CN101245020B - Process for synthesizing 2,3-difluoroaniline - Google Patents
Process for synthesizing 2,3-difluoroaniline Download PDFInfo
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- CN101245020B CN101245020B CN2008100601347A CN200810060134A CN101245020B CN 101245020 B CN101245020 B CN 101245020B CN 2008100601347 A CN2008100601347 A CN 2008100601347A CN 200810060134 A CN200810060134 A CN 200810060134A CN 101245020 B CN101245020 B CN 101245020B
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- difluoroaniline
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- HDICWUVDMSMJHH-UHFFFAOYSA-N CC(CCCC1F)=C1F Chemical compound CC(CCCC1F)=C1F HDICWUVDMSMJHH-UHFFFAOYSA-N 0.000 description 1
- BUZZBYDJBBGXNT-UHFFFAOYSA-N FC1=[F]CCC=CC=C1 Chemical compound FC1=[F]CCC=CC=C1 BUZZBYDJBBGXNT-UHFFFAOYSA-N 0.000 description 1
- 0 N*(C1F)C#CCCC1F Chemical compound N*(C1F)C#CCCC1F 0.000 description 1
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Abstract
The invention provides a method for synthesizing 2,3-difluroaniline, which adopts 2,3-dichloronitrobenzene to be reaction initiators, 2,3-difluorochlorobenzene is obtained after a fluorination reaction, a reduction reaction, and a heman reaction in order, then the 2,3-difluroaniline is obtained after an amination reaction; the synthesizing method can use the cheap 2,3-dichloronitrobenzene as initial materials to obtain high-yield 2,3-difluroaniline through the technique with low cost.
Description
Technical field
The present invention relates to 2, the synthetic method of 3-difluoroaniline.
Background technology
2, the 3-difluoroaniline serves many purposes, and can be used as the intermediate of producing medicine and LCD product.Produce 2, the known method of 3-difluoroaniline has: a, 1,2, and the amination of 3-trifluoro-benzene, but there is the shortcoming that raw material sources are difficult for, price is high, the amination yield is low in this method, is not suitable for suitability for industrialized production.
Summary of the invention
It is a kind of cheaply 2 that technical problem to be solved by this invention provides, 3-difluoroaniline synthetic method.For this reason, the present invention by the following technical solutions: it is with 2, and the 3-dichloronitrobenzene is a start material, obtains 2 through fluoridation, reduction reaction, schiemann reaction successively, and 3-two fluorochlorobenzenes obtain 2 through amination reaction again, the 3-difluoroaniline.Owing to adopt technical scheme of the present invention, the present invention can be with cheap 2, and the 3-dichloronitrobenzene is a starting raw material, obtains 2 of high yield, the 3-difluoroaniline by technology cheaply.
Embodiment
Embodiment 1
1), the preparation of 3-chloro-2-fluoronitrobenzene
With 2,3-dichloronitrobenzene 192g (1.0mol) and anhydrous K F69.6g (1.2mol) and dimethyl sulfoxide (DMSO) (DMSO) 200g join in the 500ml four-hole reaction flask and carry out fluoridation, open temperature to 170～175 ℃ of insulation reaction 8h, be cooled to 50 ℃, the 150ml toluene drip washing of filtration, filter cake, merging filtrate, elder generation's distillating recovering solvent, rectification under vacuum gets 3-chloro-2-fluoronitrobenzene 142.2g, yield 81%, content＞99.5% again.
Reaction equation:
2), the preparation of 3-chloro-2-fluoroaniline
In the withstand voltage reactor of 1000ml, add 3-chloro-2-fluoronitrobenzene 230g (1.31mol), methyl alcohol 460ml, Raney's nickel catalyst 7g, go out to use hydrogen exchange 3 times in the still behind the air again with nitrogen replacement, fill H2 to 1.5MPa then, carry out reduction reaction till do not inhale hydrogen at 35～45 ℃, filter, filtrate reclaims methyl alcohol, underpressure distillation again, obtain 3-chloro-2-fluoroaniline 182g, yield 95.5%.
Reaction equation:
In reduction reaction of the present invention, the reaction yield of hydrogenating reduction and iron powder reducing much at one, though the iron powder reducing cost is low slightly, but environmental pollution is serious, do not meet the cleaner production requirement, hydrogenating reduction more meets the recycling industries and clean production requirement, so select for use hydrogenation reaction better.
3), by schiemann reaction preparation 2,3-two fluorochlorobenzenes promptly carry out pyrolysis preparation 2,3-two fluorochlorobenzenes again after the diazotization reaction.
