How is Fluensulfone Made?

Abstract

The present invention relates to a method for producing 5-chloro-2-((3,4,4-trifluorobut-3-en-1-yl)thio)-1λ-difluoroisopropyl ester using an oxidizing agent and a metal oxide catalyst. 3 ,3λ 2 The present invention relates to a method for the oxidation of -thiazoles and their analogues to the corresponding sulfones.

Description

[Technical field]

[0001] The present invention relates to a method for the production of 5-chloro-2-((3,4,4-trifluorobut-3-en-1-yl)thio)-1λ-diaminobutyric acid using a metal oxide catalyst and an oxidizing agent. 3 ,3λ 2 -thiazoles and their analogues, the corresponding sulfones, 5-chloro-2-((3,4,4-trifluorobut-3-en-1-yl)sulfonyl)-1λ 3 ,3λ 2 -thiazole (fluensulfone) and its corresponding analogues. [Background technology]

[0002] Fluensulfone (5-chloro-2-((3,4,4-trifluorobut-3-en-1-yl)sulfonyl)-1λ 3 ,3λ 2 -thiazoles) are effective nematicides against many plant-parasitic nematodes in agricultural and horticultural crops. One method for their synthesis is to use the corresponding sulfide, 5-chloro-2-((3,4,4-trifluorobut-3-en-1-yl)thio)-1λ 3 ,3λ 2 - the oxidation of thiazoles. WO 2001 / 002378 describes the oxidation of sulfides with peroxygen reagents such as 3-chlorobenzoic acid or hydrogen peroxide in the presence of a carboxylic acid such as acetic acid.

[0003] Reaction with 3 equivalents of H2O2 in acetic acid at 60 °C was reported to give fluensulfone in 76% yield.

[0004] Improved yields have been reported by oxidation of sulfides with potassium peroxymonosulfate, the triple salt with 2KHSO5·KHSO4·K2SO4, or with Caroat as active oxidants (U.S. Pat. No. 8,901,311; WO 2004 / 005268).

[0005] Although it has been reported that the use of 2KHSO5·KHSO4·K2SO4 (U.S. Pat. No. 8,901,311) versus the use of H2O2 (WO 2001 / 002378) improves yields, significant amounts of environmentally harmful sulfates are introduced and formed during the reaction versus the formation of water with H2O2 alone.

[0006] A problem with the use of H2O2, as also described in U.S. Pat. No. 8,901,311, is that the oxidation of the intermediate sulfoxide becomes more difficult, resulting in a significant drop in yield. Further oxidation of the sulfoxide to the sulfone therefore occurs only gradually and slowly, requiring higher temperatures and longer reaction times. Even more problematic, once the sulfone is formed, it can react further via oxidative cleavage of the fluorinated double bond to give 3-((5-chloro-1λ 3 ,3λ 2 The reaction is speculated to be primarily the result of uncatalyzed nucleophilic attack of H2O2 on the double bond of the sulfone, which is highly electrophilic due to the presence of a fluorine substituent and an adjacent sulfone group. Thus, even in the absence of a catalyst, reaction of sulfone with H2O2 leads to the formation of 3-((5-chloro-1λ)-propanoic acid due to cleavage of the double bond. 3 ,3λ 2 The formation of 1,2-thiazol-2-yl)sulfonyl)propanoic acid and HF was observed. Such undesirable side reactions also occur with H2O2 in the presence of formic or acetic acid, where reactive oxygenated peracids are formed either in situ or in the presence of commonly used molybdate or tungstate catalysts. Summary of the Invention [Means for solving the problem]

[0007] The present invention relates to the synthesis of 5-chloro-2-((3,4,4-trifluorobut-3-en-1-yl)thio)-1λ oxidant using aqueous H2O2 as the oxidant / oxygen donor in an aqueous biphasic reaction medium. 3 ,3λ 2-thiazoles and their analogues, the corresponding sulfones, 5-chloro-2-((3,4,4-trifluorobut-3-en-1-yl)sulfonyl)-1λ 3 ,3λ 2 -thiazoles and their corresponding analogues.

[0008] A particular advantage of using an aqueous two-phase reaction medium is the ease of separating the aqueous phase containing the catalyst from the organic phase containing the desired product, thus allowing the catalyst to be very easily recovered and reused.

[0009] In one embodiment, the present invention provides a method for the preparation of a compound of formula (I): [ka] wherein R is a heterocycle selected from thiophene, thiazole, isothiazole, thiadiazole and thiatriazole, the heterocycle being optionally halogenated, and n is an integer from 1 to 6, comprising: [ka] wherein R and n are as defined herein above, with H2O2 in an acidic aqueous phase in the presence of a catalyst.

[0010] In another embodiment, the present invention provides 5-chloro-2-((3,4,4-trifluorobut-3-en-1-yl)thio)-1λ 3 ,3λ 2 -thiazole with H2O2 in an acidic aqueous phase in the presence of a catalyst, 3 ,3λ 2 - A process for the preparation of thiazoles is provided.

[0011] In one embodiment, the present invention provides a method for the preparation of a compound of formula (I): [ka] wherein R is a heterocycle selected from thiophene, thiazole, isothiazole, thiadiazole and thiatriazole, the heterocycle being optionally halogenated, and n is an integer from 1 to 6, comprising: [ka] wherein R and n are as defined hereinabove, with a peroxygen oxidant in an acidic aqueous phase in the presence of a catalyst.

