Process for preparation of 2-alkylsulfonyl-substituted benzoic acid derivatives

Abstract

The present invention provides a process for the preparation of 2-alkylsulfonyl substituted benzoic acid derivatives of formula (I) by conversion of 2-alkylthio substituted benzonitrile compounds of formula (II), which derivatives are useful as intermediates for the preparation of herbicidally active compounds such as sulfopyrazole or isoxaflutole. # imgabs0 #

Description

Technical Field:

[0001] The present invention relates to a method for preparing a 2-alkylsulfonyl-substituted benzoic acid compound of formula (I),

[0002]

[0003] which compound can be used as an intermediate for preparing herbicidally active compounds. Background Art:

[0004] 2-alkylsulfonyl-substituted benzoic acid compounds can be used as intermediates for preparing pesticidal compounds (such as pyraflufen-ethyl, isoxaflutole, etc.).

[0005] Patent EP 0,527,036 discloses a method for preparing 2-methylsulfonyl-4-trifluoromethylbenzoic acid by reacting 2-methylsulfinyl-4-trifluoromethylbenzoic acid with hydrogen peroxide and acetic anhydride in acetic acid. However, this patent does not disclose the preparation of 2-alkylsulfonyl-substituted benzoic acid derivatives from 2-alkylthio-substituted benzonitrile derivatives.

[0006] Patent CN 105,646,356 discloses a method for preparing 2-methylsulfonyl-4-trifluoromethylbenzoic acid by reacting methyl 2-(methylthio)-4-(trifluoromethyl)benzoate with acetic acid and hydrogen peroxide and then performing base hydrolysis. However, this patent does not disclose the preparation of 2-alkylsulfonyl-substituted benzoic acid derivatives from 2-alkylthio-substituted benzonitrile derivatives.

[0007] Patent CN 112,010,793 discloses a method for preparing 2-methylsulfonyl-4-trifluoromethylbenzoic acid by reacting 2-methylthio-4-trifluoromethylbenzonitrile with hydrogen peroxide in the presence of a metal catalyst followed by base hydrolysis. However, this method requires the use of a metal catalyst and takes a longer time.

[0008] The methods described in the prior art have the following drawbacks. For example, the long reaction time and the use of a metal catalyst make the method uneconomical; and the solvent is difficult to recover. Therefore, there is still a need for a method that eliminates the disadvantages associated with the known methods.

[0009] Therefore, there is a need to develop an effective method for preparing 2-alkylsulfonyl-substituted benzoic acid derivatives of formula (I) in high yield from 2-alkylthio-substituted benzonitrile compounds of formula (II), and thus selectivity is desired. Summary of the Invention:

[0010] The present invention provides a method for preparing a compound of formula (I):

[0011]

[0012] Wherein

[0013] R1 represents C 1-6 alkyl, C 1-6 haloalkyl, phenyl or phenyl substituted by carboxylic acid;

[0014] R2 represents hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 haloalkoxy, phenyl or phenyl substituted by halogen or carboxylic acid;

[0015] The method comprises

[0016] a) reacting a compound of formula (II):

[0017]

[0018] wherein R1 and R2 are as defined above;

[0019] with an oxidizing agent in the presence of an aqueous acid in a suitable solvent system to form a compound of formula (III), and the reaction is carried out in the absence of a metal catalyst;

[0020]

[0021] wherein R1 and R2 are as defined above;

[0022] b) reacting the compound of formula (III) with an alkali metal hydroxide;

[0023] c) mixing the reaction mixture from step (b) with a strong acid system to obtain a compound of formula (I).

[0024] In one aspect, the present invention provides the method, wherein in step (c), the strong acid system comprises the aqueous acid from step (a).

[0025] In another aspect, the present invention provides that the strong acid system comprises at least one acid stronger than the compound of formula (I).

[0026] In one aspect, the present invention provides that R1 is C 1-6 alkyl, and R2 is C 1-6 haloalkyl.

