CN111349032B - Preparation method of fenbendazole intermediate 2-nitro-4-thiophenyl aniline - Google Patents
Preparation method of fenbendazole intermediate 2-nitro-4-thiophenyl aniline Download PDFInfo
- Publication number
- CN111349032B CN111349032B CN202010325271.XA CN202010325271A CN111349032B CN 111349032 B CN111349032 B CN 111349032B CN 202010325271 A CN202010325271 A CN 202010325271A CN 111349032 B CN111349032 B CN 111349032B
- Authority
- CN
- China
- Prior art keywords
- reaction
- nitro
- fenbendazole
- preparation
- nitroaniline
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C331/00—Derivatives of thiocyanic acid or of isothiocyanic acid
- C07C331/02—Thiocyanates
- C07C331/12—Thiocyanates having sulfur atoms of thiocyanate groups bound to carbon atoms of hydrocarbon radicals substituted by nitrogen atoms, not being part of nitro or nitroso groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
- C07C319/02—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of thiols
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
- C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides
Abstract
The invention relates to the technical field of veterinary drugs, in particular to a preparation method of fenbendazole intermediate 2-nitro-4-thiophenyl aniline, which comprises the following steps: taking o-nitroaniline and ammonium thiocyanate as raw materials, taking an organic solvent as a solvent of a reaction system, uniformly stirring, introducing chlorine, and filtering after the reaction of the raw materials is finished to obtain 4-thiocyano-2-nitroaniline; adding sodium hydroxide and a reaction solvent into 4-thiocyano-2-nitroaniline, stirring and mixing, and filtering after the reaction is finished to obtain a 4-amino-3-nitrothiophenol sodium solution; reacting the 4-amino-3-nitrothiophenol sodium solution with bromobenzene under an alkaline condition, and extracting after the reaction is finished to obtain the 2-nitro-4-thiophenyl aniline. The preparation method has the advantages of simple process, reduced production cost, reduced potential safety hazard, high product yield and reduced environmental pollution.
Description
Technical Field
The invention relates to the technical field of veterinary drugs, and in particular relates to a preparation method of fenbendazole intermediate 2-nitro-4-thiophenyl aniline.
Background
Fenbendazole is a high-efficiency low-toxicity broad-spectrum anthelmintic, can repel and kill ascaris, hookworm, whipworm, part of tapeworm, roundworm and other parasites in animal gastrointestinal tracts, and has the advantages of safety, low toxicity, good applicability and the like. By influencing the transportation and energy metabolism of cells, the polymerization of microtubules is prevented, the integrity and energy transmission function of insect body cells are damaged, and the insect expelling effect is finally achieved.
The prior art discloses a preparation method of fenbendazole, which comprises (1) nitration: using m-dichlorobenzene as a raw material, carrying out nitration reaction in concentrated sulfuric acid and nitric acid, removing a waste acid layer, neutralizing with alkali, and washing an organic layer with water to obtain 2, 4-dichloronitrobenzene; (2) condensation reaction: in DMF, 2, 4-dichloronitrobenzene and thiophenol are subjected to condensation reaction under the catalysis of alkali to obtain 2-chloro-4-thiophenyl nitrobenzene, and reflux dehydration is carried out in the reaction process; (3) amination reaction: in an organic solvent or water, 2-chloro-4-thiophenyl nitrobenzene and an amination reagent are subjected to amination reaction to obtain 2-nitro-4-thiophenyl aniline; (4) and (3) carrying out cyclization reaction, namely reacting the 2-nitro-4-thiophenyl aniline with a cyclization reagent in an organic solvent to obtain the fenbendazole. The method has the advantages of high waste salt yield, high cost and no contribution to industrialization. Therefore, it is necessary to develop a new process for preparing 2-nitro-4-thiophenylaniline in view of the above problems.
