A method for synthesizing 1,2,4-1H-triazole
By adding hydrazine hydrate to a mixture of formic acid, formamide and high-temperature solvent during the synthesis of 1,2,4-1H-triazole, and subjected to negative pressure distillation and subsequent treatment, the problems of high-temperature dropping risk and low yield in the prior art are solved, and higher yield and production safety are achieved.
Patent Information
- Application Number
- CN202411959266.9
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-12-30
- Publication Date
- 2025-04-08
AI Technical Summary
The existing synthesis method of 1,2,4-1H-triazole is added dropwise to hydrazine hydrate at high temperatures, which has risks such as friction, open flame, and high heat, resulting in production safety hazards and low yields.
The hydrazine hydrate was added dropwise to a mixture of formic acid, formamide and high-temperature solvent, and maintained a negative pressure, and the resulting water and ammonia were evaporated to form a crude product of 1,2,4-1H-triazole, which was then cooled, filtered, recrystallized, rinsed and dried to obtain a fine product of 1,2,4-1H-triazole.
Effectively reduce the reaction risk, improve the yield of 1,2,4-1H-triazole to 95%, and improve the safety and efficiency of production by real-time monitoring of temperature and reusing solvents.
Abstract
Description
Technical Field
[0001] The invention relates to the technical field of fine chemicals, and in particular to a method for synthesizing 1,2,4-1H-triazole. Background Art
[0002] 1,2,4-1H-triazole is widely used in the synthesis of pesticides such as triadimefon, paclobutrazol, diniconazole, and diniconazole; the synthesized fungicide is highly efficient and low-toxic, and is widely used in the pesticide industry. It is an important organic chemical intermediate with strong market demand.
[0003] At present, there are four main methods for synthesizing 1,2,4-1H-triazole: one is to gradually add hydrazine hydrate to formamide to directly synthesize 1,2,4-1H-triazole, with a yield of 91%; the second is to first react hydrazine hydrate with formamide to generate monohydrazide, and then drop the monohydrazide into formamide to synthesize 1,2,4-1H-triazole, with a yield of 90%; the third is to pass ammonia into formic acid to generate formamide, and then drop hydrazine hydrate to obtain 1,2,4-1H-triazole, with a yield of 91%; the fourth is to first drop hydrazine hydrate into formic acid, and then drop the above reaction solution into formamide to synthesize 1,2,4-1H-triazole, with a yield of 93%.
[0004] Regardless of the above method, hydrazine hydrate needs to be dripped at a relatively high temperature (155-200°C). Hydrazine hydrate is at risk of combustion and explosion when exposed to friction, open flame, high heat, and oxidants, which poses a great safety hazard to the production of 1,2,4-1H-triazole. Summary of the invention
[0005] In order to overcome the above-mentioned defects of the prior art, the present invention provides a method for synthesizing 1,2,4-1H-triazole, which can not only effectively reduce the reaction risk, but also increase the yield of 1,2,4-1H-triazole to 95%.
[0006] In order to achieve the above purpose, the present invention adopts the following technical solutions:
[0007] A method for synthesizing 1,2,4-1H-triazole, characterized in that it comprises the following steps:
[0008] Step 1, adding hydrazine hydrate dropwise to a mixture of formic acid, formamide and a high-temperature solvent, while maintaining negative pressure, distilling off generated water and ammonia, and reacting to generate a crude 1,2,4-1H-triazole product;
[0009] Step 2: Cool, filter, recrystallize, rinse and dry the crude 1,2,4-1H-triazole produced in step 1 to obtain fine 1,2,4-1H-triazole.
[0010] Preferably, in step one, the high temperature solvent includes but is not limited to dodecane, benzyl alcohol, diformic acid esters, ethyl benzoate, 1,1,3-trimethylcyclohexenone, N-methylpyrrolidone, 1,3-dimethyl-2-imidazolidinone, cyclopentane sulfone, diphenyl ether, propylene glycol, methyl silicone oil, dimethyl silicone oil and dioctyl phthalate.
[0011] Preferably, in step 1, before adding hydrazine hydrate dropwise, the mixture of formic acid, formamide and high-temperature solvent needs to be preheated to 150-180°C.
