CN106349084A - Preparation method of 4-fluoro-3-chloroaniline - Google Patents
Preparation method of 4-fluoro-3-chloroaniline Download PDFInfo
- Publication number
- CN106349084A CN106349084A CN201610730718.5A CN201610730718A CN106349084A CN 106349084 A CN106349084 A CN 106349084A CN 201610730718 A CN201610730718 A CN 201610730718A CN 106349084 A CN106349084 A CN 106349084A
- Authority
- CN
- China
- Prior art keywords
- fluoro
- chloroaniline
- chlorine
- hydrochloric acid
- nitrosoaniline
- 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.)
- Granted
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
- C07C209/68—Preparation of compounds containing amino groups bound to a carbon skeleton from amines, by reactions not involving amino groups, e.g. reduction of unsaturated amines, aromatisation, or substitution of the carbon skeleton
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a preparation method of 4-fluoro-3-chloroaniline. The 4-fluoro-3-chloroaniline is prepared by adding fluorine to the amido para-position of the raw material 3-chloroaniline. The purity of the prepared 4-fluoro-3-chloroaniline is 99% or above; and the method has the advantages of accessible raw materials and low price, and is suitable for industrial production.
Description
Technical field
The present invention relates to organic chemical synthesis field is and in particular to arrive a kind of preparation method of 4- fluoro- 3- chloroaniline.
Background technology
3- chloro- 4- fluoroaniline is new, efficient, broad spectrum antibiotic-norfloxacin, ofloxacin, ring third newly developed in recent years
The main synthesis material intermediate of norfloxacin, chlorine norfloxacin etc., or the important source material of Fluoric Herbicides, insecticide, extensively should
For fields such as medicine, pesticide, dyestuffs.Rise with field and the popularization of medicine, the demand of 4- fluoroaniline chloro- to 3-
Increasingly increase.Therefore, its synthetic method is subject to the common concern of people.
Its synthetic method current mainly has following several:
Method 1
Method 2
Through halogenation twice in method 1, easily produce by-product, and react and be difficult completely, method 2 complex operation, need to throw
Enter equipment excessive, be therefore not suitable for large-scale production, and expensive raw material price, be not suitable for industrialized production.
Content of the invention
It is an object of the invention to provide a kind of preparation method of the fluoro- 3- chloroaniline of 4-.
In order to realize object above, the technical solution adopted in the present invention is:
Step 1, adds 3- chloroaniline in reaction vessel, dilute hydrochloric acid and sodium nitrite, crystallisation by cooling after reaction 30-60 minute,
Filtration washing obtains 3- chlorine nitrosoaniline；
Step 2,3- chlorine nitrosoaniline is dissolved in appropriate fluoroform, and Deca vikane, is heated up to 50 DEG C -70 DEG C instead
Should be through washing, being filtrated to get the fluoro- 3 chlorine nitrosoanilines of 4- after a few hours；
Step 3, by fluoro- for 4- 3 chlorine nitrosoanilines and the reaction of a certain amount of concentrated hydrochloric acid, reaction temperature is 50 DEG C -70 DEG C, reacts 2-
After 4 hours, it is cooled to room temperature, be more than 10 with the ph value of the sodium hydrate regulator solution of 20%-50%, more de- with chloroform decompression extraction
Except solvent, then rectification under vacuum obtains 4- fluoro- 3- chloroaniline.
In described step 1,3- chloroaniline, dilute hydrochloric acid, sodium nitrite mol ratio are 1:1-3:1-3, wherein the concentration of dilute hydrochloric acid
For 3mol/l, the concentration of sodium nitrite is 5mol/l.
In described step 2, for 3-5:1, vikane is sub- with 3- chlorine for the volume mass of fluoroform and 3- chlorine nitrosoaniline ratio
The mol ratio of nitroaniline is 2-3:1.
In described step 3, the concentration of concentrated hydrochloric acid is 14mol/l, the volume mass of concentrated hydrochloric acid and the fluoro- 3 chlorine nitrosoanilines of 4-
Than for 4-6:1.
Beneficial effects of the present invention:
The present invention adopts 3- chloroaniline as raw material, and raw material is easy to get and cheap, can effectively reduce production cost, and
The high conversion rate of reaction, the production cycle is shorter, and reaction condition is gentle, is suitable for industrialized production.
Specific embodiment
Embodiment 1
Add 5mol3- chloroaniline, 5mol dilute hydrochloric acid and 5mol sodium nitrite in reaction vessel, reaction cooled down knot after 30 minutes
Brilliant, filtration washing obtains 3- chlorine nitrosoaniline；3- chlorine nitrosoaniline is dissolved in fluoroform, wherein fluoroform and 3-
The volume mass of chlorine nitrosoaniline ratio is for 3:1, and the mol ratio of Deca vikane, wherein vikane and 3- chlorine nitrosoaniline
For 2:1, after being heated up to 70 DEG C of reaction a few hours through washing, be filtrated to get the fluoro- 3 chlorine nitrosoanilines of 4-, will be sub- for fluoro- for 4- 3 chlorine
Nitroaniline and the reaction of a certain amount of 14mol/l concentrated hydrochloric acid, the wherein volume mass of concentrated hydrochloric acid and the fluoro- 3 chlorine nitrosoanilines of 4-
It is 50 DEG C than for 4:1 reaction temperature, after reacting 2 hours, be cooled to room temperature, the ph value of the sodium hydrate regulator solution with 20% is
10.5, then extract desolvation with chloroform decompression, then rectification under vacuum obtains 4- fluoro- 3- chloroaniline.The 4- obtaining in the present embodiment
Fluoro- 3- chloroaniline purity is 99.5%.
