CN114516806A - Preparation method of 2, 6-dibromo-4-trifluoromethoxy aniline - Google Patents
Preparation method of 2, 6-dibromo-4-trifluoromethoxy aniline Download PDFInfo
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- CN114516806A CN114516806A CN202210156062.6A CN202210156062A CN114516806A CN 114516806 A CN114516806 A CN 114516806A CN 202210156062 A CN202210156062 A CN 202210156062A CN 114516806 A CN114516806 A CN 114516806A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C213/08—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions not involving the formation of amino groups, hydroxy groups or etherified or esterified hydroxy groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/56—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
Abstract
The invention relates to the field of organic synthesis, in particular to a preparation method of 2, 6-dibromo-4-trifluoromethoxy aniline. According to the preparation method, 4-trifluoromethoxyaniline and dibromohydantoin are used as raw materials, a target product is obtained through one-step reaction, bromine is not used or generated in the production process, the environmental pollution is reduced, the preparation method is more suitable for industrial production, the production process is safer, and the raw materials are efficiently and reasonably utilized. The obtained 2, 6-dibromo-4-trifluoromethoxyaniline is suitable for preparing pesticide bactericide thifluzamide.
Description
Technical Field
The invention relates to the field of organic synthesis, in particular to a preparation method of 2, 6-dibromo-4-trifluoromethoxy aniline.
Background
Thifluzamide is a broad-spectrum bactericide, is mainly used for treating rice sheath blight, and is widely regarded due to the characteristics of small dosage, low toxicity, high drug effect, strong metabolic capacity and the like. Among them, 2, 6-dibromo-4-trifluoromethoxyaniline is a key intermediate for preparing thifluzamide.
At present, the method for industrially producing the 2, 6-dibromo-4-trifluoromethoxyaniline is basically brominating the 4-trifluoromethoxyaniline, wherein brominating agents mainly comprise bromine, bromine-hydrogen peroxide, metal bromide-hydrogen peroxide and the like. When bromine is used alone, bromine atoms are wasted because hydrogen bromide generated by the reaction cannot be effectively recycled, and the principle of atom economy is violated; although bromine atoms are effectively utilized, bromine-hydrogen peroxide is known to be reddish brown fuming liquid, and is quickly evaporated at normal temperature, steam of bromine-hydrogen peroxide has suffocating pungent taste, high toxicity, strong corrosivity and great harm to human bodies, and is very inconvenient to apply on a large scale, and hydrogen peroxide belongs to a strong oxidant, so that the production safety cannot be guaranteed; although the use of bromine is avoided, bromine is still generated in the reaction process, and the use of hydrogen peroxide cannot be avoided.
For the industrial production of 2, 6-dibromo-4-trifluoromethoxyaniline, a more environmentally friendly, safe and low-cost preparation process is currently required. In view of the above, the present invention is particularly proposed.
Disclosure of Invention
The invention aims to provide a preparation method of 2, 6-dibromo-4-trifluoromethoxyaniline.
In order to achieve the above purpose of the present invention, the following technical solutions are adopted:
a preparation method of 2, 6-dibromo-4-trifluoromethoxyaniline comprises the steps of reacting 4-trifluoromethoxyaniline with dibromohydantoin at the temperature of 10-50 ℃ for 4-7 hours under the catalysis of strong acid to obtain 2, 6-dibromo-4-trifluoromethoxyaniline;
wherein the molar ratio of the 4-trifluoromethoxy aniline to the dibromohydantoin to the strong acid is 1: (1.0-1.3):
(0.05-0.325)。
further, the temperature of the reaction is 10-15 ℃.
Further, the molar ratio of the 4-trifluoromethoxy aniline to the dibromohydantoin to the strong acid is 1: 1.1: 0.11.
further, the strong acid comprises sulfuric acid or methanesulfonic acid, preferably methanesulfonic acid.
Further, the solvent for the reaction includes methyl acetate, ethyl acetate, isopropyl acetate, dichloromethane or 1, 2-dichloroethane, preferably isopropyl acetate.
