CN107353181B - A kind of preparation method of pentafluorophenol - Google Patents
A kind of preparation method of pentafluorophenol Download PDFInfo
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- CN107353181B CN107353181B CN201710344846.0A CN201710344846A CN107353181B CN 107353181 B CN107353181 B CN 107353181B CN 201710344846 A CN201710344846 A CN 201710344846A CN 107353181 B CN107353181 B CN 107353181B
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- XBNGYFFABRKICK-UHFFFAOYSA-N 2,3,4,5,6-pentafluorophenol Chemical compound OC1=C(F)C(F)=C(F)C(F)=C1F XBNGYFFABRKICK-UHFFFAOYSA-N 0.000 title claims abstract description 47
- IZUPBVBPLAPZRR-UHFFFAOYSA-N pentachloro-phenol Natural products OC1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1Cl IZUPBVBPLAPZRR-UHFFFAOYSA-N 0.000 title claims abstract description 47
- 238000002360 preparation method Methods 0.000 title claims description 25
- 238000001179 sorption measurement Methods 0.000 claims abstract description 52
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims abstract description 39
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 38
- 239000011347 resin Substances 0.000 claims abstract description 32
- 229920005989 resin Polymers 0.000 claims abstract description 32
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims abstract description 30
- 238000006243 chemical reaction Methods 0.000 claims abstract description 28
- ZQBFAOFFOQMSGJ-UHFFFAOYSA-N hexafluorobenzene Chemical compound FC1=C(F)C(F)=C(F)C(F)=C1F ZQBFAOFFOQMSGJ-UHFFFAOYSA-N 0.000 claims abstract description 26
- SHFJWMWCIHQNCP-UHFFFAOYSA-M hydron;tetrabutylazanium;sulfate Chemical compound OS([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC SHFJWMWCIHQNCP-UHFFFAOYSA-M 0.000 claims abstract description 26
- -1 propyl-3-methylpyridine triflate Chemical compound 0.000 claims abstract description 26
- 239000007864 aqueous solution Substances 0.000 claims abstract description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 18
- 239000002904 solvent Substances 0.000 claims abstract description 12
- AKKLAJYCGVIWBS-UHFFFAOYSA-N O=[N].CC1(C)CCCC(C)(C)N1 Chemical compound O=[N].CC1(C)CCCC(C)(C)N1 AKKLAJYCGVIWBS-UHFFFAOYSA-N 0.000 claims abstract description 9
- 238000009835 boiling Methods 0.000 claims abstract description 8
- 239000012153 distilled water Substances 0.000 claims abstract description 8
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 24
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 21
- 239000000047 product Substances 0.000 claims description 19
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 16
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 16
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 claims description 16
- 238000007265 chloromethylation reaction Methods 0.000 claims description 14
- 238000004821 distillation Methods 0.000 claims description 10
- 229910001961 silver nitrate Inorganic materials 0.000 claims description 8
- 239000011780 sodium chloride Substances 0.000 claims description 8
- 239000003153 chemical reaction reagent Substances 0.000 claims description 7
- 239000000706 filtrate Substances 0.000 claims description 7
- 238000007306 functionalization reaction Methods 0.000 claims description 7
- 238000010907 mechanical stirring Methods 0.000 claims description 7
- 239000000243 solution Substances 0.000 claims description 7
- 238000003756 stirring Methods 0.000 claims description 7
- 230000008961 swelling Effects 0.000 claims description 7
- SJLJDNHNIZKPET-UHFFFAOYSA-N 2,3,6-trifluoro-4-methylaniline Chemical compound CC1=CC(F)=C(N)C(F)=C1F SJLJDNHNIZKPET-UHFFFAOYSA-N 0.000 claims 1
- 150000001408 amides Chemical class 0.000 claims 1
- HRQGCQVOJVTVLU-UHFFFAOYSA-N bis(chloromethyl) ether Chemical compound ClCOCCl HRQGCQVOJVTVLU-UHFFFAOYSA-N 0.000 claims 1
- 238000001556 precipitation Methods 0.000 claims 1
- 238000010992 reflux Methods 0.000 claims 1
