A process for preparation of pyroxasulfone

Abstract

The present invention relates to a process for preparation of Pyroxasulfone substantially free of undesired impurity, said process comprising oxidizing compound of formula (II) at a temperature ranging from about 25°C to about 34°C.

Description

[0001] A PROCESS FOR PREPARATION OF PYROXASULFONE

[0002] FIELD OF THE INVENTION

[0003] The present invention relates to a process for preparation of Pyroxasulfone substantially free of undesired impurity.

[0004] BACKGROUND OF THE INVENTION

[0005] Pyroxasulfone is a herbicide belonging to the group of isoxazoline herbicides. Pyroxasulfone is chemically known as 3-[5-(difluoromethoxy)-l-methyl-3- (trifluoromethyl)pyrazol-4-ylmethylsulfonyl]-4,5-dihydro-5,5-dimethyl-l,2- oxazole and is represented by compound of formula (I).

[0006] Formula (I)

[0007] Pyroxasulfone is a pre-emergence herbicide that inhibits the biosynthesis of very long chain fatty acids. It can be used to effectively control grass and broad-leaved weeds in com, soybean and wheat fields.

[0008] Pyroxasulfone was first disclosed in US patent No. 7, 238, 689. Currently, few processes for preparation of Pyroxasulfone are known. One such method is described in US20120264947 which involves oxidation of compound of formula (II) in presence of sodium tungstate dihydrate, hydrogen peroxide and acetic acid at room temperature for 16 hours. The reaction can be represented as follows

[0009]

[0010] Formula (II) Formula (I)

[0011] Unfortunately, the yield of Pyroxasulfone obtained using said process is about 30% to about 35% which is very low and hence, the process is not acceptable at industrial scale. Another drawback of said process is that it leads to incomplete oxidation and generation of undesired monoxide compound of formula (III).

[0012] This compound of formula (III) remains as a by-product in the final product i.e., Pyroxasulfone, and is very difficult to remove due to structural similarities.

[0013] However, if the compound of formula (III) is not separated, it may lead to quality deterioration of Pyroxasulfone formulation and the possibility of phytotoxicity to crops. Also, if such impurity is not removed / controlled, it would raise regulatory concerns. Hence, it is important to develop a production method in which oxidation reaction proceeds sufficiently and the compound of formula (III) does not substantially remain in the product. The present invention provides an improved process for the preparation of Pyroxasulfone which is substantially free of monoxide compound of formula (III), and wherein the yield and purity of final product is considerably increased.

[0014] OBJECT OF THE INVENTION

[0015] It is an object of the present invention to provide a process for preparation of Pyroxasulfone of formula (I) substantially free of monoxide compound of formula (III).

[0016] Another object of the present invention is to provide a process for preparation of Pyroxasulfone of formula (I) having high yield.

[0017] Yet another object of the present invention is to provide a simple, cost effective and industrially viable process for preparation of Pyroxasulfone of formula (I).

[0018] SUMMARY OF THE INVENTION

[0019] According to an aspect of the present invention, there is provided a process for preparation of Pyroxasulfone of formula (I) substantially free of monoxide compound of formula (III)

[0020] Formula (I) Formula (III) said process comprising: oxidizing compound of formula (II)

[0021] in presence of an oxidizing agent, a metal catalyst and an organic acid at a temperature ranging from about 25°C to about 34°C; wherein a predetermined amount of the metal catalyst used.

[0022] According to an aspect of the present invention, there is provided a process for preparation of Pyroxasulfone of formula (I) substantially free of monoxide compound of formula (III)

[0023] Formula (I) Formula (III) said process comprising: oxidizing a compound of formula (II) in presence of an oxidizing agent, a metal catalyst and an organic acid at a temperature ranging from about 25 °C to about 34°C; wherein the amount of the metal catalyst used is more than about 0.06 moles with respect to the compound of formula (II).

