Process for removal of color from novaluron

Abstract

The present invention provides a process for decoloration of novaluron. It provides a process for removing the impurities from novaluron. More particularly, it provides a process for the removal of the color impurities from novaluron.

Description

[0001] PROCESS FOR REMOVAL OF COLOR FROM NOVALURON

[0002] Field of the Invention:

[0003] 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.

[0004] Background of the Invention:

[0005] 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.

[0006] 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.

[0007] It is difficult to effectively remove this color impurities by conventional methods. Therefore, it is a long felt need to provide a simple and environmentally friendly process for removing the color impurities from novaluron and is suitable for industrial production of colorless novaluron.

[0008] Summary of the Invention:

[0009] The following invention summary was not intended to be a comprehensive description, but rather a tool for understanding some of the novel aspects that characterize the present invention distinctive. It is possible to fully comprehend an invention various characteristic by considering the complete specification, claims, drawings, and abstract as a whole.

[0010] 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.

[0011] In an aspect, 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.

[0012] In another aspect, 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.

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

[0014] In an aspect, the process of the present invention provides that the temperature of step (a) is about 75 °C to 80 °C.

[0015] In a further aspect, the process of the present invention provides that the base in step (b) is an organic base or an inorganic base.

[0016] In an aspect, 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.

[0017] In a further aspect, 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.

[0018] In yet another aspect, 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.

[0019] In a preferred aspect, the process of the present invention provides that the base is sodium hydroxide.

[0020] In an aspect, the process of the present invention provides that the pH of step (b) is about 11 to 12.

[0021] In another aspect, 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.

[0022] In an aspect, the process of the present invention provides that the acid is an aqueous solution of phosphoric acid.

[0023] Brief Description of the Drawings:

[0024] FIG. 1A is a representation of an image of colored novaluron.

[0025] FIG. IB is a representation of an image of colorless novaluron after the completion of the process.

[0026] Description of the Invention:

[0027] For the sake of clarity, specific terminology is resorted to in describing the embodiments of the invention. However, it is not intended that the invention be limited to the specific terms so selected, and it is to be understood that each specific term includes all technical equivalents that operate in a similar manner to accomplish a similar purpose.

[0028] It will be understood that the terminology used herein is for the purpose of describing embodiments only and is not intended to be limiting. As used in this specification, the singular forms “a”, “an” and “the” include plural referents unless the context clearly dictates otherwise. Thus, for example, the reference to “a compound” includes one or more of such compounds.

[0029] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one ordinarily skilled in the art to which the invention pertains. Although other methods and materials similar to or equivalent to those described herein can be used in the practise of the present invention, the preferred materials and methods are described herein.

[0030] As used herein, 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.

[0031] Throughout the application, descriptions of various embodiments use the term “comprising”. However, it will be understood by one of skill in the art that in some specific instances, an embodiment can alternatively be described using the language “consisting essentially of’ or “consisting of.”

[0032] Accordingly, unless indicated to the contrary, the numerical parameters set forth in the following specification and attached claims are approximations that may vary depending upon the desired properties sought to be obtained. At the very least, each numerical parameter should at least be construed considering the number of reported significant digits and by applying ordinary rounding techniques.

[0033] In addition, the 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.

[0034] As used herein, the term “novaluron” refers to the colored novaluron, but not limited to, in the form of granule, powder or crystal.

[0035] As used herein, the term “solvent” refers to a material that dissolves another substance while not changing its properties. In the present invention, the solvent can be an organic solvent, or an aqueous solvent.

[0036] As used herein, the term “organic solvent” refers to an organic molecule, generally in liquid form, capable of at least partially dissolving another substance (i.e. the solute).

[0037] As used herein, the term “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.

[0038] As used herein, the term “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.

[0039] As used herein, 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.

[0040] Figure 1 A demonstrates the colored novaluron before the start of the process for the conversion of the colored novaluron to color less novaluron.

[0041] In an embodiment, the present invention relates to the solvent system in step (a) is a mixture of an organic solvent and an aqueous solvent.

[0042] In general, 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. In general, the aqueous solvent refers to water.

[0043] In another embodiment, the organic solvent is selected from the group comprising toluene, xylene, dichloromethane, 1,2-dichloroethane, mesitylene, chlorotoluene, mono chlorobenzene, ethyl benzene and mixtures thereof.

