WO2025115007A2 - Procédé d'élimination de couleur de novaluron - Google Patents

Procédé d'élimination de couleur de novaluron Download PDF

Info

Publication number
WO2025115007A2
WO2025115007A2 PCT/IL2024/051117 IL2024051117W WO2025115007A2 WO 2025115007 A2 WO2025115007 A2 WO 2025115007A2 IL 2024051117 W IL2024051117 W IL 2024051117W WO 2025115007 A2 WO2025115007 A2 WO 2025115007A2
Authority
WO
WIPO (PCT)
Prior art keywords
acid
novaluron
base
mixture
organic
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
PCT/IL2024/051117
Other languages
English (en)
Other versions
WO2025115007A3 (fr
WO2025115007A9 (fr
Inventor
Amir EZION
Shlomi Cohen
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.)
Adama Makhteshim Ltd
Original Assignee
Adama Makhteshim Ltd
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 Adama Makhteshim Ltd filed Critical Adama Makhteshim Ltd
Publication of WO2025115007A2 publication Critical patent/WO2025115007A2/fr
Publication of WO2025115007A3 publication Critical patent/WO2025115007A3/fr
Publication of WO2025115007A9 publication Critical patent/WO2025115007A9/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C273/00—Preparation of urea or its derivatives, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
    • C07C273/18—Preparation of urea or its derivatives, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups of substituted ureas
    • C07C273/189—Purification, separation, stabilisation, use of additives

