Method for producing monosulfoxide derivatives

Abstract

The present invention provides a method for producing a monosulfoxide derivative.

Description

[Technical field]

[0001] The present invention relates to a method for producing a monosulfoxide derivative. [Background technology]

[0002] Sulfoxide derivatives have been attracting attention in the field of agricultural chemicals and the like (Patent Document 1). Therefore, it is important that sulfoxide derivatives can be produced selectively and in high yield. As a method for producing sulfoxide derivatives, oxidation of sulfide derivatives is known. However, the conventional oxidation of sulfide derivatives has the following drawbacks or problems.

[0003] Examples 13 and 27 of Patent Document 1 disclose that sulfoxide derivatives can be produced by oxidation reaction with metachloroperbenzoic acid. However, considering the environmental aspect, the use of metachloroperbenzoic acid is not preferred for industrial production. The reasons are as follows. After the reaction, metachloroperbenzoic acid becomes metachlorobenzoic acid which becomes waste. As a result, the use of metachloroperbenzoic acid imposes a heavy burden on the environment. In addition, metachloroperbenzoic acid is expensive, so the method of using metachloroperbenzoic acid is not preferred industrially.

[0004] On the other hand, oxidation using hydrogen peroxide is an industrially preferred and useful method for the following reasons: Hydrogen peroxide is environmentally friendly because it becomes harmless water after the reaction, and furthermore, hydrogen peroxide is industrially inexpensive.

[0005] Patent Document 2 and Patent Document 3 disclose that sulfoxide derivatives can be produced by oxidation reaction with hydrogen peroxide using a catalyst that essentially requires a ligand. However, the ligand is difficult to obtain industrially, and must be produced in advance. Furthermore, the catalyst must be prepared from a metal compound and a ligand before the start of the reaction, and the use of the ligand is industrially undesirable from the viewpoint of the difficulty and / or cost in industrial production. In addition, a complicated operation was required to remove the ligand used. Furthermore, the method described in Patent Document 2 uses a benzoic acid derivative. From the same viewpoint as above, the use of a benzoic acid derivative is also industrially undesirable.

[0006] Furthermore, for example, it has been found that the method described in Patent Document 2 requires a complicated operation to remove the metal used as a catalyst. [Prior art documents] [Patent documents]

[0007] [Patent Document 1] International Publication No. 2013 / 157229 [Patent Document 2] International Publication No. 2017 / 150478 [Patent Document 3] US2011 / 0015405A1 (Special table 2012-532906) Summary of the Invention [Problem to be solved by the invention]

[0008] There is an urgent need for a process for the preparation of sulfoxide derivatives that can overcome one or more of the shortcomings or problems in the prior art discussed above.

[0009] Therefore, an object of the present invention is to provide a method for producing a sulfoxide derivative that is industrially favorable, economical, and environmentally friendly. In other words, it has been desired to provide a method that is inexpensive and reduces the environmental load.

[0010] For example, one of the specific objects of the present invention is to produce a sulfoxide derivative using hydrogen peroxide, which has attracted attention as a clean and excellent oxidizing agent, without using metachloroperbenzoic acid as an oxidizing agent.

[0011] Another specific object of the present invention is to provide a simple and inexpensive method for producing the compound without using ligands and benzoic acid derivatives, which also avoids the troublesome work of removing the ligands and benzoic acid. It is yet another specific object of the present invention to avoid the need for cumbersome procedures for removing the metals used as catalysts.

[0012] In addition, the following problem was found in the study of the oxidation reaction without using a ligand or the like. The sulfide derivative of the following formula (A) has a structural feature of having two sulfide sites that are oxidized in the oxidation reaction. It is necessary to selectively oxidize only one of the sulfide sites and not oxidize the other sulfide site, thereby selectively producing a monosulfoxide derivative. The details are as follows. In the oxidation reaction of the sulfide derivative of the following formula (A), due to two reaction sites, a desired compound and an undesired compound may be produced. The desired product is the monosulfoxide derivative of the following formula (B), while the disulfoxide derivative of the following formula (C) is unnecessary. The disulfoxide derivative of the formula (C), which is an unwanted by-product, reduces the yield of the desired monosulfoxide derivative of the formula (B). Furthermore, since the physical properties of both derivatives are similar, it is difficult to obtain a purified desired monosulfoxide derivative of the formula (B) by removing the by-product disulfoxide derivative of the formula (C) from the crude product after the oxidation reaction in industrial production. In other words, it is difficult to separate and purify the desired product with a high yield on an industrial scale. Therefore, it has been desired to selectively produce the desired monosulfoxide derivative of the formula (B) by avoiding non-selective oxidation (i.e., over-oxidation) to the disulfoxide derivative of the formula (C).

[0013] [ka]

[0014] In summary, a further specific object of the present invention is to provide a method for selectively producing only the desired monosulfoxide derivative in high yield from a sulfide derivative having the structural characteristic of having two sulfide sites to be oxidized. To achieve this object, it is necessary to provide a selective oxidation reaction that avoids over-oxidation. [Means for solving the problem]

[0015] In view of the above-mentioned circumstances, the present inventors have intensively studied a method for producing a sulfoxide derivative. As a result, the present inventors have unexpectedly found that the above-mentioned problems can be solved by providing the following method for producing a compound of formula (B). Based on this finding, the present inventors have completed the present invention. That is, the present invention is as follows.

[0016] [1] Formula (B):

[0017] [ka]

[0018] (In the formula, R 1 is a C1-C4 alkyl group, a C2-C4 alkenyl group, a C2-C4 alkynyl group, a C1-C4 haloalkyl group, a C2-C4 haloalkenyl group or a C2-C4 haloalkynyl group; R 2 and R 3 are each independently a hydrogen atom, a halogen atom, a C1-C4 alkyl group, a C2-C4 alkenyl group, a C2-C4 alkynyl group, a C1-C4 haloalkyl group, a C2-C4 haloalkenyl group, or a C2-C4 haloalkynyl group, a C1-C4 alkoxy group, or a C1-C4 haloalkoxy group; and n is 5 or 6, Formula (A):

[0019] [ka]

[0020] (In the formula, R 1 , R 2 , R 3 and n is as defined above. The method comprises the step of reacting a sulfide derivative of the formula (I) with hydrogen peroxide in the presence of a metal catalyst.

[0021] [2] R 1 is a C1-C4 haloalkyl group; R 2 and R 3 are each independently a halogen atom or a C1-C4 alkyl group; and The method of claim 1, wherein n is 5 or 6.

[0022] [3] R 1 is a trifluoromethyl group, R 2 is a fluorine atom, and R 3 is a chlorine atom, or R 2 and R 3 is a methyl group; and The method of claim 1, wherein n is 5 or 6.

[0023] [4] R 1 is a trifluoromethyl group, R 2 is a fluorine atom, R 3 is a chlorine atom; and The method according to [1], wherein n is 5.

[0024] [5] R 1 is a trifluoromethyl group, R2 and R 3 is a methyl group; and The method according to [1], wherein n is 6.

[0025] [6] The metal catalyst is one or more (preferably one or two, more preferably one) catalyst selected from the group consisting of vanadium catalysts, molybdenum catalysts, and titanium catalysts; The method according to any one of [1] to [5].

[0026] [7] The metal catalyst is a vanadium catalyst or a molybdenum catalyst. The method according to any one of [1] to [5].

[0027] [8] The metal catalyst is a vanadium catalyst. The method according to any one of [1] to [5].

[0028] [9] The metal catalyst is a molybdenum catalyst. The method according to any one of [1] to [5].

[0029]

[10] The metal catalyst is Vanadyl acetylacetonate, vanadium(III) acetylacetonate, vanadium(V) oxide, vanadium(V) oxytrichloride, Titanyl(IV) acetylacetonate, titanium trichloride, titanium tetrachloride, titanium(IV) tetraisopropoxide, Ammonium molybdate, sodium molybdate, potassium molybdate, molybdenum oxide, molybdenum chloride, molybdenum sulfide, phosphomolybdic acid, sodium phosphomolybdate, ammonium phosphomolybdate, silicomolybdic acid, and sodium silicomolybdate is one or more (preferably one or two, more preferably one) catalyst selected from the group consisting of The method according to any one of [1] to [5].

[0030]

[11] The metal catalyst is Vanadyl acetylacetonate, Vanadium(III) acetylacetonate, Titanyl(IV) acetylacetonate, and Ammonium Molybdate is one or more (preferably one or two, more preferably one) catalyst selected from the group consisting of The method according to any one of [1] to [5].

[0031]

[12] The metal catalyst is Vanadyl acetylacetonate, vanadium(III) acetylacetonate, vanadium(V) oxide, vanadium(V) oxytrichloride, Ammonium molybdate, sodium molybdate, potassium molybdate, molybdenum oxide, molybdenum chloride, molybdenum sulfide, phosphomolybdic acid, sodium phosphomolybdate, ammonium phosphomolybdate, silicomolybdic acid, and sodium silicomolybdate is one or more (preferably one or two, more preferably one) catalyst selected from the group consisting of The method according to any one of [1] to [5].

[0032]

[13] The metal catalyst is Vanadyl acetylacetonate, vanadium(III) acetylacetonate, and Ammonium Molybdate is one or more (preferably one or two, more preferably one) catalyst selected from the group consisting of The method according to any one of [1] to [5].

[0033]

[14] The metal catalyst is Vanadyl acetylacetonate, vanadium(III) acetylacetonate, vanadium(V) oxide, and vanadium(V) oxytrichloride is one or more (preferably one or two, more preferably one) catalyst selected from the group consisting of The method according to any one of [1] to [5].

[0034]

[15] The metal catalyst is Vanadyl acetylacetonate, and vanadium(III) acetylacetonate is one or more (preferably one or two, more preferably one) catalyst selected from the group consisting of The method according to any one of [1] to [5].

[0035]

[16] The metal catalyst is vanadyl acetylacetonate. The method according to any one of [1] to [5].

[0036]

[17] The metal catalyst is Ammonium molybdate, sodium molybdate, potassium molybdate, molybdenum oxide, molybdenum chloride, molybdenum sulfide, phosphomolybdic acid, sodium phosphomolybdate, ammonium phosphomolybdate, silicomolybdic acid, and sodium silicomolybdate is one or more (preferably one or two, more preferably one) catalyst selected from the group consisting of The method according to any one of [1] to [5].

[0037]

[18] The metal catalyst is ammonium molybdate. The method according to any one of [1] to [5].

[0038]

[19] The oxidation step is carried out in a solvent. The method according to any one of [1] to

[18] .

[0039]

[20] In the oxidation step, the concentration of the compound of formula (A) at the start of the reaction is 5 to 75% by weight. The method according to

[19] .

[0040]

[21] In the oxidation step, the concentration of the compound of formula (A) at the start of the reaction is 20 to 60% by weight. The method according to

[19] .

[0041]

[22] In the oxidation step, the concentration of the compound of formula (A) at the start of the reaction is 35 to 50% by weight. The method according to

[19] .

[0042]

[23] The solvent is a solvent in which the compound of formula (A) has a high solubility and the compound of formula (B) has a low solubility. The method according to any one of

[19] to

[22] .

[0043]

[24] The solvent is a solvent in which the solubility of the compound of formula (B) is 55% by weight or less in the range of 15 to 20°C. The method according to any one of

[19] to

[23] .

[0044]

[25] The solvent is a solvent in which the solubility of the compound of formula (B) is 40% by weight or less in the range of 15 to 20°C. The method according to any one of

[19] to

[23] .

[0045]

[26] The solvent is a solvent in which the solubility of the compound of formula (B) is 5 to 75% by weight in the range of 15 to 20°C. The method according to any one of

[19] to

[23] .

[0046]

[27] The solvent is a solvent in which the solubility of the compound of formula (B) is 20 to 55% by weight in the range of 15 to 20°C. The method according to any one of

[19] to

[23] .

[0047]

[28] The solvent is a solvent in which the solubility of the compound of formula (B) is 30 to 40% by weight in the range of 15 to 20°C. The method according to any one of

[19] to

[23] .

[0048]

[29] The solvent is a solvent in which the solubility of the compound of formula (A) is 10% by weight or more in the range of 15 to 20°C. The method according to any one of

[19] to

[28] .

[0049]

[30] The solvent is a solvent in which the solubility of the compound of formula (A) is 30% by weight or more in the range of 15 to 20°C. The method according to any one of

[19] to

[28] .

[31] The solvent is a solvent in which the solubility of the compound of formula (A) is 40% by weight or more in the range of 15 to 20°C. The method according to any one of

[19] to

[28] .

[0050]

[32] The solvent is an alcohol-containing solvent. The method according to any one of

[19] to

[31] .

[0051]

[33] The solvent is an alcohol or a mixture of alcohol and water (preferably a mixture of alcohol and water); The method according to any one of

[19] to

[31] .

[0052]

[34] The alcohol is a C1-C6 aliphatic alcohol (preferably a C1-C5 aliphatic alcohol); The method according to either

[32] or

[33] .

[0053]

[35] The alcohol is a C1-C4 aliphatic alcohol; The method according to either

[32] or

[33] .

[0054]

[36] The alcohol is methanol, ethanol, 2-propanol, t-butanol, or t-amyl alcohol (preferably, methanol, ethanol, 2-propanol, or t-butanol). The method according to either

[32] or

[33] .

[0055]

[37] The alcohol is methanol, 2-propanol, t-butanol or t-amyl alcohol. The method according to either

[32] or

[33] .

[0056]

[38] The alcohol is 2-propanol, t-butanol, or t-amyl alcohol (preferably 2-propanol or t-butanol). The method according to either

[32] or

[33] .

[0057]

[39] The alcohol is t-butanol or t-amyl alcohol. The method according to either

[32] or

[33] .

[0058]

[40] The alcohol is t-butanol. The method according to either

[32] or

[33] .

[0059]

[41] The solvent is a nitrile solvent or an alcohol solvent, or a mixture of a nitrile solvent or an alcohol solvent and water. The method according to any one of

[19] to

[31] .

[0060]

[42] The solvent is acetonitrile, methanol, 2-propanol, t-butanol, t-amyl alcohol, or a mixture thereof with water (preferably acetonitrile, 2-propanol, t-butanol, t-amyl alcohol, or a mixture thereof with water) (more preferably acetonitrile, 2-propanol, t-butanol, or a mixture thereof with water) (even more preferably a mixture of t-butanol and water, or a mixture of t-amyl alcohol and water) (particularly preferably a mixture of t-butanol and water). The method according to any one of

[19] to

[31] .

[0061]

[43] The solvent is acetonitrile or a mixture of acetonitrile and water (preferably a mixture of acetonitrile and water); The method according to any one of

[19] to

[31] .

[0062]

[44] The solvent is a halogenated solvent or a mixture of a halogenated solvent and water. The method according to any one of

[19] to

[31] .

[0063]

[45] The solvent is dichloromethane or a mixture of dichloromethane and water (preferably a mixture of dichloromethane and water); The method according to any one of

[19] to

[31] .

[0064]

[46] Adding an aqueous hydrogen peroxide solution to a solution containing a compound of formula (A) and a metal compound; The method according to any one of [1] to

[45] .

[0065]

[47] The oxidation step is carried out at -10°C to 60°C. The method according to any one of [1] to

[46] .

[0066]

[48] ​​The oxidation step is carried out at 10°C to 35°C. The method according to any one of [1] to

[46] .

[0067]

[49] The oxidation step is carried out at 25°C to 35°C. The method according to any one of [1] to

[46] .

[0068]

[50] The oxidation step is carried out at 15°C to 20°C; The method according to any one of [1] to

[46] .

[0069]

[51] The rate of adding hydrogen peroxide is 0.5 mol / hour or less (preferably 0.1 mol / hour to 0.5 mol / hour) per mol of the sulfide derivative of the formula (A). The method according to any one of [1] to

[50] .

[0070]

[52] The rate of adding hydrogen peroxide is 0.05 mol / hour to 0.5 mol / hour per mol of the sulfide derivative of the formula (A). The method according to any one of [1] to

[50] .

[0071]

[53] The oxidation step is carried out for 3 hours or more (or 6 hours or more). The method according to any one of [1] to

[52] .

[0072]

[54] The oxidation step is carried out for 48 hours or less (or 24 hours or less). The method according to any one of [1] to

[53] .

[0073]

[55] In the oxidation step, crystals of the compound of formula (B) are precipitated. The method according to any one of [1] to

[54] .

[0074]

[56] During or after the oxidation step, crystals of the compound of formula (B) are precipitated. The method according to any one of [1] to

[54] .

[0075]

[57] The method includes a step of precipitating crystals of the compound of formula (B) after the oxidation step. The method according to any one of [1] to

[54] .

[0076]

[58] The method includes a step in which a crystal of the compound of formula (B) is precipitated in the oxidation step, or a step in which a crystal of the compound of formula (B) is precipitated after the oxidation step, The method according to any one of [1] to

[54] .

[0077]

[59] The method includes recovering the crystals of the compound of formula (B) after the oxidation step. The method according to any one of [1] to

[58] .

[0078]

[60] The yield of the compound of formula (B) in the oxidation step is 85 to 100%. The method according to any one of [1] to

[59] .

[0079]

[61] The yield of the compound of formula (B) in the oxidation step is 90 to 100%. The method according to any one of [1] to

[59] .

[0080]

[62] No ligand is used in the oxidation step. The method according to any one of [1] to

[61] .

