EP4573074A1 - Process for the preparation and isolation of intermediates of certain mesoionic pesticides - Google Patents

Process for the preparation and isolation of intermediates of certain mesoionic pesticides

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Publication number
EP4573074A1
EP4573074A1 EP23765126.0A EP23765126A EP4573074A1 EP 4573074 A1 EP4573074 A1 EP 4573074A1 EP 23765126 A EP23765126 A EP 23765126A EP 4573074 A1 EP4573074 A1 EP 4573074A1
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EP
European Patent Office
Prior art keywords
phenyl
trifluoromethyl
solvent
moles
process according
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
EP23765126.0A
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German (de)
French (fr)
Inventor
Michael L. Trippeer
Chunming Zhang
Honglu Zhang
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Corteva Agriscience LLC
Original Assignee
Corteva Agriscience LLC
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Corteva Agriscience LLC filed Critical Corteva Agriscience LLC
Publication of EP4573074A1 publication Critical patent/EP4573074A1/en
Pending legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
    • C07C51/41—Preparation of salts of carboxylic acids
    • C07C51/412—Preparation of salts of carboxylic acids by conversion of the acids, their salts, esters or anhydrides with the same carboxylic acid part
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
    • C07C51/42—Separation; Purification; Stabilisation; Use of additives
    • C07C51/43—Separation; Purification; Stabilisation; Use of additives by change of the physical state, e.g. crystallisation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C57/00—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms
    • C07C57/52—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing halogen
    • C07C57/58—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing halogen containing six-membered aromatic rings

Definitions

  • Triflumezopyrim is a mesoionic pesticide that is used against rice plant hopper, as well as other pests. Ammonium, potassium, sodium, other metal salts, and organic amine salts of 2-[3-(trifluoromethyl)phenyl]propanedioate may be used as an intermediate in the synthesis of triflumezopyrim.
  • Triflumezopyrim has the following structure.
  • sodium 2-(3-(trifluoromethyl)phenyl)mal onate is prepared from dimethyl 2-(3- (trifluoromethyl)phenyl)malonate (hereafter also known as “DTPM”).
  • STPM is prepared, in general, by conducting a saponification reaction followed by crystallization to obtain STPM in a higher yield and higher purity than the prior art.
  • other alkyl substituents may be used such as diethyl 2-(3-(trifluoromethyl)phenyl)mal onate or dipropyl 2-(3- (trifluoromethyl)phenyl)malonate, as well as mixtures of alkyl substituents with or without DTPM
  • DTPM and sodium hydroxide are mixed under conditions to produce STPM.
  • about 2 moles to about 8 moles of NaOH per mole of DTPM preferably, about 2 moles to about 4 moles of NaOH per mole of DTPM, and more preferably, about 2 moles to about 3 moles of NaOH per mole of DTPM may be used.
  • the NaOH is preferably a solution of sodium hydroxide in water of 5 to 50 weight percent (wt %) concentration, and even more preferably, a solution of sodium hydroxide in water of 10 to 40 wt % concentration.
  • temperatures from about 0 °C to about 50 °C may be used; preferably temperatures from about 5 °C to about 25 °C may be used.
  • pressures from about 10 kilopascals (kPa) to about 1000 kPa may be used; preferably pressures from about 50 kPa to about 150 kPa may be used, however, generally, ambient pressure is preferred.
  • a resulting mixture comprising STPM is further mixed with additional solvent, preferably isopropyl alcohol, under temperatures from about 5 °C to about 20 °C, preferably from about 10 °C to about 15 °C, and pressures indicated above. These conditions promote better crystallization of STPM to obtain higher yield and higher purity of STPM.
  • the amount of additional solvent used is from about 1 mole to about 50 moles of solvent per mole of STPM, preferably, about 1 mole to about 30 moles of solvent per mole of STPM, and more preferably, about 1 mole to about 4 moles of solvent per mole of STPM may be used. It should be noted that a mixture of different solvents may be used, such as, for example, a mixture of isopropyl alcohol with water or other alcohols such as ethanol.
  • a process to produce sodium 2-(3-(trifluoromethyl)phenyl)mal onate from dimethyl 2-(3-(trifluoromethyl)phenyl)mal onate comprising: (1) mixing dimethyl 2-(3-(trifluoromethyl)phenyl)mal onate and NaOH in a solvent, wherein said solvent comprises isopropyl alcohol, and said mixing is under temperature and pressures to produce a mixture comprising sodium 2-(3-(trifluoromethyl)phenyl)malonate; and
  • 9D A process according to detail 7D wherein said pressure is about ambient pressure.
  • 10D A process according to details ID, 2D, 3D, 4D, 5D, 6D, 7D, 8D, or 9D, wherein the amount of solvent used is from about 1 mole to about 32 moles of solvent per mole of dimethyl 2-(3-(trifluoromethyl)phenyl)mal onate when mixing with NaOH.
  • a process according to detail 1 OD wherein the amount of solvent used is from about 1 mole to about 16 moles of solvent per mole of dimethyl 2-(3- (trifluoromethyl)phenyl)malonate when mixing with NaOH.
  • a process according to detail 10D wherein the amount of solvent to used is from about 1 mole to about 4 moles of solvent per mole of dimethyl 2-(3- (trifluoromethyl)phenyl)malonate when mixing with NaOH.
  • STPM sodium 2-(3-(trifluoromethyl)phenyl)malonate
  • DTPM dimethyl 2-(3-(trifluoromethyl)phenyl)malonate
  • Example One The procedure as in Example One was conducted four other times except that instead of using propan-2-ol, a different solvent selected from methanol, ethanol, 1 -propanol, and n- butanol, was used.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

