CN110938002A - Preparation method of m-fluoroaniline - Google Patents
Preparation method of m-fluoroaniline Download PDFInfo
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- CN110938002A CN110938002A CN201911341417.3A CN201911341417A CN110938002A CN 110938002 A CN110938002 A CN 110938002A CN 201911341417 A CN201911341417 A CN 201911341417A CN 110938002 A CN110938002 A CN 110938002A
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- bromofluorobenzene
- fluoroaniline
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
- C07C209/04—Preparation of compounds containing amino groups bound to a carbon skeleton by substitution of functional groups by amino groups
- C07C209/06—Preparation of compounds containing amino groups bound to a carbon skeleton by substitution of functional groups by amino groups by substitution of halogen atoms
- C07C209/10—Preparation of compounds containing amino groups bound to a carbon skeleton by substitution of functional groups by amino groups by substitution of halogen atoms with formation of amino groups bound to carbon atoms of six-membered aromatic rings or from amines having nitrogen atoms bound to carbon atoms of six-membered aromatic rings
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Abstract
The application relates to a preparation method of m-fluoroaniline, which comprises the following steps: carrying out amination reaction on m-bromofluorobenzene and ammonia water in the presence of N, N-dimethylformamide and cuprous oxide, wherein the ammonia water is added for multiple times until the m-bromofluorobenzene is completely reacted through chromatographic detection, and separating and purifying to obtain the m-fluoroaniline. The method has the advantages of mild reaction conditions and high molar yield, and is suitable for industrial production.
Description
Technical Field
The invention relates to the technical field of chemical synthesis, in particular to a preparation method of m-fluoroaniline.
Background
M-fluoroaniline is a key raw material for the manufacture of pharmaceuticals, pesticides, agrochemicals, and is also a key intermediate for the manufacture of azo dyes and pigments. The traditional method for producing m-fluoroaniline comprises the following steps:
(1) m-chloro aniline is used as an initial raw material, m-chloro-benzene is obtained through a Schiemann reaction, m-chloro-benzene is obtained through an amination reaction, m-fluoroaniline is obtained through the amination reaction, the pyrolysis and the amination reaction are carried out at high temperature and high pressure, and the reaction conditions are harsh.
(2) The m-bromofluorobenzene is used as an initial raw material, and CuI catalyzes the reaction of the m-bromofluorobenzene and ammonia water in the presence of PEG-400, water and sodium phosphate to obtain the m-fluoroaniline.
Therefore, the search for a preparation method of m-fluoroaniline, which has mild reaction conditions and high molar yield and is suitable for industrial production, is still needed.
Disclosure of Invention
Based on the above, it is necessary to provide a method for producing m-fluoroaniline, which has mild reaction conditions and a high molar yield and is suitable for industrial production.
A preparation method of m-fluoroaniline comprises the following steps:
carrying out amination reaction on m-bromofluorobenzene and ammonia water in the presence of N, N-dimethylformamide and cuprous oxide, adding ammonia water for multiple times until the m-bromofluorobenzene is completely reacted through chromatographic detection, and separating and purifying to obtain m-fluoroaniline;
the mass ratio of the N, N-dimethylformamide to the m-bromofluorobenzene is (2-5): 1, the molar ratio of the cuprous oxide to the m-bromofluorobenzene is (0.05-0.2): 1, and NH is added into the ammonia water3·H2The molar ratio of O to m-bromofluorobenzene is (6.25-10): 1.
In one embodiment, the temperature of the amination reaction is between 50 ℃ and 100 ℃.
In one embodiment, the temperature of the amination reaction is from 55 ℃ to 75 ℃.
In one embodiment, the molar ratio of the cuprous oxide to the m-bromofluorobenzene is (0.1-0.2): 1.
In one embodiment, the ammonia water is added in four times, the mass ratio of the adding amount of the first ammonia water to the m-bromofluorobenzene is 2:1, and the mass ratio of the adding amount of the residual ammonia water to the m-bromofluorobenzene is 1: 1.
In one embodiment, the ammonia water is 25-28% ammonia water by mass concentration.
In one embodiment, the chromatographic assay is a high performance liquid chromatographic assay.
In one embodiment, the method for separation and purification comprises the following steps: adding methyl tert-butyl ether for extraction, washing with water to remove N, N-dimethylformamide, and distilling under reduced pressure.
In one embodiment, the preparation method of the m-fluoroaniline further comprises the following steps:
recovering the methyl tert-butyl ether for recycling.