[0024]

[0025] According to another aspect of the present invention, there is provided a process for preparation of Pyroxasulfone of formula (I) substantially free of monoxide compound of formula (III)

[0026] Formula (I) Formula (III) said process comprising: oxidizing compound of formula (II) in presence of an oxidizing agent, a metal catalyst and an organic acid at a temperature ranging from about 25 °C to about 34°C; wherein the reaction is carried out in presence of an additional solvent and amount of the metal catalyst used is more than about 0.06 moles with respect to compound of formula (II).

[0027]

[0028] DETAILED DESCRIPTION OF THE INVENTION

[0029] Those skilled in art will be aware that the invention described herein is subject to variations and modifications other than those specifically described. It is to be understood that the invention described herein includes all such variations and modifications. The invention also includes all such steps, features, compositions and methods referred to or indicated in this specification, individually or collectively, and any and all combinations of any two or more said steps or features.

[0030] For convenience, before further description of the present invention, certain terms employed in the specification, examples are described here. These definitions should be read in light of the remainder of the disclosure and understood by a person of skill in art. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by a person of ordinary skill in art. The terms used throughout this specification are defined as follows, unless otherwise limited in specific instances.

[0031] The terms used herein are defined as follows.

[0032] As used in the specification and the claims, the singular forms "a", "an", and "the" include plural referents unless the context clearly dictates otherwise.

[0033] The term "about" shall be interpreted to mean "approximately" or "reasonably close to" and any statistically insignificant variations therefrom. For example, “about” can mean within one or more standard deviations, or within ± 10 or ± 5 of the stated value.

[0034] As used herein, the terms “comprising” “including,” “having,” “containing,” “involving,” and the like are to be understood to be open-ended, i.e., to mean including but not limited to.

[0035] The terms “preferred” and “preferably” refer to embodiments of the invention that may afford certain benefits, under certain circumstances. In an embodiment, the aspects and embodiments described herein shall also be interpreted to replace the clause “comprising” with either “consisting of’ or with “consisting essentially of’ or with “consisting substantially of’.

[0036] The term “room temperature” unless stated otherwise, essentially means temperature in range from about 20°C to about 34°C.

[0037] The term "purity" means purity as determined by "High Pressure Liquid Chromatography" (HPLC).

[0038] The term “Pyroxasulfone” as used herein, includes Pyroxasulfone free base or its salt and is used interchangeably throughout the disclosure.

[0039] The term “monoxide impurity” as used herein, includes “monoxide compound of formula (III)” and is used interchangeably throughout the disclosure.

[0040] As used herein, the term “substantially free of monoxide compound of formula (III)” refers to Pyroxasulfone containing less than 1% of monoxide compound of formula (III) or containing less than 0.8% w / w of monoxide compound of formula(III). Preferably, less than 0.5% w / w of monoxide compound of formula (III). More preferably less than 0.2% w / w of monoxide compound of formula (III).

[0041] The present disclosure is not to be limited in scope by the specific embodiments described herein, which are intended for the purposes of exemplification only. According to an aspect of the present invention, there is provided a process for preparation of Pyroxasulfone of formula (I) substantially free of monoxide compound of formula (III) Formula (I) Formula (III) said process comprising: oxidizing compound of formula (II)

[0042] Formula (II) in the presence of an oxidizing agent, a metal catalyst and organic acid at a temperature ranging from about 25°C to about 34°C; wherein a predetermined amount of metal catalyst is used.

[0043] According to an aspect of the present invention, there is provided a process for preparation of Pyroxasulfone of formula (I) substantially free of monoxide compound of formula (III)

[0044]

[0045] Formula (I) Formula (III) said process comprising: oxidizing compound of formula (II) in the presence of an oxidizing agent, a metal catalyst and organic acid at a temperature ranging from about 25°C to about 34°C; wherein the amount of metal catalyst used is more than about 0.06 moles with respect to compound of formula (II).

[0046] Formula (II) In an embodiment, the compound of formula (II) is 3-({ [5-(difluoromethoxy)-l- methyl-3-(trifluoromethyl)-lH-pyrazol-4-yl]methyl}sulfanyl)-5,5-dimethyl-4,5- dihydro- 1 ,2-oxazole.

