CN106748830B - A kind of preparation method of 3- amino-4-fluorophenol - Google Patents
A kind of preparation method of 3- amino-4-fluorophenol Download PDFInfo
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- CN106748830B CN106748830B CN201710111717.7A CN201710111717A CN106748830B CN 106748830 B CN106748830 B CN 106748830B CN 201710111717 A CN201710111717 A CN 201710111717A CN 106748830 B CN106748830 B CN 106748830B
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- fluorophenol
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- hydrogen
- bromo
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- VJCSFNNTQGRAKH-UHFFFAOYSA-N 3-amino-4-fluorophenol Chemical compound NC1=CC(O)=CC=C1F VJCSFNNTQGRAKH-UHFFFAOYSA-N 0.000 title claims abstract description 35
- 238000002360 preparation method Methods 0.000 title claims abstract description 22
- 239000001257 hydrogen Substances 0.000 claims abstract description 50
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 50
- UFHFLCQGNIYNRP-UHFFFAOYSA-N hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 48
- 238000006243 chemical reaction Methods 0.000 claims abstract description 44
- -1 fluoro- 5- nitrobenzene oxygen Ethyl formate Chemical compound 0.000 claims abstract description 32
- 238000005984 hydrogenation reaction Methods 0.000 claims abstract description 31
- 239000000203 mixture Substances 0.000 claims abstract description 27
- 239000003054 catalyst Substances 0.000 claims abstract description 22
- 239000003960 organic solvent Substances 0.000 claims abstract description 17
- 238000000926 separation method Methods 0.000 claims abstract description 10
- 239000000047 product Substances 0.000 claims description 42
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 32
- 239000007787 solid Substances 0.000 claims description 22
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 15
- 238000001914 filtration Methods 0.000 claims description 14
- XEKOWRVHYACXOJ-UHFFFAOYSA-N acetic acid ethyl ester Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 12
- 239000000706 filtrate Substances 0.000 claims description 11
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Chemical group [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 10
- KWYUFKZDYYNOTN-UHFFFAOYSA-M potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 8
- ZMANZCXQSJIPKH-UHFFFAOYSA-N triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 8
- 238000005406 washing Methods 0.000 claims description 8
- 235000019441 ethanol Nutrition 0.000 claims description 7
- PXHVJJICTQNCMI-UHFFFAOYSA-N nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 claims description 7
- 150000001412 amines Chemical class 0.000 claims description 6
- 150000007529 inorganic bases Chemical class 0.000 claims description 6
- 229910000564 Raney nickel Inorganic materials 0.000 claims description 5
- 238000001035 drying Methods 0.000 claims description 5
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 claims description 5
- 239000001187 sodium carbonate Substances 0.000 claims description 5
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 5
- WGYKZJWCGVVSQN-UHFFFAOYSA-N Propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 claims description 4
- QUSNBJAOOMFDIB-UHFFFAOYSA-N ethyl amine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 claims description 4
- 239000001184 potassium carbonate Substances 0.000 claims description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 4
- HYFLWBNQFMXCPA-UHFFFAOYSA-N 1-ethyl-2-methylbenzene Chemical compound CCC1=CC=CC=C1C HYFLWBNQFMXCPA-UHFFFAOYSA-N 0.000 claims description 3
- HQABUPZFAYXKJW-UHFFFAOYSA-N N-Butylamine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 239000007795 chemical reaction product Substances 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxyl anion Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims 1
- 239000001294 propane Substances 0.000 claims 1
- 238000003786 synthesis reaction Methods 0.000 abstract description 8
- 230000015572 biosynthetic process Effects 0.000 abstract description 6
- 230000002194 synthesizing Effects 0.000 abstract description 6
- 239000002699 waste material Substances 0.000 abstract description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 27
- 229910052757 nitrogen Inorganic materials 0.000 description 13
- 239000012043 crude product Substances 0.000 description 9
- 238000006073 displacement reaction Methods 0.000 description 6
- 238000004821 distillation Methods 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 238000005481 NMR spectroscopy Methods 0.000 description 5
- 238000009835 boiling Methods 0.000 description 5
- 238000004587 chromatography analysis Methods 0.000 description 5