Further, the molar volume ratio of the 4-trifluoromethoxyaniline to the solvent is 1: 1000-2500mL, preferably 1: 1500 mL.
Furthermore, the dibromohydantoin is added into the reaction liquid in batches at the temperature of 10-15 ℃ for reaction.
Further, adding water after the reaction is finished, standing for layering, washing the organic phase with a reducing agent, drying and concentrating to obtain the 2, 6-dibromo-4-trifluoromethoxyaniline.
Further, the reducing agent includes sodium thiosulfate, sodium sulfite, or sodium bisulfite.
Further, the reducing agent is sodium sulfite.
Compared with the prior art, the invention has the beneficial effects that:
(1) according to the preparation method of the 2, 6-dibromo-4-trifluoromethoxy aniline, provided by the invention, the easily obtained dibromohydantoin is used as a bromination reagent, and bromine can be slowly released to react with the 4-trifluoromethoxy aniline, so that the reaction is fully carried out, bromine which is volatile and has high toxicity and low safety, hydrogen bromide-hydrogen peroxide or metal bromide-hydrogen peroxide is avoided being used as the bromination reagent, the environmental pollution is reduced, and the preparation method is more suitable for industrial production. Meanwhile, the byproduct hydantoin is slightly soluble in the ester solvent and can be filtered and separated.
(2) In the existing preparation process, hydrogen bromide-hydrogen peroxide or metal bromide-hydrogen peroxide is required to oxidize hydrogen bromide or metal bromide to generate bromine, and bromine reacts with 4-trifluoromethoxyaniline to obtain 2, 6-dibromo-4-trifluoromethoxyaniline. Meanwhile, compared with the existing preparation method, the yield and the purity are improved, and specifically, the yield can reach 90-95%, and the purity can reach 99-99.6%.
(3) The preparation method has simple separation and purification process, is easy to operate and reduces the production cost. Meanwhile, the preparation method enables the raw materials to be efficiently and reasonably utilized, and the other product in the reaction is hydantoin which can be used as a chemical raw material for other production (such as dibromohydantoin) after purification.
Detailed Description
The invention provides a preparation method of 2, 6-dibromo-4-trifluoromethoxyaniline, wherein 4-trifluoromethoxyaniline and dibromohydantoin react for 4-7 hours at the temperature of 10-50 ℃ under the catalysis of strong acid to obtain 2, 6-dibromo-4-trifluoromethoxyaniline; wherein the molar ratio of the 4-trifluoromethoxyaniline to the dibromohydantoin to the strong acid is 1:1.0-1.3: 0.05-0.325.
The synthesis method of the invention takes 4-trifluoromethoxyaniline and dibromohydantoin as raw materials, and obtains a target product by one-step reaction, and the reaction route is as follows:
in the above preparation method, only when a strong acid is used as a catalyst, the reaction rate can be accelerated while the progress of the bromination reaction is facilitated. The dibromohydantoin is used as a new brominating agent, is different from unavoidable bromine generation in a reaction system of the prior art, can directly react with 4-trifluoromethoxyaniline to generate 2, 6-dibromo-4-trifluoromethoxyaniline, and the synthesized 2, 6-dibromo-4-trifluoromethoxyaniline is white-like in appearance and has no residual bromine. The preparation method enables the raw materials to be efficiently and reasonably utilized, and the other product in the reaction is hydantoin which can be used as a chemical raw material for other production (such as production of dibromohydantoin) after purification.
Through research and development experience combined with a great deal of work research, the inventor finds that the adding proportion of 4-trifluoromethoxy aniline, dibromohydantoin and strong acid, and the temperature and time of reaction synergistically determine the yield and purity of 2, 6-dibromo-4-trifluoromethoxy aniline, and the molar ratio of 4-trifluoromethoxy aniline, dibromohydantoin and strong acid is 1 mol: (1.0-1.3) mol: (0.05-0.325) mol, and the reaction is carried out for 4-7 hours under the reaction condition of 10-50 ℃, so that the high-efficiency production of the 2, 6-dibromo-4-trifluoromethoxyaniline can be realized.
