CN105622426A - Preparation method of 4-fluoro -N-methyl-3-nitroaniline - Google Patents
Preparation method of 4-fluoro -N-methyl-3-nitroaniline Download PDFInfo
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- C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
- C07C209/24—Preparation of compounds containing amino groups bound to a carbon skeleton by reductive alkylation of ammonia, amines or compounds having groups reducible to amino groups, with carbonyl compounds
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Abstract
The invention relates to a preparation method of 4-fluoro-N-methyl-3-nitroaniline. The preparation method includes the following steps: (1) performing methylation, to be more specific, taking 4-fluoro-3-nitroaniline as a raw material, sulfuric acid 60-98% in mass concentration as solvent and formaldehyde as a methylating agent to react with one another at the temperature of 20-60 DEG C to obtain methylation solution; (2) performing neutralization, to be more specific, dropwise adding the methylation solution into mixed solution of ammonium hydroxide 10-28% in mass concentration and organic solvent, and then performing reflux cooling filtering or liquid separation concentration to obtain a 4-fluoro-N-methyl-3-nitroaniline crude product; (3) performing purification, to be more specific, subjecting the 4-fluoro-N-methyl-3-nitroaniline crude product to crystallization and drying to obtain a 4-fluoro -N-methyl-3-nitroaniline refined product. The preparation method is simple in process, simple in product aftertreatment and low in environmental pollution, the prepared 4-fluoro-N-methyl-3-nitroaniline is high in product quality and good in stability and can be used for general purposes as well as preparation of high-end resin, and the method is suitable for industrial preparation.
Description
Technical field
The preparation method that the present invention relates to a kind of organic chemical intermediates, the preparation method especially relating to the fluoro-N-methyl-3-nitro aniline of 4-of a kind of high-quality.
Background technology
The fluoro-N-methyl-3-nitro aniline of 4-belongs to amino benzenes compounds, is a kind of important chemical industry, medicine intermediate, can be used for multiple fields such as dyestuff, hair dye, medicine, pesticide.
About 4-fluoro-N-methyl-3-nitro aniline preparation method report less, it is now known that the preparation method about 4-fluoro-N-methyl-3-nitro aniline have: adopt formaldehyde sulfuric acid system carry out the methylated method of amino benzenes compounds. With the sulphuric acid of 8 times of quality for solvent, the paraformaldehyde of 1.58 times of quality is methylating reagent, is diluted in frozen water by reactant liquor after having reacted, through product is obtained by extraction. But, above-mentioned preparation method, last handling process can generate substantial amounts of side-product, be difficult to refining removing, actual mass yield is less than 50%, and purity is extremely difficult to more than 95%, and when producing when adopting the method to amplify, problem is particularly acute. Adopt the method can produce substantial amounts of ammonium sulfate abraum salt simultaneously, seriously polluted, it is more difficult to realize industrialized production.
In order to improve the inherent quality of the fluoro-N-methyl-3-nitro aniline of 4-, improving the yield of product and the stability of production, the present invention provides a kind of method preparing the fluoro-N-methyl-3-nitro aniline of high-quality 4-through repeatedly trial.
Summary of the invention
For the deficiency overcoming prior art to exist; the preparation method that the invention provides the fluoro-N-methyl-3-nitro aniline of a kind of new high-quality 4-; reduce environmental pollution while product quality quality improving, make production clean, environmental protection, make product production in enormous quantities preferably.
The preparation method of the fluoro-N-methyl-3-nitro aniline of a kind of 4-, comprises the steps:
(1) methylation reaction: with the fluoro-3-nitroaniline of 4-for raw material, with mass concentration be 60��98% sulphuric acid for solvent, formaldehyde is methylating reagent, is obtained by reacting methylation reaction liquid at 20��60 DEG C;
(2) neutralize: methylation reaction drop is added to ammonia that mass concentration is 10��28% and in the mixed liquor of organic solvent, filters or separatory concentration obtains 4-fluoro-N-methyl-3-nitro aniline crude product through backflow cooling after being added dropwise to complete;
(3) purification: 4-fluoro-N-methyl-3-nitro aniline crude product is crystallized, obtain 4-fluoro-N-methyl-3-nitro aniline highly finished product after drying.
