CN114874147A - Preparation method of 4, 6-dichloro 5-fluoropyrimidine - Google Patents
Preparation method of 4, 6-dichloro 5-fluoropyrimidine Download PDFInfo
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- CN114874147A CN114874147A CN202210462809.0A CN202210462809A CN114874147A CN 114874147 A CN114874147 A CN 114874147A CN 202210462809 A CN202210462809 A CN 202210462809A CN 114874147 A CN114874147 A CN 114874147A
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- dichloro
- fluoropyrimidine
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
- C07D239/30—Halogen atoms or nitro radicals
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/584—Recycling of catalysts
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a preparation method of 4, 6-dichloro 5-fluoropyrimidine, which comprises the steps of taking isopentafluoro as a starting material, immersing the starting material in a solvent, slowly adding a catalyst, irradiating by ultraviolet light for 12-20 minutes, introducing chlorine, stirring for 9-10 hours at the reaction temperature of 20-25 ℃, introducing chlorine, carrying out heat preservation and reflux reaction for 2-24 hours, separating a water layer after the reflux is finished, evaporating toluene, and then distilling to obtain 4, 6-dichloro 5-fluoropyrimidine mother liquor. The invention has simple and easy technical process, mild condition, low cost, no waste residue, effective prevention of environmental pollution, obvious economic and social benefits and high purity of the obtained product, and is suitable for industrial production.
Description
Technical Field
The invention relates to the technical field of pharmaceutical chemicals, and particularly relates to a preparation method of 4, 6-dichloro-5-fluoropyrimidine.
Background
4, 6-dichloro-5-fluoropyrimidine is an important intermediate for synthesizing antifungal drug voriconazole and the like, wherein the annual production amount of 4, 6-dichloro-5-fluoropyrimidine is increased year by year. However, the existing production process has the defects of complex reaction, troublesome operation, low product yield and low purity, and the method develops a simple, convenient and effective green synthesis process due to the generation of phosphoric acid-containing wastewater and great pollution, thereby not only reducing the production cost, but also reducing the environmental pollution and achieving the purposes of energy conservation and emission reduction, and is a problem to be solved in the field for a long time.
Disclosure of Invention
The invention aims to provide a preparation method of 4, 6-dichloro-5-fluoropyrimidine aiming at the defects and shortcomings of the prior art.
In order to achieve the purpose, the invention adopts the technical scheme that: the preparation method of 4, 6-dichloro-5-fluoropyrimidine has the innovation points that: immersing iso-pentafluoro serving as a starting raw material into a solvent, slowly adding a catalyst, irradiating by ultraviolet light for 12-20 minutes, introducing chlorine gas at the reaction temperature of 20-25 ℃, introducing chlorine, stirring for 9-10 hours, carrying out heat preservation reflux reaction for 2-24 hours, separating a water layer after the reflux is finished, evaporating toluene, and then distilling to obtain the 4, 6-dichloro 5-fluoropyrimidine mother liquor.
Further, the solvent is dichloromethane, dichloroethane or chloroform.
Furthermore, the catalyst is sulfonyl chloride, and the addition amount of the sulfonyl chloride is 2-4% of the mass of 4, 6-dichloro-5-fluoropyrimidine.
Further, washing the 4, 6-dichloro-5-fluoropyrimidine mother liquor with acid water to remove impurities, and then precipitating the product again.
Further, the acid water for washing is hydrochloric acid water solution, sulfuric acid water solution, phosphoric acid water solution or citric acid water solution purple.
Further, the wavelength of the ultraviolet light is 220-280 nm.
The invention has the beneficial effects that:
the invention has simple and easy technical process, mild condition, low cost, no waste residue, effective prevention of environmental pollution, obvious economic and social benefits and high purity of the obtained product, and is suitable for industrial production.
Detailed Description
The following examples further illustrate the invention.
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is further described in detail with reference to the following embodiments. It should be understood that the detailed description and specific examples, while indicating the invention, are intended for purposes of illustration only and are not intended to limit the scope of the invention.
Example 1
A preparation method of 4, 6-dichloro 5-fluoropyrimidine, using iso-pentafluoro as a starting material, immersing the starting material in a dichloromethane solvent, slowly adding a catalyst sulfonyl chloride, wherein the adding amount is 2% of the mass of the 4, 6-dichloro 5-fluoropyrimidine, irradiating the starting material by adopting ultraviolet light with the wavelength of 220nm for 12 minutes, introducing chlorine, reacting at the temperature of 20-25 ℃, introducing chlorine, stirring for 9 hours, carrying out heat preservation and reflux reaction for 6 hours, separating a water layer after the reflux is finished, steaming to remove methylbenzene, then distilling to obtain 4, 6-dichloro 5-fluoropyrimidine mother liquor, washing the 4, 6-dichloro 5-fluoropyrimidine mother liquor by using a hydrochloric acid aqueous solution to remove impurities, and precipitating a product again; the product purity is 99.3 percent, and the total yield is 96 percent.