[0081]

[63] The method according to

[62] , wherein the ligand is (E)-2-{[(1-hydroxy-2-methylpropan-2-yl)imino]methyl}phenol and (S)-(2,4-di-tert-butyl-6-{(E)-[(1-hydroxy-3,3-dimethylbutan-2-yl)imino]methyl}phenol.

[0082]

[64] The ligand is represented by the formula (D):

[0083] [ka] (In the formula, R 4 and R 5 are each independently a hydrogen atom, a halogen atom, a C1-C6 alkyl group, a phenyl C1-C6 alkyl group, a C6-C10 aryl group, a cyano group, a nitro group, or a C1-C6 alkoxy group; R 6 is a C1-C4 alkyl group, a cyano group, a nitro group, a carboxy group, a C1-C4 alkoxycarbonyl group, a C1-C4 alkylcarbonyl group, a hydroxy C1-C4 alkyl group, a C1-C4 alkoxy C1-C4 alkyl group, an amino C1-C4 alkyl group, a cyano C1-C4 alkyl group, a nitro C1-C4 alkyl group, a carboxy C1-C4 alkyl group or a C1-C4 alkoxycarbonyl C1-C4 alkyl group, R 71 and R 72 are each independently a hydrogen atom, a C1-C6 alkyl group, a phenyl C1-C6 alkyl group, or a C6-C10 aryl group. The method according to

[62] , wherein the compound is

[0084]

[65] No carboxylic acid derivative is used in the above process. The method according to any one of [1] to

[64] .

[0085]

[66] No benzoic acid derivative is used in the above process. The method according to any one of [1] to

[65] .

[0086]

[67] The benzoic acid derivative, Formula (E):

[0087] [ka] (In the formula, A 1 , A 2 , A 3 , A 4 and A 5 are each independently a hydrogen atom, a halogen atom, a C1-C4 alkyl group, a C1-C4 alkoxy group, a (C1-C4 alkyl)amino group, a hydroxy group, or a nitro group; M is a hydrogen atom, an alkali metal atom, or an alkaline earth metal atom; n is 1 or 2. The method according to

[66] .

[0088]

[68] The benzoic acid derivative is sodium 2,6-dimethoxybenzoate. The method according to

[66] .

[0089]

[69] The amount of hydrogen peroxide used in the oxidation step is 1.0 to 1.5 moles per mole of the sulfide derivative of the formula (A). The method according to any one of [1] to

[68] .

[0090]

[70] The method according to any one of [1] to

[69] , wherein the amount of the metal catalyst used in the oxidation step is 0.4 to 3.0 mol % in terms of metal atoms relative to 1 mol of the sulfide derivative of the formula (A).

[0091]

[71] Formula (C): JPEG0007657783000006.jpg3185 (in the formula, R 1is a C1-C4 alkyl group, a C2-C4 alkenyl group, a C2-C4 alkynyl group, a C1-C4 haloalkyl group, a C2-C4 haloalkenyl group or a C2-C4 haloalkynyl group; R 2 and R 3 are each independently a hydrogen atom, a halogen atom, a C1-C4 alkyl group, a C2-C4 alkenyl group, a C2-C4 alkynyl group, a C1-C4 haloalkyl group, a C2-C4 haloalkenyl group, or a C2-C4 haloalkynyl group, a C1-C4 alkoxy group, or a C1-C4 haloalkoxy group; and n is 5 or 6. The method according to any one of [1] to

[70] , wherein the content of the disulfoxide derivative is 10% or less based on the weight of the compound of formula (B).

[0092]

[72] The method according to

[71] , The content of the disulfoxide derivative of formula (C) is 0% to 10%.

[0093]

[73] The method according to

[71] , The content of the disulfoxide derivative of formula (C) is 0% to 5%.

[0094]

[74] The method according to

[71] , The content of the disulfoxide derivative of formula (C) is 0% to 2%.

[0095]

[75] The method according to

[71] , The content of the disulfoxide derivative of formula (C) is 0% to 1%.

[0096]

[76] Formula (B): JPEG0007657783000007.jpg3182 (in the formula, R 1 is a C1-C4 alkyl group, a C2-C4 alkenyl group, a C2-C4 alkynyl group, a C1-C4 haloalkyl group, a C2-C4 haloalkenyl group or a C2-C4 haloalkynyl group; R2 and R 3 are each independently a hydrogen atom, a halogen atom, a C1-C4 alkyl group, a C2-C4 alkenyl group, a C2-C4 alkynyl group, a C1-C4 haloalkyl group, a C2-C4 haloalkenyl group, or a C2-C4 haloalkynyl group, a C1-C4 alkoxy group, or a C1-C4 haloalkoxy group; and n is 5 or 6. a monosulfoxide derivative of Formula (C): JPEG0007657783000008.jpg3185 (in the formula, R 1 is a C1-C4 alkyl group, a C2-C4 alkenyl group, a C2-C4 alkynyl group, a C1-C4 haloalkyl group, a C2-C4 haloalkenyl group or a C2-C4 haloalkynyl group; R 2 and R 3 are each independently a hydrogen atom, a halogen atom, a C1-C4 alkyl group, a C2-C4 alkenyl group, a C2-C4 alkynyl group, a C1-C4 haloalkyl group, a C2-C4 haloalkenyl group, or a C2-C4 haloalkynyl group, a C1-C4 alkoxy group, or a C1-C4 haloalkoxy group; and n is 5 or 6. The content of the disulfoxide derivative is 10% or less based on the weight of the compound of formula (B).

[0097]

[77] The monosulfoxide derivative according to

[76] , A monosulfoxide derivative having a content of the disulfoxide derivative of formula (C) of 0% to 10%.

[0098]

[78] The monosulfoxide derivative according to

[76] , A monosulfoxide derivative having a content of the disulfoxide derivative of formula (C) of 0% to 5%.

[0099]

[79] The monosulfoxide derivative according to

[76] , A monosulfoxide derivative having a content of the disulfoxide derivative of formula (C) of 0% to 2%.

[0100]

[80] The monosulfoxide derivative according to

[76] , A monosulfoxide derivative having a content of the disulfoxide derivative of formula (C) of 0% to 1%.

[0101]

[81] A solid compound of the formula (B): JPEG0007657783000009.jpg3182 (where R 1 , R 2 , R 3 and n are as defined in [1].) Monosulfoxide derivative of.

[0102]

[82] A crystalline solid having the following formula (B): JPEG0007657783000010.jpg3182 (where R 1 , R 2 , R 3 and n are as defined in [1].) Monosulfoxide derivative of.

[0103]

[83] A compound of the formula (B): JPEG0007657783000011.jpg3182 (where R 1 , R 2 , R 3 and n are as defined in [1].) Monosulfoxide derivative of.

[0104]

[84] A compound of the formula (B): having a melting point of 40°C to 50°C: JPEG0007657783000012.jpg3182 (where R 1 , R 2 , R 3 and n are as defined in [1].) Monosulfoxide derivative of.

[0105]

[85] A compound of formula (B) having a melting point of 46°C to 50°C: JPEG0007657783000013.jpg3182 (where R 1 , R 2 , R 3 and n are as defined in [1].) Monosulfoxide derivative of.

[0106]

[86] A compound of formula (B) having a melting point of 41°C to 45°C: JPEG0007657783000014.jpg3182 (where R 1 , R 2 , R 3 and n are as defined in [1].) Monosulfoxide derivative of.

[0107]

[87] The monosulfoxide derivative according to any one of

[76] to

[86] , R 1 is a C1-C4 haloalkyl group; R 2 and R 3 are each independently a halogen atom or a C1-C4 alkyl group; and Monosulfoxide derivatives, wherein n is 5 or 6.

[0108]

[88] The monosulfoxide derivative according to any one of

[76] to

[86] , R 1 is a trifluoromethyl group, R 2 is a fluorine atom and R 3 is a chlorine atom or R 2 and R 3 is a methyl group; and Monosulfoxide derivatives, wherein n is 5 or 6.

[0109]

[89] The monosulfoxide derivative according to any one of

[76] to

[86] , R 1 is a trifluoromethyl group, R 2 is a fluorine atom, R 3 is a chlorine atom; and The monosulfoxide derivative, wherein n is 5.

[0110]

[90] The monosulfoxide derivative according to any one of

[76] to

[86] , R 1 is a trifluoromethyl group, R 2 and R 3 is a methyl group; and The monosulfoxide derivative, wherein n is 6.

[91] The method according to any one of [1] to

[90] , wherein the compound of formula (B) is a crystal.

[92] Formula (B): JPEG0007657783000015.jpg3182 (in the formula, R 1 is a C1-C4 alkyl group, a C2-C4 alkenyl group, a C2-C4 alkynyl group, a C1-C4 haloalkyl group, a C2-C4 haloalkenyl group or a C2-C4 haloalkynyl group; R 2 and R 3 are each independently a hydrogen atom, a halogen atom, a C1-C4 alkyl group, a C2-C4 alkenyl group, a C2-C4 alkynyl group, a C1-C4 haloalkyl group, a C2-C4 haloalkenyl group, a C2-C4 haloalkynyl group, a C1-C4 alkoxy group, or a C1-C4 haloalkoxy group; and n is 5 or 6. A compound of the formula: Formula (C): JPEG0007657783000016.jpg3185 (in the formula, R 1 is a C1-C4 alkyl group, a C2-C4 alkenyl group, a C2-C4 alkynyl group, a C1-C4 haloalkyl group, a C2-C4 haloalkenyl group or a C2-C4 haloalkynyl group; R 2 and R 3are each independently a hydrogen atom, a halogen atom, a C1-C4 alkyl group, a C2-C4 alkenyl group, a C2-C4 alkynyl group, a C1-C4 haloalkyl group, a C2-C4 haloalkenyl group, a C2-C4 haloalkynyl group, a C1-C4 alkoxy group, or a C1-C4 haloalkoxy group; and n is 5 or 6. The content of the compound represented by formula (B) is 10% or less based on the weight of the compound represented by formula (B).

[93] A crystalline compound of formula (Ba) characterized in that the powder X-ray diffraction spectrum has characteristic peaks at diffraction angles 2θ=8.9°±0.2°, 10.3°±0.2°, 13.6°±0.2°, 17.8°±0.2°, 18.5°±0.2°, 20.5°±0.2°, 21.8°±0.2°, 22.3°±0.2°, 23.5°±0.2°, 27.2°±0.2°, 30.9°±0.2°, 33.8°±0.2°, and 37.3°±0.2°. JPEG0007657783000017.jpg38100 Effect of the Invention

[0111] The present invention provides a novel and industrially applicable method for producing the monosulfoxide derivative of the above formula (B), which is useful as an acaricide, etc. The present invention provides a method for producing a sulfoxide derivative, which can solve one or more of the above-mentioned shortcomings or problems in the prior art. Therefore, it is possible to provide a method that is inexpensive and reduces the environmental load.

[0112] For example, instead of using metachloroperbenzoic acid as an oxidizing agent, hydrogen peroxide, which has been attracting attention as a clean and excellent oxidizing agent, can be used to produce a sulfoxide derivative. In addition, a simple and inexpensive production method can be provided that does not use ligands and benzoic acid derivatives, and therefore, the troublesome work of removing the ligands and benzoic acid derivatives can be avoided. Furthermore, it is possible to avoid the need for a complicated operation for removing the metal used as the catalyst.

[0113] In addition, a method can be provided for selectively producing only the desired monosulfoxide derivative in high yield from a sulfide derivative having the structural feature of having two sulfide sites to be oxidized, i.e., a selective oxidation reaction can be provided that avoids over-oxidation.

[0114] Therefore, the process of the present invention is industrially favorable, economical and environmentally friendly. [Brief description of the drawings]

[0115] [Figure 1] This is a powder X-ray diffraction spectrum of the crystal of the compound of formula (Ba) obtained in Example 20. White crystals of the compound of formula (Ba) were obtained by the same manufacturing method as in Example 16. Here, the crystals obtained in the same manner as in Example 16 were used as seed crystals. The obtained crystals were dried in a vacuum. The melting point was 46°C to 50°C. The obtained crystals were subjected to powder X-ray diffraction measurement. The results of the powder X-ray diffraction measurement are shown in Figure 1. [Diagram 2] This is a powder X-ray diffraction spectrum of the crystal of the compound of formula (Ba) obtained in Example 21. White crystals of the compound of formula (Ba) were obtained by the same manufacturing method as in Example 16. Here, the crystals obtained in the same manner as in Example 16 were used as seed crystals. The obtained crystals were melted, dried under reduced pressure to remove moisture, and then cooled. The obtained crystals were pulverized in a mill. The melting point was 47°C to 48°C. The obtained crystals were subjected to powder X-ray diffraction measurement. The results of the powder X-ray diffraction measurement are shown in Figure 2. [Diagram 3] This is a powder X-ray diffraction spectrum of the crystals of the compound of formula (Ba) obtained in Example 22. White crystals of the compound of formula (Ba) were obtained by the same manufacturing method as in Example 1. The obtained crystals were subjected to recrystallization. Here, the recrystallization conditions were the same as the crystallization conditions in Example 1 (recrystallization from 2-propanol and water). The obtained crystals were filtered and dried. The melting point was 46°C to 50°C. The obtained crystals were subjected to powder X-ray diffraction measurement. The results of the powder X-ray diffraction measurement are shown in Figure 3. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0116] The present invention will be described in detail below.

[0117] The process according to the invention comprises the following oxidation steps:

[0118] [ka]

[0119] (In the formula, R 1 , R 2 , R 3 and n are as described in [1] above.) As shown by:

[0120] The terms and symbols used in this specification are explained below.

[0121] The halogen atom is a fluorine atom, a chlorine atom, a bromine atom or an iodine atom. From the viewpoints of the usefulness and economic efficiency of the product, preferred examples of the halogen atom are a fluorine atom and a chlorine atom.

[0122] Examples of the alkali metal atom include a lithium atom, a sodium atom, a potassium atom, a rubidium atom and a cesium atom, preferably a lithium atom, a sodium atom, a potassium atom and a cesium atom, more preferably a lithium atom, a sodium atom and a potassium atom.

[0123] Examples of alkaline earth metal atoms include magnesium atoms, calcium atoms, strontium atoms and barium atoms, preferably magnesium atoms, calcium atoms and barium atoms.

[0124] "Ca-Cb" means that the number of carbon atoms is a to b. For example, the "C1-C4" in "C1-C4 alkyl group" means that the alkyl group has 1 to 4 carbon atoms.

[0125] As used herein, general terms such as "alkyl" are intended to include both straight and branched chains, such as butyl and tert-butyl. However, for example, the specific term "butyl" refers to straight chain "normal butyl" and not branched chain "tert-butyl", and branched chain isomers such as "tert-butyl" are specifically referred to when intended. As another example, the specific term "propyl" refers to straight chain "normal propyl" and not branched chain "isopropyl", and branched chain isomers such as "isopropyl" are specifically referred to when intended.

[0126] The following abbreviations and prefixes may be used herein and have the following meanings: Me: Methyl Et: Ethyl Pr, n-Pr and Pr-n: Propyl (i.e. normal propyl) i-Pr and Pr-i: isopropyl Bu, n-Bu and Bu-n: Butyl (i.e., normal butyl) s-Bu and Bu-s: sec-butyl (i.e., secondary butyl) i-Bu and Bu-i: Isobutyl t-Bu and Bu-t: tert-butyl (i.e., tertiary butyl) Ph: Phenyl n-:Normal s- and sec-: secondary i- and iso-: iso t- and tert-: tertiary c- and cyc-: cyclo o-: Ortho m-:meta p-:para

[0127] A C1-C6 alkyl group means a straight or branched alkyl group having from 1 to 6 carbon atoms.

[0128] Examples of C1-C6 alkyl groups are methyl, ethyl, propyl, isopropyl, Butyl group, sec-butyl group, isobutyl group, tert-butyl group, These include, but are not limited to, pentyl, hexyl and the like.

[0129] A C1-C4 alkyl group means a straight or branched alkyl group having from 1 to 4 carbon atoms.

[0130] Examples of the C1-C4 alkyl group are suitable examples of the above C1-C4 alkyl groups.

[0131] The term "C2-C4 alkenyl group" refers to a straight-chain or branched-chain alkenyl group having 2 to 6 carbon atoms. Examples of C2-C4 alkenyl groups include, but are not limited to, vinyl groups (i.e., ethenyl groups), 1-propenyl groups, 2-propenyl groups, isopropenyl groups (i.e., 1-methylvinyl groups), 1-butenyl groups, 2-butenyl groups, 3-butenyl groups, 1-methyl-1-propenyl groups, 2-methyl-1-propenyl groups, 1,3-butadienyl groups, and the like.

[0132] The term "C2-C4 alkynyl group" refers to a straight or branched alkynyl group having 2 to 4 carbon atoms. Examples of C2-C4 alkynyl groups include, but are not limited to, ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, and 1-methyl-2-propynyl groups.

[0133] Haloalkyl groups refer to straight or branched chain alkyl groups substituted with one or more halogen atoms which may be the same or different.

[0134] A C1-C4 haloalkyl group means a linear or branched alkyl group having 1 to 4 carbon atoms, substituted with 1 to 9 identical or different halogen atoms, wherein the halogen atoms have the same meaning as defined above.