[0012] In another embodiment, the present invention provides 5-chloro-2-((3,4,4-trifluorobut-3-en-1-yl)thio)-1λ 3 ,3λ 2 -thiazole with a peroxygen oxidant in an acidic aqueous phase in the presence of a catalyst, 3 ,3λ 2 - A process for the preparation of thiazoles is provided.

[0013] The subject matter which is regarded as the invention is particularly pointed out and distinctly claimed in the concluding portion of this specification, however the invention, both as to organization and method of operation, together with its objects, features, and advantages, may best be understood by reference to the following detailed description taken in conjunction with the accompanying drawings. [Brief description of the drawings]

[0014] [Figure 1]FIG. 1 shows a process of the present invention for the preparation of 5-chloro-2-((3,4,4-trifluorobut-3-en-1-yl)sulfonyl)-1λ3,3λ2-thiazole, which prevents the formation of the by-product 3-((5-chloro-1λ3,3λ2-thiazol-2-yl)sulfonyl)propanoic acid. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0015] It will be appreciated that for simplicity and clarity of illustration, elements shown in the figures have not necessarily been drawn to scale. For example, the dimensions of some elements may be exaggerated relative to other elements for clarity. Further, where considered appropriate, reference numerals may be repeated among the figures to indicate corresponding or analogous elements.

[0016] In the following detailed description, numerous specific details are set forth in order to provide a thorough understanding of the present invention. However, it will be understood by those skilled in the art that the present invention may be practiced without these specific details. In other instances, well-known methods, procedures, and components have not been described in detail so as not to obscure the present invention.

[0017] The present invention relates to a method for the production of 5-chloro-2-((3,4,4-trifluorobut-3-en-1-yl)thio)-1λ-diaminobutyric acid using a metal oxide catalyst and an oxidizing agent. 3 ,3λ 2 -thiazole and its analogues, the corresponding 5-chloro-2-((3,4,4-trifluorobut-3-en-1-yl)sulfonyl)-1λ 3 ,3λ 2 The present invention relates to a method for the oxidation of -thiazole (fluensulfone) and its corresponding analogues. In another embodiment, the oxidizing agent is a peroxygen oxidizing agent. In another embodiment, the oxidizing agent is H2O2.

[0018] In one embodiment, the method of the present invention utilizes an oxidizing agent. In another embodiment, the oxidizing agent is a water-soluble peroxygen oxidizing agent. Non-limiting examples of water-soluble peroxygen oxidizing agents include H2O2, magnesium monoperoxyphthalate, sodium perborate, sodium percarbonate, urea hydrogen peroxide (UHP), or any combination thereof. In another embodiment, the peroxygen oxidizing agent is H2O2. In another embodiment, the peroxygen oxidizing agent is magnesium monoperoxyphthalate. In another embodiment, the peroxygen oxidizing agent is sodium perborate. In another embodiment, the peroxygen oxidizing agent is sodium percarbonate. In another embodiment, the peroxygen oxidizing agent is urea hydrogen peroxide (UHP). In another embodiment, the peroxygen oxidizing agent forms hydrogen peroxide under acidic reaction conditions.

[0019] In one embodiment, the present invention provides a method for the preparation of a compound of formula (I): [ka] wherein R is a heterocycle selected from thiophene, thiazole, isothiazole, thiadiazole and thiatriazole, the heterocycle being optionally halogenated, and n is an integer from 1 to 6, comprising: [ka] wherein R and n are as defined herein above, with H2O2 in an acidic aqueous phase in the presence of a catalyst.

[0020] In one embodiment, the present invention provides a method for the preparation of a compound of formula (I): [ka] wherein R is a heterocycle selected from thiophene, thiazole, isothiazole, thiadiazole and thiatriazole, the heterocycle being optionally halogenated, and n is an integer from 1 to 6, comprising: [ka] wherein R and n are as defined hereinabove, with a peroxygen oxidant in an acidic aqueous phase in the presence of a catalyst.

[0021] In another embodiment, the present invention provides a compound having the structure of formula (II) or (III): [ka] [In the formula, X 1 ~X 3 are each independently selected from CH, CF, C-Cl, C-Br, CI and N, where n is an integer from 1 to 6, comprising: [ka] [In the formula, X 1 ~X 3 and n is as defined hereinabove with H2O2 in an acidic aqueous phase in the presence of a catalyst.

[0022] In another embodiment, the present invention provides a compound having the structure of formula (II) or (III): [ka] [In the formula, X 1 ~X 3are each independently selected from CH, CF, C-Cl, C-Br, CI and N, where n is an integer from 1 to 6, comprising: [ka] [In the formula, X 1 ~X 3 and n is as defined hereinabove with a peroxygen oxidant in an acidic aqueous phase in the presence of a catalyst.

[0023] In another embodiment, X 3 is selected from CH, CF, C-Cl, C-Br and CI, X 1 and X 2 are each independently selected from CH and N.

[0024] In another embodiment, the present invention relates to a method for the preparation of 5-chloro-2-((3,4,4-trifluorobut-3-en-1-yl)thio)-1λ oxidizing agents using a metal oxide based catalyst and oxidizing agent. 3 ,3λ 2 - the corresponding sulfone of thiazole, 5-chloro-2-((3,4,4-trifluorobut-3-en-1-yl)sulfonyl)-1λ 3 ,3λ 2 In another embodiment, the oxidizing agent is a peroxygen oxidizing agent. In another embodiment, the oxidizing agent is H2O2.

