CN115108891B - Preparation method of 3, 5-difluorophenol - Google Patents
Preparation method of 3, 5-difluorophenol Download PDFInfo
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- CN115108891B CN115108891B CN202210840308.1A CN202210840308A CN115108891B CN 115108891 B CN115108891 B CN 115108891B CN 202210840308 A CN202210840308 A CN 202210840308A CN 115108891 B CN115108891 B CN 115108891B
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- HJSSBIMVTMYKPD-UHFFFAOYSA-N 3,5-difluorophenol Chemical compound OC1=CC(F)=CC(F)=C1 HJSSBIMVTMYKPD-UHFFFAOYSA-N 0.000 title claims abstract description 40
- 238000002360 preparation method Methods 0.000 title claims abstract description 10
- JXUKFFRPLNTYIV-UHFFFAOYSA-N 1,3,5-trifluorobenzene Chemical compound FC1=CC(F)=CC(F)=C1 JXUKFFRPLNTYIV-UHFFFAOYSA-N 0.000 claims abstract description 37
- RRUDCFGSUDOHDG-UHFFFAOYSA-N acetohydroxamic acid Chemical compound CC(O)=NO RRUDCFGSUDOHDG-UHFFFAOYSA-N 0.000 claims abstract description 28
- 229960001171 acetohydroxamic acid Drugs 0.000 claims abstract description 28
- 239000002904 solvent Substances 0.000 claims abstract description 24
- 239000003513 alkali Substances 0.000 claims abstract description 10
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 4
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 55
- 238000006243 chemical reaction Methods 0.000 claims description 43
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 34
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 30
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 28
- 238000000034 method Methods 0.000 claims description 26
- 239000000047 product Substances 0.000 claims description 23
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 16
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical group CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 16
- 239000003208 petroleum Substances 0.000 claims description 14
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 14
- 239000000463 material Substances 0.000 claims description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
- 239000002253 acid Substances 0.000 claims description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 8
- 238000003756 stirring Methods 0.000 claims description 8
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 7
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 6
- 238000001953 recrystallisation Methods 0.000 claims description 6
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 claims description 5
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 5
- 229910052731 fluorine Inorganic materials 0.000 claims description 5
- 239000011737 fluorine Substances 0.000 claims description 5
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 4
- 239000007810 chemical reaction solvent Substances 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 3
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 2
- 239000012043 crude product Substances 0.000 claims description 2
- 230000002209 hydrophobic effect Effects 0.000 claims description 2
- 229910017604 nitric acid Inorganic materials 0.000 claims description 2
- 238000010791 quenching Methods 0.000 claims description 2
- 230000000171 quenching effect Effects 0.000 claims description 2
- 238000006462 rearrangement reaction Methods 0.000 claims description 2
- 125000003944 tolyl group Chemical group 0.000 claims description 2
- 238000005292 vacuum distillation Methods 0.000 claims description 2
- 238000010438 heat treatment Methods 0.000 claims 1
- 238000002156 mixing Methods 0.000 claims 1
- 230000020477 pH reduction Effects 0.000 abstract description 4
- 230000007062 hydrolysis Effects 0.000 description 15
- 238000006460 hydrolysis reaction Methods 0.000 description 15
- 238000004519 manufacturing process Methods 0.000 description 14
- 239000012299 nitrogen atmosphere Substances 0.000 description 13
- 239000002994 raw material Substances 0.000 description 11
- 239000000126 substance Substances 0.000 description 5
- 229910052744 lithium Inorganic materials 0.000 description 4
- SJZATRRXUILGHH-UHFFFAOYSA-N 2,4,6-trifluorobenzoic acid Chemical compound OC(=O)C1=C(F)C=C(F)C=C1F SJZATRRXUILGHH-UHFFFAOYSA-N 0.000 description 3
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical group [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 230000007613 environmental effect Effects 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- JHLKSIOJYMGSMB-UHFFFAOYSA-N 1-bromo-3,5-difluorobenzene Chemical compound FC1=CC(F)=CC(Br)=C1 JHLKSIOJYMGSMB-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 230000006837 decompression Effects 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 238000006193 diazotization reaction Methods 0.000 description 2
- 238000005580 one pot reaction Methods 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 239000000575 pesticide Substances 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-M phenolate Chemical compound [O-]C1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-M 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 238000004065 wastewater treatment Methods 0.000 description 2
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 description 1
- SZRDJHHKIJHJHQ-UHFFFAOYSA-N 3,4,5-trifluoroaniline Chemical compound NC1=CC(F)=C(F)C(F)=C1 SZRDJHHKIJHJHQ-UHFFFAOYSA-N 0.000 description 1