Synthetic route of the present invention is as follows:
The present invention is with the fluoro-3-nitroaniline of 4-for raw material, with sulphuric acid for solvent, formaldehyde is methylating reagent, carry out methylation reaction at a certain temperature, then reactant liquor is diluted to according to a certain percentage in the mixed solution of ammonia and organic solvent and refluxes, being filtrated to get the purified rear purity of product high, quality is good, and this synthetic method is suitable for industrialized production.
As preferably, in step (1), the weight ratio of sulphuric acid and the fluoro-3-nitroaniline of raw material 4-is 2��7.5:1; Described formaldehyde is the one in metaformaldehyde, paraformaldehyde, formalin, and its weight ratio with the fluoro-3-nitroaniline of raw material 4-is 0.3��1.4:1.
As preferably, in step (1), methylation reaction temperature is 30��50 DEG C.
As preferably, in step (2), the weight ratio 4��10:1 of ammonia and the fluoro-3-nitroaniline of raw material 4-; Described organic solvent is the combination in any of one or two or more kinds in methanol, ethanol, isopropanol, toluene, oxolane, methyl tertiary butyl ether(MTBE), the weight ratio 3��10:1 of its consumption and the fluoro-3-nitroaniline of raw material 4-.
As preferably, in step (2), dropping temperature controls at-10��20 DEG C, time for adding 1��20h.
As preferably, in step (3), the organic solvent of crystallization is low-boiling point alcohol, and described low-boiling point alcohol is the one in methanol, ethanol, isopropanol, and the weight ratio of its consumption and the fluoro-N-methyl-3-nitro aniline of raw material 4-is 3��8:1.
As preferably, in step (3), baking temperature is 30��70 DEG C.
As preferably, the preparation method of the fluoro-N-methyl-3-nitro aniline of described 4-, comprise the steps:
(1) methylation reaction: with 80��98% concentration sulphuric acid for solvent, paraformaldehyde is methylating reagent, and methylation reaction temperature controls at 30��50 DEG C; Wherein, the fluoro-3-nitroaniline of 4-, sulphuric acid, paraformaldehyde weight ratio be 1:3��6:0.5��1.2;
(2) neutralize: methylation reaction drop is added in the mixed liquor of 15��25% ammonia and methanol, dropping temperature controls between 0��15 DEG C, time for adding controls at 1.5��12h, backflow it is warming up to after being added dropwise to complete, after backflow a period of time, it is cooled to less than 5 DEG C and is filtrated to get 4-fluoro-N-methyl-3-nitro aniline crude product; Wherein, the fluoro-3-nitroaniline of 4-, ammonia, methanol weight ratio be 1:5��9:4��8;
(3) purification: 4-fluoro-N-methyl-3-nitro aniline crude product adds in methanol and is warming up to backflow, then cooled crystallization, filtration, dry to obtain 4-fluoro-N-methyl-3-nitro aniline highly finished product; Wherein, methanol is 4��7:1 with the weight ratio of the fluoro-N-methyl-3-nitro aniline of 4-; Baking temperature is 40��60 DEG C.