[0025] In one embodiment, the present invention provides 5-chloro-2-((3,4,4-trifluorobut-3-en-1-yl)sulfonyl)-1λ 3 ,3λ 2 A method for preparing a thiazole or an analogue thereof of formula I, II or III, comprising the steps of: 3 ,3λ 2In another embodiment, the present invention relates to a method for the preparation of a 5-chloro-2-((3,4,4-trifluorobut-3-en-1-yl)sulfonyl)-1λ-thiazole or its corresponding analog of formula Ia, IIa, or IIa, in an acidic aqueous phase in the presence of a catalyst. 3 ,3λ 2 A method for producing thiazole (fluensulfone), comprising the steps of: 3 ,3λ 2 -thiazole with an aqueous H2O2 solution in an acidic aqueous phase in the presence of a catalyst.

[0026] In one embodiment, the present invention provides 5-chloro-2-((3,4,4-trifluorobut-3-en-1-yl)sulfonyl)-1λ 3 ,3λ 2 A method for preparing a thiazole or an analogue thereof of formula I, II or III, comprising the steps of: 3 ,3λ 2 In another embodiment, the present invention relates to a method for the treatment of a 5-chloro-2-((3,4,4-trifluorobut-3-en-1-yl)sulfonyl)-1λ-thiazole or its corresponding analog of formula Ia, IIa, or IIa, with a water-soluble peroxygen oxidant in an acidic aqueous phase in the presence of a catalyst. 3 ,3λ 2 A method for producing thiazole (fluensulfone), comprising the steps of: 3 ,3λ 2 The present invention relates to a process comprising the step of contacting a -thiazole with a water-soluble peroxygen oxidant in an acidic aqueous phase in the presence of a catalyst.

[0027] In one embodiment, 5-chloro-2-((3,4,4-trifluorobut-3-en-1-yl)sulfonyl)-1λ 3 ,3λ 2The method for preparing the -thiazole or analogs thereof of formula I-III utilizes a catalyst. In another embodiment, the catalyst is at least one metal oxide or metal oxide salt. In another embodiment, the metal oxide comprises tungsten oxide, molybdenum oxide, vanadium oxide, niobium oxide, tantalum oxide, rhenium oxide, titanium oxide, zirconium oxide, chromium oxide, hafnium oxide, or combinations thereof.

[0028] In another embodiment, the catalyst has the formula M q M'O x at least one metal oxide salt of M is hydrogen, an alkali metal or an alkaline earth metal; M' is titanium, vanadium, chromium, zirconium, niobium, molybdenum, hafnium, tantalum, rhenium or tungsten; x is an integer from 2 to 6; q is an integer from 1 to 4.

[0029] In another embodiment, the compound of formula M q M'O x In another embodiment, M is hydrogen, an alkali metal, or an alkaline earth metal. In another embodiment, M is hydrogen, sodium, potassium, calcium, or magnesium. In another embodiment, M is q M'O x M' in the formula M is titanium, vanadium, chromium, zirconium, niobium, molybdenum, hafnium, tantalum, rhenium or tungsten. q M'O x In another embodiment, x is an integer from 2 to 6. In another embodiment, x is 2, 3, 4, 5, or 6. q M'O x In another embodiment, q is an integer from 1 to 4. In another embodiment, q is 1, 2, 3, or 4.

[0030] In another embodiment, the at least one metal oxide salt is sodium vanadate, sodium molybdate, or sodium tungstate, or a combination thereof, hi another embodiment, the metal oxide salt is sodium tungstate.

[0031] In another embodiment, the catalyst is hydrated.

[0032] In another embodiment, the concentration of catalyst in the reaction mixture is greater than or equal to 100% by mass of starting material 5-chloro-2-((3,4,4-trifluorobut-3-en-1-yl)thio)-1λ 3 ,3λ 2 -thiazole or its analogues of formula Ia, IIa or IIIa, is 0.01 to 20 mol %. In another embodiment, the concentration of the catalyst in the reaction mixture is 5-chloro-2-((3,4,4-trifluorobut-3-en-1-yl)thio)-1λ 3 ,3λ 2 -thiazole or its analogues of formula Ia, IIa or IIIa. In another embodiment, the concentration of the catalyst in the reaction mixture is 5-chloro-2-((3,4,4-trifluorobut-3-en-1-yl)thio)-1λ 3 ,3λ 2 -thiazole or its analogues of formula Ia, IIa or IIIa. In another embodiment, the concentration of the catalyst in the reaction mixture is 5-chloro-2-((3,4,4-trifluorobut-3-en-1-yl)thio)-1λ 3 ,3λ 2 -thiazole or its analogues of formula Ia, IIa or IIIa. In another embodiment, the concentration of the catalyst in the reaction mixture is 5-chloro-2-((3,4,4-trifluorobut-3-en-1-yl)thio)-1λ 3 ,3λ 2 -thiazole or its analogues of formula Ia, IIa or IIIa. In another embodiment, the concentration of the catalyst in the reaction mixture is 5-chloro-2-((3,4,4-trifluorobut-3-en-1-yl)thio)-1λ 3 ,3λ 2-thiazole or its analogues of formula Ia, IIa or IIIa. In another embodiment, the concentration of the catalyst in the reaction mixture is 5-chloro-2-((3,4,4-trifluorobut-3-en-1-yl)thio)-1λ 3 ,3λ 2 -thiazole or its analogues of formula Ia, IIa or IIIa. In another embodiment, the concentration of the catalyst in the reaction mixture is 5-chloro-2-((3,4,4-trifluorobut-3-en-1-yl)thio)-1λ 3 ,3λ 2 -thiazole or its analogues of formula Ia, IIa or IIIa. In another embodiment, the concentration of the catalyst in the reaction mixture is 5-chloro-2-((3,4,4-trifluorobut-3-en-1-yl)thio)-1λ 3 ,3λ 2 -thiazole or its analogues of formula Ia, IIa or IIIa. In another embodiment, the concentration of the catalyst in the reaction mixture is 5-chloro-2-((3,4,4-trifluorobut-3-en-1-yl)thio)-1λ 3 ,3λ 2 -thiazole or its analogues of formula Ia, IIa or IIIa.