- 238000001514 detection method Methods 0.000 description 5
- 229960004756 ethanol Drugs 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 238000001291 vacuum drying Methods 0.000 description 5
- 238000010792 warming Methods 0.000 description 5
- ULDFRPKVIZMKJG-UHFFFAOYSA-N 2-amino-4-fluorophenol Chemical compound NC1=CC(F)=CC=C1O ULDFRPKVIZMKJG-UHFFFAOYSA-N 0.000 description 4
- 238000010025 steaming Methods 0.000 description 4
- XFNJVJPLKCPIBV-UHFFFAOYSA-N 1,3-Diaminopropane Chemical compound NCCCN XFNJVJPLKCPIBV-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 238000005695 dehalogenation reaction Methods 0.000 description 3
- 238000006356 dehydrogenation reaction Methods 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- HCHKCACWOHOZIP-UHFFFAOYSA-N zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 3
- RHMPLDJJXGPMEX-UHFFFAOYSA-N 4-fluorophenol Chemical compound OC1=CC=C(F)C=C1 RHMPLDJJXGPMEX-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N DMSO-d6 Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
- 238000005893 bromination reaction Methods 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000005886 esterification reaction Methods 0.000 description 2
- 150000002431 hydrogen Chemical class 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 239000011261 inert gas Substances 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 230000020477 pH reduction Effects 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- PIICEJLVQHRZGT-UHFFFAOYSA-N 1,2-ethanediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- QZVQQUVWFIZUBQ-UHFFFAOYSA-N 3-fluoroaniline Chemical compound NC1=CC=CC(F)=C1 QZVQQUVWFIZUBQ-UHFFFAOYSA-N 0.000 description 1
- MVZPZOAGXXFJRG-UHFFFAOYSA-N C(=O)OCC.[O] Chemical compound C(=O)OCC.[O] MVZPZOAGXXFJRG-UHFFFAOYSA-N 0.000 description 1
- 0 CCNC1*=C1 Chemical compound CCNC1*=C1 0.000 description 1
- 229960000935 Dehydrated Alcohol Drugs 0.000 description 1
- XYIBRDXRRQCHLP-UHFFFAOYSA-N Ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 1
- FBYAZGLIXVHWJF-UHFFFAOYSA-N [O].NC1=CC(=CC=C1)F Chemical compound [O].NC1=CC(=CC=C1)F FBYAZGLIXVHWJF-UHFFFAOYSA-N 0.000 description 1
- 238000007792 addition Methods 0.000 description 1
- 230000000844 anti-bacterial Effects 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- QNEFNFIKZWUAEQ-UHFFFAOYSA-N carbonic acid;potassium Chemical compound [K].OC(O)=O QNEFNFIKZWUAEQ-UHFFFAOYSA-N 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000005265 energy consumption Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- RYLHNOVXKPXDIP-UHFFFAOYSA-N flufenoxuron Chemical compound C=1C=C(NC(=O)NC(=O)C=2C(=CC=CC=2F)F)C(F)=CC=1OC1=CC=C(C(F)(F)F)C=C1Cl RYLHNOVXKPXDIP-UHFFFAOYSA-N 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000000118 hair dye Substances 0.000 description 1
- 239000001307 helium Substances 0.000 description 1
- 229910052734 helium Inorganic materials 0.000 description 1
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium(0) Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 description 1
- 230000000749 insecticidal Effects 0.000 description 1
- 239000002917 insecticide Substances 0.000 description 1
- 239000004973 liquid crystal related substance Chemical class 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000006011 modification reaction Methods 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 238000006396 nitration reaction Methods 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propanol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 239000006273 synthetic pesticide Substances 0.000 description 1
- 238000007039 two-step reaction 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
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C213/10—Separation; Purification; Stabilisation; Use of additives
Abstract
The present invention provides a kind of preparation methods of 3- amino-4-fluorophenol, include the following steps：The fluoro- 5- nitrobenzene oxygen Ethyl formate of the bromo- 4- of 2-, alkaline matter, hydrogenation catalyst and organic solvent are mixed, mixture is obtained；Hydrogen is passed through into the mixture in confined conditions and carries out hydrogenation reaction, obtains 3- amino-4-fluorophenol；Air in enclosed system is discharged described be passed through before hydrogen.Preparation method synthetic route provided by the invention is short, step is few, only needs single step reaction from the fluoro- 5- nitrobenzene oxygen Ethyl formate synthesis 3- amino-4-fluorophenol of the bromo- 4- of 2-, and the three wastes that reaction process generates are few, the product that purity reaches 99% or more, high income can be obtained in synthetic product simple separation.