As preferably, the preparation method of the fluoro-N-methyl-3-nitro aniline of described 4-, comprise the steps:
(1) sucking mass concentration in 1000L enamel reaction still R1 is 98% sulphuric acid 1125kg, put into the fluoro-3-nitroaniline 250kg of 4-, putting into exothermic heat of reaction during 4-fluoro-3-nitroaniline, the logical recirculated water of R1 chuck controls temperature at 30��35 DEG C, is warming up to 45 DEG C after finishing; Being dividedly in some parts 250kg paraformaldehyde at such a temperature, every 0.5h adds 25kg paraformaldehyde, finishes, and after insulation reaction 2h, sampling HPLC detection reacts completely to the fluoro-3-nitroaniline of raw material 4-, is cooled to 20 DEG C, standby;
(2) 5000L enamel reaction still R2 sucks 25% ammonia 1752kg and methanol 1440kg, the logical brine ice of R2 chuck is cooled to less than 10 DEG C, start to drip methylation reaction liquid, control dropping temperature at 12��15 DEG C, time for adding 10h, after dropwising, it is warming up to 65��70 DEG C of backflow 1h, sampling HPLC detects to the 4-fluoro-N-main content of methyl-3-nitro aniline > 95%, it is cooled to less than 5 DEG C again, it is discharged in filtering jar, 2400kg water washing filter cake, it is then centrifuged for obtaining 4-fluoro-N-methyl-3-nitro aniline crude product;
(3) fluoro-for the 4-obtained N-methyl-3-nitro aniline crude product is put in methanol 1300kg again, be warming up to 60 DEG C, insulated and stirred 30min, then 5��10 DEG C it are cooled to, it is discharged in filtering jar, centrifugal, obtain 4-fluoro-N-methyl-3-nitro aniline highly finished product after drying.
Present invention process is simple, product post processing is easy, environmental pollution is little, the 4-fluoro-N-methyl-3-nitro aniline product quality quality prepared is high, good stability, the product prepared is except may be used for general applications, it is also possible to for the preparation of high-end resin, be a kind of method of applicable preparation of industrialization.
Detailed description of the invention
Below in conjunction with specific embodiment, the invention will be further described, but invention which is intended to be protected is not limited to this.
Embodiment 1
Take the fluoro-3-nitroaniline of 40g4-and 180g mass concentration is the sulphuric acid of 90%, stir at 25 DEG C of temperature, it is warming up to 40��45 DEG C, it is dividedly in some parts 42.3g paraformaldehyde (every 0.5h adds 7.7g paraformaldehyde) at such a temperature, finish, after insulation reaction 2h, it is cooled to 20 DEG C, standby (methylation reaction liquid).
Take 280g mass concentration and be 25% ammonia and 240g methanol is cooled to less than 10 DEG C, start to drip methylation reaction liquid, control dropping temperature at 10��15 DEG C, time for adding 1.5h, after dropwising, being warming up to 65��70 DEG C of backflow 1h, then be cooled to less than 5 DEG C, crystallize is filtrated to get 4-fluoro-N-methyl-3-nitro aniline crude product 42g.
Crude product adds in 200g methanol and is warming up to backflow, is then cooled to 10 DEG C of sucking filtration, 400g water washing filter cake, and 60 DEG C dry obtains 4-fluoro-N-methyl-3-nitro aniline highly finished product 40.5g, and yield is 92.9%, product HPLC >=99.2%.
Embodiment 2
Sucking mass concentration in 1000L enamel reaction still R1 is 98% sulphuric acid 1125kg, puts into the fluoro-3-nitroaniline 250kg of 4-, puts into exothermic heat of reaction during 4-fluoro-3-nitroaniline, and the logical recirculated water of R1 chuck controls temperature at 30��35 DEG C, is warming up to 45 DEG C after finishing. Being dividedly in some parts 250kg paraformaldehyde (every 0.5h adds 25kg paraformaldehyde) at such a temperature, finish, after insulation reaction 2h, sampling HPLC detection reacts completely to the fluoro-3-nitroaniline of raw material 4-, is cooled to 20 DEG C, standby.
5000L enamel reaction still R2 sucks 25% ammonia 1752kg and methanol 1440kg, the logical brine ice of R2 chuck is cooled to less than 10 DEG C, start to drip methylation reaction liquid, control dropping temperature at 12��15 DEG C, time for adding 10h, after dropwising, it is warming up to 65��70 DEG C of backflow 1h, sampling HPLC detects to the 4-fluoro-N-main content of methyl-3-nitro aniline > 95%, it is cooled to less than 5 DEG C again, it is discharged in filtering jar, 2400kg water washing filter cake, it is then centrifuged for obtaining 4-fluoro-N-methyl-3-nitro aniline crude product 270kg, fluoro-for the 4-obtained N-methyl-3-nitro aniline crude product is put in methanol 1300kg again, it is warming up to 60 DEG C, insulated and stirred 30min, then 5��10 DEG C it are cooled to, it is discharged in filtering jar, centrifugal, 4-fluoro-N-methyl-3-nitro aniline highly finished product 260kg is obtained after drying, yield is 95.4%, product HPLC >=99.9%.
