CN116903445A - Preparation method of 2-fluoro-6-chlorophenol - Google Patents
Preparation method of 2-fluoro-6-chlorophenol Download PDFInfo
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- CN116903445A CN116903445A CN202310931354.7A CN202310931354A CN116903445A CN 116903445 A CN116903445 A CN 116903445A CN 202310931354 A CN202310931354 A CN 202310931354A CN 116903445 A CN116903445 A CN 116903445A
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- fluoro
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- chloroaniline
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- QIAQIYQASAWZPP-UHFFFAOYSA-N 2-chloro-6-fluorophenol Chemical compound OC1=C(F)C=CC=C1Cl QIAQIYQASAWZPP-UHFFFAOYSA-N 0.000 title claims abstract description 18
- 238000002360 preparation method Methods 0.000 title claims abstract description 12
- VITSNECNFNNVQB-UHFFFAOYSA-N 1,3-dichloro-2-nitrobenzene Chemical compound [O-][N+](=O)C1=C(Cl)C=CC=C1Cl VITSNECNFNNVQB-UHFFFAOYSA-N 0.000 claims abstract description 18
- 238000000034 method Methods 0.000 claims abstract description 16
- 239000003960 organic solvent Substances 0.000 claims abstract description 16
- 238000003682 fluorination reaction Methods 0.000 claims abstract description 8
- 238000006460 hydrolysis reaction Methods 0.000 claims abstract description 5
- 238000006243 chemical reaction Methods 0.000 claims description 38
- 239000003054 catalyst Substances 0.000 claims description 26
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 23
- ZJLAWMDJTMMTQB-UHFFFAOYSA-N 2-chloro-6-fluoroaniline Chemical compound NC1=C(F)C=CC=C1Cl ZJLAWMDJTMMTQB-UHFFFAOYSA-N 0.000 claims description 22
- GOIUPLBHNRTTIO-UHFFFAOYSA-N 1-chloro-3-fluoro-2-nitrobenzene Chemical compound [O-][N+](=O)C1=C(F)C=CC=C1Cl GOIUPLBHNRTTIO-UHFFFAOYSA-N 0.000 claims description 21
- 239000002904 solvent Substances 0.000 claims description 19
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 claims description 18
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 16
- 238000003756 stirring Methods 0.000 claims description 14
- 238000005984 hydrogenation reaction Methods 0.000 claims description 9
- 235000003270 potassium fluoride Nutrition 0.000 claims description 9
- 239000011698 potassium fluoride Substances 0.000 claims description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 8
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 claims description 8
- 239000007868 Raney catalyst Substances 0.000 claims description 7
- 229910000564 Raney nickel Inorganic materials 0.000 claims description 7
- 239000003153 chemical reaction reagent Substances 0.000 claims description 7
- 230000009935 nitrosation Effects 0.000 claims description 7
- 238000007034 nitrosation reaction Methods 0.000 claims description 7
- 238000000605 extraction Methods 0.000 claims description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Chemical group C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 6
- 239000000463 material Substances 0.000 claims description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- 235000010288 sodium nitrite Nutrition 0.000 claims description 4
- DSVGQVZAZSZEEX-UHFFFAOYSA-N [C].[Pt] Chemical compound [C].[Pt] DSVGQVZAZSZEEX-UHFFFAOYSA-N 0.000 claims description 3
- -1 alkyl nitrite Chemical compound 0.000 claims description 3
- 239000003849 aromatic solvent Substances 0.000 claims description 3
- 150000008282 halocarbons Chemical class 0.000 claims description 3
- 125000005842 heteroatom Chemical group 0.000 claims description 3
- NCPHGZWGGANCAY-UHFFFAOYSA-N methane;ruthenium Chemical compound C.[Ru] NCPHGZWGGANCAY-UHFFFAOYSA-N 0.000 claims description 3
- 239000002798 polar solvent Substances 0.000 claims description 3
- 150000003983 crown ethers Chemical group 0.000 claims description 2