[0027] In another aspect, the present invention provides that R1 is methyl and R2 is trifluoromethyl.

[0028] In another aspect, the present invention provides that the oxidizing agent is hydrogen peroxide, and the molar ratio of hydrogen peroxide to the compound having the formula (II) is about 2:1 to 5:1, preferably about 2.5:1.

[0029] In yet another aspect, the present invention provides an acid selected from the group consisting of sulfuric acid, phosphoric acid, nitric acid, strong carboxylic acids, or mixtures thereof, and the molar ratio of the acid to the compound having the formula (II) is about 10:1 to 0.8:1, preferably about 1:1.

[0030] In one aspect, the present invention provides that the solvent system is a mixture of an organic solvent and an aqueous solvent, wherein the organic solvent is selected from chlorobenzene, toluene, xylene, dichlorobenzene, or any other aromatic solvent or mixtures thereof that are inert to the reaction conditions.

[0031] In another aspect, the reaction of step (a) is carried out at a temperature of about 70 °C to 110 °C and preferably 70 °C to 80 °C, and the reaction mixture is cooled to a temperature of about 30 °C to 40 °C and filtered, wherein the filtrate contains an organic layer and an aqueous acidic layer.

[0032] In a further aspect, the alkali metal hydroxide is selected from the group consisting of sodium hydroxide, potassium hydroxide or calcium hydroxide, and the concentration is about 15% to 50%, preferably 45% to 50%. The alkali metal hydroxide and the compound having the formula (II) are present in a molar ratio of about 5:1 to 1:1, preferably about 1.5:1.

[0033] In yet another aspect, the present invention provides a method for preparing sulfentrazone, which method comprises preparing the compound having the formula (I) as mentioned above and further converting it into sulfentrazone.

[0034] In one aspect, the present invention provides a method for preparing isoxaflutole, which method comprises preparing the compound having the formula (I) as mentioned above and further converting it into isoxaflutole.

[0035] In a preferred aspect, the present invention provides a method for preparing 2-methylsulfonyl-4-trifluoromethylbenzoic acid, which method comprises:

[0036] a) reacting 2-(methylthio)-4-(trifluoromethyl)benzonitrile with an oxidizing agent in the presence of an aqueous acid in a suitable solvent system, and the reaction is carried out in the absence of a metal catalyst;

[0037] b) reacting the product from step (a) with an alkali metal hydroxide and over-acidifying to obtain 2-methylsulfonyl-4-trifluoromethylbenzoic acid. Detailed embodiments:

[0038] For the sake of clarity, specific terms are used when describing embodiments of the present invention. However, it is not intended to limit the present invention to the specific terms so selected, and it should be understood that each specific term includes all technical equivalents that operate in a similar manner to achieve a similar purpose.

[0039] It should be understood that the terms used herein are for the purpose of describing embodiments only and are not intended to be limiting. Unless otherwise clearly specified in the context, as used in this specification, the singular forms "a / an" and "the" include plural referents. Thus, for example, reference to "a compound" includes one or more such compounds.

[0040] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although other methods and materials similar or equivalent to those described herein can be used in the practice of the present invention, the preferred materials and methods are described herein.

[0041] As used herein, the term "or" means "and / or". It will be further understood that the terms "comprises / comprising", "includes / including", or any other variants thereof are intended to cover non-exclusive inclusion, subject to any limitations specifically stated. For example, a composition or method that includes a series of elements is not necessarily limited to those elements, but may include other elements not expressly listed or inherent to such composition or method.

[0042] 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 be construed in light of the number of reported significant digits and by applying ordinary rounding techniques.

[0043] In addition, all endpoints of all ranges involving the same component or property herein include the endpoints, are combinable independently, and include all intermediate points and ranges.

[0044] The term "mol" refers to the amount of a substance that reacts with an arbitrary amount (usually one mole) of another substance in a specific chemical reaction.