Description
Technical field
The present invention relates to the technical field of organic synthesis, in particular to a kind of preparation method of 3- amino-4-fluorophenol.
Background technique
3- amino-4-fluorophenol is the important intermediate of synthetic pesticide insecticide flufenoxuron, can be also used for synthesis medicine
Compound and liquid-crystal compounds can be used for production hair dye and antibacterial activity agent, have in organic synthesis field important
Application value.
In the art, the common synthetic method of 3- amino-4-fluorophenol can be indicated by following reaction equations：
This method synthesizes the fluoro- 5- nitrobenzene oxygen first of the bromo- 4- of 2- using p-fluorophenol as raw material, by bromination, esterification and nitration reaction
Acetoacetic ester, then reduction generates the fluoro- 5- aminobenzene oxygen Ethyl formate of the bromo- 4- of 2- in acid medium, in zinc powder and hydrogen after separation
Dehalogenation, hydrolysis and acidification in sodium hydroxide solution, are recrystallized to give 3- amino-4-fluorophenol later.
Above-mentioned preparation method needs two steps from the fluoro- 5- nitrobenzene oxygen Ethyl formate synthesis 3- amino-4-fluorophenol of the bromo- 4- of 2-
The fluoro- 5- aminobenzene oxygen Ethyl formate reduction of the bromo- 4- of 2- is generated the fluoro- 5- aminobenzene of the bromo- 4- of 2- first in acid medium by reaction
Oxygen Ethyl formate, the step wastewater flow rate is big, and product needs to separate, and causes yield lower；The fluoro- 5- aminobenzene oxygen first of the bromo- 4- of 2-
Acetoacetic ester needs a large amount of zinc powders to carry out dehalogenation, hydrolysis and acidification in sodium hydroxide solution, which equally generates a large amount of useless
Gu and waste liquid, be unfavorable for environmental protection.And this method post-processing is cumbersome, and product, which needs to recrystallize, can just obtain the higher 3- ammonia of purity
Base -4- fluorophenol, causes yield relatively low, from the fluoro- 5- nitrobenzene oxygen Ethyl formate synthesis 3- amino-4-fluorophenol of the bromo- 4- of 2-
The total recovery of two-step reaction is only 76% or so.
Summary of the invention
In view of this, that it is an object of that present invention to provide a kind of steps is few, low energy consumption, the three wastes are few, target product is with high purity, anti-
Answer the preparation method of the 3- amino-4-fluorophenol of high income.
In order to achieve the above-mentioned object of the invention, the present invention provides following technical scheme：
The present invention provides a kind of preparation methods of 3- amino-4-fluorophenol, include the following steps：
The fluoro- 5- nitrobenzene oxygen Ethyl formate of the bromo- 4- of 2-, alkaline matter, hydrogenation catalyst and organic solvent are mixed, obtained
Mixture；
Hydrogen is passed through into the mixture in confined conditions and carries out hydrogenation reaction, obtains 3- amino-4-fluorophenol；Institute
It states and the air in enclosed system is discharged before being passed through hydrogen.
Preferably, the alkaline matter is inorganic base and/or organic amine.
Preferably, the inorganic base is the mixed of one or more of sodium carbonate, potassium carbonate, sodium hydroxide and potassium hydroxide
Close object.
Preferably, the organic amine is one or more of ethamine, triethylamine, propylamine, 1,3- propane diamine and butylamine
Mixture.
Preferably, the hydrogenation catalyst is palladium carbon and/or Raney's nickel.
Preferably, the organic solvent is the mixture of one or more of methanol, ethyl alcohol, ethyl acetate and toluene.