- OCKGFTQIICXDQW-ZEQRLZLVSA-N 5-[(1r)-1-hydroxy-2-[4-[(2r)-2-hydroxy-2-(4-methyl-1-oxo-3h-2-benzofuran-5-yl)ethyl]piperazin-1-yl]ethyl]-4-methyl-3h-2-benzofuran-1-one Chemical compound C1=C2C(=O)OCC2=C(C)C([C@@H](O)CN2CCN(CC2)C[C@H](O)C2=CC=C3C(=O)OCC3=C2C)=C1 OCKGFTQIICXDQW-ZEQRLZLVSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 238000003747 Grignard reaction Methods 0.000 description 1
- 239000007818 Grignard reagent Substances 0.000 description 1
- IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000005885 boration reaction Methods 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 150000004795 grignard reagents Chemical class 0.000 description 1
- 231100000171 higher toxicity Toxicity 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 239000004973 liquid crystal related substance Substances 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- -1 phenol compound Chemical class 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 239000002351 wastewater Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C37/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring
- C07C37/01—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by replacing functional groups bound to a six-membered aromatic ring by hydroxy groups, e.g. by hydrolysis
- C07C37/055—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by replacing functional groups bound to a six-membered aromatic ring by hydroxy groups, e.g. by hydrolysis the substituted group being bound to oxygen, e.g. ether group
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C259/00—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups
- C07C259/04—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids
- C07C259/06—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids having carbon atoms of hydroxamic groups bound to hydrogen atoms or to acyclic carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a preparation method of 3, 5-difluorophenol, which belongs to the technical field of organic synthesis, and is characterized in that 1,3, 5-trifluorobenzene reacts in a solvent under the action of acetohydroxamic acid and alkali to obtain 3, 5-difluorophenol salt, and the 3, 5-difluorophenol is obtained after acidification.
Description
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to a preparation method of 3, 5-difluorophenol.
Background
Phenol and its derivatives are widely used in the chemical industry, and are important basic materials in the aspects of medicines, pesticides, materials and the like, and the preparation and the application of the phenol and its derivatives have high research values. The fluorine-containing organic compound has good structural stability and is widely applied to various fields such as medicines, dyes and the like.
The 3, 5-difluorophenol is an important fluorine-containing phenol compound, is also a common organic intermediate, and has wide application prospect in the fields of medicines, pesticides, liquid crystals and the like. In recent years, the cost of chemical raw materials is gradually increased, the safety production and the environmental protection are increasingly emphasized, and under the background, the economic, safe and environmental protection synthetic process is particularly important.
At present, the currently mainstream preparation methods of 3, 5-difluorophenol are mainly divided into the following steps:
The Grignard method takes 3, 5-difluorobromobenzene as a raw material and is prepared through the steps of Grignard reaction, boration reaction, oxidation reaction and the like:
，
The Grignard method has the advantages of relatively complicated process, active chemical properties of the Grignard reagent, certain danger, strict control of anhydrous and anaerobic conditions in the reaction, high requirements on equipment and operators, high operation difficulty, more problems in actual production, such as large and difficult removal of harmful impurities, low product yield, high overall cost, potential safety hazard and the like.
The lithium substitution method takes 3, 5-difluorobromobenzene as a raw material and is prepared through processes of lithium substitution, bromine extraction, boride reaction, oxidation reaction and the like:
，
Butyl lithium used as a raw material in the method is expensive and has relatively poor economical efficiency. The lithium metal reagent is extremely active, belongs to dangerous chemicals, needs to be carried out at a low temperature (-50 ℃ below zero) under the conditions of no water and no oxygen, has high operation difficulty, and adopts ether reagents (such as tetrahydrofuran, 2-methyltetrahydrofuran and the like) as solvents in the lithium generation method, so that the solvents have high hydrophilicity, a large amount of solvents are contained in the produced wastewater, and the wastewater treatment pressure is high, so that the environment protection is not facilitated.
Patent CN107793295A discloses a method for preparing 3, 5-difluorophenol by diazotizing 3,4, 5-trifluoroaniline, which simplifies the synthesis process and has mild reaction conditions. But the diazotization reaction has higher requirements on reaction operation, the yield of the prepared product is lower, nitrite with higher toxicity is needed in the diazotization reaction, the subsequent wastewater treatment is difficult, and the environment protection is not facilitated.