[0045] As used herein, the term "alkyl" refers to a saturated aliphatic hydrocarbon group containing 1 to 6 carbon atoms. The alkyl group can be straight-chain or branched-chain. Examples of alkyl groups include, but are not limited to, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, n-hexyl, and the like.

[0046] As used herein, the term "haloalkyl" refers to an alkyl group having one or more halogen substituents (up to perhaloalkyl, i.e., each hydrogen atom of the alkyl group has been replaced by a halogen atom). The haloalkyl can be straight-chain or branched-chain. For example, the term "C 1-6 haloalkyl" refers to a C 1-6 alkyl group having one or more halogen substituents (up to perhaloalkyl, i.e., each hydrogen atom of the alkyl group has been replaced by a halogen atom). Examples of haloalkyls include, but are not limited to, CF3, C2F5, CHF2, CH2F, CH2CF3, CH2Cl, etc.

[0047] As used herein, the term "haloalkoxy" refers to -O-haloalkyl. The haloalkoxy can be straight-chain or branched-chain. For example, the term "C 1-6 haloalkoxy" refers to an -O-(C 1-6 haloalkyl) group. Examples of haloalkoxys include, but are not limited to, -OCF3 or -OCHF2, etc.

[0048] As used herein, the term "carboxylic acid" refers to a -C(O)-OH group having 1 to 6 carbon atoms. The carboxylic acid group can be a straight-chain or branched-chain carboxylic acid group. Examples of carboxylic acid groups include formic acid, acetic acid, etc.

[0049] As used herein, the term "phenyl substituted with a carboxylic acid" refers to a phenyl group substituted with a carboxylic acid group. Examples include phenylacetic acid, etc.

[0050] As used herein, the term "phenyl substituted with a halogen" refers to a phenyl group substituted with a halogen atom. Examples include -C6H4F, -C6H4Cl, etc.

[0051] As used herein, the term "oxidizing agent" refers to a reagent whose oxidation potential is high enough to effect the desired reaction without significantly affecting any undesired reactions. Suitable oxidizing agents include hydrogen peroxide, etc.

[0052] As used herein, the term "catalyst" refers to a substance that causes a change in the reaction rate and is not consumed itself in the reaction. In the present invention, particularly suitable are such catalysts that are suitable for converting a 2-alkylthio-substituted benzonitrile compound having formula (II) into a 2-alkylsulfonyl-substituted benzoic acid compound having formula (I). The catalyst will be referred to as a metal catalyst.

[0053] As used herein, the term "suitable solvent system" refers to any solvent and mixture of solvents that are inert to the reaction being carried out and that sufficiently dissolve the reactants to provide a medium in which the desired reaction can take place.

[0054] As used herein, the term "strong acid system" refers to an acid system that contains at least one acid stronger than the compound of formula (I), such as sulfuric acid, phosphoric acid, nitric acid, strong carboxylic acids, and mixtures thereof, etc.

[0055] As used herein, the term "about" means and includes the value shown and the ranges before and after these values. In certain embodiments, the term "about" means ±10%, ±5% or ±1% of the value shown.

[0056] As used herein, the term "telescopic process" refers to a chemical process that involves a method carried out in a telescopic manner without separating the intermediates generated during the synthesis.

[0057] The 2-alkylsulfonyl-substituted benzoic acid compound can be used as an intermediate for preparing agrochemical compounds. For example, it is used as an intermediate for preparing herbicidal active substances such as sulfentrazone, isoxaflutole, etc.

[0058] The present invention provides a method for preparing a compound of formula (I):

[0059]

[0060] wherein

[0061] R1 represents C 1-6 alkyl, C 1-6 haloalkyl, phenyl or phenyl substituted by a carboxylic acid;

[0062] R2 represents hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 haloalkoxy, phenyl or phenyl substituted by a halogen or a carboxylic acid;

[0063] The method comprises

[0064] a) reacting a compound of formula (II):

[0065]

[0066] wherein R1 and R2 are as defined above;

[0067] with an oxidizing reagent in the presence of an aqueous acid in a suitable solvent system to form a compound of formula (III), and the reaction is carried out in the absence of a metal catalyst;

[0068]

[0069] wherein R1 and R2 are as defined above;

[0070] b) Reacting a compound of formula (III) with an alkali metal hydroxide;

[0071] c) Mixing the reaction mixture from step (b) with a strong acid system to obtain a compound of formula (I).