Example 2
A preparation method of 4, 6-dichloro 5-fluoropyrimidine, using iso-pentafluoro as a starting material, immersing into dichloroethane solvent, slowly adding catalyst sulfonyl chloride, wherein the adding amount is 4% of the mass of 4, 6-dichloro 5-fluoropyrimidine, irradiating by ultraviolet light with the wavelength of 280nm for 20 minutes, introducing chlorine, reacting at the temperature of 25 ℃, introducing chlorine, stirring for 10 hours, carrying out heat preservation reflux reaction for 22 hours, separating a water layer, evaporating toluene, distilling to obtain 4, 6-dichloro 5-fluoropyrimidine mother liquor, washing the 4, 6-dichloro 5-fluoropyrimidine mother liquor by using sulfuric acid aqueous solution to remove impurities, and separating out a product again; the product purity is 99.5 percent, and the total yield is 97 percent.
Example 3
A preparation method of 4, 6-dichloro 5-fluoropyrimidine, using iso-pentafluoro as a starting material, immersing the starting material in a chloroform solvent, slowly adding a catalyst sulfonyl chloride, wherein the adding amount is 3% of the mass of 4, 6-dichloro 5-fluoropyrimidine, irradiating the starting material by ultraviolet light with the wavelength of 260nm for 17 minutes, introducing chlorine, reacting at the temperature of 23 ℃, introducing chlorine, stirring for 9 hours, carrying out heat preservation reflux reaction for 15 hours, separating a water layer after the reflux is finished, evaporating toluene, then distilling to obtain 4, 6-dichloro 5-fluoropyrimidine mother liquor, washing the 4, 6-dichloro 5-fluoropyrimidine mother liquor by using citric acid aqueous solution to remove impurities, and precipitating a product again; the product purity is 99.8 percent, and the total yield is 97 percent.
The above description is only for the purpose of illustrating the technical solutions of the present invention and not for the purpose of limiting the same, and other modifications or equivalent substitutions made by those skilled in the art to the technical solutions of the present invention should be covered within the scope of the claims of the present invention without departing from the spirit and scope of the technical solutions of the present invention.
Claims (6)
1. A preparation method of 4, 6-dichloro 5-fluoropyrimidine is characterized by comprising the following steps: immersing iso-pentafluoro serving as a starting raw material into a solvent, slowly adding a catalyst, irradiating by ultraviolet light for 12-20 minutes, introducing chlorine gas at the reaction temperature of 20-25 ℃, introducing chlorine, stirring for 9-10 hours, carrying out heat preservation reflux reaction for 2-24 hours, separating a water layer after the reflux is finished, evaporating toluene, and then distilling to obtain the 4, 6-dichloro 5-fluoropyrimidine mother liquor.
2. The process for preparing 4, 6-dichloro-5-fluoropyrimidine according to claim 1, wherein: the solvent is dichloromethane, dichloroethane or chloroform.
3. The process for preparing 4, 6-dichloro-5-fluoropyrimidine according to claim 1, wherein: the catalyst is sulfonyl chloride, and the addition amount of the sulfonyl chloride is 2-4% of the mass of 4, 6-dichloro-5-fluoropyrimidine.
4. The process for preparing 4, 6-dichloro-5-fluoropyrimidine according to claim 1, wherein: washing the 4, 6-dichloro-5-fluoropyrimidine mother liquor with acid water to remove impurities, and separating out the product again.
5. The process for preparing 4, 6-dichloro-5-fluoropyrimidine according to claim 4, wherein: the acid water for washing is hydrochloric acid water solution, sulfuric acid water solution, phosphoric acid water solution or citric acid water solution purple.
6. The process for preparing 4, 6-dichloro-5-fluoropyrimidine according to claim 1, wherein: the wavelength of the ultraviolet light is 220-280 nm.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210462809.0A CN114874147A (en) | 2022-04-28 | 2022-04-28 | Preparation method of 4, 6-dichloro 5-fluoropyrimidine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210462809.0A CN114874147A (en) | 2022-04-28 | 2022-04-28 | Preparation method of 4, 6-dichloro 5-fluoropyrimidine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN114874147A true CN114874147A (en) | 2022-08-09 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210462809.0A Pending CN114874147A (en) | 2022-04-28 | 2022-04-28 | Preparation method of 4, 6-dichloro 5-fluoropyrimidine |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN114874147A (en) |
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2022
- 2022-04-28 CN CN202210462809.0A patent/CN114874147A/en active Pending
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