Disclosure of Invention
The invention aims to: aiming at the defects in the prior art, the preparation method of the fenbendazole intermediate 2-nitro-4-thiophenyl aniline is provided, and has the advantages of simple process, reduction of production cost, reduction of potential safety hazards in production, higher product yield and reduction of environmental pollution.
In order to achieve the purpose, the technical scheme of the invention is as follows:
a preparation method of fenbendazole intermediate 2-nitro-4-thiophenylaniline, which comprises the following steps:
(1) taking o-nitroaniline and ammonium thiocyanate as raw materials, taking an organic solvent as a solvent of a reaction system, uniformly stirring, introducing chlorine, and filtering after the reaction of the raw materials is finished to obtain 4-thiocyano-2-nitroaniline;
(2) adding the 4-thiocyano-2-nitroaniline and the sodium hydroxide in the step (1) into a reaction solvent, stirring and mixing, and filtering after the reaction is finished to obtain a 4-amino-3-nitrothiophenol sodium solution;
(3) and (3) reacting the sodium 4-amino-3-nitrothiophenolate solution obtained in the step (2) with bromobenzene under an alkaline condition, and extracting after the reaction is finished to obtain the 2-nitro-4-thiophenylaniline.
As an improved technical scheme, the reaction temperature of the step (1) is 15-25 ℃, and the molar ratio of the o-nitroaniline to the ammonium thiocyanate is 1: 1.05-1.2.
As an improved technical scheme, the organic solvent in the step (1) is methanol, ethanol, propanol or butanol.
As a preferable technical scheme, the organic solvent in the step (1) is methanol.
As an improved technical scheme, the reaction temperature of the step (2) is 35-50 ℃, and the molar ratio of the 4-thiocyano-2-nitroaniline to the sodium hydroxide is 1: 1.1-1.2.
As an improved technical scheme, the reaction solvent in the step (2) is water, an organic solvent or a mixture of water and the organic solvent.
As an improved technical scheme, when the reaction solvent in the step (2) is an organic solvent, the organic solvent is methanol, ethanol, propanol or butanol.
As an improved technical scheme, the reaction temperature of the step (3) is 60-75 ℃, and the molar ratio of the sodium 4-amino-3-nitrothiophenolate to bromobenzene in the sodium 4-amino-3-nitrothiophenolate solution is 1: 1.0-1.1.
As an improved technical scheme, the extractant used in the extraction in the step (3) is toluene.
The main reaction equation in the synthesis process of the invention is as follows:
the reaction equation of step (1):
the reaction equation of step (2):
the reaction equation of step (3):
by adopting the technical scheme, compared with the prior art, the invention has the following advantages:
in the method, o-nitroaniline and ammonium thiocyanate are used as reaction raw materials, an organic solvent is used as a solvent, chlorine is introduced, and 4-thiocyano-2-nitroaniline is obtained through reaction; adding the 4-thiocyano-2-nitroaniline and sodium hydroxide into a reaction solvent, and stirring and mixing to obtain a 4-amino-3-nitrothiophenol sodium solution; and finally, reacting the 4-amino-3-nitrothiophenol sodium solution with bromobenzene under an alkaline condition to obtain the 2-nitro-4-thiophenyl aniline. The whole reaction process is simple, the production cost of raw materials is reduced, the product yield is improved, the discharge amount of wastewater in the whole reaction process is small, and the pollution to the environment is reduced.
Drawings
FIG. 1 is a liquid phase mass spectrum of the anion of the target product 2-nitro-4-thiophenylaniline of the preparation process of the invention;
wherein 244.9 is 2-nitro-4-thiophenylaniline anion:
169.0 is a moiety of formula
366.9 is
Detailed Description
The present invention will be described in further detail in order to make the objects, technical solutions and advantages of the present invention more apparent. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.
Example 1
120g of methanol, 27.63g of o-nitroaniline and 15.99g of ammonium thiocyanate are added into a 250ml four-mouth bottle, the mixture is stirred uniformly, chlorine gas is introduced to control the reaction temperature to be 15 ℃, and after 4 hours of reaction, the mixture is filtered to obtain 36.88g of a solid thiocyanide product (4-thiocyano-2-nitroaniline) with the yield of 94.45 percent.
