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Synthetic method of nifuratel

A synthesis method and nifuratel technology are applied in the field of pharmaceutical synthesis and can solve the problems of low purity, many product impurities, low reaction rate and yield, etc.

Active Publication Date: 2014-04-30
BEIJING CHENGYI INVESTMENT CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] Above-mentioned two kinds of methods have no essential difference, all are to use epichlorohydrin as starting material, only when preparing 3-methylthio-2-hydroxyl-propylhydrazine, the reaction sequence is slightly different; but above-mentioned synthetic The methods are all carried out in the alkaline environment of methanol-sodium methoxide, and in industrial scale production, due to the use of metal sodium, there will be a risk of explosion
In addition, the reaction rate and yield of above-mentioned synthetic method are all lower, and product impurity is many, purity is low

Method used

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  • Synthetic method of nifuratel

Examples

Experimental program
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Effect test

Embodiment 1

[0043] Carry out the preparation of nifuratel according to the following process:

[0044] (1) Put 1mol epichlorohydrin, 280ml dichloromethane, and 0.05mol tetrabutylammonium bromide into the reaction flask, and slowly add 20% aqueous solution of sodium methylmercaptide (sodium methylmercaptan 6.5mol) dropwise under stirring , the dropping time is 2 hours, and the temperature is controlled at 15-25°C during the dropping process; after the dropping is completed, the temperature is kept at 18°C ​​for 3 hours. Epoxypropyl methyl sulfide, yield is 78%;

[0045] (2) Put hydrazine hydrate into another reaction bottle according to the molar ratio of epoxypropyl methyl sulfide and hydrazine hydrate as 1:1.05, stir and raise the temperature to 95°C, slowly drop the epoxy obtained in step (1) Propyl methyl sulfide, dropwise time is 1h; then react at 95-98°C for 3h, after the reaction is completed, lower to room temperature; first concentrate the reaction solution to viscous, then disti...

Embodiment 2

[0050] Carry out the preparation of nifuratel according to the following process:

[0051] (1) Put 1mol of epichlorohydrin, 280ml of dichloromethane, and 0.055mol of tetrabutylammonium bromide into the reaction flask, and slowly add 20% aqueous solution of sodium methyl mercaptide (7 mol of sodium methyl mercaptide) dropwise under stirring. The dropping time is 2 hours, and the temperature is controlled at 15-25°C during the dropping process; after the dropping, keep the temperature at 20°C for 3 hours, after the reaction, distill the reaction solution under reduced pressure, and collect the fractions of bp2050-55°C to obtain purified ring Oxypropyl methyl sulfide, yield is 80%;

[0052] (2) According to the molar ratio of glycidyl methyl sulfide and hydrazine hydrate as 1:1.1, put hydrazine hydrate into another reaction bottle, stir and raise the temperature to 95°C, slowly drop the epoxy obtained in step (1) Propyl methyl sulfide, dropwise time is 1h; then react at 95-98°C ...

Embodiment 3

[0057] Carry out the preparation of nifuratel according to the following process:

[0058] (1) Put 1mol of epichlorohydrin, 280ml of dichloromethane, and 0.06mol of tetrabutylammonium bromide into the reaction flask, and slowly add 20% aqueous solution of sodium methyl mercaptide (8 mol of sodium methyl mercaptide) dropwise under stirring. The dropping time is 2 hours, and the temperature is controlled at 15-25°C during the dropping process; after the dropping, keep the temperature at 20°C for 3 hours, after the reaction, distill the reaction solution under reduced pressure, and collect the fractions of bp2050-55°C to obtain purified ring Oxypropyl methyl sulfide, yield is 82%;

[0059] (2) According to the molar ratio of glycidyl methyl sulfide and hydrazine hydrate as 1:1.2, put hydrazine hydrate into another reaction bottle, stir and raise the temperature to 95°C, slowly drop the epoxy obtained in step (1) Propyl methyl sulfide, dropwise time is 1h; then react at 95-98°C f...

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Abstract

The invention discloses a synthetic method of nifuratel. The synthetic method comprises the steps of carrying out a substitution reaction between epoxy chloropropane and sodium methyl mercaptide in the presence of a phase transfer catalyst to obtain epoxy propyl dimethyl sulfide, and then performing hydrazinolysis, cyclization and condensation on the obtained epoxy propyl dimethyl sulfide to obtain the nifuratel. The synthetic method is high in nifuratel yield, high in purity and low in impurity content; besides the method has the advantages that a ring-closure reaction is carried out under the alkaline condition of sodium methoxide, the use of metal sodium is avoided, production safety is ensured, and simultaneously, the reaction is easy to arouse, easy to control in process, the used raw materials are easy to get, basically no waste liquid is generated in the reaction of each step, and therefore, industrial pollution is greatly reduced; and as a result, the synthetic method of nifuratel is applicable to industrial production.

Description

technical field [0001] The invention relates to the technical field of drug synthesis, in particular to a method for synthesizing nifuratel. Background technique [0002] Nifuratel, its chemical name is: 5-[(methylthio)methyl]-3-[[(5-nitro-2-furan)methylene]amino]-2-oxazole Alkanone, molecular formula C 10 h 11 N 3 o 5 S, the molecular weight is 285.28, the chemical structure formula is as follows: [0003] [0004] Nifuratel is a nitrofuran antibiotic drug, which has a significant effect on the treatment of mixed vaginal infections. Its trichomonadicidal activity is equivalent to that of metronidazole, has antibacterial effect, and can effectively kill Chlamydia trachomatis and Mycoplasma, and has certain activity against Candida. Oral and vaginal administration of nifuratel shows that it is well tolerated and has no drug resistance. The cure rate for bacterial vaginosis is equivalent to that of ampicillin and carbenicillin, and the incidence of adverse reactions i...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D413/12
CPCC07D413/12
Inventor 程雪翔
Owner BEIJING CHENGYI INVESTMENT CO LTD
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