Patent CN 112608220a discloses a process for preparing 3, 5-difluorophenol from 2,4, 6-trifluorobenzoic acid: the 2,4, 6-trifluoro-benzoic acid is subjected to phenate in alkali, and3, 5-difluoro phenol is obtained after acidification, so that the method reduces the steps for producing the 3, 5-difluoro phenol to a certain extent, and improves the production economy. However, the patent reports that the 2,4, 6-trifluoro benzoic acid is prepared by upstream raw materials, and the preparation needs to be carried out in the processes of catalytic hydrogenation and the like, and the defects of high potential safety hazard and high raw material cost are also caused.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provide a method for preparing 3, 5-difluorophenol by directly extracting fluorine from 1,3, 5-trifluorobenzene, which has the characteristics of low raw material cost, good atomic economy, simple preparation process, safe process, high product yield and purity and the like.
The invention aims at realizing the following steps of a preparation method of 3, 5-difluorophenol, which is characterized in that: the 1,3, 5-trifluorobenzene reacts in a solvent under the action of acetohydroxamic acid and alkali to obtain 3, 5-difluorophenoxide, and the 3, 5-difluorophenol is obtained after acidification.
In order to further realize the aim of the invention, 1,3, 5-trifluoro benzene, acetohydroxamic acid and a reaction solvent are mixed and stirred uniformly under the condition of nitrogen protection and room temperature, then corresponding alkali is added, so that the 1,3, 5-trifluoro benzene is subjected to fluorine removal by the acetohydroxamic acid under the alkaline condition to prepare an intermediate, the temperature is raised to 80-200 ℃ for a rearrangement reaction, after the reaction is finished, the acid is used for quenching until the pH value of the system is 5-7, the reaction system is extracted by a hydrophobic post-treatment solvent to obtain a3, 5-difluorophenol organic solution, the solvent is removed to obtain a3, 5-difluorophenol crude product, and finally the purified solvent is used for recrystallization or high vacuum distillation is carried out to obtain a fine product of a target product, wherein the chemical synthetic route is represented by the following reaction formula:
，
The reaction solvent is one of N, N-Dimethylformamide (DMF), dimethyl sulfoxide (DMSO), toluene, N-methylpyrrolidone (NMP) and N, N-dimethylacetamide (DMAc), the alkali is one of potassium carbonate, sodium carbonate, potassium hydroxide and sodium hydroxide, the acid is one of hydrochloric acid, nitric acid and dilute sulfuric acid, the post-treatment solvent is toluene, and the recrystallization solvent is petroleum ether.
In order to further achieve the object of the present invention, the material ratio of the 1,3, 5-trifluorobenzene to the acetohydroxamic acid may be 1: 1.5-1: 3.
In order to further achieve the object of the present invention, the material ratio of the 1,3, 5-trifluorobenzene to the acetohydroxamic acid may be 1:1.5.
To further achieve the object of the invention, it is possible that the ratio of 1,3, 5-trifluorobenzene to solvent is 1g:2.5 g-1 g:10g.
To further achieve the object of the invention, it is possible that the ratio of 1,3, 5-trifluorobenzene to solvent is 1g:5g.
In order to further achieve the object of the present invention, the material ratio of the 1,3, 5-trifluorobenzene to the acid may be 1: 2.5-1: 6.25.
In order to further achieve the object of the present invention, the material ratio of the 1,3, 5-trifluorobenzene to the acid may be 1:2.5.
Compared with the prior art, the invention has the following remarkable characteristics and positive effects:
(1) Under the action of alkali, the raw material 1,3, 5-trifluoro benzene and acetohydroxamic acid react in one pot to generate phenoxide, and the phenoxide is prepared into 3, 5-difluoro phenol through acidification, so that the conversion rate is high, the atom economy is good, and the method is suitable for industrial production.
(2) The raw materials 1,3, 5-trifluoro benzene and acetohydroxamic acid and the acid, alkali and solvent used are cheap raw materials, and have strong economical efficiency.
(3) The reaction is a one-pot method, the steps are simple, the operation is simple, and the industrial application value is high.
(4) Relates to low hazard degree of raw materials and reaction process, has small hazard degree and meets the requirements of safe production and environmental protection.