Adding 36.88g of thiocyanide product (4-thiocyano-2-nitroaniline) and 100g of purified water into a 250ml four-necked bottle, adding 8.31g of sodium hydroxide, controlling the reaction temperature to be 35 ℃, filtering after 20min of reaction to obtain 35.59g of aqueous solution containing 4-amino-3-nitrothiophenol sodium, wherein the yield is 98.12%;
heating the 4-amino-3-nitrothiophenyl sodium water solution to 60 ℃, dropwise adding an ethanol solution containing 29.10g of bromobenzene, adding an extracting agent toluene (the toluene is added according to the mass ratio of the toluene to the 4-amino-3-nitrothiophenyl sodium water solution of 1: 1) after the reaction is finished, and stirring for 10min to obtain a toluene solution containing 42.26g of 2-nitro-4-thiophenyl aniline, wherein the yield is 90.12%. The total yield of the reaction was 86.30%.
Example 2
Adding 120g of methanol, 27.63g of o-nitroaniline and 15.99g of ammonium thiocyanate into a 250ml four-neck bottle, uniformly stirring, introducing chlorine gas, controlling the reaction temperature to be 18 ℃, carrying out reaction for 4h, and filtering to obtain 36.77g of thiocyanide product (4-thiocyano-2-nitroaniline) with the yield of 94.15%.
Adding 36.77g of thiocyanide product (4-thiocyano-2-nitroaniline) and 100g of methanol into a 250ml four-necked bottle, adding 8.29g of sodium hydroxide, controlling the reaction temperature to be 38 ℃, reacting for 20min, and filtering to obtain 35.42g of alcoholic solution containing 4-amino-3-nitrothiophenol sodium, wherein the yield is 97.98%;
heating 4-amino-3-nitrobenzenesulfenyl sodium alcohol solution to 62 ℃, dropwise adding ethanol solution containing 34.76g bromobenzene, adding water (added according to the mass ratio of the water to the toluene of 1: 1) and an extractant toluene (added according to the mass ratio of the toluene to the 4-amino-3-nitrobenzenesulfenyl sodium alcohol solution of 1: 1) after the reaction is finished, and stirring for 10min to obtain toluene solution containing 43.33g 2-nitro-4-benzenesulfenylaniline with the yield of 95.47%. The total yield of the reaction was 88.07%.
Example 3
Adding 120g of methanol, 27.63g of o-nitroaniline and 15.99g of ammonium thiocyanate into a 250ml four-neck bottle, uniformly stirring, introducing chlorine gas, controlling the reaction temperature to be 20 ℃, and filtering after 4 hours of reaction to obtain 36.71g of thiocyanide product (4-thiocyano-2-nitroaniline) with the yield of 94.01%.
Adding 36.71g of thiocyanide product (4-thiocyano-2-nitroaniline) and 100g of ethanol with the volume concentration of 60% into a 250ml four-necked bottle, adding 9.02g of sodium hydroxide, controlling the reaction temperature to be 40 ℃, filtering after the reaction is finished for 20min to obtain 35.69g of alcoholic solution containing 4-amino-3-nitrothiophenol sodium, wherein the yield is 98.87%;
heating 4-amino-3-nitrobenzenesulfenyl sodium alcohol solution to 65 ℃, dropwise adding ethanol solution containing 35.02g bromobenzene, adding water (added according to the mass ratio of the water to the toluene of 1: 1) and an extractant toluene (added according to the mass ratio of the toluene to the 4-amino-3-nitrobenzenesulfenyl sodium alcohol solution of 1: 1) after the reaction is finished, and stirring for 10min to obtain toluene solution containing 43.51g 2-nitro-4-benzenesulfenylaniline with the yield of 95.14%. The total yield of the reaction was 88.43%.