[0072] In one embodiment, the present invention provides a method wherein, in step (c), the strong acid system comprises the aqueous acid from step (a).

[0073] In another embodiment, the present invention provides that the strong acid system comprises at least one acid stronger than the compound of formula (I).

[0074] In one embodiment, the present invention provides that R1 is C 1-6 alkyl, and R2 is C 1-6 haloalkyl. More preferably, R1 is methyl and R2 is trifluoromethyl.

[0075] The foregoing reaction is carried out in the presence of a suitable solvent system with an oxidizing reagent and an aqueous acid to form a compound of formula (III).

[0076] In one embodiment, the oxidizing reagent used in the oxidation reaction can be a common oxidizing reagent known to those skilled in the art.

[0077] In an embodiment of the present invention, hydrogen peroxide is used as the oxidizing reagent. In addition, to ensure the oxidation effect and assist the overall oxidation reaction, hydrogen peroxide is added dropwise within 2 to 8 hours.

[0078] In one embodiment, hydrogen peroxide and the compound of formula (II) are present in a molar ratio of about 2:1 to 5:1. In a preferred embodiment, hydrogen peroxide and the compound of formula (II) are present in a molar ratio of about 2.5:1.

[0079] The acid is selected from the group consisting of sulfuric acid, phosphoric acid, nitric acid, strong carboxylic acids, and mixtures thereof. The strong carboxylic acids are selected from the group consisting of acids stronger than the compound of formula (I), such as trifluoroacetic acid or trichloroacetic acid, etc.

[0080] In one embodiment, the acid and the compound of formula (II) are present in a molar ratio of about 10:1 to 0.8:1. In another embodiment, the acid and the compound of formula (II) are present in a molar ratio of about 3:1 to 0.8:1. In a preferred embodiment, the acid and the compound of formula (II) are present in a molar ratio of about 1:1.

[0081] Suitable solvents according to the present invention comprise organic solvents and aqueous solvents, wherein the organic solvents are selected from the group consisting of: chlorobenzene, toluene, xylene, dichlorobenzene, any other aromatic solvent inert to the reaction conditions, and mixtures thereof.

[0082] The oxidation reaction of the method of step (a) according to the present invention is generally carried out at a temperature of about 70 °C to 110 °C. In another embodiment, the temperature is about 70 °C to 100 °C. More preferably at a temperature of about 70 °C to 80 °C.

[0083] In a further step, to complete the oxidation process, the reaction mixture is heated at 70 °C to 80 °C for 6 hours to 8 hours, cooled to a temperature of about 30 °C to 40 °C and filtered. The filtrate is phase-separated. The organic layer is used for the next step, and the aqueous acidic layer is retained for the final neutralization step.

[0084] In the next step, the organic layer, the filter cake and a solution of an alkali metal hydroxide are mixed and heated to a temperature of about 90 °C to 100 °C for a certain period of time, usually for 4 hours to 6 hours.

[0085] In a further step, water and the aqueous acidic layer from the oxidation step are added and cooled to 0 °C to 5 °C for a certain period of time, usually 3 hours. The precipitated material is filtered to obtain the compound of formula (I).

[0086] The alkali metal hydroxide is selected from the group comprising sodium hydroxide, potassium hydroxide or calcium hydroxide. In one embodiment, the alkali metal hydroxide and the compound of formula (II) are present in a molar ratio of about 5:1 to 1:1. In a further embodiment, the alkali metal hydroxide and the compound of formula (II) are present in a molar ratio of about 3:1 to 1:1. In a preferred embodiment, the alkali metal hydroxide and the compound of formula (II) are present in a molar ratio of about 1.5:1.

