CN111423342A - Preparation method for co-production of N-methyl-2-fluoroaniline and crystalline sulfanilamide - Google Patents
Preparation method for co-production of N-methyl-2-fluoroaniline and crystalline sulfanilamide Download PDFInfo
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- CN111423342A CN111423342A CN202010240834.5A CN202010240834A CN111423342A CN 111423342 A CN111423342 A CN 111423342A CN 202010240834 A CN202010240834 A CN 202010240834A CN 111423342 A CN111423342 A CN 111423342A
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- C07C303/36—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids
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- C07C303/38—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids by reaction of ammonia or amines with sulfonic acids, or with esters, anhydrides, or halides thereof
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Abstract
The invention discloses a preparation method for co-producing N-methyl-2-fluoroaniline and crystalline sulfanilamide, which comprises the following steps: s1, carrying out condensation reaction on o-fluoroaniline, p-acetamido benzene sulfonyl chloride and an acid-binding agent to obtain a substance A; s2, performing methylation reaction on the extract substance A, a methylation reagent and an alkaline substance, and performing amino deprotection to obtain a substance B; and finally, carrying out ammonolysis reaction on the substance B and an aminating agent to obtain the N-methyl-2-fluoroaniline and the crystalline sulfanilamide. The invention takes o-fluoroaniline and p-acetamido benzene sulfonyl chloride as raw materials to synchronously prepare two substances, namely N-methyl-2-fluoroaniline and crystal sulfanilamide, and has higher yield.
Description
Technical Field
The invention relates to the technical field of organic synthesis, in particular to a preparation method for co-producing N-methyl-2-fluoroaniline and crystalline sulfanilamide.
Background
The N-methyl-2-fluoroaniline and the crystal sulfanilamide are important chemical intermediates and raw materials. The dosage of the N-methyl-2-fluoroaniline is increased rapidly every year, and the market demand is large. The crystal sulfanilamide is a main raw material for synthesizing sulfanilamide medicines, is also an intermediate of herbicide asulam, and can be directly used as a veterinary medicine.
Currently, the synthesis method of N-methyl-2-fluoroaniline is many and can be roughly divided into the following routes:
1. in the literature (catalysis science & Technology,6(22), 7956-. The yield of the synthetic route is too low, the total yield of the N-methyl-2-fluoroaniline is about 5 percent, and the synthetic route is not easy to be industrially produced and is shown as the following route 1:
2. in the literature (Organic L etters,14(15), 3948-:
3. in patent CN107973721, o-fluoroaniline is used as a raw material, and reacts with paraformaldehyde under the action of an acid-binding agent to obtain an intermediate 1, and the intermediate 1 is reduced by hydrogen to obtain a target product. The synthetic route needs hydrogen and an acid-binding agent, the generation cost is high, the total yield of N-methyl-2-fluoroaniline with certain potential safety hazard is about 83%, and the synthetic route is shown as a route 3:
the industrial production method of the crystalline sulfanilamide is single, and the specific synthetic route is as follows: acetanilide is used as a raw material and reacts with chlorosulfonic acid to obtain an intermediate 1, the intermediate 1 reacts with ammonia water to obtain an intermediate 2, and the intermediate 2 is hydrolyzed to obtain the crystalline sulfanilamide. The synthesis route is long and the production cost is high. The total yield of crystalline sulfonamides is about 90%, and the synthetic route is shown in scheme 4:
in summary, the existing production processes of N-methyl-2-fluoroaniline and crystal sulfanilamide often have the problems of difficulty in controlling the generation of a byproduct, namely polysubstituted methyl, higher production cost, difficulty in operation, more three wastes and the like. It is therefore desirable to provide new methods of preparation.
Disclosure of Invention
Based on the technical problems in the background art, the invention provides a preparation method for co-producing N-methyl-2-fluoroaniline and crystal sulfanilamide.
The invention provides a preparation method for co-producing N-methyl-2-fluoroaniline and crystalline sulfanilamide, which comprises the following steps:
s1, carrying out condensation reaction on o-fluoroaniline, p-acetamido benzene sulfonyl chloride and an acid-binding agent to obtain a substance A;
s2, performing methylation reaction on the extract substance A, a methylation reagent and an alkaline substance, and performing amino deprotection to obtain a substance B; finally, carrying out ammonolysis reaction on the substance B and an aminating agent to obtain N-methyl-2-fluoroaniline and crystalline sulfanilamide;
wherein the structural formulas of the substance A and the substance B are shown as follows:
the "ammonolysis reaction" refers to a process in which an organic compound having various functional groups is reacted with an aminating agent to form an amine compound.
