Description:Field of the Invention:
The present invention relates to an improved process for the preparation of Pyroxasulfone of formula-1. More particularly the present invention relates to oxidation of compound of formula-2 to provide Pyroxasulfone of formula-1.

Formula-1.
Background of the Invention:
Pyroxasulfone is member of isoxazoline derivatives having chemical name 3-[5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)pyrazol-4-yl-methylsulfonyl]-4,5-dihydro-5,5-dimethyl-1,2-oxazole. Pyroxasulfone is a pre and post emergence herbicide that controls the wide range of grasses and broadleaf weed in crops by inhibiting the production of very long chain fatty acids in weeds.
Pyroxasulfone and its generic process for preparation was disclosed in US 7238689 B2.
US 7256298 B2 disclosed the process for preparation of Pyroxasulfone by oxidizing 3-[(5-difluoromethoxy)-1-methyl-3-(trifluoromethyl)-pyrazol-4-yl- methylthio]-4,5-dihydro-5,5-dimethyl-1,2-oxazole with m-chloroperbenzoic acid in chloroform to provide Pyroxasulfone. However, m-chloroperbenzoic acid is an expensive reagent and has handling issues. Thus, the said process is not suitable for an industrial scale.
US 8921572 B2 disclosed the process for preparation of Pyroxasulfone by oxidizing 3-[(5-difluoromethoxy)-1-methyl-3-(trifluoromethyl)-pyrazol-4-yl- methylthio]-4,5-dihydro-5,5-dimethyl-1,2-oxazole with hydrogen peroxide in presence of sodium tungstate dihydrate in acetic acid at room temperature for 16 hours to provide Pyroxasulfone. However, in the said process oxidation was incomplete, and yield was below 40%. Hence the process is not suitable for an industrial scale.
WO2020240392 A1 disclosed the process for preparation of Pyroxasulfone by oxidizing 3-[(5-difluoromethoxy)-1-methyl-3-(trifluoromethyl)-pyrazol-4-yl- methylthio]-4,5-dihydro-5,5-dimethyl-1,2-oxazole with aqueous hydrogen peroxide in presence of sodium tungstate at 100℃ to provide Pyroxasulfone.
WO2021002484 A2 disclosed the process for preparation of Pyroxasulfone by oxidizing 3-[(5-difluoromethoxy)-1-methyl-3-(trifluoromethyl)-pyrazol-4-yl- methylthio]-4,5-dihydro-5,5-dimethyl-1,2-oxazole with hydrogen peroxide in the presence of a metal catalyst in an organic solvent and an aqueous solvent to provide Pyroxasulfone.
Thus, there remains a need to develop an improved process for the preparation of Pyroxasulfone, which is simple, cost-effective and industrially viable process with superior yields and high quality.
The present inventors have developed an improved process for the preparation of Pyroxasulfone which does not involve the usage of any toxic and/or costly solvents or reagents i.e., metal catalysts.
Accordingly, the present invention provides an improved process for the preparation of Pyroxasulfone, which is involves the simple operating procedure, efficient, cost effective, environmentally friendly, commercially viable for large scale production with superior yield and high quality.
Summary of the Invention
The first embodiment of the present invention provides a process for the preparation of Pyroxasulfone of formula-1.
The second embodiment of the present invention provides a process for the preparation of Pyroxasulfone of formula-1.
The third embodiment of the present invention provides a process for the preparation of Pyroxasulfone of formula-1.
The fourth embodiment of the present invention provides a process for the preparation of Pyroxasulfone of formula-1.
Detailed Description of the Invention
For the purpose of promoting an understanding of the principles of the disclosure, reference will now be made to the embodiment illustrated in the figures and specific language will be used to describe them. It will nevertheless be understood that no limitation of the scope of the disclosure is thereby intended. Such alterations and further modifications in the illustrated system, and such further applications of the principles of the disclosure as would normally occur to those skilled in the art are to be construed as being within the scope of the present disclosure.
Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art to which this disclosure belongs. The system, methods, and examples provided herein are only illustrative and not intended to be limiting.
In the following specification and the claims, reference will be made to several terms, which shall be defined to have the following meanings. The singular forms “a”, “an”, and “the” include plural references unless the context clearly dictates otherwise.
The term "solvent" used in the present invention refers but not limited to "non-polar solvents like “hydrocarbon solvents" selected from n-hexane, n-heptane, cyclohexane, petroleum ether, benzene, toluene, xylene or mixtures thereof; "ether solvents" selected from dimethyl ether, diisopropyl ether, diethyl ether, methyl tert-butyl ether, 1,2-dimethoxy ethane, tetrahydrofuran, 1,4-dioxane or mixtures thereof; "ester solvents" selected from methyl acetate, ethyl acetate, isopropyl acetate, n-butyl acetate, isobutyl acetate or mixtures thereof; "polar-aprotic solvents selected from dimethylacetamide, dimethylformamide, dimethyl sulfoxide, N-methylpyrrolidone or mixtures thereof; "chloro solvents" selected from dichloromethane, dichloroethane, chloroform, carbon tetrachloride or mixtures thereof; "ketone solvents" selected from acetone, methyl ethyl ketone, methyl isobutyl ketone and thereof; "nitrile solvents" selected from acetonitrile, propionitrile, isobutyronitrile or mixtures thereof; "alcoholic solvents" selected from methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, t-butanol or mixtures thereof; "polar solvents" selected from water or mixtures thereof.
The term "acid" used in the present invention selected from but not limited to inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, or phosphoric acid; and organic acids such as formic acid, acetic acid, propionic acid, methane sulfonic acid, para toluene sulfonic acid, ethane-1,2-disulfonic acid, camphor sulfonic acid, ethane sulfonic acid, naphthalene-2-sulfonic acid, benzene sulfonic acid, and thereof. The term “agrochemical acceptable salts” or “salts” described in hereinbefore are obtained by reacting compound with acid selected from the above description.
The term "base" used in the present invention selected from but not limited to inorganic bases selected from "alkali metal carbonates" such as sodium carbonate, potassium carbonate, lithium carbonate and the like; "alkali metal bicarbonates" such as sodium bicarbonate, potassium bicarbonate and the like; "alkali metal hydroxides" such as sodium hydroxide, potassium hydroxide, lithium hydroxide and the like; alkali metal hydrides such as sodium hydride, potassium hydride, lithium hydride and the like; alkali metal amides such as sodium amide, potassium amide, lithium amide and the like; and organic bases like dimethylamine, diethylamine, diisopropyl amine, diisopropylethylamine, diisobutylamine, trimethylamine, triethylamine, tertiary butyl amine, benzyl amine, pyridine, 4-dimethylaminopyridine (DMAP), N-methyl morpholine (NMM), 2,6-lutidine, lithium diisopropylamide; "alkali metal alkoxides" such as sodium methoxide, sodium ethoxide, potassium methoxide, potassium ethoxide, sodium tert.butoxide, potassium tert.butoxide, lithium tert.butoxide mixtures thereof.
The term "room temperature" as used in the present invention herein refers to the temperature in the range from about 25-35°C.
The first embodiment of the present invention provides a process for the preparation of Pyroxasulfone of formula-1, comprising: reacting compound of formula-2 with oxidizing compound to provide Pyroxasulfone of formula-1

