CN-122010920-A - Pyricularia sulfone continuous synthesis method

Abstract

The invention provides a continuous synthesis method of haloxyfop-methyl. The process adopts an alkaline system, particularly a phosphate system, to replace the traditional strong acid reaction medium such as sulfuric acid, trifluoroacetic acid and the like, thoroughly avoids the corrosion of strong acid to equipment, greatly reduces equipment investment cost, can obtain the high-yield and high-purity haloxyfop-methyl product without increasing the consumption of hydrogen peroxide or increasing the concentration of hydrogen peroxide or adding excessive metal catalyst, greatly shortens the reaction time, remarkably improves the reaction efficiency, and further controls the concentration of hydrogen peroxide at a lower level in the whole oxidation reaction process, reduces the reaction risk, has short reaction time, generates less impurities, and has simple and convenient post-treatment method and strong operability, thereby having good industrial practical value.

Inventors

• LI ZHIQING
• WANG XIAONING
• SONG JIAN
• LI HONGLI
• WANG SONG
• WANG ZHIKANG
• WANG PENGFEI

Assignees

• 山东润博生物科技有限公司

Dates

Publication Date

20260512

Application Date

20260330

Claims (10)

1. 1. The continuous synthesis method of the pyrifos-methyl is characterized by comprising the following steps of: The first stage is that 3- [5- (difluoromethoxy) -1-methyl-3- (trifluoromethyl) pyrazol-4-ylmethylsulfanyl ] -4, 5-dihydro-5, 5-dimethyl-1, 2-isoxazole solution (namely compound 1 solution), hydrogen peroxide solution and alkali solution are continuously fed into a first continuous reactor through a metering pump for temperature control reaction; and in the second stage, continuously introducing the reaction liquid and hydrogen peroxide in the first stage into a second continuous reactor for temperature control reaction, and after the reaction is finished, entering a crystallization kettle, crystallizing, filtering, washing and drying to obtain the fenpyrad.
2. 2. The synthesis process according to claim 1, wherein the continuous reactor is selected from one or a combination of microchannel reactors and tubular reactors.
3. 3. The synthesis process according to claim 2, wherein the first stage continuous reactor is a microchannel reactor and the second stage continuous reactor is a tubular reactor.
4. 4. The method of synthesis according to claim 1, wherein the base is one or a combination of sodium phosphate, potassium phosphate, disodium hydrogen phosphate, dipotassium hydrogen phosphate, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, sodium phosphotungstate, sodium acetate, sodium hydroxide, and potassium hydroxide.
5. 5. The method of claim 1, wherein the base is a phosphate selected from one or a combination of sodium phosphate and potassium phosphate.
6. 6. The synthesis method according to claim 1, wherein the molar ratio of the compound 1 to the base is 1.0:0.05-0.5, and more preferably 1:0.05-0.1.
7. 7. The synthesis method according to claim 1, wherein the concentration of the hydrogen peroxide solution is 10% -50% wt, preferably 20% -30% wt, particularly preferably 25% -30% wt.
8. 8. The method according to claim 1, wherein the hydrogen peroxide is used in an amount of 2.5 to 4.0 times, more preferably 2.5 to 3.0 times the amount of 1mol of the compound.
9. 9. The synthetic method of claim 1, wherein the reaction solvent is one or a combination of acetonitrile, ethanol, n-propanol, isopropanol, ethyl acetate, butyl acetate, DMF.
10. 10. The synthesis method according to claim 1, wherein the temperature of the first continuous reactor is controlled to be 30-50 ℃, more preferably 40-45 ℃, and the temperature of the second continuous reactor is controlled to be 60-80 ℃, more preferably 70-75 ℃.