- 230000003068 static effect Effects 0.000 claims 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 20
- 238000007086 side reaction Methods 0.000 abstract description 5
- 239000003814 drug Substances 0.000 abstract description 4
- 239000004973 liquid crystal related substance Substances 0.000 abstract description 4
- 239000000463 material Substances 0.000 abstract description 4
- 239000002994 raw material Substances 0.000 abstract description 4
- 229940079593 drug Drugs 0.000 abstract description 3
- 239000012535 impurity Substances 0.000 description 14
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 12
- ODGIMMLDVSWADK-UHFFFAOYSA-N 4-trifluoromethylaniline Chemical compound NC1=CC=C(C(F)(F)F)C=C1 ODGIMMLDVSWADK-UHFFFAOYSA-N 0.000 description 7
- 239000013078 crystal Substances 0.000 description 7
- 238000007670 refining Methods 0.000 description 7
- 239000008346 aqueous phase Substances 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- 238000001035 drying Methods 0.000 description 6
- 229940050176 methyl chloride Drugs 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- 239000012071 phase Substances 0.000 description 6
- 239000002244 precipitate Substances 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 238000005406 washing Methods 0.000 description 6
- 239000007818 Grignard reagent Substances 0.000 description 5
- 230000000052 comparative effect Effects 0.000 description 5
- 150000004795 grignard reagents Chemical class 0.000 description 5
- 239000003054 catalyst Substances 0.000 description 3
- XEKTVXADUPBFOA-UHFFFAOYSA-N 1-bromo-2,3,4,5,6-pentafluorobenzene Chemical compound FC1=C(F)C(F)=C(Br)C(F)=C1F XEKTVXADUPBFOA-UHFFFAOYSA-N 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 238000005336 cracking Methods 0.000 description 2
- 238000005886 esterification reaction Methods 0.000 description 2
- 238000006266 etherification reaction Methods 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 238000009776 industrial production Methods 0.000 description 2
- 238000006138 lithiation reaction Methods 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 150000002978 peroxides Chemical class 0.000 description 2
- GETTZEONDQJALK-UHFFFAOYSA-N (trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC=C1 GETTZEONDQJALK-UHFFFAOYSA-N 0.000 description 1
- WACNXHCZHTVBJM-UHFFFAOYSA-N 1,2,3,4,5-pentafluorobenzene Chemical compound FC1=CC(F)=C(F)C(F)=C1F WACNXHCZHTVBJM-UHFFFAOYSA-N 0.000 description 1
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 1
- 238000003747 Grignard reaction Methods 0.000 description 1
- 208000005176 Hepatitis C Diseases 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- 150000004791 alkyl magnesium halides Chemical class 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005265 energy consumption Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 125000000538 pentafluorophenyl group Chemical group FC1=C(F)C(F)=C(*)C(F)=C1F 0.000 description 1
- 239000003444 phase transfer catalyst Substances 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229960002063 sofosbuvir Drugs 0.000 description 1
- TTZHDVOVKQGIBA-IQWMDFIBSA-N sofosbuvir Chemical compound N1([C@@H]2O[C@@H]([C@H]([C@]2(F)C)O)CO[P@@](=O)(N[C@@H](C)C(=O)OC(C)C)OC=2C=CC=CC=2)C=CC(=O)NC1=O TTZHDVOVKQGIBA-IQWMDFIBSA-N 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
Classifications
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- 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
- C07C37/02—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 by substitution of halogen
-
- 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
- B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
- B01J31/0234—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds
- B01J31/0271—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds also containing elements or functional groups covered by B01J31/0201 - B01J31/0231
-
- 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
- C07C37/68—Purification; separation; Use of additives, e.g. for stabilisation