[0135] Examples of C1-C4 haloalkyl groups are: Fluoromethyl group, difluoromethyl group, trifluoromethyl group, chlorodifluoromethyl group, 2-fluoroethyl group, 2-chloroethyl group, 2-bromoethyl group, 2,2-difluoroethyl group, 2,2,2-trifluoroethyl group, pentafluoroethyl group, 3-fluoropropyl group, 3-chloropropyl group, 3-bromopropyl group, 2,2,3,3,3-pentafluoropropyl group, 2,2,2-trifluoro-1-trifluoromethylethyl group, heptafluoropropyl group, 1,2,2,2-tetrafluoro-1-trifluoromethylethyl group, Examples of such groups include, but are not limited to, a 4-fluorobutyl group, a 4-chlorobutyl group, a 4-bromobutyl group, and a 2,2,3,3,4,4,4-heptafluorobutyl group.

[0136] The term "C2-C4 haloalkenyl group" refers to a linear or branched alkenyl group having 2 to 4 carbon atoms substituted with 1 to 7 identical or different halogen atoms (wherein the halogen atoms have the same meaning as defined above). Examples of C2-C4 haloalkenyl groups include, but are not limited to, 1-fluorovinyl group, 1-chlorovinyl group, 2-fluorovinyl group, 2-chlorovinyl group, 2,2-difluorovinyl group, trifluorovinyl group, 2-fluoro-2-propenyl group, 2-chloro-2-propenyl group, 3-fluoro-2-propenyl group, 3-chloro-2-propenyl group, 3,3-difluoro-2-propenyl group, 3,3-dichloro-2-propenyl group, 2,3-difluoro-2-propenyl group, 2,3-dichloro-2-propenyl group, 2,3,3-trifluoro-2-propenyl group, 1-(chloromethyl)vinyl group, 1-(trifluoromethyl)vinyl group, 1-trifluoromethyl-2,2-difluorovinyl group, 4,4-difluoro-3-butenyl group, 3,4,4-trifluoro-3-butenyl group, and the like.

[0137] The term "C2-C4 haloalkynyl group" refers to a straight-chain or branched-chain alkynyl group having 2 to 4 carbon atoms substituted with 1 to 5 identical or different halogen atoms (wherein the halogen atoms have the same meaning as defined above). Examples of the C2-C4 haloalkynyl group include, but are not limited to, a 2-fluoroethynyl group, a 2-chloroethynyl group, a 3-fluoro-1-propynyl group, a 3-chloro-1-propynyl group, a 1-fluoro-2-propynyl group, a 1-chloro-2-propynyl group, a 3-fluoro-2-propynyl group, a 3-chloro-2-propynyl group, a 1,1-difluoro-2-propynyl group, a 4-fluoro-3-butynyl group, a 4-chloro-3-butynyl group, a 4,4-difluoro-2-butynyl group, a 4,4,4-trifluoro-2-butynyl group, and the like.

[0138] A C1-C4 alkoxy group means a (C1-C4 alkyl)-O- group (wherein the C1-C4 alkyl group portion has the same meaning as defined above).

[0139] Examples of C1-C4 alkoxy groups include, but are not limited to, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy, isobutoxy, tert-butoxy, and the like.

[0140] A C1-C4 haloalkoxy group means a (C1-C4 haloalkyl)-O- group (wherein the C1-C4 haloalkyl group portion has the same meaning as above).

[0141] Examples of C1-C4 haloalkoxy groups are Fluoromethoxy group, difluoromethoxy group, trifluoromethoxy group, chlorodifluoromethoxy group, 2-fluoroethoxy group, 2-chloroethoxy group, 2-bromoethoxy group, 2,2-difluoroethoxy group, 2,2,2-trifluoroethoxy group, pentafluoroethoxy group, 3-fluoropropoxy group, 3-chloropropoxy group, 3-bromopropoxy group, 2,2,3,3,3-pentafluoropropoxy group, 2,2,2-trifluoro-1-trifluoromethylethoxy group, heptafluoropropoxy group, 1,2,2,2-tetrafluoro-1-trifluoromethylethoxy group, Examples of such groups include, but are not limited to, 4-fluorobutoxy, 4-chlorobutoxy, 4-bromobutoxy, 2,2,3,3,4,4,4-heptafluorobutoxy, and the like.

[0142] The phenyl C1-C6 alkyl group means a C1-C6 alkyl group substituted by a phenyl group (wherein the C1-C6 alkyl group moiety has the same meaning as defined above).

[0143] Examples of phenyl C1-C6 alkyl groups include, but are not limited to, benzyl, 1-phenylethyl, 2-phenylethyl, 3-phenylpropyl, 4-phenylbutyl, 5-phenylpentyl, 6-phenylhexyl, and the like.

[0144] The term "C6-C10 aryl group" refers to an aromatic cyclic group in which all atoms constituting the ring are 6 to 10 carbon atoms.

[0145] Examples of C6-C10 aryl groups are phenyl, 1-naphthyl, and 2-naphthyl. The 1-naphthyl group is also called naphthalene-1-yl. The 2-naphthyl group is also called naphthalene-2-yl.

[0146] The C1-C4 alkoxycarbonyl group means a (C1-C4 alkyl)-OC(=O)- group (wherein the C1-C4 alkyl portion has the same meaning as defined above).

[0147] Examples of C1-C4 alkoxycarbonyl groups include, but are not limited to, methoxycarbonyl groups, ethoxycarbonyl groups, propoxycarbonyl groups, isopropoxycarbonyl groups, butoxycarbonyl groups, and the like.

[0148] The C1-C4 alkylcarbonyl group means a (C1-C4 alkyl)-C(=O)- group (wherein the C1-C4 alkyl group portion has the same meaning as defined above).

[0149] Examples of C1-C4 alkylcarbonyl groups include, but are not limited to, acetyl, propionyl, butyryl, isobutyryl, valeryl, and the like.

[0150] A hydroxy C1-C4 alkyl group means a C1-C4 alkyl group substituted by a hydroxy group (wherein the C1-C4 alkyl group has the same meaning as above).

[0151] Examples of hydroxy C1-C4 alkyl groups include, but are not limited to, hydroxymethyl groups, 1-hydroxyethyl groups, 2-hydroxyethyl groups, 1-hydroxypropyl groups, 2-hydroxypropyl groups, 1-hydroxybutyl groups, 2-hydroxybutyl groups, 3-hydroxybutyl groups, and the like.

[0152] A C1-C4 alkoxy C1-C4 alkyl group means a C1-C4 alkyl group substituted with a C1-C4 alkoxy group (wherein the C1-C4 alkoxy group and the C1-C4 alkyl group have the same meanings as above).

[0153] Examples of C1-C4 alkoxy C1-C4 alkyl groups are: Methoxymethyl group, ethoxymethyl group, propoxymethyl group, isopropoxymethyl group, 1-methoxyethyl group, 2-methoxyethyl group, 1-ethoxyethyl group, 2-ethoxyethyl group, 1-propoxyethyl group, 2-propoxyethyl group, 1-isopropoxyethyl group, 2-isopropoxyethyl group, 1-methoxypropyl group, 2-methoxypropyl group, 3-methoxypropyl group, Examples of methoxybutyl groups include, but are not limited to, 1-methoxybutyl, 2-methoxybutyl, 3-methoxybutyl, and 4-methoxybutyl groups.

[0154] An amino C1-C4 alkyl group means a C1-C4 alkyl group substituted by an amino group (wherein the C1-C4 alkyl group has the same meaning as above).

[0155] Examples of amino C1-C4 alkyl groups include, but are not limited to, aminomethyl, 1-aminoethyl, 2-aminoethyl, 1-aminopropyl, 2-aminopropyl, 1-aminobutyl, 2-aminobutyl, 3-aminobutyl, and the like.

[0156] A cyano C1-C4 alkyl group means a C1-C4 alkyl group substituted by a cyano group (wherein the C1-C4 alkyl group has the same meaning as above).

[0157] Examples of cyano C1-C4 alkyl groups include, but are not limited to, cyanomethyl, 1-cyanoethyl, 2-cyanoethyl, 1-cyanopropyl, 2-cyanopropyl, 1-cyanobutyl, 2-cyanobutyl, 3-cyanobutyl, and the like.

[0158] The nitro C1-C4 alkyl group means a C1-C4 alkyl group substituted by a nitro group (wherein the C1-C4 alkyl group has the same meaning as above).

[0159] Examples of nitro C1-C4 alkyl groups include, but are not limited to, a nitromethyl group, a 1-nitroethyl group, a 2-nitroethyl group, a 1-nitropropyl group, a 2-nitropropyl group, a 1-nitrobutyl group, a 2-nitrobutyl group, a 3-nitrobutyl group, and the like.

[0160] A carboxy C1-C4 alkyl group means a C1-C4 alkyl group substituted with a carboxy group (wherein the C1-C4 alkyl group has the same meaning as above).

[0161] Examples of carboxy C1-C4 alkyl groups include, but are not limited to, a carboxymethyl group, a 1-carboxyethyl group, a 2-carboxyethyl group, a 1-carboxypropyl group, a 2-carboxypropyl group, a 1-carboxybutyl group, a 2-carboxybutyl group, a 3-carboxybutyl group, and the like.

[0162] A C1-C4 alkoxycarbonyl C1-C4 alkyl group means a C1-C4 alkyl group substituted with a C1-C4 alkoxycarbonyl group (wherein the C1-C4 alkoxycarbonyl group and the C1-C4 alkyl group have the same meanings as above).

[0163] Examples of C1-C4 alkoxycarbonyl C1-C4 alkyl groups are: Methoxycarbonylmethyl group, ethoxycarbonylmethyl group, propoxycarbonylmethyl group, isopropoxycarbonylmethyl group, 1-methoxycarbonylethyl group, 2-methoxycarbonylethyl group, 1-ethoxycarbonylethyl group, 2-ethoxycarbonylethyl group, 1-propoxycarbonylethyl group, 2-propoxycarbonylethyl group, 1-isopropoxycarbonylethyl group, 2-isopropoxycarbonylethyl group, 1-methoxycarbonylpropyl group, 2-methoxycarbonylpropyl group, 3-methoxycarbonylpropyl group, Examples of such methoxycarbonylbutyl groups include, but are not limited to, a 1-methoxycarbonylbutyl group, a 2-methoxycarbonylbutyl group, a 3-methoxycarbonylbutyl group, a 4-methoxycarbonylbutyl group, and the like.

[0164] The term "(C1-C4 alkyl)amino group" means a (C1-C4 alkyl)-NH- group (wherein the C1-C4 alkyl group moiety has the same meaning as defined above).

[0165] Examples of (C1-C4 alkyl)amino groups include, but are not limited to, methylamino groups, ethylamino groups, propylamino groups, isopropylamino groups, butylamino groups, and the like.

[0166] Definitions and examples of functional groups other than those mentioned above can be understood by those skilled in the art in the same manner as the functional groups mentioned above.

[0167] In this specification, a compound having isomers includes all isomers and any mixtures thereof in any ratio. For example, xylene includes o-xylene, m-xylene, p-xylene, and any mixtures thereof in any ratio. For example, dichlorobenzene includes o-dichlorobenzene, m-dichlorobenzene, p-dichlorobenzene, and any mixtures thereof in any ratio.

[0168] As used herein, the open-ended term "comprise(s) / comprising" may be optionally replaced with the exclusive phrase "consist(s) of / consisting of," respectively. In the present specification, the term "recover / recovery" can be arbitrarily replaced with "separate / separate", respectively. In the present specification, the sulfide derivative of formula (A) is synonymous with the compound of formula (A), the monosulfoxide derivative of formula (B) is synonymous with the compound of formula (B), and the disulfoxide derivative of formula (C) is synonymous with the compound of formula (C).

[0169] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood to one of ordinary skill in the art to which this disclosure belongs.

[0170] Unless otherwise indicated, numbers expressing quantities, sizes, concentrations, reaction conditions, and the like used herein are understood to be modified by the term "about." In some aspects, the disclosed numerical values ​​are interpreted based on the number of reported significant digits and by applying ordinary rounding techniques. In some aspects, the disclosed numerical values ​​are interpreted to include errors necessarily resulting from the standard deviation found in their respective testing measurement methods.

[0171] (Starting compound: sulfide derivative of formula (A)) The preparation of the sulfide derivatives of formula (A) is described, for example, in WO 2013 / 157229 or can be carried out in a similar manner.

[0172] [ka]

[0173] The preparation of the compound (Aa), a specific example of the sulfide derivative of formula (A), is as shown in the following scheme.

[0174] [ka]

[0175] From the viewpoint of the usefulness and economic efficiency of the product, R 1 , R 2 , R 3 and preferred combinations of n are: R 1 is a C1-C4 alkyl group, a C2-C4 alkenyl group, a C2-C4 alkynyl group, a C1-C4 haloalkyl group, a C2-C4 haloalkenyl group, or a C2-C4 haloalkynyl group; R 2 and R 3 are each independently a halogen atom or a C1-C4 alkyl group; and n is 5 or 6.

[0176] From the same viewpoint as above, in formula (A), R 1 , R 2 , R 3 and more preferred combinations of n are: R 1 is a C1-C4 haloalkyl group; R 2 and R 3 are each independently a halogen atom or a C1-C4 alkyl group; and n is 5 or 6.

[0177] From the same viewpoint as above, in formula (A), R 1 , R 2 , R 3 and further preferred combinations of n are: R 1 is a trifluoromethyl group; R 2 is a fluorine atom; R 3 is a chlorine atom, or R 2 and R 3 is a methyl group; and n is 5 or 6.

[0178] In one embodiment, from the same viewpoint as above, in formula (A), R 1 , R 2 , R 3 and more preferred specific combinations of n are: R 1 is a trifluoromethyl group; R 2 is a fluorine atom; R 3 is a chlorine atom; and n is 5.

[0179] In another aspect, from the same viewpoint as above, in formula (A), R 1 , R 2 , R 3 and more preferred specific combinations of n are: R 1 is a trifluoromethyl group; R 2 and R 3 is a methyl group; and n is 6.

[0180] From the same viewpoint as above, in formula (A), R 1 , R 2 and R 3 Particularly preferred specific combinations are: R 1 is a trifluoromethyl group; R 2 is a fluorine atom; R 3 is a chlorine atom; and n is 5.

[0181] (Target compound: monosulfoxide derivative of formula (B)) From the same viewpoint as above, in formula (B), R 1 , R 2 , R 3 Preferred combinations, more preferred combinations, further preferred combinations, and particularly preferred combinations of and n are the same as those in formula (A) above.

[0182] A particularly preferred specific example of the compound of formula (B) is the compound of formula (Ba) below.

[0183] [ka]

[0184] As described above, in the method for producing a monosulfoxide derivative of formula (B) from a compound of formula (A), it is desired that the oxidation reaction proceeds sufficiently and the proportion of the disulfoxide derivative of formula (C) in the product is sufficiently low. The content of the compound of formula (C) in the reaction mixture after the oxidation reaction can be, for example, 10% or less (0% to 10%), preferably 0% to 7%, more preferably 0% to 5%, even more preferably 0% to 3%, even more preferably 0% to 2%, and particularly preferably 0% to 1%, based on the weight of the compound of formula (B).

[0185] (Oxidizing agent; hydrogen peroxide) The oxidizing agent used in the present invention may be any oxidizing agent as long as the reaction proceeds. An oxidizing agent capable of oxidizing a corresponding raw material compound (sulfide derivative) to a target compound (monosulfoxide derivative) may be used. Examples of the oxidizing agent used in the present invention include, but are not limited to, inorganic peroxides (e.g., hydrogen peroxide, urea-hydrogen peroxide adduct, etc.). From the viewpoints of safety, reactivity, selectivity, economic efficiency, etc., the preferred oxidizing agent is hydrogen peroxide. The oxidizing agents may be used alone or in combination of two or more kinds in any ratio.

[0186] In the present invention, an oxidizing agent is used. The form of the oxidizing agent may be any form as long as the reaction proceeds. The form of the oxidizing agent can be appropriately selected by a person skilled in the art. When hydrogen peroxide is used as the oxidizing agent, the form of hydrogen peroxide may be any form as long as the reaction proceeds. In consideration of safety, hazards, economic efficiency, etc., examples of preferred forms of hydrogen peroxide include a 5 to 60 wt% aqueous hydrogen peroxide solution, preferably a 5 to 40 wt% aqueous hydrogen peroxide solution, more preferably a 10 to 35 wt% aqueous hydrogen peroxide solution, and even more preferably a 25 to 35 wt% aqueous hydrogen peroxide solution. In addition, for example, in the present specification, "a 30% aqueous hydrogen peroxide solution" is also referred to as "30% hydrogen peroxide".

[0187] (Amount of oxidizing agent used) The amount of oxidizing agent (preferably hydrogen peroxide) used in the method of the present invention may be any amount as long as the reaction proceeds.

[0188] From the viewpoint of improving the yield and economic efficiency, the lower limit of the amount of the oxidizing agent (preferably hydrogen peroxide) used in the present invention can be, for example, 0.9 mol or more, preferably 1.0 mol or more, per 1 mol of the sulfide derivative of formula (A) (raw material compound).

[0189] From the viewpoints of safety, suppression of by-products, economic efficiency, and the like, the upper limit of the amount of the oxidizing agent (preferably hydrogen peroxide) used in the present invention can be, for example, 2.0 mol or less, preferably 1.7 mol or less, and more preferably 1.5 mol or less, per 1 mol of the sulfide derivative of Formula (A) (raw material compound).