The m-fluoroaniline is prepared by using N, N-dimethylformamide as a solvent, cuprous oxide as a catalyst, m-bromofluorobenzene and ammonia water as raw materials, controlling the dosage proportion of the N, N-dimethylformamide, the cuprous oxide, the m-bromofluorobenzene and the ammonia water, and adding the ammonia water for multiple times, so that the m-bromofluorobenzene and the ammonia water can perform amination reaction at a lower temperature to obtain the m-fluoroaniline, wherein the reaction conditions are mild, the molar yield can reach more than 85%, and the m-fluoroaniline is suitable for industrial production.
Detailed Description
In order that the invention may be more fully understood, a more particular description of the invention will now be rendered by reference to specific embodiments thereof that are illustrated in the appended drawings. This invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The terminology used in the description of the invention herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. As used herein, the term "and/or" includes any and all combinations of one or more of the associated listed items.
The method for preparing m-fluoroaniline of one embodiment comprises the steps of:
carrying out amination reaction on m-fluoroaniline and ammonia water in the presence of N, N-dimethylformamide and cuprous oxide, wherein the ammonia water is added for multiple times until m-bromofluorobenzene is completely reacted through chromatographic detection, and separating and purifying to obtain the m-fluoroaniline.
Wherein the mass ratio of N, N-Dimethylformamide (DMF) to m-bromofluorobenzene is (2-5) to 1. Mole of cuprous oxide and m-bromofluorobenzeneThe ratio is (0.05-0.2) to 1. NH in ammonia3·H2The molar ratio of O to m-bromofluorobenzene is (6.25-10): 1.
Furthermore, the molar ratio of the cuprous oxide to the m-bromofluorobenzene is (0.1-0.2): 1.
Further, the temperature of amination reaction is 50-100 ℃. Further, the temperature of the amination reaction is 55 ℃ to 75 ℃.
Through a large number of experiments, the inventor of the application finds that the selection of a solvent DMF and the control of the relative dosage of DMF, m-bromofluorobenzene, cuprous oxide and ammonia water are of great importance for amination of m-fluoroaniline at a lower temperature. By controlling the relative dosage of DMF and m-bromofluorobenzene, the m-fluoroaniline and ammonia water can be ensured to be in full contact reaction in the presence of cuprous oxide serving as a catalyst, the reaction yield is effectively improved, the reaction condition is mild, and the method is suitable for industrial production.
Furthermore, ammonia water is added for multiple times, so that the m-bromofluorobenzene can be ensured to react completely, and the method is crucial to the improvement of the reaction yield.
In this embodiment, the ammonia is added in four portions. The mass ratio of the added amount of the first ammonia water to the m-bromofluorobenzene is 2:1, so that the ammonia water and the m-bromofluorobenzene are in full contact reaction under the action of DMF and cuprous oxide, the mass ratio of the added amount of the remaining ammonia water to the m-bromofluorobenzene is 1:1, on one hand, the ammonia gas volatilized in the reaction process is compensated, so that the m-bromofluorobenzene is ensured to be reacted completely, the reaction yield is further improved, on the other hand, the ammonia water is used as an acid binding agent for neutralizing HBr generated in the reaction process, and the corrosion of strong acid to equipment is prevented while the reaction is promoted.
Further, in the present embodiment, the mass concentration of the aqueous ammonia is 25% to 28%, that is, NH in the aqueous ammonia3·H2The mass content of O is 25-28%.
Furthermore, in order to improve the reaction precision, the embodiment adopts high performance liquid chromatography to monitor whether the m-bromofluorobenzene reaction is complete.
Further, the separation and purification method comprises the following steps: adding methyl tert-butyl ether (MTBE) for extraction, washing with water to remove DMF, and distilling under reduced pressure.
It can be understood that MTBE is added for extraction, DMF and m-fluoroaniline can be extracted into an organic phase, impurities such as salts generated in the reaction and excessive ammonia water are removed, DMF is removed by washing with water, an organic phase containing MTBE and m-fluoroaniline is obtained, and the m-fluoroaniline can be obtained by reduced pressure distillation.
HPLC detection shows that the purity of the m-fluoroaniline obtained by the method is more than 99%.
Further, the preparation method of the m-fluoroaniline also comprises the step of recovering MTBE for recycling.
It can be understood that a small amount of m-fluoroaniline is still carried into MTBE after separation and purification, and the recovery and reuse of MTBE can further improve the reaction yield.
The preparation method of m-fluoroaniline has mild amination reaction conditions, the reaction molar yield can reach more than 85 percent, and the method is suitable for industrial production.
The following are specific examples.
