Process for producing a mono-sulfoxide derivative

Abstract

The present invention provides a method for manufacturing a mono-sulfoxide derivative.

Description

Technical Field

[0001] The present invention relates to a method for producing a mono-sulfoxide derivative. Background Art

[0002] Sulfoxide derivatives have attracted attention in the fields of pesticides and the like (Patent Document 1). Therefore, it is important to selectively and highly efficiently produce sulfoxide derivatives. As a method for producing sulfoxide derivatives, oxidation of sulfide derivatives is known. However, the oxidation of conventional sulfide derivatives has the following disadvantages or problems.

[0003] Examples 13 and 27 of Patent Document 1 disclose that sulfoxide derivatives can be produced by an oxidation reaction using m-chloroperoxybenzoic acid. However, in view of the environment, the use of m-chloroperoxybenzoic acid is not preferred for industrial production. The reasons are as follows. After the reaction, m-chloroperoxybenzoic acid becomes m-chlorobenzoic acid as a waste product. As a result, the use of m-chloroperoxybenzoic acid imposes a heavy burden on the environment. In addition, m-chloroperoxybenzoic acid is expensive, so the method using m-chloroperoxybenzoic acid is not preferred industrially.

[0004] On the other hand, oxidation using hydrogen peroxide is a method that is industrially more preferred and useful. The reasons are as follows. Since hydrogen peroxide becomes harmless water after the reaction, it is environmentally friendly. Moreover, hydrogen peroxide is relatively inexpensive industrially.

[0005] Patent Documents 2 and 3 disclose that sulfoxide derivatives can be produced by an oxidation reaction using hydrogen peroxide with a catalyst that essentially requires a ligand. However, the ligand is difficult to obtain industrially and must be prepared in advance. Further, a catalyst must be prepared from a metal compound and a ligand before the start of the reaction. From the viewpoint of the difficulty and / or cost in industrial production, the use of the ligand is not preferred industrially. In addition, complicated operations are required to remove the used ligand. Further, the method described in Patent Document 2 uses a benzoic acid derivative. From the same viewpoint as above, the use of the benzoic acid derivative is not preferred industrially.

[0006] Further, for example, it has been found that the method described in Patent Document 2 also requires complicated operations for removing the metal used as a catalyst.

[0007] Prior Art Documents

[0008] Patent Documents

[0009] Patent Document 1: International Publication No. 2013 / 157229

[0010] Patent Document 2: International Publication No. 2017 / 150478

[0011] Patent Document 3: US2011 / 0015405A1 (Japanese Patent Application Laid-Open No. 2012-532906) Summary of the Invention

[0012] Problems to be Solved by the Invention

[0013] There is an urgent need for a method for producing a sulfoxide derivative that can solve one or more of the disadvantages or problems in the above prior art.

[0014] Therefore, an object of the present invention is to provide a method for producing a sulfoxide derivative that is industrially preferable, more economical, and environmentally friendly. In other words, it is desired to provide a method that is inexpensive and can reduce the environmental load.

[0015] For example, one specific object of the present invention is to produce a sulfoxide derivative using hydrogen peroxide, which is attracting attention as a clean and excellent oxidizing agent, instead of using m-chloroperoxybenzoic acid as an oxidizing agent.

[0016] Another specific object of the present invention is to provide a simple and inexpensive production method that does not use a ligand and a benzoic acid derivative. This production method can also avoid the complicated operations for removing the ligand and benzoic acid.

[0017] Another specific object of the present invention is to avoid the complicated operations for removing the metal used as a catalyst.

[0018] In addition, in the study of oxidation reactions without using ligands, etc., the following problems were found. The thioether derivative of the following formula (A) has the following structural characteristics: it has 2 thioether moieties that are oxidized in the oxidation reaction. It is necessary to selectively produce a mono sulfoxide derivative in a case where only one of the thioether moieties is selectively oxidized and the other thioether moiety is not oxidized.

[0019] Specifically, as described below. In the oxidation reaction of the thioether derivative of the following formula (A), it is possible to generate a desired compound and an undesired compound due to 2 reaction points. The desired product is the mono sulfoxide derivative of the following formula (B), while on the other hand, the di sulfoxide derivative of the following formula (C) is not needed. The unwanted by-product, that is, the di sulfoxide derivative of formula (C), will reduce the yield of the target mono sulfoxide derivative of formula (B). Further, the physical properties of both derivatives are similar, so in industrial production, it is difficult to obtain the refined target mono sulfoxide derivative of formula (B) by removing the by-product di sulfoxide derivative of formula (C) from the crude product after the oxidation reaction. That is, it is difficult to separate and refine the target product on an industrial scale and with a high yield. Therefore, it is desired to avoid non-selective oxidation (i.e., over-oxidation) to the di sulfoxide derivative of formula (C) and thus selectively produce the target mono sulfoxide derivative of formula (B).

[0020]

[0021] In summary, another specific object of the present invention is to provide a method capable of selectively and in high yield producing only a desired mono-sulfoxide derivative from a thioether derivative having the following structural characteristics: there are two thioether sites capable of being oxidized. To achieve this object, a selective oxidation reaction that avoids over-oxidation needs to be provided.

[0022] Technical means for solving the problem

[0023] In view of the above situation, the present inventors have intensively studied the method for producing sulfoxide derivatives. As a result, the present inventors unexpectedly found that by providing the following production method of the compound of formula (B), the above problems can be solved. Based on the above knowledge and insights, the present inventors have thus completed the present invention.

[0024] That is, the present invention is as described below.

[0025] [1] A method for producing a mono-sulfoxide derivative, which is a method for producing a mono-sulfoxide derivative of formula (B),

[0026]

[0027] In formula (B),

[0028] 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,

[0029] 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, a C1-C4 haloalkoxy group, and

[0030] n is 5 or 6, wherein the production method includes the following oxidation step:

[0031] Reacting a thioether derivative of formula (A) with hydrogen peroxide in the presence of a metal catalyst,

[0032]

[0033] In formula (A), R 1 、R 2 、R 3 and n are as defined above.

[0034] [2] The method according to [1], wherein R1 is a C1-C4 haloalkyl,

[0035] R 2 and R 3 are each independently a halogen atom or a C1-C4 alkyl group, and

[0036] n is 5 or 6.

[0037] [3] The method according to [1], wherein R 1 is trifluoromethyl,

[0038] R 2 is a fluorine atom, R 3 is a chlorine atom,

[0039] or R 2 and R 3 are methyl groups, and

[0040] n is 5 or 6.

[0041] [4] The method according to [1], wherein R 1 is trifluoromethyl,

[0042] R 2 is a fluorine atom,

[0043] R 3 is a chlorine atom, and

[0044] n is 5.

[0045] [5] The method according to [1], wherein R 1 is trifluoromethyl,

[0046] R 2 and R 3 are methyl groups, and

[0047] n is 6.

[0048] [6] The method according to any one of [1] to [5], wherein the metal catalyst is one or more (more preferably 1 or 2, even more preferably 1) catalysts selected from the group consisting of vanadium catalysts, molybdenum catalysts, and titanium catalysts.

[0049] [7] The method according to any one of [1] to [5], wherein the metal catalyst is a vanadium catalyst or a molybdenum catalyst.

[0050] [8] The method according to any one of [1] to [5], wherein the metal catalyst is a vanadium catalyst.

[0051] [9] The method according to any one of [1] to [5], wherein the metal catalyst is a molybdenum catalyst.

[0052]

[10] The method according to any one of [1] to [5], wherein the metal catalyst is one or more (more preferably one or two, even more preferably one) catalysts selected from the group consisting of vanadyl acetylacetonate, vanadium(III) acetylacetonate, vanadium(V) oxide, vanadium(V) oxychloride, titanium(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.

[0053]

[11] The method according to any one of [1] to [5], wherein the metal catalyst is one or more (more preferably one or two, even more preferably one) catalysts selected from the group consisting of vanadyl acetylacetonate, vanadium(III) acetylacetonate, titanium(IV) acetylacetonate, and ammonium molybdate.

[0054]

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

[0055]

[13] The method according to any one of [1] to [5], wherein the metal catalyst is one or more (more preferably one or two, even more preferably one) catalysts selected from the group consisting of vanadyl acetylacetonate, vanadium(III) acetylacetonate, and ammonium molybdate.

[0056]

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

[0057]

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

[0058]

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

[0059]

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

[0060]

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

[0061]

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

[18] , wherein the oxidation step is carried out in a solvent.

[0062]

[20] The method according to

[19] , wherein in the oxidation step, the concentration of the compound of formula (A) at the start of the reaction is 5 to 75% by weight.

[0063]

[21] The method according to

[19] , wherein in the oxidation step, the concentration of the compound of formula (A) at the start of the reaction is 20 to 60% by weight.

[0064]

[22] The method according to

[19] , wherein in the oxidation step, the concentration of the compound of formula (A) at the start of the reaction is 35 to 50% by weight.

[0065]

[23] The method according to any one of

[19] to

[22] , wherein the solvent is a solvent in which the compound of formula (A) has a higher solubility and the compound of formula (B) has a lower solubility.

[0066]

[24] The method according to any one of

[19] to

[23] , wherein 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.

[0067]

[25] The method according to any one of

[19] to

[23] , wherein 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.

[0068]

[26] The method according to any one of

[19] to

[23] , wherein 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.

[0069]

[27] The method according to any one of

[19] to

[23] , wherein 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.

[0070]

[28] The method according to any one of

[19] to

[23] , wherein 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.

[0071]

[29] The method according to any one of

[19] to

[28] , wherein 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.

[0072]

[30] The method according to any one of

[19] to

[28] , wherein 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.

[0073]

[31] The method according to any one of

[19] to

[28] , wherein 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.

[0074]

[32] The method according to any one of

[19] to

[31] , wherein the solvent is a solvent containing alcohols.

[0075]

[33] The method according to any one of

[19] to

[31] , wherein the solvent is an alcohol or a mixture of an alcohol and water (more preferably a mixture of an alcohol and water).

[0076]

[34] The method according to

[32] or

[33] , wherein the alcohol is a C1 - C6 aliphatic alcohol (more preferably a C1 - C5 aliphatic alcohol).

[0077]

[35] The method according to

[32] or

[33] , wherein the alcohol is a C1 - C4 aliphatic alcohol.

[0078]

[36] The method according to

[32] or

[33] , wherein the alcohol is methanol, ethanol, 2 - propanol, tert - butanol or tert - pentanol (more preferably methanol, ethanol, 2 - propanol or tert - butanol).

[0079]

[37] The method according to

[32] or

[33] , wherein the alcohol is methanol, 2 - propanol, tert - butanol or tert - pentanol.

[0080]

[38] The method according to

[32] or

[33] , wherein the alcohol is 2 - propanol, tert - butanol or tert - pentanol (more preferably 2 - propanol or tert - butanol).

[0081]

[39] The method according to

[32] or

[33] , wherein the alcohol is tert - butanol or tert - pentanol.

[0082]

[40] The method according to

[32] or

[33] , wherein the alcohol is tert - butanol.

[0083]

[41] The method according to any one of

[19] to

[31] , wherein the solvent is a nitrile solvent or an alcohol solvent, or a mixture of a nitrile solvent or an alcohol solvent and water.

[0084]

[42] The method according to any one of

[19] to

[31] , wherein the solvent is acetonitrile, methanol, 2-propanol, tert-butanol or tert-pentanol, or a mixture of the solvent and water (more preferably acetonitrile, 2-propanol, tert-butanol or tert-pentanol, or a mixture of the solvent and water) (even more preferably acetonitrile, 2-propanol or tert-butanol, a mixture of the solvent and water) (even further more preferably a mixture of tert-butanol and water, or a mixture of tert-pentanol and water) (particularly preferably a mixture of tert-butanol and water).

[0085]

[43] The method according to any one of

[19] to

[31] , wherein the solvent is acetonitrile, or a mixture of acetonitrile and water (more preferably a mixture of acetonitrile and water).

[0086]

[44] The method according to any one of

[19] to

[31] , wherein the solvent is a halogenated solvent, or a mixture of a halogenated solvent and water.

[0087]

[45] The method according to any one of

[19] to

[31] , wherein the solvent is dichloromethane, or a mixture of dichloromethane and water (more preferably a mixture of dichloromethane and water).

[0088]

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

[45] , wherein an aqueous hydrogen peroxide solution is added to the solution containing the compound of formula (A) and the metal compound.

[0089]

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

[46] , wherein the aforementioned oxidation step is carried out at -10°C to 60°C.

[0090]

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

[46] , wherein the aforementioned oxidation step is carried out at 10°C to 35°C.

[0091]

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

[46] , wherein the aforementioned oxidation step is carried out at 25°C to 35°C.

[0092]

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

[46] , wherein the aforementioned oxidation step is carried out at 15°C to 20°C.

[0093]

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

[50] , wherein the rate of addition of hydrogen peroxide is 0.5 mol / h or less relative to 1 mol of the thioether derivative of formula (A) (more preferably 0.1 mol / h to 0.5 mol / h).

[0094]

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

[50] , wherein the rate of adding hydrogen peroxide is 0.05 mol / hour to 0.5 mol / hour relative to 1 mol of the thioether derivative of formula (A).

[0095]

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

[52] , wherein the aforementioned oxidation step is carried out for 3 hours or more (or 6 hours or more).

[0096]

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

[53] , wherein the aforementioned oxidation step is carried out for 48 hours or less (or 24 hours or less).

[0097]

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

[54] , wherein in the aforementioned oxidation step, crystals of the compound of formula (B) precipitate.

[0098]

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

[54] , wherein in or after the aforementioned oxidation step, crystals of the compound of formula (B) precipitate.

[0099]

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

[54] , wherein after the aforementioned oxidation step, it includes a step of precipitating crystals of the compound of formula (B).

[0100]

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

[54] , wherein in the aforementioned oxidation step, it includes the precipitation of crystals of the compound of formula (B), or after the aforementioned step, it includes a step of precipitating crystals of the compound of formula (B).

[0101]

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

[58] , wherein after the aforementioned oxidation step, it includes a step of recovering the crystals of the compound of formula (B).

[0102]

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

[59] , wherein the yield of the compound of formula (B) in the oxidation step is 85 to 100%.

[0103]

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

[59] , wherein the yield of the compound of formula (B) in the oxidation step is 90 to 100%.

[0104]

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

[59] , wherein no ligand is used in the aforementioned oxidation step.

[0105]

[63] The method as described in

[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).

[0106]

[64] The method as described in

[62] , wherein the ligand is a compound of formula (D),

[0107]

[0108] 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,

[0109] R 6 is a C1-C4 alkyl group, a cyano group, a nitro group, a carboxyl group, a C1-C4 alkoxycarbonyl group, a C1-C4 alkanoyl 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 carboxyl C1-C4 alkyl group or a C1-C4 alkoxycarbonyl C1-C4 alkyl group,

[0110] 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.

[0111]

[65] The method as described in any one of [1] to

[64] , wherein no carboxylic acid derivative is used in the foregoing step.

[0112]

[66] The method as described in any one of [1] to

[65] , wherein no benzoic acid derivative is used in the foregoing step.

[0113]

[67] The method as described in

[66] , wherein the benzoic acid derivative is a compound of formula (E),

[0114]

[0115] In formula (E), 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,

[0116] M is a hydrogen atom, an alkali metal atom or an alkaline earth metal atom,

[0117] n is 1 or 2.

[0118]

[68] The method according to

[66] , wherein the benzoic acid derivative is sodium 2,6-dimethoxybenzoate.

[0119]

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

[68] , wherein in the oxidation step, the amount of hydrogen peroxide used is 1.0 to 1.5 moles relative to 1 mole of the thioether derivative of formula (A).