[0190] Further, the amount of the oxidizing agent (preferably hydrogen peroxide) used in the present invention can be an appropriate and arbitrary combination of the above lower and upper limits. Therefore, from the viewpoints of safety, improvement of yield, suppression of by-products, and economic efficiency, the amount of the oxidizing agent (preferably hydrogen peroxide) used in the present invention can be, for example, 0.9 to 2.0 mol, preferably 1.0 to 2.0 mol, more preferably 1.0 to 1.7 mol, further preferably 1.0 to 1.5 mol, and particularly preferably 1.0 to 1.2 mol per mol of the sulfide derivative (raw material compound) of formula (A). However, the amount of the oxidizing agent (preferably hydrogen peroxide) used in the present invention can be appropriately adjusted by those skilled in the art depending on the purpose and situation.

[0191] (Metal Catalyst) The metal catalyst in the present invention will be described. The metal catalyst used in the present invention may be any metal catalyst as long as the reaction proceeds. The metal catalyst used in the present invention is a known compound or a compound that can be produced from a known compound by a known method.

[0192] Metal catalysts include, but are not limited to, metal acetylacetonates, metal oxyacetylacetonates, metal halides, metal oxyhalides, metal oxides, metal alkoxides, and the like.

[0193] The metal of the metal catalyst is preferably a transition metal.

[0194] Examples of metal catalysts include, but are not limited to, iron catalysts, vanadium catalysts, titanium catalysts, manganese catalysts, copper catalysts, molybdenum catalysts, zirconium catalysts, tungsten catalysts, niobium catalysts, tantalum catalysts, thallium catalysts, and the like.

[0195] From the viewpoints of yield, suppression of by-products, economic efficiency, and the like, the metal catalyst is preferably one or more types (preferably one or two types, more preferably one type) selected from the group consisting of vanadium catalysts, molybdenum catalysts, and titanium catalysts, more preferably a vanadium catalyst or a molybdenum catalyst, and even more preferably a vanadium catalyst.

[0196] Examples of iron catalysts include, but are not limited to, iron(III) acetylacetonate, iron(III) chloride, iron(III) bromide, iron(III) methoxide, iron(III) ethoxide, iron(III) propoxide, iron(III) isopropoxide, iron(III) nitrate, and the like, and mixtures thereof. "Iron(III) acetylacetonate" is also defined as "Fe(acac) 3 " or "tris(2,4-pentanedionato)iron(III)".

[0197] In the method described in WO2017 / 150478 (Patent Document 2), the reaction mixture was black and dirty due to the iron catalyst used. Furthermore, several washings with dilute sulfuric acid were required to remove the iron catalyst.

[0198] Examples of vanadium catalysts include, but are not limited to, vanadyl acetylacetonate, vanadium(III) acetylacetonate, vanadium(V) oxytrichloride, vanadium(V) oxide, vanadium(V) oxytriethoxide, triisopropoxyvanadium(V) oxide, and the like, and mixtures thereof. "Vanadyl acetylacetonate" is defined as "VO(acac) 2 "Vanadium(IV) oxide" is also called "bis(2,4-pentanedionato)vanadium(IV) oxide" or "vanadium(IV) oxyacetylacetonate". "Triisopropoxyvanadium(V) oxide" is also called "VO(OiPr) 3" or "triisopropoxyoxovanadium(V)". From the same viewpoint as above, preferred examples of the vanadium catalyst include vanadyl acetylacetonate, vanadium(III) acetylacetonate, vanadium(V) oxytrichloride, and vanadium(V) oxide. More preferred examples of the vanadium catalyst include vanadyl acetylacetonate, vanadium(III) acetylacetonate, and vanadium(V) oxide. Further preferred examples of the vanadium catalyst include vanadyl acetylacetonate and vanadium(III) acetylacetonate. A particularly preferred example of the vanadium catalyst is vanadyl acetylacetonate.

[0199] Examples of titanium catalysts include, but are not limited to, titanium tetrachloride, titanium trichloride, titanium(IV) methoxide, titanium(IV) ethoxide, titanium(IV) propoxide, titanium(IV) isopropoxide, titanium(IV) tert-butoxide, titanyl(IV) acetylacetonate, and the like, and mixtures thereof. "Titanyl(IV) acetylacetonate" is defined as "TiO(acac) 2 ", "bis(2,4-pentanedionato)titanium(IV) oxide" or "titanium(IV) oxyacetylacetonate". From the same viewpoint as above, preferred examples of the titanium catalyst include titanium tetrachloride, titanium trichloride, titanium(IV) tetraisopropoxide and titanyl(IV) acetylacetonate. More preferred examples of the titanium catalyst include titanium tetrachloride, titanium trichloride and titanyl(IV) acetylacetonate. A particularly preferred example of the titanium catalyst is titanyl(IV) acetylacetonate.

[0200] Examples of manganese catalysts include, but are not limited to, potassium permanganate, manganese(III) acetylacetonate, manganese(II) chloride, manganese(II) oxide, and the like, and mixtures thereof. "Manganese(III) acetylacetonate" is also referred to as "Mn(acac) 3 " It is also called.

[0201] Examples of copper catalysts include, but are not limited to, copper(II) acetylacetonate, copper(I) chloride, copper(II) chloride, copper(I) acetate, copper(II) acetate, copper(I) bromide, copper(I) iodide, and the like, and mixtures thereof. "Copper(II) acetylacetonate" is also referred to as "Cu(acac) 2 " It is also called.

[0202] Examples of molybdenum catalysts include, but are not limited to, molybdenum acetylacetonate, molybdic acid, sodium molybdate (including sodium molybdate dihydrate), potassium molybdate, ammonium molybdate (including ammonium molybdate tetrahydrate), molybdenum oxide (e.g., molybdenum(VI) oxide), molybdenum chloride (e.g., molybdenum(V) chloride), molybdenum sulfide (e.g., molybdenum(IV) sulfide), phosphomolybdic acid, sodium phosphomolybdate, ammonium phosphomolybdate, silicic acid, sodium silicic molybdate, and the like, and mixtures thereof. "Molybdenum acetylacetonate" refers to "MoO 2 (acac) 2 ", "bis(2,4-pentanedionato)molybdenum(VI)dioxide" or "molybdenum(IV)dioxyacetylacetonate". From the same viewpoint as above, preferred examples of the molybdenum catalyst include ammonium molybdate, sodium molybdate, potassium molybdate, molybdenum oxide, molybdenum chloride, molybdenum sulfide, phosphomolybdic acid, sodium phosphomolybdate, ammonium phosphomolybdate, silicomolybdic acid and sodium silicomolybdate. More preferred examples of the molybdenum catalyst include ammonium molybdate, sodium molybdate, potassium molybdate and molybdenum oxide. Further preferred examples of the molybdenum catalyst include ammonium molybdate, sodium molybdate and potassium molybdate. A particularly preferred example of the molybdenum catalyst is ammonium molybdate (e.g., ammonium molybdate tetrahydrate).

[0203] Among molybdenum compounds, ammonium molybdate is a catalyst used in the Trost oxidation. As described in Journal of the American Chemical Society 2009, 131, 47, 17087-17089, the Trost oxidation is usually used to oxidize sulfide compounds to sulfone compounds. However, surprisingly, in this reaction, the reaction is completed with the monosulfoxide compound, and over-oxidation to the compound of formula (C) is also suppressed.

[0204] Examples of zirconium catalysts include zirconium(IV) acetylacetonate, zirconium tetrachloride, zirconium oxychloride (e.g., zirconium(IV) oxychloride octahydrate (ZrCl 2 O·8H 2 "Zirconium(IV) acetylacetonate" includes, but is not limited to, "Zr(acac) 4 " or "tetrakis(2,4-pentanedionato)zirconium(IV)".

[0205] Examples of tungsten catalysts include, but are not limited to, tungstic acid, sodium tungstate (including sodium tungstate dihydrate and sodium tungstate decahydrate), potassium tungstate, calcium tungstate, ammonium tungstate (including ammonium paratungstate pentahydrate), tungsten(VI) oxide (also known as tungsten trioxide), tungsten(VI) chloride (also known as tungsten hexachloride), tungsten(V) bromide, tungsten(IV) sulfide (also known as tungsten disulfide), phosphotungstic acid, sodium phosphotungstate, ammonium phosphotungstate, silicotungstic acid, sodium silicotungstate, and the like, and mixtures thereof.

[0206] Examples of niobium catalysts include, but are not limited to, niobium carbide, niobium(V) chloride, niobium(V) pentaethoxide, and the like, and mixtures thereof.

[0207] Examples of tantalum catalysts are tantalum carbide (TaC), tantalum(V) chloride (TaCl 5 ), Tantalum(V) pentaethoxide (Ta(OEt) 5 ) and the like and mixtures thereof.

[0208] Examples of thallium catalysts include, but are not limited to, thallium (III) nitrate, thallium (III) acetate, thallium (III) trifluoroacetate, and the like, and mixtures thereof.

[0209] The metal compounds in the present invention may be used alone or in combination of two or more kinds in any ratio. The form of the metal catalyst in the present invention may be any form as long as the reaction proceeds. The form of the metal catalyst in the present invention may be appropriately selected by those skilled in the art.

[0210] (Amount of metal catalyst used) The amount of the metal catalyst used in the method of the present invention may be any amount as long as the reaction proceeds. In one embodiment, from the viewpoints of improving the yield, reducing the environmental load, and economic efficiency, the amount of the metal catalyst used in the present invention may be, for example, 0.1 to 20.0 mol%, preferably 0.1 to 10.0 mol%, more preferably 0.1 to 5.0 mol%, even more preferably 0.1 to 3.0 mol%, even more preferably 0.1 to 2.0 mol%, and even more preferably 0.1 to 1.0 mol% relative to 1 mol of the sulfide derivative of formula (A) (raw material compound). Further, in another embodiment, from the same viewpoint as above, for example, the amount of the metal compound used in the present invention may be, as metal atoms, preferably 0.3 to 6.0 mol%, more preferably 0.3 to 5.0 mol%, even more preferably 0.4 to 5.0 mol%, even more preferably 0.4 to 4.0 mol%, even more preferably 0.4 to 3.0 mol%, and particularly preferably 0.5 to 2.0 mol% relative to 1 mol of the sulfide derivative (raw material compound) of formula (A). However, the amount of the metal catalyst used in the present invention may be appropriately adjusted by those skilled in the art depending on the purpose and circumstances.

[0211] (ligand) The following describes ligands that may not be used in the present invention. The reaction of the present invention proceeds sufficiently even without the use of ligands. Therefore, from the viewpoint of economic efficiency, etc., it is preferable not to use ligands in the present invention.

[0212] Examples of ligands not used in the present invention include those of formula (D):

[0213] [ka]

[0214] (In the formula, R 4 , R 5 , R 6 , R 71 and R 72 is as follows: Compounds of the formula:

[0215] In formula (D), R 4 and R 5 are each independently a hydrogen atom, a halogen atom, a C1-C6 alkyl group, a phenyl C1-C6 alkyl group, a C6-C10 aryl group, a cyano group, a nitro group, or a C1-C6 alkoxy group.

[0216] In formula (D), R 6 is a C1-C4 alkyl group, a cyano group, a nitro group, a carboxy group, a C1-C4 alkoxycarbonyl group, a C1-C4 alkylcarbonyl group, a hydroxy C1-C4 alkyl group, a C1-C4 alkoxy C1-C4 alkyl group, an amino C1-C4 alkyl group, a cyano C1-C4 alkyl group, a nitro C1-C4 alkyl group, a carboxy C1-C4 alkyl group or a C1-C4 alkoxycarbonyl C1-C4 alkyl group.

[0217] In formula (D), R 71 and R 72 are each independently a hydrogen atom, a C1-C6 alkyl group, a phenyl C1-C6 alkyl group, or a C6-C10 aryl group.

[0218] Specific examples of ligands not used in the present invention are shown below.

[0219] For example, 2,4-di-t-butyl-6-{(E)-[(1-hydroxy-3,3-dimethylbutan-2-yl)imino]methyl}phenol described in WO2011 / 006646 (Patent Document 3) and compounds (3-1) to (3-13) described in WO2017 / 150478 (Patent Document 2), i.e., (E)-2-{[(1-hydroxy-3-methylbutan-2-yl)imino]methyl}phenol, (E)-2-{[(1-hydroxybutan-2-yl)imino]methyl}phenol, (E)-2-{[(1-hydroxypropan-2-yl)imino]methyl}phenol, (E)-2-{[(1-hydroxy-2-methylpropan-2-yl)imino]methyl}phenol, (E)-2-{[(2-hydroxyethyl)imino]methyl}phenol, (E)-2-{[(1-hydroxy-2-methylpropan-2-yl)imino]methyl}-4-methylphenol, (E)-2-{[(1-hydroxy-2-methylpropan-2-yl)imino]methyl}-4-methoxyphenol, (E)-4-fluoro-2-{[( 1-hydroxy-2-methylpropan-2-yl)imino]methyl}phenol, (E)-4-chloro-2-{[(1-hydroxy-2-methylpropan-2-yl)imino]methyl}phenol, (E)-4-bromo-2-{[(1-hydroxy-2-methylpropan-2-yl)imino]methyl}phenol, (E)-2-{[(1-hydroxy-2-methylpropan-2-yl)imino]methyl}-4-iodophenol, (E)-2-{[(2-hydroxy-1-phenylethyl)imino]methyl}phenol, (E)-4-chloro-2-{[(1-hydroxy-3-methylbutan-2-yl)imino]methyl}phenol, (E)-4-chloro-2-{[(2-hydroxyethyl)imino]methyl}phenol, Compounds 1a to 1d, namely, compounds 1a to 1d described in J. Legros et al., Chemical European Journal, 2005, 11, 1086-1092, Examples of such phenols include, but are not limited to, (E)-2-{[(1-hydroxy-3,3-dimethylbutanon-2-yl)imino]methyl}-4,6-diiodophenol, (E)-2-{[(1-hydroxy-3,3-dimethylbutanon-2-yl)imino]methyl}-4,6-dibromophenol, (E)-2-{[(1-hydroxy-3,3-dimethylbutanon-2-yl)imino]methyl}phenol, and (E)-2-{[(1-hydroxy-3-methylbutan-2-yl)imino]methyl}-4,6-diiodophenol.

[0220] (benzoic acid derivative) Benzoic acid derivatives that may not be used in the present invention will be described. The reaction of the present invention proceeds sufficiently even without using carboxylic acid derivatives such as benzoic acid derivatives. Therefore, from the viewpoint of economic efficiency, etc., it is preferable not to use carboxylic acid derivatives such as benzoic acid derivatives in the present invention.

[0221] An example of a benzoic acid derivative not used in the present invention is a compound represented by the formula (E):

[0222] [ka]

[0223] (In the formula, A 1 , A 2 , A 3 , A 4 , A 5 , M and n are as follows: Compounds of the formula:

[0224] In formula (E), A 1 is a hydrogen atom, a halogen atom, a C1-C4 alkyl group, a C1-C4 alkoxy group, a (C1-C4 alkyl)amino group, a hydroxy group, or a nitro group; A 2 is a hydrogen atom, a halogen atom, a C1-C4 alkyl group, a C1-C4 alkoxy group, a (C1-C4 alkyl)amino group, a hydroxy group, or a nitro group; A 3 is a hydrogen atom, a halogen atom, a C1-C4 alkyl group, a C1-C4 alkoxy group, a (C1-C4 alkyl)amino group, a hydroxy group, or a nitro group; A 4 is a hydrogen atom, a halogen atom, a C1-C4 alkyl group, a C1-C4 alkoxy group, a (C1-C4 alkyl)amino group, a hydroxy group, or a nitro group; A 5is a hydrogen atom, a halogen atom, a C1-C4 alkyl group, a C1-C4 alkoxy group, a (C1-C4 alkyl)amino group, a hydroxy group, or a nitro group.

[0225] In formula (E), M is a hydrogen atom, an alkali metal atom or an alkaline earth metal atom.

[0226] Specific examples of M include, but are not limited to, a hydrogen atom, a lithium atom, a sodium atom, a potassium atom, a cesium atom, a magnesium atom, a calcium atom, and a barium atom.

[0227] In formula (E), n is 1 or 2. More specifically, n may be 1 or 2, so long as it is chemically permissible. For example, when M is a hydrogen atom or an alkali metal atom, n is 1. As another example, when M is an alkaline earth metal atom, n is 2.

[0228] Specific examples of carboxylic acid derivatives such as benzoic acid derivatives which are not used in the present invention are shown below.

[0229] For example, benzoic acid derivatives (4-1) to (4-19) described in WO2017 / 150478 (Patent Document 2), namely, sodium 2,6-dimethoxybenzoate, sodium 2,4,6-trimethoxybenzoate, sodium 2,4-dimethoxybenzoate, sodium 3,4,5-trimethoxybenzoate, sodium 4-methoxybenzoate, sodium 4-dimethylaminobenzoate, sodium 2,6-dihydroxybenzoate, sodium 4- ... Sodium 2,6-dimethoxybenzoate, sodium 4-aminobenzoate, sodium 2,4,6-trimethylbenzoate, sodium 4-t-butylbenzoate, sodium benzoate, lithium 2,6-dimethoxybenzoate, potassium 2,6-dimethoxybenzoate, cesium 2,6-dimethoxybenzoate, magnesium 2,6-dimethoxybenzoate, calcium 2,6-dimethoxybenzoate, barium 2,6-dimethoxybenzoate, sodium 2-methoxybenzoate, AH1 to AH18 and ANa7, ALi7, AK7, ACs7, and ABu, as described in J. Legros et al., Chemical European Journal, 2005, 11, 1086-1092. 4 Carboxylic acid derivatives of N7, including but not limited to benzoic acid derivatives.