- C07C37/685—Processes comprising at least two steps in series
-
- 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
- C07C37/68—Purification; separation; Use of additives, e.g. for stabilisation
- C07C37/70—Purification; separation; Use of additives, e.g. for stabilisation by physical treatment
-
- 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
- C07C37/68—Purification; separation; Use of additives, e.g. for stabilisation
- C07C37/70—Purification; separation; Use of additives, e.g. for stabilisation by physical treatment
- C07C37/82—Purification; separation; Use of additives, e.g. for stabilisation by physical treatment by solid-liquid treatment; by chemisorption
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Hydrogenated Pyridines (AREA)
Abstract
本发明提供一种五氟苯酚的制备方法，步骤如下：以六氟苯和氢氧化钾为原料，在质量分数80‑85%的叔丁醇水溶液中，加入适量的四丁基硫酸氢铵、N‑磺酸丙基‑3‑甲基吡啶三氟甲磺酸盐、N‑甲基‑2‑[(2‑甲基苯氧基)乙酰基]肼甲硫代酰胺和2,2,6,6‑四甲基哌啶‑氮氧化物，加热至微沸，回流反应2‑3 h，加入适量的水，蒸馏回收叔丁醇溶剂。剩余水溶液用精制盐酸调节PH=9‑10，通过功能化D101大孔吸附树脂吸附后，用精制盐酸酸化至PH=1‑2，分层，上层水相蒸馏至无油状物，收集蒸馏得到的产物与下层油相合并，精馏，收集142‑144℃的馏分，冷却至室温，得无色透明结晶五氟苯酚。本发明工艺简单合理、副反应少、反应收率及产品纯度高，可以满足制备高品质液晶材料和药物的质量要求。The invention provides a method for preparing pentafluorophenol. The steps are as follows: using hexafluorobenzene and potassium hydroxide as raw materials, adding an appropriate amount of tetrabutylammonium hydrogen sulfate, N-sulfonic acid propyl-3-methylpyridine triflate, N-methyl-2-[(2-methylphenoxy)acetyl]hydrazine methylthioamide and 2,2,6 ,6-tetramethylpiperidine-nitrogen oxide, heated to slightly boiling, refluxed for 2-3 h, added an appropriate amount of water, and distilled to recover the tert-butanol solvent. The remaining aqueous solution is adjusted to pH=9-10 with refined hydrochloric acid, adsorbed by functionalized D101 macroporous adsorption resin, acidified to pH=1-2 with refined hydrochloric acid, layered, the upper water phase is distilled to no oily matter, and the distilled water is collected. The product was combined with the lower oil phase, rectified, and the fractions at 142-144°C were collected, cooled to room temperature, and colorless and transparent crystalline pentafluorophenol was obtained. The invention has the advantages of simple and reasonable process, few side reactions, high reaction yield and high product purity, and can meet the quality requirements for preparing high-quality liquid crystal materials and medicines.
Description
Technical Field
The invention relates to the technical field of organic synthesis, in particular to a preparation method of pentafluorophenol.
Background
The pentafluorophenol is a valuable intermediate of medicines, liquid crystals and high molecular materials, and is mainly used for preparing a full oral medicament sofosbuvir for treating hepatitis C, a pentafluoro phenyl active ester synthesized by polypeptide and an intermediate of a high-performance polyfluoro liquid crystal material.
CN1847210A proposes a method for preparing pentafluorophenol by carrying out a Grignard reaction on bromopentafluorobenzene as a raw material to prepare a Grignard reagent and then carrying out an oxidation reaction on the Grignard reagent and peroxide. CN103420801A is prepared through displacement reaction of bromopentafluorobenzene and alkyl magnesium halide to prepare Grignard reagent, and then the Grignard reagent is oxidized with peroxide to prepare pentafluorophenol. The methods all relate to the preparation and the use of the Grignard reagent, have great potential safety hazard and great difficulty in industrial production. CN102718635A proposes a method for preparing pentafluorophenol by taking pentafluorobenzene as a raw material through lithiation, esterification, hydrolysis and oxidation in one pot, wherein the lithiation reaction and the esterification reaction are required to be carried out at a very low temperature (-60 ℃ to-80 ℃), the energy consumption of industrial production is large, and the control is not easy.
