TWI648254B - Method for producing pest control agent and intermediate thereof - Google Patents

Abstract

An object of the present invention is to provide a production intermediate suitable for producing a compound of general formula (4) having pest control activity on an industrial scale, and a method for producing the same.

The solution is: oxidize the mercaptophenol derivative, and then in the presence of a base, make the compound represented by the general formula (a): R ³ -X (wherein R ³ is C1 to C4 haloalkylthio C2 ~ C10 alkyl; X is a halogen atom, etc.) to obtain a compound represented by the general formula (3):

(Wherein R ¹ and R ² are each independently a halogen atom or a C1 to C4 alkyl group), and in the presence of a base, a compound represented by the general formula (b): R ⁴ -Y (wherein R ⁴ is C1 ~ C4 haloalkyl; Y is a halogen atom, etc.) to produce a compound represented by the general formula (4):

(Wherein R ¹ to R ⁴ are synonymous with the above).

Description

Method for producing pest control agent and intermediate thereof

The present invention relates to a method for producing a compound of the general formula (4) and an intermediate thereof,

(In the formula, R ¹ and R ² are each independently a halogen atom or a C1 to C4 alkyl group; R ³ is a C1 to C4 haloalkylthio group C2 to C10 alkyl group; R ⁴ is a C1 to C4 haloalkyl group).

In particular, the present invention relates to a manufacturing intermediate of the compound of the above general formula (4): a compound of the general formula (2):

(Wherein R ¹ and R ² are as defined above); and a compound of the general formula (3):

(Wherein R ¹ , R ² and R ³ are as defined above); and a compound of the general formula (5):

(Wherein R ¹ , R ² and R ³ are as defined above).

The compound of the above general formula (4) is used as a pest control agent for pesticides and the like and its manufacturing intermediate (refer to Examples 12, 13, 17, 18, 26, and 27 of Patent Document 1).

Patent Document 1 has disclosed, for example, that by making 6-cyanothiohexyl- [2,4-dimethyl-5- (2,2,2-trifluoroethylsulfide) in the presence of tetra-n-butylammonium fluoride A method in which the group) phenyl] ether is reacted with trifluoromethyltrimethylsilane to obtain the product of Example 26.

In this method, there are problems in the industrial production of 6-cyanothiohexyl- [2,4-dimethyl-5- (2,2,2-trifluoroethylthio) phenyl] ether as a raw material. For example, it is possible to cite the need for special devices for the large-scale use of boric acid derivatives as raw materials, and the problems of large-scale use of high-priced reagents, special reagents, and use of excessive reagents (see patents). Examples 21, 24, and 25 of Document 1).

Furthermore, in the prior art, 1-iodo-2,2,2-trifluoroethane and p-toluenesulfonic acid 2,2,2-trifluoroethyl etc. have been used in the production of compounds of general formula (4). Halogenated alkylating agents, but these halogenated alkylating agents are expensive and are based on the general formula (4) In the industrial manufacture of the compounds, such a large amount of use has also become a major issue in terms of cost. For example, Patent Literature 1 has specifically disclosed the manufacturing methods 6 and 7 through examples. However, in these manufacturing methods, at an earlier stage in the production path of the pest control agent of the final target compound, a halogenated alkylation reaction using these halogenated alkylating agents is performed, resulting in the need for a high-valent halogenated alkylating agent. The problem of heavy usage.

In addition, in general, sulfur-containing organic compounds mostly have a characteristic odor, and there is a need to consider the prevention of this odor when it is manufactured in industry.

As described above, there are various problems in performing reactions on an industrial scale.

Under these circumstances, the establishment of a method for industrially and inexpensively producing a compound of the general formula (4) without a simple method such as special equipment or complicated operations is eagerly expected.

[Prior technical literature] [Patent Literature]

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

[Invention Summary]

An object of the present invention is to provide an industrially preferable manufacturing intermediate of the above-mentioned general formula (4). In other words, the object of the present invention is to provide a manufacturing intermediate suitable for large-scale manufacturing in industrial production.

Another object of the present invention is to provide the industrially preferred ones described above. A method for producing a compound of the general formula (4).