Add 30% hydrochloric acid 130g, water 60ml in the 500ml four-hole reaction flask, add 3-chloro-2-fluoroaniline 72.8g (0.5mol) again, carry out diazotization reaction, be cooled to-5 ℃ then, drip 30% sodium nitrite solution 120g (0.52mol), finish, insulation reaction 30min drips 40% fluoroboric acid 137.5g (0.625mol) at-5～0 ℃ then, finish at-5～0 ℃ of reaction 30min, filter,, get the diazonium fluoride borate with the drip washing of 50ml methyl alcohol, oven dry.
Above-mentioned diazonium fluoride borate can get 2 180～220 ℃ of thermolysiss, 3-two fluorochlorobenzene 58.3g, yield 78.5%.
Reaction equation:
4), 2, the preparation of 3-difluoroaniline
Add 29% ammoniacal liquor 230g, 2 in the withstand voltage reactor of 500ml, 3-two fluorochlorobenzene 74.25g (0.5mol), Red copper oxide 1.6g airtightly are warming up to 175～180 ℃, the about 4.0MPa reaction of pressure 10h, cooling adds 50%NaOH solution 40g, add methyl tertiary butyl ether 100g again and stir 30min to extract 2, the 3-difluoroaniline is told organic layer, rectification under vacuum behind the recovery solvent, get 2,3-difluoroaniline 58.0g, yield is about 90%, content＞99.5%.
Reaction equation:
Embodiment 2
Present embodiment provides the embodiment of one group of fluoridation of the present invention, in the present embodiment, and except temperature of reaction, the step among other condition and the embodiment 1 " 1) " identical, following table is the cartogram of experimental data:
| ?DMSO(g) | 2,3-dichloronitrobenzene (g) | Potassium monofluoride (g) | Temperature of reaction (℃) | Yield (%) |
| ?200 | 192 | ?69.6 | 100-110 | 18.9 |
| 200 | 192 | 69.6 | 160-165 | 69.7 |
| 200 | 192 | 69.6 | 170-175 | 81.0 |
| 200 | 192 | 69.6 | 180-185 | 75.3 |
| 200 | 192 | 69.6 | 190-195 | 64.6 |
| 200 | 192 | 69.6 | 240-250 | 21.2 |
Conclusion: on fluoridation temperature of reaction of the present invention is selected, best with 170-175 ℃ effect.
Embodiment 3, in the fluoridation of the present invention, and the selection of strong polar aprotic solvent.
Fluoridation of the present invention is preferably in the strong polar aprotic solvent carries out, described strong polar aprotic solvent serves as preferred with following material: N, dinethylformamide (DMF), dimethyl sulfoxide (DMSO) (DMSO), tetramethylene sulfone or 1,3-dimethyl-2-imidazolone (DMI).
In the present embodiment, respectively with N, dinethylformamide (DMF), tetramethylene sulfone or 1, dimethyl sulfoxide (DMSO) (DMSO) in the 3-dimethyl-2-imidazolone (DMI) alternate embodiment 1 step " 1) ", carry out fluoridation at 170～175 ℃ respectively, step among other reaction conditions and the embodiment 1 " 1) " identical
Following table is the cartogram of experimental data:
| Solvent | 2,3-dichloronitrobenzene (g) | Potassium monofluoride (g) | Temperature of reaction (℃) | Content (%) | Yield (%) | |
| Title | Quantity (g) | |||||
| DMSO | ?200 | 192 | 69.6 | 170-175 | 99.8 | 81.0 |
| DMF | ?200 | 192 | 69.6 | 170-175 | 99.6 | 67.8 |
| DMI | ?200 | 192 | 69.6 | 170-175 | 99.6 | 55.6 |
| Tetramethylene sulfone | ?200 | 192 | 69.6 | 170-175 | 99.8 | 70.1 |
Conclusion: in synthetic method of the present invention to select for use dimethyl sulfoxide (DMSO) (DMSO) best as the solvent effect of fluoridation.
Embodiment 4
In amination reaction of the present invention, selection of catalysts is preferably the oxide compound of copper.Present embodiment provides the embodiment of one group of amination reaction of the present invention, and following table is the cartogram of experimental data:
| 2.3-two fluorochlorobenzenes (g) | Red copper oxide (g) | Ammoniacal liquor (g) | Temperature (℃) | Pressure (MPa) | Yield (%) |
| 74.25 | 1.0 | 230 | 175-180 | 4.0 | 43.1 |
| 74.25 | 1.45 | 230 | 175-180 | 4.0 | 86.7 |
| 74.25 | 1.60 | 230 | 175-180 | 4.0 | 90.1 |
| 74.25 | 1.75 | 230 | 175-180 | 4.0 | 90 |
| 74.25 | 1.90 | 230 | 175-180 | 4.0 | 90.1 |
Conclusion: in the amination reaction of the present invention, 2,3-two fluorochlorobenzenes are when the weight ratio of Red copper oxide is more than 1: 0.0215 times, and yield is basic identical, so this ratio is a preferred forms.