Preferably, the temperature of the hydrogenation reaction is 30~60 DEG C；The initial pressure of the hydrogenation reaction be 1.0~
2.0MPa, pressure drop are added hydrogen to initial pressure, are reacted until not inhaling hydrogen when being greater than 0.5MPa.
Preferably, the molar ratio of the fluoro- 5- nitrobenzene oxygen Ethyl formate of the bromo- 4- of the 2- and alkaline matter is 1:3~6；Institute
The mass ratio for stating hydrogenation catalyst and the fluoro- 5- nitrobenzene oxygen Ethyl formate of the bromo- 4- of 2- is 0.05~0.15:1.
Preferably, the mass ratio of the organic solvent and the fluoro- 5- nitrobenzene oxygen Ethyl formate of the bromo- 4- of 2- is 4~10:1.
It preferably, further include product separation after the hydrogenation reaction, the product separation includes the following steps：
Reaction solution is filtered to remove hydrogenation catalyst, obtains filtrate；
The filtrate is distilled, solid matter is obtained；
By solid matter washing, filtering and drying, 3- amino-4-fluorophenol is obtained.
The present invention provides a kind of preparation methods of 3- amino-4-fluorophenol, include the following steps：By the fluoro- 5- of the bromo- 4- of 2-
Nitrobenzene oxygen Ethyl formate, alkaline matter, hydrogenation catalyst and organic solvent mixing, obtain mixture；It is passed through into mixture
Hydrogen is reacted, and 3- amino-4-fluorophenol is obtained.Preparation method synthetic route provided by the invention is short, and step is few, from 2-
The bromo- fluoro- 5- nitrobenzene oxygen Ethyl formate synthesis 3- amino-4-fluorophenol of 4- only needs single step reaction, and only needs in production process
Organic solvent eliminates the step of acid medium reduction is with zinc powder dehalogenation, entire production process only generates few as reaction medium
The waste liquid of amount, environmentally friendly, obtained product purity is high, high income.
Further, the synthetic product of preparation method provided by the invention is without further purification, it is only necessary to simple solid-liquid point
From the product that high-purity can be obtained.The 3- amino-4-fluorophenol that experiment shows that preparation method provided by the invention obtains is not necessarily to
Purifying purity can reach 99% or more, and yield is 90% or so.
Specific embodiment
The present invention provides a kind of preparation methods of 3- amino-4-fluorophenol, include the following steps：
The fluoro- 5- nitrobenzene oxygen Ethyl formate of the bromo- 4- of 2-, alkaline matter, hydrogenation catalyst and organic solvent are mixed, obtained
Mixture；
Hydrogen is passed through into the mixture in confined conditions and carries out hydrogenation reaction, obtains 3- amino-4-fluorophenol；Institute
It states and the air in enclosed system is discharged before being passed through hydrogen.
The present invention mixes the fluoro- 5- nitrobenzene oxygen Ethyl formate of the bromo- 4- of 2-, alkaline matter, hydrogenation catalyst and organic solvent
It closes, obtains mixture.In the present invention, the alkaline matter is preferably inorganic base and/or organic amine；The inorganic base is preferably
The mixture of one or more of sodium carbonate, potassium carbonate, sodium hydroxide and potassium hydroxide, more preferably sodium carbonate or carbonic acid
Potassium；The organic amine is preferably the mixture of one or more of ethamine, triethylamine, propylamine, 1,3- propane diamine and butylamine；More
Preferably ethamine and/or triethylamine.
In the present invention, the hydrogenation catalyst is preferably palladium carbon and/or Raney's nickel, more preferably palladium carbon；The present invention couple
The source of hydrogenation catalyst does not have particular/special requirement, uses commodity commercially.
In the present invention, the organic solvent is preferably one or more of methanol, ethyl alcohol, ethyl acetate and toluene
Mixture, more preferably methanol or ethyl alcohol；The mixture of the organic solvent is preferably the mixture of 2~3 kinds of organic solvents, more
The preferably mixture of the mixture of methanol and ethyl alcohol or methanol and toluene；Methanol and second in the mixture of the methanol and ethyl alcohol
The volume ratio of alcohol is preferably 1~1.2:1, more preferably 1.05~1.1:1；Methanol and first in the mixture of the methanol and toluene
The volume ratio of benzene is preferably 1~1.2:1, more preferably 1.05~1.1:1.