[0033] In another embodiment, the catalyst is recycled and reused. In another embodiment, the catalyst is reused. In another embodiment, the catalyst is not isolated and is reused in the reaction mixture.

[0034] In one embodiment, 5-chloro-2-((3,4,4-trifluorobut-3-en-1-yl)sulfonyl)-1λ 3 ,3λ 2The method for preparing 3-((5-chloro-1λ-thiazole or its analogs of formula I, II, or III utilizes an aqueous acid. The use of an aqueous acid reduces the nucleophilicity of the hydrogen peroxide oxidant, especially when adjacent sulfone or sulfoxide groups are present, and reduces its reactivity towards the electrophilic trifluoro-alkene moiety, thereby inhibiting the reaction of the double bond with a peroxygen oxidant such as H2O2, and 3-((5-chloro-1λ-thiazole or its analogs of formula I, II, or III). 3 ,3λ 2 It has been found that the compound of formula (I)-(III): [ka] The method for producing a compound represented by formula (Ib)-(IIIb): [ka] [In the formula, R, 1 ~X 3 and n is as defined herein above. In another embodiment, the yield of the compounds of formula (Ib)-(IIIb) is 0-2 wt%. In another embodiment, the yield of the compounds of formula (Ib)-(IIIb) is 2-5 wt%. In another embodiment, the yield of the compounds of formula (Ib)-(IIIb) is 5-10 wt%. In another embodiment, the yield of the compounds of formula (Ib)-(IIIb) is 10-15 wt%. In another embodiment, the yield of the compounds of formula (Ib)-(IIIb) is 5-chloro-2-((3,4,4-trifluorobut-3-en-1-yl)sulfonyl)-1λ 3 ,3λ 2 The method for producing thiazole contains less than 2% by weight of 3-((5-chloro-1λ 3 ,3λ 2 This produces the by-product 1-thiazol-2-yl)sulfonyl)propanoic acid.

[0035] In one embodiment, 5-chloro-2-((3,4,4-trifluorobut-3-en-1-yl)sulfonyl)-1λ 3 ,3λ 2 The method for preparing the -thiazole or its analogs of formula I-III utilizes an acidic aqueous solution. In another embodiment, the acidic aqueous phase comprises HCl, HBr, H2SO4, H3PO4, MeSO3H, CF3SO3H, or a combination thereof. In another embodiment, the acidic aqueous phase comprises H2SO4. In another embodiment, the concentration of the acid in the acidic aqueous phase is 0.5-8M. In another embodiment, the concentration of the acid in the acidic aqueous phase is 1-6M. In another embodiment, the concentration of the acid in the acidic aqueous phase is 2-5M.

[0036] In one embodiment, 5-chloro-2-((3,4,4-trifluorobut-3-en-1-yl)sulfonyl)-1λ 3 ,3λ 2 The method for preparing the -thiazole or its analogs of formula I-III utilizes an oxidizing agent. In another embodiment, the oxidizing agent is a peroxygen oxidizing agent. In another embodiment, the oxidizing agent is H2O2. In another embodiment, the oxidizing agent is 5-chloro-2-((3,4,4-trifluorobut-3-en-1-yl)thio)-1λ 3 ,3λ 2 In another embodiment, 2 to 10 molar equivalents of an oxidizing agent are added to the 5-chloro-2-((3,4,4-trifluorobut-3-en-1-yl)thio)-1λ-thiazole or its analogs of formula Ia-IIIa. 3 ,3λ 2 In another embodiment, 2 to 5 molar equivalents of an oxidizing agent are added to the 5-chloro-2-((3,4,4-trifluorobut-3-en-1-yl)thio)-1λ-thiazole or its analogs of formula Ia-IIIa. 3 ,3λ 2 In another embodiment, 2 to 4 molar equivalents of an oxidizing agent are added to the 5-chloro-2-((3,4,4-trifluorobut-3-en-1-yl)thio)-1λ-thiazole or its analogs of formula Ia-IIIa. 3 ,3λ 23 to 3.5 molar equivalents of oxidizing agent are added relative to the -thiazole or analogs of formula Ia-IIIa. In another embodiment, the concentration of hydrogen peroxide used is 3% to 90% by volume (i.e., the commercially available concentration of hydrogen peroxide). In another embodiment, the concentration of hydrogen peroxide used is 20% to 60% by weight (i.e., the commercially available concentration of hydrogen peroxide).