Detailed Description
The invention will be further illustrated with reference to the following specific embodiments, which are intended to illustrate the invention and not to limit the invention itself. The embodiments described below do not fully describe all features of the invention, and only representative embodiments have been chosen to describe the invention.
Example 1, a method for preparing 3, 5-difluorophenol, wherein 132.1g of 1,3, 5-trifluorobenzene, 112.5g of acetohydroxamic acid and 660g of N, N-dimethylformamide (DMF for short) are added into a 1L three-neck flask under the protection of nitrogen at room temperature, 276g of potassium carbonate is added under stirring, the addition is finished, the temperature is raised to 90 ℃ from the room temperature, the reaction is carried out for 5 hours, and the GC over-control conversion is finished. Adding 300g of hydrochloric acid for hydrolysis, extracting with 260g of toluene, decompressing and desolventizing to obtain 117.1g of product, and recrystallizing with petroleum ether for one time, wherein the content is more than 99.8%, and the yield is 80.9%.
Example 2A process for producing 3, 5-difluorophenol, wherein 132.1g of 1,3, 5-trifluorobenzene, 112.5g of acetohydroxamic acid and 660g of dimethyl sulfoxide (hereinafter referred to as DMSO) were charged into a 1L three-necked flask under nitrogen atmosphere at room temperature, followed by stirring, followed by adding 276g of potassium carbonate. After the addition, the temperature is raised to 90 ℃ from room temperature, the reaction is carried out for 5 hours, and the GC overcontrol conversion is finished. Adding 300g of hydrochloric acid for hydrolysis, extracting with 260g of toluene, decompressing and desolventizing to obtain 125g of product, and recrystallizing with petroleum ether for one time, wherein the content is more than 99.8%, and the yield is 75.3%.
Example 3A process for preparing 3, 5-difluorophenol was carried out by adding 132.1g of 1,3, 5-trifluorobenzene, 112.5g of acetohydroxamic acid and 212g of sodium carbonate to a 1L three-necked flask at room temperature under nitrogen atmosphere, stirring. After the addition, the temperature is raised to 90 ℃ from room temperature, the reaction is carried out for 5 hours, and the GC overcontrol conversion is finished. Adding 300g of hydrochloric acid for hydrolysis, extracting with 260g of toluene, decompressing and desolventizing to obtain 118.4g of product, and recrystallizing with petroleum ether for one time, wherein the content is more than 99.8%, and the yield is 80.0%.
Example 4A process for preparing 3, 5-difluorophenol was carried out by adding 132.1g of 1,3, 5-trifluorobenzene, 112.5g of acetohydroxamic acid and 80g of sodium hydroxide to a 1L three-necked flask at room temperature under nitrogen atmosphere, stirring. After the addition, the temperature is raised to 90 ℃ from room temperature, the reaction is carried out for 5 hours, and the GC overcontrol conversion is finished. Adding 300g of hydrochloric acid for hydrolysis, extracting with 260g of toluene, decompressing and desolventizing to obtain 109.1g of product, and recrystallizing with petroleum ether for one time with the content more than 99.8 percent and the yield of 74.5 percent.
Example 5A process for preparing 3, 5-difluorophenol was carried out by adding 132.1g of 1,3, 5-trifluorobenzene, 112.5g of acetohydroxamic acid and 112.2g of DMF to a 1L three-necked flask at room temperature under nitrogen atmosphere, and stirring. After the addition, the temperature is raised to 90 ℃ from room temperature, the reaction is carried out for 5 hours, and the GC overcontrol conversion is finished. Adding 300g of hydrochloric acid for hydrolysis, extracting with 260g of toluene, decompressing and desolventizing to obtain 105.6g of product, and recrystallizing with petroleum ether for one time, wherein the content is more than 99.8%, and the yield is 72.8%.
Example 6A process for preparing 3, 5-difluorophenol comprising adding 132.1g of 1,3, 5-trifluorobenzene, 112.5g of acetohydroxamic acid, 660g of DMF and 276g of potassium carbonate to a 1L three-necked flask at room temperature under nitrogen atmosphere. After the addition, the temperature is raised to 120 ℃ from room temperature, the reaction is carried out for 3 hours, and the GC overcontrol conversion is finished. Adding 300g of hydrochloric acid for hydrolysis, extracting with 260g of toluene, decompressing and desolventizing to obtain 117.6g of product, and recrystallizing with petroleum ether for the first time, wherein the content is more than 99.8%, and the yield is 81.1%.