[0230] (Method for producing sulfoxide derivatives) The monosulfoxide derivative of formula (B) can be produced by dropping an oxidizing agent into a solution containing the sulfide derivative of formula (A) and a metal catalyst. However, as long as the reaction proceeds, the order of adding the raw materials, reagents, solvent, etc. can be appropriately selected and adjusted by those skilled in the art.

[0231] (solvent) The solvent in the reaction of the present invention may be any solvent as long as the reaction proceeds. However, from the viewpoint of smooth progress of the reaction, it is preferable to carry out the reaction of the present invention in the presence of a solvent. Furthermore, a solvent having a high solubility of the compound of formula (A) and a low solubility of the compound of formula (B) is preferable. In other words, a solvent having a higher solubility of the compound of formula (A) than that of the compound of formula (B) is preferable.

[0232] The type of solvent in the reaction of the present invention is, for example, water, Halogenated aliphatic hydrocarbons (e.g., dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane, 1,3-dichloropropane, 1,4-dichlorobutane, trichloroethane, trichloroethylene, tetrachloroethane, tetrachloroethylene, pentachloroethane, etc., preferably dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane, more preferably dichloromethane) Aromatic hydrocarbon derivatives (e.g., benzene, toluene, xylene, trimethylbenzene, chlorobenzene, dichlorobenzene, trichlorobenzene, chlorotoluene, benzotrifluoride, 4-chlorobenzotrifluoride, difluorobenzene, bromobenzene, nitrobenzene, etc., preferably toluene, xylene, chlorobenzene, dichlorobenzene, and chlorotoluene); Nitriles (e.g., acetonitrile, propionitrile, butyronitrile, etc., preferably acetonitrile); Carboxylic acid esters (e.g., ethyl acetate, isopropyl acetate, butyl acetate, etc.); amides (e.g., N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAC), N,N-diethylacetamide, N-methylpyrrolidone (NMP), etc., preferably N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAC), N-methylpyrrolidone (NMP), more preferably N,N-dimethylformamide (DMF)); Alkyl ureas (e.g., N,N'-dimethylimidazolidinone (DMI) etc.), Sulfones (e.g., sulfolane, etc.), Carbonate esters (e.g., ethylene carbonate, propylene carbonate, etc.) Alcohols (e.g., C1-C6 aliphatic alcohols such as methanol, ethanol, propanol (i.e., 1-propanol), 2-propanol, n-butanol, s-butanol, i-butanol, t-butanol, pentanol (i.e., 1-pentanol), s-amyl alcohol, isoamyl alcohol, t-amyl alcohol, hexanol (i.e., 1-hexanol), cyclohexanol, and ethylene glycol; preferably, C1-C5 aliphatic alcohols such as methanol, ethanol, propanol, 2-propanol, n-butanol, s-butanol, i-butanol, t-butanol, pentanol, s-amyl alcohol, isoamyl alcohol, t-amyl alcohol, and ethylene glycol; more preferably, C1-C4 aliphatic alcohols such as methanol, ethanol, propanol, 2-propanol, butanol, s-butanol, i-butanol, t-butanol, and ethylene glycol); Ethers (e.g., tetrahydrofuran (THF), 2-methyltetrahydrofuran, 1,4-dioxane, diethyl ether, diisopropyl ether, dibutyl ether, di-tert-butyl ether, cyclopentyl methyl ether (CPME), methyl tert-butyl ether (MTBE), tert-amyl methyl ether (TAME), 1,2-dimethoxyethane (DME), diglyme, triglyme, 4-methoxybenzene, diphenyl ether, etc.), and Including, but not limited to, any combination thereof in any proportion. However, in one embodiment, it is preferable that an alcohol is contained. In another embodiment, it is preferable that a nitrile is contained. In yet another embodiment, it is preferable that an alcohol and / or a nitrile is contained. These can be applied to any of the following "Preferred examples of solvents", "More preferred examples of solvents", "More preferred examples of solvents", "Preferred specific examples of solvents", "More preferred specific examples of solvents", and "More preferred specific examples of solvents".

[0233] "2-propanol" is also called "isopropyl alcohol" or "isopropanol."

[0234] "t-butanol" is also called "tert-butanol" or "tert-butyl alcohol."

[0235] From the viewpoints of reactivity and economic efficiency, preferred examples of the solvent include water, halogenated aliphatic hydrocarbons, aromatic hydrocarbon derivatives, nitriles, carboxylic acid esters, amides, alcohols, and any combination thereof in any ratio.

[0236] More preferred examples of solvents include water, nitriles, amides, alcohols and any combination thereof in any proportion.

[0237] Further preferred examples of solvents include water, nitriles, alcohols and any combination thereof in any proportion.

[0238] Particularly preferred examples of solvents include water, alcohols, and any combination thereof in any proportion.

[0239] Preferred examples of solvents include water, dichloromethane, chloroform, 1,2-dichloroethane, toluene, xylene, chlorobenzene, dichlorobenzene, chlorotoluene, acetonitrile, ethyl acetate, isopropyl acetate, butyl acetate, N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAC), N-methylpyrrolidone (NMP), methanol, ethanol, propanol, 2-propanol, butanol, t-butanol, t-amyl alcohol, and any combination thereof in any proportion.

[0240] More preferred examples of solvents include water, acetonitrile, N,N-dimethylformamide (DMF), methanol, ethanol, propanol, 2-propanol, butanol, t-butanol, t-amyl alcohol, and any combination thereof in any proportion.

[0241] More preferred examples of solvents include water, acetonitrile, methanol, ethanol, propanol, 2-propanol, butanol, t-butanol, t-amyl alcohol, and any combination thereof in any proportion.

[0242] In one embodiment, more preferred examples of the solvent include water, 2-propanol, t-butanol, and any combination thereof in any proportion.

[0243] In another embodiment, more preferred examples of the solvent include water, t-butanol, t-amyl alcohol, and any combination thereof in any ratio. Among them, t-butanol solvent, t-amyl alcohol solvent, mixed solvent of t-butanol and water, or mixed solvent of t-amyl alcohol and water are more preferred. In the present invention, from the viewpoint of safety, it has been found that tertiary alcohols such as t-butanol and t-amyl alcohol are preferred as solvents among alcohols. From the viewpoint of price, economic efficiency, etc., t-butanol solvent or mixed solvent of t-butanol and water is more preferred. From the viewpoint of ease of handling, it has been found that mixed solvent of t-butanol and water is more preferred. In still another embodiment, from the same viewpoint as above, a mixed solvent of t-butanol and water, or a mixed solvent of t-amyl alcohol and water is preferred, and a mixed solvent of t-butanol and water is particularly preferred.

[0244] The amount of the solvent used may be any amount as long as the reaction proceeds. From the viewpoints of improving the yield, suppressing by-products, and economic efficiency, the amount of the solvent used may be, for example, 0.01 to 10.0 L (liters), preferably 0.1 to 5.0 L, more preferably 0.3 to 2.0 L, more preferably 0.4 to 1.5 L, more preferably 0.4 to 1.2 L, more preferably 0.5 to 1.2 L, and more preferably 0.5 to 1.0 L per mole of the sulfide derivative of formula (A) (raw material compound). However, the amount of the solvent used in the reaction of the present invention can be appropriately adjusted by a person skilled in the art. When a combination of two or more solvents is used, the ratio of the two or more solvents may be any ratio as long as the reaction proceeds. However, from the viewpoints of yield, by-product suppression, economic efficiency, and the like, in one embodiment, the amount of water solvent in the total solvent consisting of a solvent other than water and water solvent is, for example, 0 vol% to 100 vol%, preferably 0 vol% to 30 vol%, more preferably 0 vol% to 20 vol%, and even more preferably 0 vol% to 15 vol%, based on the total solvent amount (100 vol%). In another embodiment, the amount of water solvent in the total solvent consisting of a solvent other than water and water solvent is, for example, 5 vol% to 100 vol%, preferably 5 vol% to 30 vol%, more preferably 5 vol% to 20 vol%, and even more preferably 5 vol% to 15 vol%, based on the total solvent amount (100 vol%). Examples of solvents other than water include, but are not limited to, alcohols (eg, methanol, 2-propanol, t-butanol, t-amyl alcohol) and nitriles (eg, acetonitrile).

[0245] (Solubility) From the viewpoint of simple operation etc., the solubility of the compound in the solvent is preferably such that the target compound of formula (B) does not dissolve but precipitates, but is not limited thereto. The solubility of the compound in the reaction solvent of the present invention, for example, in the range of 15°C to 20°C, may be preferably 5 to 75% by weight, more preferably 10 to 60% by weight, further preferably 20 to 55% by weight, and particularly preferably 30 to 40% by weight, for the target compound of formula (B). In addition, from the viewpoint of smooth progress of the reaction, it is preferable that the compound of formula (A) as the raw material is dissolved in the solvent. In the range of 15° C. to 20° C., the solubility of the compound of formula (A) as the raw material can be, for example, preferably 5 to 75% by weight, more preferably 10 to 55% by weight, and particularly preferably 30 to 40% by weight. In one embodiment, for example, the solubility of the compound of formula (Ba) in 2-propanol was found to be 30-40% by weight in the range of 15° C. to 20° C. In another embodiment, from the viewpoint of crystallization and filtration, the solubility of the compound of formula (Ba) in a 70% by weight t-butanol / water mixed solution was found to be 4-6% by weight in the range of 15° C. to 20° C. and about 2% by weight at 5° C.

[0246] (concentration) From the viewpoints of smooth progress of the reaction and simple operation, the concentration of the compound of formula (A) at the start of the reaction may be, for example, 5 to 75% by weight, more preferably 20 to 60% by weight, and particularly preferably 35 to 50% by weight. The concentration of the compound of formula (A) is the concentration relative to the entire reaction system.

[0247] (Reaction temperature) The reaction temperature of the present invention is not particularly limited. In one embodiment, from the viewpoints of improving the yield, suppressing by-products, and economic efficiency, the reaction temperature is, for example, -10℃~60℃ (i.e. minus 10℃~plus 60℃), Preferably 0°C to 60°C (i.e. zero°C to plus 60°C), More preferably, it is 5°C to 40°C (i.e., plus 5°C to plus 40°C), More preferably, the temperature is 10°C to 35°C (i.e., plus 10°C to plus 35°C), More preferably, the reaction temperature is in the range of 10° C. to 20° C. (i.e., plus 10° C. to plus 20° C.). In another embodiment, from the same viewpoint as above, the reaction temperature is, for example, -20℃~50℃ (i.e. minus 20℃~plus 50℃), Preferably, -10°C to 40°C (i.e., minus 10°C to plus 40°C), More preferably, it is -5°C to 35°C (i.e., minus 5°C to plus 35°C). More preferably, the temperature is 15°C to 35°C (i.e., plus 15°C to plus 30°C). More preferably, the reaction temperature may be in the range of 25° C. to 35° C. (i.e., plus 25° C. to plus 35° C.). In yet another embodiment, from the same viewpoint as above, the reaction temperature is, for example, -10℃~60℃ (i.e. minus 10℃~plus 60℃), Preferably, -10°C to 50°C (i.e., minus 10°C to plus 50°C), More preferably, the temperature is 0°C to 50°C (i.e., zero°C to 50°C). More preferably, the temperature may be in the range of 0° C. to 40° C. (that is, zero° C. to 40° C.).

[0248] (Reaction time) The reaction time of the present invention is not particularly limited. The lower limit of the reaction time can be, for example, 2 hours or more, preferably 3 hours or more, more preferably 6 hours or more, but is not limited thereto. The upper limit of the reaction time can be, for example, 48 hours or less, preferably 24 hours or less, more preferably 12 hours or less, but is not limited thereto. The range of the reaction time in the present invention can be appropriately adjusted by a person skilled in the art by combining the above upper and lower limits. The combination of the upper and lower limits of the reaction time can be, for example, 2 hours to 48 hours, preferably 2 hours to 24 hours, more preferably 3 hours to 12 hours, but is not limited thereto. However, the reaction time of the present invention can be appropriately adjusted by a person skilled in the art. "Reaction time" means the time from the start of addition of hydrogen peroxide to the end of the reaction. The reaction time in the present invention is the maturation period during which unreacted raw materials are consumed. In the present invention, the reaction time is preferably equal to the time of addition of hydrogen peroxide, but the present invention is not limited thereto. In the present invention, the raw materials are consumed immediately after the addition of hydrogen peroxide, and hydrogen peroxide does not accumulate in the reaction mixture. Therefore, the present invention is a safe and industrially applicable production method.

[0249] (Hydrogen peroxide addition rate) The addition rate of hydrogen peroxide is preferably 0.5 mol / hour or less per mol of the compound of formula (A).When the addition rate is 0.5 mol / hour or less, hydrogen peroxide does not accumulate in the reaction mixture.The upper limit of the addition rate can be, for example, 0.5 mol / hour or less, 0.4 mol / hour or less, and 0.3 mol / hour or less. In addition, from the viewpoints of by-product suppression, economic efficiency, and the like, the lower limit of the addition rate can be, for example, 0.05 mol / hour or more, 0.1 mol / hour or more, and 0.2 mol / hour or more. The range of the addition rate in the present invention can be appropriately adjusted by a person skilled in the art by combining the above upper and lower limits. The combination of the upper and lower limits of the addition rate can be, for example, 0.05 to 0.5 mol / hour or 0.1 to 0.5 mol / hour. However, the present invention is not limited to these combinations.

[0250] (Post-processing; isolation and / or purification) The target compound of formula (B), particularly 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl]ether (Ba), can be isolated and purified from the reaction mixture by methods known to those skilled in the art (e.g., extraction, washing, crystallization including recrystallization, filtration, crystal washing and / or other operations) and modifications thereof, and any combination thereof.

[0251] In the post-treatment, crystallization of the target product, including recrystallization, and washing of the crystals may be performed. Crystallization of the target product, including recrystallization, may be performed by a conventional method known to those skilled in the art. For example, a poor solvent may be added to a solution of the target product in a good solvent. As another example, a saturated solution of the target product may be cooled. In either case, seed crystals may be used. The crystals may be washed with a solvent after filtration, or a suspension (slurry) of the crystals may be stirred and then filtered. In addition, from the viewpoints of yield, purity, economic efficiency, and the like, the filtration temperature can be in the range of, for example, 0°C (zero°C) to 30°C, preferably 0°C (zero°C) to 20°C, and more preferably 5°C to 15°C.

[0252] In any of the above cases (crystallization including recrystallization, filtration, crystal washing, etc.), a solvent such as an organic solvent (including a water-miscible organic solvent) or water is used. Examples of water-miscible organic solvents include, but are not limited to, nitriles (e.g., acetonitrile), alcohols (e.g., methanol, ethanol, 2-propanol, t-butanol), ethers (e.g., tetrahydrofuran (THF), 1,4-dioxane), ketones (e.g., acetone), amides (e.g., N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAC), N-methylpyrrolidone (NMP), etc.), and combinations thereof, preferably acetonitrile, methanol, ethanol, 2-propanol, t-butanol, acetone, and combinations thereof, more preferably acetonitrile, methanol, ethanol, 2-propanol, t-butanol, and combinations thereof, and even more preferably 2-propanol or t-butanol. The amount of the organic solvent, such as a water-miscible organic solvent, and the amount of water may be any ratio as long as the purpose is achieved. When a combination of a water-miscible organic solvent and water is used, the ratio thereof may be any ratio as long as the purpose is achieved. When a combination of two or more solvents, such as a water-miscible organic solvent, is used, the ratio thereof may be any ratio as long as the purpose is achieved. Those amounts and ratios can be appropriately adjusted by those skilled in the art depending on the purpose and circumstances.

[0253] In any of the above operations (extraction operation, washing operation, crystallization operation including recrystallization, filtration operation, crystal washing operation, etc.), the temperature can be appropriately adjusted by those skilled in the art. However, from the viewpoint of yield, purity, economic efficiency, etc., the temperature is, for example, 0°C (zero°C) to 100°C, preferably 0°C to 50°C, more preferably 0°C to 35°C, and even more preferably 5°C to 35°C. Heating and cooling may be performed within these temperature ranges.

[0254] In any of the above operations (extraction operation, washing operation, crystallization operation including recrystallization, filtration operation, crystal washing operation, etc.), the amount of organic solvent (including water-miscible organic solvent) and / or water can be appropriately adjusted by those skilled in the art by adding and removing them. Furthermore, in some cases, the solvent may be recovered and recycled. For example, the solvent used in the reaction may be recovered and recycled, and the solvent used in the post-treatment (isolation and / or purification) may be recovered and recycled.

[0255] Post-treatment (isolation and / or purification) can be performed by appropriately combining all or part of the above operations. In some cases, the above operations may be repeated depending on the purpose of isolation and / or purification. In addition, any combination of the above operations and their order can be appropriately selected by those skilled in the art. However, in the present invention, the target compound of formula (B), particularly 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl]ether (Ba) has a solubility of 30% to 40% in an alcohol solvent in the range of 15 to 20°C, so that the target crystals are precipitated at the end of the reaction. This makes it possible to easily purify the target product by just filtration. This allows the target product with a low melting point to be crystallized from the reaction mixture, and the target compound of formula (B) with high purity can be industrially and efficiently produced by just filtration.

[0256] (Reaction yield and yield) As used herein, the terms "reaction yield" and "yield" have the following respective meanings.