In view of the circumstances as described above, the present inventors have devotedly studied a method for producing the compound of the general formula (4). As a result, it was unexpectedly found that by providing the compound of the general formula (2), the compound of the general formula (3) and / or the formula (5), and by providing the compound of the above general formula (4) In the method for producing a compound of (2), the aforementioned problems may be solved. Based on this knowledge, the present inventors have completed the present invention.

That is, the present invention is as follows.

[1] A compound represented by the general formula (2):

(Wherein R ¹ and R ² are each independently a halogen atom or a C1 to C4 alkyl group).

[2] The compound according to the above [1], wherein R ¹ and R ² are each independently a halogen atom; or R ¹ and R ² are each independently a C1 to C4 alkyl group.

[3] The compound according to the above [1], wherein R ¹ is a fluorine atom and R ² is a chlorine atom; or R ¹ and R ² are each a methyl group.

[4] The compound according to the above [1], wherein R ¹ and R ² are each independently a halogen atom.

[5] The compound according to the above [1], wherein R ¹ is a fluorine atom and R ² is a chlorine atom.

[6] The compound according to the above [1], wherein R ¹ and R ² are each independently a C1 to C4 alkyl group.

[7] The compound according to the above [1], wherein each of R ¹ and R ² is a methyl group.

[8] A compound represented by the general formula (3):

(Wherein R ¹ and R ² are each independently a halogen atom or a C1 to C4 alkyl group; R ³ is a C1 to C4 haloalkylthio group C2 to C10 alkyl group).

[9] The compound according to the above [8], wherein R ¹ and R ² are each independently a halogen atom, and R ³ is a C1 to C4 haloalkylthio group C2 to C10 alkyl; or R ¹ and R ² are each independently C1 ~ C4 alkyl, R ³ is C1 ~ C4 haloalkylthio, C2 ~ C10 alkyl.

[10] The compound according to the above [8], wherein R ¹ is a fluorine atom; R ² is a chlorine atom; R ³ is a 5-trifluoromethylthiopentyl group; or R ¹ and R ² are each a methyl group; R ³ is 6-trifluoromethylthiohexyl.

[11] The compound according to the above [8], wherein R ¹ and R ² are each independently a halogen atom; R ³ is a C1 to C4 haloalkylthio group C2 to C10 alkyl group.

[12] The compound according to the above [8], wherein R ¹ is a fluorine atom; R ² is a chlorine atom; R ³ is 5 to trifluoromethylthiopentyl.

[13] The compound according to the above [8], wherein R ¹ and R ² are each independently a C1 to C4 alkyl group; and R ³ is a C1 to C4 haloalkylthio group C2 to C10 alkyl group.

[14] The compound according to the above [8], wherein R ¹ and R ² are each a methyl group; and R ³ is 6-trifluoromethylthiohexyl.

[15] A compound represented by the general formula (5):

(Wherein R ¹ and R ² are each independently a halogen atom or a C1 to C4 alkyl group; R ³ is a C1 to C4 haloalkylthio group C2 to C10 alkyl group).

[16] The compound according to the above [15], wherein R ¹ and R ² are each independently a halogen atom; R ³ is a C1 to C4 haloalkylthio group C2 to C10 alkyl group; or R ¹ and R ² are each independently C1 ~ C4 alkyl group; R ³ is a halo C1 ~ C4 alkylthio C2 ~ C10 alkyl group.

[17] The compound according to the above [15], wherein R ¹ is a fluorine atom; R ² is a chlorine atom; R ³ is 5-trifluoromethylthiopentyl; or R ¹ and R ² are each a methyl group; R ³ is 6-trifluoromethylthiohexyl.

[18] The compound according to the above [15], wherein R ¹ and R ² are each independently a halogen atom; R ³ is a C1 to C4 haloalkylthio group and a C2 to C10 alkyl group.

[19] The compound according to the above-mentioned [15], wherein R ¹ is a fluorine atom; R ² is a chlorine atom; R ³ is 5-trifluoromethylthiopentyl.

[20] The compound according to the above [15], wherein R ¹ and R ² are each independently a C1 to C4 alkyl group; R ³ is a C1 to C4 haloalkylthio group C2 to C10 alkyl group.

[21] The compound according to [15], wherein R ¹ and R ² are each a methyl group; and R ³ is 6-trifluoromethylthiohexyl.

