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CN-121975880-A - Cycloxazin ester, green continuous synthesis method thereof and application thereof in herbicide

CN121975880ACN 121975880 ACN121975880 ACN 121975880ACN-121975880-A

Abstract

The invention belongs to the technical field of herbicides, and aims to solve the problems of high safety risk, low production efficiency and poor product quality caused by the adoption of hazardous reagents and gap technology in the existing preparation of fenpyrazamine. The invention provides a method for synthesizing and applying a cyclic pyridazine ester and a green continuous synthesis method thereof in herbicide, which comprises the steps of continuously diazotizing 2, 6-dimethylaniline, photo-catalyzing and extracting and purifying by ionic liquid to prepare 2-cyclopropyl-6-methylphenol, continuously cyclizing maleic anhydride and hydrazine hydrate, electrochemically chlorinating and continuously hydrolyzing to prepare 6-chloro-3, 4-dihydroxypyridazine, and carrying out ionic liquid catalytic coupling, immobilized enzyme catalytic acylation and continuous crystallization purification on the 2-cyclopropyl-6-methylphenol and the 6-chloro-3, 4-dihydroxypyridazine to finally obtain the cyclic pyridazine ester. The preparation method adopts a continuous preparation process, avoids using a highly toxic reagent, ensures the safety of the preparation of the aciclofen, and improves the production efficiency and the product quality.

Inventors

  • SUN JIALE

Assignees

  • 上海群力化工有限公司

Dates

Publication Date
20260505
Application Date
20260330

Claims (10)