[0012] Preferably, in step 1, during the process of dripping hydrazine hydrate, the dripping time is 60 to 300 minutes.
[0013] Preferably, in step 1, during the dropwise addition of hydrazine hydrate, the reaction system maintains a slight negative pressure, and the vacuum indication number is 0.01 to 0.03 MPa.
[0014] Preferably, in step 1, after the dropwise addition of hydrazine hydrate is completed, the negative pressure value of the reaction system is increased, and the vacuum indication number is 0.04 to 0.09 MPa.
[0015] Preferably, in step 1, after the dropwise addition of hydrazine hydrate is completed, the temperature of the reaction system is increased to a temperature range of 165 to 185°C.
[0016] Preferably, in step 1, after the dropwise addition of hydrazine hydrate is completed, the reaction is maintained for 15 to 150 minutes.
[0017] Preferably, in step 1, the mass ratio of the hydrazine hydrate to the high-temperature solvent is 1:1-4.0; the molar ratio of the hydrazine hydrate to formic acid is 1:0.05-0.15; and the molar ratio of the hydrazine hydrate to formamide is 1:1.5-2.5.
[0018] Preferably, in step 2, the solvent used for recrystallization includes but is not limited to water, ethanol, methanol, benzene, toluene, xylene, ethyl acetate, dichloromethane, chloroform and acetonitrile.
[0019] Compared with the prior art, the present invention has the following beneficial effects:
[0020] 1. The present invention monitors the temperature in the process of synthesizing 1,2,4-1H-triazole in real time. When the temperature is lower than the minimum value, the heating power is increased to raise the temperature to a specified range; when the temperature is higher than the maximum value, the heating power is reduced to lower the temperature to a specified range.
[0021] 2. The high-temperature solvent and recrystallization solvent involved in the present invention can be reused.
[0022] 3. The present invention performs harmless absorption treatment on water and ammonia generated during the reaction. DETAILED DESCRIPTION
[0023] To make the purpose, technical scheme and advantages of the embodiments of the present invention clearer, the technical scheme in the embodiments of the present invention will be clearly and completely described below. If the specific conditions are not specified in the embodiments, they are carried out according to the normal conditions or the conditions recommended by the manufacturer. If the manufacturer is not specified in the reagents or instruments used, they are all conventional products that can be purchased commercially. The present invention can be illustrated by the following examples, but the present invention is not limited to the listed implementation examples.
[0024] Example 1
[0025] Add formamide (99g, 2.2mol), formic acid (12g, 0.26mol) and dodecane (100g) to a 1000ml three-necked flask, stir and heat to 160℃, then slowly drop 80% hydrazine hydrate (62.5g, 1.0mol); during the dropwise addition of hydrazine hydrate, keep the vacuum reading at about 0.02MPa; after the dropwise addition of hydrazine hydrate, keep the vacuum reading at about 0.05MPa, and slowly distill out the generated water and ammonia. As the water content of the system decreases, the reaction temperature gradually rises to about 185℃, and the reaction is terminated after 60 minutes. After the temperature drops to ~5℃, filter and obtain a crude white powder product. After the crude product is recrystallized from ethanol, 67.2g of a white needle-shaped product is obtained, with a yield of 97%.
[0026] Example 2
[0027] Add formamide (92g, 2.02mol), formic acid (6g, 0.13mol) and N-methylpyrrolidone (75g) to a 1000ml three-necked flask, stir and heat to 165℃, then slowly drop 80% hydrazine hydrate (62.5g, 1.0mol); during the dropwise addition of hydrazine hydrate, keep the vacuum reading at about 0.03MPa; after the dropwise addition of hydrazine hydrate, keep the vacuum reading at about 0.06MPa, and slowly distill out the generated water and ammonia. As the water content of the system decreases, the reaction temperature gradually rises to about 180℃, and the reaction is stopped after 45 minutes. After the temperature drops to ~10℃, filter and obtain a crude white powder product. After the crude product is recrystallized from acetonitrile, 66.9g of a white needle-shaped product is obtained, with a yield of 97%.