In a preferred embodiment, the temperature of the reaction may be in the range of 10 to 15 ℃, which may further increase the yield and purity of 2, 6-dibromo-4-trifluoromethoxyaniline.
In a preferred embodiment, the molar ratio of 4-trifluoromethoxyaniline, dibromohydantoin, and strong acid is 1: 1.1: 0.11.
in a preferred embodiment, the strong acid catalyst used in the reaction may be sulfuric acid or methanesulfonic acid, preferably methanesulfonic acid. The methanesulfonic acid is organic strong acid, is widely used in the pharmaceutical and chemical industries, has stable property, is easy to dissolve in polar organic solvents, overcomes the defect that the traditional inorganic acid is not dissolved in organic solvents, and improves the utilization rate.
In a preferred embodiment, the solvent used in the reaction system may be methyl acetate, ethyl acetate, isopropyl acetate, dichloromethane or dichloroethane, preferably isopropyl acetate. The amount of the solvent is as follows: the molar volume ratio of the 4-trifluoromethoxyaniline to the solvent is 0.1 mol: (100-250mL), preferably 0.1 mol: 150 mL. The isopropyl acetate has stable property, is not easy to hydrolyze, is convenient to recover, improves the recovery utilization rate of the solvent and reduces the production cost.
In a preferred embodiment, the dibromohydantoin is added to the reaction liquid in portions at 10-15 ℃ for reaction in order to make the reaction more complete and improve the product yield. When the dibromohydantoin is added into the reaction liquid, the temperature of the reaction liquid is within the range of 10-15 ℃, so that the reaction can be fully carried out.
In a preferred embodiment, after the reaction of the 4-trifluoromethoxyaniline and the dibromohydantoin is finished, the 2, 6-dibromo-4-trifluoromethoxyaniline is obtained through separation and purification, and the specific steps are filtration after the reaction is finished, a byproduct hydantoin is filtered out, the filtrate is taken and added with water to be subjected to standing and layering, and the organic phase is subjected to water washing by a reducing agent, drying and concentration in turn to obtain the 2, 6-dibromo-4-trifluoromethoxyaniline. The amount of the added water can be equal to the volume of the reaction system, the organic phase is washed by a reducing agent once, and the white-like high-purity 2, 6-dibromo-4-trifluoromethoxyaniline is obtained after drying and concentration.
In a preferred embodiment, the reducing agent comprises sodium thiosulfate, sodium sulfite or sodium bisulfite, preferably sodium sulfite.
In a preferred embodiment, the 2, 6-dibromo-4-trifluoromethoxyaniline is prepared by the following steps:
adding a solvent and strong acid into a reaction bottle, adding 4-trifluoromethoxyaniline, then adding dibromohydantoin in batches at 10-15 ℃, and preserving heat for 4-7 hours at 10-50 ℃ after the addition is finished to obtain a reaction solution; filtering to separate out byproduct hydantoin;
The mol volume ratio of the 4-trifluoromethoxy aniline, the solvent and the dibromohydantoin is 0.1 mol: 150mL of: 0.11 mol;
adding water with the same volume into the reaction solution filtrate obtained in the step I, standing and layering; and washing the organic phase once by using a reducing agent aqueous solution, drying the organic phase, and concentrating to obtain a white-like solid 2, 6-dibromo-4-trifluoromethoxyaniline.
The 2, 6-dibromo-4-trifluoromethoxy aniline obtained by the invention can be used for preparing thifluzamide.
The invention will be further described with reference to specific embodiments, and the advantages and features of the invention will become apparent as the description proceeds. These examples are illustrative only and do not limit the scope of the present invention in any way. It will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention, and that such changes and modifications may be made without departing from the spirit and scope of the invention.
The experimental methods are conventional methods unless specified otherwise; the biomaterial is commercially available unless otherwise specified.
