CN110642763A - Synthetic method of thiamphenicol - Google Patents
Synthetic method of thiamphenicol Download PDFInfo
- Publication number
- CN110642763A CN110642763A CN201810678508.5A CN201810678508A CN110642763A CN 110642763 A CN110642763 A CN 110642763A CN 201810678508 A CN201810678508 A CN 201810678508A CN 110642763 A CN110642763 A CN 110642763A
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- CN
- China
- Prior art keywords
- thiamphenicol
- synthesis method
- ethyl ester
- dichloroacetonitrile
- borohydride
- 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.)
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C315/00—Preparation of sulfones; Preparation of sulfoxides
- C07C315/04—Preparation of sulfones; Preparation of sulfoxides by reactions not involving the formation of sulfone or sulfoxide groups
Abstract
The invention discloses a synthesis method of thiamphenicol, which comprises the steps of taking D-p-methylsulfonyl phenyl serine ethyl ester as a starting material, reducing by using potassium borohydride or sodium borohydride, adding organic acid to regulate the pH value, cyclizing with dichloroacetonitrile, and hydrolyzing by hydrochloric acid to obtain thiamphenicol; the invention has simple process operation, easily obtained raw materials, high conversion rate and greatly reduced cost.
Description
Technical Field
The invention relates to the field of compound synthesis, in particular to a synthetic method of thiamphenicol.
Background
Thiamphenicol is firstly reported by Cutler and the like as a synthesis process and antibacterial activity, is widely applied to immunosuppressive states and feed additives abroad, and has large demand. The synthetic route adopts levorotatory amino compound as an intermediate for producing chloramphenicol to obtain a final product through several steps of reactions. The 70 s reported the synthesis route of phenylserine, p-methylsulfonylbenzaldehyde was used as the starting material and condensed with glycine to prepare p-methylsulfonylphenylserine or copper salt thereof, and then the p-methylsulfonylphenylserine or copper salt thereof is esterified, resolved, reduced, dichloroacetylated, concentrated and crystallized to prepare thiamphenicol, wherein the related resolved product has been produced in mass production and is low in price in the market at present. The synthesis method provided by the invention is mainly characterized in that the step of reducing the resolution product of the original process, namely D-p-methylsulfonylphenylserine ethyl ester, replaces the steps of acylation, concentration and crystallization of the original process by a method of cyclization and hydrolysis, and has the advantages of simpler process operation, high conversion rate and low cost.
Disclosure of Invention
The invention aims to provide a synthetic method of thiamphenicol.
The invention is realized by the following technical scheme: using D-p-methylsulfonylphenylserine ethyl ester as a starting material, reducing by using potassium borohydride or sodium borohydride, adding organic acid to regulate the pH value, cyclizing with dichloroacetonitrile, and hydrolyzing with hydrochloric acid to obtain thiamphenicol. Compared with the most advanced synthesis method at present, the method of firstly cyclizing and then hydrolyzing replaces the steps of acylation, concentration and crystallization, the process operation is simple, the raw materials are easy to obtain, the conversion rate is high, and the cost can be greatly reduced.
The weight ratio of D-p-methylsulfonylphenylserine ethyl ester to potassium borohydride or sodium borohydride to dichloroacetonitrile in the invention is =1:0.1 ~ 0.5.5: 0.1 ~ 0.5.5.
The invention has the reduction reaction temperature of 20 ~ 55 ℃, the cyclization reaction temperature of 20 ~ 80 ℃ and the hydrolysis temperature of 60 ~ 90 ℃.
The invention has the beneficial effects that: the invention has simple process operation, easily obtained raw materials, high conversion rate and greatly reduced cost.
Detailed Description
Example 1
50g D-p-methylsulfonylphenylserine ethyl ester and 400ml methanol are put into a 500ml reaction bottle, the temperature is controlled to be not more than 40 ℃, 25g of potassium borohydride is added, after the reduction is finished, glacial acetic acid is added to adjust the pH to be =7, 21g of dichloroacetonitrile is added, heat preservation at 65 ℃ is carried out to form a ring, 6N hydrochloric acid is added, the reaction is carried out for 2.5 hours at 85 ℃, the temperature is reduced, the filtration is carried out, and the thiamphenicol is obtained after drying, 49.2g, and the yield is 79.4%.
Claims (3)
1. A synthesis method of thiamphenicol is characterized in that D-p-methylsulfonylphenylserine ethyl ester is used as a starting material, potassium borohydride or sodium borohydride is used for reduction, glacial acetic acid is added to adjust the pH value to be cyclized with dichloroacetonitrile under the environment of 4 ~ 9, and hydrochloric acid is hydrolyzed to obtain the thiamphenicol.
2. The synthesis method of thiamphenicol, according to claim 1, is characterized in that the weight ratio of D-p-methylsulfonylphenylserine ethyl ester to potassium borohydride or sodium borohydride to dichloroacetonitrile is =1:0.1 ~ 0.5.5: 0.1 ~ 0.5.5.
3. The synthesis method of thiamphenicol according to claim 1, which is characterized in that the reduction reaction temperature is 20 ~ 55 ℃, the cyclization reaction temperature is 20 ~ 80 ℃, and the hydrolysis temperature is 60 ~ 90 ℃.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810678508.5A CN110642763A (en) | 2018-06-27 | 2018-06-27 | Synthetic method of thiamphenicol |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810678508.5A CN110642763A (en) | 2018-06-27 | 2018-06-27 | Synthetic method of thiamphenicol |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN110642763A true CN110642763A (en) | 2020-01-03 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810678508.5A Pending CN110642763A (en) | 2018-06-27 | 2018-06-27 | Synthetic method of thiamphenicol |
Country Status (1)
| Country | Link |
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| CN (1) | CN110642763A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114605296A (en) * | 2022-03-17 | 2022-06-10 | 无锡鸣鹭医药科技有限公司 | Thiomycin preparation and separation process |
-
2018
- 2018-06-27 CN CN201810678508.5A patent/CN110642763A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114605296A (en) * | 2022-03-17 | 2022-06-10 | 无锡鸣鹭医药科技有限公司 | Thiomycin preparation and separation process |
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Legal Events
| Date | Code | Title | Description |
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| PB01 | Publication | ||
| PB01 | Publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20200103 |
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| WD01 | Invention patent application deemed withdrawn after publication |