Embodiment 2
Add 5mol3- chloroaniline, 10mol dilute hydrochloric acid and 10mol sodium nitrite in reaction vessel, reaction cooled down after 40 minutes
Crystallization, filtration washing obtain 3- chlorine nitrosoaniline；3- chlorine nitrosoaniline is dissolved in fluoroform, wherein fluoroform and
The volume mass of 3- chlorine nitrosoaniline ratio for 4:1, and Deca vikane, wherein vikane and 3- chlorine nitrosoaniline mole
Ratio for 2:1, after being heated up to 60 DEG C of reaction a few hours through washing, be filtrated to get the fluoro- 3 chlorine nitrosoanilines of 4-, by fluoro- for 4- 3 chlorine
Nitrosoaniline and the reaction of a certain amount of 14mol/l concentrated hydrochloric acid, the wherein volume matter of concentrated hydrochloric acid and the fluoro- 3 chlorine nitrosoanilines of 4-
Amount is 60 DEG C than for 5:1 reaction temperature, after reacting 2 hours, is cooled to room temperature, the ph value of the sodium hydrate regulator solution with 20%
For 11, then reduced pressure extraction desolvation with chloroform, then rectification under vacuum obtains 4- fluoro- 3- chloroaniline.The 4- obtaining in the present embodiment
Fluoro- 3- chloroaniline purity is 99.8%.
The examining report of embodiment 1 and the fluoro- 3- chloroaniline of embodiment 2 gained 4- is as shown in table 1 below
Table 1.
Claims (4)
1. a kind of preparation method of the fluoro- 3- chloroaniline of 4- is it is characterised in that comprise the following steps:
Step 1, adds 3- chloroaniline in reaction vessel, dilute hydrochloric acid and sodium nitrite, crystallisation by cooling after reaction 30-60 minute,
Filtration washing obtains 3- chlorine nitrosoaniline；
Step 2,3- chlorine nitrosoaniline is dissolved in appropriate fluoroform, and Deca vikane, is heated up to 50 DEG C -70 DEG C instead
Should be through washing, being filtrated to get the fluoro- 3 chlorine nitrosoanilines of 4- after a few hours；
Step 3, by fluoro- for 4- 3 chlorine nitrosoanilines and the reaction of a certain amount of concentrated hydrochloric acid, reaction temperature is 50 DEG C -70 DEG C, reacts 2-
After 4 hours, it is cooled to room temperature, be more than 10 with the ph value of the sodium hydrate regulator solution of 20%-50%, more de- with chloroform decompression extraction
Except solvent, then rectification under vacuum obtains 4- fluoro- 3- chloroaniline.
2. a kind of 4- fluoro- 3- chloroaniline according to claim 1 preparation method it is characterized in that, in described step 1
3- chloroaniline, dilute hydrochloric acid, sodium nitrite mol ratio are 1:1-3:1-3, and wherein the concentration of dilute hydrochloric acid is 3mol/l, sodium nitrite
Concentration is 5mol/l.
3. a kind of 4- fluoro- 3- chloroaniline according to claim 1 preparation method it is characterized in that, in described step 2
Than for 3-5:1, vikane with the mol ratio of 3- chlorine nitrosoaniline is the volume mass of fluoroform and 3- chlorine nitrosoaniline
2-3:1.