Preferably, in S1, the acid scavenger comprises triethylamine, pyridine, or N, N-diisopropylethylamine, etc.
Preferably, in S1, the acid scavenger is triethylamine.
Preferably, in S2, the methylating agent includes methyl iodide, methyl bromide or dimethyl sulfate, etc.
Preferably, in S2, the methylating agent is methyl iodide.
Preferably, in S2, the basic substance includes sodium hydride, methyl lithium, butyl lithium or the like.
Preferably, in S2, the basic substance is sodium hydride.
The sodium hydride is commercially available, and is usually a solution of sodium hydride in an oil such as kerosene, liquid paraffin, or the like.
Preferably, in S2, the aminating agent is aqueous ammonia.
Preferably, in S1, the condensation reaction temperature is room temperature and the reaction time is 2-3 h.
Preferably, in S2, the temperature of the methylation reaction is-5 to 0 ℃ and the reaction time is 2 to 4 hours.
Preferably, in S2, the temperature of the amino deprotection reaction is 25-60 ℃ and the reaction time is 5-30 min.
Preferably, in S2, the ammonolysis reaction time is 4-5 h.
Preferably, in S1, the molar ratio of the o-fluoroaniline, the p-acetamidobenzenesulfonyl group and the acid-binding agent is 1:1.01-1.1: 1.1-1.5.
Preferably, in S2, the molar ratio of the substance A, the methylating agent and the basic substance is 1:1.05-1.5: 1.05-2.0.
Preferably, in S2, the molar ratio of substance B to aminating agent is 1: 1.5-5.0.
Preferably, in S1, the reaction solvent for the condensation reaction includes dichloromethane, tetrahydrofuran, N-dimethylaniline, or the like.
Preferably, in S2, the reaction solvent for methylation is tetrahydrofuran or n.n-dimethylaniline.
Preferably, in S1, the specific preparation step of substance a includes: dissolving o-fluoroaniline and p-acetamido benzene sulfonyl chloride in a reaction solvent, adding an acid-binding agent, and carrying out condensation reaction to obtain a substance A.
Preferably, the condensation reaction is followed by purification to give substance A.
Preferably, the specific steps of purification are: after condensation reaction, dichloromethane and water are added for extraction, and a dichloromethane layer is taken, washed, dried and concentrated to obtain a substance A.
Preferably, in S2, the specific preparation step of substance B includes: and (3) uniformly mixing the substance A, the methylation reagent and the reaction solvent, adding an alkaline substance, uniformly mixing, carrying out methylation reaction, adding water for quenching reaction, removing the reaction solvent, and carrying out amino deprotection reaction to obtain a substance B.
In the preparation of substance B, the next ammonolysis reaction was carried out without purification.
Preferably, in S2, the specific steps of the ammonolysis reaction include: and (3) uniformly mixing the substance B with an aminating agent, refluxing for ammonolysis reaction, then crystallizing, filtering to obtain a filter cake to obtain crystalline sulfanilamide, extracting the filtrate with an organic solvent, and concentrating an organic layer to obtain the N-methyl-2-fluoroaniline.
Preferably, the organic solvent includes dichloromethane, ethyl acetate, toluene, and the like.
Preferably, the crystallization temperature is 0-5 ℃.
Has the advantages that:
1. the invention creatively uses o-fluoroaniline and p-acetamido benzene sulfonyl chloride as raw materials to obtain a substance A through condensation reaction, the substance A performs methylation and amino deprotection reaction to obtain a substance B, the substance B performs ammonolysis reaction to synchronously prepare two substances of N-methyl-2-fluoroaniline and crystalline sulfonamide, the production cost and the production period are reduced, the atom economy is facilitated, the yield of the N-methyl-2-fluoroaniline and the yield of the crystalline sulfonamide are both high, the yield of the N-methyl-2-fluoroaniline reaches 83%, and the yield of the crystalline sulfonamide reaches 85%;
2. the raw materials of the invention are cheap and easy to obtain; the route is short, the operation is simple, and the post-treatment is simple and convenient; and the operation process is simplified, the pollution to the environment is reduced, and the method is suitable for industrial mass production.