CN105016983A proposes a method for preparing pentafluorophenol by using hexafluorobenzene as an initial raw material through etherification and cracking reactions and a method for preparing pentafluorophenol by using a one-step method, wherein the two-step method for preparing pentafluorophenol through etherification and cracking is relatively complex, the total yield is only 65.6%, the method for preparing pentafluorophenol by using the one-step method is relatively simple, but anhydrous tertiary butyl alcohol is used as a solvent, and the yield is only 70%. J. Org. chem. 1991,56, 7350 and 7354 proposed to prepare pentafluorophenol by hydrolysis of hexafluorobenzene with tetrabutylammonium hydrogen sulfate as phase transfer catalyst, with large catalyst usage and 71% yield.
By adopting the conventional post-treatment purification technology, the product generally has the technical problems of high content of single impurities and difficulty in meeting the requirements of preparing high-quality liquid crystal materials and medicines, and CN106187706A provides a refining process of high-purity pentafluorophenol, but the process is complex, and the separation difficulty and the production cost are high.
Disclosure of Invention
The invention aims to solve the technical problems of more side reactions, poor solvent recycling effect, low product yield and purity and particularly high single impurity content in the prior art, and provides a pentafluorophenol preparation method with simple and reasonable process, less side reactions, high reaction yield and high product purity.
In order to solve the technical problems, the technical scheme adopted by the invention is as follows:
a preparation method of pentafluorophenol, comprising the steps of:
(1) preparation of functionalized D101 macroporous adsorption resin
Sequentially adding 1000g of D101-Cl macroporous adsorption resin with chloromethylation degree of 1.5mmol/g, which is prepared by taking methyl chloride as a chloromethylation reagent, 13.5L of dimethylformamide, standing and swelling for 15h, adding 3500g of sodium chloride, 350g of p-aminobenzotrifluoride and 500g of sodium hydroxide, stirring and reacting for 48h at 65 ℃, repeatedly washing with ethanol and distilled water until no precipitate is generated after adding a silver nitrate solution, and drying to prepare the functionalized D101 macroporous adsorption resin with the functionalization degree of 1.05 mmol/g;
(2) preparation of pentafluorophenol
According to the weight portion, 100 portions of hexafluorobenzene, 500 portions of tert-butyl alcohol aqueous solution with the mass fraction of 80-85 percent, 65-90 portions of potassium hydroxide, 2-5 portions of tetrabutylammonium hydrogen sulfate, 0.5-1 portion of N-sulfopropyl-3-methylpyridine triflate, 0.05-0.1 portion of N-methyl-2- [ (2-methylphenoxy) acetyl ] hydrazine methylthio amide and 0.02-0.05 portion of 2,2,6, 6-tetramethylpiperidine-nitrogen oxide are added into a reaction kettle, and the mixture is heated to slight boiling under the mechanical stirring and is refluxed for 2-3 hours. After the reaction is finished, adding 450-600 parts of water, distilling, and recovering the tert-butyl alcohol solvent;
(3) refining of pentafluorophenol
Adjusting the pH of the residual aqueous solution to be 9-10 by using refined hydrochloric acid, adding the residual aqueous solution into an adsorption column filled with 1000 parts of prepared functional D101 macroporous adsorption resin for adsorption at the flow rate of 1-2BV/h, adding the refined hydrochloric acid into the filtrate after adsorption again, adjusting the pH to be 1-2, layering, distilling the upper aqueous phase to be an oil-free substance, collecting the product obtained by distillation and combining the product with the lower oil phase, rectifying, collecting the fraction with the temperature of 142-144 ℃, and cooling to room temperature to obtain colorless transparent crystal pentafluorophenol.