Description

Pyricularia sulfone continuous synthesis method Technical Field The invention relates to the technical field of medicines, in particular to a continuous synthesis method of fenpyrad. Background Pyroxasulfane (Pyroxasulfone) is an isoxazole herbicide, which is developed by Japanese chemical Co-Ltd under the chemical name of 3- [5- (difluoromethoxy) -1-methyl-3- (trifluoromethyl) pyrazol-4-ylmethyl sulfonyl ] -4, 5-dihydro-5, 5-dimethyl-1, 2-isoxazole, and has the molecular formula of C 12H14F5N3O4 S, the molecular weight of 391.32 and the CAS registry number of 447399-55-5. The haloxyfop-methyl has the characteristics of wide weed killing spectrum, high activity, low dosage, good safety and the like, and is therefore widely concerned. The paraquat sulfone can be used as a pre-emergence soil treatment agent for most crop fields, and is an ultra-long chain fatty acid extension synthase inhibitor herbicide, so that the paraquat sulfone plays a role by inhibiting ultra-long chain fatty acid extension synthase (VLCFAE). The compound can inhibit stearic acid in the biosynthesis pathway of super long chain fatty acid synthetase in plants from being converted into arachidic acid, arachidic acid from being converted into behenic acid, behenic acid from being converted into lignoceric acid, lignoceric acid from being converted into cerotic acid, and cerotic acid from being converted into montanic acid, and finally inhibit synthesis of myristic acid. The structure is as follows: , at present, the final reaction of the fenpyrad basically uses hydrogen peroxide as an oxidant for oxidation reaction, and the reaction is as follows: Serious accidents such as reaction runaway, fire and explosion are very easy to occur due to the inherent dangers of ‌ strong oxidants, strong exothermic property, inflammability and explosiveness of raw materials/products and the accuracy of process control required ‌. Therefore, it is classified by the country as one of 18 important regulatory hazardous chemical processes. The hydrogen peroxide disclosed in the prior art is taken as an oxidant to carry out two reaction systems of oxidation reaction, namely an acid system of catalytic reaction of strong acid such as trifluoroacetic acid, sulfuric acid and the like, the acid system is easy to corrode pipeline equipment, the equipment cost requirement is high, in addition, concentrated sulfuric acid, trifluoroacetic acid and the like can release a large amount of heat when being mixed with hydrogen peroxide, the decomposition rate of hydrogen peroxide under the acidic condition is 8-10 times that of that under the alkaline condition, if the temperature is improperly controlled, flushing and even explosion risks are particularly unfavorable for continuous reaction, and the other catalytic reaction alkali system such as carbonate is low in yield and has a plurality of byproducts, the curing/reaction time is as long as ten hours, excessive metal catalyst sodium tungstate and the like are often required to be additionally added to improve the reaction rate, and the alkali system without the transition metal catalyst is influenced by the reaction rate, so that continuous reaction in the microchannel equipment is difficult to realize. For the characteristics of the oxidation reaction for synthesizing the pyribenzoxim, the hydrogen peroxide can be decomposed and lost along with the consumption of the reaction and the unstable heating of substances, so that the concentration is lower and lower, the oxidation reaction is incomplete, and the excessive impurity sulfoxide with adverse effect on the drug effect is remained. The technological routes disclosed in the patent CN117924265A, CN113831333A, CN117417333A, CN118255757A, the patent CN117794925A and the like adopt methods of adding an excessive metal catalyst, increasing the hydrogen peroxide dosage or improving the hydrogen peroxide concentration to solve the problem of incomplete reaction. However, the excessive hydrogen peroxide in the reaction system aggravates the safety risk of the reaction, the post-treatment is complicated, the reaction mother solution needs more reducing agents such as sodium sulfite, sodium thiosulfate and the like to quench, the three wastes are increased, the environment is not friendly, and sodium tungstate is used as a catalyst, so that the production cost is high and the method is not suitable for industrial production. In view of the problems in the prior art, research and development of a process which accords with the industrial production economy and efficiency are needed. Disclosure of Invention Aiming at the defects of high oxidation reaction risk, long curing time, low reaction efficiency, more impurities, complex post-treatment and the like in the synthesis process of the haloxyfop-R-methyl in the prior art, the invention provides a continuous synthesis method of the haloxyfop-R-methyl. The method adopts continuous reaction, the concentration of hydrogen peroxide i