Example 4
Adding 120g of methanol, 27.63g of o-nitroaniline and 15.99g of ammonium thiocyanate into a 250ml four-mouth bottle, uniformly stirring, introducing chlorine, controlling the reaction temperature to be 18 ℃, and filtering after 4 hours of reaction to obtain 36.70g of thiocyanide product with the yield of 93.98%.
36.70g of thiocyanide product and 100g of purified water are added into a 250ml four-mouth bottle, 9.02g of sodium hydroxide is added, the reaction temperature is controlled to be 48 ℃, and after 20min of reaction, the mixture is filtered to obtain 35.62g of aqueous solution containing 4-amino-3-nitrothiophenol sodium, and the yield is 98.71%;
heating the 4-amino-3-nitrothiophenyl sodium water solution to 68 ℃, dropwise adding an ethanol solution containing 29.13g of bromobenzene, adding an extracting agent toluene (the toluene is added according to the mass ratio of the toluene to the 4-amino-3-nitrothiophenyl sodium water solution of 1: 1) after the reaction is finished, and stirring for 10min to obtain a toluene solution containing 42.47g of 2-nitro-4-thiophenyl aniline with the yield of 93.04%. The total yield of the reaction was 86.31%.
Example 5
Adding 120g of methanol, 27.63g of o-nitroaniline and 18.27g of ammonium thiocyanate into a 250ml four-mouth bottle, and uniformly stirring; chlorine gas is introduced to control the reaction temperature to be 20 ℃, and after 4 hours of reaction, 37.62g of thiocyanide product is obtained by filtration, and the yield is 96.34%.
Adding 37.62g of thiocyanide product and 100g of purified water into a 250ml four-neck bottle, adding 8.48g of sodium hydroxide, controlling the reaction temperature to be 45 ℃, filtering after 20min of reaction to obtain 36.26g of aqueous solution containing 4-amino-3-nitrothiophenol sodium, wherein the yield is 98.01%;
heating the 4-amino-3-nitrothiophenyl sodium water solution to 63 ℃, dropwise adding an ethanol solution containing 29.65g of bromobenzene, adding an extracting agent toluene (the toluene is added according to the mass ratio of the toluene to the 4-amino-3-nitrothiophenyl sodium water solution of 1: 1) after the reaction is finished, and stirring for 10min to obtain a toluene solution containing 43.24g of 2-nitro-4-thiophenyl aniline with the yield of 93.08%. The total yield of the reaction was 87.89%.
Example 6
Adding 120g of methanol, 27.63g of o-nitroaniline and 18.27g of ammonium thiocyanate into a 250ml four-mouth bottle, and uniformly stirring; chlorine is introduced to control the reaction temperature to be 20 ℃, and after 4 hours of reaction, 37.54g of thiocyanide product is obtained by filtration, with the yield of 96.12%;
adding 37.54g of thiocyanide product and 100g of purified water into a 250ml four-neck bottle, adding 8.46g of sodium hydroxide, controlling the reaction temperature to be 40 ℃, filtering after 20min of reaction to obtain 36.21g of aqueous solution containing 4-amino-3-nitrothiophenol sodium, wherein the yield is 98.10%;
heating the 4-amino-3-nitrothiophenyl sodium water solution to 70 ℃, dropwise adding an ethanol solution containing 35.53g of bromobenzene, adding an extracting agent toluene (the toluene is added according to the mass ratio of the toluene to the 4-amino-3-nitrothiophenyl sodium water solution of 1: 1) after the reaction is finished, and stirring for 10min to obtain a toluene solution containing 44.17g of 2-nitro-4-thiophenyl aniline with the yield of 95.20%. The total yield of the reaction was 89.77%.