Example 1
Dissolving 1.05g of methanesulfonic acid and 17.7g of 4-trifluoromethoxy aniline in 150mL of isopropyl acetate, then adding 31.5g of dibromohydantoin in batches at 10-15 ℃, and preserving the temperature for 4 hours at the same temperature after adding to obtain a reaction solution; filtering to remove byproduct hydantoin;
② adding water with the same volume into the filtrate of the reaction solution, standing for layering, washing the organic phase with sodium sulfite aqueous solution once, drying the organic phase, and concentrating to obtain white-like solid 31.7g, wherein the yield is 95% by 4-trifluoromethoxyaniline, and the purity is 99.6%. Recrystallizing the crude hydantoin product with ethanol to obtain a finished product with the purity of more than 97 percent.
Example 2
By taking the example 1 as a reference, different molar ratios of the 4-trifluoromethoxyaniline, the dibromohydantoin and the strong acid are set, the other conditions are unchanged, and the detection yield and purity, the proportion and the results are shown in the following table:
from the above experimental data, it can be seen that the amount of dibromohydantoin used in group 3 is outside the range defined in the present invention, the purity of 2, 6-dibromo-4-trifluoromethoxyaniline is lower than that in inventive example 1, group 4 has no strong acid catalyst, the yield and purity of 2, 6-dibromo-4-trifluoromethoxyaniline are lower than that in inventive example 1 and groups 1-2, the amount of methanesulfonic acid used in group 5 is outside the range defined in the present invention, the yield and purity of 2, 6-dibromo-4-trifluoromethoxyaniline are substantially equivalent to that in inventive example 1, but the raw materials are wasted, and the substitution of methanesulfonic acid with sulfuric acid in group 6 is lower than that in inventive example 1.
With the reference of example 1, different reaction temperatures and times were set, the remaining conditions were unchanged, and the yields and purities, ratios and results were as shown in the following table:
| reaction temperature | Reaction time | Yield of the product | Purity of |
| 20℃ | 4 hours | 93.4％ | 99％ |
| 30℃ | 4 hours | 92％ | 99％ |
| 40℃ | 4 hours | 89％ | 96％ |
| 50℃ | 4 hours | 89％ | 93％ |
| 10-15℃ | 7 hours | 95％ | 99.5％ |
From the above table, the reaction temperature and reaction time of the present invention determine the yield and purity of the product. In addition, too low a reaction temperature may result in failure of the reaction and risk of material accumulation.
Example 3
With the reference of example 1, different solvents and reducing agents were set, the remaining conditions were unchanged, and the yields and purities of the assay, the ratios and the results are shown in the following table:
| solvent(s) | Reducing agent | Yield of | Purity of |
| Acetic acid methyl ester | Sodium sulfite | 91.7％ | 98.5％ |
| Ethyl acetate | Sodium sulfite | 92％ | 99.5％ |
| Acetic acid isopropyl ester | Sodium thiosulfate | 95％ | 99.3％ |
| Acetic acid isopropyl ester | Sodium bisulfite | 94.8％ | 99.3％ |
| 1, 2-dichloroethane | Sodium sulfite | 91％ | 99.0％ |
As can be seen from the above table, methyl formate, ethyl acetate, isopropyl acetate and 1, 2-dichloroethane as solvents, sodium sulfite, sodium bisulfite and sodium thiosulfate as reducing agents all gave better yields and purities.
In addition, with reference to example 1, the addition temperature of dibromohydantoin is too low, so that the reaction cannot be smoothly carried out, and the danger of material accumulation is caused; the dibromohydantoin is added at an excessively high temperature, and the reaction is too violent, so that excessive heat release is caused, and danger is easily caused.
Example 4
Dissolving 1.3g of sulfuric acid and 17.7g of 4-trifluoromethoxy aniline in 180mL of ethyl acetate, then adding 32.0g of dibromohydantoin in batches at 10-15 ℃, and preserving the temperature for 5 hours at the same temperature after the addition to obtain a reaction solution; filtering to remove a byproduct hydantoin;
② adding water with the same volume into the reaction solution, standing and layering, washing the organic phase with sodium sulfite aqueous solution once again, drying the organic phase, and concentrating to obtain off-white solid 28.8g, wherein the yield is 86 percent based on 4-trifluoromethoxyaniline, and the purity is 98 percent.