[0044] In a preferred embodiment, the process of the present invention the solvent system in step (a) is a mixture of toluene and water.

[0045] The solution of 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.

[0046] In a further embodiment, the present invention relates to the base in step (b) is an organic base or an inorganic base.

[0047] In an 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 present invention provides that the organic base is selected from the group consisting of aliphatic amines, amidine compound and mixtures thereof. In a further embodiment, 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).

[0048] The high pH of the mixture / solution is preferably achieved by adding an inorganic base. As used herein, 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. Also, 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. Preferably, 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.

[0049] In a preferred embodiment, 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%.

[0050] 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.

[0051] The process, according to the present invention, 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.

[0052] 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. In a preferred embodiment, 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%. In an embodiment, 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). For example, the aqueous weak acid solution of phosphoric acid added first, and later hydrochloric acid is added to maintain the pH.

[0053] 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.

[0054] 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.

[0055] 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.

[0056] Figure IB demonstrates the color less novaluron after the completion of the process for the conversion of the colored novaluron to color less novaluron.

[0057] In an embodiment, 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.

[0058] 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.

[0059] It has been found that the provided processes for forming a decolorized novaluron is superior. The inventive processes provide a decolorized novaluron that is fully decolorized and suitable for use in formulation as per specifications standard of different countries.

[0060] Various aspects of the present invention are illustrated by the following non-limiting examples. The examples are for illustrative purposes and are not a limitation on any practice of the present invention. It will be understood that variations and modifications can be made without departing from the spirit and scope of the invention. Reagents illustrated herein are commonly commercially available, and a person of ordinary skill in the art readily understands where such reagents may be obtained.

[0061] EXAMPLE

[0062] Example 1: Process for decoloration of Novaluron:

[0063] 50 g of Novaluron powder, 375 g of toluene, and 150 g of water was added in a glass flask. The flask was heated to 78 °C to ensure complete dissolution of the components. The solution of sodium hydroxide 15% was used to adjust the pH to 12 and hold for at least 10 minutes during dissolution. Afterward, separate and discard the lower phase. 125 g of phosphoric acid 15% was added to adjust the pH in the range of 6.5 to 7.5, followed by another separation of the lower phase. The flask was cooled to 0°C, then filter the organic phase through a Buchner filter under vacuum. The filter cake was washed with 50 g of toluene and proceed to dry the filtered cake at 70°C using vacuum conditions.

[0064] Various modifications of the present invention, in addition to those shown and described herein, will be apparent to those skilled in the art of the above description. Such modifications are also intended to fall within the scope of the appended claims.

[0065] It is appreciated that all reagents are obtainable by sources known in the art unless otherwise specified.

[0066] 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.

[0067] The foregoing description is illustrative of particular embodiments of the invention but is not meant to be a limitation upon the practice thereof. The following claims, including all equivalents thereof, are intended to define the scope of the invention.

Claims

We Claim:

1. 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.

2. The process as claimed in claim 1 , wherein the solvent system is a mixture of an organic solvent and an aqueous solvent.

3. The process as claimed in claim 2, wherein the organic solvent is selected from the group comprising toluene, xylene, dichloromethane, 1,2-dichloroethane, mesitylene, chlorotoluene, mono chlorobenzene, ethyl benzene and mixtures thereof.

4. The process as claimed in claim 2, wherein the solvent system is a mixture of toluene and water.

5. The process as claimed in claim 1, wherein the temperature of step (a) is about 75 °C to 80 °C.

6. The process as claimed in claim 1, wherein the base is an organic base or an inorganic base.

7. The process as claimed in 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 process as claimed in claim 6, wherein the organic base is selected from the group consisting of an aliphatic amine compound, amidine compound and mixtures thereof.

9. The process as claimed in claim 8, wherein the aliphatic amine compound 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.

10. The process as claimed in claim 6, wherein the base is sodium hydroxide.

11. The process as claimed in claim 1, wherein the pH of step (b) is about 11 to 12.

12. The process as claimed in claim 1, wherein 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.

13. The process as claimed in claim 12, wherein the acid is an aqueous solution of phosphoric acid.

14. The process as claimed in claim 1, wherein in step (c) the acid is selected from an aqueous weak acid or a strong acid, wherein the aqueous weak acid is added first and the strong acid is added later to maintain the pH.

15. The process as claimed in claim 1, wherein the process reduces the amount of 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 from the novaluron.

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