Definitions

  • the invention relates to a process for the decoloration of novaluron. It relates to a process for removing the impurities from novaluron. More particularly, it relates to a process for the removal of the color impurities from novaluron.
  • Novaluron is used widely as a chemical pesticide belonging to the class of insecticides called insect growth regulators. It is a benzoylphenyl urea derivative which inhibits the chitin biosynthesis in the insects. It is used to control a range of pests including Lepidoptera, Coleoptera, and Diptera.
  • Novaluron is synthesized from 2,6-difluorobenzamide and oxalyl chloride as starting material.
  • the synthesis of novaluron yields a product that may be colored and as per the specification standard of different countries, it is necessary to remove the color impurities from novaluron.
  • the present invention provides a process for removing the color from novaluron comprising: a) mixing said the novaluron with a solvent system and heating the mixture, b) adjusting the pH of the mixture of step (a) up to 12 with a base, c) separating and neutralizing the organic phase of step (b) with an acid and d) separating, cooling and filtering the organic phase of step (c) to obtain colorless novaluron.
  • the process of the present invention provides that the solvent system in step (a) is a mixture of an organic solvent or an aqueous solvent.
  • the process of the present invention provides that the organic solvent is selected from the group comprising toluene, xylene, dichloromethane, 1,2-dichloroethane, mesitylene, chlorotoluene, mono chlorobenzene, ethyl benzene and mixtures thereof.
  • the process of the present invention provides that the solvent system in step (a) is a mixture of toluene and water.
  • the process of the present invention provides that the temperature of step (a) is about 75 °C to 80 °C.
  • the process of the present invention provides that the base in step (b) is an organic base or an inorganic base.
  • the process of the present invention provides that the inorganic base is selected from the group consisting of sodium hydroxide, potassium hydroxide, magnesium hydroxide, ammonium hydroxide, sodium carbonate, potassium carbonate and mixtures thereof.
  • the process of the present invention provides that the organic base is selected from the group consisting of an aliphatic amine compound, amidine compound and mixtures thereof.
  • the process of the present invention provides that the aliphatic amine is triethylamine and the amidine compound is l,8-diazabicyclo[5.4.0]undec-7-ene or 1,5- diazabicyclo[4.3.0]non-5-ene.
  • the process of the present invention provides that the base is sodium hydroxide.
  • the process of the present invention provides that the pH of step (b) is about 11 to 12.
  • the process of the present invention provides that the acid in step (c) is selected from the group comprising an aqueous solution of phosphoric acid, phosphorus acid, formic acid, acetic acid, benzoic acid, oxalic acid, hydrofluoric acid, nitrous acid, sulfurous acid and mixtures thereof.
  • the process of the present invention provides that the acid is an aqueous solution of phosphoric acid.
  • FIG. 1A is a representation of an image of colored novaluron.
  • FIG. IB is a representation of an image of colorless novaluron after the completion of the process.
  • the term “or” has the meaning of both “and” and “or”. It will be further understood that the terms “comprises”, “comprising”, “includes”, “including”, or any other variation thereof, are intended to cover a non-exclusive inclusion, subject to any limitation explicitly indicated. For example, a method that comprises a list of elements is not necessarily limited to only those elements but may include other elements not expressly listed or inherent to such method.
  • endpoints of all ranges directed to the same component or property herein are inclusive of the endpoints, are independently combinable, and include all intermediate points and ranges.
  • novaluron refers to the colored novaluron, but not limited to, in the form of granule, powder or crystal.
  • solvent refers to a material that dissolves another substance while not changing its properties.
  • the solvent can be an organic solvent, or an aqueous solvent.
  • organic solvent refers to an organic molecule, generally in liquid form, capable of at least partially dissolving another substance (i.e. the solute).
  • pH is a measure of hydrogen-ion concentration, as commonly used in the art.
  • the pH provides a measure on a scale from 0 to 14 of the acidity or alkalinity of a solution.
  • base refers to any chemical compound or material that, when dissolved in water, gives a solution with a hydrogen ion activity lower than that of pure water (i.e. a pH higher than 7.0 at standard conditions).
  • Bases include, but are not limited to, inorganic base or organic base, as commonly known in the art.
  • the term “weak acid” refers to an acid that dissociates incompletely and does not release all of its hydrogens in a solution, i.e., it does not completely donate all of its protons.
  • the present invention subject matter relates to a process for removing the color from novaluron comprising: a) mixing the novaluron with a solvent system and heating the mixture, b) adjusting the pH of the mixture of step (a) up to 12 with a base, c) separating and neutralizing the organic phase of step (b) with an acid and d) separating, cooling and filtering the organic phase of step (c) to obtain the colorless novaluron.
  • Figure 1 A demonstrates the colored novaluron before the start of the process for the conversion of the colored novaluron to color less novaluron.
  • the present invention relates to the solvent system in step (a) is a mixture of an organic solvent and an aqueous solvent.
  • the organic solvent may comprise one or more of alcohols selected from 1 -butanol, and t-butyl alcohol; esters selected from ethyl acetate, isopropyl acetate, t-butyl acetate, and isobutyl acetate; chlorinated hydrocarbons selected from 1,2-dichloroethane, dichloromethane, chlorotoluene, and chlorobenzene; hydrocarbons selected from pentane, hexane, heptane, and cyclohexane; ethers selected from tetrahydrofuran, diisopropyl ether, diethyl ether, and methyl tert-butyl ether; and mixture thereof.