[0047] In an embodiment, the compound of formula (II) is prepared by methods known in art. In another embodiment, the compound of formula (II) is prepared by a process comprising: i) reacting 3-bromo-4,5-dihydro-5,5-dimethylisoxazole with thiourea at 50-75°C in presence of sulfuric acid and an ester solvent to obtain [5,5- dimethyl(4,5-dihydroisoxazol-3-yl)]thiocarboxamidine hydrobromide; ii) reacting [5 ,5-dimethyl(4,5-dihydroisoxazol-3 -yl)] thiocarboxamidine hydrobromide with sodium salt of 5 -hydroxy- l-methyl-3-

[0048] (trifluoromethyl)- lH-Pyrazole-4-methanol to obtain 4-[[(4,5-dihydro- 5,5-dimethyl-3-isoxazolyl)thio]methyl]-l-methyl-3-(trifluoromethyl)- l / / -Pyrazol-5-ol at a temperature ranging from about -5 to about 10°C; and iii) fluoromethylating 4-[[(4,5-dihydro-5,5-dimethyl-3- isoxazolyl)thio]methyl]-l-methyl-3-(trifluoromethyl)- 1 / 7-Pyrazol-5-ol to obtain the compound of formula (II).

[0049] In another embodiment, 3-bromo-4,5-dihydro-5,5-dimethylisoxazole used in step i) is prepared by reacting hydroxycarbonimidic dibromide with isobutylene gas in presence of base such as sodium carbonate in an ester solvent.

[0050] In another embodiment, the ester solvent / s used in step i) is selected from methyl acetate, ethyl acetate, butyl acetate, and propyl acetate; preferably butyl acetate is used.

[0051] In another embodiment, the 4-[[(4,5-dihydro-5,5-dimethyl-3- isoxazolyl)thio]methyl]-l-methyl-3-(trifluoromethyl)- l / 7-Pyrazol-5-ol obtained in step ii) is precipitated by addition of mineral acid such as hydrochloric acid, sulfuric acid and the likes; preferably sulfuric acid is used.

[0052] In another embodiment, the fluoromethylating step is carried out by reacting 4- [ [(4, 5-dihy dro-5 ,5-dimethyl-3 -isoxazolyl)thio] methyl] - 1 -methyl-3 -

[0053] (trifluoromethyl)- lH-Pyrazol-5-ol with freon gas in presence of a base and a solvent at temperature ranging from 0°C to 25°C.

[0054] In an embodiment, the oxidizing agent is selected from an organic peroxide or an inorganic peroxide. In an embodiment, the oxidizing agent used is selected from, but not limited to, an organic peroxide such as m-chloroperbenzoic acid, performic acid, peracetic acid and the like; or an inorganic peroxide such as hydrogen peroxide, potassium permanganate, sodium periodate, potassium peroxymonosulfate and the like.

[0055] In an embodiment, the oxidizing agent used is hydrogen peroxide.

[0056] In an embodiment, the amount of oxidizing agent used is in the range from about 2.5 to about 6 moles with respect to compound of formula (II).

[0057] In another embodiment, the compound of formula (II) is oxidized in the presence of a metal catalyst.

[0058] In an embodiment, the metal catalyst used is selected from, but not limited to, tungsten catalyst, molybdenum catalyst, titanium catalyst, zirconium catalyst or mixture thereof

[0059] Preferably, the catalyst used is tungsten catalyst, tungstic acid, tungstic acid salt, metallic tungsten, tungsten oxide, tungsten carbide or mixtures thereof.

[0060] More preferably, the tungsten catalyst used is sodium tungstate or its dihydrate.

[0061] In an embodiment, the amount of the metal catalyst used is in the range from about 0.06 moles to about 0.35 moles with respect to compound of formula (II).

[0062] In a preferred embodiment, the amount of the metal catalyst used is in the range from about 0.07 moles to about 0.25 moles with respect to compound of formula (II).

[0063] In an embodiment, the metal from the spent metal catalyst can be recovered by known methods.