Example 7
Adding 120g of methanol, 27.63g of o-nitroaniline and 18.27g of ammonium thiocyanate into a 250ml four-mouth bottle, and uniformly stirring; chlorine is introduced to control the reaction temperature to be 25 ℃, and after 4 hours of reaction, 37.57g of thiocyanide product is obtained by filtration, and the yield is 96.21%;
adding 37.57g of thiocyanide product and 100g of purified water into a 250ml four-neck bottle, adding 9.24g of sodium hydroxide, controlling the reaction temperature to be 42 ℃, filtering after 20min of reaction to obtain an aqueous solution containing 36.52g of 4-amino-3-nitrothiophenol sodium, wherein the yield is 98.84%;
heating the 4-amino-3-nitrothiophenyl sodium water solution to 72 ℃, dropwise adding an ethanol solution containing 35.83g of bromobenzene, adding an extracting agent toluene (the toluene is added according to the mass ratio of the toluene to the 4-amino-3-nitrothiophenyl sodium water solution of 1: 1) after the reaction is finished, and stirring for 10min to obtain a toluene solution containing 44.6g of 2-nitro-4-thiophenyl aniline with the yield of 95.33%. The total yield of the reaction was 90.65%.
Example 8
Adding 120g of methanol, 27.63g of o-nitroaniline and 18.27g of ammonium thiocyanate into a 250ml four-mouth bottle, and uniformly stirring; chlorine gas is introduced to control the reaction temperature to be 15 ℃, and after 4 hours of reaction, 37.56g of thiocyanide product is obtained by filtration, and the yield is 96.17%.
Adding 37.56g of thiocyanide product and 100g of purified water into a 250ml four-neck bottle, adding 9.23g of sodium hydroxide, controlling the reaction temperature to be 50 ℃, filtering after 20min of reaction to obtain 36.39g of aqueous solution containing 4-amino-3-nitrothiophenol sodium, wherein the yield is 98.54%;
heating the 4-amino-3-nitrothiophenyl sodium water solution to 75 ℃, dropwise adding an ethanol solution containing 29.76g of bromobenzene, adding an extracting agent toluene (the toluene is added according to the mass ratio of the toluene to the 4-amino-3-nitrothiophenyl sodium water solution of 1: 1) after the reaction is finished, and stirring for 10min to obtain a toluene solution containing 43.66g of 2-nitro-4-thiophenyl aniline with the yield of 93.64%. The total yield of the reaction was 88.74%.
Example 9
Taking a toluene solution containing 12.3g of 2-nitro-4-thiophenylaniline (prepared by adopting any process condition of the above examples 1-8), adding 0.6g of Raney nickel catalyst, and putting the mixture into an autoclave for complete catalytic hydrogenation reaction; directly filtering, adding a cyclization agent for cyclization reaction to obtain a white solid, and finding that ultraviolet absorption of the white solid is completely overlapped with fenbendazole through liquid phase detection to confirm that the white solid is the fenbendazole.
The present patent is not limited to the above-mentioned embodiments, and those skilled in the art can make various changes without creative efforts from the above-mentioned conception, and fall within the protection scope of the present patent.
Claims (9)
1. A preparation method of fenbendazole intermediate 2-nitro-4-thiophenyl aniline is characterized by comprising the following steps:
(1) taking o-nitroaniline and ammonium thiocyanate as raw materials, taking an organic solvent as a solvent of a reaction system, uniformly stirring, introducing chlorine, and filtering after the reaction of the raw materials is finished to obtain 4-thiocyano-2-nitroaniline;
(2) adding sodium hydroxide and a reaction solvent into the 4-thiocyano-2-nitroaniline in the step (1), stirring and mixing, and filtering after the reaction is finished to obtain a 4-amino-3-nitrothiophenol sodium solution;
(3) and (3) reacting the sodium 4-amino-3-nitrothiophenolate solution obtained in the step (2) with bromobenzene under an alkaline condition, and extracting after the reaction is finished to obtain the 2-nitro-4-thiophenylaniline.
2. The preparation method of fenbendazole intermediate 2-nitro-4-thiophenylaniline according to claim 1, which is characterized in that: the reaction temperature of the step (1) is 15-25 ℃, and the molar ratio of the o-nitroaniline to the ammonium thiocyanate is 1: 1.05-1.2.