Example 7A process for preparing 3, 5-difluorophenol was carried out by adding 132.1g of 1,3, 5-trifluorobenzene, 112.5g of acetohydroxamic acid, 660g of DMSO and 276g of potassium carbonate to a 1L three-necked flask at room temperature under nitrogen atmosphere. After the addition, the temperature is raised to 120 ℃ from room temperature, the reaction is carried out for 3 hours, and the GC overcontrol conversion is finished. Adding 300g of hydrochloric acid for hydrolysis, extracting with 260g of toluene, decompressing and desolventizing to obtain 121g of product, and recrystallizing with petroleum ether for one time, wherein the content is more than 99.8%, and the yield is 75.2%.
Example 8A process for preparing 3, 5-difluorophenol comprising adding 132.1g of 1,3, 5-trifluorobenzene, 112.5g of acetohydroxamic acid, 660g of DMSO and 276g of potassium carbonate to a 1L three-necked flask at room temperature under nitrogen atmosphere. After the addition, the temperature is raised to 150 ℃ from room temperature, the reaction is carried out for 5 hours, and the GC overcontrol conversion is finished. Adding 300g of hydrochloric acid for hydrolysis, extracting with 260g of toluene, decompressing and desolventizing to obtain 119.1g of product, and recrystallizing with petroleum ether for one time, wherein the content is more than 99.8%, and the yield is 79.8%.
Example 9A process for producing 3, 5-difluorophenol wherein 132.1g of 1,3, 5-trifluorobenzene, 225.2g of acetohydroxamic acid, 660g of DMF and 690g of potassium carbonate were added to a 2L three-necked flask at room temperature under nitrogen atmosphere was stirred. After the addition, the temperature is raised to 90 ℃ from room temperature, the reaction is carried out for 5 hours, and the GC overcontrol conversion is finished. 750g of hydrochloric acid is added for hydrolysis, 260g of toluene is used for extraction, 101g of product is obtained after decompression and desolventization, and the petroleum ether is used for primary recrystallization, the content is more than 99.8%, and the yield is 69.2%.
Example 10A process for preparing 3, 5-difluorophenol comprising adding 132.1g of 1,3, 5-trifluorobenzene, 225.2g of acetohydroxamic acid, 1320g of DMF, 690g of potassium carbonate to a 2L three-necked flask at room temperature under nitrogen protection. After the addition, the temperature is raised to 90 ℃ from room temperature, the reaction is carried out for 5 hours, and the GC overcontrol conversion is finished. 750g of hydrochloric acid is added for hydrolysis, 520g of toluene is used for extraction, 92.7g of product is obtained after decompression and desolventization, and petroleum ether is used for primary recrystallization, the content is more than 99.8%, and the yield is 63.3%.
Example 11A process for preparing 3, 5-difluorophenol was carried out by adding 132.1g of 1,3, 5-trifluorobenzene, 112.5g of acetohydroxamic acid, 660g of DMF and 276g of potassium carbonate to a 1L three-necked flask at room temperature under nitrogen atmosphere. After the addition, the temperature is raised to 90 ℃ from room temperature, the reaction is carried out for 5 hours, and the GC overcontrol conversion is finished. Adding 300g of hydrochloric acid for hydrolysis, extracting with 260g of toluene, and removing solvent under reduced pressure to obtain 117.1g of product with the distilled content more than 99.8% and the yield of 85.5%.
Example 12A process for preparing 3, 5-difluorophenol wherein 132.1g of 1,3, 5-trifluorobenzene, 112.5g of acetohydroxamic acid, 660g of DMSO and 276g of potassium carbonate were added to a 1L three-necked flask at room temperature under nitrogen atmosphere. After the addition, the temperature is raised to 90 ℃ from room temperature, the reaction is carried out for 5 hours, and the GC overcontrol conversion is finished. Adding 300g of hydrochloric acid for hydrolysis, extracting with 260g of toluene, and removing solvent under reduced pressure to obtain 118.2g of product with the distilled content more than 99.8% and the yield of 76.5%.