  • the aqueous solvent refers to water.
  • the organic solvent is selected from the group comprising toluene, xylene, dichloromethane, 1,2-dichloroethane, mesitylene, chlorotoluene, mono chlorobenzene, ethyl benzene and mixtures thereof.
  • the solvent system in step (a) is a mixture of toluene and water.
  • step (a) is heated at a temperature of about 75 °C to 85 °C, specifically at a temperature of about 75 °C to 80 °C for a specified period of time.
  • the present invention relates to the base in step (b) is an organic base or an inorganic base.
  • the inorganic base is selected from the group consisting of sodium hydroxide, potassium hydroxide, magnesium hydroxide, ammonium hydroxide, sodium carbonate, potassium carbonate and mixtures thereof.
  • the present invention provides that the organic base is selected from the group consisting of aliphatic amines, amidine compound and mixtures thereof.
  • the aliphatic amine compound is triethylamine and the amidine compound is l,8-diazabicyclo[5.4.0]undec-7-ene (DBU) or l,5-diazabicyclo[4.3.0]non-5-ene (DBN).
  • the high pH of the mixture/ solution is preferably achieved by adding an inorganic base.
  • an inorganic base is defined as a chemical that contains a free hydroxide or carbonate ion that can spontaneously accept a proton from water and is used for adjusting the pH of the bulk solution to the target value.
  • the preferred inorganic bases are sodium hydroxide, potassium hydroxide, other alkaline hydroxides, divalent hydroxides such as magnesium hydroxide, and volatile hydroxide such as ammonium hydroxide.
  • an organic base such as primary-, secondary- and tertiary-amines can be used. A combination of both organic and inorganic bases is also appropriate for the process of the present invention.
  • the base is added so that the pH of the solution up to 12, preferably the pH of step is in between 11 to 12.
  • the base for use with the process of the present invention in step (b) is sodium hydroxide.
  • the strength of sodium hydroxide is in the range of between 10% to 20%, preferably 15%.
  • the sodium hydroxide base is used in the process of the present invention to adjust the pH of the solution between 11 to 12. If the pH is below 11, the process will not be efficient and pH above 12 leads to novaluron itself undergoing some decomposition. Therefore, the pH range is critical for the above process for the efficient decoloration of novaluron. Otherwise, the process will be less effective in decoloration of novaluron.
  • step (b) the solution of step (b) is kept for at least 10 to 30 min, followed by phase separation.
  • the organic phase is separated for the next step, and the aqueous phase is discarded.
  • the organic phase is further treated with an acid to neutralize the organic phase in step (c) up to pH 7.
  • the acid is selected from the group comprising an aqueous solution of phosphoric acid, phosphorus acid, formic acid, acetic acid, benzoic acid, oxalic acid, hydrofluoric acid, nitrous acid, malonic acid and mixtures thereof.
  • the acid in step (c) is an aqueous solution of phosphoric acid.
  • the strength of phosphoric acid is in the range of between 10% to 20%, preferably 15%.
  • the acid is selected from the group comprising ana aqueous weak acid or a strong acid and the aqueous weak acid is added first and strong acid (hydrochloric acid, sulfuric acid, chlorosulfonic acid, etc.) is added later to maintain the pH in step (c).
  • strong acid hydrochloric acid, sulfuric acid, chlorosulfonic acid, etc.
  • the aqueous weak acid solution of phosphoric acid added first, and later hydrochloric acid is added to maintain the pH.
  • the aqueous weak acid is used to neutralize the organic phase.
  • the mixture is allowed to stand for some time, which leads to phase separation.
  • the organic phase is separated for the next step, and the aqueous phase is discarded.
  • step (d) The organic phase separated in step (d) is cooled to a temperature of about 0 °C to 5 °C, preferably about 0 °C. It is further filter over the Buchner funnel with vacuum.
  • the filter cake is obtained by the filtration of the organic phase. It is further washed with the organic solvent, preferably toluene. Finally, the filter cake is dried with vacuum to obtain color less novaluron.
  • Figure IB demonstrates the color less novaluron after the completion of the process for the conversion of the colored novaluron to color less novaluron.
  • the process of the present invention reduces the amount of the l-(3-chloro- 4-( 1 , 1 ,2-trifluoro-2-(trifluoromethoxy)ethoxy)phenyl)-5-fluoroquinazoline-2,4( 1 /7,3/7)-dionc and N-((3-chloro-4-hydroxyphenyl)carbamoyl)-2,6-difluorobenzamide impurities.
  • the decolorization time, amount of base and weak acid is optionally itself subjected to a process to remove color from the novaluron.
  • the purification of the solvent used in the process is optionally achieved by passing the used solvent through activated carbon, mechanical filtering, skimming, distillation or combinations thereof.
  • the activated carbon may be in the form of a column, a bed, or any other configuration that will allow the passage of the used solvent resulting in a novaluron-free solvent suitable for reuse.
  • the inventive processes provide a decolorized novaluron that is fully decolorized and suitable for use in formulation as per specifications standard of different countries.
  • Example 1 Process for decoloration of Novaluron:
  • Patents and publications mentioned in the specification are indicative of the levels of those skilled in the art to which the invention pertains. These patents and publications are incorporated herein by reference to the same extent as if each individual application or publication was specifically and individually incorporated herein by reference.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Coloring Foods And Improving Nutritive Qualities (AREA)

