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Synthesis method of high-selectivity 1-methyl-3-(trifluoromethyl)-1H-pyrazole-5-alcohol

A trifluoromethyl, high-selectivity technology, applied in organic chemistry and other directions, can solve problems such as poor selectivity, unfavorable industrial production, and violent reaction process, and achieve improved selectivity and yield, easy control of the reaction process, and reaction conditions. mild effect

Active Publication Date: 2022-01-28
杭州欧晨科技有限公司
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] J.Heterocyclic Chem.27, 243 (1990). Disclosed a kind of method for preparing 5-MTP: methylhydrazine is added in the mixture of ETFAA and water at room temperature, after reaction subsides, mixture keeps reflux 2 hours, yield 24.2g (49%) 5-MTP and 4.2g (8%) 3-MTP, the selectivity is 6:1, the reaction process of this method is violent, the yield of the product is low, the selectivity is poor, and it is not suitable for industrial production
[0011] Both WO2005 / 095352 and WO2007 / 094225 disclosed the method for preparing 5-MTP in the same reference example 1: ETFAA was dissolved in 2 equivalents of acetic acid, and an aqueous solution of methylhydrazine was added within 1 hour at 10°C, and then The solution was stirred at room temperature for 1 hour, then stirred at 80° C. for 5 hours, the yield was 86.5%, repeating Reference Example 1, showing a selectivity of 96:4 as described in Comparative Example 1 of the present invention, the method Additional acetic acid needs to be added, and acetic acid is difficult to recycle and reuse, and the cost is high, which is not conducive to industrial production
ACS Chemical Neuroscience.8, 2746-2758 (2017). Reported a method to pass ammonia gas into ETFAA and react at 85°C for 3 hours to form an intermediate product, then add methylhydrazine and stir for 1 hour and then react overnight at 85°C. The ratio of 5-MTP to 3-MTP is 85:15. This method requires additional feeding of ammonia gas, cumbersome operation, long reaction time and low selectivity.
WO2017 / 08499 discloses a method for preparing 5-MTP: ETFAA is mixed with 1.1 equivalent methylhydrazine aqueous solution at 85°C, then reacted at 90-94°C for 2 hours, a certain amount of water is added, ethanol and water are distilled off, cooled Crystallization, the product yield was 72.4%, the selectivity of 5-MTP and 3-MTP was 98.1:1.9, the method had high selectivity, but the product yield was low
The above-mentioned methods basically all have the problem of low yield or low selectivity, and are not suitable for industrialized production.

Method used

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  • Synthesis method of high-selectivity 1-methyl-3-(trifluoromethyl)-1H-pyrazole-5-alcohol
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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] 92 g (0.5 mol) 4,4-trifluoroacetate ethyl ester, 80 ml of ethanol and 0.92 gm cm-41 mesoporous molecular sieve catalyst were added to the reactor at room temperature, and the reaction system was maintained at 40 ° C, and then 69 g started ( 0.6 mol) 40% methylhydrazine solution, the control temperature was at 45 to 50 ° C, and the retained reagent was 50 ° C for 5 hours, the reaction was completed, filtered, a small amount of water washing filter, 79.31G1 - Methyl-3- (trifluoromethyl) -1H-pyrazole-5-alcohol, yield 95.55%; selectivity is 99.6: 0.4.

[0032] 1 H NMR (500 MHz, DMSO- d 6 δ 11.66 (S, 1H), 5.71 (S, 1H), 3.58 (S, 3H). 13 CNMR (126 MHz, DMSO- d 6 ) δ 153.07, 138.33 (q, 2 J F-C = 36.54 hz), 121.56 (q, 1 J F-C = 268.38 Hz), 84.41, 33.71.

Embodiment 2

[0034] 92 g (0.5 mol) 4,4,4-trifluoroacetate, 80 ml of ethanol and 0.92 g of ZSM-5 molecular sieve catalyst were added to the reactor at room temperature, and the reaction system was maintained at 40 ° C, and then 138 g (0.6 mol) 20% methylhydrazine aqueous solution, the control temperature was at 80 ° C after 5 hours after the measuring temperature of 45 ~ 50 ° C. The reaction was completed to cool to room temperature, filtered, a small amount of water washing filter cake, 74.64 g 1-methyl-3- (trifluoromethyl) -1H-pyrazole-5-alcohol, yield was 89.92%, selectivity was 99.1 : 0.9.