[0037] In one embodiment, 5-chloro-2-((3,4,4-trifluorobut-3-en-1-yl)sulfonyl)-1λ 3 ,3λ 2 The reaction mixture for the preparation of -thiazole or its analogs of formula I-III is biphasic. In another embodiment, biphasic refers to an aqueous phase containing the oxidant, catalyst, and acid, and an organic phase containing the sulfide substrate, the sulfone product, and optionally a water-immiscible organic solvent. In another embodiment, biphasic refers to an aqueous phase containing the oxidant, catalyst, and acid, and an organic phase containing the sulfide substrate and the sulfone product without a water-immiscible organic solvent.

[0038] In one embodiment, 5-chloro-2-((3,4,4-trifluorobut-3-en-1-yl)sulfonyl)-1λ 3 ,3λ 2 The process for the preparation of -thiazoles or analogues thereof of formula I, II or III is a one-phase reaction.

[0039] In one embodiment, 5-chloro-2((3,4,4-trifluorobut-3-en-1-yl)sulfonyl)-1λ 3 ,3λ 2The reaction mixture for the preparation of .alpha.-thiazole or its analogs of formula I-III comprises water and does not comprise a water-immiscible organic solvent. In another embodiment, the reaction mixture comprises water and a water-immiscible organic solvent. Non-limiting examples of water-immiscible organic solvents include hexane, pentane, toluene, methylcyclohexane, chlorobenzene, ethyl acetate, and various ethers. In another embodiment, the reaction mixture comprises water and a water-miscible solvent and / or a surfactant. Non-limiting examples of water-miscible solvents include acetonitrile, methanol, ethanol, acetone, dimethylformamide, dimethylacetamide, n-methylpyrrolidone, or combinations thereof. In another embodiment, the reaction mixture comprises water and a water-immiscible organic solvent and / or a surfactant.

[0040] In some embodiments, the surfactant may include, but is not limited to, polyalkylene glycol, alkoxylated alcohol, alkyl sulfate, or any combination thereof. In some embodiments, the surfactant includes polyalkylene glycol, alkoxylated alcohol, alkyl sulfate, or any combination thereof. Non-limiting examples of surfactants include polyethylene glycol (such as PEG400), polyoxyethylene lauryl ether (such as Brij35), dodecyl sulfate (such as SDS).

[0041] In one embodiment, 5-chloro-2-((3,4,4-trifluorobut-3-en-1-yl)sulfonyl)-1λ 3 ,3λ 2The reaction for preparing the -thiazole or its analogues of formula I-III is carried out at a temperature ranging from 0°C to 100°C. In another embodiment, at a temperature of 20°C to 40°C. In another embodiment, at a temperature of 20°C to 50°C. In another embodiment, at a temperature of 20°C to 60°C. In another embodiment, at a temperature of 20°C to 70°C. In another embodiment, at a temperature of 25°C to 40°C. In another embodiment, at a temperature of 25°C to 50°C. In another embodiment, at a temperature of 25°C to 60°C. In another embodiment, at a temperature of 25°C to 70°C. In another embodiment, at a temperature of 26°C to 100°C. In another embodiment, at a temperature of 30°C to 80°C. In another embodiment, at a temperature of 10°C to 80°C. In another embodiment, at a temperature of 20°C to 80°C. In another embodiment, at a temperature of 10°C to 50°C. In another embodiment, at a temperature of 15°C to 35°C. In another embodiment, at a temperature of at least 15°C. In another embodiment, at a temperature of at least 20°C. In another embodiment, at a temperature of at least 25°C.

[0042] In one embodiment, the present invention relates to a method for producing 5-chloro-2-((3,4,4-trifluorobut-3-en-1-yl)sulfonyl)-1λ 3 ,3λ 2 -thiazole or its analogs of formula I-III. In another embodiment, the present invention relates to a 5-chloro-2-((3,4,4-trifluorobut-3-en-1-yl)sulfonyl)-1λ-thiazole prepared by the method of the present invention. 3 ,3λ 2 In another embodiment, the 5-chloro-2-((3,4,4-trifluorobut-3-en-1-yl)sulfonyl)-1λ-thiazole or analogs thereof of formula I-III have a purity of greater than 97%. 3 ,3λ 2 -thiazole or its analogs of formulas I-III is present in an amount of 1% by weight or less of 3-((5-chloro-1λ 3 ,3λ 2 -thiazol-2-yl)sulfonyl)propanoic acid or an analog thereof represented by formula (Ib-IIIb), and in another embodiment, less than 2% by weight of 3-((5-chloro-1λ 3,3λ 2 -thiazol-2-yl)sulfonyl)propanoic acid or analogs thereof represented by formulas (Ib-IIIb), wherein formulas (Ib-IIIb) are described above.