Embodiment 3
Take the fluoro-3-nitroaniline of 40g4-and 220g mass concentration is the sulphuric acid of 80%, stir at 25 DEG C of temperature, it is warming up to 40��45 DEG C, it is dividedly in some parts 30g paraformaldehyde (every 0.5h adds 6g paraformaldehyde) at such a temperature, finish, after insulation reaction 2h, it is cooled to 20 DEG C, standby (methylation reaction liquid).
Take 320g mass concentration and be 15% ammonia and 320g methanol is cooled to less than 10 DEG C, start to drip methylation reaction liquid, control dropping temperature at 5��10 DEG C, time for adding 1.5h, after dropwising, being warming up to 65��70 DEG C of backflow 1h, then be cooled to less than 5 DEG C, crystallize is filtrated to get 4-fluoro-N-methyl-3-nitro aniline crude product 40g.
Crude product adds in 240g methanol and is warming up to backflow, is then cooled to 10 DEG C of sucking filtration, 400g water washing filter cake, and 50 DEG C dry obtains 4-fluoro-N-methyl-3-nitro aniline highly finished product 36.4g, and yield is 83.5%, product HPLC >=99.0%.
Embodiment 4
Take the fluoro-3-nitroaniline of 40g4-and 150g mass concentration is the sulphuric acid of 90%, stir at 25 DEG C of temperature, it is warming up to 45��50 DEG C, it is dividedly in some parts 45g paraformaldehyde (every 0.5h adds 7.5g paraformaldehyde) at such a temperature, finish, after insulation reaction 2h, it is cooled to 20 DEG C, standby (methylation reaction liquid).
Take 250g mass concentration and be 25% ammonia and 200g methanol is cooled to less than 10 DEG C, start to drip methylation reaction liquid, control dropping temperature at 10��15 DEG C, time for adding 1.5h, after dropwising, being warming up to 65��70 DEG C of backflow 1h, then be cooled to less than 5 DEG C, crystallize is filtrated to get 4-fluoro-N-methyl-3-nitro aniline crude product 39.8g.
Crude product adds in 180g methanol and is warming up to backflow, is then cooled to 10 DEG C of sucking filtration, 400g water washing filter cake, and 55 DEG C dry obtains 4-fluoro-N-methyl-3-nitro aniline highly finished product 36g, and yield is 82.6%, product HPLC >=99.0%.
Embodiment 5
Take the fluoro-3-nitroaniline of 40g4-and 120g mass concentration is the sulphuric acid of 90%, stir at 25 DEG C of temperature, it is warming up to 35��40 DEG C, it is dividedly in some parts 15g paraformaldehyde (every 0.5h adds 3g paraformaldehyde) at such a temperature, finish, after insulation reaction 2h, it is cooled to 20 DEG C, standby (methylation reaction liquid).
Take 400g mass concentration and be 10% ammonia and 360g methanol is cooled to less than 10 DEG C, start to drip methylation reaction liquid, control dropping temperature at 10��15 DEG C, time for adding 3h, after dropwising, being warming up to 65��70 DEG C of backflow 1h, then be cooled to less than 5 DEG C, crystallize is filtrated to get 4-fluoro-N-methyl-3-nitro aniline crude product 40.2g.
Crude product adds in 150g methanol and is warming up to backflow, is then cooled to 10 DEG C of sucking filtration, 400g water washing filter cake, and 70 DEG C dry obtains 4-fluoro-N-methyl-3-nitro aniline highly finished product 37.6g, and yield is 86.3%, product HPLC >=99.0%.