Example 1
DMF (700g) was added to a 2.0L three-necked flask, m-bromofluorobenzene (350g, 2mol) was added, ammonia (700g) was added, and cuprous oxide (28.6g, 0.2mol) was added. Heating to 70 ℃, supplementing 350g of ammonia water every other time for 3 times (all ammonia water is 12.5mol), monitoring the reaction by HPLC, and judging whether the raw materials are completely reacted at the wavelength of 194nm and 17 min.
And (3) post-treatment:
MTBE is adopted for extraction, the spot plate is washed by water, the light product spot is washed by water, the extraction is clean, the upper layer organic phase is combined, after DMF is removed by water washing, reduced pressure distillation is carried out, 185g m-fluoroaniline is obtained, and the molar yield is 85%.
The purity of the m-fluoroaniline is over 99 percent through HPLC detection.
Example 2
DMF (1750g) was added to a 2.0L three-necked flask, m-bromofluorobenzene (350g, 2mol) was added, ammonia was added, and cuprous oxide (57.2g, 0.4mol) was added. Heating to 75 ℃, replenishing ammonia water (2800 g and 20mol of all ammonia water) at intervals, monitoring the reaction by HPLC, and judging whether the raw materials react completely at the wavelength of 194nm and 17 min.
And (3) post-treatment:
the MTBE recovered in example 1 is used for extraction, washing the dotted plate with water to obtain a very light product dot, the extraction is clean, the upper organic phases are combined, DMF is removed by washing with water, and the reduced pressure distillation is carried out to obtain 193g of m-fluoroaniline with the molar yield of 87%.
The purity of the m-fluoroaniline is over 99 percent through HPLC detection.
Comparative example 1
Comparative example 1 was substantially the same as in example 1 except that the amount of DMF added in comparative example 1 was 350g, resulting in 35.5g of m-fluoroaniline with a molar yield of 16%.
Comparative example 2
Comparative example 2 was substantially the same as in example 1 except that aqueous ammonia in comparative example 2 was added in one portion, resulting in 162g of m-fluoroaniline with a molar yield of 73%.
The above-mentioned embodiments only express several embodiments of the present invention, and the description thereof is more specific and detailed, but not construed as limiting the scope of the present invention. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention. Therefore, the protection scope of the present patent shall be subject to the appended claims.
Claims (9)
1. The preparation method of m-fluoroaniline is characterized by comprising the following steps:
carrying out amination reaction on m-bromofluorobenzene and ammonia water in the presence of N, N-dimethylformamide and cuprous oxide, adding ammonia water for multiple times until the m-bromofluorobenzene is completely reacted through chromatographic detection, and separating and purifying to obtain m-fluoroaniline;
the mass ratio of the N, N-dimethylformamide to the m-bromofluorobenzene is (2-5): 1, the molar ratio of the cuprous oxide to the m-bromofluorobenzene is (0.05-0.2): 1, and NH is added into the ammonia water3·H2The molar ratio of O to m-bromofluorobenzene is (6.25-10): 1.
2. A process for the preparation of m-fluoroaniline according to claim 1, wherein the temperature of the amination reaction is from 50 ℃ to 100 ℃.
3. A process for the preparation of m-fluoroaniline according to claim 2, wherein the temperature of the amination reaction is from 55 ℃ to 75 ℃.
4. The method for preparing m-fluoroaniline according to claim 1, wherein the molar ratio of the cuprous oxide to the m-bromofluorobenzene is (0.1-0.2): 1.
5. The preparation method of m-fluoroaniline according to claim 1, characterized in that the ammonia water is added in four times, the mass ratio of the amount of the first ammonia water to the m-bromofluorobenzene is 2:1, and the mass ratio of the amount of the remaining ammonia water to the m-bromofluorobenzene is 1: 1.
6. The process for producing m-fluoroaniline according to claim 1, wherein the aqueous ammonia is 25% to 28% by mass aqueous ammonia.
7. The process for preparing m-fluoroaniline according to claim 1, wherein the chromatographic detection is high performance liquid chromatographic detection.
8. The process for producing m-fluoroaniline according to claim 1, wherein the separation and purification is carried out by: adding methyl tert-butyl ether for extraction, washing with water to remove N, N-dimethylformamide, and distilling under reduced pressure.
9. The process for preparing m-fluoroaniline according to claim 8, further comprising the steps of:
recovering the methyl tert-butyl ether for recycling.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201911341417.3A CN110938002A (en) | 2019-12-24 | 2019-12-24 | Preparation method of m-fluoroaniline |
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| CN201911341417.3A CN110938002A (en) | 2019-12-24 | 2019-12-24 | Preparation method of m-fluoroaniline |
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