The hexafluorobenzene, the p-aminobenzotrifluoride, the D101-Cl macroporous adsorbent resin, the tert-butyl alcohol, the potassium hydroxide, the sodium hydroxide, the tetrabutylammonium hydrogen sulfate, the N-sulfopropyl-3-methylpyridine trifluoromethanesulfonate, the N-methyl-2- [ (2-methylphenoxy) acetyl ] hydrazine methylthioamide, the 2,2,6, 6-tetramethylpiperidine-nitrogen oxide, the sodium chloride, the ethanol, the silver nitrate and the refined hydrochloric acid are all commercially available products.
Compared with the prior art, the invention has the following beneficial effects:
(1) the method has the advantages that tetrabutylammonium hydrogen sulfate and N-sulfopropyl-3-methylpyridine trifluoromethanesulfonate with catalyst amount are utilized, a tert-butyl alcohol aqueous solution with the mass fraction of 80-85% is used as a solvent, the catalyst amount is small, the reaction conditions are mild, side reactions are few, and the solvent can be recycled and reused.
(2) The N-methyl-2- [ (2-methylphenoxy) acetyl ] hydrazine methylthio amide and 2,2,6, 6-tetramethyl piperidine-nitrogen oxide can effectively inhibit the generation of side reactions and improve the selectivity and yield of the reaction.
(3) The functionalized D101 macroporous adsorption resin modified by the benzotrifluoride has good compatibility with fluorine-containing aromatic organic matters, is beneficial to adsorbing some organic impurities which are difficult to separate, and the prepared product has low maximum single impurity content and good product quality.
Detailed Description
The following examples are intended to further illustrate the invention and are not intended to limit the scope of the invention.
Example 1
(1) Preparation of functionalized D101 macroporous adsorption resin
Sequentially adding 1000g of D101-Cl macroporous adsorption resin with chloromethylation degree of 1.5mmol/g, which is prepared by taking methyl chloride as a chloromethylation reagent, 13.5L of dimethylformamide, standing and swelling for 15h, adding 3500g of sodium chloride, 350g of p-aminobenzotrifluoride and 500g of sodium hydroxide, stirring and reacting for 48h at 65 ℃, repeatedly washing with ethanol and distilled water until no precipitate is generated after adding a silver nitrate solution, and drying to prepare the functionalized D101 macroporous adsorption resin with the functionalization degree of 1.05 mmol/g;
(2) preparation of pentafluorophenol
100g of hexafluorobenzene, 500g of an 80 mass percent tert-butyl alcohol aqueous solution, 90g of potassium hydroxide, 5g of tetrabutylammonium hydrogen sulfate, 1g of N-sulfopropyl-3-methylpyridine trifluoromethanesulfonate and 0.1g of N-methyl-2- [ (2-methylphenoxy) acetyl ] hydrazine methylthioamide are added into a reaction kettle, and the mixture is heated to slight boiling under mechanical stirring and refluxed for reaction for 3 hours. After the reaction is finished, 600g of water is added, and the tertiary butanol solvent is recovered by distillation;
(3) refining of pentafluorophenol
Adjusting the pH of the residual aqueous solution to be =9 by refined hydrochloric acid, adding the residual aqueous solution into an adsorption column filled with 1000 parts of prepared functional D101 macroporous adsorption resin for adsorption at the flow rate of 1BV/h, adding the refined hydrochloric acid into the filtrate after adsorption again, adjusting the pH to be =2, layering, distilling the upper-layer aqueous phase to be an oil-free substance, collecting the product obtained by distillation, combining the product with the lower-layer oil phase, rectifying, collecting the fraction at 142 ℃ and 144 ℃, cooling to the room temperature to obtain 88.15g of colorless transparent crystal pentafluorophenol, wherein the yield is 89.1%, the purity (GC) is 99.91%, and the maximum single impurity content is 0.06%.