[0064] In an embodiment, the compound of formula (II) is oxidized in a single solvent i.e., organic acid.

[0065] The organic acid used is selected from, but not limited to, formic acid, acetic acid and the likes. In an embodiment, said organic acid is acetic acid.

[0066] In an embodiment, the amount of said organic acid used is in the range from about 1 to about 150 moles with respect to compound of formula (II).

[0067] In an embodiment, the amount of said organic acid used is in the range from about 50 to about 150 moles with respect to compound of formula (II).

[0068] In an embodiment, the amount of said organic acid used is in the range from about 80 to about 110 moles with respect to compound of formula (II).

[0069] In an embodiment, the amount of organic acid used is recovered and reused.

[0070] In an embodiment, more than about 50% of organic acid used is recovered, preferably more than about 80% of organic acid used is recovered.

[0071] In an embodiment, about 70% to 90% of the organic acid used is recovered.

[0072] In an embodiment, the organic acid is recovered after isolation of Pyroxasulfone by extracting the mother liquor with a water immiscible organic solvent, wherein said water immiscible organic solvent is selected from, but not limited to, chlorinated solvents like dichloromethane (methylene chloride) and dichloroethane, esters like ethyl acetate, and hydrocarbons such as toluene.

[0073] In an embodiment, the process further comprise additional solvent selected from, but not limited to, water, alcohols, aromatic hydrocarbons, halogenated aliphatic hydrocarbons, esters, ethers, nitriles or mixtures thereof.

[0074] In an embodiment, the process may further comprise a catalyst such as inorganic acid. The inorganic acid may be selected from, but not limited to, hydrochloric acid, nitric acid, sulfuric acid, phosphoric acid and the likes.

[0075] In an embodiment, the oxidation reaction is carried out at temperature ranging from about 28°C to about 33°C.

[0076] In an embodiment, the oxidation reaction is carried out within 20 hours, preferably within 18 hours. In an embodiment, there is provided a process for preparation of Pyroxasulfone of formula (I) substantially free of monoxide compound of formula (III) said process comprising: oxidizing compound of formula (II) in the presence of an oxidizing agent, a metal catalyst and acetic acid at a temperature ranging from about 25°C to about 34°C; wherein the amount of metal catalyst used is more than about 0.06 moles with respect to compound of formula (II).

[0077] In an embodiment, there is provided a process for preparation of Pyroxasulfone of formula (I) substantially free of monoxide compound of formula (III) said process comprising: oxidizing compound of formula (II) in the presence of an oxidizing agent, a metal catalyst and acetic acid at a temperature ranging from about 25°C to about 34°C; wherein the amount of metal catalyst used is in range from about 0.06 moles to about 0.35 moles with respect to compound of formula (II); and wherein the acetic acid used is recovered and reused.

[0078] According to another aspect of the present invention, there is provided a process for preparation of Pyroxasulfone of formula (I) substantially free of monoxide compound of formula (III) said process comprising: oxidizing compound of formula (II) in the presence of an oxidizing agent, a metal catalyst and organic acid at a temperature ranging from about 25°C to about 34°C; wherein the reaction is carried out in presence of an additional solvent and the amount of metal catalyst used is above 0.06 moles with respect to compound of formula (II).

[0079] In accordance with the above aspect, oxidation of compound of formula (II) is carried out as per the embodiments of the invention as described hereinabove.

[0080] In an embodiment, the amount of organic acid used is less than 20 moles with respect to compound of formula (II), preferably less than 18 moles. In an embodiment, the amount of organic acid used is in range from about 0.1 moles to about 18 moles.

[0081] In an embodiment, the additional solvent is selected from, but not limited to, water, alcohols, aromatic hydrocarbons, halogenated aliphatic hydrocarbons, esters, ethers, nitriles or mixtures thereof.

[0082] In an embodiment, the amount of additional solvent used is in the range of about 1% to about 10% of total solvent used.

[0083] In an embodiment the present invention provides Pyroxasulfone of formula (I) having monoxide compound of formula (III) content less than or equal to 0.5% w / w.