[0035]1 H NMR (500 MHz, DMSO- d 6 δ 11.66 (S, 1H), 5.71 (S, 1H), 3.58 (S, 3H). 13 CNMR (126 MHz, DMSO- d 6 ) δ 153.07, 138.33 (q, 2 J F-C = 36.54 hz), 121.56 (q, 1 J F-C = 268.38 Hz), 84.41, 33.71.

Embodiment 3

[0037] 92 g (0.5 mol) of 4,4,4-trifluoroacetate, 80 ml of ethanol and 0.92 gsba-15 molecular sieve catalyst were added to the reactor at room temperature, and the reaction system was maintained at 40 ° C, and then 69 g (0.6 mol) 40% methylhydrazine aqueous solution, the control temperature was at 45 to 50 ° C, and the maintenance system was reacted at 80 ° C after 5 hours after the drop was completed. The reaction ends for cooling to room temperature, filtration, small amount of water washing cake, 76.13 g 1-methyl-3- (trifluoromethyl) -1H-pyrazole-5-alcohol, yield 91.72%, selectivity is 99.2 : 0.8.

[0038] 1 H NMR (500 MHz, DMSO- d 6 δ 11.66 (S, 1H), 5.71 (S, 1H), 3.58 (S, 3H). 13 CNMR (126 MHz, DMSO- d 6 ) δ 153.07, 138.33 (q, 2 J F-C = 36.54 hz), 121.56 (q, 1 J F-C = 268.38 Hz), 84.41, 33.71.

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Abstract

The invention discloses a synthesis method of high-selectivity 1-methyl-3-(trifluoromethyl)-1H-pyrazole-5-alcohol, the synthesis method comprises the following steps: taking ethyl 4, 4, 4-trifluoroacetoacetate and a methylhydrazine aqueous solution as raw materials, carrying out condensation cyclization reaction in the presence of an organic solvent and a catalyst, after the reaction is finished, filtering the reaction system, washing and drying, and obtaining the target product 1-methyl-3-(trifluoromethyl)-1H-pyrazole-5-alcohol. According to the invention, cheap raw materials and solvents are adopted, and the reagent ethanol can be generated in the reaction, so that the reaction can be carried out in the forward direction, the reaction efficiency is improved, the reaction conditions are mild, and the reaction process is easy to control; by adding the limited catalyst, the selectivity and the yield of the reaction can be further improved, the yield reaches up to 95% or above, the selectivity of the target product to the byproduct is greater than 99: 1, and the method not only ensures high-selectivity preparation of the target product, but also is relatively high in overall yield, relatively low in cost, less in environmental pollution and suitable for industrial production.

Description

Technical field [0001] The present invention relates to the field of organic chemical synthesis, and in particular, 1-methyl-3-methyl-1-pyrazole-3-alcohol-1-pyrazol-3-alcohol-1H-pyrazol-3-alcohol-1H-pyrazole-3-alcohol-1H-(trifluoromethyl) -1H-pyrazole-3-alcohol-1H Synthesis of 3- (trifluoromethyl) -1H-pyrazole-5-alcohol. Background technique [0002] The pyrazole compound is a very valuable organic compound that has a high biological activity in many pyrazole compounds, and has a wide range of applications in many fields. As in medical applications, pyrazole compounds have efficacy to many diseases; in the application of pesticide applications, the pyrazole compound has insecticidal, bactericidal and removal activity, and exhibits efficient, low toxicity and structural diversity; Such compounds are also in chemicals in various fields such as dyes, coatings, perfumes, detergents, surfactants. Therefore, it is important to study and develop pyrazole compounds. [0003] 1-methyl-3- ...

Claims

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Application Information

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IPC IPC(8): C07D231/20
CPCC07D231/20Y02P20/584
Inventor 姜正成姜正金
Owner 杭州欧晨科技有限公司
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