqueous layer vacuum distillation water removal；Upper organic phase obtains after recycling tert-butyl acetate
2,3,4,5- tetrafluorobenzoic aid 70.9kg, yield 87%, purity are 98.3% (HPLC).
Embodiment 8
Keeping tubular reactor temperature is 250 DEG C, prepared in advance to contain 100kg2,3,4,5- tetrafluoro O-phthalics
The solution pump of acid, 5kg copper sulphate, 3kg vitamin C, 50kg water and 600kg sulfolane is continuously injected into tubular reactor, material
Remaining time is 3 minutes in tubular reactor.Reaction terminates, and flows out and 2000kg water is added in material, tert-butyl acetate extraction,
Sulfolane mother liquid recycle is to lower batch after lower aqueous layer vacuum distillation water removal；Upper organic phase obtains 2,3,4 after recycling tert-butyl acetate,
5- tetrafluorobenzoic aid 75.0kg, yield 92%, purity are 98.8% (HPLC).
Embodiment 9
Keeping tubular reactor temperature is 180 DEG C, prepared in advance to contain 100kg2,3,4,5- tetrafluoro O-phthalics
The solution pump of acid, 3kg copper sulphate, 8kg vitamin C, 100kg water and 1000kg sulfolane is continuously injected into tubular reactor, object
Material remaining time in tubular reactor is 3 minutes.Reaction terminates, and flows out and 3000kg water, 1200kg acetic acid second are added in material
Ester extraction, sulfolane mother liquid recycle is to lower batch after lower aqueous layer vacuum distillation water removal；Upper organic phase obtains after recycling ethyl acetate
2,3,4,5- tetrafluorobenzoic aid 66.0kg, yield 81%, purity are 98.8% (HPLC).
Embodiment 10
Keeping tubular reactor temperature is 230 DEG C, prepared in advance to contain 100kg2,3,4,5- tetrafluoro O-phthalics
The solution pump of acid, 1kg copper sulphate, 3kg vitamin C, 100kg water and 1000kg sulfolane is continuously injected into tubular reactor, object
Material remaining time in tubular reactor is 8 minutes.Reaction terminates, and flows out and 3000kg water, 1300kg acetic acid second are added in material
Ester extraction, sulfolane mother liquid recycle is to lower batch after lower aqueous layer vacuum distillation water removal；Upper organic phase obtains after recycling ethyl acetate
2,3,4,5- tetrafluorobenzoic aid 61.1kg, yield 75%, purity are 96.9% (HPLC).
Embodiment 11
Keeping tubular reactor temperature is 220 DEG C, prepared in advance to contain 100kg2,3,4,5- tetrafluoro O-phthalics
The solution pump of acid, 5kg copper sulphate, 3kg vitamin C, 20kg water and 300kg sulfolane is continuously injected into tubular reactor, material
Remaining time is 5 minutes in tubular reactor.Reaction terminates, and flows out and 1000kg water is added in material, 280kg ethyl acetate extraction
It takes, sulfolane mother liquid recycle is to lower batch after lower aqueous layer vacuum distillation water removal；Upper organic phase obtains 2,3 after recycling ethyl acetate,
4,5- tetrafluorobenzoic aid 71.7kg, yield 88%, purity are 98.6% (HPLC).
Embodiment 12
Keeping tubular reactor temperature is 250 DEG C, prepared in advance to contain 100kg2,3,4,5- tetrafluoro O-phthalics
The solution pump of acid, 3kg copper sulphate, 6kg vitamin C, 20kg water and 300kg sulfolane is continuously injected into tubular reactor, material
Remaining time is 3 minutes in tubular reactor.Reaction terminates, and flows out and 1000kg water is added in material, 300kg ethyl acetate extraction
It takes, sulfolane mother liquid recycle is to lower batch after lower aqueous layer vacuum distillation water removal；Upper organic phase obtains 2,3 after recycling ethyl acetate,
4,5- tetrafluorobenzoic aid 74.2kg, yield 91%, purity are 99.0% (HPLC).
Embodiment 13
Keeping tubular reactor temperature is 220 DEG C, prepared in advance to contain 100kg2,3,4,5- tetrafluoro O-phthalics
The solution pump of acid, 3kg copper sulphate, 3kg vitamin C, 30kg water and 600kg sulfolane is continuously injected into tubular reactor, material
Remaining time is 8 minutes in tubular reactor.Reaction terminates, and flows out and 2000kg water is added in material, 500kg ethyl acetate extraction
It takes, sulfolane mother liquid recycle is to lower batch after lower aqueous layer vacuum distillation water removal；Upper organic phase obtains 2,3 after recycling ethyl acetate,
4,5- tetrafluorobenzoic aid 72.5kg, yield 89%, purity are 98.3% (HPLC).
Embodiment 14
Keeping tubular reactor temperature is 220 DEG C, prepared in advance to contain 100kg2,3,4,5- tetrafluoro O-phthalics
The solution pump of acid, 1kg copper sulphate, 6kg vitamin C, 20kg water and 600kg sulfolane is continuously injected into tubular reactor, material
Remaining time is 3 minutes in tubular reactor.Reaction terminates, and flows out and 2000kg water, 550kg tert-butyl acetate are added in material
Extraction, sulfolane mother liquid recycle is to lower batch after lower aqueous layer vacuum distillation water removal；Upper organic phase obtains after recycling tert-butyl acetate
2,3,4,5- tetrafluorobenzoic aid 69.3kg, yield 85%, purity are 97.9% (HPLC).
