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A kind of preparation method of 1-methyl-1h-1,2,4-triazole-3-carboxylic acid methyl ester

A technology of methyl formate and aminotriazole, applied in the direction of organic chemistry, can solve the problems of unfavorable industrial production, volatile methyl iodide, toxic price, etc., and achieve the effect of low production cost, easy availability of raw materials, and cheap price

Active Publication Date: 2022-06-24
SHANGHAI TBBMED CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Because the raw material price of 1H-1,2,4-triazole-3-carboxylic acid methyl ester is relatively high, and methyl iodide is volatile, toxic and expensive, the dosage often needs to be excessive, which is not conducive to industrial production

Method used

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  • A kind of preparation method of 1-methyl-1h-1,2,4-triazole-3-carboxylic acid methyl ester
  • A kind of preparation method of 1-methyl-1h-1,2,4-triazole-3-carboxylic acid methyl ester
  • A kind of preparation method of 1-methyl-1h-1,2,4-triazole-3-carboxylic acid methyl ester

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Experimental program
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Effect test

Embodiment 1

[0028]

[0029] Under nitrogen protection, oxalic acid dihydrate (63g, 0.5mol) was added into water (120mL); the temperature was raised to 80-85°C to dissolve, and aminoguanidine bicarbonate (44.9g, 0.33mol) was added in batches. Raise the temperature to 98-100°C to react for 5 hours, lower the temperature to 50-60°C, and then add 30% NaOH aqueous solution to adjust the pH=11-12. Then it was warmed to reflux for 1 hour, cooled to room temperature and adjusted to pH=3-4 with concentrated hydrochloric acid. Filter and rinse the filter cake with water and cold methanol. 40.45 g of 3-aminotriazole-5-carboxylic acid was obtained, yield 95.7%, HPLC 99.3%.

[0030] Synthesis of 1,2,4-triazole-3-carboxylic acid

Embodiment 2

[0032]

[0033] Under the protection of nitrogen, mix 3-aminotriazole-5-carboxylic acid (38.4g, 0.3mol) and acetonitrile (40mL), cool down to 0°C, add 126g of 45% hydrobromic acid and stir to dissolve -2~2 Add at ℃ and then slowly dropwise add a solution containing sodium nitrite (22.1g, 0.32mol) dissolved in 31mL of water, after the dropwise addition, stir for 2 hours, then add a methanol solution containing hypophosphorous acid (40g). After 4 hours of reaction, the color gradually changed from orange to colorless. Slowly raise the temperature to 25-35°C and react for 3 hours. The layers were separated, and the aqueous layer was extracted with ethyl acetate. The organic phases were combined and washed with sodium bicarbonate and saturated brine. The organic phase was concentrated to no liquid, 30% aqueous methanol was added to make a slurry, and 26.5 g of 1,2,4-triazole-3-carboxylic acid was obtained by filtration, with a yield of 78.1%, and HPLC of 97.9%. m / z=114.0470[...

Embodiment 3

[0035]

[0036] Under the protection of nitrogen, mix 3-aminotriazole-5-carboxylic acid (38.4g, 0.3mol) and acetonitrile (40mL), cool down to 0°C, add 90.5g of 65% sulfuric acid and stir to dissolve -2~2°C Add and then slowly add dropwise a solution containing sodium nitrite (22.1g, 0.32mol) dissolved in 31mL of water, and then stir for 2 hours after the dropwise addition, then add sodium hypophosphite (56g) and 30mL of ethanol. After 3 hours of reaction, the color gradually changed from orange to colorless. Slowly raise the temperature to 25-35°C and continue the reaction for 5 hours. The layers were separated, and the aqueous layer was extracted with ethyl acetate. The organic phases were combined and washed with sodium bicarbonate and saturated brine. The organic phase was concentrated to stagnant liquid, 30% methanol aqueous solution was added to make a slurry, and 27.5 g of 1,2,4-triazole-3-carboxylic acid was obtained by filtration, the yield was 81.2%, and the HPLC...

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Abstract

The invention discloses a preparation method of methyl 1-methyl-1H-1,2,4-triazole-3-carboxylate, which belongs to the technical field of organic synthesis. Using aminoguanidine bicarbonate and oxalic acid as raw materials, adding an inorganic strong base for cyclization to obtain 3-aminotriazole-5-carboxylic acid, and then reacting with sodium nitrite under acidic conditions to obtain diazonium salt and then reacting with hypophosphorous acid to obtain 1,2,4-Triazole-3-carboxylic acid, followed by reaction with a methylating reagent to give methyl 1-methyl-1H-1,2,4-triazole-3-carboxylate. The invention has simple operation, easy-to-obtain raw materials and strong economic applicability.

Description

technical field [0001] The invention relates to a preparation method of 1-methyl-1H-1,2,4-triazole-3-carboxylic acid methyl ester, which belongs to the technical field of organic synthesis. Background technique [0002] 1-Methyl-1H-1,2,4-triazole-3-carboxylic acid methyl ester, CAS: 57031-66-0, English name: 1-Methyl-1H-[1,2,4]triazole-3- Carboxylic acid methylester. Triazoles are heterocyclic compounds containing three nitrogen atoms, and their pharmacophore exhibits a variety of biological activities, such as antifungal, antituberculosis, and antiviral. Compounds containing triazoles have become one of the hotspots and important fields in drug synthesis research and development in recent years. At present, many triazole-containing antimicrobial drugs have been used clinically and play various roles. Among them, 1,2,4-triazole can inhibit the growth of Mycobacterium tuberculosis by blocking lipid biosynthesis or other mechanism of action. 1,2,4-Triazole not only has ant...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D249/10
CPCC07D249/10
Inventor 高峰曾赛兰
Owner SHANGHAI TBBMED CO LTD