Example 13A process for producing 3, 5-difluorophenol was carried out by adding 132.1g of 1,3, 5-trifluorobenzene, 112.5g of acetohydroxamic acid, 660g of N, N-dimethylacetamide (DMAc) and 276g of potassium carbonate to a 1L three-necked flask at room temperature under nitrogen atmosphere. After the addition, the temperature is raised to 90 ℃ from room temperature, the reaction is carried out for 5 hours, and the GC overcontrol conversion is finished. Adding 300g of hydrochloric acid for hydrolysis, extracting with 260g of toluene, decompressing and desolventizing to obtain the product 114.2 g, recrystallizing with petroleum ether for one time with the content more than 99.8 percent and the yield of 71.3 percent.
Example 14 to a 1L three-necked flask, 132.1g of 1,3, 5-trifluorobenzene, 112.5g of acetohydroxamic acid and 660g of N-methylpyrrolidone (NMP) were charged under nitrogen atmosphere at room temperature, and 276g of potassium carbonate was added while stirring. After the addition, the temperature is raised to 90 ℃ from room temperature, the reaction is carried out for 5 hours, and the GC overcontrol conversion is finished. Adding 300g of hydrochloric acid for hydrolysis, extracting with 260g of toluene, decompressing and desolventizing to obtain a product 115.2 g, recrystallizing with petroleum ether for one time, wherein the content is more than 99.8%, and the yield is 73.3%.
Example 15A process for producing 3, 5-difluorophenol was carried out by adding 132.1g of 1,3, 5-trifluorobenzene, 112.5g of acetohydroxamic acid and 660g of N-methylpyrrolidone (NMP) to a 1L three-necked flask at room temperature under nitrogen atmosphere, and adding 276g of potassium carbonate while stirring. After the addition, the temperature is raised to 90 ℃ from room temperature, the reaction is carried out for 5 hours, and the GC overcontrol conversion is finished. Adding 300g of hydrochloric acid for hydrolysis, extracting with 260g of toluene, and removing solvent under reduced pressure to obtain a product 115.1 g, wherein the distilled content of the product is more than 99.8%, and the yield is 74.5%.
Claims (6)
1. A preparation method of 3, 5-difluorophenol is characterized in that: reacting 1,3, 5-trifluorobenzene in a solvent under the action of acetohydroxamic acid and alkali to obtain 3, 5-difluorophenoxide, and acidifying to obtain 3, 5-difluorophenol; under the condition of nitrogen protection and room temperature, mixing and stirring 1,3, 5-trifluoro benzene, acetohydroxamic acid and a reaction solvent uniformly, adding corresponding alkali, carrying out fluorine removal on the 1,3, 5-trifluoro benzene under the alkaline condition by using the acetohydroxamic acid to prepare an intermediate, heating to 80-200 ℃ to carry out rearrangement reaction, quenching by using acid until the pH value of a system is 5-7 after the reaction is finished, extracting the reaction system by using a hydrophobic aftertreatment solvent to obtain a 3, 5-difluorophenol organic solution, removing the solvent to obtain a 3, 5-difluorophenol crude product, and finally carrying out recrystallization by using a purified solvent or carrying out high vacuum distillation to obtain a fine product of a target product, wherein the chemical synthesis route is represented by the following reaction formula:
，
the reaction solvent is N, N-dimethylformamide, dimethyl sulfoxide, toluene, N-methylpyrrolidone or N, N-dimethylacetamide; the alkali is potassium carbonate, sodium carbonate, potassium hydroxide or sodium hydroxide; the acid is hydrochloric acid, nitric acid or dilute sulfuric acid; the post-treatment solvent is toluene; the recrystallization solvent is petroleum ether; the material ratio of the 1,3, 5-trifluoro-benzene to the acetohydroxamic acid is 1: 1.5-1: 3.
2. The method for preparing 3, 5-difluorophenol according to claim 1, wherein: the material ratio of the 1,3, 5-trifluoro-benzene to the acetohydroxamic acid is 1:1.5.
3. The method for preparing 3, 5-difluorophenol according to claim 1, wherein: the ratio of the 1,3, 5-trifluoro benzene to the solvent is 1g:2.5 g-1 g:10g.
4. The method for preparing 3, 5-difluorophenol according to claim 1, wherein: the ratio of 1,3, 5-trifluorobenzene to solvent was 1g:5g.
5. The method for preparing 3, 5-difluorophenol according to claim 1, wherein: the material ratio of the 1,3, 5-trifluoro benzene to the acid is 1: 2.5-1: 6.25.
6. The method for preparing 3, 5-difluorophenol according to claim 1, wherein: the material ratio of the 1,3, 5-trifluoro benzene to the acid is 1:2.5.
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