[0120]

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

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

[0121]

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

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

[0122]

[0123] In formula (C),

[0124] 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,

[0125] 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, a C1-C4 haloalkoxy group, and

[0126] n is 5 or 6.

[0127]

[72] The method according to

[71] , wherein,

[0128] the content of the sulfoxide derivative of formula (C) is 0% to 10%.

[0129]

[73] The method according to

[71] , wherein,

[0130] the content of the sulfoxide derivative of formula (C) is 0% to 5%.

[0131]

[74] The method according to

[71] , wherein,

[0132] The content of the sulfoxide derivative of formula (C) is 0% to 2%.

[0133]

[75] The method as described in

[71] , wherein,

[0134] The content of the sulfoxide derivative of formula (C) is 0% to 1%.

[0135]

[76] A mono-sulfoxide derivative, which is a mono-sulfoxide derivative of formula (B),

[0136]

[0137] In formula (B),

[0138] 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,

[0139] 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, a C1-C4 haloalkoxy group, and

[0140] n is 5 or 6, wherein,

[0141] The content of the sulfoxide derivative of formula (C) is 10% or less relative to the weight of the compound of formula (B),

[0142]

[0143] In formula (C),

[0144] 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,

[0145] 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, a C1-C4 haloalkoxy group, and

[0146] n is 5 or 6.

[0147]

[77] The mono-sulfoxide derivative as described in

[76] , wherein,

[0148] The content of the sulfoxide derivative of formula (C) is 0% to 10%.

[0149]

[78] The mono-sulfoxide derivative as described in

[76] , wherein,

[0150] The content of the di-sulfoxide derivative of formula (C) is 0% to 5%.

[0151]

[79] The mono-sulfoxide derivative as described in

[76] , wherein,

[0152] The content of the di-sulfoxide derivative of formula (C) is 0% to 2%.

[0153]

[80] The mono-sulfoxide derivative as described in

[76] , wherein,

[0154] The content of the di-sulfoxide derivative of formula (C) is 0% to 1%.

[0155]

[81] A mono-sulfoxide derivative of formula (B), which is a solid,

[0156]

[0157] wherein, 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, a C1-C4 haloalkoxy group, and n is 5 or 6.

[0158]

[82] A mono-sulfoxide derivative of the following formula (B), which is a crystalline solid,

[0159]

[0160] wherein, 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, a C1-C4 haloalkoxy group, and n is 5 or 6.

[0161]

[83] A mono-sulfoxide derivative of formula (B), which is a solid at 25 °C,

[0162]

[0163] wherein, 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, a C1-C4 haloalkoxy group, and n is 5 or 6.

[0164]

[84] A monosulfoxide derivative of formula (B), which has a melting point of 40°C to 50°C,

[0165]

[0166] wherein, 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, a C1-C4 haloalkoxy group, and n is 5 or 6.

[0167]

[85] A monosulfoxide derivative of formula (B), which has a melting point of 46°C to 50°C,

[0168]

[0169] wherein, 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, a C1-C4 haloalkoxy group, and n is 5 or 6.

[0170]

[86] A monosulfoxide derivative of formula (B), which has a melting point of 41°C to 45°C,

[0171]

[0172] wherein, 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, a C1-C4 haloalkoxy group, and n is 5 or 6.

[0173]

[87] The mono sulfoxide derivative according to any one of

[76] to

[86] , wherein,

[0174] R 1 is a C1-C4 haloalkyl group,

[0175] R 2 and R 3 are each independently a halogen atom or a C1-C4 alkyl group, and

[0176] n is 5 or 6.

[0177]

[88] The mono sulfoxide derivative according to any one of

[76] to

[86] , wherein,

[0178] R 1 is trifluoromethyl,

[0179] R 2 is a fluorine atom and R 3 is a chlorine atom, or R 2 and R 3 are methyl groups, and

[0180] n is 5 or 6.

[0181]

[89] The mono sulfoxide derivative according to any one of

[76] to

[86] , wherein,

[0182] R 1 is trifluoromethyl,

[0183] R 2 is a fluorine atom,

[0184] R 3 is a chlorine atom, and

[0185] n is 5.

[0186]

[90] The mono sulfoxide derivative according to any one of

[76] to

[86] , wherein,

[0187] R 1 is trifluoromethyl,

[0188] R 2 and R3 is methyl, and

[0189] n is 6.

[0190]

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

[90] , wherein

[0191] The compound of formula (B) is a crystal.

[0192]

[92] A compound of formula (B),

[0193]

[0194] In formula (B),

[0195] R 1 is C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C2-C4 haloalkenyl or C2-C4 haloalkynyl,

[0196] R 2 and R 3 are each independently a hydrogen atom, a halogen atom, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C2-C4 haloalkenyl, C2-C4 haloalkynyl, C1-C4 alkoxy, or C1-C4 haloalkoxy, and

[0197] n is 5 or 6, wherein

[0198] The content of the compound of formula (C) is 10% or less by weight relative to the compound of formula (B),

[0199]

[0200] In formula (C),

[0201] R 1 is C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C2-C4 haloalkenyl or C2-C4 haloalkynyl,

[0202] R 2 and R 3 are each independently a hydrogen atom, a halogen atom, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C2-C4 haloalkenyl, C2-C4 haloalkynyl, C1-C4 alkoxy, or C1-C4 haloalkoxy, and

[0203] n is 5 or 6.

[0204]

[93] A crystal of a compound of formula (B-a), 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°.

[0205]

[0206] Advantages of the invention

[0207] According to the present invention, it is possible to provide a novel and industrially applicable manufacturing method of the above-mentioned mono-sulfoxide derivative of formula (B), which is useful as an acaricide, etc. According to the present invention, it is possible to provide a manufacturing method of a sulfoxide derivative, which can solve one or more of the above-mentioned drawbacks or problems in the prior art. Therefore, it is possible to provide a method that is inexpensive and can reduce the environmental load.

[0208] For example, it is possible to use hydrogen peroxide, which is attracting attention as a clean and excellent oxidizing agent, to manufacture a sulfoxide derivative without using m-chloroperoxybenzoic acid as an oxidizing agent.

[0209] In addition, it is possible to provide a simple and inexpensive manufacturing method that does not use a ligand and a benzoic acid derivative. Therefore, it is also possible to avoid the complicated operations for removing the ligand and benzoic acid.

[0210] Furthermore, it is possible to avoid the complicated operations for removing the metal used as a catalyst.

[0211] In addition, it is possible to provide a method that can selectively and in high yield produce only the desired mono-sulfoxide derivative from a thioether derivative, which has the following structural characteristics: there are two thioether sites that can be oxidized. That is, it is possible to provide a selective oxidation reaction that avoids over-oxidation.

[0212] Therefore, the method of the present invention is preferably used industrially, more economical, and also environmentally friendly. BRIEF DESCRIPTION OF THE DRAWINGS

[0213] Figure 1The powder X-ray diffraction spectrum of the crystal of the compound of formula (B-a) obtained in Example 20. White crystals of the compound of formula (B-a) were obtained by the same production 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 under vacuum. The melting point was 46°C to 50°C. The obtained crystals were used for powder X-ray diffraction measurement. The results of the powder X-ray diffraction measurement are shown in Figure 1 .

[0214] Figure 2 The powder X-ray diffraction spectrum of the crystal of the compound of formula (B-a) obtained in Example 21. White crystals of the compound of formula (B-a) were obtained by the same production 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, and water was removed by drying under reduced pressure, and then cooled. The obtained crystals were pulverized with a grinder. The melting point was 47°C to 48°C. The obtained crystals were used for powder X-ray diffraction measurement. The results of the powder X-ray diffraction measurement are shown in Figure 2 .

[0215] Figure 3 The powder X-ray diffraction spectrum of the crystal of the compound of formula (B-a) obtained in Example 22. White crystals of the compound of formula (B-a) were obtained by the same production method as in Example 1. The obtained crystals were used for recrystallization. Here, the recrystallization conditions were the same as the crystallization conditions of Example 1 (recrystallization with 2-propanol and water). The obtained crystals were filtered and dried. The melting point was 46°C to 50°C. The obtained crystals were used for powder X-ray diffraction measurement. The results of the powder X-ray diffraction measurement are shown in Figure 3 . Detailed Description of the Invention

[0216] Hereinafter, the present invention will be described in detail.

[0217] The method of the present invention is represented by the following oxidation step:

[0218]

[0219] In formulas (A) and (B), R 1 , R 2 , R 3 and n are as described in [1] above.

[0220] Hereinafter, the terms and symbols used in this specification will be described.

[0221] The halogen atom means a fluorine atom, a chlorine atom, a bromine atom or an iodine atom. From the viewpoints of the usefulness and economy of the product, etc., preferred examples of the halogen atom are a fluorine atom and a chlorine atom.

[0222] Examples of alkali metal atoms include lithium atoms, sodium atoms, potassium atoms, rubidium atoms, and cesium atoms. More preferably, they include lithium atoms, sodium atoms, potassium atoms, and cesium atoms. Even more preferably, they include lithium atoms, sodium atoms, and potassium atoms.

[0223] Examples of alkaline earth metal atoms include magnesium atoms, calcium atoms, strontium atoms, and barium atoms. More preferably, they include magnesium atoms, calcium atoms, and barium atoms.

[0224] 「Ca to Cb」 means that the number of carbon atoms is from a to b. For example, 「C1 - C4 alkyl」 in 「C1 - C4 alkyl」 means that the number of carbon atoms in the alkyl group is from 1 to 4.

[0225] In this specification, general terms such as 「alkyl」 are interpreted to include both straight-chain and branched-chain forms such as butyl and tert-butyl. On the other hand, for example, the specific term 「butyl」 means the straight-chain 「n-butyl」 and does not mean the branched-chain 「tert-butyl」. Moreover, branched-chain isomers such as 「tert-butyl」 are specifically mentioned when intended. As another example, the specific term 「propyl」 means the straight-chain 「n-propyl」 and does not mean the branched-chain 「isopropyl」. Moreover, branched-chain isomers such as 「isopropyl」 are specifically mentioned when intended.

[0226] In this specification, the following abbreviations and prefixes are sometimes used, and their meanings are as described below.

[0227] Me: Methyl

[0228] Et: Ethyl

[0229] Pr, n-Pr, and Pr-n: Propyl (i.e., n-propyl)

[0230] i-Pr and Pr-i: Isopropyl

[0231] Bu, n-Bu, and Bu-n: Butyl (i.e., n-butyl)

[0232] s-Bu and Bu-s: sec-Butyl (i.e., sec-butyl)

[0233] i-Bu and Bu-i: Isobutyl

[0234] t-Bu and Bu-t: tert-Butyl (i.e., tert-butyl)

[0235] Ph: Phenyl

[0236] n-: Normal

[0237] s- and sec-: Secondary

[0238] i- and iso-: Iso

[0239] t- and tert-: tertiary

[0240] c- and cyc-: cyclo

[0241] o-: ortho

[0242] m-: meta

[0243] p-: para

[0244] C1-C6 alkyl means a straight-chain alkyl or branched-chain alkyl having 1 to 6 carbon atoms.

[0245] Examples of C1-C6 alkyl include: methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, isobutyl, tert-butyl, pentyl, hexyl, etc.; however, it is not limited to these examples.

[0246] C1-C4 alkyl means a straight-chain alkyl or branched-chain alkyl having 1 to 4 carbon atoms.

[0247] Examples of C1-C4 alkyl are appropriate examples among the examples of the above C1-C4 alkyl.

[0248] C2-C4 alkenyl means a straight-chain alkenyl or branched-chain alkenyl having 2 to 6 carbon atoms. Examples of C2-C4 alkenyl include: vinyl (i.e., ethenyl), 1-propenyl, 2-propenyl, isopropenyl (i.e., 1-methylethenyl), 1-butenyl, 2-butenyl, 3-butenyl, 1-methyl-1-propenyl, 2-methyl-1-propenyl, 1,3-butadienyl, etc.; however, it is not limited to these examples.

[0249] C2-C4 alkynyl means a straight-chain alkynyl or branched-chain alkynyl having 2 to 4 carbon atoms. Examples of C2-C4 alkynyl include: ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-methyl-2-propynyl, etc.; however, it is not limited to these examples.

[0250] Haloalkyl means a straight-chain alkyl or branched-chain alkyl substituted with one or more halogen atoms which may be the same or different.

[0251] C1-C4 haloalkyl means a straight-chain alkyl or branched-chain alkyl having 1 to 4 carbon atoms substituted with 1 to 9 halogen atoms which may be the same or different (here, the halogen atom has the same meaning as defined above).

[0252] Examples of C1-C4 haloalkyl groups include: fluoromethyl, difluoromethyl, trifluoromethyl, chlorodifluoromethyl, 2-fluoroethyl, 2-chloroethyl, 2-bromoethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, pentafluoroethyl, 3-fluoropropyl, 3-chloropropyl, 3-bromopropyl, 2,2,3,3,3-pentafluoropropyl, 2,2,2-trifluoro-1-trifluoromethylethyl, heptafluoropropyl, 1,2,2,2-tetrafluoro-1-trifluoromethylethyl, 4-fluorobutyl, 4-chlorobutyl, 4-bromobutyl, 2,2,3,3,4,4,4-heptafluorobutyl, etc.; however, it is not limited to these examples.

[0253] C2-C4 haloalkenyl means a straight-chain or branched alkenyl group having 2 to 4 carbon atoms substituted by the same or different 1 to 7 halogen atoms (here, the halogen atom has the same meaning as defined above). Examples of C2-C4 haloalkenyl groups include: 1-fluoroethenyl, 1-chloroethenyl, 2-fluoroethenyl, 2-chloroethenyl, 2,2-difluoroethenyl, trifluoroethenyl, 2-fluoro-2-propenyl, 2-chloro-2-propenyl, 3-fluoro-2-propenyl, 3-chloro-2-propenyl, 3,3-difluoro-2-propenyl, 3,3-dichloro-2-propenyl, 2,3-difluoro-2-propenyl, 2,3-dichloro-2-propenyl, 2,3,3-trifluoro-2-propenyl, 1-(chloromethyl)ethenyl, 1-(trifluoromethyl)ethenyl, 1-trifluoromethyl-2,2-difluoroethenyl, 4,4-difluoro-3-butenyl, 3,4,4-trifluoro-3-butenyl, etc.; however, it is not limited to these examples.

[0254] C2-C4 haloalkynyl means a straight-chain or branched alkynyl group having 2 to 4 carbon atoms substituted by the same or different 1 to 5 halogen atoms (here, the halogen atom has the same meaning as defined above). Examples of C2-C4 haloalkynyl groups include: 2-fluoroethynyl, 2-chloroethynyl, 3-fluoro-1-propynyl, 3-chloro-1-propynyl, 1-fluoro-2-propynyl, 1-chloro-2-propynyl, 3-fluoro-2-propynyl, 3-chloro-2-propynyl, 1,1-difluoro-2-propynyl, 4-fluoro-3-butynyl, 4-chloro-3-butynyl, 4,4-difluoro-2-butynyl, 4,4,4-trifluoro-2-butynyl, etc.; however, it is not limited to these examples.

[0255] C1-C4 alkoxy means (C1-C4 alkyl)-O- group (here, the C1-C4 alkyl moiety has the same meaning as defined above).

[0256] Examples of C1-C4 alkoxy groups include: methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy, isobutoxy, tert-butoxy, etc.; however, it is not limited to these examples.

[0257] C1-C4 haloalkoxy means a (C1-C4 haloalkyl)-O-group (wherein the C1-C4 haloalkyl moiety has the same meaning as defined above).