- JBTWLSYIZRCDFO-UHFFFAOYSA-N ethyl methyl carbonate Chemical compound CCOC(=O)OC JBTWLSYIZRCDFO-UHFFFAOYSA-N 0.000 claims description 2
- 238000004817 gas chromatography Methods 0.000 claims description 2
- 239000002608 ionic liquid Substances 0.000 claims description 2
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 claims description 2
- RPNNPZHFJPXFQS-UHFFFAOYSA-N methane;rhodium Chemical compound C.[Rh] RPNNPZHFJPXFQS-UHFFFAOYSA-N 0.000 claims description 2
- VQTGUFBGYOIUFS-UHFFFAOYSA-N nitrosylsulfuric acid Chemical compound OS(=O)(=O)ON=O VQTGUFBGYOIUFS-UHFFFAOYSA-N 0.000 claims description 2
- 238000010606 normalization Methods 0.000 claims description 2
- 150000004714 phosphonium salts Chemical group 0.000 claims description 2
- 150000003242 quaternary ammonium salts Chemical class 0.000 claims description 2
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 239000002994 raw material Substances 0.000 abstract description 8
- 238000006193 diazotization reaction Methods 0.000 abstract description 5
- 238000006722 reduction reaction Methods 0.000 abstract description 4
- 230000009286 beneficial effect Effects 0.000 abstract description 3
- 230000007062 hydrolysis Effects 0.000 abstract description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Natural products CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 6
- 238000010438 heat treatment Methods 0.000 description 6
- BRKFQVAOMSWFDU-UHFFFAOYSA-M tetraphenylphosphanium;bromide Chemical compound [Br-].C1=CC=CC=C1[P+](C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 BRKFQVAOMSWFDU-UHFFFAOYSA-M 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- 238000004821 distillation Methods 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- HFHFGHLXUCOHLN-UHFFFAOYSA-N 2-fluorophenol Chemical compound OC1=CC=CC=C1F HFHFGHLXUCOHLN-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 238000005660 chlorination reaction Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- OLZQTUCTGLHFTQ-UHFFFAOYSA-N octan-2-yl 2-(4-amino-3,5-dichloro-6-fluoropyridin-2-yl)oxyacetate Chemical group CCCCCCC(C)OC(=O)COC1=NC(F)=C(Cl)C(N)=C1Cl OLZQTUCTGLHFTQ-UHFFFAOYSA-N 0.000 description 2
- 238000004064 recycling Methods 0.000 description 2
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 2
- 238000001308 synthesis method Methods 0.000 description 2
- NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 description 2
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- CMVQZRLQEOAYSW-UHFFFAOYSA-N 1,2-dichloro-3-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC(Cl)=C1Cl CMVQZRLQEOAYSW-UHFFFAOYSA-N 0.000 description 1
- XEZNGIUYQVAUSS-UHFFFAOYSA-N 18-crown-6 Chemical compound C1COCCOCCOCCOCCOCCO1 XEZNGIUYQVAUSS-UHFFFAOYSA-N 0.000 description 1
- POVPOADUCDQYMB-UHFFFAOYSA-N 3-butyl-1h-imidazol-3-ium;chloride Chemical compound [Cl-].CCCCN1C=C[NH+]=C1 POVPOADUCDQYMB-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical group CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 1
- 239000005456 alcohol based solvent Substances 0.000 description 1
- 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 239000003759 ester based solvent Substances 0.000 description 1
- DUKQZMHSXLRNSN-UHFFFAOYSA-N ethanol;nickel Chemical compound [Ni].CCO DUKQZMHSXLRNSN-UHFFFAOYSA-N 0.000 description 1
- 239000004210 ether based solvent Substances 0.000 description 1
- 238000004880 explosion Methods 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 239000008096 xylene Substances 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
- C07C37/045—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 a group bound to the ring by nitrogen
- C07C37/05—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 a group bound to the ring by nitrogen by substitution of a NH2 group
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
- C07C201/06—Preparation of nitro compounds