[0087] In another embodiment, the concentration of the alkali metal hydroxide solution is 15% to 50%. In a further embodiment, the concentration of the alkali metal hydroxide solution is 35% to 50%. In yet another embodiment, the concentration of the alkali metal hydroxide solution is 40% to 50%. In a preferred embodiment, the concentration of the alkali metal hydroxide solution is 48%.

[0088] The method according to the invention is generally carried out at atmospheric pressure. However, it is also possible to carry out the method according to the invention at elevated or reduced pressure. In one embodiment, the method for preparing 2-alkylsulfonylbenzoic acid of formula (I) can be carried out at a pressure of from about 1 bar to about 10 bar. In another embodiment, the method can be carried out at a pressure of from about 1 bar to about 5 bar. In yet another embodiment, the method for preparing 2-alkylsulfonylbenzoic acid of formula (I) can be carried out at atmospheric pressure. In additional embodiments, the method can be carried out at about 10 bar. In certain embodiments, it may be preferred that the method is carried out at a pressure below atmospheric pressure. For example, the method can be carried out at 0.7 bar, 0.75 bar, 0.8 bar, 0.9 bar or 0.95 bar.

[0089] In yet another embodiment, the present invention provides a method for preparing sulfentrazone, which method comprises preparing a compound of formula (I) as mentioned above and further converting it into sulfentrazone. The compound of formula (I) can be converted into sulfentrazone as described, for example, in PCT application No. WO 2001 / 074785 in the art.

[0090]

[0091] In one embodiment, the present invention provides a method for preparing isoxaflutole, which method comprises preparing a compound of formula (I) as mentioned above and further converting it into isoxaflutole.

[0092] In one embodiment, the present invention provides a method for preparing 2-methylsulfonyl-4-trifluoromethylbenzoic acid, which method comprises:

[0093] a) reacting 2-(methylthio)-4-(trifluoromethyl)benzonitrile with an oxidizing agent in the presence of an aqueous acid in a suitable solvent; and the reaction is carried out in the absence of a metal catalyst;

[0094] b) reacting the product from step (a) with an alkali metal hydroxide and over-acidifying to obtain 2-methylsulfonyl-4-trifluoromethylbenzoic acid.

[0095] In another embodiment, in the above method, the acid used for acidification is an acid stronger than 2-methylsulfonyl-4-trifluoromethylbenzoic acid and / or the aqueous acid from step (a).

[0096] In a preferred embodiment, the present invention provides a method for preparing 2-methylsulfonyl-4-trifluoromethylbenzoic acid, which method comprises:

[0097] a) React 2-(methylthio)-4-(trifluoromethyl)benzonitrile with hydrogen peroxide in the presence of an aqueous sulfuric acid solution in a chlorobenzene or toluene solvent; and the reaction is carried out in the absence of a metal catalyst;

[0098] b) React the product from step (a) with potassium hydroxide and acidify with an aqueous sulfuric acid solution, optionally with the aqueous sulfuric acid solution from step (a), to produce 2-(methylsulfonyl)-4-(trifluoromethyl)benzoic acid.

[0099] The process of the present invention is advantageous because it is efficient, providing shorter reaction times and less effluent. It also provides high conversion and selectivity as well as a higher yield of the final product.

[0100] A telescoping process for preparing a 2-alkylsulfonyl-substituted benzoic acid derivative having formula (I):

[0101]

[0102] wherein

[0103] R1 represents C 1-6 alkyl, C 1-6 haloalkyl, phenyl or phenyl substituted with a carboxylic acid;

[0104] R2 represents hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 haloalkoxy, phenyl or phenyl substituted with a halogen;

[0105] The process comprises

[0106] a) React a compound having formula (II):

[0107]

[0108] wherein R1 and R2 are as defined above;

[0109] with an oxidizing agent in the presence of an aqueous acid in a suitable solvent system to form a compound having formula (III), and the reaction is carried out in the absence of a metal catalyst;

[0110]

[0111] wherein R1 and R2 are as defined above;

[0112] b) React the compound having formula (III) with an alkali metal hydroxide;

[0113] c) Mix the reaction mixture from step (b) with a strong acid system to obtain a compound having formula (I).

