Method for removing color from fluroxure

Abstract

This invention provides a method for decolorizing fluorourea. This invention provides a method for removing impurities from fluorourea. More particularly, this invention provides a method for removing colored impurities from fluorourea.

Description

Technical Field

[0001] This invention relates to a method for decolorizing fluorourea. This invention also relates to a method for removing impurities from fluorourea. More particularly, this invention relates to a method for removing colored impurities from fluorourea. Background Technology

[0002] Fluorouracil is widely used as a chemical pest control agent, belonging to the insecticide category known as insect growth regulators. It is a benzoylphenyl urea derivative that inhibits chitin biosynthesis in insects. Fluorouracil is used to control a range of pests, including Lepidoptera, Coleoptera, and Diptera.

[0003] Fluoroureas are synthesized from 2,6-difluorobenzamide and oxalyl chloride as starting materials. The synthesis of fluoroureas produces potentially colored products, and depending on the specifications and standards of different countries, it is necessary to remove colored impurities from the fluoroureas.

[0004] This colored impurity is difficult to remove effectively using conventional methods. Therefore, there has long been an urgent need for a simple and environmentally friendly method for removing colored impurities from fluorourea, and for a method suitable for the industrial production of colorless fluorourea. Summary of the Invention

[0005] The following summary is not intended to be a comprehensive description, but rather to provide a tool for understanding some of the novel aspects that make this invention unique. The various features of the invention can be fully understood by considering the complete specification, claims, drawings, and abstract as a whole.

[0006] This invention provides a method for removing color from fluorourea, the method comprising:

[0007] a) Mix fluorourea with the solvent system and heat the mixture.

[0008] b) Adjust the pH of the mixture from step (a) to a maximum of 12 using alkali.

[0009] c) Separate the organic phase from step (b) and neutralize it with acid, and

[0010] d) Separate, cool and filter the organic phase from step (c) to obtain colorless fluorourea.

[0011] In one respect, the method of the present invention specifies that the solvent system in step (a) is a mixture of organic solvents or aqueous solvents.

[0012] In another aspect, the method of the present invention specifies that the organic solvent is selected from the group consisting of toluene, xylene, dichloromethane, 1,2-dichloroethane, mesitylene, chlorotoluene, monochlorobenzene, ethylbenzene, and mixtures thereof.

[0013] In a preferred aspect, the method of the present invention specifies that the solvent system in step (a) is a mixture of toluene and water.

[0014] In one respect, the method of the present invention specifies that the temperature of step (a) is about 75°C to 80°C.

[0015] In another aspect, the method of the present invention specifies that the base in step (b) is an organic base or an inorganic base.

[0016] In one aspect, the method of the present invention specifies 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.

[0017] In another aspect, the method of the present invention specifies that the organic base is selected from the group consisting of aliphatic amine compounds, amidine compounds, and mixtures thereof.

[0018] In another aspect, the method of the present invention specifies that the aliphatic amine is triethylamine and the amidine compound is 1,8-diazabicyclo[5.4.0]undec-7-ene or 1,5-diazabicyclo[4.3.0]non-5-ene.

[0019] In a preferred embodiment, the method of the present invention specifies that the alkali is sodium hydroxide.

[0020] In one respect, the method of the present invention specifies that the pH of step (b) is about 11 to 12.

[0021] In another aspect, the method of the present invention specifies that the acid in step (c) is selected from the group consisting of: phosphoric acid, phosphorous acid, formic acid, acetic acid, benzoic acid, oxalic acid, hydrofluoric acid, nitrous acid, sulfurous acid, and aqueous solutions of mixtures thereof.

[0022] In one aspect, the method of the present invention specifies that the acid is an aqueous solution of phosphoric acid. Attached Figure Description

[0023] Figure 1A This is an image representation of colored fluorourea.

[0024] Figure 1B This is a representation of the colorless fluorourea image after the method is completed. Detailed Implementation

[0025] For clarity, specific terminology is used in describing embodiments of the invention. However, it is not intended to limit the invention to the specific terminology chosen so far, and it should be understood that each specific term includes all technical equivalents that operate in a similar manner to achieve a similar purpose.