Example 2
(1) Preparation of functionalized D101 macroporous adsorption resin
Sequentially adding 1000g of D101-Cl macroporous adsorption resin with chloromethylation degree of 1.5mmol/g, which is prepared by taking methyl chloride as a chloromethylation reagent, 13.5L of dimethylformamide, standing and swelling for 15h, adding 3500g of sodium chloride, 350g of p-aminobenzotrifluoride and 500g of sodium hydroxide, stirring and reacting for 48h at 65 ℃, repeatedly washing with ethanol and distilled water until no precipitate is generated after adding a silver nitrate solution, and drying to prepare the functionalized D101 macroporous adsorption resin with the functionalization degree of 1.05 mmol/g;
(2) preparation of pentafluorophenol
100g of hexafluorobenzene, 500g of an 80 mass percent tert-butanol aqueous solution, 90g of potassium hydroxide, 5g of tetrabutylammonium hydrogen sulfate, 1g of N-sulfopropyl-3-methylpyridine trifluoromethanesulfonate, 0.1g of N-methyl-2- [ (2-methylphenoxy) acetyl ] hydrazine methylthioamide and 0.05g of 2,2,6, 6-tetramethylpiperidine-nitrogen oxide are added into a reaction kettle, and the mixture is heated to slight boiling under mechanical stirring and refluxed for reaction for 3 hours. After the reaction is finished, 600g of water is added, and the tertiary butanol solvent is recovered by distillation;
(3) refining of pentafluorophenol
Adjusting the pH of the residual aqueous solution to be =9 by refined hydrochloric acid, adding the residual aqueous solution into an adsorption column filled with 1000 parts of prepared functional D101 macroporous adsorption resin for adsorption at the flow rate of 1BV/h, adding the refined hydrochloric acid into the filtrate after adsorption again, adjusting the pH to be =2, layering, distilling the upper aqueous phase to be an oil-free substance, collecting the product obtained by distillation, combining the product with the lower oil phase, rectifying, collecting the fraction at 142 ℃ and 144 ℃, cooling to the room temperature to obtain 91.51g of colorless transparent crystal pentafluorophenol, wherein the yield is 92.5%, the purity (GC) is 99.93%, and the maximum single impurity content is 0.05%.
Example 3
(1) Preparation of functionalized D101 macroporous adsorption resin
Sequentially adding 1000g of D101-Cl macroporous adsorption resin with chloromethylation degree of 1.5mmol/g, which is prepared by taking methyl chloride as a chloromethylation reagent, 13.5L of dimethylformamide, standing and swelling for 15h, adding 3500g of sodium chloride, 350g of p-aminobenzotrifluoride and 500g of sodium hydroxide, stirring and reacting for 48h at 65 ℃, repeatedly washing with ethanol and distilled water until no precipitate is generated after adding a silver nitrate solution, and drying to prepare the functionalized D101 macroporous adsorption resin with the functionalization degree of 1.05 mmol/g;
(2) preparation of pentafluorophenol
100g of hexafluorobenzene, 300g of an 85% by mass aqueous solution of tert-butanol, 75g of potassium hydroxide, 2g of tetrabutylammonium hydrogen sulfate, 0.75g of N-sulfopropyl-3-methylpyridine trifluoromethanesulfonate, 0.1g of N-methyl-2- [ (2-methylphenoxy) acetyl ] hydrazine methylthioamide and 0.02g of 2,2,6, 6-tetramethylpiperidine-nitrogen oxide are added into a reaction kettle, and the mixture is heated to slight boiling under mechanical stirring and refluxed for reaction for 2 hours. After the reaction is finished, adding 450g of water, distilling, and recovering the tert-butyl alcohol solvent;
(3) refining of pentafluorophenol
Adjusting the pH of the residual aqueous solution to be =10 by refined hydrochloric acid, adding the residual aqueous solution into an adsorption column filled with 1000 parts of prepared functional D101 macroporous adsorption resin for adsorption at the flow rate of 1BV/h, adding the refined hydrochloric acid into the filtrate after adsorption again, adjusting the pH to be =1, layering, distilling the upper-layer aqueous phase to be an oil-free substance, collecting the product obtained by distillation, combining the product with the lower-layer oil phase, rectifying, collecting the fraction at 142 ℃ and 144 ℃, cooling to the room temperature to obtain 90.42g of colorless transparent crystal pentafluorophenol, wherein the yield is 91.4%, the purity (GC) is 99.90%, and the maximum single impurity content is 0.06%.