[0043] The following examples are presented in order to more fully illustrate preferred embodiments of the invention, but they should in no way be construed as limiting the broad scope of the invention. EXAMPLES

[0044] Example 1 5-Chloro-2-((3,4,4-trifluorobut-3-en-1-yl)sulfonyl)-1λ 3 ,3λ 2 -Production of thiazoles Sulfide, 5-chloro-2-((3,4,4-trifluorobut-3-en-1-yl)thio)-1λ 3 ,3λ 2 A mixture of 14 g (54 mmol)-thiazole, 20 mL of 4 M sulfuric acid, 780 mg of Na2WO4 (2.3 mmol, 4 mol%) was prepared, followed by the dropwise addition of 7 mL of 60% H2O2 (140 mmol) over 2 h. After 20 h at 22 °C, analysis of the reaction mixture by HPLC showed total conversion of starting material and the desired sulfone, 5-chloro-2-((3,4,4-trifluorobut-3-en-1-yl)sulfonyl)-1λ. 3 ,3λ 2 The formation of -thiazole was achieved with 96% selectivity. The by-product was 3% sulfoxide, 5-chloro-2-((3,4,4-trifluorobut-3-en-1-yl)sulfinyl)-1λ 3 ,3λ 2 -thiazole and 1% 3-((5-chloro-1λ 3 ,3λ 2 -thiazol-2-yl)sulfonyl)propanoic acid. Yield-14.7 g of Fluensulfone.

[0045] Example 2 5-Chloro-2-((3,4,4-trifluorobut-3-en-1-yl)sulfonyl)-1λ 3,3λ 2 -Production of thiazoles Sulfide, 5-chloro-2-((3,4,4-trifluorobut-3-en-1-yl)thio)-1λ 3 ,3λ 2 A mixture of 14 g (54 mmol)-thiazole, 20 mL of 4 M sulfuric acid, 780 mg of Na2WO4 (2.3 mmol, 4 mol%) was prepared, followed by the dropwise addition of 7 mL of 60% H2O2 (140 mmol) over 2 h. After 7 h at 35 °C, analysis of the reaction mixture by HPLC showed total conversion of starting material and the desired sulfone, 5-chloro-2-((3,4,4-trifluorobut-3-en-1-yl)sulfonyl)-1λ. 3 ,3λ 2 -thiazole formation with 91% selectivity.

[0046] Example 3 5-Chloro-2-((3,4,4-trifluorobut-3-en-1-yl)sulfonyl)-1λ 3 ,3λ 2 -Production of thiazoles Sulfide, 5-chloro-2-((3,4,4-trifluorobut-3-en-1-yl)thio)-1λ 3 ,3λ 2 A mixture of 14 g (54 mmol)-thiazole, 20 mL of 4 M sulfuric acid, 390 mg of Na2WO4 (1.65 mmol, 2 mol%) was prepared, followed by the dropwise addition of 7 mL of 60% H2O2 (140 mmol) over 2 h. After 20 h at 22 °C, analysis of the reaction mixture by HPLC showed total conversion of starting material and the desired sulfone, 5-chloro-2-((3,4,4-trifluorobut-3-en-1-yl)sulfonyl)-1λ. 3 ,3λ 2 -thiazole formation with 86% selectivity.

[0047] Example 4 5-Chloro-2-((3,4,4-trifluorobut-3-en-1-yl)sulfonyl)-1λ 3 ,3λ 2 -Production of thiazoles Sulfide, 5-chloro-2-((3,4,4-trifluorobut-3-en-1-yl)thio)-1λ 3 ,3λ 2 A mixture of 14 g (54 mmol)-thiazole, 20 mL of 4 M phosphoric acid, 780 mg of Na2WO4 (2.3 mmol, 4 mol%) was prepared, followed by the dropwise addition of 7 mL of 60% H2O2 (140 mmol) over 2 h. After 20 h at 22 °C, analysis of the reaction mixture by HPLC showed total conversion of starting material and the desired sulfone, 5-chloro-2-((3,4,4-trifluorobut-3-en-1-yl)sulfonyl)-1λ. 3 ,3λ 2 The formation of -thiazole was demonstrated with 75% selectivity due to the extensive decomposition of H2O2.

[0048] Example 5 Water phase recycling experiment Using the procedure of Example 1, the sulfide, 5-chloro-2-((3,4,4-trifluorobut-3-en-1-yl)thio)-1λ 3 ,3λ 2 A mixture of 14 g (54 mmol)-thiazole, 20 mL of 4 M sulfuric acid, 780 mg of Na2WO4 (2.3 mmol, 4 mol%) was prepared, followed by the dropwise addition of 7 mL of 60% H2O2 (140 mmol) over 2 h. After 20 h at 22 °C, analysis of the reaction mixture by HPLC showed total conversion of starting material and the desired fluenesulfone, 5-chloro-2-((3,4,4-trifluorobut-3-en-1-yl)sulfonyl)-1λ. 3 ,3λ 2 -thiazole formation with 96% selectivity. After separation of the organic phase (containing the sulfone product and no organic solvent) from the aqueous phase, 33% of the aqueous phase was removed by adding 1 / 3 of the initial amount of Na2WO4, H2SO4 and H2O2 to keep the reaction volume constant. The recycle experiment carried out in this way showed that 5-chloro-2-((3,4,4-trifluorobut-3-en-1-yl)thio)-1λ-thiazole was formed with 96% selectivity. 3 ,3λ 2 The conversion of -thiazole and the selectivity towards fluensulfone were found to be identical within ±1%.