[0257] (Reaction yield) In the present invention, the organic layer of the reaction mixture was analyzed under the following HPLC analysis conditions (A) or GC analysis conditions to determine the reaction yield. In this specification, the reaction yield is expressed as the HPLC area percentage of the target compound.

[0258] The reaction yield in the present invention can be in the range of, for example, 80 to 100%, preferably 85 to 100%, more preferably 90 to 100%, and further preferably 95 to 100%.

[0259] (yield) The yield in the present invention can be calculated from the mole number of the obtained monosulfoxide compound of formula (B) (target compound) relative to the mole number of the sulfide derivative of formula (A) (starting compound). That is, the yield in the present invention is represented by the following formula: Yield (%) = (number of moles of target compound obtained) / (number of moles of raw material compound) x 100

[0260] The yield in the present invention can be, for example, in the range of 85 to 100%, preferably 90 to 100%.

[0261] The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these examples in any way.

[0262] In the present specification, the following instruments and conditions were used to measure the properties and yields of the examples and comparative examples.

[0263] (GC: Gas Chromatography) Equipment: GC-2030 (Shimadzu Corporation) Column: DB-17 (Aglient J&W) Detection temperature: 280℃ Inlet temperature: 280℃ Total flow rate: 34mL / min Split ratio: 1:30 Injection volume: 1μL Oven temperature: JPEG0007657783000024.jpg31170

[0264] Regarding the GC analysis method, the following documents can be referred to as necessary. "New Experimental Chemistry Lectures 9: Analytical Chemistry II" edited by the Chemical Society of Japan, pp. 60-86 (1977), published by Shingo Iizumi and Maruzen Co., Ltd. Chemical Society of Japan, ed., Experimental Chemistry Lectures 20-1 Analytical Chemistry, 5th ed., pp. 121-129 (2007), published by Seishiro Murata, Maruzen Co., Ltd.

[0265] (HPLC: High Performance Liquid Chromatography) (HPLC analysis conditions) Equipment:LC-20 Pump: LC-20AT (Shimadzu Corporation) Detector: SPD-20A (Shimadzu Corporation) Column: CERI L-column ODS (4.6x250mm), L-C18, 5μm, 12nm Eluent: JPEG0007657783000025.jpg48170Flow rate: 1.0mL / min Detection: UV 228nm Column temperature: 40℃

[0266] As described above, the reaction yield was evaluated using the area percentage under the above HPLC analysis conditions or GC analysis conditions.

[0267] Regarding the HPLC analysis method, the following documents can be referred to, if necessary. "New Experimental Chemistry Lectures 9: Analytical Chemistry II" edited by the Chemical Society of Japan, pp. 86-112 (1977), published by Shingo Iizumi and Maruzen Co., Ltd. Chemical Society of Japan, ed., Experimental Chemistry Lectures 20-1 Analytical Chemistry, 5th ed., pp. 130-151 (2007), published by Seishiro Murata, Maruzen Co., Ltd.

[0268] ( 1 H-NMR: 1 H nuclear magnetic resonance spectrum; analytical conditions) Equipment: JEOL JMN-ECS-300 or JEOL JMN-Lambda-400 (manufactured by JEOL RESONANCE Co., Ltd.) Internal standard: Tetramethylsilane (TMS)

[0269] (Method of measuring melting point) Measurement was performed using a DSC differential scanning calorimeter. Differential scanning calorimetry was performed using a DSC-60 model (manufactured by Shimadzu Corporation) at a heating rate of 10°C / min in the temperature range of 0 to 400°C. For the differential scanning calorimetry method, the following literature can be referred to as necessary: ​​"4th Edition Experimental Chemistry Lectures 4 Heat and Pressure," edited by the Chemical Society of Japan, pp. 57-93 (1992), published by Ebihara Kumao, Maruzen Co., Ltd. The Chemical Society of Japan, ed., "5th Edition Experimental Chemistry Lectures 6: Temperature, Heat, and Pressure", pp. 203-205 (2005), published by Seishiro Murata, Maruzen Co., Ltd.

[0270] In the examples and comparative examples of the present invention, a reaction vessel that is commonly used by those skilled in the art was used as a reaction vessel for preparing the catalyst solution and producing the title compound, etc. For example, in Comparative Example 11, a screw vial (vial with a screw cap) of about 6 mL with an inner diameter of 15 mm and a height of 40 mm, equipped with a cross-shaped magnetic stirrer with an outer diameter (length) of 10 mm and a height (thickness) of 5 mm and a magnetic stirrer with a thermostatic bath, was used.

[0271] (Powder X-ray diffraction measurement) Equipment :Rigaku MultiFlex X-ray: Cu-Kα Measurement method: Reflection mode Voltage: 40kV Current: 40mA Measurement range: 5~80° Measurement interval: 0.02°

[0272] In this specification, room temperature is usually within the range of 10°C to 35°C.

[0273] As used herein, "age / aged / aging" includes that the mixture is stirred by conventional methods known to those skilled in the art.

[0274] Example 1 Preparation of 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether

[0275] [ka]

[0276] In a 50 mL reaction flask, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl]ether (14.96 g, 87% purity, 30 mmol, 100 mol%), vanadyl acetylacetonate (79.5 mg, 0.3 mmol, 1 mol%), and 2-propanol (24 mL, 0.8 L / mol) were added. The mixture was stirred at an internal temperature of 15-20°C for 30 minutes. 35% hydrogen peroxide (3.5 g, 36 mmol, 120 mol%) was added dropwise at an internal temperature of 15°C to 20°C over 3 hours, and the mixture was aged for 1 hour while maintaining the internal temperature at 15°C to 20°C. The reaction mixture was analyzed by HPLC (area percentage). As a result, the components in the reaction mixture, excluding the solvent, were as follows: 5-Trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl]ether (target compound): 95.5%, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl]ether (raw material): 0.5%, 5-Trifluoromethylsulfinylpentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl]ether (by-product; disulfoxide derivative): 0.9%.

[0277] The reaction mixture was an orange-brown suspension at 15°C. Crystals of the target product were precipitated. A 2.5% aqueous solution of sodium sulfite (24.6 g, 6 mmol, 20 mol%) was added to the reaction mixture, and the mixture was stirred at an internal temperature of 5°C for 1 hour. The resulting crude product was filtered off at 5°C. The resulting crystals were washed successively with a mixed solution of 12 mL (0.4 L / mol) of 2-propanol and 12 mL (0.4 L / mol) of water, and 24 mL (0.8 L / mol) of water. As a result, white crystals of the target product (compound Ba) were obtained in a yield of 90.5% (12.73 g, purity 95.2%).

[0278] 1 H-NMR (300MHz, CDCl3 )δ(ppm,TMS standard):1.57-1.66(m,2H),1.74-1.93(m,4H),2.92(t,2H),3.30-3.43(m,1H),3.66-3.78(m,1H),4.13(t,2H),7.21(d,1H),7.54(d,1H)

[0279] Melting point: 43℃

[0280] This is an industrially excellent production method in which the target substance, which has a low melting point, is crystallized from the reaction mixture and a high-purity product can be obtained simply by filtration.

[0281] Example 2 Preparation of 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether

[0282] [ka]

[0283] In a 50 mL reaction flask, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl]ether (9.78 g, 88% purity, 20 mmol, 100 mol%) and vanadyl acetylacetonate (53 mg, 0.2 mmol, 1 mol%) were added to 2-propanol (20 mL, 1.0 L / mol). The mixture was stirred at an internal temperature of 15-20°C for 30 minutes. 33% hydrogen peroxide (3.09 g, 30 mmol, 150 mol%) was added dropwise at an internal temperature of 15°C to 20°C over 3 hours, and the mixture was aged for 1 hour while maintaining the internal temperature at 15°C to 20°C. The reaction mixture was analyzed by HPLC (area percentage). As a result, the components in the reaction mixture, excluding the solvent, were as follows: 5-Trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl]ether (target compound): 94.0%, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl]ether (raw material): 0.2%, 5-Trifluoromethylsulfinylpentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl]ether (by-product; disulfoxide derivative): 0.9%. The reaction mixture was an orange-brown suspension at 15°C. Crystals of the target product were precipitated. A 13.3% aqueous solution of sodium sulfite (8.5 g, 10 mmol, 0.5 mol%) was added to the reaction mixture, and the mixture was stirred at an internal temperature of 5°C for 1 hour. The resulting crude product was filtered off at 5°C. The resulting crystals were washed successively with a mixed solution of 5 mL (0.4 L / mol) of 2-propanol and 9 mL (0.4 L / mol) of water, and then with 20 mL (0.8 L / mol) of water. As a result, white crystals of the target product (compound Ba) were obtained in a yield of 94.5% (8.73 g, purity 96.7%).

[0284] Example 3 Preparation of 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether

[0285] [ka]

[0286] In a 50 mL reaction flask, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl]ether (9.78 g, 88% purity, 20 mmol, 100 mol%) and vanadyl acetylacetonate (53 mg, 0.2 mmol, 1 mol%) were added to 2-propanol (10 mL, 0.5 L / mol). The mixture was stirred at an internal temperature of 15-20°C for 30 minutes. 33% hydrogen peroxide (3.09 g, 30 mmol, 150 mol%) was added dropwise at an internal temperature of 15°C to 20°C over 3 hours, and the mixture was aged for 1 hour while maintaining the internal temperature at 15°C to 20°C. The reaction mixture was analyzed by HPLC (area percentage). As a result, the components in the reaction mixture, excluding the solvent, were as follows: 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl]ether (target compound): 91.4%, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl]ether (raw material): 3.5%, 5-Trifluoromethylsulfinylpentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl]ether (by-product; disulfoxide derivative): 0.5%.

[0287] Example 4 Preparation of 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether

[0288] [ka]

[0289] In a 50 mL reaction flask, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl]ether (9.78 g, 88% purity, 20 mmol, 100 mol%) and vanadyl acetylacetonate (53 mg, 0.2 mmol, 1 mol%) were added to 2-propanol (20 mL, 1.0 L / mol). The mixture was cooled to an internal temperature of 5°C and stirred for 30 minutes. 33% hydrogen peroxide (3.09 g, 30 mmol, 150 mol%) was added dropwise at an internal temperature of 5°C over 3 hours, and the mixture was aged for 1 hour while maintaining the internal temperature at 5°C. The reaction mixture was analyzed by HPLC (area percentage). As a result, the components in the reaction mixture, excluding the solvent, were as follows: 5-Trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl]ether (target compound): 93.2%, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl]ether (raw material): 1.9%, 5-Trifluoromethylsulfinylpentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl]ether (by-product; disulfoxide derivative): 0.5%.

[0290] Example 5 Preparation of 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether

[0291] [ka]

[0292] In a 30 mL test tube, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl]ether (2.47 g, 87% purity, 5 mmol, 100 mol%), vanadyl acetylacetonate (26.5 mg, 0.1 mmol, 2 mol%) were added to methanol (4 mL, 0.8 L / mol). The mixture was cooled to 0° C. 35% hydrogen peroxide (0.728 g, 7.5 mmol, 150 mol%) was added thereto. The mixture was stirred at 0° C. for 30 min and then aged at room temperature for 24 h. The reaction mixture was analyzed by HPLC (area percentage). As a result, the components in the reaction mixture, excluding the solvent, were as follows: 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl]ether (target compound): 94.8%, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl]ether (raw material): 0.6%, 5-Trifluoromethylsulfinylpentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl]ether (by-product; disulfoxide derivative): 1.9%.

[0293] Example 6 Preparation of 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether

[0294] [ka]

[0295] In a 30 mL test tube, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl]ether (2.47 g, 87% purity, 5 mmol, 100 mol%) and vanadium(III) acetylacetonate (34.8 mg, 0.1 mmol, 2 mol%) were added to methanol (4 mL, 0.8 L / mol). The mixture was cooled to 0° C. 35% hydrogen peroxide (0.728 g, 7.5 mmol, 150 mol%) was added thereto. The mixture was stirred at 0° C. for 30 min and then aged at room temperature for 24 h. The reaction mixture was analyzed by HPLC (area percentage). As a result, the components in the reaction mixture, excluding the solvent, were as follows: 5-Trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl]ether (target compound): 95.5%, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl]ether (raw material): 0.8%, 5-Trifluoromethylsulfinylpentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl]ether (by-product; disulfoxide derivative): 1.4%.

[0296] Example 7 Preparation of 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether

[0297] [ka]

[0298] In a 30 mL test tube, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl]ether (2.47 g, 87% purity, 5 mmol, 100 mol%), vanadium(III) acetylacetonate (34.8 mg, 0.1 mmol, 2 mol%) were added to acetonitrile (4 mL, 0.8 L / mol). The mixture was cooled to 0° C. 35% hydrogen peroxide (0.728 g, 7.5 mmol, 150 mol%) was added thereto. The mixture was stirred at 0° C. for 30 min and then aged at room temperature for 24 h. The reaction mixture was analyzed by HPLC (area percentage). As a result, the components in the reaction mixture, excluding the solvent, were as follows: 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl]ether (target compound): 85.6%, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl]ether (raw material): 8.4%, 5-Trifluoromethylsulfinylpentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl]ether (by-product; disulfoxide derivative): 1.3%.

[0299] Example 8 Preparation of 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether

[0300] [ka]

[0301] In a 30 mL test tube, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl]ether (2.29 g, 93% purity, 5 mmol, 100 mol%) and titanyl(IV) acetylacetonate (26.2 mg, 0.1 mmol, 2 mol%) were added to methanol (4 mL, 0.8 L / mol). The mixture was cooled to 0° C. 35% hydrogen peroxide (0.728 g, 7.5 mmol, 150 mol%) was added thereto. The mixture was stirred at 0° C. for 30 min and then aged at room temperature for 63 h. The reaction mixture was analyzed by HPLC (area percentage). As a result, the components in the reaction mixture, excluding the solvent, were as follows: 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl]ether (target compound): 87.2%, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl]ether (raw material): 2.0%, 5-Trifluoromethylsulfinylpentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl]ether (by-product; disulfoxide derivative): 5.2%.

[0302] Example 9 Preparation of 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether

[0303] [ka]

[0304] In a 30 mL test tube, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl]ether (2.47 g, 87% purity, 5 mmol, 100 mol%) and ammonium molybdate tetrahydrate (8.7 mg, 0.007 mmol, 0.14 mol%, 1 mol% as molybdenum atom) were added to 2-propanol (4 mL, 0.8 L / mol). The mixture was cooled to an internal temperature of 0°C. 35% hydrogen peroxide (0.728 g, 7.5 mmol, 150 mol%) was added thereto. The mixture was stirred at an internal temperature of 0°C for 30 minutes and then aged at room temperature for 17 hours. The reaction mixture was analyzed by HPLC (area percentage). As a result, the components in the reaction mixture, excluding the solvent, were as follows: 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl]ether (target compound): 95.6%, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl]ether (raw material): 0.5%, 5-Trifluoromethylsulfinylpentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl]ether (by-product; disulfoxide derivative): 1.2%. The reaction mixture was a yellow suspension at 25° C. Crystals of the target substance were precipitated.

[0305] Example 10 Preparation of 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether

[0306] [ka]

[0307] In a 30 mL test tube, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl]ether (2.15 g, 94% purity, 5 mmol, 100 mol%), ammonium molybdate tetrahydrate (8.7 mg, 0.007 mmol, 0.14 mol%, 1 mol% as molybdenum atom) were added to acetonitrile (4 mL, 0.8 L / mol). The mixture was cooled to 0° C. 35% hydrogen peroxide (0.728 g, 7.5 mmol, 150 mol%) was added thereto. The mixture was stirred at 0° C. for 30 minutes and then aged at room temperature for 24 hours. The reaction mixture was analyzed by HPLC (area percentage). As a result, the components in the reaction mixture, excluding the solvent, were as follows: 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl]ether (target compound): 87.6%, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl]ether (raw material): 0.3%, 5-Trifluoromethylsulfinylpentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl]ether (by-product; disulfoxide derivative): 7.0%.

[0308] Example 11 Preparation of 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether

[0309] [ka]

[0310] In a 250 mL reaction flask, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl]ether (33.1 g, 88% purity, 80 mmol, 100 mol%) and vanadyl acetylacetonate (212.1 mg, 0.8 mmol, 1 mol%) were added to t-butanol (60 mL, 0.8 L / mol). The mixture was stirred at an internal temperature of 25° C. for 30 minutes. 35% hydrogen peroxide (9.3 g, 96 mmol, 120 mol%) was added dropwise at an internal temperature of 25° C. over 3 hours, and the mixture was aged for 1 hour while maintaining the internal temperature at 25° C. The reaction mixture was analyzed by HPLC (area percentage). As a result, the components in the reaction mixture, excluding the solvent, were as follows: 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl]ether (target compound): 96.1%, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl]ether (raw material): 0.2%, 5-Trifluoromethylsulfinylpentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl]ether (by-product; disulfoxide derivative): 1.4%. The reaction mixture was an orange-brown solution at 25°C. t-Butanol (8mL, 0.1L / mol) and 2% aqueous sodium hydrogen sulfite solution (40.8g, 8mmol, 10mol%) were added to the reaction mixture, and the mixture was stirred at an internal temperature of 20°C for 1 hour. The resulting crude product was filtered off at 20°C. The resulting crystals were washed successively with a mixed solution of 20mL (0.3L / mol) of 2-propanol and 36mL (0.5L / mol) of water, and then with 24mL (0.3L / mol) of water. As a result, white crystals of the target product (compound Ba) were obtained in a yield of 85.1% (31.5g, purity 96.6%).