Embodiment 15
Keeping tubular reactor temperature is 180 DEG C, prepared in advance to contain 100kg2,3,4,5- tetrafluoro O-phthalics
The solution pump of acid, 5kg copper sulphate, 6kg vitamin C, 50kg water and 1000kg sulfolane is continuously injected into tubular reactor, material
Remaining time is 5 minutes in tubular reactor.Reaction terminates, and flows out and 3000kg water is added in material, tert-butyl acetate extraction,
Sulfolane mother liquid recycle is to lower batch after lower aqueous layer vacuum distillation water removal；Upper organic phase obtains 2,3,4 after recycling tert-butyl acetate,
5- tetrafluorobenzoic aid 66.0kg, yield 81%, purity are 97.5% (HPLC).
Embodiment 16
Keeping tubular reactor temperature is 250 DEG C, prepared in advance to contain 100kg2,3,4,5- tetrafluoro O-phthalics
The solution pump of acid, 5kg copper sulphate, 8kg vitamin C, 200kg water and 1000kg sulfolane is continuously injected into tubular reactor, object
Material remaining time in tubular reactor is 8 minutes.Reaction terminates, and flows out and 3000kg water, 1000kg acetic acid uncle are added in material
Butyl ester extraction, sulfolane mother liquid recycle is to lower batch after lower aqueous layer vacuum distillation water removal；Upper organic phase recycles tert-butyl acetate
2,3,4,5- tetrafluorobenzoic aid 80.7kg, yield 99% are obtained afterwards, and purity is 99.5% (HPLC).
Specific embodiment described herein is only an example for the spirit of the invention, and help understands the present invention,
But it does not constitute a limitation of the invention.As long as in addition, technical characteristic involved in the described each embodiment of the present invention
It does not constitute a conflict with each other, so that it may be combined with each other.Those skilled in the art can be to described
Specific embodiment does various modifications or additions or is substituted in a similar manner, and however, it does not deviate from the spirit of the invention
Or beyond the scope of the appended claims.
Claims (10)
1. a kind of method of 2,3,4,5- tetrafluorobenzoic aid of preparation of industrialization, which is characterized in that 2,3,4,5- tetrafluoros neighbour will be contained
Phthalic acid, catalyst, water and sulfolane mixed solution pump be injected into tubular reactor, it is anti-between 180-250 DEG C
It should be 3~8 minutes, the sulfolane solution up to 2,3,4,5- tetrafluorobenzoic aids is flowed out in tubular reactor outlet, in the sulfolane
Water is added in solution and is extracted with the immiscible organic solvent of water, after stratification, is obtained after taking upper organic phase to distill
2,3,4,5 tetra fluoro benzoic acid.
2. the method for 2,3,4,5- tetrafluorobenzoic aid of preparation of industrialization as described in claim 1, which is characterized in that described urges
Agent is copper sulphate and vitamin C.
3. the method for 2,3,4,5- tetrafluorobenzoic aid of preparation of industrialization as claimed in claim 2, which is characterized in that the sulphur
The additional amount of sour copper is the 1-5% of 2,3,4,5- ptfe phthalate quality, and the ascorbic additional amount is 2,3,4,
The 3-8% of 5- ptfe phthalate quality.
4. the method for 2,3,4,5- tetrafluorobenzoic aid of preparation of industrialization as described in claim 1, which is characterized in that the ring
The additional amount of fourth sulfone is the 300-1000% of 2,3,4,5- ptfe phthalate quality, the addition of water in the mixed solution
Amount is the 5-20% of sulfolane quality.
5. the method for 2,3,4,5- tetrafluorobenzoic aid of preparation of industrialization as described in claim 1, which is characterized in that the ring
Water is added in fourth sulfolane solution and it is 4:1-3:1 with the immiscible organic solvent ratio of water, the amount that water is added in sulfolane solution is ring
3-4 times of fourth sulfone quality.
6. the method for 2,3,4,5- tetrafluorobenzoic aid of preparation of industrialization as claimed in claim 5, which is characterized in that the ring
Water is added in fourth sulfolane solution and it is 3:1 with the immiscible organic solvent ratio of water, described is second with the immiscible organic solvent of water
Tert-butyl acrylate or ethyl acetate.
7. the method for 2,3,4,5- tetrafluorobenzoic aid of preparation of industrialization as claimed in claim 6, which is characterized in that it is described with
The immiscible organic solvent of water is tert-butyl acetate.
8. the method for 2,3,4,5- tetrafluorobenzoic aid of preparation of industrialization as described in claim 1, which is characterized in that described has
The additional amount of solvent is the 900-3000% of 2,3,4,5- ptfe phthalate quality.
9. a kind of method of 2,3,4,5- tetrafluorobenzoic aid of preparation of industrialization, which is characterized in that it will contain 100kg2,3,4,5- tetra-
Fluorine phthalic acid, 5kg copper sulphate, 8kg vitamin C, 20kg water and 1000kg sulfolane solution pump to be injected into tubular type anti-
It answers in device, material is 8 minutes in 250 DEG C of reactions in tubular reactor, and tubular reactor outlet outflow obtains 2,3,4,5- tetra-
The sulfolane solution of fluobenzoic acid is added 3000kg water in the sulfolane solution and 1000kg tert-butyl acetate is extracted,
After stratification, 2,3,4,5- tetrafluorobenzoic aids are obtained after taking upper organic phase to distill.
10. the method for 2,3,4,5- tetrafluorobenzoic aid of preparation of industrialization described in -9 any one according to claim 1, feature
It is, upper organic phase is evaporated under reduced pressure again by first air-distillation, and in decompression process, vacuum degree is no more than -0.09MPa,
Lower water is mutually evaporated under reduced pressure water removal recycling sulfolane.
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| 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 |
| CN115417761A (en) * | 2022-08-31 | 2022-12-02 | 福建华药生物技术有限公司 | Industrial continuous production method of 2,3,4,5-tetrafluorobenzoic acid |
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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 |