In the first aspect of the first embodiment, wherein oxidizing compound is hydrogen peroxide and promoter.
Wherein promoter is selected from maleic acid, succinic acid, boric acid and their salts or anhydrides or mixtures thereof.
In the second aspect of the first embodiment, the mixture of hydrogen peroxide with promoter provides highly reactive and potential per acid compound which will effectively and completely oxidize compound of formula-2.
In the third aspect of first embodiment, the above said reaction is carried out in a solvent selected from hydrocarbon solvents, ether solvents, ester solvents, chloro solvents, ketone solvents, nitrile solvents, alcoholic solvents, polar solvents or mixtures thereof; preferably ester solvents or hydrocarbon solvents; more preferably ethyl acetate or toluene.
In the fourth aspect of the first embodiment, the above said reaction is carried out at the temperature of ranges from about from 20-80°C and reaction time is ranges from 2-8 hours.
The second embodiment of the present invention provides a process for the preparation of Pyroxasulfone of formula-1, comprising: reacting compound of formula-2 with hydrogen peroxide in presence of maleic anhydride to provide Pyroxasulfone of formula-1

In the first aspect of second embodiment, the above said reaction is carried out in a solvent selected from hydrocarbon solvents, ether solvents, ester solvents, chloro solvents, ketone solvents, nitrile solvents, polar solvents or mixtures thereof; preferably ester solvents or hydrocarbon solvents; more preferably ethyl acetate or toluene.
The third embodiment of the present invention provides a process for the preparation of Pyroxasulfone of formula-1, comprising: reacting compound of formula-2 with hydrogen peroxide in presence of succinic anhydride to provide Pyroxasulfone of formula-1