[0258] Examples of C1-C4 haloalkoxy include: fluoromethoxy, difluoromethoxy, trifluoromethoxy, chlorodifluoromethoxy, 2-fluoroethoxy, 2-chloroethoxy, 2-bromoethoxy, 2,2-difluoroethoxy, 2,2,2-trifluoroethoxy, pentafluoroethoxy, 3-fluoropropoxy, 3-chloropropoxy, 3-bromopropoxy, 2,2,3,3,3-pentafluoropropoxy, 2,2,2-trifluoro-1-trifluoromethylethoxy, heptafluoropropoxy, 1,2,2,2-tetrafluoro-1-trifluoromethylethoxy, 4-fluorobutoxy, 4-chlorobutoxy, 4-bromobutoxy, 2,2,3,3,4,4,4-heptafluorobutoxy, etc.; however, it is not limited to these examples.

[0259] Phenyl C1-C6 alkyl means a C1-C6 alkyl substituted with a phenyl group (wherein the C1-C6 alkyl moiety has the same meaning as defined above).

[0260] Examples of phenyl C1-C6 alkyl include: benzyl, 1-phenylethyl, 2-phenylethyl, 3-phenylpropyl, 4-phenylbutyl, 5-phenylpentyl, 6-phenylhexyl, etc.; however, it is not limited to these examples.

[0261] C6-C10 aryl means an aromatic cyclic group in which all atoms constituting the ring are 6-10 carbon atoms.

[0262] Examples of C6-C10 aryl are: phenyl, 1-naphthyl, and 2-naphthyl. 1-Naphthyl is also called naphthalen-1-yl. 2-Naphthyl is also called naphthalen-2-yl.

[0263] C1-C4 alkoxycarbonyl means a (C1-C4 alkyl)-O-C(=O)-group (wherein the C1-C4 alkyl moiety has the same meaning as defined above).

[0264] Examples of C1-C4 alkoxycarbonyl include: methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, etc.; however, it is not limited to these examples.

[0265] C1-C4 alkanoyl means a (C1-C4 alkyl)-C(=O)-group (wherein the C1-C4 alkyl moiety has the same meaning as defined above).

[0266] Examples of C1-C4 alkanoyl include: acetyl, propionyl, butyryl, isobutyryl, valeryl, etc.; however, it is not limited to these examples.

[0267] Hydroxy C1-C4 alkyl means a C1-C4 alkyl group substituted by a hydroxy group (here, the C1-C4 alkyl group has the same meaning as defined above).

[0268] Examples of hydroxy C1-C4 alkyl include: hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 1-hydroxypropyl, 2-hydroxypropyl, 1-hydroxybutyl, 2-hydroxybutyl, 3-hydroxybutyl, etc.; however, it is not limited to these examples.

[0269] C1-C4 alkoxy C1-C4 alkyl means a C1-C4 alkyl group substituted by a C1-C4 alkoxy group (here, the C1-C4 alkoxy group and the C1-C4 alkyl group have the same meaning as defined above).

[0270] Examples of C1-C4 alkoxy C1-C4 alkyl include: methoxymethyl, ethoxymethyl, propoxymethyl, isopropoxymethyl, 1-methoxyethyl, 2-methoxyethyl, 1-ethoxyethyl, 2-ethoxyethyl, 1-propoxyethyl, 2-propoxyethyl, 1-isopropoxyethyl, 2-isopropoxyethyl, 1-methoxypropyl, 2-methoxypropyl, 3-methoxypropyl, 1-methoxybutyl, 2-methoxybutyl, 3-methoxybutyl, 4-methoxybutyl, etc.; however, it is not limited to these examples.

[0271] Amino C1-C4 alkyl means a C1-C4 alkyl group substituted by an amino group (here, the C1-C4 alkyl group has the same meaning as defined above).

[0272] Examples of amino C1-C4 alkyl include: aminomethyl, 1-aminoethyl, 2-aminoethyl, 1-aminopropyl, 2-aminopropyl, 1-aminobutyl, 2-aminobutyl, 3-aminobutyl, etc.; however, it is not limited to these examples.

[0273] Cyano C1-C4 alkyl means a C1-C4 alkyl group substituted by a cyano group (here, the C1-C4 alkyl group has the same meaning as defined above).

[0274] Examples of cyano C1-C4 alkyl include: cyanomethyl, 1-cyanoethyl, 2-cyanoethyl, 1-cyanopropyl, 2-cyanopropyl, 1-cyanobutyl, 2-cyanobutyl, 3-cyanobutyl, etc.; however, it is not limited to these examples.

[0275] Nitro C1-C4 alkyl means a C1-C4 alkyl group substituted by a nitro group (here, the C1-C4 alkyl group has the same meaning as defined above).

[0276] Examples of nitro C1-C4 alkyl groups include: nitromethyl, 1-nitroethyl, 2-nitroethyl, 1-nitropropyl, 2-nitropropyl, 1-nitrobutyl, 2-nitrobutyl, 3-nitrobutyl, etc.; however, it is not limited to these examples.

[0277] Carboxy C1-C4 alkyl means a C1-C4 alkyl group substituted by a carboxy group (here, the C1-C4 alkyl group has the same meaning as defined above).

[0278] Examples of carboxy C1-C4 alkyl groups include: carboxymethyl, 1-carboxyethyl, 2-carboxyethyl, 1-carboxypropyl, 2-carboxypropyl, 1-carboxybutyl, 2-carboxybutyl, 3-carboxybutyl, etc.; however, it is not limited to these examples.

[0279] C1-C4 alkoxycarbonyl C1-C4 alkyl means a C1-C4 alkyl group substituted by a C1-C4 alkoxycarbonyl group (here, the C1-C4 alkoxycarbonyl group and the C1-C4 alkyl group have the same meaning as defined above).

[0280] Examples of C1-C4 alkoxycarbonyl C1-C4 alkyl groups include: methoxycarbonylmethyl, ethoxycarbonylmethyl, propoxycarbonylmethyl, isopropoxycarbonylmethyl, 1-methoxycarbonylethyl, 2-methoxycarbonylethyl, 1-ethoxycarbonylethyl, 2-ethoxycarbonylethyl, 1-propoxycarbonylethyl, 2-propoxycarbonylethyl, 1-isopropoxycarbonylethyl, 2-isopropoxycarbonylethyl, 1-methoxycarbonylpropyl, 2-methoxycarbonylpropyl, 3-methoxycarbonylpropyl, 1-methoxycarbonylbutyl, 2-methoxycarbonylbutyl, 3-methoxycarbonylbutyl, 4-methoxycarbonylbutyl, etc.; however, it is not limited to these examples.

[0281] (C1-C4 alkyl)amino means a (C1-C4 alkyl)-NH- group (here, the C1-C4 alkyl moiety has the same meaning as defined above).

[0282] Examples of (C1-C4 alkyl)amino groups include: methylamino, ethylamino, propylamino, isopropylamino, butylamino, etc.; however, it is not limited to these examples.

[0283] (Those) with ordinary knowledge in the technical field to which the invention pertains can understand the definitions and examples of functional groups other than the above in the same way as the above functional groups.

[0284] In this specification, compounds having isomers include all isomers and any arbitrary mixture of these in any proportion. For example, xylene includes: o-xylene, m-xylene, p-xylene, and any arbitrary mixture of these in any proportion. For example, dichlorobenzene includes: o-dichlorobenzene, m-dichlorobenzene, p-dichlorobenzene, and any arbitrary mixture of these in any proportion.

[0285] In this specification, the non-limiting term "comprise(s) / comprising" can be replaced, respectively, with the limiting term "consist(s) of / consisting of)".

[0286] In this specification, the terms "recover / recovery" can be replaced, respectively, with "separate / separation". In this specification, the thioether derivative of formula (A) is synonymous with the compound of formula (A), the mono-sulfoxide derivative of (B) is synonymous with the compound of (B), and the di-sulfoxide derivative of formula (C) is synonymous with the compound of formula (C).

[0287] Unless otherwise specified, all technical and scientific terms used in this specification have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains.

[0288] Unless otherwise indicated, the numbers expressing quantities, sizes, concentrations, reaction conditions and other characteristics used in this specification are to be understood as being modified by the term "about". In some embodiments, the disclosed numerical values are to be interpreted in light of the number of significant digits reported and the ordinary rounding method. In some embodiments, the disclosed numerical values are to be interpreted as including the error necessarily resulting from the standard deviation found in the respective test method.

[0289] (Starting Compound: Thioether Derivative of Formula (A))

[0290] The preparation of the thioether derivative of formula (A) can be carried out, for example, by the method described in International Publication No. 2013 / 157229 (Patent Document 1) or a similar method.

[0291]

[0292] The preparation of the compound of the specific example (A-a) of the thioether derivative of formula (A) is shown below.

[0293]

[0294] From the viewpoints of the usefulness and economy of the product, etc., in formula (A), R 1 , R 2 , R 3 and the more preferred combinations of n are:

[0295] R 1 is C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C2-C4 haloalkenyl, C2-C4 haloalkynyl;

[0296] R 2 and R 3Each independently is a halogen atom or a C1-C4 alkyl group; and

[0297] n is 5 or 6.

[0298] From the same viewpoint as above, in formula (A), R 1 , R 2 , R 3 and n have a more preferred combination of:

[0299] R 1 is a C1-C4 haloalkyl group;

[0300] R 2 and R 3 each independently is a halogen atom or a C1-C4 alkyl group; and

[0301] n is 5 or 6.

[0302] From the same viewpoint as above, in formula (A), R 1 , R 2 , R 3 and n have a further more preferred combination of:

[0303] R 1 is trifluoromethyl;

[0304] R 2 is a fluorine atom;

[0305] R 3 is a chlorine atom, or

[0306] R 2 and R 3 are methyl groups; and

[0307] n is 5 or 6.

[0308] In one embodiment, from the same viewpoint as above, in formula (A), R 1 , R 2 , R 3 and n have a further more preferred specific combination of:

[0309] R 1 is trifluoromethyl;

[0310] R 2 is a fluorine atom;

[0311] R 3 is a chlorine atom; and

[0312] n is 5.

[0313] In another embodiment, from the same viewpoint as above, in formula (A), R 1 , R 2, R 3 Even more preferably specific combinations of R and n are:

[0314] R 1 is trifluoromethyl;

[0315] R 2 and R 3 are methyl; and

[0316] n is 6.

[0317] From the same viewpoint as above, in formula (A), particularly preferably specific combinations of R, R, and R are: 1 R 2 R 3 are:

[0318] R 1 is trifluoromethyl;

[0319] R 2 is a fluorine atom;

[0320] R 3 is a chlorine atom; and

[0321] n is 5.

[0322] (Target compound: mono sulfoxide derivative of formula (B))

[0323] From the same viewpoint as above, in formula (B), relatively preferably, more preferably, even more preferably, and particularly preferably specific combinations of R, R, R, and n are the same as those of formula (A) above. 1 R 2 R 3 and n are the same as those combinations above in formula (A).

[0324] Particularly preferably specific examples of the compound of formula (B) are compounds of the following formula (B-a).

[0325]

[0326] As described above, in the method for producing the mono sulfoxide derivative of formula (B) from the compound of formula (A), it is desirable that the oxidation reaction proceeds sufficiently and the proportion of the di sulfoxide derivative of formula (C) in the product is sufficiently low. In the reaction mixture after the oxidation reaction, the content of the compound of formula (C) relative to the weight of the compound of formula (B) can be, for example, 10% or less (0% - 10%), relatively preferably 0% - 7%, more preferably 0% - 5%, even more preferably 0% - 3%, even more preferably 0% - 2%, and particularly preferably 0% - 1%.

[0327] (Oxidizing agent: hydrogen peroxide)

[0328] As long as the reaction can proceed, the oxidizing agent used in the present invention can be any oxidizing agent. An oxidizing agent capable of oxidizing the corresponding starting compound (sulfide derivative) to the target compound (monosulfoxide derivative) can be used. Examples of the oxidizing agent used in the present invention include inorganic peroxides (such as hydrogen peroxide, urea-hydrogen peroxide adduct, etc.), but are not limited to these examples. From the viewpoints of safety, reactivity, selectivity, and economic efficiency, a more preferred oxidizing agent is hydrogen peroxide. The oxidizing agent can be used alone or in combination of two or more in any ratio.

[0329] An oxidizing agent is used in the present invention. As long as the reaction can proceed, the form of the oxidizing agent can be any form. Those with ordinary knowledge in the technical field to which the invention pertains can appropriately select the form of the oxidizing agent. When hydrogen peroxide is used as the oxidizing agent, as long as the reaction can proceed, the form of hydrogen peroxide can be any form. Considering safety, danger, economic efficiency, etc., examples of the more preferred form of hydrogen peroxide include 5 - 60 wt% hydrogen peroxide aqueous solution, more preferably 5 - 40 wt% hydrogen peroxide aqueous solution, still more preferably 10 - 35 wt% hydrogen peroxide aqueous solution, and even more preferably 25 - 35 wt% hydrogen peroxide aqueous solution. Furthermore, in this specification, for example, "30% hydrogen peroxide aqueous solution" is also referred to as "30% hydrogen peroxide".

[0330] Usage amount of the oxidizing agent

[0331] As long as the reaction can proceed, the usage amount of the oxidizing agent (more preferably hydrogen peroxide) in the method of the present invention can be any amount.

[0332] From the viewpoints of improving the yield and economic efficiency, etc., the lower limit of the usage amount of the oxidizing agent (more preferably hydrogen peroxide) in the present invention relative to 1 mole of the sulfide derivative (starting compound) of formula (A) can be, for example, 0.9 mole or more, more preferably 1.0 mole or more.

[0333] From the viewpoints of safety, suppression of by-products, and economic efficiency, etc., the upper limit of the usage amount of the oxidizing agent (more preferably hydrogen peroxide) in the present invention relative to 1 mole of the sulfide derivative (starting compound) of formula (A) can be, for example, 2.0 moles or less, more preferably 1.7 moles or less, still more preferably 1.5 moles or less.

[0334] Furthermore, the usage amount of the oxidizing agent (more preferably hydrogen peroxide) in the present invention can be any appropriate combination of the above-mentioned lower limit and upper limit. Therefore, from the viewpoints of safety, improvement of yield, suppression of by-products, economic efficiency, etc., the usage amount of the oxidizing agent (more preferably hydrogen peroxide) in the present invention is, for example, 0.9 to 2.0 moles, more preferably 1.0 to 2.0 moles, still more preferably 1.0 to 1.7 moles, further still more preferably 1.0 to 1.5 moles, and particularly preferably 1.0 to 1.2 moles, relative to 1 mole of the thioether derivative (raw material compound) of formula (A). However, those of ordinary skill in the art to which the invention pertains can appropriately adjust the usage amount of the oxidizing agent (more preferably hydrogen peroxide) in the present invention according to the purpose and circumstances.

[0335] Metal catalyst

[0336] The metal catalyst in the present invention will be described. As long as the reaction can proceed, the metal catalyst used in the present invention can be any metal catalyst. The metal catalyst used in the present invention is a known compound or a compound that can be produced from a known compound according to a known method.

[0337] The metal catalyst is a metal acetylacetonate, a metal oxyacetylacetonate, a metal halide, a metal oxohalide, a metal oxide, a metal alkoxide, etc., but is not limited to these metal catalysts.

[0338] The metal of the metal catalyst is more preferably a transition metal.

[0339] Examples of the metal catalyst include: iron catalyst, vanadium catalyst, titanium catalyst, manganese catalyst, copper catalyst, molybdenum catalyst, zirconium catalyst, tungsten catalyst, niobium catalyst, tantalum catalyst, thallium catalyst, etc.; but are not limited to these examples.

[0340] From the viewpoints of yield, suppression of by-products, economic efficiency, etc., the metal catalyst is more preferably one or more selected from the group consisting of a vanadium catalyst, a molybdenum catalyst, and a titanium catalyst (more preferably 1 or 2, still more preferably 1), still more preferably a vanadium catalyst or a molybdenum catalyst, and further still more preferably a vanadium catalyst.