A process to produce sodium 2-(3-(trifluoromethyl)phenyl)malonate from dimethyl 2-(3-(trifluoromethyl)phenyl)malonate is disclosed.

Description

PROCESS FOR THE PREPARATION AND ISOLATION OF INTERMEDIATES OF CERTAIN MESOIONIC PESTICIDES
BACKGROUND FOR THIS DISCLOSURE
Mesoionic pesticides and methods for preparing them have been previously disclosed in, for example, WO 2009/099929 Al, WO 2011/017334 Al, WO 2011/017342 Al, WO 2011/017347 Al, WO 2012/092115 Al, WO 2013/090547 Al, WO 2017/189339 Al, and WO 2019/173173 Al. Triflumezopyrim is a mesoionic pesticide that is used against rice plant hopper, as well as other pests. Ammonium, potassium, sodium, other metal salts, and organic amine salts of 2-[3-(trifluoromethyl)phenyl]propanedioate may be used as an intermediate in the synthesis of triflumezopyrim. However, certain synthesis steps disclosed previously have one or more drawbacks for large-scale manufacture of triflumezopyrim. For example, WO 2013/090547 Example 2, located on page 38, discloses a process that, in general, includes does a saponification reaction followed by azeotropic removal of excess water in the presence of toluene to produce sodium 2-(3-(trifluoromethyl)phenyl)malonate. This process requires more operation units and longer cycle time, generates more waste, and thus limits the manufacturing capacity. Thus, there remains a need for alternative ways of preparing triflumezopyrim in high yield and high quality.
DETAIL DESCRIPTION FOR THIS DISCLOSURE
Triflumezopyrim has the following structure.
It is also known 2,4-dioxo-l-(pyrimidin-5-ylmethyl)-3-(3-(trifluoromethyl)phenyl)-3,4-dihydro- 2/7-pyrido[l ,2-a]pyrimidin- 1 -ium-3 -ide. Sodium 2-[3-(trifluoromethyl)phenyl]propanedioate has the following structure (hereafter also known as “STPP”). It is also known as sodium 2-(3-(trifluoromethyl)phenyl)malonate (hereafter also known as “STPM”).
In the following Scheme One: sodium 2-(3-(trifluoromethyl)phenyl)mal onate is prepared from dimethyl 2-(3- (trifluoromethyl)phenyl)malonate (hereafter also known as “DTPM”). STPM is prepared, in general, by conducting a saponification reaction followed by crystallization to obtain STPM in a higher yield and higher purity than the prior art. If desired, other alkyl substituents may be used such as diethyl 2-(3-(trifluoromethyl)phenyl)mal onate or dipropyl 2-(3- (trifluoromethyl)phenyl)malonate, as well as mixtures of alkyl substituents with or without DTPM
In Scheme One, DTPM and sodium hydroxide (NaOH) are mixed under conditions to produce STPM. In general, about 2 moles to about 8 moles of NaOH per mole of DTPM, preferably, about 2 moles to about 4 moles of NaOH per mole of DTPM, and more preferably, about 2 moles to about 3 moles of NaOH per mole of DTPM may be used. The NaOH is preferably a solution of sodium hydroxide in water of 5 to 50 weight percent (wt %) concentration, and even more preferably, a solution of sodium hydroxide in water of 10 to 40 wt % concentration.
In Scheme One, currently, temperatures from about 0 °C to about 50 °C may be used; preferably temperatures from about 5 °C to about 25 °C may be used. Currently, pressures from about 10 kilopascals (kPa) to about 1000 kPa may be used; preferably pressures from about 50 kPa to about 150 kPa may be used, however, generally, ambient pressure is preferred.
The mixing of DTPM and NaOH is conducted in the presence a solvent. While a variety of solvents may be used, such as, for example, nonpolar hydrocarbon solvents, polar aprotic solvents, polar protic solvents, etc., it has been discovered that using isopropyl alcohol (also known as, propan-2-ol) as a solvent provides unexpected and important benefits. The amount of solvent used is from about 1 mole to about 32 moles of solvent per mole of DTPM, preferably, about 1 mole to about 16 moles of solvent per mole of DTPM, and more preferably, about 1 mole to about 4 moles of solvent per mole of DTPM may be used.