[0049] Example 6 5-Chloro-2-((3,4,4-trifluorobut-3-en-1-yl)sulfonyl)-1λ 3 ,3λ 2 -Production of thiazoles Sulfide, 5-chloro-2-((3,4,4-trifluorobut-3-en-1-yl)thio)-1λ 3 ,3λ 2 A mixture of 100 g of 2-thiazole (370 mmol), 150 mL of 2 M sulfuric acid, 5.5 g of Na2WO4 was prepared, followed by the dropwise addition of 65 g of 50% H2O2 (955 mmol) over 1.5 h at 10 °C. The reaction mixture was stirred at room temperature for 30 min, then warmed to 40 °C and stirred for 13 h. Analysis of the reaction mixture by HPLC showed total conversion of starting material and the desired sulfone, 5-chloro-2-((3,4,4-trifluorobut-3-en-1-yl)sulfonyl)-1λ. 3 ,3λ 2 The formation of -thiazole was demonstrated. The product was isolated in 77% yield with 97% selectivity.

[0050] While certain features of the invention have been illustrated and described herein, many modifications, substitutions, changes, and equivalents will occur to those skilled in the art. It is therefore to be understood that the appended claims are intended to cover all such modifications and changes that fall within the true spirit of the invention. One embodiment of the present invention will be described below, but the present invention is not limited thereto. [Invention 1] A method for preparing a compound represented by the structure of formula (I): [C1] JPEG0007662612000015.jpg2843 In the reaction mixture, a compound of formula (Ia): [C2] JPEG0007662612000016.jpg2843 wherein R is a heterocycle selected from thiophene, thiazole, isothiazole, thiadiazole, and thiatriazole, said heterocycle being optionally halogenated, and n is an integer of 1 to 6. with a peroxygen oxidant in an acidic aqueous phase in the presence of a catalyst. [Invention 2] A method for preparing a compound represented by the structure of formula (I): [C3] JPEG0007662612000017.jpg2843 In the reaction mixture, a compound of formula (Ia): [C4] JPEG0007662612000018.jpg2843 wherein R is a heterocycle selected from thiophene, thiazole, isothiazole, thiadiazole, and thiatriazole, said heterocycle being optionally halogenated, and n is an integer of 1 to 6. In the presence of a catalyst, H 2 O 2 The method comprises the step of contacting the [Invention 3] The compound of formula (I) is represented by the structure of formula (II) or (III): [5] JPEG0007662612000019.jpg6977 The above H 2 O 2 in an acidic aqueous phase in the presence of a catalyst, [6] JPEG0007662612000020.jpg6977 [In the formula, X 1 ~X 3 are each independently selected from CH, CF, C-Cl, C-Br, CI, and N. The method according to Invention 1 or Invention 2, comprising contacting a compound represented by the formula: [Invention 4] The compound of the formula (I) is 5-chloro-2-((3,4,4-trifluorobut-3-en-1-yl)sulfonyl)-1λ 3 ,3λ 2 -thiazole, 2 O 2 In the presence of a catalyst, 5-chloro-2-((3,4,4-trifluorobut-3-en-1-yl)thio)-1λ is reacted with 5-chloro-2-((3,4,4-trifluorobut-3-en-1-yl)thio)-1λ in an acidic aqueous phase. 3 ,3λ 2 -The method according to Invention 1 or Invention 2, wherein the compound is contacted with thiazole. [Invention 5] 5. The method according to any one of claims 1 to 4, wherein the catalyst is at least one metal oxide. [Invention 6] 6. The method of claim 5, wherein the metal oxide comprises tungsten oxide, molybdenum oxide, vanadium oxide, niobium oxide, tantalum oxide, rhenium oxide, titanium oxide, zirconium oxide, chromium oxide, hafnium oxide, or a combination thereof. [Invention 7] The catalyst has the formula M q M'O x at least one metal oxide salt of M is hydrogen, an alkali metal or an alkaline earth metal; M' is titanium, vanadium, chromium, zirconium, niobium, molybdenum, hafnium, tantalum, rhenium or tungsten; x is an integer from 2 to 6; q is an integer from 1 to 4; The method according to claim 5. [Invention 8] 8. The method of claim 7, wherein the catalyst is sodium vanadate, sodium molybdate, or sodium tungstate, or a combination thereof. [Invention 9] 9. The method of claim 8, wherein the catalyst is sodium tungstate. [Invention 10] 10. The method according to any one of claims 1 to 9, wherein the catalyst is hydrated. [Invention 11] 11. The method according to any one of Inventions 1 to 10, wherein the concentration of the catalyst is 0.01 to 20 mol % relative to the compound represented by formula (I). [Invention 12] 12. The method according to claim 11, wherein the concentration of the catalyst is 1 to 10 mol % relative to the compound represented by formula (I). [Invention 13] 12. The method according to claim 11, wherein the concentration of the catalyst is 1 to 5 mol % relative to the compound represented by formula (I). [Invention 14] The acidic aqueous phase contains HCl, HBr, H 2 SO 4 、H 3 PO 4 , MeSO 3 H, C.F. 3 SO 3 14. The method according to any one of claims 1 to 13, comprising: [Invention 15] The acidic aqueous phase is H 2 SO 4 The method according to claim 14, comprising: [Invention 16] 16. The method according to any one of Inventions 1 to 15, wherein the concentration of the acid in the acidic aqueous phase is 0.5 to 8M. [Invention 17] 17. The method according to claim 16, wherein the concentration of the acid in the acidic aqueous phase is 2 to 5 M. [Invention 18] 2 to 10 molar equivalents of the H relative to the compound represented by formula (I) 2 O 2 The method according to claim 1, wherein [Invention 19] water-based H 2 O 2 19. The method according to claim 18, wherein the concentration of the compound is between 3% and 90% by volume. [Invention 20] 20. The method according to any one of claims 1 to 19, wherein the reaction mixture comprises water and does not comprise a water-immiscible organic solvent. [Invention 21] 21. The method according to any one of claims 1 to 20, wherein the reaction is carried out at a temperature in the range of 0°C to 100°C. [Invention 22] 22. The method according to claim 21, wherein the reaction is carried out at a temperature in the range of 15°C to 35°C. [Invention 23] 23. The method according to any one of claims 1 to 22, wherein the catalyst is recycled.