Drawings
FIG. 1 is a synthetic route diagram of the present invention.
Detailed Description
The technical solution of the present invention will be described in detail below with reference to specific examples.
Example 1
A preparation method for co-producing N-methyl-2-fluoroaniline and crystalline sulfanilamide comprises the following steps:
s1, dissolving 11.1g (0.1mol) of o-fluoroaniline and 23.8g (0.102mol) of p-acetamidobenzenesulfonyl chloride in 200m L dichloromethane, cooling the system to 0 ℃, dropwise adding 11.1g (0.11mol) of triethylamine, adjusting the temperature to room temperature after dropwise adding, stirring for 2 hours to perform condensation reaction, then adding 100m L dichloromethane and 100m L water, mixing uniformly, standing for layering for extraction, taking a dichloromethane layer, washing with 100m L saturated sodium chloride aqueous solution, drying with anhydrous sodium sulfate, and concentrating to obtain 29.6g of a substance A, wherein the yield is 96%;
s2, dissolving 18.5g (0.06mol) of a substance A, 9.4g (0.066mol) of methyl iodide in 200m L tetrahydrofuran, cooling the system to 0 ℃, adding 2.9g (0.072 mol) of sodium hydride oil solution with the mass fraction of 60% in batches, mixing uniformly, then carrying out methylation reaction at 0 ℃ under heat preservation and stirring for 2h, then dropwise adding 50m L water to quench the reaction, carrying out reduced pressure distillation to remove tetrahydrofuran, recycling the tetrahydrofuran, carrying out amino deprotection reaction at 45 ℃ under heat preservation and stirring for 20min to obtain a substance B, and carrying out no purification treatment;
finally, all the substance B (theoretical value is 0.06mol) is taken out and added into a reaction bottle, and 22.5g (NH) of ammonia water solution with the mass fraction of 28 percent is added3·H2O is 0.18mol), refluxing, ammonolysis reaction is carried out for 4h, then cooling to 2 ℃ for crystallization, filtering, taking filter cake, washing with water, drying to obtain 8.6g of off-white solid, namely crystalline sulfanilamide, taking filtrate, extracting with dichloromethane for 2 times, wherein the dosage of dichloromethane for each time is 50m L,the organic layers were combined, washed with 50m L30 deg.C water to remove residual crystalline sulfanilamide, then washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated to give 6.4g of a pale yellow liquid, i.e., N-methyl-2-fluoroaniline, with a total yield of 83% for crystalline sulfanilamide and 85% for N-methyl-2-fluoroaniline.
The substance A, the crystalline sulfanilamide and the N-methyl-2-fluoroaniline obtained in example 1 were subjected to nuclear magnetic resonance detection, and the results were as follows:
the result of the nuclear magnetic detection of the substance A is as follows:1H NMR(400MHz,d6-DMSO):(ppm):10.20(s,1H),9.66(s,1H),7.68-7.72(d,4H),6.65-6.93(m,4H),2.06(s,3H)；
the result of the nuclear magnetic detection of the crystalline sulfanilamide is as follows:1H NMR(400MHz,d6-DMSO):(ppm):7.54(dd,2H),6.88(s,1H),6.57(dd,2H),6.06(s,2H)；
the result of the N-methyl-2-fluoroaniline nuclear magnetic detection is as follows:1H NMR(400MHz,d6-DMSO):(ppm):6.99(t,2H),6.72(s,1H),6.65-6.69(m,2H),2.64(s,3H)。
example 2
A preparation method for co-producing N-methyl-2-fluoroaniline and crystalline sulfanilamide comprises the following steps:
s1, dissolving 1.11kg (10.0mol) of o-fluoroaniline and 2.4kg (10.2mol) of p-acetamido benzenesulfonyl chloride in 40000m L dichloromethane, cooling the system to 0 ℃, dropwise adding 1.1kg (11.0mol) of triethylamine, adjusting the temperature to room temperature after dropwise adding, stirring for 3 hours to perform condensation reaction, then adding 10000m L dichloromethane and 10000m L water, uniformly mixing, standing for layering for extraction, taking a dichloromethane layer, washing with 10000m L saturated sodium chloride aqueous solution, drying with anhydrous sodium sulfate, and concentrating to obtain 3022g of a substance A, wherein the yield is 98%;