Following the mixing of DTPM with NaOH in the presence of a solvent, preferably isopropyl alcohol, a resulting mixture comprising STPM is further mixed with additional solvent, preferably isopropyl alcohol, under temperatures from about 5 °C to about 20 °C, preferably from about 10 °C to about 15 °C, and pressures indicated above. These conditions promote better crystallization of STPM to obtain higher yield and higher purity of STPM.
The amount of additional solvent used is from about 1 mole to about 50 moles of solvent per mole of STPM, preferably, about 1 mole to about 30 moles of solvent per mole of STPM, and more preferably, about 1 mole to about 4 moles of solvent per mole of STPM may be used. It should be noted that a mixture of different solvents may be used, such as, for example, a mixture of isopropyl alcohol with water or other alcohols such as ethanol.
In light of the above and the examples below the following additional details (D) are provided.
ID. A process to produce sodium 2-(3-(trifluoromethyl)phenyl)mal onate from dimethyl 2-(3-(trifluoromethyl)phenyl)mal onate said process comprising: (1) mixing dimethyl 2-(3-(trifluoromethyl)phenyl)mal onate and NaOH in a solvent, wherein said solvent comprises isopropyl alcohol, and said mixing is under temperature and pressures to produce a mixture comprising sodium 2-(3-(trifluoromethyl)phenyl)malonate; and
(2) crystallizing said mixture comprising sodium 2-(3- (trifluoromethyl)phenyl)malonate in the presence of added solvent, wherein said solvent comprises isopropyl alcohol, and said crystallizing is under temperatures and pressures to crystallize said sodium 2-(3-(trifluoromethyl)phenyl)mal onate.
2D. A process according to detail ID wherein about 2 moles to about 8 moles of NaOH per mole of dimethyl 2-(3-(trifluoromethyl)phenyl)malonate is used.
3D. A process according to detail ID wherein about 2 moles to about 4 moles of NaOH per mole of dimethyl 2-(3-(trifluoromethyl)phenyl)malonate is used.
4D. A process according to detail ID wherein about 2 moles to about 3 moles of NaOH per mole of dimethyl 2-(3-(trifluoromethyl)phenyl)malonate is used.
5D. A process according to details ID, 2D, 3D, or 4D, wherein said temperature is from about 0 °C to about 50 °C.
6D. A process according to detail 5D wherein said temperature is from about 5 °C to about 25 °C.
7D. A process according to details ID, 2D, 3D, 4D, 5D, or 6D, wherein said pressure is from about 10 kilopascals (kPa) to about 1000 kPa.
8D. A process according to detail 7D wherein said pressure is from about 50 kilopascals (kPa) to about 150 kPa.
9D. A process according to detail 7D wherein said pressure is about ambient pressure. 10D. A process according to details ID, 2D, 3D, 4D, 5D, 6D, 7D, 8D, or 9D, wherein the amount of solvent used is from about 1 mole to about 32 moles of solvent per mole of dimethyl 2-(3-(trifluoromethyl)phenyl)mal onate when mixing with NaOH.
1 ID. A process according to detail 1 OD wherein the amount of solvent used is from about 1 mole to about 16 moles of solvent per mole of dimethyl 2-(3- (trifluoromethyl)phenyl)malonate when mixing with NaOH.
12D. A process according to detail 10D wherein the amount of solvent to used is from about 1 mole to about 4 moles of solvent per mole of dimethyl 2-(3- (trifluoromethyl)phenyl)malonate when mixing with NaOH.
13D. A process according to details ID, 2D, 3D, 4D, 5D, 6D, 7D, 8D, 9D, 10D, 11D, or 12D, wherein said mixture comprising sodium 2-(3-(trifluoromethyl)phenyl)mal onate is in the presence of additional isopropyl alcohol, and said crystalizing is conducted at a temperature from about 5 °C to about 20 °C.
14D. A process according to detail 13D wherein the additional solvent is from about 1 mole to about 50 moles of solvent per mole of sodium 2-(3-(trifhioromethyl)phenyl)malonate.