[0311] Example 12 Preparation of 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether

[0312] [ka]

[0313] In a 50 mL reaction flask, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl]ether (12.2 g, 88% purity, 25 mmol, 100 mol%) and vanadyl acetylacetonate (66.3 mg, 0.25 mmol, 1 mol%) were added to t-butanol (19 mL, 0.8 L / mol). The mixture was stirred at an internal temperature of 40° C. for 30 minutes. 35% hydrogen peroxide (2.9 g, 30 mmol, 120 mol%) was added dropwise at an internal temperature of 40° C. over 3 hours, and the mixture was aged for 1 hour while maintaining the internal temperature at 40° C. The reaction mixture was analyzed by HPLC (area percentage). As a result, the components in the reaction mixture, excluding the solvent, were as follows: 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl]ether (target compound): 94.6%, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl]ether (raw material): 0.7%, 5-Trifluoromethylsulfinylpentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl]ether (by-product; disulfoxide derivative): 1.4%. To the reaction mixture, 9.4% aqueous sodium hydrogen sulfite solution (2.8 g, 2.5 mmol, 10 mol%) and 10 mL of water (0.4 L / mol) were added, and the mixture was stirred at an internal temperature of 20°C for 1 hour. The resulting crude product was filtered off at 20°C. The resulting crystals were washed successively with a mixed solution of 6 mL of 2-propanol (0.3 L / mol) and 11 mL of water (0.5 L / mol) and 8 mL of water (0.3 L / mol). As a result, white crystals of the target product (compound Ba) were obtained with a yield of 86.2% (9.9 g, purity 96.9%).

[0314] Example 13 Preparation of 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether

[0315] [ka]

[0316] In a 50 mL reaction flask, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl]ether (12.2 g, 88% purity, 25 mmol, 100 mol%) and vanadyl acetylacetonate (66.3 mg, 0.25 mmol, 1 mol%) were added to t-butanol (19 mL, 0.8 L / mol). The mixture was stirred at an internal temperature of 30°C for 30 minutes. 35% hydrogen peroxide (2.9 g, 30 mmol, 120 mol%) was added dropwise at an internal temperature of 30°C over 3 hours, and the mixture was aged for 1 hour while maintaining the internal temperature at 30°C. The reaction mixture was analyzed by HPLC (area percentage). As a result, the components in the reaction mixture, excluding the solvent, were as follows: 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl]ether (target compound): 95.1%, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl]ether (raw material): 0%, 5-Trifluoromethylsulfinylpentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl]ether (by-product; disulfoxide derivative): 1.9%. A 2% aqueous solution of sodium hydrogen sulfite (12.8 g, 2.5 mmol, 10 mol%) was added to the reaction mixture, and the mixture was stirred at an internal temperature of 15° C. for 1 hour. The resulting crude product was filtered off at 15° C. The resulting crystals were washed successively with a mixed solution of 6 mL (0.3 L / mol) of 2-propanol and 11 mL (0.5 L / mol) of water, and then with 8 mL (0.3 L / mol) of water. As a result, white crystals of the target product (compound Ba) were obtained in a yield of 84.4% (9.69 g, purity 97.3%).

[0317] Example 14 Preparation of 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether

[0318] [ka]

[0319] In a 50 mL reaction flask, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl]ether (12.2 g, 88% purity, 25 mmol, 100 mol%) and vanadyl acetylacetonate (33.2 mg, 0.13 mmol, 0.5 mol%) were added to t-butanol (19 mL, 0.8 L / mol). The mixture was stirred at an internal temperature of 30°C for 30 minutes. 35% hydrogen peroxide (2.9 g, 30 mmol, 120 mol%) was added dropwise at an internal temperature of 30°C over 3 hours, and the mixture was aged for 1 hour while maintaining the internal temperature at 30°C. The reaction mixture was analyzed by HPLC (area percentage). As a result, the components in the reaction mixture, excluding the solvent, were as follows: 5-Trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl]ether (target compound): 96.6%, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl]ether (raw material): 0.6%, 5-Trifluoromethylsulfinylpentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl]ether (by-product; disulfoxide derivative): 1.4%. A 2% aqueous solution of sodium hydrogen sulfite (12.8 g, 2.5 mmol, 10 mol%) was added to the reaction mixture, and the mixture was stirred at an internal temperature of 15° C. for 1 hour. The resulting crude product was filtered off at 15° C. The resulting crystals were washed successively with a mixed solution of 6 mL (0.3 L / mol) of 2-propanol and 11 mL (0.5 L / mol) of water, and then with 8 mL (0.3 L / mol) of water. As a result, white crystals of the target product (compound Ba) were obtained with a yield of 87.3% (9.84 g, purity 99.1%).

[0320] Example 15 Preparation of 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether

[0321] [ka]

[0322] In a 50 mL reaction flask, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl]ether (12.2 g, 88% purity, 25 mmol, 100 mol%) and vanadyl acetylacetonate (66.4 mg, 0.25 mmol, 1 mol%) were added to t-butanol (13 mL, 0.5 L / mol). The mixture was stirred at an internal temperature of 30° C. for 30 minutes. 35% hydrogen peroxide (2.9 g, 30 mmol, 120 mol%) was added dropwise at an internal temperature of 30° C. over 3 hours, and the mixture was aged for 2 hours while maintaining the internal temperature at 30° C. Further, 35% hydrogen peroxide (0.24 g, 2.5 mmol, 10 mol%) was added at an internal temperature of 30° C., and the mixture was aged for 30 minutes while maintaining the internal temperature at 30° C. The reaction mixture was analyzed by HPLC (area percentage). As a result, the components in the reaction mixture, excluding the solvent, were as follows: 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl]ether (target compound): 94.6%, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl]ether (raw material): 0.6%, 5-Trifluoromethylsulfinylpentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl]ether (by-product; disulfoxide derivative): 1.3%.

[0323] Example 16 Preparation of 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether

[0324] [ka]

[0325] In a 250 mL reaction flask, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl]ether (44.0 g, purity 88%, 90 mmol, 100 mol%), vanadyl acetylacetonate (239 mg, 0.9 mmol, 1 mol%), t-butanol (77 mL, 0.9 L / mol), and water (6 mL, 0.1 L / mol) were added. The mixture was stirred at an internal temperature of 30° C. for 30 minutes. 34% hydrogen peroxide (11 g, 108 mmol, 120 mol%) was added dropwise at an internal temperature of 30° C. over 3 hours, and the mixture was aged for 1 hour while maintaining the internal temperature at 30° C. The reaction mixture was analyzed by GC (area percentage). As a result, the components in the reaction mixture, excluding the solvent, were as follows: 5-Trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl]ether (target compound): 96.8%, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl]ether (raw material): 0.5%, 5-Trifluoromethylsulfinylpentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl]ether (by-product; disulfoxide derivative): 0.9%. The reaction mixture was an orange-brown solution at 30°C. A 9.4% aqueous sodium hydrogen sulfite solution (9.9 g, 9.0 mmol, 10 mol%) was added to the reaction mixture, and the mixture was stirred at an internal temperature of 20°C for 30 minutes. Seed crystals were added to the mixture at an internal temperature of 20°C, and the mixture was cooled to an internal temperature of 5°C over 1 hour and aged for 14 hours. The resulting crude product was filtered at 5°C. The resulting crystals were washed sequentially with a mixed solution of 23 mL (0.3 L / mol) of t-butanol and 41 mL (0.5 L / mol) of water, and 27 mL (0.3 L / mol) of water. As a result, white crystals of the target product (compound Ba) were obtained in a yield of 88.9% (37.1 g, purity 96.6%).

[0326] As the seed crystals used in the above examples, crystals obtained in the same manner as in Example 1 were used.

[0327] Example 17 Preparation of 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether

[0328] [ka]

[0329] In a 250 mL reaction flask, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl]ether (38.9 g, 89% purity, 80 mmol, 100 mol%), vanadyl acetylacetonate (212 mg, 0.8 mmol, 1 mol%), t-butanol (68 mL, 0.9 L / mol), and water (5 mL, 0.1 L / mol) were added. The mixture was stirred at an internal temperature of 30° C. for 30 minutes. 35% hydrogen peroxide (9.3 g, 96 mmol, 120 mol%) was added dropwise at an internal temperature of 30° C. over 3 hours, and the mixture was aged for 1 hour while maintaining the internal temperature at 30° C. The reaction mixture was analyzed by GC (area percentage). As a result, the components in the reaction mixture, excluding the solvent, were as follows: 5-Trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl]ether (target compound): 97.1%, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl]ether (raw material): 0.6%, 5-Trifluoromethylsulfinylpentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl]ether (by-product; disulfoxide derivative): 1.4%. The reaction mixture was an orange-brown solution at 30°C. A 3.7% aqueous sodium hydrogen sulfite solution (22.7g, 8mmol, 10mol%) was added to the reaction mixture, and the mixture was cooled from an internal temperature of 30°C to 25°C over 30 minutes. Seed crystals were added to the mixture at an internal temperature of 25°C, and the mixture was cooled to an internal temperature of 5°C over 1 hour and aged for 2 hours. The resulting crude product was filtered off at 5°C. The resulting crystals were washed sequentially with a mixed solution of 20mL (0.3L / mol) of t-butanol and 36mL (0.5L / mol) of water, and 24mL (0.3L / mol). As a result, white crystals of the target product (compound Ba) were obtained in a yield of 91.5% (33.6g, purity 97.4%).

[0330] As the seed crystals used in the above examples, crystals obtained in the same manner as in Example 1 were used.

[0331] Example 18 Preparation of 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether

[0332] [ka]

[0333] In a 50 mL reaction flask, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl]ether (12.1 g, 88% purity, 25 mmol, 100 mol%) and vanadyl acetylacetonate (66.4 mg, 0.25 mmol, 1 mol%) were added to t-butanol (19 mL, 0.8 L / mol). The mixture was stirred at an internal temperature of 30° C. for 30 minutes. 35% hydrogen peroxide (1.0 g, 10 mmol, 40 mol%) was added dropwise at an internal temperature of 30° C. over 1 hour, and then 35% hydrogen peroxide (2.0 g, 20 mmol, 80 mol%) was added dropwise over 2 hours while cooling to an internal temperature of 20° C., and the mixture was aged for 1 hour while maintaining the internal temperature at 20° C. The reaction mixture was analyzed by GC (area percentage). As a result, the components in the reaction mixture, excluding the solvent, were as follows: 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl]ether (target compound): 97.6%, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl]ether (raw material): 0.6%, 5-Trifluoromethylsulfinylpentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl]ether (by-product; disulfoxide derivative): 0.9%. The reaction mixture was an orange-brown suspension at 20°C. Crystals of the target substance were precipitated. A 5% aqueous solution of sodium hydrogen sulfite (5.3 g, 2.5 mmol, 10 mol%) and 5 mL of water (0.2 L / mol) were added to the reaction mixture. The mixture was stirred at an internal temperature of 15°C for 1 hour. The resulting crystals were filtered off at 15°C. The resulting crystals were washed successively with a mixed solution of 6 mL of 2-propanol (0.3 L / mol) and 11 mL of water (0.5 L / mol) and 8 mL of water (0.3 L / mol). As a result, white crystals of the target substance (compound Ba) were obtained in a yield of 86.2% (9.9 g, purity 97.7%).

[0334] Example 19 Preparation of 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether

[0335] [ka]

[0336] In a 50 mL reaction flask, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl]ether (12.1 g, 88% purity, 25 mmol, 100 mol%), vanadyl acetylacetonate (66.4 mg, 0.25 mmol, 1 mol%), and t-amyl alcohol (19 mL, 0.8 L / mol) were added. The mixture was stirred at an internal temperature of 17°C for 30 minutes. 33.7% hydrogen peroxide (3.0 g, 30 mmol, 120 mol%) was added dropwise at an internal temperature of 17°C over 3 hours, and the mixture was aged for 1 hour. The reaction mixture was analyzed by GC (area percentage). As a result, the components in the reaction mixture, excluding the solvent, were as follows: 5-Trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl]ether (target compound): 97.4%, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl]ether (raw material): 0.7%, 5-Trifluoromethylsulfinylpentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl]ether (by-product; disulfoxide derivative): 0.5%. The reaction mixture was an orange-brown suspension at 17°C. 5% aqueous sodium hydrogen sulfite solution (5.3g, 2.5mmol, 10mol%) and 15mL of water (0.6L / mol) were added to the reaction mixture, and the mixture was stirred at an internal temperature of 40°C for 5 minutes. The resulting mixture was separated into an organic layer and an aqueous layer. The organic layer was then concentrated under reduced pressure, and the solvent was removed by distillation. 2-propanol (19mL, 0.8L / mol) and water (5mL, 0.2L / mol) were added to the crude product, and the mixture was heated to an internal temperature of 40°C. The mixture was cooled to an internal temperature of 10°C over 2 hours, and aged for 1 hour. The resulting crystals were filtered off at 10°C. The resulting crystals were washed successively with a mixed solution of 6mL of 2-propanol (0.3L / mol) and 11mL of water (0.5L / mol), and 8mL of water (0.3L / mol). As a result, white crystals of the target product (compound Ba) were obtained with a yield of 85.9% (9.9 g, purity 96.6%).

[0337] The NMR data of the by-product disulfoxide derivative is shown below. 1 H-NMR (300MHz, CDCl 3 )δ(ppm,TMS standard):1.67-1.79(m,2H),1.90-2.01(m,4H),2.86-2.96(m,1H),3.08-3.17 (m,1H),3.33-3.41(m,1H),3.68-3.76(m,1H),4.15(t,2H),7.23(d,1H),7.55(d,1H)

[0338] R 1 No compounds in which the sulfide adjacent to was oxidized were identified in the above examples.

[0339] Comparative Example 1 Preparation of 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether

[0340] [ka]

[0341] In a 30 mL test tube, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl]ether (2.60 g, 82.7% purity, 5 mmol, 100 mol%), manganese(III) acetylacetate (35 mg, 0.1 mmol, 2 mol%) were added to methanol (4 mL, 0.8 L / mol). The mixture was cooled to 0° C. 35% hydrogen peroxide (0.728 g, 7.5 mmol, 150 mol%) was added thereto. The mixture was stirred at 0° C. for 30 min and then aged at room temperature for 24 h. The reaction mixture was analyzed by HPLC (area percentage). As a result, the components in the reaction mixture, excluding the solvent, were as follows: 5-Trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl]ether (target compound): 0%, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl]ether (raw material): 93.6%, 5-Trifluoromethylsulfinylpentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl]ether (by-product; disulfoxide derivative): 0%.

[0342] Comparative Example 2 Preparation of 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether

[0343] [ka]

[0344] In a 30 mL test tube, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl]ether (2.30 g, 93.9% purity, 5 mmol, 100 mol%), iron(III) acetylacetate (17.7 mg, 0.05 mmol, 1 mol%) were added to methanol (4 mL, 0.8 L / mol). The mixture was cooled to 0° C. 35% hydrogen peroxide (0.728 g, 7.5 mmol, 150 mol%) was added thereto. The mixture was stirred at 0° C. for 30 min and then aged at room temperature for 24 h. The reaction mixture was analyzed by HPLC (area percentage). As a result, the components in the reaction mixture, excluding the solvent, were as follows: 5-Trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl]ether (target compound): 0%, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl]ether (raw material): 93.6%, 5-Trifluoromethylsulfinylpentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl]ether (by-product; disulfoxide derivative): 0%.

[0345] Comparative Example 3 Preparation of 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether

[0346] [ka]

[0347] In a 30 mL test tube, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl]ether (2.47 g, 87% purity, 5 mmol, 100 mol%) and zirconium(IV) oxychloride octahydrate (32 mg, 0.1 mmol, 2 mol%) were added to methanol (4 mL, 0.8 L / mol). The mixture was cooled to 0° C. 35% hydrogen peroxide (0.728 g, 7.5 mmol, 150 mol%) was added thereto. The mixture was stirred at 0° C. for 30 min and then aged at room temperature for 20 h. The reaction mixture was analyzed by HPLC (area percentage). As a result, the components in the reaction mixture, excluding the solvent, were as follows: 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl]ether (target compound): 2.1%, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl]ether (raw material): 93.4%, 5-Trifluoromethylsulfinylpentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl]ether (by-product; disulfoxide derivative): 0%.

[0348] Comparative Example 4 Preparation of 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether

[0349] [ka]

[0350] In a 30 mL test tube, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl]ether (2.47 g, 87% purity, 5 mmol, 100 mol%) and sodium tungstate dihydrate (29.3 mg, 0.1 mmol, 2 mol%) were added to 2-propanol (4 mL, 0.8 L / mol). The mixture was cooled to 0° C. 35% hydrogen peroxide (0.728 g, 7.5 mmol, 150 mol%) was added thereto. The mixture was stirred at 0° C. for 30 min and then aged at room temperature for 20 h. The reaction mixture was analyzed by HPLC (area percentage). As a result, the components in the reaction mixture, excluding the solvent, were as follows: 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl]ether (target compound): 23.4%, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl]ether (raw material): 72.2%, 5-Trifluoromethylsulfinylpentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl]ether (by-product; disulfoxide derivative): 0.1%.