Abstract

La présente invention concerne un procédé de décoloration de novaluron. L'invention concerne un procédé d'élimination des impuretés du novaluron. Plus particulièrement, l'invention concerne un procédé d'élimination des impuretés de couleur du novaluron.
PCT/IL2024/051117 2023-11-28 2024-11-25 Procédé d'élimination de couleur de novaluron Pending WO2025115007A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US202363603213P 2023-11-28 2023-11-28
US63/603,213 2023-11-28

Publications (3)

Publication Number Publication Date
WO2025115007A2 true WO2025115007A2 (fr) 2025-06-05
WO2025115007A3 WO2025115007A3 (fr) 2025-09-04
WO2025115007A9 WO2025115007A9 (fr) 2026-03-26

Family

ID=93924806

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IL2024/051117 Pending WO2025115007A2 (fr) 2023-11-28 2024-11-25 Procédé d'élimination de couleur de novaluron

Country Status (1)

Country Link
WO (1) WO2025115007A2 (fr)

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IT1213420B (it) * 1986-12-19 1989-12-20 Donegani Guido Ist "n(-2,6-difluorobenzoil)-n'-3-cloro -41,1,2-trifluoro-2-(trifluorometossi ) etossi fenil urea ad attivita'insetticida.
CN103214400B (zh) * 2013-04-15 2014-12-31 衢州学院 一种氟铃脲的制备方法

Also Published As

Publication number Publication date
WO2025115007A3 (fr) 2025-09-04
WO2025115007A9 (fr) 2026-03-26

Similar Documents

Publication Publication Date Title
JP6303186B2 (ja) タウリンを製造するための循環方法
WO2025115007A2 (fr) Procédé d'élimination de couleur de novaluron
JP2012140390A (ja) α−アミノ−γ−ブチロラクトンの製造方法
CN120943886B (zh) 一种三肽Fmoc-Pro-Pro-Pro-OH的合成方法
JP2010143857A (ja) カルニチンの精製方法
CN113248351A (zh) 6-氯-2-甲氧基甲苯的制备方法及甲氧虫酰肼的合成工艺
RU2373193C2 (ru) Способ очистки мезотриона
WO2007080470A2 (fr) Procede de purification de levetiracetame
DE69828777T2 (de) Verfahren zur herstellung von buttersäureester-derivaten
CA2510272C (fr) Procede de production de gamma-cyhalothrine
JPS60161958A (ja) ａ‐シアノ‐３‐フエノキシ‐４‐フルオロ‐ベンジルパーメトレートのある種の光学的対掌体の対の調整方法
KR20080086463A (ko) 라미프릴의 제조를 위한 개선된 방법
EP0575925A1 (fr) Procédé de purification de l'indigo
CN1312122C (zh) 一种制备和纯化氰酸酯的方法
CN109651432B (zh) 一种制备o,o-二甲基-s-(n-甲基氨基甲酰甲基)硫代磷酸酯的方法
KR20040010649A (ko) 결정질 이미페넴의 분리 방법
DE19835866B4 (de) Verfahren zur Herstellung von 5-Perfluoralkyluracilderivaten
JPS6328058B2 (fr)
CN102718681A (zh) 一种发黄的二苯甲酮腙的提纯方法
DE69102896T2 (de) Verfahren zur Racemisierung von einem optisch aktiven Aminosäure-Amid.
KR100472806B1 (ko) 4-시아노-3-히드록시 부탄오일 히드라지드, 그 유도체 및 제조방법
EP0728736B1 (fr) Procédé pour la préparation de tert-leucinol optiquement actif et son utilisation
CA2375234A1 (fr) Procede de separation des bases diastereo-isomeres de 2-[(dimethylamino)methyl]-1-(3-methoxy-phenyl)-cyclohexanol
DE69524737T2 (de) 2-isoxazolin-derivate, verfahren zu deren herstellung sowie verfahren zur herstellung von verwandten verbindungen
CN110590610A (zh) 一种高品质烷基硫酸钠的制备方法