[0114] In one embodiment, the present invention provides a method, wherein in step (c), the strong acid system comprises the aqueous acid from step (a).

[0115] In another embodiment, the present invention provides that the strong acid system comprises at least one acid stronger than the compound having formula (I).

[0116] In a preferred embodiment, R1 is methyl and R2 is trifluoromethyl.

[0117] In one embodiment, the oxidizing agent in the condensation method is hydrogen peroxide, and the molar ratio of hydrogen peroxide to the compound having formula (II) is about 5:1 to 2:1, preferably about 2.5:1.

[0118] In another embodiment, the acid in the condensation method is sulfuric acid; and the molar ratio of sulfuric acid to the compound having formula (II) is about 10:1 to 0.8:1, preferably about 1:1.

[0119] In a further embodiment, the solvents used in the condensation method include organic solvents and aqueous solvents, and the organic solvents are selected from the group consisting of: chlorobenzene, toluene, xylene, dichlorobenzene, or any other aromatic solvent inert to the reaction conditions and mixtures thereof.

[0120] In yet another embodiment, the alkali metal hydroxide in the condensation method is selected from sodium hydroxide, potassium hydroxide, or calcium hydroxide, and the molar ratio of the alkali metal hydroxide to the compound having formula (II) is about 5:1 to 1:1, preferably about 1.5:1. The concentration of the alkali metal hydroxide solution is about 15% to 50%, preferably 45% to 50%.

[0121] Any suitable method can be used to monitor the progress of the synthesis reaction of the compound having formula (I), and such method can include, for example, chromatographic methods such as high performance liquid chromatography (HPLC), thin layer chromatography (TLC), etc. In yet another embodiment, the compound having formula (I) can be separated from the reaction mixture by any conventional technique well known in the art. Such separation techniques can be selected from, but not limited to, the group consisting of: extraction, crystallization, or precipitation by concentration, cooling, or addition of an anti-solvent; filtration; centrifugation, and combinations thereof, followed by drying.

[0122] In yet another embodiment, the compound having formula (I) can optionally be purified by any conventional technique well known in the art. Such purification techniques can be selected from, but not limited to, the group consisting of: precipitation, crystallization, extraction, slurrying, washing in a suitable solvent, filtration through a packed bed column, dissolution in a proper solvent, re-precipitation by adding a second solvent in which the compound is insoluble, and combinations thereof.

[0123] The following examples illustrate the practice of the present invention in some of its embodiments but should not be construed as limiting the scope of the present invention. Other embodiments will be apparent to those skilled in the art from consideration of the specification and examples. It is intended that the specification, including the examples, be considered merely exemplary, without limiting the scope and spirit of the present invention.

[0124] An exemplary experimental procedure for producing 2-methylsulfonyl-4-trifluoromethylbenzoic acid is described below:

[0125] Example 1:

[0126] In a four-necked flask, concentrated sulfuric acid (49 g, 0.49 mol) was added to 2-methylthio-4-trifluoromethylbenzonitrile (106 g, 0.49 mol) in 330 g of chlorobenzene, and the mixture was heated to 60 °C. An aqueous solution of 30% hydrogen peroxide (138.9 g, 1.23 mol) was added dropwise to the mixture while maintaining the temperature below 80 °C over 3 h. The reaction mixture was heated at 70 °C to 80 °C for 8 h and cooled to 30 °C to 40 °C. The precipitated compound was filtered. The resulting filtrate was phase-separated, and the lower sulfuric acid phase (177.9 g) was extracted with chlorobenzene (54.6 g). The combined organic phase (321.6 g) was used directly for the next step, and the collected aqueous sulfuric acid solution (174.0 g) was used for acidification in the next step.