- C07C201/12—Preparation of nitro compounds by reactions not involving the formation of nitro groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
- C07C209/30—Preparation of compounds containing amino groups bound to a carbon skeleton by reduction of nitrogen-to-oxygen or nitrogen-to-nitrogen bonds
- C07C209/32—Preparation of compounds containing amino groups bound to a carbon skeleton by reduction of nitrogen-to-oxygen or nitrogen-to-nitrogen bonds by reduction of nitro groups
- C07C209/36—Preparation of compounds containing amino groups bound to a carbon skeleton by reduction of nitrogen-to-oxygen or nitrogen-to-nitrogen bonds by reduction of nitro groups by reduction of nitro groups bound to carbon atoms of six-membered aromatic rings in presence of hydrogen-containing gases and a catalyst
- C07C209/365—Preparation of compounds containing amino groups bound to a carbon skeleton by reduction of nitrogen-to-oxygen or nitrogen-to-nitrogen bonds by reduction of nitro groups by reduction of nitro groups bound to carbon atoms of six-membered aromatic rings in presence of hydrogen-containing gases and a catalyst by reduction with preservation of halogen-atoms in compounds containing nitro groups and halogen atoms bound to the same carbon skeleton
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/584—Recycling of catalysts
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The invention discloses a preparation method of 2-fluoro-6-chlorophenol, which is characterized in that 2, 6-dichloronitrobenzene is used as a raw material in an organic solvent at a certain temperature to obtain a product 2-fluoro-6-chlorophenol through three steps of fluorination, reduction, diazotization and hydrolysis. The method has the advantages of multiple sources of raw materials, obvious cost advantage, safer and more convenient preparation method, high total yield and less three wastes, and is beneficial to industrialization.
Description
Technical Field
The invention relates to a preparation method of 2-fluoro-6-chlorophenol, in particular to a method for obtaining a product 2-fluoro-6-chlorophenol by three steps of reaction of fluorination, reduction and diazotization hydrolysis by taking 2, 6-dichloronitrobenzene as a raw material.
Background
2-fluoro-6-chlorophenol is an important intermediate of Tao Shiyi pesticide fluroxypyr-meptyl and fluroxypyr-meptyl, and is also an important medical intermediate. The synthesis methods reported in the literature are mainly three kinds of: 1. CN1301949C and CN103435452A adopt 2-fluorophenol for chlorination, the process involves poor control of chlorination selectivity, the raw material price of the 2-fluorophenol is high, and the discharge cost is high; 2. CN104844399B adopts a palladium-catalyzed C-H bond fluorination synthesis method, and in the process, a guide group is introduced to improve the selectivity, but the palladium catalyst has high price, and a deprotection group is not easy and has high cost; 3. in CN103787846A, 2, 3-dichloronitrobenzene is adopted as a raw material, and through methoxy substitution, nitro reduction and diazotization and fluorination, the diazotization and fluorination in the process have larger safety risks and larger explosion probability.
Disclosure of Invention
Aiming at the defects in the prior art, the invention provides a preparation method of 2-fluoro-6-chlorophenol, which is a method for obtaining a product 2-fluoro-6-chlorophenol by three steps of reaction of fluorination, reduction and diazotization hydrolysis by taking 2, 6-dichloronitrobenzene as a raw material in an organic solvent at a certain temperature. The method has the advantages of multiple sources of raw materials, obvious cost advantage, safer and more convenient preparation method, high total yield and less three wastes, and is beneficial to industrialization.