Embodiment 6
Sucking mass concentration in 1000L enamel reaction still R1 is 98% sulphuric acid 750kg, puts into the fluoro-3-nitroaniline 250kg of 4-, puts into exothermic heat of reaction during 4-fluoro-3-nitroaniline, and the logical recirculated water of R1 chuck controls temperature at 30��35 DEG C, is warming up to 50 DEG C after finishing. Being dividedly in some parts 125kg paraformaldehyde (every 0.5h adds 20kg paraformaldehyde) at such a temperature, finish, after insulation reaction 2h, sampling HPLC detection reacts completely to the fluoro-3-nitroaniline of raw material 4-, is cooled to 20 DEG C, standby.
5000L enamel reaction still R2 sucks 25% ammonia 1250kg and methanol 1000kg, the logical brine ice of R2 chuck is cooled to less than 10 DEG C, start to drip methylation reaction liquid, control dropping temperature at 10��15 DEG C, time for adding 10h, after dropwising, it is warming up to 65��70 DEG C of backflow 1h, sampling HPLC detects to the 4-fluoro-N-main content of methyl-3-nitro aniline > 95%, it is cooled to less than 5 DEG C again, it is discharged in filtering jar, 2400kg water washing filter cake, it is then centrifuged for obtaining 4-fluoro-N-methyl-3-nitro aniline crude product 252kg, fluoro-for the 4-obtained N-methyl-3-nitro aniline crude product is put in methanol 800kg again, it is warming up to 60 DEG C, insulated and stirred 30min, then 5��10 DEG C it are cooled to, it is discharged in filtering jar, centrifugal, 4-fluoro-N-methyl-3-nitro aniline highly finished product 241kg is obtained after drying, yield is 88.5%, product HPLC >=99.0%.
Embodiment 7
Sucking mass concentration in 1000L enamel reaction still R1 is 98% sulphuric acid 1750kg, puts into the fluoro-3-nitroaniline 250kg of 4-, puts into exothermic heat of reaction during 4-fluoro-3-nitroaniline, and the logical recirculated water of R1 chuck controls temperature at 30��35 DEG C, is warming up to 50 DEG C after finishing. Being dividedly in some parts 300kg paraformaldehyde (every 0.5h adds 30kg paraformaldehyde) at such a temperature, finish, after insulation reaction 2h, sampling HPLC detection reacts completely to the fluoro-3-nitroaniline of raw material 4-, is cooled to 20 DEG C, standby.
5000L enamel reaction still R2 sucks 25% ammonia 2000kg and methanol 2000kg, the logical brine ice of R2 chuck is cooled to less than 10 DEG C, start to drip methylation reaction liquid, control dropping temperature at 10��15 DEG C, time for adding 15h, after dropwising, it is warming up to 65��70 DEG C of backflow 1h, sampling HPLC detects to the 4-fluoro-N-main content of methyl-3-nitro aniline > 95%, it is cooled to less than 5 DEG C again, it is discharged in filtering jar, 2400kg water washing filter cake, it is then centrifuged for obtaining 4-fluoro-N-methyl-3-nitro aniline crude product 258kg, fluoro-for the 4-obtained N-methyl-3-nitro aniline crude product is put in methanol 1700kg again, it is warming up to 60 DEG C, insulated and stirred 30min, then 5��10 DEG C it are cooled to, it is discharged in filtering jar, centrifugal, 4-fluoro-N-methyl-3-nitro aniline highly finished product 243kg is obtained after drying, yield is 89.2%, product HPLC >=99.1%.
Embodiment 8
Take the fluoro-3-nitroaniline of 40g4-and 280g mass concentration is the sulphuric acid of 85%, stir at 25 DEG C of temperature, it is warming up to 45��50 DEG C, it is dividedly in some parts 56g paraformaldehyde (every 0.5h adds 7.5g paraformaldehyde) at such a temperature, finish, after insulation reaction 2h, it is cooled to 20 DEG C, standby (methylation reaction liquid).