[0341] Examples of the iron catalyst include: iron(III) acetylacetonate, iron(III) chloride, iron(III) bromide, iron(III) methoxide, iron(III) ethoxide, iron(III) propoxide, iron(III) isopropoxide, iron(III) nitrate, etc., and mixtures thereof, etc.; but are not limited to these examples. "Iron(III) acetylacetonate" is also referred to as "Fe(acac)3" or "tris(2,4-pentanedionato)iron(III)".

[0342] In the method described in WO2017 / 150478 (Patent Document 2), due to the iron catalyst used, the reaction mixture is black and dirty. Further, in order to remove the iron catalyst, it is necessary to wash it several times with dilute sulfuric acid.

[0343] Examples of vanadium catalysts include: vanadyl acetylacetonate, vanadium(III) acetylacetonate, vanadium(V) oxychloride, vanadium(V) oxide, vanadium(V) triethanolate, vanadium(V) triisopropoxide, etc., and mixtures thereof; however, it is not limited to these examples. "Vanadyl acetylacetonate" is also known as "VO(acac)2", "bis(2,4-pentanedionato)oxovanadium(IV)", or "vanadyl acetylacetonate(IV)". "Vanadium(V) triisopropoxide" is also known as "VO(OiPr)3" or "vanadium(V) triisopropanolate". From the same viewpoint as above, more preferred examples of vanadium catalysts include: vanadyl acetylacetonate, vanadium(III) acetylacetonate, vanadium(V) oxychloride, and vanadium(V) oxide. Even more preferred examples of vanadium catalysts include: vanadyl acetylacetonate, vanadium(III) acetylacetonate, and vanadium(V) oxide. Further even more preferred examples of vanadium catalysts include: vanadyl acetylacetonate and vanadium(III) acetylacetonate. A particularly preferred example of a vanadium catalyst is vanadyl acetylacetonate.

[0344] Examples of titanium catalysts include: titanium tetrachloride, titanium trichloride, titanium(IV) methoxide, titanium(IV) ethoxide, titanium(IV) propoxide, titanium(IV) isopropoxide, titanium(IV) tert-butoxide, titanium(IV) oxoacetylacetonate, etc., and mixtures thereof; however, it is not limited to these examples. "Titanium(IV) oxoacetylacetonate" is also known as "TiO(acac)2", "bis(2,4-pentanedionato)oxotitanium(IV)", or "titanium(IV) oxoacetylacetonate". From the same viewpoint as above, more preferred examples of titanium catalysts include: titanium tetrachloride, titanium trichloride, titanium(IV) tetraisopropoxide, and titanium(IV) oxoacetylacetonate. Even more preferred examples of titanium catalysts include: titanium tetrachloride, titanium trichloride, and titanium(IV) oxoacetylacetonate. A particularly preferred example of a titanium catalyst is titanium(IV) oxoacetylacetonate.

[0345] Examples of manganese catalysts include: potassium permanganate, manganese(III) acetylacetonate, manganese(II) chloride, manganese(II) oxide, etc., and mixtures thereof; however, it is not limited to these examples. "Manganese(III) acetylacetonate" is also known as "Mn(acac)3".

[0346] Examples of the copper catalyst include: copper(II) acetylacetonate, copper(I) chloride, copper(II) chloride, copper(I) acetate, copper(II) acetate, copper(I) bromide, copper(I) iodide, etc., and mixtures thereof; however, it is not limited to these examples. "Copper(II) acetylacetonate" is also referred to as "Cu(acac)2".

[0347] Examples of the molybdenum catalyst include: molybdenum(VI) 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, silicomolybdic acid, sodium silicomolybdate, etc., and mixtures thereof; however, it is not limited to these examples. "Molybdenum(VI) acetylacetonate" is also referred to as "MoO2(acac)2", "bis(2,4-pentanedionato) dioxomolybdenum(VI)", or "acetylacetonato dioxomolybdenum(IV)". 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 more 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).

[0348] Among molybdenum compounds, ammonium molybdate is a catalyst used for Trost oxidation. As described in Journal of the American Chemical Society 2009, 131, 47, 17087-17089, Trost oxidation is generally used for the reaction of oxidizing a thioether compound into a sulfone compound. However, unexpectedly, this reaction ends with a mono sulfoxide compound, and further, overoxidation into the compound of formula (C) can also be suppressed.

[0349] Examples of the zirconium catalyst include: zirconium(IV) acetylacetonate, zirconium tetrachloride, zirconium oxychloride (including, for example, zirconium(IV) oxychloride octahydrate (ZrCl2O·8H2O)), etc.; however, it is not limited to these examples. "Zirconium(IV) acetylacetonate" is also referred to as "Zr(acac)4" or "tetrakis(2,4-pentanedionato) zirconium(IV)".

[0350] Examples of tungsten catalysts include: 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, etc., and mixtures thereof; however, it is not limited to these examples.

[0351] Examples of niobium catalysts include: niobium carbide, niobium(V) chloride, niobium(V) pentaethoxide, etc., and mixtures thereof; however, it is not limited to these examples.

[0352] Examples of tantalum catalysts include: tantalum carbide (TaC), tantalum(V) chloride (TaCl5), tantalum(V) pentaethoxide (Ta(OEt)5), etc., and mixtures thereof; however, it is not limited to these examples.

[0353] Examples of thallium catalysts include: thallium(III) nitrate, thallium(III) acetate, thallium(III) trifluoroacetate, etc., and mixtures thereof; however, it is not limited to these examples.

[0354] The metal compounds in the present invention can be used alone or in combination of two or more in any proportion. As long as the reaction can proceed, the form of the metal catalyst in the present invention can be any form. Those with ordinary knowledge in the technical field to which the invention pertains can appropriately select the form of the metal catalyst in the present invention.

[0355] (Amount of metal catalyst used)

[0356] As long as the reaction can proceed, the amount of the metal catalyst used in the method of the present invention can be any amount. In one embodiment, from the viewpoints of improving the yield, reducing the environmental load, and economic efficiency, etc., relative to 1 mole of the thioether derivative (raw material compound) of formula (A), the amount of the metal catalyst used in the present invention can be, for example, 0.1 to 20.0 mol%, more preferably 0.1 to 10.0 mol%, still 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%. Further, in another embodiment, from the same viewpoints as above, for example, relative to 1 mole of the thioether derivative (raw material compound) of formula (A), the amount of the metal compound used in the present invention can also be: in terms of metal atoms, more preferably 0.3 to 6.0 mol%, still 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%. However, those of ordinary skill in the art to which the invention pertains can appropriately adjust the amount of the metal catalyst used in the present invention according to the purpose and circumstances.

[0357] Ligand

[0358] The ligands that can be not used in the present invention are described. Even without using ligands, the reaction of the present invention can still proceed sufficiently. Therefore, from the viewpoints of economic efficiency, etc., it is more preferable in the present invention not to use ligands.

[0359] Examples of the ligands not used in the present invention include the compounds of formula (D), but are not limited to these compounds.

[0360]

[0361] In formula (D), R 4 , R 5 , R 6 , R 71 and R 72 are as follows.

[0362] 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.

[0363] In formula (D), R 6is a C1-C4 alkyl group, a cyano group, a nitro group, a carboxyl group, a C1-C4 alkoxycarbonyl group, a C1-C4 alkanoyl 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 carboxyl C1-C4 alkyl group or a C1-C4 alkoxycarbonyl C1-C4 alkyl group.

[0364] 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.

[0365] Specific examples of the ligands not used in the present invention are shown below.

[0366] For example, 2,4-di-tert-butyl-6-{[(1-hydroxy-3,3-dimethylbutan-2-yl)imino]methyl}phenol described in WO2011 / 006646 (Patent Document 3), and the compounds (3-1) to (3-13) described in WO2017 / 150478 (Patent Document 2), namely, (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, the compounds 1a to 1d described in Chemical European Journal, 2005, 11, 1086-1092, J. Legros et al., namely, (E)-2-{[(1-hydroxy-3,3-dimethylbutan-2-yl)imino]methyl}-4,6-diiodophenol, (E)-2-{[(1-hydroxy-3,3-dimethylbutan-2-yl)imino]methyl}-4,6-dibromophenol, (E)-2-{[(1-hydroxy-3,3-dimethylbutan-2-yl)imino]methyl}phenol, (E)-2-{[(1-hydroxy-3-methylbutan-2-yl)imino]methyl}-4,6-diiodophenol, etc.; however, it is not limited to these examples.

[0367] Benzoic acid derivatives

[0368] The benzoic acid derivatives that can be not used in the present invention are described. Even without using carboxylic acid derivatives such as benzoic acid derivatives, the reaction of the present invention can still proceed sufficiently. Therefore, from the viewpoint of economic efficiency and the like, it is more preferable in the present invention not to use carboxylic acid derivatives such as benzoic acid derivatives.

[0369] Examples of the benzoic acid derivatives not used in the present invention include the compounds of formula (E), but are not limited to these compounds

[0370]

[0371] In formula (E), A 1 , A 2 , A 3 , A 4 , A 5 , M and n are as described below.

[0372] 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 hydroxyl 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 hydroxyl 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 hydroxyl 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 hydroxyl group or a nitro group; A 5 is a hydrogen atom, a halogen atom, a C1-C4 alkyl group, a C1-C4 alkoxy group, a (C1-C4 alkyl)amino group, a hydroxyl group or a nitro group.

[0373] In formula (E), M is a hydrogen atom, an alkali metal atom or an alkaline earth metal atom.

[0374] Specific examples of M include: 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; but are not limited to these examples.

[0375] In formula (E), n is 1 or 2. More specifically, as long as it is chemically admissible, n can be 1 or 2. 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.

[0376] Specific examples of the carboxylic acid derivatives such as benzoic acid derivatives not used in the present invention are shown below.

[0377] For example, the benzoic acid derivatives of (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-hydroxybenzoate, sodium 4-aminobenzoate, sodium 2,4,6-trimethylbenzoate, sodium 4-tert-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, carboxylic acid derivatives (including benzoic acid derivatives) of AH1 to AH18 and ANa7, ALi7, AK7, ACs7, ABu4N7 described in Chemical European Journal, 2005, 11, 1086-1092, J. Legros et al.; however, it is not limited to these examples.

[0378] Method for manufacturing sulfoxide derivatives

[0379] The monosulfoxide derivative of formula (B) can be manufactured 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 can proceed, those with ordinary knowledge in the technical field to which the invention pertains can appropriately select and adjust the addition order of raw materials, reagents, solvents, etc.

[0380] Solvent

[0381] As long as the reaction can proceed, the solvent in the reaction of the present invention can be any solvent. However, from the viewpoint of smooth progress of the reaction, etc., the reaction of the present invention is preferably carried out in the presence of a solvent. Further, a solvent in which the solubility of the compound of formula (A) is high and the solubility of the compound of formula (B) is low is more preferable. In other words, a solvent in which the solubility of the compound of formula (A) is higher than the solubility of the compound of formula (B) is more preferable.

[0382] The types of solvents in the reaction of the present invention include, for example: water, halogenated aliphatic hydrocarbons (such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane, 1,3-dichloropropane, 1,4-dichlorobutane, trichloroethane, trichloroethylene, tetrachloroethane, tetrachloroethylene, pentachloroethane, etc., more preferably dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane, and even more preferably dichloromethane), aromatic hydrocarbon derivatives (such as benzene, toluene, xylene, trimethylbenzene, chlorobenzene, dichlorobenzene, trichlorobenzene, chlorotoluene, trifluorotoluene, 4-chlorotrifluorotoluene, difluorobenzene, bromobenzene, nitrobenzene, etc., more preferably toluene, xylene, chlorobenzene, dichlorobenzene, chlorotoluene), nitriles (such as acetonitrile, propionitrile, butyronitrile, etc., more preferably acetonitrile), carboxylic acid esters (such as ethyl acetate, isopropyl acetate, butyl acetate, etc.), amides (such as N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAC), N,N-diethylacetamide, N-methylpyrrolidone (NMP), etc., more preferably N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAC), N-methylpyrrolidone (NMP), and even more preferably N,N-dimethylformamide (DMF)), alkylureas (such as N,N'-dimethylimidazolidinone (DMI), etc.), sulfones (such as sulfolane, etc.), carbonates (such as ethylene carbonate, propylene carbonate, etc.), alcohols (such as methanol, ethanol, propanol (i.e., 1-propanol), 2-propanol, n-butanol, sec-butanol, isobutanol, tert-butanol, pentanol (i.e., 1-pentanol), sec-pentanol, isopentanol, tert-pentanol, hexanol (i.e., 1-hexanol), cyclohexanol, ethylene glycol, etc., C1-C6 aliphatic alcohols; more preferably methanol, ethanol, propanol, 2-propanol, n-butanol, sec-butanol, isobutanol, tert-butanol, pentanol, sec-pentanol, isopentanol, tert-pentanol, ethylene glycol, etc., C1-C5 aliphatic alcohols; even more preferably methanol, ethanol, propanol, 2-propanol, butanol, sec-butanol, isobutanol, tert-butanol, ethylene glycol, etc., C1-C4 aliphatic alcohols), ethers (such as 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), diethylene glycol dimethyl ether (diglyme), triethylene glycol dimethyl ether (triglyme), 4-methoxybenzene, diphenyl ether, etc.), and any combination of these solvents in any proportion; however, it is not limited to these solvents.

[0383] Among them, in one embodiment, it is more preferable to contain alcohols. In another embodiment, it is more preferable to contain nitriles. In another embodiment, it is more preferable to contain alcohols and / or nitriles. These solvents can also be applied to any one of the more preferable examples, the more preferable examples, the further more preferable examples, the more preferable specific examples, the more preferable specific examples, and the further more preferable specific examples of the following solvents.

[0384] "2-propanol" is also called "isopropyl alcohol" or "isopropanol".

[0385] "t-butanol" is also called "tert-butanol" or "tert-butyl alcohol".

[0386] From the viewpoints of reactivity and economic efficiency, etc., the more preferable examples of the solvent include: water, halogenated aliphatic hydrocarbons, aromatic hydrocarbon derivatives, nitriles, carboxylic acid esters, amides, alcohols, and any combination of these solvents in any proportion.

[0387] The more preferable examples of the solvent include: water, nitriles, amides, alcohols, and any combination of these solvents in any proportion.

[0388] The further more preferable examples of the solvent include: water, nitriles, alcohols, and any combination of these solvents in any proportion.

[0389] The particularly preferable examples of the solvent include: water, alcohols, and any combination of these solvents in any proportion.

[0390] The more preferable specific examples of the solvent 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, tert-butanol, tert-amyl alcohol, and any combination of these solvents in any proportion.

[0391] The more preferable specific examples of the solvent include: water, acetonitrile, N,N-dimethylformamide (DMF), methanol, ethanol, propanol, 2-propanol, butanol, tert-butanol, tert-amyl alcohol, and any combination of these solvents in any proportion.

[0392] The further more preferable specific examples of the solvent include: water, acetonitrile, methanol, ethanol, propanol, 2-propanol, butanol, tert-butanol, tert-amyl alcohol, and any combination of these solvents in any proportion.

[0393] In one embodiment, the further more preferable specific examples of the solvent include: water, 2-propanol, tert-butanol, and any combination of these solvents in any proportion.