In the present invention, the molar ratio of the fluoro- 5- nitrobenzene oxygen Ethyl formate of the bromo- 4- of the 2- and alkaline matter is preferably 1:
3~6, more preferably 1:4~5；The mass ratio of the hydrogenation catalyst and the fluoro- 5- nitrobenzene oxygen Ethyl formate of the bromo- 4- of 2- is preferred
It is 0.05~0.15:1, more preferably 0.08~0.12:1, most preferably 0.1:1；The organic solvent and the fluoro- 5- of the bromo- 4- of 2-
The mass ratio of nitrobenzene oxygen Ethyl formate is preferably 4~10:1, more preferably 5~8:1, most preferably 6~7:1.
The source of the fluoro- 5- nitrobenzene oxygen Ethyl formate of present invention 4- bromo- to 2- does not have particular/special requirement, uses the normal of this field
Rule method is synthesized.In the art, usually using p-fluorophenol as starting material, pass through three steps of bromination, esterification and nitrification
Reaction, synthesizes the fluoro- 5- nitrobenzene oxygen Ethyl formate of the bromo- 4- of 2-, and reaction equation is as shown in Equation 1：
After obtaining mixture, the present invention is passed through hydrogen into the mixture in confined conditions and carries out hydrogenation reaction, obtains
To 3- amino-4-fluorophenol；Air in enclosed system is discharged described be passed through before hydrogen.The present invention preferably passes through inert gas
Air in enclosed system is discharged displaced method, and the inert gas is preferably nitrogen, argon gas and helium, more preferably nitrogen
Gas；The present invention does not have particular/special requirement to the method for specific displaced air, uses the method for replacing of this field routine.
In the present invention, the temperature of the hydrogenation reaction is preferably 30~60 DEG C, and more preferably 40~50 DEG C；Described plus hydrogen
The initial pressure of reaction is preferably 1.0~2.0MPa, more preferably 1.3~1.8MPa；The present invention is preferably greater than in pressure drop
Hydrogen is added when 0.5MPa to initial pressure.In the present invention, the hydrogenation reaction preferably reacts the overall reaction until not inhaling hydrogen
Time is preferably 5~8h, more preferably 6~7h.
The present invention does not have particular/special requirement to the rate for being passed through hydrogen, in the particular embodiment, can be according to reaction kettle
Size and the volume of mixture adjust the rate that is passed through of hydrogen, and the present invention, which preferably passes through control hydrogen and is passed through rate, to be made in kettle
Rate of pressure rise is controlled in 0.3~0.8MPa/min, more preferably 0.5MPa/min；The preferably logical hydrogen of the present invention extremely reacts
Stop being passed through for hydrogen after beginning pressure, observe pressure in kettle during the reaction, adds hydrogen extremely when pressure drop is greater than 0.5MPa
Initial pressure.
The present invention preferably carries out hydrogen abstraction reaction under agitation, and the rate of the stirring is preferably 300~500 turns/
Min, more preferably 350~450 turns/min.The present invention does not have special limitation to the hydrogenation reaction equipment, using ability
Autoclave known to field technique personnel.
It, can be at normal temperature by the fluoro- 5- nitrobenzene oxygen formic acid second of the bromo- 4- of 2- in some embodiments of the invention
Ester, alkaline matter, hydrogenation catalyst and organic solvent are added in reaction kettle, then seal reaction kettle, with nitrogen displacement 3~
5 times, empty the air in reaction kettle, backward reaction kettle in be passed through in hydrogen to kettle pressure be 1.0~2.0MPa, and heat up
To reaction temperature, hydrogen abstraction reaction is carried out under agitation, and hydrogen is added when pressure drop is greater than 0.5MPa to initial pressure, repeatedly
Operation is until reaction until not inhaling hydrogen.