[0026] It should be understood that the terminology used herein is for the purpose of describing embodiments only and is not intended to be limiting. Unless the context clearly specifies otherwise, as used in this specification, the singular forms “a / an” and “the” include plural referents. Thus, for example, references to “compound” include one or more such compounds.

[0027] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. Although other methods and materials similar to or equivalent to those described herein may be used in the practice of this invention, preferred materials and methods are described herein.

[0028] As used herein, the term “or” has both meanings of “and” and “or”. It will be further understood that the terms “comprises / comprising,” “includes / including,” or any other variations thereof are intended to cover non-exclusive inclusion, subject to any expressly indicated limitations. For example, a method of including a list of elements is not necessarily limited to those elements, but may include other elements not expressly listed or inherent to such a method.

[0029] Throughout this application, the descriptions of various embodiments use the term "comprising". However, those skilled in the art will understand that in certain specific circumstances, the language "substantially consisting of" or "consisting of" may be used to describe embodiments.

[0030] Therefore, unless otherwise indicated, the numerical parameters listed in the following specification and appended claims are approximate values ​​and may vary depending on the desired characteristics sought to be obtained. At a minimum, each numerical parameter should be interpreted taking into account the number of significant figures reported and by applying common rounding techniques.

[0031] Furthermore, the endpoints of all ranges involving the same component or property in this document include endpoints, are independently combinable, and include all intermediate points and ranges.

[0032] As used herein, the term "fluorourea" refers to colored fluorourea, but is not limited to colored fluorourea in particulate, powder or crystalline form.

[0033] As used herein, the term "solvent" refers to a material that dissolves another substance without altering its properties. In this invention, the solvent may be an organic solvent or an aqueous solvent.

[0034] As used herein, the term "organic solvent" refers to an organic molecule that is usually in liquid form and is capable of dissolving at least partially another substance (i.e., a solute).

[0035] As used herein, the term “pH” is a measure of hydrogen ion concentration, as commonly used in the art. pH provides a measure of the acidity or alkalinity of a solution on a scale of 0 to 14.

[0036] As used herein, the term "base" refers to any compound or material that, when dissolved in water, produces a solution with hydrogen ion activity lower than that of pure water (i.e., a pH greater than 7.0 under standard conditions). Bases include, but are not limited to, inorganic or organic bases, as commonly known in the art.

[0037] As used in this article, the term "weak acid" refers to an acid that does not completely dissociate and does not release all of its hydrogen atoms in solution, meaning it does not completely supply all of its protons.

[0038] The present invention relates to a method for removing color from fluorourea, the method comprising:

[0039] a) Mix fluorourea with the solvent system and heat the mixture.

[0040] b) Adjust the pH of the mixture from step (a) to a maximum of 12 using alkali.

[0041] c) Separate the organic phase from step (b) and neutralize it with acid, and

[0042] d) Separate, cool and filter the organic phase from step (c) to obtain colorless fluorourea.

[0043] Figure 1A The image shows colored fluorourea before the process of converting colored fluorourea to colorless fluorourea begins.

[0044] In one embodiment, the present invention relates to the solvent system in step (a) as a mixture of an organic solvent and an aqueous solvent.

[0045] Generally, organic solvents may include one or more of the following: alcohols selected from 1-butanol and tert-butanol; esters selected from ethyl acetate, isopropyl acetate, tert-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 mixtures thereof. Generally, aqueous solvents refer to water.

[0046] In another embodiment, the organic solvent is selected from the group consisting of toluene, xylene, dichloromethane, 1,2-dichloroethane, mesitylene, chlorotoluene, monochlorobenzene, ethylbenzene, and mixtures thereof.

[0047] In a preferred embodiment, in the method of the present invention, the solvent system in step (a) is a mixture of toluene and water.

[0048] The solution from 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.

[0049] In another embodiment, the present invention relates to the base in step (b) as an organic or inorganic base.

[0050] In one embodiment, 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. In another embodiment, the invention specifies that the organic base is selected from the group consisting of aliphatic amines, amidine compounds, and mixtures thereof. In yet another embodiment, the aliphatic amine compound is triethylamine, and the amidine compound is 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) or 1,5-diazabicyclo[4.3.0]non-5-ene (DBN).