[0127] The organic phase (321.6 g) and the filter cake (167.0 g) were mixed with an aqueous solution of 48% potassium hydroxide (87.7 g, 0.75 mol) in a four-necked flask, and the mixture was heated to 90 °C to 95 °C. The mixture was stirred at this temperature for 5 h. Water (813.2 g) and the aqueous sulfuric acid phase from the previous step were added to the mixture and stirred at 90 °C to 100 °C for 1 h. The reaction mixture was cooled to 0 °C to 5 °C over 3 h and filtered to collect 2-methylsulfonyl-4-trifluoromethylbenzoic acid. The solid was rinsed with water (54.6 g) and cooled chlorobenzene (54.6 g). The filter cake was dried at 60 °C to 65 °C to obtain an off-white solid (118.4 g). The yield of 2-methylsulfonyl-4-trifluoromethylbenzoic acid was 89%.

[0128] Example 2:

[0129] In a four-necked flask, concentrated sulfuric acid (49 g, 0.49 mol) was added to 2-(methylthio)-4-(trifluoromethyl)benzonitrile (106 g, 0.49 mol) in 300 g of toluene, and the mixture was heated to 60 °C. An aqueous solution of 30% hydrogen peroxide (138.9 g, 1.23 mol) was added dropwise to the mixture while maintaining the temperature below 80 °C for 3 h. The reaction mixture was heated at 70 °C to 80 °C for 8 h and then cooled to 30 °C to 40 °C. The precipitated compound was filtered. The resulting filtrate was subjected to phase separation, and the lower sulfuric acid phase was extracted with toluene. The combined organic phase (about 320 g) was directly used for the next step, and the collected aqueous sulfuric acid solution (about 170 g) was used for acidification in the next step.

[0130] The organic phase (about 320 g) and the filter cake (164.0 g) were mixed with an aqueous solution of 18% potassium hydroxide (235 g, 0.75 mol) in a four-necked flask, and the mixture was heated to 90 °C to 95 °C. The mixture was stirred at this temperature for 10 h. Water (700 g) and the aqueous sulfuric acid phase from the previous step were added to the mixture and stirred at 90 °C to 95 °C for 1 h. The reaction mixture was cooled to 0 °C to 5 °C over 3 h and filtered to collect 2-(methylsulfonyl)-4-(trifluoromethyl)benzoic acid. The solid was rinsed with water (50 g) and cooled toluene (50 g). The filter cake was dried at 60 °C to 65 °C to obtain an off-white solid (113 g). The yield of 2-(methylsulfonyl)-4-(trifluoromethyl)benzoic acid was 85%.

Claims

1. A method for preparing a compound of formula (I): Wherein R1 represents C 1-6 alkyl, C 1-6 haloalkyl, phenyl or phenyl substituted by carboxylic acid; R2 represents hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 haloalkoxy, phenyl or phenyl substituted by halogen, carboxylic acid; The method comprises a) Reacting a compound of formula (II): Wherein R1 and R2 are as defined above; With an oxidizing agent in the presence of an aqueous acid in a suitable solvent system to form a compound of formula (III), and the reaction is carried out in the absence of a metal catalyst; Wherein R1 and R2 are as defined above; b) Reacting the compound of formula (III) with an alkali metal hydroxide; c) Mixing the reaction mixture from step (b) with a strong acid system to obtain the compound of formula (I).

2. The method according to claim 1, wherein, In step (c), the strong acid system comprises the aqueous acid from step (a).

3. The method according to any one of claims 1-2, wherein, The strong acid system comprises at least one acid stronger than the compound of formula (I).

4. The method according to claim 1, wherein, R1 is C 1-6 alkyl, and R2 is C 1-6 haloalkyl.

5. The method according to claim 4, wherein R1 is methyl and R2 is trifluoromethyl.

6. The method according to claim 1, wherein, The oxidizing agent is hydrogen peroxide.

7. The method according to claim 6, wherein, The hydrogen peroxide and the compound of formula (II) are present in a molar ratio of about 5:1 to 2:

1.