After the completion of the hydrogen abstraction reaction, product is preferably separated by solid-liquid separation by the present invention, obtains 3- amino-4-fluorophenol.
The present invention preferably passes through following steps and separates product：
Reaction solution is filtered to remove hydrogenation catalyst, obtains filtrate；
The filtrate is distilled, solid matter is obtained；
By solid matter washing, filtering and drying, 3- amino-4-fluorophenol is obtained.
The present invention uses the filter method of this field routine to the no particular/special requirement of filtering.
In the present invention, the distillation is preferably air-distillation, is steamed the organic solvent in the filtrate by distilling,
Obtain solid matter；The present invention does not have particular/special requirement, in a specific embodiment of the present invention, Ke Yigen to the actual temp of distillation
The organic solvent type used when according to reaction determines vapo(u)rizing temperature.
It is 6.8~7.2, more preferably 6.9~7.1 that solid matter is preferably washed to water lotion pH value by the present invention.
In the present invention, the temperature of the drying is preferably 70~80 DEG C, and more preferably 75~78 DEG C；The present invention is to drying
The specific time there is no particular/special requirement, product is dry to constant weight.
In some embodiments of the invention, after the reaction was completed, reaction solution can be cooled to room temperature with reaction kettle,
Then remaining hydrogen therein is replaced using nitrogen, replaces 3~5 times, empties the hydrogen in kettle, then open kettle and take reaction solution
The separation of product is carried out out.
The present invention, which only passes through single step reaction, to synthesize 3- amino -4- fluorine for the fluoro- 5- nitrobenzene oxygen Ethyl formate of the bromo- 4- of 2-
Phenol, reaction equation are as shown in Equation 2：
Preparation method synthetic route provided by the invention is short, and step is few, and the three wastes that reaction process generates are few, to environment friend
Good, reaction condition is mild, and synthetic product is without further purification, it is only necessary to simple separation, and obtained product purity is high,
High income is suitble to industrialized production.
It is described in detail below with reference to preparation method of the embodiment to 3- amino-4-fluorophenol provided by the invention,
But they cannot be interpreted as limiting the scope of the present invention.
Embodiment 1
The fluoro- 5- nitrobenzene oxygen Ethyl formate 183g (0.59mol) of the bromo- 4- of 2-, dehydrated alcohol are added into 2L autoclave
916g, palladium carbon 5g and potassium carbonate 244.3g (1.77mol), seal kettle after adding, and start stirring, and nitrogen is replaced three times, lead to hydrogen extremely
Pressure is 1.0MPa in kettle, is warming up to 45 DEG C and is reacted, works as Hydrogen Vapor Pressure<When 0.5MPa, benefit hydrogen to pressure 1.0MPa, instead
Multiple operation is cooled to room temperature until not falling pressure after the reaction was completed, nitrogen displacement three times afterwards by reaction solution Filtration of catalyst,
Filtrate air-distillation obtains solid crude product after steaming methanol, by 100g washing, filtering, then obtains after 70 DEG C of vacuum drying light
Yellow solid 3- amino-4-fluorophenol 68.3g；
Product structure is identified using nuclear magnetic resonance, gained appraising datum is as follows：1H NMR(DMSO-d6,
400MHz)δ8.857(s,1H),6.509-6.761(t,1H),6.126-6.206(d,1H),5.871-5.901(s,1H),
4.948 (s, 2H) are according to appraising datum it is found that products therefrom is 3- amino-4-fluorophenol really；
Use GC chromatography (chromatographic column is SPB-5 column, and hydrogen flame detector, detector temperature is 250 DEG C) detection product purity
And calculated yield, can obtain product purity is 99.2%, yield 91%.136 DEG C/the 20mmHg of boiling point of product.