s2, dissolving a fetching substance A1850 g (6mol) and methyl iodide 9400g (6.6mol) in 20000m L tetrahydrofuran, cooling the system to 0 ℃, adding sodium hydride oil solution 2900g (7.2 mol) with the mass fraction of 60% in batches, mixing uniformly, preserving heat at 0 ℃ and stirring for 4 hours for methylation reaction, then dropwise adding 5000m L for water quenching reaction, carrying out reduced pressure distillation to remove tetrahydrofuran, recovering and reusing tetrahydrofuran, preserving heat at 45 ℃ and stirring for 30 minutes for carrying out amino deprotection reaction to obtain a substance B, and not carrying out purification treatment;
finally, all the substance B (theoretical value is 6mol) is taken out and added with 22500g of ammonia solution (NH) with the mass fraction of 28 percent3·H218.0mol of O), refluxing, ammonolysis reaction is carried out for 5h, then cooling to 2 ℃ for crystallization, suction filtration is carried out, filter cakes are washed by water, drying is carried out to obtain 868g of white-like solid, namely crystalline sulfanilamide, filtrate is extracted by dichloromethane for 2 times, the dosage of dichloromethane for each time is 5000m L, organic layers are combined, then 5000m L30 ℃ water is used for washing to remove residual crystalline sulfanilamide, then saturated sodium chloride aqueous solution is used for washing, anhydrous sodium sulfate is used for drying, 646g of light yellow liquid, namely N-methyl-2-fluoroaniline, is obtained by concentration, the total yield of the crystalline sulfanilamide is 84%, and the total yield of the N-methyl-2-fluoroaniline is 86%.
Example 3
A preparation method for co-producing N-methyl-2-fluoroaniline and crystalline sulfanilamide comprises the following steps:
s1, dissolving 11.1g (0.1mol) of o-fluoroaniline and 25.7g (0.11mol) of p-acetamidobenzenesulfonyl chloride in 200m L tetrahydrofuran, cooling the system to 0 ℃, dropwise adding 15.1g (0.15mol) of triethylamine, adjusting the temperature to room temperature after dropwise adding, stirring for 2.5h to perform condensation reaction, then adding 100m L dichloromethane and 100m L water, uniformly mixing, standing for layering for extraction, taking a dichloromethane layer, washing with 100m L saturated sodium chloride aqueous solution, drying with anhydrous sodium sulfate, and concentrating to obtain 29.9g of a substance A, wherein the yield is 97%;
s2, dissolving 18.5g (0.06mol) of a substance A, 8.6g (0.063mol) of methyl iodide in 200m L tetrahydrofuran, cooling the system to 0 ℃, adding 2.5g (0.063mol) of sodium hydride oil solution with the mass fraction of 60% in batches, mixing uniformly, then carrying out methylation reaction at-5 ℃ under heat preservation and stirring for 3h, then dropwise adding 50m L water for quenching reaction, carrying out reduced pressure distillation to remove tetrahydrofuran, recycling tetrahydrofuran, carrying out amino deprotection reaction at 25 ℃ under heat preservation and stirring for 30min to obtain a substance B, and not carrying out purification treatment;
finally, all the substance B (theoretical value is 0.06mol) is taken out and added into a reaction bottle, 11.25g (NH) of ammonia water solution with the mass fraction of 28 percent is added3·H2O is 0.09mol) under refluxAmmonolysis reaction is carried out for 4.5h, then cooling to 5 ℃ for crystallization, suction filtration is carried out, filter cakes are washed by water and dried to obtain 8.5g of off-white solid which is crystal sulfanilamide, filtrate is extracted by toluene for 2 times, the dosage of the toluene for each time is 50m L, organic layers are combined, then the filtrate is washed by water with the temperature of 50m L30 ℃ to remove residual crystal sulfanilamide, then saturated sodium chloride aqueous solution is used for washing, anhydrous sodium sulfate is used for drying, 6.3g of light yellow liquid which is N-methyl-2-fluoroaniline is obtained by concentration, the total yield of the crystal sulfanilamide is 82 percent, and the total yield of the N-methyl-2-fluoroaniline is 84 percent.