[0084] In an embodiment the present invention provides Pyroxasulfone of formula (I) having monoxide compound of formula (III) content less than or equal to 0.2% w / w.

[0085] In a preferred embodiment the present invention provides Pyroxasulfone of formula (I) wherein monoxide compound of formula (III) is not detectable.

[0086] In an embodiment the present invention provides Pyroxasulfone of formula (I) having purity of more than 95%, preferably more than 98%.

[0087] EXAMPLES

[0088] The following examples are presented to provide what is believed to be the most useful and readily understood description of procedures and conceptual aspects of this invention. The examples provided below are merely illustrative of the invention and are not intended to limit the same to disclosed embodiments. Variations and changes obvious to one skilled in art are intended to be within the scope and nature of the invention.

[0089] Example 1: Preparation of Pyroxasulfone

[0090] To 17.01g of 3-({ [5-(difluoromethoxy)-l-methyl-3-(trifluoromethyl)-lH-pyrazol- 4-yl]methyl}sulfanyl)-5,5-dimethyl-4,5-dihydro-l,2-oxazole was added 278.72g of acetic acid, 3.12g of sodium tungstate dihydrate and 11.82g of 50% hydrogen peroxide. The mixture was stirred at 25-34°C for 10 to 12 hours. After completion of reaction, 73.45g of water was added to reaction mixture to precipitate product. The product was filtered out and the mother liquor was collected in a different vessel. The filtered product was washed with water and petroleum ether and dried to yield 17.50g of Pyroxasulfone (Yield: 94.4%; Purity: 99.73% A / A; Monoxide impurity: 0.03%).

[0091] The collected mother liquor was extracted using a water-immiscible organic solvent, and the layers were separated. The organic layer was then subjected to distillation to separate the water-immiscible organic solvent from acetic acid, resulting in the recovery of 236g of acetic acid (i.e., 80% to 85% of acetic acid used) with a purity of 98.5% and a moisture content of less than 1%.

[0092] Example 2: Preparation of Pyroxasulfone

[0093] To 14.32g of 3-({ [5-(difluoromethoxy)-l-methyl-3-(trifluoromethyl)-lH-pyrazol- 4-yl]methyl}sulfanyl)-5,5-dimethyl-4,5-dihydro-l,2-oxazole was added 234.6g of acetic acid, 1.15g of sodium tungstate dihydrate and 10.03g of 50% hydrogen peroxide. The mixture was stirred at 25-34°C for 16 to 18 hours. After completion of reaction, 61.88g of water was added to reaction mixture to precipitate product. The product was filtered out washed with water and petroleum ether and dried to yield 14.67g of Pyroxasulfone (Yield: 94%; Purity: 99.77% A / A; Monoxide impurity: 0.03%).

[0094] Example 3: Preparation of [5,5-dimethyl(4,5-dihydroisoxazol-3- yl)]thiocarboxamidine hydrobromide

[0095] To a solution of 100g of 3-Bromo-4,5-dihydro-5,5-dimethylisoxazole and 700g of n-butyl acetate was added 44g of thiourea and the suspension thus obtained was heated to 60-65°C. To this suspension was then added 11g of concentrated sulfuric acid and the reaction mixture stirred continuously for 10 hours. After completion of reaction, the mixture was cooled, and layers were separated. The aqueous layer comprising product i.e., [5,5-dimethyl(4,5-dihydroisoxazol-3- yl)]thiocarboxamidine hydrobromide was carried forward to next step. Example 4: Preparation of 4-[[(4,5-dihydro-5,5-dimethyl-3- isoxazolyl)thio]methyl]-l-methyl-3-(trifluoromethyl)- lH-Pyrazol-5-ol

[0096] Part A:

[0097] To 239g of 15% aqueous solution of sodium hydroxide, 70g of 5-Hydroxy-l- methyl-3-trifluoromethylpyrazole was added. Subsequently, 70.02g of 37% formalin solution was added, to obtain part A solution comprising sodium salt of 5- hydroxy- l-methyl-3-(trifluoromethyl)- lH-Pyrazole-4-methanol.