Embodiment 5
Present embodiment carries out amination reaction with cupric oxide as catalyzer, and the consumption of Red copper oxide is corresponding identical respectively among cupric oxide consumption and the embodiment 4, and other reaction conditions is also identical with embodiment 4, and following table is the cartogram of experimental data:
| 2,3-two fluorochlorobenzenes (g) | Cupric oxide (g) | Ammoniacal liquor (g) | Temperature (℃) | Pressure (MPa) | Yield (%) |
| 74.25 | 1.0 | 230 | 175-180 | 4.0 | 31.6 |
| 74.25 | 1.45 | 230 | 175-180 | 4.0 | 73.4 |
| 74.25 | 1.60 | 230 | 175-180 | 4.0 | 85.1 |
| 74.25 | 1.75 | 230 | 175-180 | 4.0 | 85.3 |
| 74.25 | 1.90 | 230 | 175-180 | 4.0 | 85.1 |
Conclusion: in the amination reaction of the present invention, select for use Red copper oxide best as catalyst effect.
Claims (8)
1.2,3-difluoroaniline synthetic method, it is characterized in that it is with 2, the 3-dichloronitrobenzene is a start material, obtains 3-chloro-2-fluoronitrobenzene through fluoridation successively, obtains 3-chloro-2-fluoroaniline through reduction reaction then, obtain 2 through schiemann reaction again, 3-two fluorochlorobenzenes, after amination reaction obtains 2, the 3-difluoroaniline.
2. as claimed in claim 12,3-difluoroaniline synthetic method is characterized in that it is carrying out fluoridation in strong polar aprotic solvent.
3. as claimed in claim 22,3-difluoroaniline synthetic method is characterized in that described strong polar aprotic solvent is N, dinethylformamide DMF, dimethyl sulfoxide (DMSO) DMSO, tetramethylene sulfone or 1,3-dimethyl-2-imidazolone DMI.
4. as claimed in claim 12,3-difluoroaniline synthetic method is characterized in that it carries out fluoridation in dimethyl sulfoxide (DMSO) DMSO.
5. as claimed in claim 12,3-difluoroaniline synthetic method, the temperature that it is characterized in that fluoridation is 100～250 degrees centigrade.
6. as claimed in claim 12,3-difluoroaniline synthetic method, the temperature that it is characterized in that fluoridation is 170～175 degrees centigrade.
7. as claimed in claim 12,3-difluoroaniline synthetic method is characterized in that described reduction reaction adopts hydrogenating reduction or iron powder reducing.
8. as claimed in claim 12,3-difluoroaniline synthetic method is characterized in that it is catalyzer that described amination reaction adopts Red copper oxide or cupric oxide.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102173995B (en) * | 2011-03-28 | 2013-01-23 | 郓城县世炬化工有限公司 | Synthesis method of m-fluoroaniline |
| WO2014103947A1 (en) | 2012-12-25 | 2014-07-03 | 日本曹達株式会社 | Halogenated aniline and method for producing same |
| CN103497111B (en) * | 2013-09-09 | 2015-10-21 | 江苏德峰药业有限公司 | A kind of synthetic method of 2,3,4-trifluoromethyl aniline |
| JP6182507B2 (en) * | 2014-05-30 | 2017-08-16 | 日本曹達株式会社 | Method for producing 2,3-dihalogenoaniline |
| CN113024372A (en) * | 2021-03-12 | 2021-06-25 | 内蒙古蓝科生物科技有限公司 | Synthetic method of 2-chloro-3-fluoro-4-trifluoromethyl benzoyl chloride |
| CN113666828B (en) * | 2021-09-22 | 2023-12-05 | 黔南高新区绿色化工技术研究院有限公司 | Method for preparing p-nitroaniline by catalyzing ammonolysis of p-nitrochlorobenzene |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5091580A (en) * | 1991-03-27 | 1992-02-25 | Dowelanco | Process for the preparation of 2,6-difluoroaniline |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5091580A (en) * | 1991-03-27 | 1992-02-25 | Dowelanco | Process for the preparation of 2,6-difluoroaniline |
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