In order to achieve the above purpose, the present invention adopts the following technical scheme:
a process for the preparation of a 4-cyclopropyl substituted benzoic acid analogue comprising the steps of:
(1) Adding 2, 6-dichloronitrobenzene and potassium fluoride into an organic solvent at a certain temperature to carry out a fluorination reaction to obtain a product 2-fluoro-6-chloro-nitrobenzene intermediate;
(2) Adding 2-fluoro-6-chloro-nitrobenzene intermediate and catalyst B into an organic solvent at a certain temperature in a high-pressure hydrogenation kettle to carry out hydrogenation reaction to obtain a product 2-fluoro-6-chloroaniline intermediate;
(3) Adding sulfuric acid with the concentration of 30% of 2-fluoro-6-chloroaniline and nitrosation reagent C into a reaction kettle at a certain temperature, and performing denitrification hydrolysis reaction to obtain a product 2-fluoro-6-chlorophenol;
the reaction formula is:
in the technical scheme, the preparation method specifically comprises the following steps:
(1) Sequentially adding an organic solvent, 2, 6-dichloronitrobenzene, potassium fluoride and a catalyst A into a reaction container under the protection of nitrogen, stirring uniformly, and then raising the temperature to a set temperature; preserving the temperature until the normalized content of the 2, 6-dichloronitrobenzene in the total material is less than 1 percent; recovering solvent after desolventizing, and distilling under reduced pressure to obtain intermediate 2-fluoro-6-chloro-nitrobenzene;
(2) Sequentially adding an organic solvent, 2-fluoro-6-chloro-nitrobenzene and a catalyst B into a high-pressure hydrogenation kettle, uniformly stirring, and then raising the temperature to a set temperature and setting the pressure; preserving the temperature until the normalized content of the 2-fluoro-6-chloro-nitrobenzene in the total material is less than 1 percent; after desolventizing, decompressing and distilling to obtain a product 2-fluoro-6-chloroaniline intermediate;
(3) Sequentially adding 30% sulfuric acid, a 2-fluoro-6-chloroaniline intermediate and a nitrosation reagent C into a reaction container under the protection of nitrogen, stirring uniformly, and then raising the temperature to a set temperature; preserving the temperature until the gas chromatography normalization content of the 2-fluoro-6-chloroaniline in the total material is less than 1%; after the reaction is completed, adding a solvent for extraction, desolventizing and then distilling under reduced pressure to obtain the 2-fluoro-6-chlorophenol.
In the technical scheme, in the step (1), the molar ratio of the 2, 6-dichloronitrobenzene to the potassium fluoride is 1:1-5, the molar ratio of the dosage of the organic solvent to the 2, 6-dichloronitrobenzene is 1-10:1, and the molar ratio of the 2, 6-dichloronitrobenzene to the catalyst A is 1-20:1; in the step (2), the molar ratio of the 2-fluoro-6-chloro-nitrobenzene intermediate to the catalyst B is 1-50:1, and the molar ratio of the dosage of the organic solvent to the 2-fluoro-6-chloro-nitrobenzene intermediate is 1-10:1; in the step (3), the molar ratio of the 2-fluoro-6-chloroaniline intermediate to sulfuric acid is 1:1-5, wherein the molar ratio of the 2-fluoro-6-chloroaniline intermediate to the nitrosation reagent is 1:1-5, wherein the molar ratio of the dosage of the organic extraction solvent to the 2-fluoro-6-chloroaniline intermediate is 1-10:1.
In the technical scheme, the reaction temperature in the steps (2) and (3) is 20-80 ℃; the reaction temperature in the step (1) is 100-220 ℃.
In the above technical scheme, the organic solvent in the steps (1), (2) and (3) is any one of halogenated hydrocarbon solvents, aromatic solvents, ether solvents, ester solvents or alcohol solvents, and strong polar solvents containing hetero atoms.
In the above technical scheme, the catalyst A in the step (1) is any one or two of quaternary ammonium salt, quaternary phosphonium salt, crown ether and imidazole ionic liquid.
The catalyst B in the step (2) is any one or two of palladium carbon, raney nickel, ruthenium carbon, rhodium carbon and platinum carbon.
The nitrosation reagent C in the step (3) is any one or two of sodium nitrite, nitrosyl sulfate and alkyl nitrite.