Example 4
A preparation method for co-producing N-methyl-2-fluoroaniline and crystalline sulfanilamide comprises the following steps:
s1, dissolving 11.1g (0.1mol) of o-fluoroaniline and 24.5g (0.105mol) of p-acetamidobenzenesulfonyl chloride in 200m L dichloromethane, cooling the system to 5 ℃, dropwise adding 12.1g (0.12mol) of triethylamine, adjusting the temperature to room temperature after dropwise adding, stirring for 2.7h to perform condensation reaction, then adding 100m L dichloromethane and 100m L water, uniformly mixing, standing for layering for extraction, taking a dichloromethane layer, washing with 100m L saturated sodium chloride aqueous solution, drying with anhydrous sodium sulfate, and concentrating to obtain 30.2g of a substance A, wherein the yield is 98%;
s2, dissolving 18.5g (0.06mol) of a substance A and 12.8g (0.09mol) of methyl iodide in 200m L of N.N-dimethylaniline, cooling the system to-5 ℃, adding 4.8g (0.12mol) of a sodium hydride oil solution with the mass fraction of 60% in batches, mixing uniformly, then carrying out methylation reaction at-2 ℃ under heat preservation and stirring for 3.5h, then dropwise adding 50m L water quenching reaction, carrying out reduced pressure distillation to remove tetrahydrofuran, recycling the tetrahydrofuran, carrying out amino deprotection reaction at 60 ℃ under heat preservation and stirring for 5min to obtain a substance B, and not carrying out purification treatment;
finally, all the substance B (theoretical value is 0.06mol) is taken out and added with 37.5g (NH) of ammonia water solution with the mass fraction of 28 percent3·H2O is 0.3mol), refluxing for ammonolysis reaction for 4.8h, then cooling to 0 ℃ for crystallization, performing suction filtration, taking filter cake for washing, drying to obtain 8.7g of off-white solid, namely crystalline sulfanilamide, taking filtrate, extracting with ethyl acetate for 2 times, wherein the dosage of ethyl acetate is 50m L each time, combining organic layers, then using 50m L30 ℃ to perform ammonolysis reaction for 4.8h, and performing crystallization by cooling, wherein the ethyl acetate is used for extracting for 2 times, the dosage of ethyl acetate is 50Washing with water to remove residual crystal sulfanilamide, washing with saturated sodium chloride aqueous solution, drying with anhydrous sodium sulfate, and concentrating to obtain 6.5g of light yellow liquid, namely N-methyl-2-fluoroaniline; the total yield of the crystalline sulfanilamide is 84 percent, and the total yield of the N-methyl-2-fluoroaniline is 86 percent.
It can be seen from the above table that the present invention has good wear resistance and at the same time good mechanical properties.
The above description is only for the preferred embodiment of the present invention, but the scope of the present invention is not limited thereto, and any person skilled in the art should be considered to be within the technical scope of the present invention, and the technical solutions and the inventive concepts thereof according to the present invention should be equivalent or changed within the scope of the present invention.
Claims (10)
1. A preparation method for co-producing N-methyl-2-fluoroaniline and crystalline sulfanilamide is characterized by comprising the following steps:
s1, carrying out condensation reaction on o-fluoroaniline, p-acetamido benzene sulfonyl chloride and an acid-binding agent to obtain a substance A;
s2, performing methylation reaction on the extract substance A, a methylation reagent and an alkaline substance, and performing amino deprotection to obtain a substance B; finally, carrying out ammonolysis reaction on the substance B and an aminating agent to obtain N-methyl-2-fluoroaniline and crystalline sulfanilamide;
wherein the structural formulas of the substance A and the substance B are shown as follows:
2. the process for the preparation of a co-product of N-methyl-2-fluoroaniline and a crystalline sulfonamide as claimed in claim 1, wherein in S1 the acid-binding agent comprises triethylamine, pyridine or N, N-diisopropylethylamine; preferably, in S1, the acid scavenger is triethylamine.