[0394] In another embodiment, further more preferred specific examples of the solvent include: water, tert-butanol, tert-amyl alcohol, and any combination of these solvents in any proportion. Among them, further more preferred are tert-butanol solvent, tert-amyl alcohol solvent, a mixed solvent of tert-butanol and water, or a mixed solvent of tert-amyl alcohol and water. In the present invention, from the perspective of safety, it is found that among alcohols, tert-alcohols such as tert-butanol and tert-amyl alcohol are more preferred as solvents. From the perspectives of price, economic efficiency, etc., more preferred is tert-butanol solvent or a mixed solvent of tert-butanol and water. From the perspective of ease of operation, it is found that further more preferred is a mixed solvent of tert-butanol and water.

[0395] Furthermore, in another embodiment, from the same perspective as above, more preferred is a mixed solvent of tert-butanol and water or a mixed solvent of tert-amyl alcohol and water, and particularly preferred is a mixed solvent of tert-butanol and water.

[0396] As long as the reaction can proceed, the amount of the solvent used can be any amount. From the perspectives of improving the yield, suppressing by-products, and economic efficiency, etc., relative to 1 mole of the thioether derivative (raw material compound) of formula (A), the amount of the solvent used can be, for example, 0.01 to 10.0 L (liters), more preferably 0.1 to 5.0 L, still more preferably 0.3 to 2.0 L, further more preferably 0.4 to 1.5 L, further more preferably 0.4 to 1.2 L, further more preferably 0.5 to 1.2 L, further more preferably 0.5 to 1.0 L. However, those of ordinary skill in the art to which the present invention pertains can appropriately adjust the amount of the solvent used in the reaction of the present invention. When using a combination of two or more solvents, as long as the reaction can proceed, the ratio of the two or more solvents can be any ratio.

[0397] However, from the perspectives of yield, suppression of by-products, economic efficiency, etc., in one embodiment, the amount of the water solvent in the total solvent composed of a solvent other than water and the water solvent is, for example, 0 vol% to 100 vol% relative to the amount of the total solvent (100 vol%), more preferably 0 vol% to 30 vol%, still more preferably 0 vol% to 20 vol%, further more preferably 0 vol% to 15 vol%. In another embodiment, the amount of the water solvent in the total solvent composed of a solvent other than water and the water solvent is, for example, 5 vol% to 100 vol% relative to the amount of the total solvent (100 vol%), more preferably 5 vol% to 30 vol%, still more preferably 5 vol% to 20 vol%, further more preferably 5 vol% to 15 vol%.

[0398] Solvents other than water are, for example: alcohols (such as methanol, 2-propanol, tert-butanol, tert-amyl alcohol), nitriles (such as acetonitrile); but are not limited to these solvents.

[0399] Solubility

[0400] From the viewpoint of easy operation and the like, the solubility of the compound in the solvent is preferably such that the compound of formula (B) as the target does not dissolve and can precipitate, but is not limited thereto.

[0401] As the solubility of the compound in the solvent for the reaction of the present invention, for example, in the range of 15°C to 20°C, the solubility of the compound of formula (B) as the target is preferably 5 to 75% by weight, more preferably 10 to 60% by weight, still more preferably 20 to 55% by weight, and particularly preferably 30 to 40% by weight.

[0402] In addition, from the viewpoint of the smooth progress of the reaction and the like, the compound of formula (A) as the raw material is preferably 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, still more preferably 10 to 55% by weight, and particularly preferably 30 to 40% by weight.

[0403] In one embodiment, it was found that, for example, the solubility of the compound of formula (B-a) in 2-propanol was 30 to 40% by weight in the range of 15°C to 20°C. In another embodiment, from the viewpoints of crystallization and filtration, it was found that the solubility of the compound of formula (B-a) in a 70% by weight tert-butanol / water mixed solution was 4 to 6% by weight in the range of 15°C to 20°C and about 2% by weight at 5°C.

[0404] Concentration

[0405] From the viewpoints of the smooth progress of the reaction and easy operation and the like, the concentration of the compound of formula (A) at the start of the reaction can 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 with respect to the whole reaction system.

[0406] Reaction temperature

[0407] The reaction temperature of the present invention is not particularly limited. In one embodiment, from the viewpoints of yield improvement, by-product suppression, and economic efficiency, etc., the reaction temperature can be, for example, in the range of -10°C to 60°C (i.e., negative 10°C to positive 60°C), more preferably in the range of 0°C to 60°C (i.e., 0°C to positive 60°C), still more preferably in the range of 5°C to 40°C (i.e., positive 5°C to positive 40°C), even more preferably in the range of 10°C to 35°C (i.e., positive 10°C to positive 35°C), and even more preferably in the range of 10°C to 20°C (i.e., positive 10°C to positive 20°C). In another embodiment, from the same viewpoints as above, the reaction temperature can also be, for example, in the range of -20°C to 50°C (i.e., negative 20°C to positive 50°C), more preferably in the range of -10°C to 40°C (i.e., negative 10°C to positive 40°C), still more preferably in the range of -5°C to 35°C (i.e., negative 5°C to positive 35°C), even more preferably in the range of 15°C to 35°C (i.e., positive 15°C to positive 30°C), and even more preferably in the range of 25°C to 35°C (i.e., positive 25°C to positive 35°C). In another embodiment, from the same viewpoints as above, the reaction temperature can also be, for example, in the range of -10°C to 60°C (i.e., negative 10°C to positive 60°C), more preferably in the range of -10°C to 50°C (i.e., negative 10°C to positive 50°C), still more preferably in the range of 0°C to 50°C (i.e., 0°C to 50°C), and even more preferably in the range of 0°C to 40°C (i.e., 0°C to 40°C).

[0408] (Reaction time)

[0409] 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, more preferably 3 hours or more, and even more preferably 6 hours or more, but is not limited to these times. The upper limit of the reaction time can be, for example, 48 hours or less, more preferably 24 hours or less, and even more preferably 12 hours or less, but is not limited to these times. Those of ordinary skill in the art to which the invention pertains can appropriately adjust the range of the reaction time in the present invention 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, more preferably 2 hours to 24 hours, and still more preferably 3 hours to 12 hours, but is not limited to these times. However, those of ordinary skill in the art to which the invention pertains can appropriately adjust the reaction time of the present invention.

[0410] "Reaction time" means the time from the start of adding hydrogen peroxide to the end of the reaction. The reaction time in the present invention is the aging period for consuming unreacted raw materials. In the present invention, the reaction time is more preferably equal to the addition time of hydrogen peroxide, but the present invention is not limited thereto. In the present invention, immediately after adding hydrogen peroxide, the raw materials are consumed immediately, and hydrogen peroxide does not accumulate in the reaction mixture. Therefore, the present invention is a safe and industrial manufacturing method.

[0411] (Addition rate of hydrogen peroxide)

[0412] The addition rate of hydrogen peroxide is more preferably 0.5 mol / h or less relative to 1 mol of the compound of formula (A). If the addition rate is 0.5 mol / h or less, hydrogen peroxide will not accumulate in the reaction mixture. The upper limit of the addition rate can be, for example, 0.5 mol / h or less, 0.4 mol / h or less, and 0.3 mol / h or less.

[0413] Furthermore, from the viewpoints of by-product inhibition and economic efficiency, etc., the lower limit of the addition rate can be, for example, 0.05 mol / h or more, 0.1 mol / h or more, and 0.2 mol / h or more.

[0414] Those having ordinary knowledge in the technical field to which the invention pertains can appropriately adjust the range of the addition rate in the present invention by combining the above upper and lower limits. Combinations of the upper and lower limits of the addition rate can be, for example, 0.05 - 0.5 mol / h, 0.1 - 0.5 mol / h. However, the present invention is not limited to these combinations at all.

[0415] (Post-treatment: isolation and / or purification)

[0416] The compound of formula (B), particularly 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether (B-a), which is the target product, can be isolated and purified from the reaction mixture according to methods well-known to those having ordinary knowledge in the technical field to which the invention pertains (such as extraction, washing, crystallization including recrystallization, filtration, crystal washing, and / or other operations), methods obtained by modifying these methods, and any combination of these methods.

[0417] In the post-treatment, crystallization of the target product including recrystallization and washing of the crystals can be carried out. Crystallization of the target product including recrystallization can be carried out by conventional methods well-known to those having ordinary knowledge in the technical field to which the invention pertains. For example, a poor solvent can be added to a solution of a good solvent for the target product. As another example, a saturated solution of the target product can be cooled.

[0418] In any of the above cases, seed crystals can be used.

[0419] For the crystal cleaning operation, the obtained crystals by filtration can be cleaned with a solvent. After stirring the crystal suspension (slurry), filtration can be carried out.

[0420] In addition, from the viewpoints of yield, purity, economic efficiency, etc., the filtration temperature can be, for example, in the range of 0 °C (zero °C) to 30 °C, more preferably in the range of 0 °C (zero °C) to 20 °C, and even more preferably in the range of 5 °C to 15 °C.

[0421] In any of the above cases (including crystallization operations such as recrystallization, filtration operations, crystal cleaning operations, etc.), solvents such as water can be used for organic solvents (including water-miscible organic solvents). Examples of water-miscible organic solvents include the following solvents, but are not limited to these solvents: nitriles (such as acetonitrile), alcohols (such as methanol, ethanol, 2-propanol, tert-butanol), ethers (such as tetrahydrofuran (THF), 1,4-dioxane), ketones (such as acetone), amides (such as N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAC), N-methylpyrrolidone (NMP), etc.), and combinations of these solvents. More preferably, they are acetonitrile, methanol, ethanol, 2-propanol, tert-butanol, acetone, and combinations of these solvents. Even more preferably, they are acetonitrile, methanol, ethanol, 2-propanol, tert-butanol, and combinations of these solvents. Further more preferably, they are 2-propanol or tert-butanol.

[0422] As long as the purpose can be achieved, the amounts of organic solvents such as water-miscible organic solvents and the amount of water can be in any proportion. When using a combination of a water-miscible organic solvent and water, as long as the purpose can be achieved, the proportions of these solvents can be in any proportion. When using a combination of two or more solvents such as water-miscible organic solvents, as long as the purpose can be achieved, the proportions of these solvents can be in any proportion. Those with ordinary knowledge in the technical field to which the invention pertains can appropriately adjust the amounts and proportions of these solvents according to the purpose and situation.

[0423] In any of the above operations (extraction operation, cleaning operation, crystallization operation including recrystallization, filtration operation, crystal cleaning operation, etc.), those with ordinary knowledge in the technical field to which the invention pertains can appropriately adjust the temperature. However, from the viewpoints of yield, purity, economic efficiency, etc., for example, the temperature is 0 °C (zero °C) to 100 °C, more preferably 0 °C to 50 °C, even more preferably 0 °C to 35 °C, and further more preferably 5 °C to 35 °C. As long as heating and cooling are carried out within these temperature ranges.

[0424] In any of the above operations (extraction operation, washing operation, crystallization operation including recrystallization, filtration operation, crystal washing operation, etc.), those skilled in the art to which the invention pertains can appropriately adjust the amount of the organic solvent (including water-miscible organic solvents) and / or water by adding and removing these solvents. Further, the recovery and recycling of the solvent can be carried out as appropriate. For example, the recovery and recycling of the solvent used for the reaction can be carried out, and the recovery and recycling of the solvent used in the post-treatment (isolation and / or purification) can also be carried out.

[0425] The post-treatment (isolation and / or purification) can be carried out by appropriately combining all or part of the above operations. The above operations can be repeated as appropriate in accordance with the purpose of isolation and / or purification, etc. In addition, those skilled in the art to which the invention pertains can appropriately select the combination of any of the above operations and the order of these operations.

[0426] However, in the present invention, by setting the solubility of the compound of formula (B), particularly 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether (B-a), which is the target substance, to 30% to 40% with respect to the alcohol solvent in the range of 15 to 20 °C, crystals of the target substance are precipitated at the end of the reaction. Thereby, the target substance can be simply purified only by filtration. Thereby, the target substance having a low melting point can be crystallized from the reaction mixture, and the compound of formula (B) as the target substance with high purity can be efficiently produced industrially only by filtration.

[0427] Reaction yield and yield

[0428] In the present specification, the terms "reaction yield" and "yield" have the following meanings, respectively.

[0429] Reaction yield

[0430] In the present invention, the reaction yield is obtained by analyzing the organic layer of the reaction mixture according to the following high performance liquid chromatography (HPLC) analysis conditions (A) or gas chromatography (GC) analysis conditions. In the present specification, the reaction yield is expressed as the HPLC area percentage of the target compound.

[0431] The reaction yield in the present invention can be, for example, in the range of 80 to 100%, more preferably in the range of 85 to 100%, still more preferably in the range of 90 to 100%, and even more preferably in the range of 95 to 100%.

[0432] Yield

[0433] The yield in the present invention can be calculated based on the molar ratio of the mono-sulfoxide compound of formula (B) (target compound) obtained to the molar ratio of the thioether derivative of formula (A) (starting compound). That is, the yield in the present invention is represented by the following formula:

[0434] Yield (%) = (moles of target compound obtained) / (moles of starting compound) × 100

[0435] The yield in the present invention can be, for example, in the range of 85 to 100%, more preferably in the range of 90 to 100%.

[0436] Hereinafter, the present invention will be further described in detail by way of examples, but the present invention is not limited to these examples at all.

[0437] In this specification, the following machines and conditions were used for the measurement of various physical properties and yields in the examples and comparative examples.

[0438] GC: Gas chromatography

[0439] Machine: GC-2030 (trade name manufactured by Shimadzu Corporation)

[0440] Column: DB-17 (trade name Aglient J&W)

[0441] Detection temperature: 280 °C

[0442] Inlet temperature: 280 °C

[0443] Total flow rate: 34 mL / min

[0444] Split ratio: 1:30

[0445] Injection volume: 1 μL

[0446] Oven temperature:

[0447] Time (min) Temperature (°C) Hold (min) 0 80 4 10 300 4

[0448] Regarding the GC analysis method, the following literature can be referred to as needed.

[0449] Edited by The Chemical Society of Japan, "New Experimental Chemistry Course 9 Analytical Chemistry II", pp. 60-86 (1977), publisher Shingo Iizumi, Maruzen Co., Ltd.

[0450] Edited by The Chemical Society of Japan, "Experimental Chemistry Course 20-1 Analytical Chemistry", 5th edition, pp. 121-129 (2007), publisher Seishiro Murata, Maruzen Co., Ltd.

[0451] HPLC: High performance liquid chromatography

[0452] HPLC analysis conditions

[0453] Machine: LC-20

[0454] Pump: LC-20AT (trade name manufactured by Shimadzu Corporation)

[0455] Detector: SPD-20A (trade name manufactured by Shimadzu Corporation)

[0456] Column: CERI L-column ODS (4.6x250mm), L-C18, 5μm, 12nm

[0457] Eluent:

[0458]

[0459]

[0460] Flow rate: 1.0 mL / min

[0461] Detection: UV 228 nm

[0462] Column temperature: 40 °C

[0463] As described above, in the evaluation of the reaction yield, the area percentage obtained according to the above HPLC analysis conditions or GC analysis conditions was used.

[0464] Regarding the HPLC analysis method, the following literature can be referred to as needed.

[0465] Edited by The Chemical Society of Japan, "New Experimental Chemistry Course 9 Analytical Chemistry II", pp. 86-112 (1977), published by Shingo Iizumi, Maruzen Co., Ltd.

[0466] Edited by The Chemical Society of Japan, "Experimental Chemistry Course 20-1 Analytical Chemistry", 5th edition, pp. 130-151 (2007), published by Seishiro Murata, Maruzen Co., Ltd.

[0467] (1H-NMR: 1H nuclear magnetic resonance spectrum; analysis conditions)

[0468] Machine: JEOL JMN-ECS-300 or JEOL JMN-Lambda-400 (trade name manufactured by JEOL RESONANCE Co., Ltd.)