Example 5
Dissolving 2g of methanesulfonic acid and 17.7g of 4-trifluoromethoxyaniline in 250mL of dichloromethane, adding 37.0g of dibromohydantoin in batches at 10-15 ℃, and preserving the temperature for 7 hours at 40 ℃ after the addition is finished to obtain a reaction solution; filtering to remove byproduct hydantoin;
② adding water with the same volume into the reaction solution, standing and layering, washing the organic phase with sodium sulfite aqueous solution once again, drying the organic phase, and concentrating to obtain 30.0g of white-like solid, wherein the yield is 90 percent based on 4-trifluoromethoxyaniline, and the purity is 99.0 percent.
Example 6
Dissolving 2g of sulfuric acid and 17.7g of 4-trifluoromethoxyaniline in 250mL of 1, 2-dichloroethane, adding 34.4g of dibromohydantoin in batches at 10-15 ℃, and preserving heat for 7 hours at 50 ℃ after the addition is finished to obtain a reaction solution; filtering to remove byproduct hydantoin;
② adding water with the same volume into the reaction solution, standing and layering, washing the organic phase with sodium sulfite aqueous solution once again, drying the organic phase, and concentrating to obtain 30.3g of white-like solid, wherein the yield is 91 percent based on 4-trifluoromethoxyaniline, and the purity is 99.0 percent.
Comparative example 1 reaction with bromine as bromination System
80mL of chloroform, 80mL of water and 35.16g of bromine were sequentially added to a 500mL three-necked flask, stirred rapidly, and after 17.7g of p-trifluoroanisidine (the molar amount of the p-trifluoroanisidine was 0.1mol) was slowly added and stirred for 30 minutes, the mixture was reacted at 40 ℃ for 1 hour. Cooling to room temperature, adding sodium thiosulfate, stirring for 30min, standing and layering. The organic layer was dried, filtered under suction, and the dichloromethane was distilled under reduced pressure to give 27.4g of 2, 6-dibromo-4-trifluoromethoxyaniline of 82% yield and 90% purity.
Comparative example 2 reaction of hydrogen bromide and hydrogen peroxide serving as bromination system
80mL of 1, 2-dichloroethane, 80mL of water, and 17.8g of hydrogen bromide (molar amount of hydrogen bromide is 0.22mol) were sequentially added to a 500mL three-necked flask, stirred rapidly, and after 17.7g of p-trifluoromethoxyaniline (molar ratio of hydrogen bromide to p-trifluoromethoxyaniline: 1.0: 2.2) was slowly added and stirred for 30min, the mixture was reacted at 40 ℃ for 1 h. Cooling to room temperature, adding sodium thiosulfate, stirring for 30min, standing, and layering. The organic layer was dried, suction-filtered, and methylene chloride was distilled off under reduced pressure to give 25.8g of 2, 6-dibromo-4-trifluoromethoxyaniline, the yield was 77%, and the purity was 90%.
Comparative example 3 reaction of metal bromide and hydrogen peroxide serving as bromination system
Adding 138.7g of 7.5% sulfuric acid aqueous solution, 17.7g of p-trifluoromethoxyaniline and 1g of benzyltriethylammonium chloride into a 1000mL three-necked bottle in sequence, stirring, controlling the temperature to be 25-30 ℃, adding 27g of potassium bromide, dropping 24.7g of hydrogen peroxide at the same temperature after the addition, keeping the temperature at 50-55 ℃ for reaction till the end, cooling, filtering, and drying to obtain 24.8g of 2, 6-dibromo-4-trifluoromethoxyaniline with the yield of 75% and the purity of 96%.
The application example is as follows: preparation of thifluzamide
2-methyl-4-trifluoromethyl-5-thiazolecarbonyl chloride (0.1mol, 23g), 2, 6-dibromo-4-trifluoromethoxyaniline (0.1mol, 33.5g) and toluene (250mL) were added to a 500mL three-necked flask at room temperature, and reacted at 110 ℃ for about 15 hours. Cooled to 5-10 deg.C, filtered, and the filter cake was air dried to give an off-white thifluzamide crystal (39.6g, 75%).