[0098] Part B:

[0099] In another reaction vessel, to 400g of 14% aqueous solution of sodium hydroxide was added 35g of acetonitrile and an aqueous layer comprising product i.e., [5,5- dimethyl(4,5-dihydroisoxazol-3-yl)]thiocarboxamidine hydrobromide was obtained in Example 3. The mixture was then cooled to 0-5 °C and part A solution was slowly added. After the reaction was completed, the mixture was extracted with dichloromethane. To the extracted organic layer, 30% concentrated sulfuric acid was added. The precipitated solid was collected by filtration, washed with water, and dried to obtain 115g of 4-[[(4,5-dihydro-5,5-dimethyl-3- isoxazolyl)thio]methyl]-l-methyl-3-(trifluoromethyl)- l / Z-Pyrazol-5-ol with a purity of 93% to 95%.

[0100] Example 5: Preparation of 3-({[5-(difluoromethoxy)-l-methyl-3- (trifluoromethyl)-lH-pyrazol-4-yl]methyl}sulfanyl)-5,5-dimethyl-4,5- dihydro- 1 ,2-oxazole

[0101] To a mixture of 452g of acetonitrile and 115g of 4-[[(4,5-dihydro-5,5-dimethyl-3- isoxazolyl)thio]methyl]-l-methyl-3-(trifluoromethyl)-l / Z-Pyrazol-5-ol was added 36.13g of sodium hydroxide pellets and the mixture was stirred. The mixture was then cooled to 5-10°C and 32g of freon gas was purged in the mixture. After completion of reaction, the solvent was evaporated, and 826g of methylene dichloride was added to the mixture followed by addition of 402g of water and 56g of 30% hydrochloric acid. The organic and aqueous layers were separated. The organic layer was washed with brine and distilled to yield 95% of 3-({[5- (difluoromethoxy)-l-methyl-3-(trifluoromethyl)-lH-pyrazol-4- yljmethyl} sulfanyl)-5, 5-dimethyl-4, 5-dihydro-l,2-oxazole.

Claims

CLAIMS:

1. A process for preparation of pyroxasulfone of formula (I) substantially free of monoxide compound of formula (III),said process comprising: oxidizing a compound of formula (II)Formula (II) in the presence of an oxidizing agent, a metal catalyst and an organic acid at a temperature ranging from about 25°C to about 34°C.

2. The process as claimed in claim 1, wherein the oxidizing agent used is selected from organic peroxide such as m-chloroperbenzoic acid, performic acid, and peracetic acid; or an inorganic peroxide such as hydrogen peroxide, potassium permanganate, sodium periodate, and potassium peroxymonosulfate.

3. The process as claimed in claim 1, wherein amount of the oxidizing agent used is in a range from about 2.5 moles to about 6 moles with respect to the compound of formula (II).

4. The process as claimed in claim 1, wherein the metal catalyst used is selected from the group comprising tungsten catalyst, molybdenum catalyst, titanium catalyst, zirconium catalyst, or mixture thereof.

5. The process as claimed in claim 1, wherein amount of the metal catalyst used is in a range from about 0.06 moles to about 0.35 moles with respect to the compound of formula (II).

6. The process as claimed in claim 1, wherein the organic acid is acetic acid.

7. The process as claimed in claim 1, wherein amount of said organic acid used is in a range from about 80 moles to about 110 moles with respect to the compound of formula (II).

8. The process as claimed in claim 1, wherein 70% to 90% of the organic acid used is recovered.

9. A process for preparation of pyroxasulfone of formula (I) substantially free of monoxide compound of formula (III), said process comprising: oxidizing a compound of formula (II) in the presence of an oxidizing agent, a metal catalyst and acetic acid at a temperature ranging from about 25°C to about 34°C; wherein amount of the metal catalyst used is in a range from about 0.06 moles to about 0.35 moles with respect to the compound of formula (II); and wherein the acetic acid used is recovered and reused.

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