[0051] A high pH in the mixture / solution is preferably achieved by adding an inorganic base. As used herein, an inorganic base is defined as a chemical substance containing free hydroxide or carbonate ions that can spontaneously accept protons from water and be used to adjust the pH of the bulk solution to a target value. Preferred inorganic bases are sodium hydroxide, potassium hydroxide, other basic hydroxides, divalent hydroxides such as magnesium hydroxide, and volatile hydroxides such as ammonium hydroxide. Additionally, organic bases such as primary, secondary, and tertiary amines can be used. Combinations of both organic and inorganic bases are also suitable for the method of the present invention. Preferably, the base is added to achieve a pH of up to 12, and preferably, the pH of the step is between 11 and 12.

[0052] In a preferred embodiment, the base used in step (b) of the method of the present invention is sodium hydroxide. The strength of the sodium hydroxide is in the range of 10% to 20%, preferably 15%.

[0053] Sodium hydroxide is used in the method of this invention to adjust the pH of the solution to between 11 and 12. If the pH is below 11, the method will not be effective, and a pH above 12 causes the fluorourea itself to undergo some decomposition. Therefore, the pH range is crucial for the effective decolorization of fluorourea using the above method. Otherwise, the method will be less effective in decolorizing fluorourea.

[0054] In the method according to the invention, the solution from step (b) is held for at least 10 to 30 minutes, followed by phase separation. The organic phase is used for the next step, and the aqueous phase is discarded.

[0055] The organic phase is further treated with acid to neutralize the organic phase in step (c) to a pH of up to 7. The acid is selected from aqueous solutions of phosphoric acid, phosphorous acid, formic acid, acetic acid, benzoic acid, oxalic acid, hydrofluoric acid, nitrous acid, malonic acid, and mixtures thereof. In a preferred embodiment, the acid in step (c) is an aqueous solution of phosphoric acid. The strength of the phosphoric acid is in the range of 10% to 20%, preferably 15%.

[0056] In one embodiment, the acid is selected from the group consisting of aqueous solutions of weak acids or strong acids, and the aqueous solution of the weak acid is added first, followed by the addition of a strong acid (hydrochloric acid, sulfuric acid, chlorosulfonic acid, etc.) to maintain the pH in step (c). For example, an aqueous solution of phosphoric acid is added first, followed by the addition of hydrochloric acid to maintain the pH.

[0057] Neutralize the organic phase with a weak acid aqueous solution. Allow the mixture to stand for a period of time, which results in phase separation. Use the separated organic phase for the next step and discard the aqueous phase.

[0058] 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 then further filtered under vacuum through a Buchner funnel.

[0059] A filter cake was obtained by filtering the organic phase. It was then washed with an organic solvent, preferably toluene. Finally, the filter cake was dried under vacuum to obtain colorless fluorourea.

[0060] Figure 1B The colorless fluorourea is shown after the method for converting colored fluorourea to colorless fluorourea has been completed.

[0061] In one embodiment, the method of the present invention reduces the amount of 1-(3-chloro-4-(1,1,2-trifluoro-2-(trifluoromethoxy)ethoxy)phenyl)-5-fluoroquinazoline-2,4(1H,3H)-dione and N-((3-chloro-4-hydroxyphenyl)carbamoyl)-2,6-difluorobenzamide impurities.

[0062] The decolorization time, alkali concentration, and weak acid concentration are optionally inherently dependent on the process of removing color from fluorourea. Purification of the solvent used in this method can optionally be achieved by passing the solvent through activated carbon, mechanical filtration, skimming, distillation, or a combination thereof. The activated carbon can be in the form of a column, bed, or any other configuration that will allow the solvent to pass through, thereby producing a fluorourea-free solvent suitable for reuse.

[0063] It has been found that the provided method for forming decolorized fluorourea is superior. The method of the present invention provides a decolorized fluorourea that is completely decolorized and suitable for use in formulations according to the specifications and standards of different countries.