Take 325g mass concentration and be 25% ammonia and 300g methanol is cooled to less than 10 DEG C, start to drip methylation reaction liquid, control dropping temperature at 10��15 DEG C, time for adding 4.5h, after dropwising, being warming up to 65��70 DEG C of backflow 1h, then be cooled to less than 5 DEG C, crystallize is filtrated to get 4-fluoro-N-methyl-3-nitro aniline crude product 41g.
Crude product adds in 280g methanol and is warming up to backflow, is then cooled to 10 DEG C of sucking filtration, 400g water washing filter cake, and 55 DEG C dry obtains 4-fluoro-N-methyl-3-nitro aniline highly finished product 36.5g, and yield is 83.7%, product HPLC >=99.0%.
Claims (9)
1. the preparation method of the fluoro-N-methyl-3-nitro aniline of 4-, it is characterised in that: described in comprise the steps:
(1) methylation reaction: with the fluoro-3-nitroaniline of 4-for raw material, with mass concentration be 60��98% sulphuric acid for solvent, formaldehyde is methylating reagent, is obtained by reacting methylation reaction liquid at 20��60 DEG C;
(2) neutralize: methylation reaction drop is added to ammonia that mass concentration is 10��28% and in the mixed liquor of organic solvent, filters or separatory concentration obtains 4-fluoro-N-methyl-3-nitro aniline crude product through backflow cooling after being added dropwise to complete;
(3) purification: 4-fluoro-N-methyl-3-nitro aniline crude product is crystallized, obtain 4-fluoro-N-methyl-3-nitro aniline highly finished product after drying.
2. the preparation method of the fluoro-N-methyl-3-nitro aniline of 4-according to claim 1, it is characterised in that: in step (1), the weight ratio of sulphuric acid and the fluoro-3-nitroaniline of raw material 4-is 2��7.5:1; Described formaldehyde is the one in metaformaldehyde, paraformaldehyde, formalin, and its weight ratio with the fluoro-3-nitroaniline of raw material 4-is 0.3��1.4:1.
3. the preparation method of the fluoro-N-methyl-3-nitro aniline of 4-according to claim 1, it is characterised in that: in step (1), methylation reaction temperature is 30��50 DEG C.
4. the preparation method of the fluoro-N-methyl-3-nitro aniline of 4-according to claim 1, it is characterised in that: in step (2), the weight ratio 4��10:1 of ammonia and the fluoro-3-nitroaniline of raw material 4-; Described organic solvent is the combination in any of one or two or more kinds in methanol, ethanol, isopropanol, toluene, oxolane, methyl tertiary butyl ether(MTBE), the weight ratio 3��10:1 of its consumption and the fluoro-3-nitroaniline of raw material 4-.
5. the preparation method of the fluoro-N-methyl-3-nitro aniline of 4-according to claim 1, it is characterised in that: in step (2), dropping temperature controls at-10��20 DEG C, time for adding 1��20h.
6. the preparation method of the fluoro-N-methyl-3-nitro aniline of 4-according to claim 1, it is characterized in that: in step (3), the organic solvent of crystallization is low-boiling point alcohol, described low-boiling point alcohol is the one in methanol, ethanol, isopropanol, and the weight ratio of its consumption and the fluoro-N-methyl-3-nitro aniline of raw material 4-is 3��8:1.
7. the preparation method of the fluoro-N-methyl-3-nitro aniline of 4-according to claim 1, it is characterised in that: in step (3), baking temperature is 30��70 DEG C.