[0351] Comparative Example 5 Preparation of 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether

[0352] [ka]

[0353] In a 30 mL test tube, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl]ether (2.47 g, 87% purity, 5 mmol, 100 mol%) and ammonium paratungstate pentahydrate (13.1 mg, 0.004 mmol, 0.08 mol%, 1 mol% as tungsten atom) were added to methanol (4 mL, 0.8 L / mol). The mixture was cooled to 0° C. 35% hydrogen peroxide (0.728 g, 7.5 mmol, 150 mol%) was added thereto. The mixture was stirred at 0° C. for 30 minutes and then aged at room temperature for 20 hours. The reaction mixture was analyzed by HPLC (area percentage). As a result, the components in the reaction mixture, excluding the solvent, were as follows: 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl]ether (target compound): 7.3%, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl]ether (raw material): 88.3%, 5-Trifluoromethylsulfinylpentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl]ether (by-product; disulfoxide derivative): 0%.

[0354] Comparative Example 6 Preparation of 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether

[0355] [ka]

[0356] In a 30 mL test tube, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl]ether (2.60 g, 82.7% purity, 5 mmol, 100 mol%), manganese(III) acetylacetate (35 mg, 0.1 mmol, 2 mol%) were added to acetonitrile (4 mL, 0.8 L / mol). The mixture was cooled to 0° C. 35% hydrogen peroxide (0.728 g, 7.5 mmol, 150 mol%) was added thereto. The mixture was stirred at 0° C. for 30 min and then aged at room temperature for 24 h. The reaction mixture was analyzed by HPLC (area percentage). As a result, the components in the reaction mixture, excluding the solvent, were as follows: 5-Trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl]ether (target compound): 0%, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl]ether (raw material): 93.3%, 5-Trifluoromethylsulfinylpentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl]ether (by-product; disulfoxide derivative): 0%.

[0357] Comparative Example 7 Preparation of 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether

[0358] [ka]

[0359] In a 30 mL test tube, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl]ether (2.30 g, 93.9% purity, 5 mmol, 100 mol%), iron(III) acetylacetate (17.7 mg, 0.05 mmol, 1 mol%) were added to acetonitrile (4 mL, 0.8 L / mol). The mixture was cooled to 0° C. 35% hydrogen peroxide (0.728 g, 7.5 mmol, 150 mol%) was added thereto. The mixture was stirred at 0° C. for 30 min and then aged at room temperature for 24 h. The reaction mixture was analyzed by HPLC (area percentage). As a result, the components in the reaction mixture, excluding the solvent, were as follows: 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl]ether (target compound): 0.9%, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl]ether (raw material): 93.8%, 5-Trifluoromethylsulfinylpentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl]ether (by-product; disulfoxide derivative): 0%.

[0360] Comparative Example 8 Preparation of 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether

[0361] [ka]

[0362] In a 30 mL test tube, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl]ether (2.47 g, 87% purity, 5 mmol, 100 mol%), zirconium(IV) oxychloride octahydrate (32 mg, 0.1 mmol, 2 mol%) were added to acetonitrile (4 mL, 0.8 L / mol). The mixture was cooled to 0° C. 35% hydrogen peroxide (0.728 g, 7.5 mmol, 150 mol%) was added thereto. The mixture was stirred at 0° C. for 30 min and then aged at room temperature for 20 h. The reaction mixture was analyzed by HPLC (area percentage). As a result, the components in the reaction mixture, excluding the solvent, were as follows: 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl]ether (target compound): 1%, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl]ether (raw material): 94.4%, 5-Trifluoromethylsulfinylpentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl]ether (by-product; disulfoxide derivative): 0%.

[0363] Comparative Example 9 Preparation of 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether

[0364] [ka]

[0365] In a 30 mL test tube, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl]ether (4.7 g, 90.4% purity, 10 mmol, 100 mol%), sodium tungstate dihydrate (164 mg, 0.5 mmol, 5 mol%) were added to acetonitrile (5 mL, 0.5 L / mol). The mixture was cooled to 0° C. 35% hydrogen peroxide (1.2 g, 12 mmol, 120 mol%) was added thereto. The mixture was stirred at 0° C. for 30 min and then aged at room temperature for 69 h. The reaction mixture was analyzed by HPLC (area percentage). As a result, the components in the reaction mixture, excluding the solvent, were as follows: 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl]ether (target compound): 26%, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl]ether (raw material): 65.8%, 5-Trifluoromethylsulfinylpentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl]ether (by-product; disulfoxide derivative): 0%.

[0366] Comparative Example 10 Preparation of 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether

[0367] [ka]

[0368] In a 30 mL test tube, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl]ether (2.47 g, 87% purity, 5 mmol, 100 mol%), ammonium paratungstate pentahydrate (13.1 mg, 0.004 mmol, 0.08 mol%, 1 mol% as tungsten atom) were added to acetonitrile (4 mL, 0.8 L / mol). The mixture was cooled to 0°C. 35% hydrogen peroxide (0.728 g, 7.5 mmol, 150 mol%) was added thereto. The mixture was stirred at 0°C for 30 minutes and then aged at room temperature for 20 hours. The reaction mixture was analyzed by HPLC (area percentage). As a result, the components in the reaction mixture, excluding the solvent, were as follows: 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl]ether (target compound): 1.5%, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl]ether (raw material): 94.1%, 5-Trifluoromethylsulfinylpentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl]ether (by-product; disulfoxide derivative): 0%.

[0369] Comparative Example 11 Preparation of 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether

[0370] [ka]

[0371] (1) Preparation of catalyst solution To a screw-capped vial, vanadyl acetylacetonate (1.3 mg, 0.005 mmol, 1 mol%), (E)-2-{[(1-hydroxy-2-methylpropan-2-yl)imino]methyl}phenol (ligand (3-4) described in WO2017 / 150478 (Patent Document 2), 1.0 mg, 0.005 mmol, 1 mol%), sodium 2,6-dimethoxybenzoate (benzoic acid derivative (4-1) described in WO2017 / 150478 (Patent Document 2), 5.1 mg, 0.025 mmol, 5 mol%), and dichloromethane (1 mL, 0.5 L / mol) were added. The mixture was stirred at room temperature for 30 min. (2) Preparation of the Title Compound 5-Trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl]ether (244 mg, purity 88.2%, 0.500 mmol, 100 mol%) was dissolved in dichloromethane (1 mL, 0.5 L / mol). The catalyst solution prepared in (1) above was added thereto. The mixture was cooled to 0°C. 35% hydrogen peroxide (97.1 mg, 1.0 mmol, 200 mol%) was added thereto. The mixture was stirred at 0°C for 15 hours. The organic layer of the reaction mixture was analyzed by HPLC (area percentage). As a result, the components in the reaction mixture excluding the solvent, etc. were as follows; 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl]ether (target compound): 1.2%, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl]ether (raw material): 92.3%, 5-Trifluoromethylsulfinylpentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl]ether (by-product; disulfoxide derivative): 0%.

[0372] Comparative Example 11 was carried out by changing the metal catalyst in WO2017 / 150478 (Patent Document 2) from an iron catalyst to a vanadium catalyst. It is difficult to obtain the target product (B) of the present invention by only changing the metal catalyst. By-products;

[0373] Comparative Example 12 Preparation of 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether

[0374] [ka]

[0375] In a 30 mL test tube, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl]ether (2.30 g, 93.9% purity, 5 mmol, 100 mol%), iron(III) acetylacetate (17.7 mg, 0.05 mmol, 1 mol%) were added to dichloromethane (4 mL, 0.8 L / mol). The mixture was cooled to 0° C. 35% hydrogen peroxide (0.728 g, 7.5 mmol, 150 mol%) was added thereto. The mixture was stirred at 0° C. for 30 min and then aged at room temperature for 24 h. The reaction mixture was analyzed by HPLC (area percentage). As a result, the components in the reaction mixture, excluding the solvent, were as follows: 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl]ether (target compound): 2.3%, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl]ether (raw material): 93.2%, 5-Trifluoromethylsulfinylpentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl]ether (by-product; disulfoxide derivative): 0%.

[0376] Comparative Example 13 Preparation of 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether

[0377] [ka]

[0378] 5-Trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl]ether (14.65g, purity 88%, 30mmol, 100mol%), vanadyl acetylacetonate (318mg, 1.2mmol, 4mol%) and chloroform (40mL, 1.3L / mol) were added to a 250mL reaction flask and stirred at an internal temperature of 25°C for 10 minutes. Then, 35% hydrogen peroxide (5.24g, 54mmol, 180mol%) was added dropwise to the mixture over 10 minutes. After aging at an internal temperature of 25°C for 4 hours, the organic layer of the reaction mixture was analyzed by HPLC (area percentage). As a result, the components in the reaction mixture excluding the solvent, etc. were as follows; 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl]ether (target compound): 2.2%, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl]ether (raw material): 93.7%, 5-Trifluoromethylsulfinylpentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl]ether (by-product; disulfoxide derivative): 0%.

[0379] Comparative Example 14 Preparation of 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether

[0380] [ka]

[0381] 5-Trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl]ether (14.65 g, purity 88%, 30 mmol, 100 mol%), vanadyl acetylacetonate (318 mg, 1.2 mmol, 4 mol%) and chloroform (40 mL, 1.3 L / mol) were added to a 250 mL reaction flask and stirred at an internal temperature of 25° C. for 10 minutes. Then, (S)-(2,4-di-tert-butyl-6-{(E)-[(1-hydroxy-3,3-dimethylbutan-2-yl)imino]methyl}phenol (600 mg, 1.8 mmol, 6 mol%) was added. After 10 minutes, 35% hydrogen peroxide (5.24 g, 54 mmol, 180 mol%) was added dropwise over 10 minutes. After aging for 4 hours at an internal temperature of 25°C, the organic layer of the reaction mixture was analyzed by HPLC (area percentage). As a result, the components in the reaction mixture excluding the solvent, etc. were as follows; 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl]ether (target compound): 17.5%, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl]ether (raw material): 70.5%, 5-Trifluoromethylsulfinylpentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl]ether (by-product; disulfoxide derivative): 0%. The reaction was continued for another 20 hours, but the reaction rate was unchanged from that after 4 hours.

[0382] Comparative Example 13 and Comparative Example 14 are follow-up tests of the prior art using a ligand and a vanadium catalyst. In Comparative Example 13, the reaction was carried out in the method of US2011 / 0015405A1 (JP2012-532906) (Patent Document 3) and Example 1 without using a ligand, as in the examples of the present invention. It is difficult to obtain the target product (B) of this reaction by simply changing the presence or absence of the ligand. In Comparative Example 14, the reaction was carried out in the same manner using the same metal catalyst, ligand, oxidizing agent, and solvent as in US2011 / 0015405A1 (JP2012-532906) (Patent Document 3) and Example 1. As shown in Comparative Example 14, even when the method of the prior art was applied to the raw material of the present invention, the reaction did not proceed sufficiently. It was confirmed that the prior art cannot be applied to the production of the target product of the present invention.

[0383] Example 20 White crystals of the compound of formula (Ba) were obtained by the same manufacturing method as in Example 16. Here, the crystals obtained by the same method as in Example 16 were used as seed crystals. The obtained crystals were dried in a vacuum. The melting point was 46°C to 50°C. The obtained crystals were subjected to powder X-ray diffraction measurement. The results of the powder X-ray diffraction measurement are shown in Figure 1.

[0384] Example 21 White crystals of the compound of formula (Ba) were obtained by the same manufacturing method as in Example 16. Here, the crystals obtained by the same method as in Example 16 were used as seed crystals. The obtained crystals were melted, dried under reduced pressure to remove water, and then cooled. The obtained crystals were pulverized in a mill. The melting point was 47°C to 48°C. The obtained crystals were subjected to powder X-ray diffraction measurement. The results of the powder X-ray diffraction measurement are shown in Figure 2.

[0385] Example 22 White crystals of the compound of formula (Ba) were obtained by the same manufacturing method as in Example 1. The obtained crystals were subjected to recrystallization. Here, the recrystallization conditions were the same as the crystallization conditions in Example 1 (recrystallization from 2-propanol and water). The obtained crystals were filtered and dried. The melting point was 46°C to 50°C. The obtained crystals were subjected to powder X-ray diffraction measurement. The results of the powder X-ray diffraction measurement are shown in Figure 3.

[0386] [Table 1]

[0387] Reference manufacturing example 1 Production of 4-fluoro-2-chlorophenol

[0388] [ka]

[0389] In a 1000 mL reaction flask, 2-fluorophenol (112.1 g, 100% purity, 1000 mmol, 100 mol%), diphenyl sulfide (372.5 mg, 2.000 mmol, 0.2 mol%), and anhydrous iron(III) chloride (162.2 mg, 1.000 mmol, 0.1 mol%) were added to dichloromethane (610 mL, 0.61 L / mol). The mixture was stirred at an internal temperature of 5-10°C for 30 minutes. Chlorine gas (70.9 g, 1000 mmol, 100 mol%) was bubbled in at an internal temperature of 5-10°C for 6 hours, and the mixture was aged for 1 hour while maintaining the internal temperature at 5-10°C. The reaction mixture was a clear yellow liquid at 10° C. Nitrogen gas was blown into the reaction mixture at 60 mL / min for 2 hours. As a result, the target dichloromethane solution was obtained in a yield of 97% (909.7 g, purity 15.6%).

[0390] 1 H-NMR (300MHz, CDCl 3 )δ(ppm,TMS standard):5.09(d,1H),6.94(dd,1H),7.02(ddd,1H),7.11(dd,1H) [Industrial Applicability]

[0391] As disclosed in Patent Document 1, the monosulfoxide derivative of formula (B) has excellent acaricidal activity.

[0392] According to the present invention, there is provided a novel, industrially preferred process for producing the monosulfoxide derivatives of the formula (B), which are useful as agricultural chemicals such as acaricides. As described herein above, the method of the present invention is economical, environmentally friendly and has high industrial applicability. In particular, the method of the present invention can selectively produce the desired monosulfoxide derivatives while avoiding over-oxidation to disulfoxide derivatives, and further allows simple operations without using ligands. Thus, the present invention has the advantage that it does not require removal of the by-product disulfoxide derivative, which is difficult to remove.

[0393] In summary, the present invention has high industrial applicability.

[0394] All publications, patents, and patent applications mentioned herein are fully incorporated herein by reference in their entirety for the purpose of describing and disclosing the methods described therein that may be used in connection with the description herein. To the extent necessary to understand or complete the disclosure of the present invention, all publications, patents, and patent applications mentioned herein are expressly incorporated herein by reference to the same extent as if each were individually incorporated. All publications, patents, and patent applications discussed above and throughout the specification are provided solely for their disclosure prior to the filing date of this application.

[0395] Any methods and reagents similar or equivalent to those described herein can be used in the methods and practice of this invention. Thus, it is intended that the invention not be limited by the above description, but be defined by the claims and their equivalents. Such equivalents are within the scope of the invention as defined by the appended claims.

Claims

1. Formula (B): (In the formula, R １ is a C1-C4 alkyl group, a C2-C4 alkenyl group, a C2-C4 alkynyl group, a C1-C4 haloalkyl group, a C2-C4 haloalkenyl group, or a C2-C4 haloalkynyl group; R ２ and R ３ are each independently a hydrogen atom, a halogen atom, a C1-C4 alkyl group, a C2-C4 alkenyl group, a C2-C4 alkynyl group, a C1-C4 haloalkyl group, a C2-C4 haloalkenyl group, or a C2-C4 haloalkynyl group, a C1-C4 alkoxy group, or a C1-C4 haloalkoxy group; and n is 5 or 6, Formula (A): (In the formula, R １ , R ２ , R 3 and n is as defined above. with hydrogen peroxide in the presence of a metal catalyst, wherein the metal catalyst is one or more catalysts selected from the group consisting of vanadium catalysts, molybdenum catalysts and titanium catalysts, the oxidation step is carried out in a solvent which is a nitrile or an alcohol, or a mixture of a nitrile or an alcohol and water, and no benzoic acid derivative is used in the oxidation step.

2. The method of claim 1 , wherein the metal catalyst is a vanadium catalyst.

3. 2. The method of claim 1, wherein the alcohol is a C1-C6 aliphatic alcohol.

4. 2. The method of claim 1, wherein the alcohol is methanol, ethanol, 2-propanol, t-butanol or t-amyl alcohol.

5. 2. The method of claim 1, wherein the alcohol is methanol, 2-propanol, t-butanol or t-amyl alcohol.

6. 2. The process of claim 1, wherein the solvent is acetonitrile, methanol, 2-propanol, t-butanol, or t-amyl alcohol, or a mixture thereof with water.

7. The method according to any one of claims 1 to 6, further comprising recovering the crystals of the compound of formula (B) after the oxidation step.

8. Formula (C): (In the formula, R １ is a C1-C4 alkyl group, a C2-C4 alkenyl group, a C2-C4 alkynyl group, a C1-C4 haloalkyl group, a C2-C4 haloalkenyl group, or a C2-C4 haloalkynyl group; R ２ and R ３ are each independently a hydrogen atom, a halogen atom, a C1-C4 alkyl group, a C2-C4 alkenyl group, a C2-C4 alkynyl group, a C1-C4 haloalkyl group, a C2-C4 haloalkenyl group, a C2-C4 haloalkynyl group, a C1-C4 alkoxy group, or a C1-C4 haloalkoxy group; and n is 5 or 6. The method according to any one of claims 1 to 7, wherein the content of the compound of formula (B) is 10% or less by weight based on the weight of the compound of formula (B).

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