[0064] The various aspects of the invention are illustrated by the following non-limiting examples. These examples are for illustrative purposes and are not intended to limit any practice of the invention. It should be understood that variations and modifications can be made without departing from the spirit and scope of the invention. The reagents shown herein are generally commercially available, and those skilled in the art will readily understand where such reagents can be obtained. Example

[0065] Example 1: A method for decolorizing fluorourea:

[0066] Add 50 g of fluorourea powder, 375 g of toluene, and 150 g of water to a glass flask. Heat the flask to 78°C to ensure complete dissolution of the components. Adjust the pH to 12 using a 15% sodium hydroxide solution and maintain this pH for at least 10 minutes during dissolution. Then, separate and discard the lower phase. Add 125 g of 15% phosphoric acid to adjust the pH to the range of 6.5 to 7.5, followed by another separation of the lower phase. Cool the flask to 0°C and then filter the organic phase through a Buchner filter under vacuum. Wash the filter cake with 50 g of toluene and continue drying the filter cake under vacuum at 70°C.

[0067] In addition to those shown and described herein, various modifications to the invention will be apparent to those skilled in the art based on the foregoing description. Such modifications are also intended to fall within the scope of the appended claims.

[0068] It should be understood that, unless otherwise stated, all reagents are available from sources known in the art.

[0069] The patents and publications mentioned in this specification indicate the level of expertise of those skilled in the art to which this invention relates. These patents and publications are incorporated herein by reference to the same extent that each individual application or publication is specifically and individually incorporated herein by reference.

[0070] The foregoing description is an illustration of specific embodiments of the invention, but does not imply limitation on its practice. The following claims (including all their equivalents) are intended to define the scope of the invention.

Claims

1. A method for removing color from fluorourea, the method comprising: a) Mix the fluorourea with the solvent system and heat the mixture. b) Adjust the pH of the mixture from step (a) to a maximum of 12 using alkali. c) Separate the organic phase from step (b) and neutralize it with acid, and d) Separate, cool and filter the organic phase from step (c) to obtain colorless fluorourea.

2. The method as described in claim 1, wherein, The solvent system is a mixture of organic solvents and aqueous solvents.

3. The method as described in claim 2, wherein, The organic solvent is selected from the group consisting of toluene, xylene, dichloromethane, 1,2-dichloroethane, mesitylene, chlorotoluene, monochlorobenzene, ethylbenzene, and mixtures thereof.

4. The method of claim 2, wherein, The solvent system is a mixture of toluene and water.

5. The method of claim 1, wherein, The temperature in step (a) is approximately 75°C to 80°C.

6. The method of claim 1, wherein, The base is an organic base or an inorganic base.

7. The method of claim 6, wherein, 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.

8. The method of claim 6, wherein, The organic base is selected from the group consisting of aliphatic amine compounds, amidine compounds, and mixtures thereof.

9. The method of claim 8, wherein, The aliphatic amine compound is triethylamine and the amidine compound is 1,8-diazabicyclo[5.4.0]undec-7-ene or 1,5-diazabicyclo[4.3.0]non-5-ene.

10. The method of claim 6, wherein, The alkali is sodium hydroxide.

11. The method of claim 1, wherein, The pH in step (b) is approximately 11 to 12.

12. The method of claim 1, wherein, The acid is selected from the group consisting of: phosphoric acid, phosphorous acid, formic acid, acetic acid, benzoic acid, oxalic acid, hydrofluoric acid, nitrous acid, malonic acid, and aqueous solutions of mixtures thereof.

13. The method of claim 12, wherein, The acid is an aqueous solution of phosphoric acid.

14. The method of claim 1, wherein, In step (c), the acid is selected from a weak acid aqueous solution or a strong acid, wherein the weak acid aqueous solution is added first and the strong acid is added later to maintain the pH.

15. The method of claim 1, wherein, The method reduces the amount of 1-(3-chloro-4-(1,1,2-trifluoro-2-(trifluoromethoxy)ethoxy)phenyl)-5-fluoroquinazoline-2,4(1H,3H)-dione and N-((3-chloro-4-hydroxyphenyl)carbamoyl)-2,6-difluorobenzamide impurities in the fluorourea.

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