Preferably, the halogenated hydrocarbon solvent is dichloromethane, dichloroethane, etc., the aromatic solvent is toluene, xylene, etc., the ether solvent is tetrahydrofuran, etc., the ester solvent is methyl acetate, ethyl acetate, etc., the alcohol solvent is methanol, ethanol, ethylene glycol, etc., and the heteroatom-containing strong polar solvent DMF, DMA, DMSO, NMP, sulfolane, DMI, etc.
In the technical scheme, in the steps (2) and (3), the reaction temperature is preferably 20-50 ℃; in the step (1), the reaction temperature is preferably 150-180deg.C
The method has the advantages of multiple sources of raw materials, obvious cost advantage, safer and more convenient preparation method, high total yield and less three wastes, and is beneficial to industrialization.
Detailed Description
The following detailed description of the technical scheme of the present invention is provided, but the present invention is not limited to the following descriptions:
example 1: 2-fluoro-6-chlorophenol
Preparing a target product by a small test:
(1) 19.1g (0.10 mol) of 2, 6-dichloronitrobenzene, 100mL of DMF, 8.7g (0.15 mol) of potassium fluoride and 1g of tetraphenyl phosphonium bromide solid serving as a catalyst are put into a 500mL reaction kettle, heated to 150 ℃ and stirred for reaction for 12 hours, DMF is recovered under reduced pressure (directly applied to the next batch of reaction), the recovery rate is 90%, and 14g of 2-fluoro-6-chloronitrobenzene intermediate with the concentration of more than 98% is obtained through reduced pressure distillation, and the yield is 80%;
(2) Adding 17.5g (0.10 mol) of 2-fluoro-6-chloronitrobenzene intermediate, 50mL of ethanol and 1g of Raney nickel into a 500mL hydrogenation reaction kettle, setting the pressure to 0.5MPa, heating to 60 ℃, stirring for reaction for 8 hours, cooling, filtering, recovering the catalyst, recovering ethanol under reduced pressure (directly applying to the next batch reaction), recovering 92 percent, and distilling under reduced pressure to obtain 13.4g of 2-fluoro-6-chloroaniline intermediate with the yield of more than 99 percent, wherein the yield is 92.5 percent;
(3) Adding 14.5g (0.10 mol) of a 2-fluoro-6-chloroaniline intermediate and 150mL of 30% sulfuric acid into a 500mL reaction kettle, uniformly stirring, dropwise adding 41.4g of a 20% sodium nitrite (0.12 mol) aqueous solution at 0 ℃, stirring for 3h after the dropwise adding is finished, heating to 50 ℃ and preserving heat for 1h, then finishing the reaction, adding 50mL of dichloromethane for extraction, liquid separation and desolventizing to recover dichloromethane (directly applied to the next batch reaction), recovering the recovery rate of 93%, and carrying out reduced pressure distillation to obtain 11.7g of a target product 2-fluoro-6-chlorophenol with the concentration of more than 99%, wherein the yield is 80%.
Example 2: 2-fluoro-6-chlorophenol
Pilot plant preparation of target product:
(1) 19.1kg (100 mol) of 2, 6-dichloronitrobenzene, 200L of DMF, 8.7kg (0.15 mol) of potassium fluoride and 1g of tetraphenyl phosphonium bromide solid as a catalyst are put into a 500L reaction kettle, heated to 150 ℃ and stirred for reaction for 12 hours, DMF is recovered under reduced pressure (directly applied to the next batch of reaction), the recovery rate is 95%, and 14.35kg of 2-fluoro-6-chloronitrobenzene intermediate with the concentration of more than 98% is obtained through reduced pressure distillation, and the yield is 82%;
(2) Adding 17.5kg (100 mol) of 2-fluoro-6-chloronitrobenzene intermediate, 150L of ethanol and 100g of Raney nickel into a 500L hydrogenation reaction kettle, setting the pressure to 0.5MPa, heating to 60 ℃, stirring for reaction for 8 hours, cooling, filtering, recovering the catalyst, recovering the ethanol under reduced pressure (directly applying to the next batch of reaction), recovering the ethanol under reduced pressure, and distilling under reduced pressure to obtain 13kg of 2-fluoro-6-chloroaniline intermediate with the yield of more than 99 percent, wherein the yield is 89.7%;
(3) Adding 14.5kg (100 mol) of 2-fluoro-6-chloroaniline intermediate and 150L of 30% sulfuric acid into a 500L reaction kettle, dropwise adding 41.4kg of 20% sodium nitrite (120 mol) aqueous solution at 0 ℃ after uniformly stirring, stirring and reacting for 3 hours at 0 ℃, heating to 50 ℃ and preserving heat for 1 hour, then finishing the reaction, adding 50L of dichloromethane for extraction, separating liquid, desolventizing and recycling dichloromethane (directly applying to the next batch of reaction), recycling rate is 90%, and obtaining 12.4kg of target product 2-fluoro-6-chlorophenol with the yield of more than 99% by reduced pressure distillation, wherein the yield is 85%.