[0469] Internal standard: Tetramethylsilane (TMS)

[0470] Method for measuring melting point

[0471] The measurement was carried out using a DSC differential scanning calorimeter. Differential scanning thermal analysis was performed using a model DSC-60 (trade name manufactured by Shimadzu Corporation) at a heating rate of 10 °C / min in the temperature range of 0 to 400 °C. Regarding the differential scanning calorimetry method, the following documents can be referred to as needed.

[0472] Edited by The Chemical Society of Japan, "The 4th Edition of Experimental Chemistry Course 4 Heat, Pressure", pp. 57-93 (1992), published by Kumao Ebihara, Maruzen Co., Ltd.

[0473] Edited by The Chemical Society of Japan, "The 5th Edition of Experimental Chemistry Course 6 Temperature, Heat, Pressure", pp. 203-205 (2005), published by Seishiro Murata, Maruzen Co., Ltd.

[0474] In the examples and comparative examples of the present invention, as the reaction vessel for the preparation of the catalyst solution and the production of the title compound, etc., a reaction vessel commonly used by those of ordinary skill in the art to which the invention pertains was used. For example, in Comparative Example 11, a screw-cap sample bottle of about 6 mL with an inner diameter of 15 mm and a height of 40 mm (a sample bottle with a screw cap) was used, which was 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 thermostat.

[0475] Powder X-ray diffraction measurement

[0476] Machine: Rigaku MultiFlex

[0477] X-ray: Cu-Kα

[0478] Measurement method: Reflection method (reflection mode)

[0479] Voltage: 40 kV

[0480] Current: 40 mA

[0481] Measurement range: 5 to 80°

[0482] Measurement interval: 0.02°

[0483] In this specification, room temperature is generally in the range of 10 °C to 35 °C.

[0484] In this specification, "aging" includes stirring the mixture according to the conventional methods known to those of ordinary skill in the art to which the invention pertains.

[0485] Example 1

[0486] Production of 5-(Trifluoromethylthio)pentyl [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] Ether

[0487]

[0488] In a 50 mL reaction flask, 5-(trifluoromethylthio)pentyl [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl] ether (14.96 g, purity 87%, 30 mmol, 100 mol%) and vanadyl acetylacetonate (79.5 mg, 0.3 mmol, 1 mol%) were added to 2-propanol (24 mL, 0.8 L / mol). The mixture was stirred for 30 minutes at an internal temperature of 15 - 20 °C. 35% hydrogen peroxide (3.5 g, 36 mmol, 120 mol%) was added dropwise thereto over 3 hours at an internal temperature of 15 - 20 °C, and the mixture was aged for 1 hour while maintaining the internal temperature at 15 °C - 20 °C.

[0489] The reaction mixture was analyzed by HPLC (area percentage). As a result, the components other than the solvent, etc. in the reaction mixture were as follows:

[0490] 5-(Trifluoromethylthio)pentyl [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether (target compound): 95.5%;

[0491] 5-(Trifluoromethylthio)pentyl [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl] ether (starting compound): 0.5%;

[0492] 5-(Trifluoromethylsulfinyl)pentyl [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether (by-product: disulfoxide derivative): 0.9%.

[0493] The reaction mixture was an orange-brown suspension at 15 °C. Crystals of the target substance precipitated. A 2.5% aqueous sodium sulfite solution (24.6 g, 6 mmol, 20 mol%) was added to the reaction mixture, and the mixture was stirred for 1 hour at an internal temperature of 5 °C. The obtained crude product was separated by filtration at 5 °C. The obtained 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 substance (Compound B-a) were obtained in a yield of 90.5% (12.73 g, purity 95.2%).

[0494] 11H-NMR (300 MHz, CDCl3) δ (ppm, referenced to TMS): 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)

[0495] Melting point: 43 °C

[0496] This is an excellent manufacturing method in industry, which can crystallize the target substance with a lower melting point from the reaction mixture and obtain a high-purity product only by filtration.

[0497] Example 2

[0498] Preparation of 5-(Trifluoromethylthio)pentyl [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether

[0499]

[0500] In a 50 mL reaction flask, 5-(trifluoromethylthio)pentyl [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl] ether (9.78 g, purity 88%, 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 for 30 minutes at an internal temperature of 15 - 20 °C. 33% hydrogen peroxide (3.09 g, 30 mmol, 150 mol%) was added dropwise to the mixture over 3 hours at an internal temperature of 15 - 20 °C, and the mixture was aged for 1 hour while maintaining the internal temperature at 15 °C - 20 °C.

[0501] The reaction mixture was analyzed by HPLC (area percentage). As a result, the components other than the solvent etc. in the reaction mixture are as follows:

[0502] 5-(Trifluoromethylthio)pentyl [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether (target compound): 94.0%;

[0503] 5-(Trifluoromethylthio)pentyl [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl] ether (starting compound): 0.2%;

[0504] 5-(Trifluoromethylsulfinyl)pentyl [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether (by-product: disulfoxide derivative): 0.9%.

[0505] The reaction mixture was an orange-brown suspension at 15 °C. Crystals of the target substance precipitated. A 13.3% aqueous sodium sulfite solution (8.5 g, 10 mmol, 0.5 mol%) was added to the reaction mixture, and the mixture was stirred for 1 hour at an internal temperature of 5 °C. The obtained crude product was filtered and separated at 5 °C. The obtained crystals were washed successively with a mixed solution of 5 mL of 2-propanol (0.4 L / mol) and 9 mL of water (0.4 L / mol) and 20 mL of water (0.8 L / mol). As a result, white crystals of the target substance (Compound B-a) were obtained in a yield of 94.5% (8.73 g, purity 96.7%).

[0506] Example 3

[0507] Preparation of 5-(Trifluoromethylthio)pentyl [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] Ether

[0508]

[0509] In a 50 mL reaction flask, 5-(trifluoromethylthio)pentyl [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl] ether (9.78 g, purity 88%, 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 for 30 minutes at an internal temperature of 15 - 20 °C. 33% hydrogen peroxide (3.09 g, 30 mmol, 150 mol%) was added dropwise thereto over 3 hours at an internal temperature of 15 - 20 °C, and the mixture was aged for 1 hour while maintaining the internal temperature at 15 °C - 20 °C.

[0510] The reaction mixture was analyzed by HPLC (area percentage). As a result, the components other than the solvent, etc. in the reaction mixture were as follows:

[0511] 5-(Trifluoromethylthio)pentyl [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether (target compound): 91.4%;

[0512] 5-(Trifluoromethylthio)pentyl [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl] ether (starting compound): 3.5%;

[0513] 5-(Trifluoromethylsulfinyl)pentyl [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether (by-product: disulfoxide derivative): 0.5%.

[0514] Example 4

[0515] Production of 5-(Trifluoromethylthio)pentyl [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] Ether

[0516]

[0517] In a 50 mL reaction flask, 5-(trifluoromethylthio)pentyl [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl] ether (9.78 g, purity 88%, 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 thereto over 3 hours at an internal temperature of 5°C, and the mixture was aged for 1 hour while maintaining the internal temperature at 5°C.

[0518] The reaction mixture was analyzed by HPLC (area percentage). As a result, the components other than the solvent and the like in the reaction mixture were as follows:

[0519] 5-(Trifluoromethylthio)pentyl [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether (target compound): 93.2%;

[0520] 5-(Trifluoromethylthio)pentyl [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl] ether (starting compound): 1.9%;

[0521] 5-(Trifluoromethylsulfinyl)pentyl [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether (by-product: disulfoxide derivative): 0.5%.

[0522] Example 5

[0523] Production of 5-(Trifluoromethylthio)pentyl [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] Ether

[0524]

[0525] In a 30 mL test tube, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl] ether (2.47 g, purity 87%, 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. After stirring the mixture at 0 °C for 30 minutes, it was aged at room temperature for 24 hours.

[0526] The reaction mixture was analyzed by HPLC (area percentage). As a result, the components other than the solvent, etc. in the reaction mixture are as follows:

[0527] 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether (target compound): 94.8%;

[0528] 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl] ether (starting compound): 0.6%;

[0529] 5-trifluoromethylsulfinylpentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether (by-product: disulfoxide derivative): 1.9%.

[0530] Example 6

[0531] Production of 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether

[0532]

[0533] In a 30 mL test tube, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl] ether (2.47 g, purity 87%, 5 mmol, 100 mol%), 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. After stirring the mixture at 0 °C for 30 minutes, it was aged at room temperature for 24 hours.

[0534] The reaction mixture was analyzed by HPLC (area percentage). As a result, the components other than the solvent, etc. in the reaction mixture are as follows:

[0535] 5-Trifluoromethylthiopentyl - [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether (target compound): 95.5%;

[0536] 5-Trifluoromethylthiopentyl - [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl] ether (starting material compound): 0.8%;

[0537] 5-Trifluoromethylsulfinylpentyl - [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether (by-product: disulfoxide derivative): 1.4%.

[0538] Example 7

[0539] Preparation of 5-Trifluoromethylthiopentyl - [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether

[0540]

[0541] In a 30 mL test tube, 5-trifluoromethylthiopentyl - [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl] ether (2.47 g, purity 87%, 5 mmol, 100 mol%) and 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. After stirring the mixture at 0 °C for 30 minutes, it was aged at room temperature for 24 hours.

[0542] The reaction mixture was analyzed by HPLC (area percentage). As a result, the components other than the solvent, etc. in the reaction mixture were as follows:

[0543] 5-Trifluoromethylthiopentyl - [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether (target compound): 85.6%;

[0544] 5-Trifluoromethylthiopentyl - [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl] ether (starting material compound): 8.4%;

[0545] 5-Trifluoromethylsulfinylpentyl - [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether (by-product: disulfoxide derivative): 1.3%.

[0546] Example 8

[0547] Preparation of 5-(trifluoromethylthio)pentyl [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether

[0548]

[0549] In a 30 mL test tube, 5-(trifluoromethylthio)pentyl [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl] ether (2.29 g, purity 93%, 5 mmol, 100 mol%) and titanium(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. After stirring the mixture at 0 °C for 30 minutes, it was aged at room temperature for 63 hours.

[0550] The reaction mixture was analyzed by HPLC (area percentage). As a result, the components other than the solvent, etc. in the reaction mixture were as follows:

[0551] 5-(trifluoromethylthio)pentyl [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether (target compound): 87.2%;

[0552] 5-(trifluoromethylthio)pentyl [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl] ether (starting compound): 2.0%;

[0553] 5-(trifluoromethylsulfinyl)pentyl [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether (by-product: disulfoxide derivative): 5.2%.

[0554] Example 9

[0555] Preparation of 5-(trifluoromethylthio)pentyl [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether

[0556]

[0557] In a 30 mL test tube, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl] ether (2.47 g, purity 87%, 5 mmol, 100 mol%) and ammonium molybdate tetrahydrate (8.7 mg, 0.007 mmol, 0.14 mol%, 1 mol% in terms of 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. After stirring the mixture at an internal temperature of 0 °C for 30 minutes, it was aged at room temperature for 17 hours.

[0558] The reaction mixture was analyzed by HPLC (area percentage). As a result, the components other than the solvent and the like in the reaction mixture are as described below:

[0559] 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether (target compound): 95.6%;

[0560] 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl] ether (starting compound): 0.5%;

[0561] 5-trifluoromethylsulfinylpentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether (by-product: disulfoxide derivative): 1.2%.

[0562] The reaction mixture was a yellow suspension at 25 °C. Crystals of the target substance precipitated.

[0563] Example 10

[0564] Production of 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether

[0565]

[0566] In a 30 mL test tube, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl] ether (2.15 g, purity 94%, 5 mmol, 100 mol%) and ammonium molybdate tetrahydrate (8.7 mg, 0.007 mmol, 0.14 mol%, 1 mol% in terms of 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. After stirring the mixture at 0 °C for 30 minutes, it was aged at room temperature for 24 hours.

[0567] The reaction mixture was analyzed by HPLC (area percentage). As a result, the components other than the solvent etc. in the reaction mixture were as follows:

[0568] 5-Trifluoromethylthiopentyl - [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether (target compound): 87.6%;

[0569] 5-Trifluoromethylthiopentyl - [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl] ether (starting compound): 0.3%;

[0570] 5-Trifluoromethylsulfinylpentyl - [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether (by-product: disulfoxide derivative): 7.0%.

[0571] Example 11

[0572] Production of 5-Trifluoromethylthiopentyl - [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether

[0573]

[0574] In a 250 mL reaction flask, 5-trifluoromethylthiopentyl - [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl] ether (33.1 g, purity 88%, 80 mmol, 100 mol%) and vanadyl acetylacetonate (212.1 mg, 0.8 mmol, 1 mol%) were added to tert-butanol (60 mL, 0.8 L / mol). The mixture was stirred for 30 minutes at an internal temperature of 25°C. 35% hydrogen peroxide (9.3 g, 96 mmol, 120 mol%) was added dropwise thereto over 3 hours at an internal temperature of 25°C, and the mixture was aged for 1 hour while maintaining the internal temperature at 25°C.

[0575] The reaction mixture was analyzed by HPLC (area percentage). As a result, the components other than the solvent etc. in the reaction mixture were as follows:

[0576] 5-Trifluoromethylthiopentyl - [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether (target compound): 96.1%;

[0577] 5-Trifluoromethylthiopentyl - [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl] ether (starting compound): 0.2%;

[0578] 5-Trifluoromethylsulfinylpentyl - [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether (by-product: disulfoxide derivative): 1.4%.

[0579] The reaction mixture was an orange-brown solution at 25 °C. To the reaction mixture was added tert-butanol (8 mL, 0.1 L / mol) and an aqueous solution of 2% sodium bisulfite (40.8 g, 8 mmol, 10 mol%), and the mixture was stirred for 1 hour at an internal temperature of 20 °C. The crude product obtained was separated by filtration at 20 °C. The crystals obtained were washed successively with a mixed solution of 20 mL (0.3 L / mol) of 2-propanol and 36 mL (0.5 L / mol) of water and 24 mL (0.3 L / mol) of water. As a result, white crystals of the target compound (Compound B-a) were obtained in a yield of 85.1% (31.5 g, purity 96.6%).

[0580] Example 12

[0581] Production of 5-Trifluoromethylthiopentyl - [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether

[0582]

[0583] In a 50 mL reaction flask, 5-trifluoromethylthiopentyl - [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl] ether (12.2 g, purity 88%, 25 mmol, 100 mol%) and vanadyl acetylacetonate (66.3 mg, 0.25 mmol, 1 mol%) were added to tert-butanol (19 mL, 0.8 L / mol). The mixture was stirred for 30 minutes at an internal temperature of 40 °C. 35% hydrogen peroxide (2.9 g, 30 mmol, 120 mol%) was added dropwise thereto over 3 hours at an internal temperature of 40 °C, and the mixture was aged for 1 hour while maintaining the internal temperature at 40 °C.

[0584] The reaction mixture was analyzed by HPLC (area percentage). As a result, the components other than the solvent, etc. in the reaction mixture were as follows:

[0585] 5-Trifluoromethylthiopentyl - [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether (target compound): 94.6%;

[0586] 5-Trifluoromethylthiopentyl - [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl] ether (starting compound): 0.7%;

[0587] 5-Trifluoromethylsulfinylpentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether (by-product: disulfoxide derivative): 1.4%.

[0588] To the reaction mixture was added an aqueous solution of 9.4% sodium bisulfite (2.8 g, 2.5 mmol, 10 mol%) and 10 mL of water (0.4 L / mol), and the mixture was stirred for 1 hour at an internal temperature of 20°C. The crude product obtained was separated by filtration at 20°C. The crystals obtained 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 compound (Compound B-a) were obtained in a yield of 86.2% (9.9 g, purity 96.9%).