[0028] Example 3
[0029] Add formamide (95g, 2.1mol), formic acid (9.2g, 0.2mol) and 1,3-dimethyl-2-imidazolidinone (130g) to a 1000ml three-necked flask, stir and heat to 160℃, then slowly drop 80% hydrazine hydrate (62.5g, 1.0mol); during the dropwise addition of hydrazine hydrate, keep the vacuum reading at about 0.02MPa; after the dropwise addition of hydrazine hydrate, keep the vacuum reading at about 0.07MPa, and slowly distill out the generated water and ammonia. As the water content of the system decreases, the reaction temperature gradually rises to about 178℃, and the reaction is stopped after 120 minutes. After the temperature drops to ~5℃, filter and obtain a crude white powder product. After the crude product is recrystallized from toluene, 67.5g of a white needle-shaped product is obtained, with a yield of 98%.
[0030] The above are only preferred specific implementation modes of the present invention, but the protection scope of the present invention is not limited thereto. Any technician familiar with the technical field can make equivalent replacements or changes according to the technical solutions and inventive concepts of the present invention within the technical scope disclosed by the present invention, which should be covered by the protection scope of the present invention.
Claims
1. A method for synthesizing 1,2,4-1H-triazole, characterized in that: The following steps are involved: Step 1, adding hydrazine hydrate dropwise to a mixture of formic acid, formamide and a high-temperature solvent, while maintaining negative pressure, distilling off generated water and ammonia, and reacting to generate a crude 1,2,4-1H-triazole product; Step 2: Cool, filter, recrystallize, rinse and dry the crude 1,2,4-1H-triazole produced in step 1 to obtain fine 1,2,4-1H-triazole.
2. The method for synthesizing 1,2,4-1H-triazole according to claim 1, characterized in that: In step one, the high temperature solvent includes but is not limited to dodecane, benzyl alcohol, diformic acid esters, ethyl benzoate, 1,1,3-trimethylcyclohexenone, N-methylpyrrolidone, 1,3-dimethyl-2-imidazolidinone, cyclopentane sulfone, diphenyl ether, propylene glycol, methyl silicone oil, dimethyl silicone oil and dioctyl phthalate.
3. The method for synthesizing 1,2,4-1H-triazole according to claim 1, characterized in that: In step 1, before adding hydrazine hydrate dropwise, the mixture of formic acid, formamide and high-temperature solvent needs to be preheated to 150-180°C.
4. The method for synthesizing 1,2,4-1H-triazole according to claim 1, characterized in that: In step 1, during the process of dripping hydrazine hydrate, the dripping time is 60 to 300 minutes.
5. The method for synthesizing 1,2,4-1H-triazole according to claim 1, characterized in that: In step 1, during the process of adding hydrazine hydrate, the reaction system maintains a slight negative pressure, and the vacuum indication number is 0.01 to 0.03 MPa.
6. The method for synthesizing 1,2,4-1H-triazole according to claim 1, characterized in that: In step 1, after the addition of hydrazine hydrate is completed, the negative pressure of the reaction system is increased, and the vacuum indication value is 0.04-0.09 MPa.
7. The method for synthesizing 1,2,4-1H-triazole according to claim 1, characterized in that: In step 1, after the addition of hydrazine hydrate is completed, the temperature of the reaction system is increased to a temperature range of 165 to 185°C.
8. The method for synthesizing 1,2,4-1H-triazole according to claim 1, characterized in that: In step 1, after the addition of hydrazine hydrate is completed, the reaction time is maintained at 15 to 150 minutes.
9. The method for synthesizing 1,2,4-1H-triazole according to claim 1, characterized in that: In step 1, the mass ratio of the hydrazine hydrate to the high-temperature solvent is 1:1-4.0; the molar ratio of the hydrazine hydrate to formic acid is 1:0.05-0.15; and the molar ratio of the hydrazine hydrate to formamide is 1:1.5-2.
5.
10. The method for synthesizing 1,2,4-1H-triazole according to claim 1, characterized in that: In step 2, the solvent used for the recrystallization includes but is not limited to water, ethanol, methanol, benzene, toluene, xylene, ethyl acetate, dichloromethane, chloroform and acetonitrile.