Example 4
(1) Preparation of functionalized D101 macroporous adsorption resin
Sequentially adding 1000g of D101-Cl macroporous adsorption resin with chloromethylation degree of 1.5mmol/g, which is prepared by taking methyl chloride as a chloromethylation reagent, 13.5L of dimethylformamide, standing and swelling for 15h, adding 3500g of sodium chloride, 350g of p-aminobenzotrifluoride and 500g of sodium hydroxide, stirring and reacting for 48h at 65 ℃, repeatedly washing with ethanol and distilled water until no precipitate is generated after adding a silver nitrate solution, and drying to prepare the functionalized D101 macroporous adsorption resin with the functionalization degree of 1.05 mmol/g;
(2) preparation of pentafluorophenol
100g of hexafluorobenzene, 500g of an 80 mass percent tert-butanol aqueous solution, 65g of potassium hydroxide, 5g of tetrabutylammonium hydrogen sulfate, 1g of N-sulfopropyl-3-methylpyridine trifluoromethanesulfonate, 0.05g of N-methyl-2- [ (2-methylphenoxy) acetyl ] hydrazine methylthioamide and 0.05g of 2,2,6, 6-tetramethylpiperidine-nitrogen oxide are added into a reaction kettle, and the mixture is heated to slight boiling under mechanical stirring and refluxed for reaction for 3 hours. After the reaction is finished, adding 450g of water, distilling, and recovering the tert-butyl alcohol solvent;
(3) refining of pentafluorophenol
Adjusting the pH of the residual aqueous solution to be =9 by refined hydrochloric acid, adding the residual aqueous solution into an adsorption column filled with 1000 parts of prepared functional D101 macroporous adsorption resin for adsorption at the flow rate of 2BV/h, adding the refined hydrochloric acid into the filtrate after adsorption again, adjusting the pH to be =1, layering, distilling the upper-layer aqueous phase to be an oil-free substance, collecting the product obtained by distillation, combining the product with the lower-layer oil phase, rectifying, collecting the fraction at 142 ℃ and 144 ℃, cooling to the room temperature to obtain 88.15g of colorless transparent crystal pentafluorophenol, wherein the yield is 89.1%, the purity (GC) is 99.90%, and the maximum single impurity content is 0.06%.
Example 5
(1) Preparation of functionalized D101 macroporous adsorption resin
Sequentially adding 1000g of D101-Cl macroporous adsorption resin with chloromethylation degree of 1.5mmol/g, which is prepared by taking methyl chloride as a chloromethylation reagent, 13.5L of dimethylformamide, standing and swelling for 15h, adding 3500g of sodium chloride, 350g of p-aminobenzotrifluoride and 500g of sodium hydroxide, stirring and reacting for 48h at 65 ℃, repeatedly washing with ethanol and distilled water until no precipitate is generated after adding a silver nitrate solution, and drying to prepare the functionalized D101 macroporous adsorption resin with the functionalization degree of 1.05 mmol/g;
(2) preparation of pentafluorophenol
100g of hexafluorobenzene, 500g of an 80 mass percent tert-butanol aqueous solution, 90g of potassium hydroxide, 5g of tetrabutylammonium hydrogen sulfate, 0.5g of N-sulfopropyl-3-methylpyridine trifluoromethanesulfonate, 0.1g of N-methyl-2- [ (2-methylphenoxy) acetyl ] hydrazine methylthioamide and 0.05g of 2,2,6, 6-tetramethylpiperidine-nitrogen oxide are added into a reaction kettle, and the mixture is heated to slight boiling under mechanical stirring and refluxed for reaction for 3 hours. After the reaction is finished, 600g of water is added, and the tertiary butanol solvent is recovered by distillation;
(3) refining of pentafluorophenol
Adjusting the pH of the residual aqueous solution to be =10 by refined hydrochloric acid, adding the residual aqueous solution into an adsorption column filled with 1000 parts of prepared functional D101 macroporous adsorption resin for adsorption at the flow rate of 1.5BV/h, adding the refined hydrochloric acid into the filtrate after adsorption again, adjusting the pH to be =2, layering, distilling the upper aqueous phase to be an oil-free substance, collecting the product obtained by distillation, combining the product with the lower oil phase, rectifying, collecting the fraction at 142 ℃ and 144 ℃, cooling to the room temperature to obtain 87.95g of colorless transparent crystal pentafluorophenol, wherein the yield is 88.9%, the purity (GC) is 99.91%, and the maximum single impurity content is 0.06%.