Example 3: 2-fluoro-6-chloronitrobenzene
Preparing target products by small tests, comparing different solvents and catalysts A:
(1) Adding 19.1g (0.10 mol) of 2, 6-dichloronitrobenzene, 100mL of solvent, 8.7g (0.15 mol) of potassium fluoride and 1g of catalyst solid into a 500mL reaction kettle, heating to 150 ℃ and stirring for reaction for 12 hours, recovering DMF (directly applying to the next batch of reaction) under reduced pressure, and distilling under reduced pressure to obtain 2-fluoro-6-chloronitrobenzene with concentration of more than 98%;
| sequence number | Solvent(s) | Catalyst | Yield is good |
| 1 | DMSO | Tetraphenyl phosphonium bromide | 62％ |
| 2 | DMF | Tetraphenyl phosphonium bromide | 80％ |
| 3 | DMI | Tetraphenyl phosphonium bromide | 80％ |
| 4 | Sulfolane (TMP) | Tetraphenyl phosphonium bromide | 50％ |
| 5 | DMF | 18 crown-6 | 38％ |
| 6 | DMF | N-butylimidazole hydrochloride | 5％ |
| 7 | DMF | Tetrabutylammonium chloride | 65％ |
Example 4: 2-fluoro-6-chloroaniline
Preparing target products by small tests, comparing different solvents and catalysts B:
(1) Adding 17.5g (0.10 mol) of 2-fluoro-6-chloronitrobenzene intermediate, 50mL of solvent and 1g of catalyst B into a 500mL hydrogenation reaction kettle, setting the pressure to 0.5MPa, heating to 60 ℃, stirring and reacting for 8 hours, cooling, filtering and recovering the catalyst, and recovering ethanol under reduced pressure (directly applying to the next batch of reaction), and distilling under reduced pressure to obtain the 2-fluoro-6-chloroaniline intermediate with the concentration of more than 99%;
| sequence number | Solvent(s) | Catalyst | Yield is good |
| 1 | Ethanol | Raney nickel | 92.5％ |
| 2 | Methanol | Raney nickel | 90％ |
| 3 | Toluene (toluene) | Raney nickel | 15％ |
| 4 | THF | Raney nickel | 60％ |
| 5 | Ethanol | 5% Palladium on carbon | 65％ |
| 6 | Ethanol | 2% ruthenium carbon | 58％ |
| 7 | Ethanol | 1% platinum carbon | 96％ |
The foregoing examples are merely illustrative of the technical concept and technical features of the present invention, and are not intended to limit the scope of the present invention. All equivalent changes or modifications made according to the essence of the present invention should be included in the scope of the present invention.