8. the preparation method of the fluoro-N-methyl-3-nitro aniline of 4-according to claim 1, it is characterised in that comprise the steps:
(1) methylation reaction: with 80��98% concentration sulphuric acid for solvent, paraformaldehyde is methylating reagent, and methylation reaction temperature controls at 30��50 DEG C; Wherein, the fluoro-3-nitroaniline of 4-, sulphuric acid, paraformaldehyde weight ratio be 1:3��6:0.5��1.2;
(2) neutralize: methylation reaction drop is added in the mixed liquor of 15��25% ammonia and methanol, dropping temperature controls between 0��15 DEG C, time for adding controls at 1.5��12h, backflow it is warming up to after being added dropwise to complete, after backflow a period of time, it is cooled to less than 5 DEG C and is filtrated to get 4-fluoro-N-methyl-3-nitro aniline crude product; Wherein, the fluoro-3-nitroaniline of 4-, ammonia, methanol weight ratio be 1:5��9:4��8;
(3) purification: 4-fluoro-N-methyl-3-nitro aniline crude product adds in methanol and is warming up to backflow, then cooled crystallization, filtration, dry to obtain 4-fluoro-N-methyl-3-nitro aniline highly finished product; Wherein, methanol is 4��7:1 with the weight ratio of the fluoro-N-methyl-3-nitro aniline of 4-; Baking temperature is 40��60 DEG C.
9. the preparation method of the fluoro-N-methyl-3-nitro aniline of 4-according to claim 1, it is characterised in that comprise the steps:
(1) sucking mass concentration in 1000L enamel reaction still R1 is 98% sulphuric acid 1125kg, put into the fluoro-3-nitroaniline 250kg of 4-, putting into exothermic heat of reaction during 4-fluoro-3-nitroaniline, the logical recirculated water of R1 chuck controls temperature at 30��35 DEG C, is warming up to 45 DEG C after finishing; Being dividedly in some parts 250kg paraformaldehyde at such a temperature, every 0.5h adds 25kg paraformaldehyde, finishes, and after insulation reaction 2h, sampling HPLC detection reacts completely to the fluoro-3-nitroaniline of raw material 4-, is cooled to 20 DEG C, standby;
(2) 5000L enamel reaction still R2 sucks 25% ammonia 1752kg and methanol 1440kg, the logical brine ice of R2 chuck is cooled to less than 10 DEG C, start to drip methylation reaction liquid, control dropping temperature at 12��15 DEG C, time for adding 10h, after dropwising, it is warming up to 65��70 DEG C of backflow 1h, sampling HPLC detects to the 4-fluoro-N-main content of methyl-3-nitro aniline > 95%, it is cooled to less than 5 DEG C again, it is discharged in filtering jar, 2400kg water washing filter cake, it is then centrifuged for obtaining 4-fluoro-N-methyl-3-nitro aniline crude product;
(3) fluoro-for the 4-obtained N-methyl-3-nitro aniline crude product is put in methanol 1300kg again, be warming up to 60 DEG C, insulated and stirred 30min, then 5��10 DEG C it are cooled to, it is discharged in filtering jar, centrifugal, obtain 4-fluoro-N-methyl-3-nitro aniline highly finished product after drying.
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| CN108191684A (en) * | 2018-01-12 | 2018-06-22 | 浙江鼎龙科技有限公司 | The preparation method of 2- methylamino -5- chlorobenzophenones |
| CN113354542A (en) * | 2021-07-12 | 2021-09-07 | 无锡双启科技有限公司 | Preparation method of 2-fluoro-6-nitroaniline |
| CN114805102A (en) * | 2022-05-27 | 2022-07-29 | 上海陶术生物科技有限公司 | Bisamide derivative intermediate and process for producing bisamide derivative |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN108191684A (en) * | 2018-01-12 | 2018-06-22 | 浙江鼎龙科技有限公司 | The preparation method of 2- methylamino -5- chlorobenzophenones |
| CN113354542A (en) * | 2021-07-12 | 2021-09-07 | 无锡双启科技有限公司 | Preparation method of 2-fluoro-6-nitroaniline |
| CN113354542B (en) * | 2021-07-12 | 2022-03-11 | 无锡双启科技有限公司 | Preparation method of 2-fluoro-6-nitroaniline |
| CN114805102A (en) * | 2022-05-27 | 2022-07-29 | 上海陶术生物科技有限公司 | Bisamide derivative intermediate and process for producing bisamide derivative |
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