15D. A process according to detail 13D wherein the additional solvent is from about 1 mole to about 25 moles of solvent per mole of sodium 2-(3-(trifhioromethyl)phenyl)malonate.
16D. A process according to detail 13D wherein the additional solvent is from about 1 mole to about 4 moles of solvent per mole of sodium 2-(3-(trifluoromethyl)phenyl)mal onate.
EXAMPLES
The following examples are for illustration purposes and are not to be construed as limiting. Starting materials, reagents, and solvents that were obtained from commercial sources were used without further purification. Anhydrous solvents were purchased as Sure/Seal™ from Aldrich and were used as received. Molecules are given their known names, named according to the naming program within ChemDraw (version 17.1.0.105 (19)). If such a program is unable to name a molecule, such molecule is named using conventional naming rules. 3H NMR spectral data are in ppm (8) and were recorded at 400 MHz, and 13C NMR spectral data are in ppm (8) and were recorded at 101 MHz, unless otherwise stated.
Prior art example: Preparation of sodium 2-[3-(trifluoromethyl)phenyl]propanedioate from 1,3 -dimethyl 2-[3-(trifluoromethyl)phenyl]propanedioate
The procedure in Example 2, located on page 38 of WO 2013/090547 Al, was recreated in order to determine the purity of the product, sodium 2-[3-(trifluoromethyl)phenyl]propanedioate, produced by this two-step procedure. This was done because the purity was not specified in the example. The yield obtained in conducting this procedure was 80% and the purity was 87.3%.
Example One: Preparing sodium 2-(3-(trifluoromethyl)phenyl)malonate (hereafter “STPM”) from dimethyl 2-(3-(trifluoromethyl)phenyl)malonate (hereafter “DTPM”)
To a 250 mL jacketed reactor was charged 25% sodium hydroxide (17.51 g, 109 mmol) and propan-2-ol (7.5 mL, 98 mmol). This reaction mixture was cooled to 10-15 °C. A mixture of dimethyl 2-(3-(trifluoromethyl)phenyl)malonate (15 g, 49.7 mmol, hereafter “DTPM”) and propan-2-ol (7.5 mL, 98 mmol) at 10-15 °C was slowly added (about 30 minutes) while maintaining the temperature of the reaction mixture between 10-15 °C. After this addition, the reaction mixture was stirred at 15 °C for 30 minutes. The reaction mixture was then warmed to 21-23 °C and stirred for one hour until analysis by HPLC showed that the reaction was complete.
The reaction mixture was then cooled to 15 °C and propan-2-ol (45 mL, 589 mmol) was slowly added while stirring at 15 °C over 30 minutes. The resulting slurry was stirred for an additional one hour at 15 °C. Afterwards, propan-2-ol (60 mL, 785 mmol) was slowly added over 20 minutes at 15 °C and was stirred for three hours at 15 °C. The slurry was cooled to 5 °C and stirred for one hour. The slurry was filtered. The resulting solid was washed with propan-2- ol; the white filter cake was dried under nitrogen (N2)/vacuum for 30 minutes and then was dried under vacuum at 40 °C for 48 hours. The product, sodium 2-(3-trifluoromethyl)phenyl)malonate (14.3 g, 46.9 mmol, 94% yield) was obtained as a white solid (95.78 wt % purity).
The procedure as in Example One was conducted four other times except that instead of using propan-2-ol, a different solvent selected from methanol, ethanol, 1 -propanol, and n- butanol, was used.
A summary of the results of prior art example, the results of Example One, and the results of using the procedures of Example One with different solvents, is disclosed in Table One. As can be seen from Table One, propan-2-ol is much better than the prior art example which is a two-step process with toluene as the solvent. In fact, the yield was 14% better, and the purity was almost 10% better. Furthermore, propan-2-ol provides much better yields and purity than any of the other solvents (methanol, ethanol, 1 -propanol, or //-butanol).