In the first aspect of third embodiment, the above said reaction is carried out in a solvent selected from hydrocarbon solvents, ether solvents, ester solvents, chloro solvents, ketone solvents, nitrile solvents, polar solvents or mixtures thereof; preferably ester solvents or hydrocarbon solvents; more preferably ethyl acetate or toluene.
The fourth embodiment of the present invention provides a process for the preparation of Pyroxasulfone of formula-1, comprising: reacting compound of formula-2 with hydrogen peroxide in presence of boric anhydride to provide Pyroxasulfone of formula-1

In the first aspect of fourth embodiment, the above said reaction is carried out in a solvent selected from hydrocarbon solvents, ether solvents, ester solvents, chloro solvents, ketone solvents, nitrile solvents, polar solvents or mixtures thereof; preferably ester solvents or hydrocarbon solvents; more preferably ethyl acetate or toluene.
The inventors of the present invention have also carried out the above reaction in the absence of said promoter. However, the reaction was slow and incomplete. Apart from this, the reaction is also carried out in the presence of acetic acid or other acids or their anhydrides. But these reactions are also incomplete, and yields are below 85%.
Starting materials utilized in the present invention are commercially available in the market (or) they can be prepared according to any of the processes known in the prior art.
The present invention described in embodiments and examples are merely to help understand the present invention. These examples are for illustrative purposes only, no way limit the scope of the present invention.
Process Advantages of the Present Invention:
• The process of the present invention is simple, safe, economical and involves the usage of readily available reagents and solvents.
• The process of present invention avoids the usage costly metal tungstates catalysts. Instead, replace the metal tungstates with simple and effective reaction promoter which will provide more potential per acid for the complete oxidation of formula-2.
• In the process of present invention, the oxidation of formula-2 was complete and provides superior yields and higher purities compared to prior arts with high reproducibility. This makes the process suitable on commercial scale and cost-effective.
• Solvents used in the present invention are 85-90% recovered and reused in the process.
Examples:
Example-1: Process for Preparation of Pyroxasulfone of formula-1
Maleic anhydride (27.2 g) and of 30% hydrogen peroxide (49.5 g) was added to the mixture of 3-[(5-difluoromethoxy)-1-methyl-3-(trifluoromethyl)-pyrazol-4-yl-methylthio]-4,5-dihydro-5,5-dimethyl-1,2-oxazole of formula-2 (50 g) and ethyl acetate (150 ml) at room temperature. Heated the reaction mixture to 60-65°C and stirred at same temperature for six hours. Cooled the reaction mixture to room temperature, quench the reaction mixture with 20% aq. sodium thiosulfate. Distilled out solvent from the reaction mixture. Water was added to the above obtained residue and stirred at 55-60°C. Filtered the solid and dried to get the title compound.
Example-2: Purification of Pyroxasulfone of formula-1
Methanol (50 ml) was added to above obtained compound (52 g) at room temperature and stirred for one hour. Cooled the mixture to 0 to -5°C and stirred for one hour at same temperature. Filtered the solid and dried to get the pure compound.
Yield: 48.8 g (90%); HPLC purity: 99.54%; M.R: 129-130°C.
 