[0589] Example 13

[0590] Production of 5-Trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether

[0591]

[0592] In a 50 mL reaction flask, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl] ether (12.2 g, purity 88%, 25 mmol, 100 mol%) and vanadyl acetylacetonate (66.3 mg, 0.25 mmol, 1 mol%) were added to tert-butanol (19 mL, 0.8 L / mol). The mixture was stirred for 30 minutes at an internal temperature of 30°C. 35% hydrogen peroxide (2.9 g, 30 mmol, 120 mol%) was added dropwise thereto over 3 hours at an internal temperature of 30°C, and the mixture was aged for 1 hour while maintaining the internal temperature at 30°C.

[0593] The reaction mixture was analyzed by HPLC (area percentage). As a result, the components other than the solvent, etc. in the reaction mixture were as follows:

[0594] 5-Trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether (target compound): 95.1%;

[0595] 5-Trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl] ether (starting compound): 0%;

[0596] 5-Trifluoromethylsulfinylpentyl - [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether (by-product: disulfoxide derivative): 1.9%.

[0597] To the reaction mixture was added an aqueous solution of 2% sodium bisulfite (12.8 g, 2.5 mmol, 10 mol%), and the mixture was stirred for 1 hour at an internal temperature of 15 °C. The crude product obtained was separated by filtration at 15 °C. The crystals obtained 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 then with 8 mL of water (0.3 L / mol). As a result, white crystals of the target compound (Compound B-a) were obtained in a yield of 84.4% (9.69 g, purity 97.3%).

[0598] Example 14

[0599] Preparation of 5-Trifluoromethylthiopentyl - [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether

[0600]

[0601] In a 50 mL reaction flask, 5-trifluoromethylthiopentyl - [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl] ether (12.2 g, purity 88%, 25 mmol, 100 mol%) and vanadyl acetylacetonate (33.2 mg, 0.13 mmol, 0.5 mol%) were added to tert-butanol (19 mL, 0.8 L / mol). The mixture was stirred for 30 minutes at an internal temperature of 30 °C. To this was added dropwise 35% hydrogen peroxide (2.9 g, 30 mmol, 120 mol%) over 3 hours at an internal temperature of 30 °C, and the mixture was allowed to age for 1 hour while maintaining the internal temperature at 30 °C.

[0602] The reaction mixture was analyzed by HPLC (area percentage). As a result, the components other than the solvent, etc. in the reaction mixture were as follows:

[0603] 5-Trifluoromethylthiopentyl - [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether (target compound): 96.6%;

[0604] 5-Trifluoromethylthiopentyl - [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl] ether (starting compound): 0.6%;

[0605] 5-Trifluoromethylsulfinylpentyl - [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether (by-product: disulfoxide derivative): 1.4%.

[0606] To the reaction mixture was added an aqueous solution of 2% sodium bisulfite (12.8 g, 2.5 mmol, 10 mol%). The mixture was stirred for 1 hour at an internal temperature of 15 °C. The resulting crude product was separated by filtration at 15 °C. The obtained 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 then with 8 mL of water (0.3 L / mol). As a result, white crystals of the target compound (Compound B-a) were obtained in a yield of 87.3% (9.84 g, purity 99.1%).

[0607] Example 15

[0608] Production of 5-(trifluoromethylthio)pentyl [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether

[0609]

[0610] In a 50 mL reaction flask, 5-(trifluoromethylthio)pentyl [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl] ether (12.2 g, purity 88%, 25 mmol, 100 mol%) and vanadyl acetylacetonate (66.4 mg, 0.25 mmol, 1 mol%) were added to tert-butanol (13 mL, 0.5 L / mol). The mixture was stirred for 30 minutes at an internal temperature of 30 °C. To this was added dropwise 35% hydrogen peroxide (2.9 g, 30 mmol, 120 mol%) over 3 hours at an internal temperature of 30 °C, 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.

[0611] The reaction mixture was analyzed by HPLC (area percentage). As a result, the components other than the solvent, etc. in the reaction mixture were as follows:

[0612] 5-(trifluoromethylthio)pentyl [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether (target compound): 94.6%;

[0613] 5-(trifluoromethylthio)pentyl [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl] ether (starting compound): 0.6%;

[0614] 5-(trifluoromethylsulfinyl)pentyl [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether (by-product: disulfoxide derivative): 1.3%.

[0615] Example 16

[0616] Preparation of 5-(trifluoromethylthio)pentyl [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether

[0617]

[0618] In a 250 mL reaction flask, 5-(trifluoromethylthio)pentyl [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl] ether (44.0 g, purity 88%, 90 mmol, 100 mol%) and vanadyl acetylacetonate (239 mg, 0.9 mmol, 1 mol%) were added to tert-butanol (77 mL, 0.9 L / mol) and water (6 mL, 0.1 L / mol). The mixture was stirred for 30 minutes at an internal temperature of 30 °C. 34% hydrogen peroxide (11 g, 108 mmol, 120 mol%) was added dropwise thereto over 3 hours at an internal temperature of 30 °C, and the mixture was aged for 1 hour while maintaining the internal temperature at 30 °C.

[0619] The reaction mixture was analyzed by GC (area percentage). As a result, the components other than solvents and the like in the reaction mixture were as follows:

[0620] 5-(trifluoromethylthio)pentyl [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether (target compound): 96.8%;

[0621] 5-(trifluoromethylthio)pentyl [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl] ether (starting compound): 0.5%;

[0622] 5-(trifluoromethylsulfinyl)pentyl [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether (by-product: disulfoxide derivative): 0.9%.

[0623] The reaction mixture was an orange-brown solution at 30 °C. To the reaction mixture was added an aqueous solution of 9.4% sodium bisulfite (9.9 g, 9.0 mmol, 10 mol%), and the mixture was stirred for 30 minutes at an internal temperature of 20 °C. The mixture was added 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 off at 5 °C. The obtained crystals were washed successively with a mixed solution of 23 mL of tert-butanol (0.3 L / mol) and 41 mL of water (0.5 L / mol) and 27 mL of water (0.3 L / mol). As a result, white crystals of the target compound (Compound B-a) were obtained in a yield of 88.9% (37.1 g, purity 96.6%).

[0624] As the seed crystal used in the above example, the crystal obtained in the same manner as in Example 1 was used.

[0625] Example 17

[0626] Production of 5-(trifluoromethylthio)pentyl [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether

[0627]

[0628] In a 50 mL reaction flask, 5-(trifluoromethylthio)pentyl [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl] ether (38.9 g, purity 89%, 80 mmol, 100 mol%) and vanadyl acetylacetonate (212 mg, 0.8 mmol, 1 mol%) were added to tert-butanol (68 mL, 0.9 L / mol) and water (5 mL, 0.1 L / mol). The mixture was stirred for 30 minutes at an internal temperature of 30 °C. To this was added dropwise 35% hydrogen peroxide (9.3 g, 96 mmol, 120 mol%) over 3 hours at an internal temperature of 30 °C, and the mixture was aged for 1 hour while maintaining the internal temperature at 30 °C.

[0629] The reaction mixture was analyzed by GC (area percentage). As a result, the components other than the solvent, etc. in the reaction mixture were as follows:

[0630] 5-(trifluoromethylthio)pentyl [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether (target compound): 97.1%;

[0631] 5-(trifluoromethylthio)pentyl [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl] ether (starting compound): 0.6%;

[0632] 5-Trifluoromethylsulfinylpentyl - [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether (by-product: disulfoxide derivative): 1.4%.

[0633] The reaction mixture was an orange-brown solution at 30 °C. To the reaction mixture was added an aqueous solution of 3.7% sodium bisulfite (22.7 g, 8 mmol, 10 mol%), and the internal temperature of the mixture was cooled from 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 obtained crude product was filtered off at 5 °C. The obtained crystals were washed successively with a mixed solution of 20 mL of tert-butanol (0.3 L / mol) and 36 mL of water (0.5 L / mol) and 24 mL of water (0.3 L / mol). As a result, white crystals of the target compound (Compound B-a) were obtained in a yield of 91.5% (33.6 g, purity 97.4%).

[0634] As the seed crystals used in the above examples, the crystals obtained in the same manner as in Example 1 were used.

[0635] Example 18

[0636] Production of 5-Trifluoromethylthiopentyl - [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether

[0637]

[0638] In a 50 mL reaction flask, 5-trifluoromethylthiopentyl - [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl] ether (12.1 g, purity 88%, 25 mmol, 100 mol%) and vanadyl acetylacetonate (66.4 mg, 0.25 mmol, 1 mol%) were added to tert-butanol (19 mL, 0.8 L / mol). The mixture was stirred at an internal temperature of 30 °C for 30 minutes. To this, 35% hydrogen peroxide (1.0 g, 10 mmol, 40 mol%) was added dropwise over 1 hour at an internal temperature of 30 °C, and then 35% hydrogen peroxide (2.0 g, 20 mmol, 80 mol%) was added dropwise over 2 hours while cooling the internal temperature to 20 °C, and the mixture was aged for 1 hour while maintaining the internal temperature at 20 °C.

[0639] The reaction mixture was analyzed by GC (area percentage). As a result, the components other than the solvent, etc. in the reaction mixture were as follows:

[0640] 5-(Trifluoromethylthio)pentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether (target compound): 97.6%;

[0641] 5-(Trifluoromethylthio)pentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl] ether (starting compound): 0.6%;

[0642] 5-(Trifluoromethylsulfinyl)pentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether (by-product: disulfoxide derivative): 0.9%.

[0643] The reaction mixture was an orange-brown suspension at 20 °C. Crystals of the target compound precipitated. To the reaction mixture was added an aqueous solution of 5% sodium bisulfite (5.3 g, 2.5 mmol, 10 mol%) and 5 mL of water (0.2 L / mol). The mixture was stirred for 1 hour at an internal temperature of 15 °C. The crystals obtained were filtered off at 15 °C. The crystals obtained 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 compound (Compound B-a) were obtained in a yield of 86.2% (9.9 g, purity 97.7%).

[0644] Example 19

[0645] Preparation of 5-(Trifluoromethylthio)pentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether

[0646]

[0647] In a 50 mL reaction flask, 5-(Trifluoromethylthio)pentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl] ether (12.1 g, purity 88%, 25 mmol, 100 mol%) and vanadyl acetylacetonate (66.4 mg, 0.25 mmol, 1 mol%) were added to tertiary amyl alcohol (19 mL, 0.8 L / mol). The mixture was stirred for 30 minutes at an internal temperature of 17 °C. To this was added dropwise 33.7% hydrogen peroxide (3.0 g, 30 mmol, 120 mol%) over 3 hours at an internal temperature of 17 °C, and the mixture was aged for 1 hour.

[0648] The reaction mixture was analyzed by GC (area percentage). As a result, the components other than the solvent, etc. in the reaction mixture were as follows:

[0649] 5-Trifluoromethylthiopentyl - [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether (target compound): 97.4%;

[0650] 5-Trifluoromethylthiopentyl - [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl] ether (starting compound): 0.7%;

[0651] 5-Trifluoromethylsulfinylpentyl - [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether (by-product: disulfoxide derivative): 0.5%.

[0652] The reaction mixture was an orange-brown suspension at 17°C. To the reaction mixture was added an aqueous solution of 5% sodium bisulfite (5.3 g, 2.5 mmol, 10 mol%) and 15 mL of water (0.6 L / mol), and the mixture was stirred for 5 minutes under the condition that the internal temperature was 40°C. The obtained mixture was separated into an organic layer and an aqueous layer. Then, the obtained organic layer was concentrated under reduced pressure to distill off the solvent. To the crude product was added 2-propanol (19 mL, 0.8 L / mol) and water (5 mL, 0.2 L / mol), and the mixture was heated to an internal temperature of 40°C. It took 2 hours to cool to an internal temperature of 10°C and was aged for 1 hour. The crystals obtained were filtered off at 10°C. The obtained 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 compound (Compound B-a) were obtained in a yield of 85.9% (9.9 g, purity 96.6%).

[0653] Record the NMR data of the disulfoxide derivative as a by-product.

[0654] 1H-NMR (300 MHz, CDCl3) δ (ppm, referenced to TMS): 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)

[0655] In the above example, no compound in which the thioether adjacent to R1 was oxidized was confirmed.

[0656] Comparative Example 1

[0657] Preparation of 5-Trifluoromethylthiopentyl - [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether

[0658]

[0659] In a 30 mL test tube, 5-(trifluoromethylthio)pentyl [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl] ether (2.60 g, purity 82.7%, 5 mmol, 100 mol%), manganese(III) acetylacetonate (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. After stirring the mixture at 0 °C for 30 minutes, it was aged at room temperature for 24 hours.

[0660] The reaction mixture was analyzed by HPLC (area percentage). As a result, the components other than the solvent etc. in the reaction mixture were as follows:

[0661] 5-(trifluoromethylthio)pentyl [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether (target compound): 0%;

[0662] 5-(trifluoromethylthio)pentyl [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl] ether (starting compound): 93.6%;

[0663] 5-(trifluoromethylsulfinyl)pentyl [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether (by-product: disulfoxide derivative): 0%.

[0664] Comparative Example 2

[0665] Production of 5-(trifluoromethylthio)pentyl [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether

[0666]

[0667] In a 30 mL test tube, 5-(trifluoromethylthio)pentyl [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl] ether (2.30 g, purity 93.9%, 5 mmol, 100 mol%), iron(III) acetylacetonate (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. After stirring the mixture at 0 °C for 30 minutes, it was aged at room temperature for 24 hours.

[0668] The reaction mixture was analyzed by HPLC (area percentage). As a result, the components other than the solvent, etc. in the reaction mixture are as follows:

[0669] 5-Trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether (target compound): 0%;

[0670] 5-Trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl] ether (starting compound): 93.6%;

[0671] 5-Trifluoromethylsulfinylpentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether (by-product: disulfoxide derivative): 0%.

[0672] Comparative Example 3

[0673] Production of 5-Trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether

[0674]

[0675] In a 30 mL test tube, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl] ether (2.47 g, purity 87%, 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. After stirring the mixture at 0 °C for 30 minutes, it was aged at room temperature for 20 hours.

[0676] The reaction mixture was analyzed by HPLC (area percentage). As a result, the components other than the solvent, etc. in the reaction mixture are as follows:

[0677] 5-Trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether (target compound): 2.1%;

[0678] 5-Trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl] ether (starting compound): 93.4%;

[0679] 5-Trifluoromethylsulfinylpentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether (by-product: disulfoxide derivative): 0%.

[0680] Comparative Example 4

[0681] Production of 5-(trifluoromethylthio)pentyl [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether

[0682]

[0683] In a 30 mL test tube, 5-(trifluoromethylthio)pentyl [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl] ether (2.47 g, purity 87%, 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. After stirring the mixture at 0 °C for 30 minutes, it was aged at room temperature for 20 hours.

[0684] The reaction mixture was analyzed by HPLC (area percentage). As a result, the components other than the solvent etc. in the reaction mixture are as follows:

[0685] 5-(trifluoromethylthio)pentyl [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether (target compound): 23.4%;

[0686] 5-(trifluoromethylthio)pentyl [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl] ether (starting compound): 72.2%;

[0687] 5-(trifluoromethylsulfinyl)pentyl [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether (by-product: disulfoxide derivative): 0.1%.

[0688] Comparative Example 5

[0689] Production of 5-(trifluoromethylthio)pentyl [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether

[0690]

[0691] In a 30 mL test tube, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl] ether (2.47 g, purity 87%, 5 mmol, 100 mol%) and ammonium paratungstate pentahydrate (13.1 mg, 0.004 mmol, 0.08 mol%, 1 mol% based on tungsten atoms) 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. After stirring the mixture at 0 °C for 30 minutes, it was aged at room temperature for 20 hours.