Embodiment 2
The fluoro- 5- nitrobenzene oxygen Ethyl formate 183g (0.59mol) of the bromo- 4- of 2-, methanol 916g, thunder are added into 2L autoclave
Buddhist nun's nickel 5g and 1,3- propane diamine 174.9g (2.36mol), seal kettle after adding, and start stirring, and nitrogen is replaced three times, lead to hydrogen to kettle
Interior pressure is 1.5MPa, is warming up to 40 DEG C and starts to react, works as Hydrogen Vapor Pressure<When 1.0MPa, benefit hydrogen to pressure 1.5MPa, repeatedly
Operation is cooled to room temperature, nitrogen displacement is three times afterwards by reaction solution Filtration of catalyst, filter until not falling pressure after the reaction was completed
Liquid air-distillation obtains solid crude product after steaming methanol, and solid crude product is by 100g washing, filtering, then after 70 DEG C of vacuum drying
Obtain faint yellow solid 3- amino-4-fluorophenol 68.3g；
Product structure is identified using nuclear magnetic resonance, qualification result is consistent with embodiment 1, it is known that product is 3- really
Amino-4-fluorophenol；
Use GC chromatography (chromatographic column is SPB-5 column, and hydrogen flame detector, detector temperature is 250 DEG C) detection product purity
And calculated yield, can obtain product purity is 99.2%, yield 89%.136 DEG C/the 20mmHg of boiling point of product.
Embodiment 3
The fluoro- 5- nitrobenzene oxygen Ethyl formate 183g (0.59mol) of the bromo- 4- of 2-, methanol 916g, palladium are added into 2L autoclave
Carbon 5g and propylamine 104.4g (1.77mol), seals kettle after adding, and starts stirring, and nitrogen is replaced three times, leads to hydrogen to pressure
2.0MPa is warming up to 40 DEG C and starts to react, works as Hydrogen Vapor Pressure<When 1.5MPa, hydrogen is mended to pressure 2.0MPa, is operated repeatedly to not
Until falling pressure, it is cooled to room temperature after the reaction was completed, by reaction solution Filtration of catalyst after nitrogen displacement, filtrate air-distillation is steamed
Solid crude product is obtained after methanol out, by solid crude product by 100g washing, filtering, is then obtained after 70 DEG C of vacuum drying faint yellow
Solid 3- amino-4-fluorophenol 68.3g；
Product structure is identified using nuclear magnetic resonance, qualification result is consistent with embodiment 1, it is known that product is 3- really
Amino-4-fluorophenol；
Use GC chromatography (chromatographic column is SPB-5 column, and hydrogen flame detector, detector temperature is 250 DEG C) detection product purity
And calculated yield, can obtain product purity is 99.2%, yield 92%.136 DEG C/the 20mmHg of boiling point of product.
Embodiment 4
The fluoro- 5- nitrobenzene oxygen Ethyl formate 183g (0.59mol) of the bromo- 4- of 2-, ethyl acetate are added into 2L autoclave
916g, Raney's nickel 18.3g and ethylenediamine 177g (2.95mol), seal kettle after adding, and start stirring, and nitrogen is replaced three times, lead to hydrogen
To pressure 2.0MPa, it is warming up to 50 DEG C and starts to react, work as Hydrogen Vapor Pressure<When 1.5MPa, hydrogen is mended to pressure 2.0MPa, is grasped repeatedly
Make until not falling pressure, room temperature is cooled to after the reaction was completed, by reaction solution Filtration of catalyst, filtrate normal pressure after nitrogen displacement
Solid crude product is obtained after steaming methanol, by solid crude product by 100g washing, filtering, is then obtained after 75 DEG C of vacuum drying
Faint yellow solid 3- amino-4-fluorophenol 68.5g；
Product structure is identified using nuclear magnetic resonance, qualification result is consistent with embodiment 1, it is known that product is 3- really
Amino-4-fluorophenol；
Use GC chromatography (chromatographic column is SPB-5 column, and hydrogen flame detector, detector temperature is 250 DEG C) detection product purity
And calculated yield, can obtain product purity is 99.1%, yield 91.3%.136 DEG C/the 20mmHg of boiling point of product.
