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Method for preparing 1H-imidazole-4-formic acid

A technology of ethyl imidazole formate and imidazole, which is applied in the field of preparation of 1H-imidazole-4-carboxylic acid raw materials, can solve the problems of toxicity of catalyst RaneyNi, increase of industrial production cost, catalyst poisoning, etc., and achieve reasonable and feasible synthetic route design, Reduced consumption and less by-products

Inactive Publication Date: 2014-12-03
WUHAN UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0011] In the first method, Raney Ni is used to remove mercapto groups. The problem is that heteroatom sulfur, phosphorus, etc. are toxic to the catalyst Raney Ni, which leads to catalyst poisoning. Therefore, in actual operation, the catalyst The amount used is much higher than the theoretical value, resulting in an increase in the amount used, thereby increasing the cost of industrial production; at the same time, Raney Ni catalysis requires high pressure, which is inconvenient to operate;
The oxidation system mainly includes hydrogen peroxide / acetic acid system, hydrogen peroxide / formic acid system, hydrogen peroxide / heteropolyacid system; however, the main problem of directly using hydrogen peroxide oxidation is that the amount of hydrogen peroxide required is relatively large , it takes 7-8 times the amount to completely oxidize and remove the mercapto group, and an organic acid is needed as the reaction medium. Therefore, it is necessary to quench the excess hydrogen peroxide and neutralize the excess organic acid medium after the reaction

Method used

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  • Method for preparing 1H-imidazole-4-formic acid
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  • Method for preparing 1H-imidazole-4-formic acid

Examples

Experimental program
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Effect test

Embodiment 1

[0044] 1), the preparation of ethyl 2-mercapto-4-imidazole carboxylate:

[0045] In a 1-liter three-neck reaction flask equipped with a thermometer, a reflux condenser, and a stirrer, add 14.5 grams of ethyl acetylglycinate and 50 milliliters of ethanol to dissolve, add 37 grams of potassium tert-butoxide and 150 milliliters of ethyl formate, and store at 40 ° C. Stir the reaction until it is thick. After standing still, remove the solvent by rotary evaporation to obtain a light yellow viscous liquid. Dissolve the above liquid in water, add 22 grams of potassium thiocyanate under ice bath to dissolve, slowly add 160 milliliters of concentrated hydrochloric acid, and dissolve at 40 The reaction was stirred at ℃, and the progress of the reaction was monitored by TLC. After the reaction was completed, the solvent was removed by rotary evaporation to obtain 14.67 g of a yellow powdery solid, namely ethyl 2-mercapto-4-imidazole carboxylate, with a yield of 85.3%.

[0046] 2), the ...

Embodiment 2

[0052] 1), the preparation of ethyl 2-mercapto-4-imidazole carboxylate:

[0053] In a 500 ml three-neck reaction flask equipped with a thermometer, a reflux condenser, and a stirrer, add 7 g of ethyl acetylglycinate and 22 ml of acetone to dissolve, add 23 g of sodium ethoxide and 120 ml of ethyl formate, and stir the reaction at 40°C After standing still, the solvent was removed by rotary evaporation to obtain a light yellow viscous liquid. Dissolve the above liquid in water, add 12 grams of potassium thiocyanate under ice cooling to dissolve, slowly add 75 milliliters of concentrated hydrochloric acid, at 40 ° C The reaction was stirred, and the progress of the reaction was monitored by TLC. After the reaction was completed, the solvent was removed by rotary evaporation to obtain 7.3 g of a yellow powdery solid, namely ethyl 2-mercapto-4-imidazole carboxylate, with a yield of 88.0%.

[0054] 2), the preparation of ethyl imidazole-4-carboxylate:

[0055] In a 150 ml three-n...

Embodiment 3

[0059] 1), the preparation of ethyl 2-mercapto-4-imidazole carboxylate:

[0060] In a 500 ml three-neck reaction flask equipped with a thermometer, a reflux condenser, and a stirrer, add 10.5 g of ethyl acetylglycine and 35 ml of isopropyl ether to dissolve, add 30 g of sodium methoxide and 115 ml of ethyl formate, and store at 45 ° C. Stir the reaction until thick. After standing still, remove the solvent by rotary evaporation to obtain a light yellow viscous liquid. Dissolve the above liquid in water, add 18 grams of potassium thiocyanate under ice cooling to dissolve, slowly add 86 milliliters of concentrated hydrochloric acid, and dissolve at 45 The reaction was stirred at ℃, and the progress of the reaction was monitored by TLC. After the reaction was completed, the solvent was removed by rotary evaporation to obtain 11.2 g of a yellow powdery solid, namely ethyl 2-mercapto-4-imidazole carboxylate, with a yield of 89.5%.

[0061] 2), the preparation of ethyl imidazole-4-...

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Abstract

The invention relates to a method for preparing 1H-imidazole-4-formic acid. The method comprises the following steps of: performing cyclization on ethyl acetamidoacetate serving as a raw material and potassium thiocyanate to obtain 2-sulfydryl-4-imidazole ethyl formate; and performing catalytic oxidation by using a catalyst to remove sulfydryl to obtain sulfydryl removed imidazole-4-ethyl formate, hydrolyzing, and thus obtaining a target compound, namely 1H-imidazole-4-formic acid. The method has the advantages of high selectivity, improvement on yield, wide raw material source, low price and reasonable and feasible process design.

Description

technical field [0001] The invention belongs to the technical field of resources and medicine and chemical industry, and in particular relates to a preparation method of 1H-imidazole-4-carboxylic acid bulk drug which can be used for producing medicines for treating heart diseases, anemia, rheumatoid arthritis and digestive tract ulcers. Background technique [0002] Imidazole is a component of histidine, skin and even nucleic acid in organisms, and 1H-imidazole-4-carboxylic acid is one of the important ones and has significant biological activity. It can be used as an intermediate to form a series of physiologically active compounds. Some imidazole drugs, such as purines and adenosines, have anti-viral and anti-cancer components; some of these compounds have anti-viral and anti-tumor properties, and some have anti-leukemia effects. At the same time, 1H-imidazole-4-carboxylic acid is also used to synthesize imidazole functionalized poly(propyleneimine) dendritic structure com...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D233/90
Inventor 岳智洲韩晓东徐波杨婷
Owner WUHAN UNIV OF TECH
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