  1. 1. The green continuous synthesis method of the fenpyrazamine is characterized by comprising the following steps of: S1, continuously diazotizing 2, 6-dimethylaniline, performing photocatalysis and ion liquid extraction and purification to prepare 2-cyclopropyl-6-methylphenol; s2, continuously cyclizing, electrochemically chlorinating and continuously hydrolyzing maleic anhydride and hydrazine hydrate to prepare 6-chloro-3, 4-dihydroxypyridazine; S3, carrying out ionic liquid catalytic coupling, immobilized enzyme catalytic acylation and continuous crystallization purification on the 2-cyclopropyl-6-methylphenol and the 6-chloro-3, 4-dihydroxypyridazine to finally obtain the fendazomet; the electrochemical chlorination takes hydrochloric acid as a chlorine source, the photocatalysis takes cyclopropyl boric acid as a cyclopropyl source, and the immobilized enzyme catalyzes and acylates morpholine-4-methyl formate as an acylating agent.
  2. 2. The green continuous synthesis method of the aciclofen-sodium according to claim 1, wherein in the step S1, the continuous diazotization comprises the steps of continuously introducing 2, 6-dimethylaniline, sodium nitrite and hydrochloric acid into a micro-tube reactor, and performing continuous diazotization reaction at 0-5 ℃ to obtain 2, 6-dimethylphenyl diazonium salt solution; wherein the molar ratio of the reactants of the continuous diazotization is 2, 6-dimethylaniline to sodium nitrite to hydrochloric acid=1:1.05:2.5.
  3. 3. The green continuous synthesis method of the aciclofen-sodium according to claim 2, wherein in the step S1, the photocatalysis comprises the steps of mixing the 2, 6-dimethylphenyl diazonium salt solution with cyclopropylboric acid and a photocatalyst of tris (2-phenylpyridine) iridium in ionic liquid 1-octyl-3-methylimidazolium tetrafluoroborate, and carrying out photocatalysis reaction under the illumination of 365nm LEDs and the protection of nitrogen; Wherein the molar ratio of the photocatalytic reactant is diazonium salt, cyclopropylboronic acid and tris (2-phenylpyridine) iridium=1:1.2:0.005.
  4. 4. The green continuous synthesis method of the aciclofen according to claim 1, wherein in the step S2, the continuous cyclization comprises continuously introducing aqueous solutions of maleic anhydride and hydrazine hydrate into a continuous cyclization reactor to react at 80-85 ℃ to generate 3, 6-dihydroxypyridazine; wherein the molar ratio of the reactants of the continuous cyclization is maleic anhydride, and the mass fraction of the hydrazine hydrate is 80 percent=1:1.1.
  5. 5. The green continuous synthesis method of the aciclofen according to claim 4, wherein in the step S2, the electrochemical chlorination comprises the steps of mixing the obtained 3, 6-dihydroxypyridazine with hydrochloric acid and acetonitrile cosolvent, continuously introducing the mixture into a diaphragm-free continuous flow electrochemical microreactor, and performing electrochemical chlorination reaction under the conditions of a graphite anode, a copper cathode, a current density of 15-25mA/cm < 2 > and an anode potential of 1.2V to generate 3,4, 6-trichloropyridazine; The ratio of the reactants of the electrochemical chlorination is 1:1 of 3, 6-dihydroxypyridazine, the concentration of the hydrochloric acid solution is 1.5mol/L, the mol ratio of the hydrochloric acid solution to the acetonitrile cosolvent is 1:10.
  6. 6. The green continuous synthesis method of the aciclofen according to claim 5, wherein in the step S2, the continuous hydrolysis comprises continuously introducing 3,4, 6-trichloropyridazine and sodium hydroxide aqueous solution into a hydrolysis microtubule reactor, and continuously hydrolyzing at 5-10 ℃ to obtain 6-chloro-3, 4-dihydroxypyridazine.
  7. 7. The green continuous synthesis method of the aciclofen-sodium according to claim 1, wherein in the step S3, the ionic liquid catalytic coupling comprises the steps of mixing the 2-cyclopropyl-6-methylphenol with the 6-chloro-3, 4-dihydroxypyridazine, the ionic liquid [ HDBN + ] [ TFE- ] and anhydrous sodium hydroxide, continuously introducing the mixture into a micro-packed bed reactor filled with an ionic liquid supported catalyst, and carrying out solvent-free catalytic coupling reaction at 120-130 ℃ to generate an etherification product 6-chloro-3- (2-cyclopropyl-6-methylphenoxy) pyridazin-4-ol; Wherein the molar ratio of the ionic liquid catalytic coupling is 2-cyclopropyl-6-methylphenol, 6-chloro-3, 4-dihydroxypyridazine: [ HDBN + ] [ TFE- ] =1:1.02:0.5; [ HDBN + ] [ TFE- ] is 1, 5-diazabicyclo [4.3.0] non-5-ene 2, 2-trifluoroethanol ionic liquid.
  8. 8. The green continuous synthesis method of the cyclopyridazin ester according to claim 7, wherein in the step S3, the immobilized enzyme catalyzed acylation comprises the steps of dissolving an etherification product of 6-chloro-3- (2-cyclopropyl-6-methylphenoxy) pyridazin-4-ol and morpholine-4-methyl formate in tertiary butanol, continuously introducing an immobilized enzyme reactor filled with immobilized lipase, and carrying out enzyme catalyzed acylation reaction at 40-45 ℃ to obtain a crude cyclopyridazin ester; Wherein the molar ratio of the reactants of the immobilized enzyme catalytic acylation is 6-chloro-3- (2-cyclopropyl-6-methylphenoxy) pyridazin-4-ol, morpholine-4-methyl formate=1:1.3; The continuous crystallization uses an isopropanol-water mixed solvent.
  9. 9. A cyclic pyridazinone ester, characterized in that it is prepared by the green continuous synthesis method according to any one of claims 1 to 8.
  10. 10. Use of the aciclofen of claim 9 in herbicides.

Description

Cycloxazin ester, green continuous synthesis method thereof and application thereof in herbicide Technical Field The invention relates to the technical field of herbicides, in particular to a fenpyrazamine, a green continuous synthesis method thereof and application thereof in herbicides. Background The market demand for fenpyrazamine as an important post-emergence herbicide continues to grow, but the industrial production technology associated therewith has long been limited by a traditional synthetic route with inherent drawbacks. The route not only depends on various highly toxic high-risk chemicals seriously, so that the production safety and the environmental risk are outstanding, but also adopts a multi-step intermittent operation mode, so that the production efficiency is low and the product quality is unstable. In particular, in the traditional process, a critical chlorination step must use a highly toxic chlorination reagent such as phosphorus oxychloride and severely decomposed when meeting water, high-difficulty wastewater containing phosphorus and chlorine is generated in subsequent treatment, important coupling reaction is carried out in halogenated aromatic hydrocarbon solvents with high toxicity such as o-dichlorobenzene and strong bioaccumulation, continuous threat is formed to operators and environment, in addition, morpholine formyl chloride adopted in the acylation reaction has strong irritation and corrosiveness, the danger of the process is further increased, the use of toxic and harmful materials is originally determined, the process can generate three wastes with complex components, the treatment cost is high and the environmental hidden trouble exists, besides the fundamental defect brought by chemicals, the whole process flow of the process also brings serious problems for batch operation modes of kettle type series connection, the process is from an initial raw material to a final product, the independent reaction with more than seven steps such as diazotization, cyclization, chlorination, hydrolysis, coupling and acylation is necessarily involved, quenching, separation, intermediate drying and transfer after each step, the mode is caused by long production period, equipment utilization is low, the quality is greatly increased when the batch is greatly influenced, the quality is greatly reduced, and the batch is difficult to be degraded when the batch is more than stable, and the quality is greatly guaranteed, and the batch is difficult to be degraded and is more safe and stable when the batch is expected to be stored. In view of this, there is a need in the art for a method of green continuous synthesis of cloxazin esters and their use in herbicides to solve the above problems. Disclosure of Invention In order to solve the technical problems, namely the problems of high safety risk, low production efficiency and poor product quality caused by the adoption of hazardous reagents and a gap process in the existing preparation of the fenpyrad. In one aspect, the invention provides a green continuous synthesis method of aciclofen, which comprises the following steps: S1, continuously diazotizing 2, 6-dimethylaniline, performing photocatalysis and ion liquid extraction and purification to prepare 2-cyclopropyl-6-methylphenol; s2, continuously cyclizing, electrochemically chlorinating and continuously hydrolyzing maleic anhydride and hydrazine hydrate to prepare 6-chloro-3, 4-dihydroxypyridazine; S3, carrying out ionic liquid catalytic coupling, immobilized enzyme catalytic acylation and continuous crystallization purification on the 2-cyclopropyl-6-methylphenol and the 6-chloro-3, 4-dihydroxypyridazine to finally obtain the fendazomet; the electrochemical chlorination takes hydrochloric acid as a chlorine source, the photocatalysis takes cyclopropyl boric acid as a cyclopropyl source, and the immobilized enzyme catalyzes and acylates morpholine-4-methyl formate as an acylating agent. The synthesis of the intermediate 2-cyclopropyl-6-methylphenol, the intermediate 6-chloro-3, 4-dihydroxypyridazine precursor and the final product is disassembled into three parallel and connected continuous steps, so that the traditional kettle type intermittent operation is abandoned, the large-scale isolated storage and transfer of the intermediate are fundamentally avoided, and the production period is greatly compressed. The method adopts hydrochloric acid combined with electrochemical technology as chlorine source to replace phosphorus oxychloride from source, adopts ionic liquid as reaction medium to replace o-dichlorobenzene and other toxic solvents, and adopts methyl morpholinate combined with enzyme to catalyze and complete acylation, so as to avoid the highly-irritating morpholinyl chloride, and the systematic substitution of the green reagents thoroughly eliminates the safety and environmental risks brought by extremely toxic substances, has mild reaction characteristics highly compatible with co