Claims (8)
1. The preparation method of the 2-fluoro-6-chlorophenol is characterized by comprising the following steps of:
(1) Adding 2, 6-dichloronitrobenzene and potassium fluoride into an organic solvent at a certain temperature to carry out a fluorination reaction to obtain a product 2-fluoro-6-chloro-nitrobenzene intermediate;
(2) Adding 2-fluoro-6-chloro-nitrobenzene intermediate and catalyst B into an organic solvent at a certain temperature in a high-pressure hydrogenation kettle to carry out hydrogenation reaction to obtain a product 2-fluoro-6-chloroaniline intermediate;
(3) Adding sulfuric acid with the concentration of 30% of 2-fluoro-6-chloroaniline and nitrosation reagent C into a reaction kettle at a certain temperature, and performing denitrification hydrolysis reaction to obtain a product 2-fluoro-6-chlorophenol;
the reaction formula is:
2. the method according to claim 1, comprising the steps of:
(1) Sequentially adding an organic solvent, 2, 6-dichloronitrobenzene, potassium fluoride and a catalyst A into a reaction container under the protection of nitrogen, stirring uniformly, and then raising the temperature to a set temperature; preserving the temperature until the normalized content of the 2, 6-dichloronitrobenzene in the total material is less than 1 percent; recovering solvent after desolventizing, and distilling under reduced pressure to obtain intermediate 2-fluoro-6-chloro-nitrobenzene;
(2) Sequentially adding an organic solvent, 2-fluoro-6-chloro-nitrobenzene and a catalyst B into a high-pressure hydrogenation kettle, uniformly stirring, and then raising the temperature to a set temperature and setting the pressure; preserving the temperature until the normalized content of the 2-fluoro-6-chloro-nitrobenzene in the total material is less than 1 percent; after desolventizing, decompressing and distilling to obtain a product 2-fluoro-6-chloroaniline intermediate;
(3) Sequentially adding 30% sulfuric acid, a 2-fluoro-6-chloroaniline intermediate and a nitrosation reagent C into a reaction container under the protection of nitrogen, stirring uniformly, and then raising the temperature to a set temperature; preserving the temperature until the gas chromatography normalization content of the 2-fluoro-6-chloroaniline in the total material is less than 1%; after the reaction is completed, adding a solvent for extraction, desolventizing and then distilling under reduced pressure to obtain the 2-fluoro-6-chlorophenol.
3. The method according to claim 2, wherein in the step (1), the molar ratio of the 2, 6-dichloronitrobenzene to the potassium fluoride is 1:1-5, the molar ratio of the organic solvent to the 2, 6-dichloronitrobenzene is 1-10:1, and the molar ratio of the 2, 6-dichloronitrobenzene to the catalyst A is 1-20:1; in the step (2), the molar ratio of the 2-fluoro-6-chloro-nitrobenzene intermediate to the catalyst B is 1-50:1, and the molar ratio of the dosage of the organic solvent to the 2-fluoro-6-chloro-nitrobenzene intermediate is 1-10:1; in the step (3), the molar ratio of the 2-fluoro-6-chloroaniline intermediate to sulfuric acid is 1:1-5, wherein the molar ratio of the 2-fluoro-6-chloroaniline intermediate to the nitrosation reagent is 1:1-5, wherein the molar ratio of the dosage of the organic extraction solvent to the 2-fluoro-6-chloroaniline intermediate is 1-10:1.
4. The method according to claim 2, wherein the reaction temperature in steps (2) and (3) is 20 to 80 ℃; the reaction temperature in the step (1) is 100-220 ℃.
5. The method according to claim 2, wherein the organic solvent in the steps (1), (2) and (3) is any one of a halogenated hydrocarbon solvent, an aromatic solvent, an ether solvent, an ester solvent, an alcohol solvent and a strong polar solvent containing a hetero atom.
6. The method according to claim 2, wherein the catalyst A in the step (1) is any one or two of quaternary ammonium salt, quaternary phosphonium salt, crown ether and imidazole ionic liquid.
7. The method according to claim 2, wherein the catalyst B in step (2) is any one or two of palladium carbon, raney nickel, ruthenium carbon, rhodium carbon, and platinum carbon.
8. The method according to claim 2, wherein the nitrosating agent C in the step (3) is any one or two of sodium nitrite, nitrosyl sulfate and alkyl nitrite.
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