3. The preparation method of fenbendazole intermediate 2-nitro-4-thiophenylaniline according to claim 1, which is characterized in that: the organic solvent in the step (1) is methanol, ethanol, propanol or butanol.
4. The preparation method of fenbendazole intermediate 2-nitro-4-thiophenylaniline according to claim 3, characterized by comprising the following steps: the organic solvent in the step (1) is methanol.
5. The preparation method of fenbendazole intermediate 2-nitro-4-thiophenylaniline according to claim 1, which is characterized in that: the reaction temperature of the step (2) is 35-50 ℃, and the molar ratio of the 4-thiocyano-2-nitroaniline to the sodium hydroxide is 1: 1.1-1.2.
6. The preparation method of fenbendazole intermediate 2-nitro-4-thiophenylaniline according to claim 5, characterized in that: the reaction solvent in the step (2) is water, an organic solvent or a mixture of water and an organic solvent.
7. The preparation method of fenbendazole intermediate 2-nitro-4-thiophenylaniline according to claim 6, characterized by: the organic solvent is methanol, ethanol, propanol or butanol.
8. The preparation method of fenbendazole intermediate 2-nitro-4-thiophenylaniline according to claim 1, which is characterized in that: the reaction temperature of the step (3) is 60-75 ℃, and the molar ratio of the sodium 4-amino-3-nitrothiophenolate to bromobenzene in the sodium 4-amino-3-nitrothiophenolate solution is 1: 1.0-1.1.
9. The preparation method of fenbendazole intermediate 2-nitro-4-thiophenylaniline according to claim 1, which is characterized in that: the extractant used in the extraction in the step (3) is toluene.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010325271.XA CN111349032B (en) | 2020-04-23 | 2020-04-23 | Preparation method of fenbendazole intermediate 2-nitro-4-thiophenyl aniline |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010325271.XA CN111349032B (en) | 2020-04-23 | 2020-04-23 | Preparation method of fenbendazole intermediate 2-nitro-4-thiophenyl aniline |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN111349032A CN111349032A (en) | 2020-06-30 |
| CN111349032B true CN111349032B (en) | 2021-08-06 |
Family
ID=71191560
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010325271.XA Active CN111349032B (en) | 2020-04-23 | 2020-04-23 | Preparation method of fenbendazole intermediate 2-nitro-4-thiophenyl aniline |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN111349032B (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113185436A (en) * | 2021-07-01 | 2021-07-30 | 山东国邦药业有限公司 | Preparation method of 4-thiophenyl-o-phenylenediamine |
| CN114716428B (en) * | 2022-05-06 | 2024-02-06 | 山东潍坊润丰化工股份有限公司 | Method for preparing metazopyr intermediate |
| CN114716354B (en) * | 2022-06-10 | 2022-08-09 | 山东国邦药业有限公司 | Synthesis method of fenbendazole intermediate 2-nitro-4-thiophenylaniline |
| CN116496192B (en) * | 2023-06-21 | 2023-09-19 | 山东国邦药业有限公司 | Preparation method of 4-phenylthio-1, 2-phenylenediamine |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4331817A (en) * | 1981-01-16 | 1982-05-25 | Minnesota Mining And Manufacturing Co. | Process for the preparation of 4-arylthioanilines |
| CN102241635A (en) * | 2011-04-28 | 2011-11-16 | 江苏宝众宝达药业有限公司 | Preparation method for anthelmintic benzimidazole fenbendazole |
| CN103242237A (en) * | 2013-05-10 | 2013-08-14 | 常州亚邦齐晖医药化工有限公司 | New preparation method for anthelmintic fenbendazole |
| CN108299259A (en) * | 2018-01-16 | 2018-07-20 | 珠海优润医药科技有限公司 | The preparation method of 2- amino -5- thiophenyls-(2- methoxyl groups) antifebrin |