3. The production process for co-producing N-methyl-2-fluoroaniline and crystalline sulfonamide as claimed in claim 1 or 2, characterized in that in S2, the methylating agent comprises methyl iodide, methyl bromide or dimethyl sulfate; preferably, in S2, the methylating agent is methyl iodide; preferably, in S2, the basic substance includes sodium hydride, methyl lithium or butyl lithium; preferably, in S2, the basic substance is sodium hydride.
4. The process for the co-production of N-methyl-2-fluoroaniline and crystalline sulfonamide according to any one of claims 1-3, characterized in that in S2 the aminating agent is aqueous ammonia.
5. The process for the preparation of co-production of N-methyl-2-fluoroaniline and crystalline sulfonamide as claimed in any one of claims 1 to 4, wherein in S1, the condensation reaction is carried out at room temperature for a reaction time of 2 to 3 hours; preferably, in S2, the temperature of the methylation reaction is-5 to 0 ℃, and the reaction time is 2-4 h; preferably, in S2, the temperature of the amino deprotection reaction is 25-60 ℃, and the reaction time is 5-30 min; preferably, in S2, the ammonolysis reaction time is 4-5 h.
6. The process for the preparation of a co-product of N-methyl-2-fluoroaniline and a crystalline sulfonamide as claimed in any one of claims 1 to 5, wherein in S1, the molar ratio of o-fluoroaniline, p-acetamidobenzenesulfonyl group and acid-binding agent is 1:1.01 to 1.1:1.1 to 1.5; preferably, in S2, the molar ratio of the substance A, the methylating agent and the basic substance is 1:1.05-1.5: 1.05-2.0; preferably, in S2, the molar ratio of substance B to aminating agent is 1: 1.5-5.0.
7. The process for the co-production of N-methyl-2-fluoroaniline and crystalline sulfonamide according to any one of claims 1 to 6, characterized in that, in S1, the reaction solvent for the condensation reaction comprises dichloromethane, tetrahydrofuran or N, N-dimethylaniline; preferably, in S2, the reaction solvent for methylation is tetrahydrofuran or n.n-dimethylaniline.
8. The process for the preparation of co-production of N-methyl-2-fluoroaniline and crystalline sulfonamide according to any one of claims 1 to 7, characterized in that in S1 the specific preparation step of substance a comprises: dissolving o-fluoroaniline and p-acetamido benzene sulfonyl chloride in a reaction solvent, adding an acid-binding agent, and carrying out condensation reaction to obtain a substance A; preferably, after the condensation reaction, the product is purified to obtain a substance A; preferably, the specific steps of purification are: after condensation reaction, dichloromethane and water are added for extraction, and a dichloromethane layer is taken, washed, dried and concentrated to obtain a substance A.
9. The process for the preparation of co-production of N-methyl-2-fluoroaniline and crystalline sulfonamide according to any one of claims 1-8, characterized in that in S2 the specific preparation step of substance B comprises: and (3) uniformly mixing the substance A, the methylation reagent and the reaction solvent, adding an alkaline substance, uniformly mixing, carrying out methylation reaction, adding water for quenching reaction, removing the reaction solvent, and carrying out amino deprotection reaction to obtain a substance B.
10. The process for the preparation of co-production of N-methyl-2-fluoroaniline and crystalline sulfonamide according to any one of claims 1 to 9, wherein in S2, the specific steps of the ammonolysis reaction comprise: uniformly mixing the substance B with an aminating agent, refluxing for ammonolysis reaction, then crystallizing, filtering to obtain a filter cake to obtain crystalline sulfanilamide, extracting the filtrate with an organic solvent, and concentrating an organic layer to obtain N-methyl-2-fluoroaniline; preferably, the organic solvent comprises dichloromethane, ethyl acetate, toluene; preferably, the crystallization temperature is 0-5 ℃.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN115197072A (en) * | 2022-07-12 | 2022-10-18 | 合肥星宇化学有限责任公司 | Preparation method of N-alkyl-2-fluoroaniline |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN115197072A (en) * | 2022-07-12 | 2022-10-18 | 合肥星宇化学有限责任公司 | Preparation method of N-alkyl-2-fluoroaniline |
| CN115197072B (en) * | 2022-07-12 | 2024-05-03 | 合肥星宇化学有限责任公司 | Preparation method of N-alkyl-2-fluoroaniline |
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