Claims

1. A process for preparing a compound represented by the structure of formula (I): 【Chemistry 1】 In the reaction mixture, a compound of formula (Ia): 【Chemistry 2】 wherein R is a heterocycle selected from thiophene, thiazole, isothiazole, thiadiazole and thiatriazole, said heterocycle being optionally halogenated, and n is an integer from 1 to 6. with a peroxygen oxidant in an acidic aqueous phase in the presence of a catalyst, the acidic aqueous phase comprises HCl, HBr, H2SO4, H3PO4, MeSO3H, CF3SO3H, or combinations thereof; method.

2. A process for preparing a compound represented by the structure of formula (I): 【Chemistry 3】 In the reaction mixture, a compound of formula (Ia): 【Chemistry 4】 wherein R is a heterocycle selected from thiophene, thiazole, isothiazole, thiadiazole and thiatriazole, said heterocycle being optionally halogenated, and n is an integer from 1 to 6. In the presence of a catalyst, in an acidic aqueous phase, ２ O ２ and contacting said compound with said compound, the acidic aqueous phase comprises HCl, HBr, H2SO4, H3PO4, MeSO3H, CF3SO3H, or combinations thereof; method.

3. The compound of formula (I) is represented by the structure of formula (II) or (III): 【Chemistry 5】 The H ２ O ２ in an acidic aqueous phase in the presence of a catalyst to produce a compound of formula (IIa) or (IIIa): 【Chemistry 6】 [In the formula, X １ ~X ３ are each independently selected from C-H, C-F, C-Cl, C-Br, C-I, and N. The method of claim 1 or claim 2, wherein the compound is contacted with a compound represented by the formula:

4. The compound of the formula (I) is 5-chloro-2-((3,4,4-trifluorobut-3-en-1-yl)sulfonyl)-1λ ３ , 3λ ２ -thiazole, ２ O ２ In the presence of a catalyst, 5-chloro-2-((3,4,4-trifluorobut-3-en-1-yl)thio)-1λ ３ , 3λ ２ The method according to claim 1 or 2, wherein the compound is contacted with a thiazole.

5. 5. The method of claim 1, wherein the catalyst is at least one metal oxide.

6. 6. The method of claim 5, wherein the metal oxide comprises tungsten oxide, molybdenum oxide, vanadium oxide, niobium oxide, tantalum oxide, rhenium oxide, titanium oxide, zirconium oxide, chromium oxide, hafnium oxide, or a combination thereof.

7. The catalyst has the formula M ｑ M'O ｘ at least one metal oxide salt of M is hydrogen, an alkali metal or an alkaline earth metal; M' is titanium, vanadium, chromium, zirconium, niobium, molybdenum, hafnium, tantalum, rhenium or tungsten; x is an integer from 2 to 6; q is an integer from 1 to 4; The method according to claim 5.

8. 8. The method of claim 7, wherein the catalyst is sodium vanadate, sodium molybdate, or sodium tungstate, or a combination thereof.

9. 9. The method of claim 8, wherein the catalyst is sodium tungstate.

10. 10. The method of any one of claims 1 to 9, wherein the catalyst is hydrated.

11. The method according to any one of claims 1 to 10, wherein the concentration of the catalyst is 0.01 to 20 mol% relative to the compound represented by formula (I).

12. The method according to claim 11, wherein the concentration of the catalyst is 1-10 mol % relative to the compound represented by formula (I).

13. The method according to claim 11, wherein the concentration of the catalyst is 1-5 mol% relative to the compound represented by formula (I).

14. The acidic aqueous phase is H ２ SO ４ 14. The method of any one of claims 1 to 13, comprising:

15. 15. The method according to any one of claims 1 to 14, wherein the concentration of the acid in the acidic aqueous phase is from 0.5 to 8M.

16. The method of claim 15, wherein the concentration of the acid in the acidic aqueous phase is 2 to 5 M.

17. 2 to 10 molar equivalents of said H relative to the compound represented by formula (I). ２ O ２ The method of claim 1 , wherein

18. Aqueous H ２ O ２ The method according to claim 17, wherein is used in a concentration of 3% to 90% by volume.

19. 19. The method of any one of claims 1 to 18, wherein the reaction mixture comprises water and no water-immiscible organic solvent.

20. 20. The process of any one of claims 1 to 19, wherein the reaction is carried out at a temperature in the range of from 0°C to 100°C.

21. 21. The method of claim 20, wherein the reaction is carried out at a temperature in the range of 15°C to 35°C.

22. 22. The method of any one of claims 1 to 21, wherein the catalyst is recycled.

Images