| CN109467535A (en) * | 2018-11-14 | 2019-03-15 | 江苏宝众宝达药业有限公司 | A kind of preparation method of Fenbendazole |
-
2020
- 2020-04-23 CN CN202010325271.XA patent/CN111349032B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4331817A (en) * | 1981-01-16 | 1982-05-25 | Minnesota Mining And Manufacturing Co. | Process for the preparation of 4-arylthioanilines |
| CN102241635A (en) * | 2011-04-28 | 2011-11-16 | 江苏宝众宝达药业有限公司 | Preparation method for anthelmintic benzimidazole fenbendazole |
| CN103242237A (en) * | 2013-05-10 | 2013-08-14 | 常州亚邦齐晖医药化工有限公司 | New preparation method for anthelmintic fenbendazole |
| CN108299259A (en) * | 2018-01-16 | 2018-07-20 | 珠海优润医药科技有限公司 | The preparation method of 2- amino -5- thiophenyls-(2- methoxyl groups) antifebrin |
| CN109467535A (en) * | 2018-11-14 | 2019-03-15 | 江苏宝众宝达药业有限公司 | A kind of preparation method of Fenbendazole |
Also Published As
| Publication number | Publication date |
|---|---|
| CN111349032A (en) | 2020-06-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN111349032B (en) | Preparation method of fenbendazole intermediate 2-nitro-4-thiophenyl aniline | |
| CN101821293B (en) | Conversion method | |
| US8921557B2 (en) | Preparation of low impurity opiates in a continuous flow reactor | |
| CN111100012B (en) | Method for preparing m-phenylenediamine | |
| WO2017024608A1 (en) | Preparation method for nylon weather resistant additive | |
| CN1911907A (en) | Preparation method of dyestuff intermediate H acid | |
| Rahmatpour | An efficient, high yielding, and eco-friendly method for the synthesis of 14-aryl-or 14-alkyl-14 H-dibenzo [a, j] xanthenes using polyvinylsulfonic acid as a recyclable Brønsted acid catalyst | |
| Liu et al. | H 2 O 2-promoted C–C bond oxidative cleavage of β-O-4 lignin models to benzanilides using water as a solvent under metal-free conditions | |
| CN102432517A (en) | Method for producing chlorfenapyr raw material pesticide | |
| CN102558555B (en) | High-temperature-resistant ultraviolet absorbent containing polyfluorene triazole and preparation method thereof | |
| EP1205469B1 (en) | Process for the preparation of 4-amino diphenylamine | |
| CN108299259B (en) | Preparation method of 2-amino-5-thiophenyl- (2-methoxy) acetanilide | |
| CN107881201A (en) | A kind of method of m-hydroxybenzoic acid synthesis resorcinol | |
| CN116496192B (en) | Preparation method of 4-phenylthio-1, 2-phenylenediamine | |
| KR20040002719A (en) | Process for the preparation of polyisocyanates of the diphenylmethane group having a reduced color value | |
| US11673857B2 (en) | Preparation method of 1-(4-aminophenyl)cyclopentanecarbonitrile | |
| CN114656465A (en) | Preparation method of avibactam sodium | |
| CN111153804A (en) | Preparation method of p-nitrobenzyl bromide | |
| CN114716354B (en) | Synthesis method of fenbendazole intermediate 2-nitro-4-thiophenylaniline | |
| CN114456084B (en) | Synthesis method of aromatic azo compound | |
| CN112266317B (en) | Process for preparing 1,2, 4-trifluorobenzene | |
| CN114057632B (en) | Environment-friendly synthesis method of 3-chloro-2-hydrazinopyridine | |
| KR910005767B1 (en) | Process for the preparation of 2,4-dinitro aniline | |
| Gondake et al. | Green approach to Chemo-Selective N-Boc Protection of Amines using Catalytic amount of Lithium Hydroxide Monohydrate under Solvent Free Condition | |
| Chapman et al. | Benzylamine-Free, heavy-metal-free synthesis of CL-20 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |