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CN-122010976-A - Pinoxaden and its preparing process Process for the preparation of esters

CN122010976ACN 122010976 ACN122010976 ACN 122010976ACN-122010976-A

Abstract

The invention relates to a preparation method of pinoxaden, comprising the following steps of S1, carrying out cyclization reaction on hydrazine hydrate and a compound shown in a formula (I) to generate an intermediate 1, S2, carrying out reaction on the intermediate 1 and the compound shown in a formula (II) in the presence of alkali to generate an intermediate 2, S3, carrying out reaction on the intermediate 2 and 2, 6-diethyl-4-methyl bromobenzene under the action of a catalyst to generate an intermediate 3, S4, and carrying out reaction on the intermediate 3 and pivaloyl chloride in the presence of alkali to obtain the pinoxaden, wherein the formula (I) is The structural formula of the intermediate 1 is Formula (II) is Intermediate 2 has the structural formula The structural formula of the intermediate 3 is The preparation method has the advantages of few steps, high yield, low cost and good safety.

Inventors

  • ZHANG HU
  • XU QIULONG
  • LI YONGLING

Assignees

  • 江苏七洲绿色科技研究院有限公司
  • 江苏七洲绿色化工股份有限公司

Dates

Publication Date
20260512
Application Date
20241111

Claims (10)

  1. 1. The preparation method of pinoxaden is characterized by comprising the following steps: S1, carrying out cyclization reaction on hydrazine hydrate and a compound shown in a formula (I) to generate an intermediate 1; s2, reacting the intermediate 1 with a compound shown in a formula (II) in the presence of a base to generate an intermediate 2; S3, reacting the intermediate 2 with 2, 6-diethyl-4-methyl bromobenzene under the action of a catalyst to generate an intermediate 3; s4, reacting the intermediate 3 with pivaloyl chloride in the presence of alkali to obtain the pinoxaden, Wherein the formula (I) is R 1 、R 2 is independently selected from alkyl groups with 1-5 carbon atoms; The structural formula of the intermediate 1 is The formula (II) is X 1 、X 2 is independently selected from halogen and R 3 SO 3 -,R 3 is alkyl with 1-5 carbon atoms; the structural formula of the intermediate 2 is The structural formula of the intermediate 3 is
  2. 2. The method for producing pinoxaden according to claim 1, characterized in that the compound represented by the formula (I) is diethyl malonate and/or, The feeding mole ratio of the hydrazine hydrate to the compound shown in the formula (I) is 1 (1-2).
  3. 3. The method for producing pinoxaden according to claim 1, wherein the reaction system of step S1 further comprises a solvent selected from one or more of methanol, ethanol, isopropanol, n-butanol, water, and/or, The reaction temperature in the step S1 is 60-100 ℃.
  4. 4. The method for preparing pinoxaden according to claim 1, wherein the base in step S2 is selected from one or more of hydroxide, carbonate and bicarbonate of alkali metal or alkaline earth metal.
  5. 5. The method for preparing pinoxaden according to claim 4, wherein the alkali in step S2 is potassium hydroxide and/or potassium carbonate, and/or, And the feeding mole ratio of the intermediate 1 to the alkali in the step S2 is 1 (1.5-3).
  6. 6. The method for producing pinoxaden according to claim 1, wherein the compound represented by formula (II) is selected from one or more of dichloro diethyl ether, dibromodiethyl ether, diiododiethyl ether, dimethyl sulfonate diethyl ether, and/or, The feeding mole ratio of the intermediate 1 to the compound shown in the formula (II) is 1 (1-2).
  7. 7. The method for preparing pinoxaden according to claim 1, wherein the reaction temperature in the step S2 is 80-150 ℃ and/or, The reaction system of the step S2 further comprises a solvent, wherein the solvent is one or more selected from N, N-dimethylformamide, dimethylacetamide, dimethyl sulfoxide and N-methyl-2-pyrrolidone.
  8. 8. The method for preparing pinoxaden according to claim 1, wherein the catalyst is a palladium catalyst and/or, The feeding mole ratio of the intermediate 2 to the catalyst is 1 (0.0001-0.01).
  9. 9. The method for preparing pinoxaden according to claim 1, wherein the molar ratio of the intermediate 2 to the 2, 6-diethyl-4-methyl bromobenzene is 1 (0.9-1.5), and/or, The reaction temperature in the step S3 is 120-150 ℃ and/or, The reaction system of the step S3 further comprises a solvent, wherein the solvent is selected from one or more of toluene, xylene, dimethylformamide, dimethylacetamide, N-methylpyrrolidone and dimethyl sulfoxide.
  10. 10. The method for preparing pinoxaden according to claim 1, wherein the feeding molar ratio of the intermediate 3 to pivaloyl chloride is 1 (1-1.5), and/or, The reaction system of the step S4 also comprises a solvent, wherein the solvent is selected from one or more of toluene, xylene, chlorobenzene and dichloroethane, and/or, The alkali in the step S4 is selected from one or more of triethylamine, N-dimethylethylamine, pyridine and 4-dimethylaminopyridine, and/or, And the feeding mole ratio of the intermediate 3 to the alkali in the step S4 is 1 (1-1.5).

Description

Pinoxaden and its preparing process Process for the preparation of esters Technical Field The invention belongs to the technical field of organic synthesis, and particularly relates to a preparation method of pinoxaden. Background The pinoxaden has the English generic name of pinoxaden and the chemical name of 8- (2, 6-diethyl-4-methylphenyl) -1,2,4, 5-tetrahydro-7-oxo-7H-pyrazolo [1,2-d ] [1,4,5] oxadiazepin-9-yl 2, 2-dimethylpropionate, and the structural formula is shown as follows The pinoxaden is a new phenylpyrazole herbicide which is successfully developed by the Zhengda company through experiments, has a unique chemical structure, can inhibit the activity of acetyl coenzyme A carboxylase (ACCase), block the biosynthesis of fatty acid, interfere the formation of cell membranes, and lead the growth of weeds to stop and finally die. The herbicide has special effects on preventing and killing off annual gramineous weeds in wheat and barley fields after germination, such as alopecuroides, japanese alopecuroides, wild oat, ryegrass, phalaris arundinacea, green bristlegrass, hard grass, sesamum indicum, and clavate grass, and particularly has special effects on phalaris arundinacea, and also has excellent preventing and killing off intractable gramineous weeds such as ryegrass multiflora. The reported methods for synthesizing pinoxaden include: 1. Route one 2. Route two 3. Route three The first route and the second route are represented by the Zhengda company and the CN108864144B, CN116514837A patent, the hydrazine hydrate and acetic anhydride are adopted to synthesize N, N-diacetylhydrazine, and finally the (1, 4, 5) oxydiazepine is obtained through deacetylation, so that the protection/deprotection steps are needed, the steps are complex, and the production cost is high. The above route three is represented by CN110294768B, WO2022123541A1 patent, avoiding the protection/deprotection step, but the key intermediate 2, 6-diethyl-4-methylbenzo malonate usually requires the use of malononitrile coupled with 2, 6-diethyl-4-methylbenzo bromobenzene, which is a highly toxic compound and is unstable, with potential safety hazard. Disclosure of Invention The invention aims to provide a preparation method of pinoxaden, which has the advantages of few steps, good safety, high yield and low cost. In order to achieve the above purpose, the invention adopts the following technical scheme: the preparation method of pinoxaden comprises the following steps: S1, carrying out cyclization reaction on hydrazine hydrate and a compound shown in a formula (I) to generate an intermediate 1; s2, reacting the intermediate 1 with a compound shown in a formula (II) in the presence of a base to generate an intermediate 2; S3, reacting the intermediate 2 with 2, 6-diethyl-4-methyl bromobenzene under the action of a catalyst to generate an intermediate 3; s4, reacting the intermediate 3 with pivaloyl chloride in the presence of alkali to obtain the pinoxaden, Wherein the formula (I) isR 1、R2 is independently selected from alkyl groups with 1-5 carbon atoms; The structural formula of the intermediate 1 is The formula (II) isX 1、X2 is independently selected from halogen and R 3SO3-,R3 is alkyl with 1-5 carbon atoms; the structural formula of the intermediate 2 is The structural formula of the intermediate 3 is The reaction route of the pinoxaden of the invention is as follows: The prior preparation method inevitably needs to synthesize key intermediates of [1,4,5] oxydiazepine and/or 2, 6-diethyl-4-methylbenzenesulfonate, however, the synthesis of [1,4,5] oxydiazepine needs to be subjected to protection/deprotection steps, the steps are complicated, and the synthesis of 2, 6-diethyl-4-methylbenzenesulfonate has the problems of potential safety hazard or low yield. The preparation method creatively avoids the preparation of the key intermediate, and the intermediate 1 is generated by reacting hydrazine hydrate with the compound shown in the formula (I), then the intermediate 2 is generated by reacting hydrazine hydrate with the compound shown in the formula (II), and finally the intermediate 2 is reacted with 2, 6-diethyl-4-methyl bromobenzene and pivaloyl chloride, so that pinoxaden can be prepared. Preferably, R 1、R2 is independently selected from alkyl with 1-3 carbon atoms, such as methyl, ethyl and propyl. In some embodiments, the compound of formula (I) is diethyl malonate. Preferably, the molar ratio of hydrazine hydrate to the compound shown in the formula (I) is 1 (1-2), more preferably 1 (1.2-1.5), for example 1:1.2, 1:1.3, 1:1.4 and 1:1.5. Preferably, the reaction system of the step S1 further comprises a solvent, wherein the solvent is one or more selected from methanol, ethanol, isopropanol, n-butanol and water. Further preferably, the mass ratio of the solvent to the compound represented by the formula (I) is (2 to 4): 1, and more preferably (2.4 to 3.5): 1. Preferably, the reaction temperature in the step S1 is 60 to 100 ℃,