4. a kind of 4- fluoro- 3- chloroaniline according to claim 1 preparation method it is characterized in that, in described step 3
The concentration of concentrated hydrochloric acid is 14mol/l, and the volume mass of concentrated hydrochloric acid 3 chlorine nitrosoanilines fluoro- with 4- ratio is for 4-6:1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610730718.5A CN106349084B (en) | 2016-08-26 | 2016-08-26 | A kind of preparation method of the fluoro- 3- chloroanilines of 4- |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610730718.5A CN106349084B (en) | 2016-08-26 | 2016-08-26 | A kind of preparation method of the fluoro- 3- chloroanilines of 4- |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN106349084A true CN106349084A (en) | 2017-01-25 |
| CN106349084B CN106349084B (en) | 2018-08-07 |
Family
ID=57854723
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610730718.5A Active CN106349084B (en) | 2016-08-26 | 2016-08-26 | A kind of preparation method of the fluoro- 3- chloroanilines of 4- |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106349084B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111574411A (en) * | 2020-04-24 | 2020-08-25 | 常州齐晖药业有限公司 | Preparation method of diclazuril impurity B |
| CN113416139A (en) * | 2021-06-23 | 2021-09-21 | 江苏笃行致远新材料科技有限公司 | 4-fluorine substituted aryl amine compound and synthetic method thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3338966A (en) * | 1964-04-01 | 1967-08-29 | Hercules Inc | Manufacture of p-nitrosoaniline |
| WO2003037831A2 (en) * | 2001-10-31 | 2003-05-08 | Korea Kumho Petrochemical Co., Ltd. | Method for preparing 4-nitroso-substituted aromatic amine |
| CN104292113A (en) * | 2014-03-04 | 2015-01-21 | 多氟多化工股份有限公司 | Preparation method of 3-chloro-4-fluoroaniline |
| CN105418439A (en) * | 2015-11-17 | 2016-03-23 | 山东沾化天九化工有限公司 | Method and device for producing 3-chlorine-4-fluoroaniline |
-
2016
- 2016-08-26 CN CN201610730718.5A patent/CN106349084B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3338966A (en) * | 1964-04-01 | 1967-08-29 | Hercules Inc | Manufacture of p-nitrosoaniline |
| WO2003037831A2 (en) * | 2001-10-31 | 2003-05-08 | Korea Kumho Petrochemical Co., Ltd. | Method for preparing 4-nitroso-substituted aromatic amine |
| CN104292113A (en) * | 2014-03-04 | 2015-01-21 | 多氟多化工股份有限公司 | Preparation method of 3-chloro-4-fluoroaniline |
| CN105418439A (en) * | 2015-11-17 | 2016-03-23 | 山东沾化天九化工有限公司 | Method and device for producing 3-chlorine-4-fluoroaniline |
Non-Patent Citations (3)
| Title |
|---|
| GERALD PRATSCH等: "The Gomberg–Bachmann Reaction for the Arylation of Anilines with Aryl Diazotates", 《CHEM.EUR.J.》 * |
| 刘庆文 等: "N-亚硝基化合物催化脱亚硝基反应的研究", 《中国化学会第四届有机化学学术会议》 * |
| 刘福萍: "3-氯-4-氟苯胺的合成研究", 《中国优秀硕士学位论文全文数据库 工程科技I辑》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111574411A (en) * | 2020-04-24 | 2020-08-25 | 常州齐晖药业有限公司 | Preparation method of diclazuril impurity B |
| CN113416139A (en) * | 2021-06-23 | 2021-09-21 | 江苏笃行致远新材料科技有限公司 | 4-fluorine substituted aryl amine compound and synthetic method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN106349084B (en) | 2018-08-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN106349084A (en) | Preparation method of 4-fluoro-3-chloroaniline | |
| CN103382166A (en) | Method for preparing 2, 6-dichlorobenzonitrile | |
| CN103224451B (en) | Method for synthesizing 3,5-dichlorobenzoic acid | |
| CN101177418B (en) | Method for synthesizing thiazine ketone | |
| CN103396301B (en) | One prepares the method for 2,6-dichlorobenzaldehyde | |
| CN105293512A (en) | Direct synthesis method of lithium tetrafluoroborate | |
| CN104059670A (en) | Water phase preparation method of CdTeSeS alloy quantum dot | |
| CN101875640B (en) | Method for preparing pyrazinecarboxylic acid in ionic liquid | |
| CN103804321A (en) | Method for preparing (Z)-5-amino-alpha-(ethoxy imino group)-1, 2, 4-thiadiazole-3-acetic acid | |
| CN102173995B (en) | Synthesis method of m-fluoroaniline | |
| CN106316870A (en) | Synthesis method of L-glycine methyl ester salt product | |
| CN108947868B (en) | Preparation process of 2, 4-difluorobenzonitrile | |
| CN105061137A (en) | Synthetic method for 4, 4'-bis(chloromethyl) biphenyl | |
| CN102382000A (en) | Production method of D- para hydroxybenzene glycine | |
| CN109761894A (en) | A kind of preparation method of 5- bromo-2-pyridyl formic acid | |
| CN104974077A (en) | Synthetic method of 2-chloromethylpyridinehydrochloride | |
| CN110981719A (en) | Preparation method of 3-carboxyl benzaldehyde | |
| CN103382165A (en) | Production device for preparing 2, 6-dichlorobenzonitrile | |
| CN103664765A (en) | Preparation method of 2-amino-3-bromopyridine | |
| CN103553890A (en) | Synthesis method of 4-chloro-2-butanone | |
| CN103232344A (en) | Method for synthesizing S-2-methyl chloropropionate | |
| CN105523921A (en) | Method for preparing 2,3-difluoro-6-methoxybenzoic acid | |
| CN103508925A (en) | Preparation method for methanesulfonic acid | |
| CN104945280A (en) | Method for preparing vitamin B1 intermediate by sodium modification | |
| CN203360338U (en) | Production device for preparing 2, 6-dichlorobenzaldehyde |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | 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 | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20191202 Address after: 264200 room 428, Beihai building, sunjiatuan Shawo community, Huancui District, Weihai City, Shandong Province Patentee after: Weihai Haiwo Biotechnology Co., Ltd Address before: 233700 Guzhen Economic Development Zone, Bengbu, Anhui Patentee before: Anhui Hongsheng biological Limited by Share Ltd |
|
| TR01 | Transfer of patent right |