Comparative example 1
No tetrabutylammonium hydrogen sulfate, N-sulfopropyl-3-methylpyridine trifluoromethanesulfonate, 2,2,6, 6-tetramethylpiperidine-nitroxide, N-methyl-2- [ (2-methylphenoxy) acetyl ] hydrazine methylthio amide, or the like was added, and the reaction conditions and the post-treatment method were the same as in example 2, whereby 39.57g of colorless transparent crystalline pentafluorophenol was obtained in a yield of 40%, a purity (GC) of 99.85%, and a maximum single impurity content of 0.09%.
Comparative example 2
The same procedure as in example 2 was repeated except for adding tetrabutylammonium hydrogensulfate and N-sulfopropyl-3-methylpyridine trifluoromethanesulfonate, and other reaction conditions and post-treatment were changed to give 45.50g of colorless transparent crystalline pentafluorophenol, which was obtained in 46% yield, 99.88% purity (GC) and 0.09% maximum single impurity content.
Comparative example 3
No N-sulfopropyl-3-methylpyridine trifluoromethanesulfonate was added, and the colorless transparent crystalline pentafluorophenol 74.20g, yield 75%, purity (GC) 99.89%, maximum single impurity content 0.07% was obtained in the same manner as in example 2 except for the other reaction conditions and the post-treatment method.
Comparative example 4
The same procedure as in example 2 was repeated except for adding N-methyl-2- [ (2-methylphenoxy) acetyl ] hydrazinomethanesulphonylamide and the other reaction conditions and post-treatment to give 81.02g of colorless transparent crystalline pentafluorophenol, yield 81.9%, purity (GC) 99.88%, maximum single impurity content 0.08%.
Comparative example 5
In the step (3), the pH of the aqueous solution is not adjusted to be =9 by refined hydrochloric acid, the aqueous solution is not adsorbed by the functionalized D101 macroporous adsorption resin, the refined hydrochloric acid is directly added, the pH is adjusted to be =2, and other reaction conditions and post-treatment methods are the same as those in example 2, so that 91.02g of colorless transparent crystal pentafluorophenol is obtained, the yield is 92%, the purity (GC) is 99.5%, and the maximum single impurity content is 0.48%.
The present invention is not limited to the above-described embodiments, which are described in the above-mentioned embodiments and the description only for illustrating the principle of the present invention, and the present invention may have various insubstantial variations and modifications without departing from the spirit and scope of the present invention, which are within the scope of the claims of the present invention.
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| CN105384603A (en) * | 2015-12-09 | 2016-03-09 | 陕西省石油化工研究设计院 | Synthesis method of poly-fluorinated phenol compound |
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| CN105384603A (en) * | 2015-12-09 | 2016-03-09 | 陕西省石油化工研究设计院 | Synthesis method of poly-fluorinated phenol compound |
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| 大孔吸附树脂D101的氯甲基化及功能化改性研究;董方;《中国优秀硕士学位论文全文数据库 工程科技Ⅰ辑》;20110930;第B016-130页 * |
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