CN106748830B - A kind of preparation method of 3- amino-4-fluorophenol - Google Patents

A kind of preparation method of 3- amino-4-fluorophenol Download PDF

Info

Publication number
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
Authority
CN
China
Prior art keywords
fluorophenol
amino
hydrogen
bromo
fluoro
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
CN201710111717.7A
Other languages
Chinese (zh)
Other versions
CN106748830A (en
Inventor
李艳凤
王安钢
姜志鹏
胡志山
马莹
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Jinkai (Liaoning) Life Technology Co.,Ltd.
Original Assignee
KINGCHEM (LIAONING) LLC
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by KINGCHEM (LIAONING) LLC filed Critical KINGCHEM (LIAONING) LLC
Priority to CN201710111717.7A priority Critical patent/CN106748830B/en
Publication of CN106748830A publication Critical patent/CN106748830A/en
Application granted granted Critical
Publication of CN106748830B publication Critical patent/CN106748830B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C213/00Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C213/00Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
    • C07C213/10Separation; Purification; Stabilisation; Use of additives

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

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

A kind of preparation method of 3- amino-4-fluorophenol
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.
CN201710111717.7A 2017-02-28 2017-02-28 A kind of preparation method of 3- amino-4-fluorophenol Active CN106748830B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201710111717.7A CN106748830B (en) 2017-02-28 2017-02-28 A kind of preparation method of 3- amino-4-fluorophenol

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201710111717.7A CN106748830B (en) 2017-02-28 2017-02-28 A kind of preparation method of 3- amino-4-fluorophenol

Publications (2)

Publication Number Publication Date
CN106748830A CN106748830A (en) 2017-05-31
CN106748830B true CN106748830B (en) 2018-11-30

Family

ID=58959700

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201710111717.7A Active CN106748830B (en) 2017-02-28 2017-02-28 A kind of preparation method of 3- amino-4-fluorophenol

Country Status (1)

Country Link
CN (1) CN106748830B (en)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110590570B (en) * 2019-10-10 2023-05-05 西安凯立新材料股份有限公司 Method for preparing halogenated p-aminophenol by catalytic hydrogenation of non-para-halogenated nitrobenzene

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5053557A (en) * 1989-09-12 1991-10-01 Sagami Chemical Research Center Process for preparing 2-chloro-4-fluorophenol
US5191105A (en) * 1981-09-01 1993-03-02 Sumitomo Chemical Company, Ltd. Tetrahydrophthalimides, and their production and use as herbicides
JPH05286912A (en) * 1992-04-08 1993-11-02 Sumitomo Chem Co Ltd Production of aminophenol derivative
CN101519357A (en) * 2008-12-30 2009-09-02 滨海康杰化学有限公司 Method for preparing 3-amino-4-fluorophenol
CN101541801A (en) * 2006-08-04 2009-09-23 武田药品工业株式会社 Fused heterocyclic derivative and use thereof
CN102256493A (en) * 2008-10-29 2011-11-23 迪赛孚尔制药有限公司 Cyclopropane amides and analogs exhibiting anti-cancer and anti-proliferative activities

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS62212353A (en) * 1986-03-13 1987-09-18 Suketaka Harada Production of phenol bearing amino group in the meta position

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5191105A (en) * 1981-09-01 1993-03-02 Sumitomo Chemical Company, Ltd. Tetrahydrophthalimides, and their production and use as herbicides
US5053557A (en) * 1989-09-12 1991-10-01 Sagami Chemical Research Center Process for preparing 2-chloro-4-fluorophenol
JPH05286912A (en) * 1992-04-08 1993-11-02 Sumitomo Chem Co Ltd Production of aminophenol derivative
CN101541801A (en) * 2006-08-04 2009-09-23 武田药品工业株式会社 Fused heterocyclic derivative and use thereof
CN102256493A (en) * 2008-10-29 2011-11-23 迪赛孚尔制药有限公司 Cyclopropane amides and analogs exhibiting anti-cancer and anti-proliferative activities
CN101519357A (en) * 2008-12-30 2009-09-02 滨海康杰化学有限公司 Method for preparing 3-amino-4-fluorophenol

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
4-氨基-2-氟苯酚的合成工艺改进;徐丹等;《山东化工》;20151231;第44卷(第16期);第7-8页 *
Kazuhisa Ishimoto等.Development of a Scalable Synthesis of a Vascular Endothelial Growth Factor Receptor‑2 Kinase Inhibitor: Efficient Construction of a 6‑Etherified [1,2,4]Triazolo[1,5‑a]pyridine-2-amine Core.《Org. Process Res. Dev.》.2014,第18卷第122-134页. *

Also Published As

Publication number Publication date
CN106748830A (en) 2017-05-31

Similar Documents

Publication Publication Date Title
CN103153940B (en) Method for producing trans-1,4-bis(aminomethyl)cyclohexane
CN101575269B (en) Preparation method of aromatic methyl ether compound
CN105985248B (en) A kind of method of synthesizing amino Diaromatic compound
CN103124715A (en) Method for producing bis(aminomethyl)cyclohexanes
CN102952039A (en) Synthesis method of 4-chloro-2-trifluoromethylbenzonitrile
CN102351651A (en) Preparation method of 3,3,3-trifluoropropanol
CN108358913A (en) A kind of green synthesis process of rotundine sulfate
CN106748830B (en) A kind of preparation method of 3- amino-4-fluorophenol
CN103113240B (en) Process for directly synthesizing p-aminophenol through hydrogenation of nitrobenzene
CN103044471A (en) Method for preparing 4-amino benzene boric acid hydrochloride
CN105367431B (en) 3 N of one kind, the preparation method of N dimethylamino ethyl acrylates
CN109232447A (en) The preparation method of 1H-1,2,3- triazole
CN102180811A (en) Method for preparing closantel sodium intermediate by catalytic hydrogenation
CN103193660B (en) Synthetic method of 4-alkoxy phenylamine compound
JPH02279657A (en) Production of aniline
CN106957235B (en) A kind of preparation method of tamoxifen
CN109265385B (en) Synthesis process of chiral catalyst
CA1101429A (en) Process for preparing 2-pyrrolidone
DE102015000119A1 (en) A process for the preparation of bis [4- (6-acryloyloxy-hexyl) -phenyl] cyclohexane-1,4-dicarboxylic acid ester
CN111116378A (en) Method for synthesizing 1, 8-diaminonaphthalene by selective reduction of 1, 8-dinitronaphthalene
CN111718266A (en) Purification method and application of p-nitroaniline
CN111808021B (en) Preparation method of indacaterol and salt thereof
CN103450028B (en) Method for preparing cyclohexylamine and dicyclohexylamine from nitrobenzene through one-step catalytic hydrogenation
CN114957042B (en) Synthesis process of 2, 2-trifluoroacetamidine
CN113105354B (en) Method for preparing N- (4-hydroxy-3-methoxybenzyl) nonanamide without catalyst

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant
CP01 Change in the name or title of a patent holder
CP01 Change in the name or title of a patent holder

Address after: 123100 100 100 meters east of yimatu town railway station, Fumeng County, Fuxin City, Liaoning Province

Patentee after: Jinkai (Liaoning) Life Technology Co.,Ltd.

Address before: 123100 100 100 meters east of yimatu town railway station, Fumeng County, Fuxin City, Liaoning Province

Patentee before: KINGCHEM LIAONING CHEMICAL Co.,Ltd.