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Synthesis method of 5-nitroimidazole drugs

A technology of nitroimidazoles and nitroimidazoles, which is applied in the field of synthesis of 5-nitroimidazoles, can solve the problems of difficulty in obtaining sulfate esters, instability of sulfate esters, and low total yield, so as to reduce energy consumption and The effect of cost, reduction of three wastes, and high catalytic activity

Inactive Publication Date: 2020-03-27
湖南九典宏阳制药有限公司
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The defect of this synthesis method is that the intermediate (3-chloro-2-hydroxypropyl) sulfate is difficult to obtain, and the synthesis needs to use sulfuryl chloride with high reactivity and strong corrosion, and this sulfate is unstable. Three-step synthesis, low total yield, large amount of three wastes, high cost

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  • Synthesis method of 5-nitroimidazole drugs
  • Synthesis method of 5-nitroimidazole drugs
  • Synthesis method of 5-nitroimidazole drugs

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[0026] The invention provides a method for synthesizing 5-nitroimidazoles, comprising:

[0027] A) mixing 2-methyl-5-nitroimidazole, ethyl acetate and an aluminum chloride catalyst supported on a macroporous resin to obtain a mixed system;

[0028] B) Add epichlorohydrin or propylene oxide dropwise into the above mixed system and react to obtain 5-nitroimidazole antibacterial drugs.

[0029] The 5-nitroimidazole drug of the present invention is ornidazole or secnidazole. That is to say, the present invention discloses a synthetic method of ornidazole and a synthetic method of secnidazole.

[0030] The present invention mixes 2-methyl-5-nitroimidazole, ethyl acetate and an aluminum chloride catalyst supported on a macroporous resin to obtain a mixed system; 5-nitroimidazole, ethyl acetate and the aluminum trichloride catalyst supported on the macroporous resin are mixed.

[0031] The above mixing is preferably mixed in a reaction bottle, preferably a reactor with a stirring ...

Embodiment 1

[0057] Embodiment 1 (ornidazole)

[0058] In reaction bottle, add 330 g 2-methyl-5-nitroimidazoles, 1650 g ethyl acetate, add the aluminum chloride catalyst 1650 g that is loaded on the macroporous resin after opening stirring, stir well, stirring speed is 150 g rpm-200 rpm;

[0059] Add 330 g of epichlorohydrin dropwise to the reaction system at a rate of 3-5 ml / min, and control the internal temperature to not exceed 50 degrees;

[0060] After dripping epichlorohydrin, keep 45 degrees to react for 1.5 hours, filter, the catalyst is washed with 660 grams of ethyl acetate, filter again, and dry to be used mechanically; Pressure precipitation; add 330 grams of ethanol to the residue, heat to dissolve, cool down and crystallize, filter with suction, and dry to obtain the finished product of ornidazole.

[0061] Detected by HPLC, the results are as follows: figure 1 said, figure 1 The HPLC figure of the ornidazole prepared for the embodiment of the present invention 1; By fig...

Embodiment 2

[0063] Embodiment 2 (secnidazole)

[0064] In reaction flask, add 330 g 2-methyl-5-nitroimidazoles, 1650 g ethyl acetate, add the aluminum chloride catalyst 1650 g that is loaded on the macroporous resin after starting to stir, stir well; Stir to be 150 rpm -200 rpm;

[0065] Add 300 g of propylene oxide dropwise to the reaction system at a rate of 3-5 ml / min, and control the internal temperature to not exceed 50 degrees;

[0066] After dropping the propylene oxide, keep it at 40°C for 1.5 hours, filter, wash the catalyst with 660 g of ethyl acetate, filter again, and dry it to be used mechanically; Precipitate; add 330 g of purified water to the residue, heat to dissolve, cool down and crystallize, filter with suction, and dry to obtain the finished product of ornidazole.

[0067] Detected by HPLC, the results are as follows: figure 2 said, figure 2 For the HPLC figure of the secnidazole prepared by the embodiment of the present invention 2, by figure 2 It can be calc...

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Abstract

The invention provides a synthesis method of 5-nitroimidazole drugs. The synthesis method comprises the steps: A) mixing 2-Methyl-5-nitroimidazole, ethyl acetate and aluminum trichloride catalyst supported on macroporous resin to obtain a mixed system; B) dropwise adding epichlorohydrin or propylene oxide to the mixed system and reacting to obtain a 5-Nitroimidazole antimicrobial drug. The aluminum trichloride catalyst supported on resin is adopted, the high catalytic activity of aluminum trichloride is retained, the post-reaction treatment process is simplified, the catalyst can be separatedonly through simple filtration, and the catalyst can be recycled for 3-5 times and activity basically remains unchanged, thus greatly reducing the three wastes of the catalyst used in the traditionalprocess and reducing the energy consumption and cost. Meanwhile, the aluminum trichloride catalyst supported on the resin is adopted and the reaction temperature does not need low temperature reaction, thus saving more energy and improving the reaction yield which can reach 75% ~ 80%.

Description

technical field [0001] The invention relates to the technical field of organic synthesis, in particular to a method for synthesizing 5-nitroimidazole drugs. Background technique [0002] Ornidazole is the latest generation of 5-nitroimidazole drugs, which has highly effective anti-anaerobic bacteria, anti-trichomonas and anti-amoeba activities. It was first listed in Germany by Roche in 1977. Ornidazole has a wide range of indications, long-lasting action, and less side effects of the drug, and its drug effect is obviously better than traditional 5-nitroimidazoles such as metronidazole and tinidazole. At present, ornidazole has become the drug of choice in many countries in the prevention of anaerobic infection and the treatment of amebiasis, trichomoniasis, and various vaginal inflammations, and the market demand is large. [0003] Secnidazole is used to treat various acute and chronic hepatic and intestinal amoebiasis and trichomoniasis such as urethra, female vagina and ...

Claims

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Application Information

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IPC IPC(8): C07D233/94B01J31/06
CPCB01J31/069C07D233/94Y02P20/584
Inventor 谭军华胡矿
Owner 湖南九典宏阳制药有限公司
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