Example-3: Process for Preparation of Pyroxasulfone of formula-1
Boric anhydride (14.08 g) and of 30% hydrogen peroxide (22.5 g) was added to the mixture of 3-[(5-difluoromethoxy)-1-methyl-3-(trifluoromethyl)-pyrazol-4-yl-methylthio]-4,5-dihydro-5,5-dimethyl-1,2-oxazole of formula-2 (25 g) and ethyl acetate (75 ml) at room temperature. Heated the reaction mixture to 60-65°C and stirred at same temperature for six hours. Cooled the reaction mixture to room temperature, quench the reaction mixture with 20% aq. sodium thiosulfate. pH was adjusted to 7-8 by using 48% sodium hydroxide. Ethyl acetate and water were added to the mixture at room temperature. Heated the reaction mixture to 55-60°C and stirred at same temperature for two hours. Kept the reaction mixture for settling. Layer separated. Distilled out the solvent completely from organic layer. Methanol (25 ml) was added to the above obtained crude compound at room temperature and stirred for one hour. Filtered the solid and dried to get the pure compound.
Yield: 20.3 g (77.3%); HPLC purity: 99.64%.
Example-4: Process for Preparation of Pyroxasulfone of formula-1
Succinic anhydride (8.01 g) and of 30% hydrogen peroxide (9 g) was added to the mixture of 3-[(5-difluoromethoxy)-1-methyl-3-(trifluoromethyl)-pyrazol-4-yl-methylthio]-4,5-dihydro-5,5-dimethyl-1,2-oxazole of formula-2 (10 g) and ethyl acetate (30 ml) at room temperature. Heated the reaction mixture to 60-65°C and stirred at same temperature for eight hours. Cooled the reaction mixture to room temperature, quench the reaction mixture with 20% aq. sodium thiosulfate. pH was adjusted to 7-8 by using 48% sodium hydroxide. Ethyl acetate and water were added to the mixture at room temperature. Heated the reaction mixture to 55-60°C and stirred at same temperature for 30 minutes. Kept the reaction mixture for settling. Layer separated. Distilled out the solvent completely from organic layer. Methanol (15 ml) was added to the above obtained crude compound (10.5 g) at room temperature and stirred for one hour. Filtered the solid and dried to get the pure compound.
Yield: 7.5 g (71.2%); HPLC purity: 96.87%.
Example-5: Process for Preparation of Pyroxasulfone of formula-1
Maleic anhydride (27.2 g) and of 30% hydrogen peroxide (49.5 g) was added to the mixture of 3-[(5-difluoromethoxy)-1-methyl-3-(trifluoromethyl)-pyrazol-4-yl-methylthio]-4,5-dihydro-5,5-dimethyl-1,2-oxazole of formula-2 (50 g) and toluene (150 ml) at room temperature. Heated the reaction mixture to 60-65°C and stirred at same temperature for six hours. Cooled the reaction mixture to room temperature, quench the reaction mixture with 20% aq. sodium thiosulfate. Layers separated. Distilled out the solvent completely from the organic layer. Methanol (50 ml) was added to the above obtained crude compound (51 g) at room temperature and stirred for one hour. Filtered the solid and dried to get the pure compound.
Yield: 48.8 g (90%); HPLC purity: 99.54%
Example-6-9: Process for Preparation of Pyroxasulfone of formula-1
Example 6-9 were shown in the table below with the variation of different solvents. Other reaction conditions and procedure were same as examples 1&2. The yields of Pyroxasulfone after purification were given in the below table.
Solvent Reaction Temperature Reaction Time Yield (%)
Example 6 MTBE 60-65°C 6-8 hours 85
Example 7 MIBK 60-65°C 6-8 hours 83
Example 8 EDC 60-65°C 6-8 hours 82
Example 9 Acetonitrile 60-65°C 6-8 hours 86

The process provided by the present invention provides higher yields and purity of the pyroxasulfone than the conventional methods.
While specific language has been used to describe the invention, any limitations arising on account of the same are not intended. As would be apparent to a person skilled in the art, various working modifications may be made to the methods in order to implement the inventive concept as taught herein.
Those skilled in the art will appreciate that one or more of the described elements may well be combined into a single functional element. Alternatively, certain elements may be split into multiple functional elements. Elements from one embodiment may be added to another embodiment. For example, order of processes described herein may be changed and are not limited to the manner described herein. Moreover, the actions of any flow diagram need not be implemented in the order shown; nor do all the acts need to be necessarily performed. Also, those acts that are not dependent on other acts may be performed in parallel with the other acts. The scope of embodiments is by no means limited by these specific examples. , C , Claims:We Claim:
1. A process for the preparation of Pyroxasulfone of formula-1, comprising: the reacting compound of formula-2 with the oxidizing compound to provide the Pyroxasulfone of formula-1
wherein the oxidizing compound is hydrogen peroxide and promoter.
2. The process as claimed in claim 1, wherein the promoter is selected from maleic acid, succinic acid, boric acid and their salts or anhydrides or mixtures thereof.
3. The process as claimed in claim 1, wherein the above said reaction is carried out in a solvent selected from hydrocarbon solvents, ether solvents, ester solvents, chloro solvents, ketone solvents, nitrile solvents, polar solvents or mixtures thereof.
4. A process for the preparation of the Pyroxasulfone of formula-1, comprising: the reacting compound of formula-2 with the hydrogen peroxide in presence of maleic anhydride to provide Pyroxasulfone of formula-1.
5. The process as claimed in claim 4, wherein the above said reaction is carried out in ester solvents or hydrocarbon solvents.
6. The process as claimed in claim 5, wherein the ester solvent is ethyl acetate, and the hydrocarbon solvent is toluene.
7. A process for the preparation of Pyroxasulfone of formula-1, comprising: reacting compound of formula-2 with hydrogen peroxide in presence of boric anhydride to provide Pyroxasulfone of formula-1.
8. The process as claimed in claim 7, wherein the above said reaction is carried out in ester solvents or hydrocarbon solvents.
9. The process as claimed in claim 8, wherein the ester solvent is ethyl acetate, and the hydrocarbon solvent is toluene.
10. A process for the preparation of Pyroxasulfone of formula-1, comprising: reacting compound of formula-2 with hydrogen peroxide in presence of succinic anhydride in ethyl acetate to provide Pyroxasulfone of formula-1.