[0692] The reaction mixture was analyzed by HPLC (area percentage). As a result, the components other than the solvent and the like in the reaction mixture are as described below:

[0693] 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether (target compound): 7.3%;

[0694] 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl] ether (starting compound): 88.3%;

[0695] 5-trifluoromethylsulfinylpentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether (by-product: disulfoxide derivative): 0%.

[0696] Comparative Example 6

[0697] Production of 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether

[0698]

[0699] In a 30 mL test tube, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl] ether (2.60 g, purity 82.7%, 5 mmol, 100 mol%) and manganese(III) acetylacetonate (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. After stirring the mixture at 0 °C for 30 minutes, it was aged at room temperature for 24 hours.

[0700] The reaction mixture was analyzed by HPLC (area percentage). As a result, the components other than the solvent and the like in the reaction mixture are as described below:

[0701] 5-(Trifluoromethylthio)pentyl - [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether (target compound): 0%;

[0702] 5-(Trifluoromethylthio)pentyl - [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl] ether (starting material compound): 93.3%;

[0703] 5-(Trifluoromethylsulfinyl)pentyl - [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether (by-product: disulfoxide derivative): 0%;

[0704] Comparative Example 7

[0705] Preparation of 5-(Trifluoromethylthio)pentyl - [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether

[0706]

[0707] In a 30 mL test tube, 5-(Trifluoromethylthio)pentyl - [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl] ether (2.30 g, purity 93.9%, 5 mmol, 100 mol%) and iron(III) acetylacetonate (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. After stirring the mixture at 0 °C for 30 minutes, it was aged at room temperature for 24 hours.

[0708] The reaction mixture was analyzed by HPLC (area percentage). As a result, the components other than the solvent, etc. in the reaction mixture were as follows:

[0709] 5-(Trifluoromethylthio)pentyl - [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether (target compound): 0.9%;

[0710] 5-(Trifluoromethylthio)pentyl - [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl] ether (starting material compound): 93.8%;

[0711] 5-(Trifluoromethylsulfinyl)pentyl - [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether (by-product: disulfoxide derivative): 0%;

[0712] Comparative Example 8

[0713] Production of 5-(trifluoromethylthio)pentyl [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether

[0714]

[0715] In a 30 mL test tube, 5-(trifluoromethylthio)pentyl [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl] ether (2.47 g, purity 87%, 5 mmol, 100 mol%) and 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. After stirring the mixture at 0 °C for 30 minutes, it was aged at room temperature for 20 hours.

[0716] The reaction mixture was analyzed by HPLC (area percentage). As a result, the components other than the solvent etc. in the reaction mixture were as follows:

[0717] 5-(trifluoromethylthio)pentyl [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether (target compound): 1%;

[0718] 5-(trifluoromethylthio)pentyl [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl] ether (starting compound): 94.4%;

[0719] 5-(trifluoromethylsulfinyl)pentyl [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether (by-product: disulfoxide derivative): 0%.

[0720] Comparative Example 9

[0721] Production of 5-(trifluoromethylthio)pentyl [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether

[0722]

[0723] In a 30 mL test tube, 5-(trifluoromethylthio)pentyl [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl] ether (4.7 g, purity 90.4%, 10 mmol, 100 mol%) and 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. After stirring the mixture at 0 °C for 30 minutes, it was aged at room temperature for 69 hours.

[0724] The reaction mixture was analyzed by HPLC (area percentage). As a result, the components other than the solvent, etc. in the reaction mixture are as follows:

[0725] 5-Trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether (target compound): 26%;

[0726] 5-Trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl] ether (starting compound): 65.8%;

[0727] 5-Trifluoromethylsulfinylpentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether (by-product: disulfoxide derivative): 0%.

[0728] Comparative Example 10

[0729] Production of 5-Trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether

[0730]

[0731] In a 30 mL test tube, 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl] ether (2.47 g, purity 87%, 5 mmol, 100 mol%), ammonium paratungstate pentahydrate (13.1 mg, 0.004 mmol, 0.08 mol%, 1 mol% in terms of 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. After stirring the mixture at 0 °C for 30 minutes, it was aged at room temperature for 20 hours.

[0732] The reaction mixture was analyzed by HPLC (area percentage). As a result, the components other than the solvent, etc. in the reaction mixture are as follows:

[0733] 5-Trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether (target compound): 1.5%;

[0734] 5-Trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl] ether (starting compound): 94.1%;

[0735] 5-Trifluoromethylsulfinylpentyl - [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether (by-product: disulfoxide derivative): 0%.

[0736] Comparative Example 11

[0737] Production of 5-Trifluoromethylthiopentyl - [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether

[0738]

[0739] Preparation of catalyst solution

[0740] (1) Preparation of catalyst solution

[0741] Add vanadyl acetylacetonate (1.3 mg, 0.005 mmol, 1 mol%), (E)-2-{[(1-hydroxy-2-methylpropan-2-yl)imino]methyl}phenol (ligand of (3-4) described in WO2017 / 150478 (Patent Document 2), 1.0 mg, 0.005 mmol, 1 mol%), sodium 2,6-dimethoxybenzoate (benzoic acid derivative of (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) to a sample bottle with a screw cap. Stir the mixture at room temperature for 30 minutes.

[0742] (2) Production of the title compound

[0743] Dissolve 5-trifluoromethylthiopentyl - [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl] ether (244 mg, purity 88.2%, 0.500 mmol, 100 mol%) in dichloromethane (1 mL, 0.5 L / mol). Add the catalyst solution prepared in (1) above thereto. Cool the mixture to 0 °C. Add 35% hydrogen peroxide (97.1 mg, 1.0 mmol, 200 mol%) thereto. Stir the mixture at 0 °C for 15 hours. Analyze the organic layer of the reaction mixture by HPLC (area percentage). As a result, the components other than the solvent, etc. in the reaction mixture are as follows:

[0744] 5-Trifluoromethylthiopentyl - [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether (target compound): 1.2%;

[0745] 5-Trifluoromethylthiopentyl - [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl] ether (starting compound): 92.3%;

[0746] 5-Trifluoromethylsulfinylpentyl - [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether (by-product: disulfoxide derivative): 0%.

[0747] 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. By only changing the metal catalyst, it was difficult to obtain the target substance (B) of the present invention.

[0748] By-product:

[0749] Comparative Example 12

[0750] Production of 5-Trifluoromethylthiopentyl - [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether

[0751]

[0752] In a 30 mL test tube, 5-trifluoromethylthiopentyl - [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl] ether (2.30 g, purity 93.9%, 5 mmol, 100 mol%) and iron(III) acetylacetonate (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. After stirring the mixture at 0 °C for 30 minutes, it was aged at room temperature for 24 hours.

[0753] The reaction mixture was analyzed by HPLC (area percentage). As a result, the components other than the solvent, etc. in the reaction mixture were as follows:

[0754] 5-Trifluoromethylthiopentyl - [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether (target compound): 2.3%;

[0755] 5-Trifluoromethylthiopentyl - [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl] ether (starting compound): 93.2%;

[0756] 5-Trifluoromethylsulfinylpentyl - [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether (by-product: disulfoxide derivative): 0%.

[0757] Comparative Example 13

[0758] Production of 5-Trifluoromethylthiopentyl - [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether

[0759]

[0760] In a 250 mL reaction flask, 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, and the mixture was stirred for 10 minutes at an internal temperature of 25°C. Then, 35% hydrogen peroxide (5.24 g, 54 mmol, 180 mol%) was added dropwise to the mixture 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 other than the solvent and the like in the reaction mixture were as follows:

[0761] 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether (target compound): 2.2%;

[0762] 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl] ether (starting compound): 93.7%;

[0763] 5-trifluoromethylsulfinylpentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether (by-product: disulfoxide derivative): 0%.

[0764] Comparative Example 14

[0765] Production of 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether

[0766]

[0767] In a 250 mL reaction flask, 5-(trifluoromethylthio)pentyl [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, and the mixture was stirred for 10 minutes at an internal temperature of 25°C. 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 thereto 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 other than the solvent, etc. in the reaction mixture were as follows:

[0768] 5-(trifluoromethylthio)pentyl [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether (target compound): 17.5%;

[0769] 5-(trifluoromethylthio)pentyl [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio)phenyl] ether (starting compound): 70.5%;

[0770] 5-(trifluoromethylsulfinyl)pentyl [4-chloro-2-fluoro-5-(2,2,2-trifluoroethylsulfinyl)phenyl] ether (by-product: disulfoxide derivative): 0%.

[0771] The aging was further continued for 20 hours, but the reaction was not different from that at 4 hours.

[0772] Comparative Examples 13 and 14 are additional tests, etc. of the prior art using a ligand and a vanadium catalyst. In Comparative Example 13, in the method of Example 1 of US2011 / 0015405A1 (Japanese Patent Application Laid-Open No. 2012-532906, Patent Document 3), the reaction was carried out without using a ligand in the same manner as in the examples of the present invention. It is difficult to obtain the target substance (B) of this reaction only by changing the presence or absence of the use of a ligand. In Comparative Example 14, the same metal catalyst, ligand, oxidizing agent, and solvent as those in US2011 / 0015405A1 (Japanese Patent Application Laid-Open No. 2012-532906) (Patent Document 3), Example 1 were used to carry out the reaction in the same manner. As shown in Comparative Example 14, even when the method of the prior art was applied to the starting materials of the present invention, the reaction could not proceed sufficiently. It was confirmed that the prior art could not be applied to the production of the target substance of the present invention.

[0773] Example 20

[0774] White crystals of the compound of formula (B-a) were obtained by the same production 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 under vacuum. The melting point was 46 °C to 50 °C. The obtained crystals were used for powder X-ray diffraction measurement. The results of the powder X-ray diffraction measurement are shown in Figure 1 .

[0775] Example 21

[0776] White crystals of the compound of formula (B-a) were obtained by the same production 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, and water was removed by drying under reduced pressure, and then cooled. The obtained crystals were pulverized with a grinder. The melting point was 47 °C to 48 °C. The obtained crystals were used for powder X-ray diffraction measurement. The results of the powder X-ray diffraction measurement are shown in Figure 2 .

[0777] Example 22

[0778] White crystals of the compound of formula (B-a) were obtained by the same production method as in Example 1. The obtained crystals were used for recrystallization. Here, the recrystallization conditions were the same as the crystallization conditions of Example 1 (recrystallization with 2-propanol and water). The obtained crystals were filtered and dried. The melting point was 46 °C to 50 °C. The obtained crystals were used for powder X-ray diffraction measurement. The results of the powder X-ray diffraction measurement are shown in Figure 3 .

[0779] [Table 1]

[0780]

[0781] Reference Production Example 1

[0782] Production of 4-fluoro-2-chlorophenol

[0783]

[0784] In a 1000 mL reaction flask, 2-fluorophenol (112.1 g, purity 100%, 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 for 30 minutes at an internal temperature of 5 - 10 °C. Chlorine gas (70.9 g, 1000 mmol, 100 mol%) was blown into it for 6 hours at an internal temperature of 5 - 10 °C, and the mixture was aged for 1 hour while maintaining the internal temperature at 5 °C - 10 °C.

[0785] The reaction mixture was a yellow clear liquid at 10 °C. Nitrogen gas was blown into the reaction mixture at 60 mL / min for 2 hours. As a result, a dichloromethane solution of the target product was obtained in a yield of 97% (909.7 g, purity 15.6%).

[0786] 1 1H-NMR (300 MHz, CDCl3) δ (ppm, based on TMS): 5.09 (d, 1H), 6.94 (dd, 1H), 7.02 (ddd, 1H), 7.11 (dd, 1H)

[0787] Industrial applicability

[0788] As disclosed in Patent Document 1, the mono sulfoxide derivative of formula (B) has excellent acaricidal activity.

[0789] According to the present invention, an industrially more preferred and novel manufacturing method of a mono sulfoxide derivative of formula (B) can be provided, and the mono sulfoxide derivative of formula (B) is useful as a pesticide such as an acaricide.

[0790] In the present specification, as described above, the method of the present invention is more economical and has a high industrial utilization value for the environment.

[0791] In particular, the method of the present invention can avoid over-oxidation to a di sulfoxide derivative to selectively manufacture the target mono sulfoxide derivative. Further, a simple operation without using a ligand can be carried out.

[0792] Therefore, the present invention has the following advantages: it is not necessary to remove the di sulfoxide derivative of the by-product that is difficult to remove.

[0793] In summary, the present invention has a high industrial applicability.

[0794] All publications, patents, and patent applications cited in this specification are hereby incorporated by reference in their entirety into this specification to describe and disclose the methods described in such publications, patents, and patent applications that may be relevant to the description of this specification. To the extent necessary for understanding or carrying out the disclosure of the present invention, all publications, patents, and patent applications cited in this specification are hereby expressly incorporated by reference to the same extent as if each were individually incorporated. All publications, patents, and patent applications discussed above and throughout this specification are provided solely for the purpose of disclosing the present application as of the filing date of this application.

[0795] Any methods and reagents that are the same as or equivalent to those described in this specification can be used in the methods and implementations of the present invention. Accordingly, the present invention is not limited by the foregoing description, but is intended to be defined by the claims and their equivalents. These equivalents fall within the scope of the present invention as defined by the appended claims.

Claims

1. A method for preparing a compound of formula (B), wherein in formula (B), R 1 is a C1-C4 alkyl group, C2-C4 alkenyl group, C2-C4 alkynyl group, C1-C4 haloalkyl group, C2-C4 haloalkenyl group or C2-C4 haloalkynyl group, R 2 and R 3 each independently represents 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, a C1-C4 haloalkoxy group, and n is 5 or 6, wherein, the method comprises the following oxidation step: reacting a compound of formula (A) with hydrogen peroxide in the presence of a metal catalyst, In formula (A), R 1 , R 2 , R 3 and n are as defined above, wherein the metal catalyst is selected from vanadyl acetylacetonate, one or more catalysts selected from the group consisting of vanadyl acetylacetonate, vanadium oxide, vanadyl trichloride, titanium oxoacetylacetonate, titanium tetraisopropoxide, ammonium molybdate, sodium molybdate, potassium molybdate, molybdenum oxide, molybdenum chloride and molybdenum sulfide, wherein the oxidation step is carried out in a solvent, wherein the solvent is a nitrile solvent or an alcohol solvent, or a mixture of a nitrile solvent and water or an alcohol solvent and water, and wherein no ligand and benzoic acid derivative are used in the oxidation step.

2. The method according to claim 1, characterized in that, The metal catalyst is one or more catalysts selected from the group consisting of vanadyl acetylacetonate, vanadyl acetylacetonate, titanium oxoacetylacetonate and ammonium molybdate.

3. The method according to claim 1, characterized in that, The metal catalyst is one or more catalysts selected from the group consisting of vanadyl acetylacetonate and vanadyl acetylacetonate.

4. The method according to claim 1, characterized in that The alcohol is a C1-C6 aliphatic alcohol.

5. The method according to claim 4, wherein The alcohol is methanol, ethanol, 2-propanol, tert-butanol or tert-amyl alcohol.

6. The method according to claim 4, wherein The alcohol is methanol, 2-propanol, tert-butanol or tert-amyl alcohol.

7. The method according to claim 1, wherein The solvent is acetonitrile, methanol, 2-propanol, tert-butanol or tert-amyl alcohol, or a mixture of the solvent and water.

8. The method according to claim 1, wherein The content of the compound of formula (C) is 10% or less by weight based on the compound of formula (B), wherein in formula (C), 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 each independently represents 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.

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