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Method for synthesizing econazole nitrate by using one-pot method

A technology of econazole nitrate and imidazole, which is applied in the field of one-pot synthesis of econazole nitrate, which can solve the problems of easy harm to people and the environment, difficult storage of metal sodium, and cumbersome operation procedures, so as to reduce pollution and reduce solvent recovery The number of times, the effect of improving the reaction efficiency

Active Publication Date: 2020-01-14
XUZHOU COLLEGE OF INDAL TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Benzene is a carcinogen with a melting point of 5°C and is difficult to handle in winter
Sodium metal is not easy to preserve, sodium methoxide is flammable, explosive, easy to absorb moisture, and has strong irritation and corrosion
[0008] As can be seen from the above, the current method for synthesizing econazole nitrate also has defects such as cumbersome operation process, low yield, and easy generation of hazards to people and the environment. The synthetic method of econazole nitrate with simple operation, environmental protection and high yield still needs Continue to study

Method used

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  • Method for synthesizing econazole nitrate by using one-pot method

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] A method for the one-pot synthesis of econazole nitrate, such as figure 1 shown, including the following steps:

[0027] (1)K 2 CO 3 / KOH / A1 2 o 3 Preparation: 90g K 2 CO 3 , 35g KOH dissolved in 110g water, add 145gA1 2 o 3 , with stirring at 60°C, heat preservation for 1h, rotary evaporation, and drying at 120°C for 4h to obtain 258.7g K 2 CO 3 / KOH / A1 2 o 3 ;

[0028] (2) preparation of econazole nitrate: 80gK 2 CO 3 / KOH / A1 2 o 3 Ⅰ, 30g imidazole, 190g toluene Ⅰ, 2.5g PEG-200Ⅰ were added to a 500mL reaction bottle, the temperature was raised to reflux and the water was separated for 30 minutes, the temperature was lowered to 60°C, and 90g 1-(2,4-dichlorophenyl)-2-chloro - Mixed solution of ethanol and 120g toluene II, heated to 72°C, reacted for 3.5h; filtered, washed with water, combined the filtrate and washing liquid, left to separate the organic layer, washed the organic layer with water once, added 0.5g activated carbon I, Insulated for 10 minut...

Embodiment 2

[0031] A method for synthesizing econazole nitrate in one pot, comprising the following steps:

[0032] (1)K 2 CO 3 / KOH / A1 2 o 3 Preparation: 90g K 2 CO 3 , 35g KOH dissolved in 110g water, add 145gA1 2 o 3 , with stirring at 65°C, heat preservation for 1h, rotary evaporation, and drying at 120°C for 4h to obtain 257.6g K 2 CO 3 / KOH / A1 2 o 3 ;

[0033] (2) preparation of econazole nitrate: 90gK 2 CO 3 / KOH / A1 2 o 3 Ⅰ, 29.5g imidazole, 180g toluene Ⅰ, 1.6g PEG-200Ⅰ were added to a 500mL reaction bottle, the temperature was raised to reflux and water was separated for 25 minutes, the temperature was lowered to 60°C, and 90g 1-(2,4-dichlorophenyl)-2-chloro -The mixture of ethanol and 130g of toluene II was heated up to 71°C and reacted for 3.0h. Filtrate, wash with water, combine the filtrate and washing liquid, let stand to separate the organic layer, wash the organic layer once with water, add 0.7g of activated carbon I, keep warm for 10 minutes, heat filter, ...

Embodiment 3

[0036] A method for synthesizing econazole nitrate in one pot, comprising the following steps:

[0037] (1)K 2 CO 3 / KOH / A1 2 o 3 Preparation: 90g K 2 CO 3 , 35g KOH dissolved in 110g water, add 145gA1 2 o 3 , with stirring at 62°C, heat preservation for 1h, rotary evaporation, and drying at 120°C for 4h to obtain 256.5g K 2 CO 3 / KOH / A1 2 o 3 ;

[0038] (2) preparation of econazole nitrate: 95gK 2 CO 3 / KOH / A1 2 o 3 Ⅰ, 28.6g imidazole, 170g toluene Ⅰ, 3.2g PEG-200Ⅰ were added to a 500mL reaction bottle, the temperature was raised to reflux for 35 minutes, the temperature was lowered to 60°C, and 90g 1-(2,4-dichlorophenyl)-2-chloro- The mixture of ethanol and 140g of toluene II was heated to 73°C and reacted for 3.5 hours; filtered, washed with water, combined with the filtrate and washing liquid, left to separate the organic layer, washed the organic layer with water once, added 0.9g of activated carbon Ⅰ, and kept warm 10min, heat filtration, obtain the imida...

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Abstract

The invention discloses a method for synthesizing econazole nitrate by using a one-pot method, and belongs to the technical field of synthesis methods of econazole nitrate. The method comprises: carrying out an N-alkylation reaction under the actions of K2CO3 / KOH / Al2O3 and PEG-200 by using 1-(2,4-dichlorophenyl)-2-chloro-ethanol and imidazole as raw materials to obtain toluene-containing imidazoleethanol; and carrying out an O-alkylation reaction on the toluene-containing imidazole ethanol and p-chlorobenzyl chloride under the actions of K2CO3 / KOH / Al2O3 and PEG-200 to obtain econazole nitrate. According to the method of the invention, the intermediate imidazole ethanol is directly subjected to the O-alkylation reaction without water washing to achieve nearly neutral state, re-crystallization and drying, so that the environmental pollution caused by drying is reduced, the imidazole ethanol dissolving process is shortened, the reaction efficiency is improved, and the solvent recovery frequency is reduced; and after the O-alkylation reaction is finished, the impurity removal is performed before the acidification, so that the high product viscosity caused by many impurities is greatlyreduced, the solid-liquid separation is easy to realize, the one-pot production is realized, the cost is low, the operation is simple and convenient, and the method is suitable for industrial popularization.

Description

technical field [0001] The invention belongs to the technical field of synthesis methods of econazole nitrate, and in particular relates to a method for synthesizing econazole nitrate in one pot. Background technique [0002] Econazole nitrate is called Econazole nitrate in English, and its chemical name is 1-[2,4-dichloro-β(4-chlorobenzyloxy)phenethyl]imidazole nitrate. Bacteria, yeast, etc. have bactericidal and bacteriostatic effects, and are the first choice for the clinical treatment of tinea cruris, tinea manus, tinea versicolor, candidal dermatitis and other superficial fungal infection diseases. [0003] There are many methods reported in the literature to synthesize econazole nitrate. Liao Yongwei et al. used 1-(2,4-dichlorophenyl)-2-chloro-ethanol and imidazole as raw materials, NaOH as base, and BuN+Br- as phase transfer Catalyst, DMF as solvent, react at 80°C for 5h to obtain crude imidazole ethanol, recrystallize to obtain imidazole ethanol, then react with p-c...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D233/60
CPCC07D233/60
Inventor 李敢田华王德堂乔德阳李想刘颖黄雨石桂莉莉
Owner XUZHOU COLLEGE OF INDAL TECH
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