Embodiment 5
The addition fluoro- 5- nitrobenzene oxygen Ethyl formate 183g (0.59mol) of the bromo- 4- of 2- into 2L autoclave, toluene 1800g,
Raney's nickel 14.64g and sodium carbonate 250.16g (2.36mol), seals kettle after adding, and starts stirring, and nitrogen is replaced three times, leads to hydrogen
To pressure 1.0MPa, it is warming up to 50 DEG C and starts to react, work as Hydrogen Vapor Pressure<When 0.5MPa, hydrogen is mended to pressure 1.0MPa, is grasped repeatedly
Make until not falling pressure, room temperature is cooled to after the reaction was completed, by reaction solution Filtration of catalyst, filtrate normal pressure after nitrogen displacement
Solid crude product is obtained after steaming methanol, by solid crude product by 100g washing, filtering, is then obtained after 75 DEG C of vacuum drying
Faint yellow solid 3- amino-4-fluorophenol 68.0g；
Product structure is identified using nuclear magnetic resonance, qualification result is consistent with embodiment 1, it is known that product is 3- really
Amino-4-fluorophenol；
Use GC chromatography (chromatographic column is SPB-5 column, and hydrogen flame detector, detector temperature is 250 DEG C) detection product purity
And calculated yield, can obtain product purity is 99.3%, yield 90.3%.136 DEG C/the 20mmHg of boiling point of product.
As seen from the above embodiment, preparation method synthetic route provided by the invention is short, and step is few, from the fluoro- 5- of the bromo- 4- of 2-
Nitrobenzene oxygen Ethyl formate synthesis 3- amino-4-fluorophenol only needs single step reaction, and the three wastes that reaction process generates are few, be easy into
Row industrialized production, synthetic product is without further purification, it is only necessary to which the product of high-purity can be obtained in simple separation, and yield is
90% or so.
As seen from the above embodiment, the present invention is the above is only a preferred embodiment of the present invention, it is noted that for
For those skilled in the art, without departing from the principle of the present invention, can also make it is several improvement and
Retouching, these modifications and embellishments should also be considered as the scope of protection of the present invention.
Claims (6)
1. a kind of preparation method of 3- amino-4-fluorophenol, which is characterized in that include the following steps：
The fluoro- 5- nitrobenzene oxygen Ethyl formate of the bromo- 4- of 2-, alkaline matter, hydrogenation catalyst and organic solvent are mixed, mixed
Object；The alkaline matter be inorganic base and/or organic amine, the hydrogenation catalyst be palladium carbon and/or Raney's nickel, it is described organic molten
Agent is the mixture of one or more of methanol, ethyl alcohol, ethyl acetate and toluene；
Hydrogen is passed through into the mixture in confined conditions and carries out hydrogenation reaction, obtains 3- amino-4-fluorophenol；It is described logical
The air in enclosed system is discharged before entering hydrogen；The temperature of the hydrogenation reaction is 30~60 DEG C, and the hydrogenation reaction rises
Beginning pressure is 1.0~2.0MPa, and pressure drop is added hydrogen to initial pressure, reacted until not inhaling hydrogen when being greater than 0.5MPa.
2. preparation method according to claim 1, which is characterized in that the inorganic base is sodium carbonate, potassium carbonate, hydroxide
The mixture of one or more of sodium and potassium hydroxide.
3. preparation method according to claim 1, which is characterized in that the organic amine be ethamine, triethylamine, propylamine, 1,
The mixture of one or more of 3- propane diamine and butylamine.
4. preparation method according to claim 1, which is characterized in that the fluoro- 5- nitrobenzene oxygen Ethyl formate of the bromo- 4- of 2-
Molar ratio with alkaline matter is 1: 3~6；The quality of the hydrogenation catalyst and the fluoro- 5- nitrobenzene oxygen Ethyl formate of the bromo- 4- of 2-
Than being 0.05~0.15: 1.
5. preparation method according to claim 1 or 4, which is characterized in that the organic solvent and the fluoro- 5- nitre of the bromo- 4- of 2-
The mass ratio of base benzene oxygen Ethyl formate is 4~10: 1.
6. preparation method according to claim 1, which is characterized in that further include product separation, institute after the hydrogenation reaction
Product separation is stated to include the following steps：
Reaction solution is filtered to remove hydrogenation catalyst, obtains filtrate；
The filtrate is distilled, solid matter is obtained；
By solid matter washing, filtering and drying, 3- amino-4-fluorophenol is obtained.
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