Claims

WE CLAIM
1. A process to produce sodium 2-(3-(trifluoromethyl)phenyl)malonate from dimethyl 2-(3- (trifluoromethyl)phenyl)malonate said process comprising:
(1) mixing dimethyl 2-(3-(trifluoromethyl)phenyl)mal onate and NaOH in a solvent, wherein said solvent comprises isopropyl alcohol under temperatures and pressures to produce a mixture comprising sodium 2-(3-(trifluoromethyl)phenyl)malonate; and
(2) crystallizing said mixture comprising sodium 2-(3- (trifluoromethyl)phenyl)malonate in the presence of a solvent wherein said solvent comprises isopropyl alcohol under temperatures and pressures to crystallize said sodium 2-(3- (trifluoromethyl)phenyl)malonate.
2. A process according to claim 1 wherein about 2 moles to about 8 moles of NaOH per mole of dimethyl 2-(3-(trifluoromethyl)phenyl)malonate is used.
3. A process according to claim 1 wherein about 2 moles to about 4 moles of NaOH per mole of dimethyl 2-(3-(trifluoromethyl)phenyl)malonate is used.
4. A process according to claim 1 wherein about 2 moles to about 3 moles of NaOH per mole of dimethyl 2-(3-(trifluoromethyl)phenyl)malonate is used.
5. A process according to any of the previous claims 1, 2, 3, or 4, wherein said temperature is from about 0 °C to about 50 °C.
6. A process according to claim 5 wherein said temperature is from about 5 °C to about 25
7. A process according to any of the previous claims 1, 2, 3, 4, 5, or 6, wherein said pressure is from about 10 kilopascals (kPa) to about 1000 kPa.
8. A process according to claim 7 wherein said pressure is from about 50 kilopascals (kPa) to about 150 kPa.
9. A process according to claim 7 wherein said pressure is about ambient pressure.
10. A process according to any of the previous claims 1, 2, 3, 4, 5, 6, 7, 8, or 9, wherein the amount of solvent used is from about 1 mole to about 32 moles of solvent per mole of dimethyl 2-(3-(trifluoromethyl)phenyl)malonate when mixing with NaOH.
11. A process according to claim 10 wherein the amount of solvent used is from about 1 mole to about 16 moles of solvent per mole of dimethyl 2-(3-(trifluoromethyl)phenyl)mal onate when mixing with NaOH.
12. A process according to claim 10 wherein the amount of solvent to used is from about 1 mole to about 4 moles of solvent per mole of dimethyl 2-(3-(trifluoromethyl)phenyl)mal onate when mixing with NaOH.
13. A process according to any of the previous claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12, wherein said mixture comprising sodium 2-(3-(trifluoromethyl)phenyl)malonate is in the presence of additional isopropyl alcohol, and said crystalizing is conducted at a temperature from about 5 °C to about 20 °C.
14. A process according to claim 13 wherein the additional solvent is from about 1 mole to about 50 moles of solvent per mole of sodium 2-(3-(trifluoromethyl)phenyl)malonate.
15. A process according to claim 13 wherein the additional solvent is from about 1 mole to about 25 moles of solvent per mole of sodium 2-(3-(trifluoromethyl)phenyl)mal onate.
16. A process according to claim 13 wherein the additional solvent is from about 1 mole to about 4 moles of solvent per mole of sodium 2-(3-(trifluoromethyl)phenyl)mal onate.
EP23765126.0A 2022-08-18 2023-08-16 Process for the preparation and isolation of intermediates of certain mesoionic pesticides Pending EP4573074A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US202263371760P 2022-08-18 2022-08-18
PCT/US2023/072301 WO2024040111A1 (en) 2022-08-18 2023-08-16 Process for the preparation and isolation of intermediates of certain mesoionic pesticides

Publications (1)

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EP4573074A1 true EP4573074A1 (en) 2025-06-25

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EP (1) EP4573074A1 (en)
JP (1) JP2025526908A (en)
KR (1) KR20250051696A (en)
CN (1) CN119698404A (en)
WO (1) WO2024040111A1 (en)

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TWI401023B (en) 2008-02-06 2013-07-11 Du Pont Mesoionic pesticides
AU2010279574A1 (en) 2009-08-05 2012-02-09 E. I. Du Pont De Nemours And Company Mesoionic pesticides
MX2012001646A (en) 2009-08-05 2012-03-21 Du Pont Mesoionic pesticides.
UA110924C2 (en) 2009-08-05 2016-03-10 Е. І. Дю Пон Де Немур Енд Компані Mesoionic pesticides
TWI528899B (en) 2010-12-29 2016-04-11 杜邦股份有限公司 Mesoionic pesticides
TWI572587B (en) 2011-12-15 2017-03-01 杜邦股份有限公司 Malonic acid di-salts and a method for preparing malonyl dihalides
TW201738229A (en) 2016-04-26 2017-11-01 杜邦股份有限公司 Process for the preparation of N-[(5-pyrimidinyl)methyl]-2-pyridinamines
CA3086552A1 (en) 2018-03-05 2019-09-12 E. I. Du Pont De Nemours And Company Process and intermidiates for the preparation of certain mesoionic pesticides

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JP2025526908A (en) 2025-08-15
WO2024040111A1 (en) 2024-02-22
KR20250051696A (en) 2025-04-17
CN119698404A (en) 2025-03-25

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