8. The method according to claim 6, wherein, The hydrogen peroxide is added to the reaction mixture in a dropwise manner over 2 to 8 hours.

9. The method according to claim 1, wherein The acid is selected from the group consisting of sulfuric acid, phosphoric acid, nitric acid, strong carboxylic acids and mixtures thereof.

10. The method according to claim 1, wherein, The acid and the compound of formula (II) are present in a molar ratio of about 10:1 to 0.8:

1.

11. The method according to claim 1, wherein, The solvent system includes an organic solvent and an aqueous solvent.

12. The method according to claim 11, wherein, The organic solvent is selected from chlorobenzene, toluene, xylene, dichlorobenzene or any other aromatic solvent inert to the reaction conditions and mixtures thereof.

13. The method according to claim 1, wherein The reaction of step (a) is carried out at a temperature of about 70 °C to 110 °C.

14. The method according to claim 1, wherein The reaction mixture of step (a) is cooled to a temperature of about 30 °C to 40 °C and filtered.

15. The method according to claim 14, wherein, The filtrate from step (a) contains an organic layer and an aqueous acidic layer.

16. The method according to claim 1, wherein, The alkali metal hydroxide is selected from the group consisting of sodium hydroxide, potassium hydroxide or calcium hydroxide.

17. The method according to claim 1, wherein, The alkali metal hydroxide and the compound of formula (II) are present in a molar ratio of about 5:1 to 1:

1.

18. The method according to claim 1, wherein, The concentration of the alkali metal hydroxide solution is about 15% to 50%.

19. The method according to claim 15, wherein, The organic layer, the filter cake from step (a) and the alkali metal hydroxide are heated at a temperature of about 90 °C to 100 °C.

20. The method according to claim 1, wherein, The reaction mixture from step (c) is cooled to a temperature of about 0 °C to 5 °C and filtered to obtain the compound of formula (I).

21. A method for preparing sulfentrazone, the method comprising preparing a compound of formula (I) as claimed in claim 1 and further converting it to sulfentrazone.

22. A method for preparing 2-methylsulfonyl-4-trifluoromethylbenzoic acid, the method comprising: a) Reacting 2-(methylthio)-4-(trifluoromethyl)benzonitrile with an oxidizing agent in the presence of an aqueous acid in a suitable solvent system, and the reaction is carried out in the absence of a metal catalyst; b) Reacting the product from step (a) with an alkali metal hydroxide and over-acidifying to obtain 2-methylsulfonyl-4-trifluoromethylbenzoic acid.

23. The method according to claim 22, wherein, The oxidation reagent is hydrogen peroxide, and the molar ratio of hydrogen peroxide to 2-(methylthio)-4-(trifluoromethyl)benzonitrile is from about 5:1 to 2:

1.

24. The method according to claim 22, wherein, The acid is sulfuric acid, phosphoric acid, nitric acid, a strong carboxylic acid, and mixtures thereof; and the molar ratio of the acid to 2-(methylthio)-4-(trifluoromethyl)benzonitrile is from about 10:1 to 0.8:

1.

25. The method according to claim 22, wherein The solvent includes an organic solvent and an aqueous solvent, and the organic solvent is selected from the group consisting of chlorobenzene, toluene, xylene, dichlorobenzene, or any other aromatic solvent inert to the reaction conditions and mixtures thereof.

26. The method according to claim 22, wherein, The alkali metal hydroxide is selected from sodium hydroxide, potassium hydroxide, or calcium hydroxide, and the molar ratio of the alkali metal hydroxide to 2-(methylthio)-4-(trifluoromethyl)benzonitrile is from about 5:1 to 1:

1.

27. The method according to claim 22, wherein, The concentration of the alkali metal hydroxide solution is from about 15% to 50%.

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