Although the present invention has been described with reference to the preferred embodiments, it should be understood that various changes, substitutions and alterations can be made herein without departing from the spirit and scope of the invention as defined by the appended claims.
Claims (10)
1. A preparation method of 2, 6-dibromo-4-trifluoromethoxyaniline is characterized in that 4-trifluoromethoxyaniline and dibromohydantoin react for 4-7 hours at 10-50 ℃ under the catalysis of strong acid to obtain 2, 6-dibromo-4-trifluoromethoxyaniline;
wherein the molar ratio of the 4-trifluoromethoxy aniline to the dibromohydantoin to the strong acid is 1 mol:
(1.0-1.3)mol：(0.05-0.325)mol。
2. the method of claim 1, wherein the reaction temperature is 10-15 ℃.
3. The method according to claim 1, wherein the molar ratio of 4-trifluoromethoxyaniline to dibromohydantoin to the strong acid is 1 mol: 1.1 mol: 0.11 mol.
4. The method of claim 1, wherein the strong acid comprises sulfuric acid or methanesulfonic acid, preferably methanesulfonic acid.
5. The process according to claim 1, wherein the solvent for the reaction comprises methyl acetate, ethyl acetate, isopropyl acetate, dichloromethane or 1, 2-dichloroethane, preferably isopropyl acetate.
6. The preparation method according to claim 5, wherein the molar volume ratio of the 4-trifluoromethoxyaniline to the solvent is 1 mol: (1000-2500mL), preferably 1 mol: 1500 mL.
7. The method according to claim 1, wherein the dibromohydantoin is added to the reaction mixture in portions at 10 to 15 ℃ for reaction.
8. The process according to any one of claims 1 to 7, wherein the reaction is completed, water is added, the mixture is allowed to stand for layering, and the organic phase is washed with water with a reducing agent, dried and concentrated to obtain 2, 6-dibromo-4-trifluoromethoxyaniline.
9. The method of claim 8, wherein the reducing agent comprises sodium thiosulfate, sodium sulfite, or sodium bisulfite.
10. The method of claim 9, wherein the reducing agent is sodium sulfite.
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| JP2001199943A (en) * | 2000-01-21 | 2001-07-24 | Kemikurea:Kk | Method for producing 2,6-dibromo-4- trifluoromethoxyaniline |
| CN103570566A (en) * | 2013-11-12 | 2014-02-12 | 河北科技大学 | Method for preparing 2,6-dibromo-4-trifluoromethoxyaniline |
| CN113347970A (en) * | 2018-10-24 | 2021-09-03 | 诺华股份有限公司 | Compounds and compositions for treating conditions associated with NLRP activity |
| CN113651702A (en) * | 2021-08-17 | 2021-11-16 | 内蒙古融创宜博科技有限公司 | Preparation method of 6-bromo-2, 4-dinitroaniline |
| CN113801010A (en) * | 2021-11-18 | 2021-12-17 | 山东诚创蓝海医药科技有限公司 | Preparation method of 5-bromo-2-chlorobenzoic acid |
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2022
- 2022-02-21 CN CN202210156062.6A patent/CN114516806A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2001199943A (en) * | 2000-01-21 | 2001-07-24 | Kemikurea:Kk | Method for producing 2,6-dibromo-4- trifluoromethoxyaniline |
| CN103570566A (en) * | 2013-11-12 | 2014-02-12 | 河北科技大学 | Method for preparing 2,6-dibromo-4-trifluoromethoxyaniline |
| CN113347970A (en) * | 2018-10-24 | 2021-09-03 | 诺华股份有限公司 | Compounds and compositions for treating conditions associated with NLRP activity |
| CN113651702A (en) * | 2021-08-17 | 2021-11-16 | 内蒙古融创宜博科技有限公司 | Preparation method of 6-bromo-2, 4-dinitroaniline |
| CN113801010A (en) * | 2021-11-18 | 2021-12-17 | 山东诚创蓝海医药科技有限公司 | Preparation method of 5-bromo-2-chlorobenzoic acid |
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