[22] A method for producing a compound represented by the general formula (4),

(Wherein R ¹ and R ² are each independently a halogen atom or a C1 to C4 alkyl group; R ³ is a C1 to C4 haloalkylthio group C2 to C10 alkyl group; R ⁴ is a C1 to C4 haloalkyl group), which Including the following steps: (i) a step of producing a compound represented by the general formula (2) from a compound represented by the general formula (1),

(Wherein R ¹ and R ² are as defined above),

(Wherein R ¹ and R ² are as defined above); (ii) the compound of the general formula (2) is reacted with a compound of the general formula (a) in the presence of a base to produce a general compound; Step of the compound represented by formula (3), R ³ -X (a)

(Wherein R ³ is as defined above; X is a halogen atom, C1-C4 alkylsulfonyloxy, C1-C4 haloalkylsulfonyloxy, or may be substituted by C1-C4 alkyl or halogen atom Phenylsulfonyloxy),

(Wherein R ¹ , R ² and R ³ are as defined above); and (iii) a step of converting the compound of the aforementioned general formula (3) to the compound of the aforementioned general formula (4).

[23] The method according to the above [22], wherein step (iii) is the following step: (iii-a) the compound represented by the general formula (3) is reacted with the general formula (3) in the presence of a base. a step of reacting a compound represented by b) to convert a compound of the aforementioned general formula (3) into a compound of the aforementioned general formula (4),

(Wherein R ¹ and R ² are each independently a halogen atom or a C1 to C4 alkyl group; R ³ is a C1 to C4 haloalkylthio group C2 to C10 alkyl group), R ⁴ -Y (b)

(Wherein R ⁴ is a C1 to C4 haloalkyl group; Y is a halogen atom, C1 to C4 alkylsulfonyloxy group, C1 to C4 haloalkylsulfonyloxy group, or C1 to C4 alkyl group or halogen Atom substituted phenylsulfonyloxy).

[24] The method according to the above [22], wherein step (iii) includes the following steps: (iii-b) converting the compound represented by the general formula (3) into a compound represented by the general formula (5) A step of,

(Wherein R ¹ and R ² are each independently a halogen atom or a C1 to C4 alkyl group; R ³ is a C1 to C4 haloalkylthio group C2 to C10 alkyl group),

(Wherein R ¹ , R ² and R ³ are as defined above); and (iii ~ c) by using the compound of the general formula (5) in the presence of a base, A step of reacting a compound represented by the formula (5) to convert the compound of the aforementioned general formula (5) to the compound of the aforementioned general formula (4), R ⁴ -Y (b)

(Wherein R ⁴ is a C1 to C4 haloalkyl group; Y is a halogen atom, C1 to C4 alkylsulfonyloxy group, C1 to C4 haloalkylsulfonyloxy group, or C1 to C4 alkyl group or halogen Atom substituted phenylsulfonyloxy).

[25] The method according to the above [23] or [24], wherein R ¹ and R ² are each independently a halogen atom, or R ¹ and R ² are each independently a C1 to C4 alkyl group.

[26] The method according to the above [23] or [24], wherein R ¹ is a fluorine atom; R ² is a chlorine atom; R ³ is 5-trifluoromethylthiopentyl; R ⁴ is 2, 2, 2-trifluoroethyl; X is chlorine atom, bromine atom, iodine atom, methanesulfonyloxy group, benzenesulfonyloxy group, p-toluenesulfonyloxy group or p-chlorobenzenesulfonyloxy group; Y is chlorine atom, Bromine atom, iodine atom, methanesulfonyloxy, benzenesulfonyloxy, p-toluenesulfonyloxy or p-chlorobenzenesulfonyloxy; or R ¹ and R ² are each methyl; R ³ is 6-tri Fluoromethylthiohexyl; R ⁴ is 2,2,2-trifluoroethyl; X is chlorine, bromine, iodine, methanesulfonyloxy, benzenesulfonyloxy, p-toluenesulfonyloxy Or p-chlorobenzenesulfonyloxy; Y is chlorine atom, bromine atom, iodine atom, methanesulfonyloxy, benzenesulfonyloxy, p-toluenesulfonyloxy or p-chlorobenzenesulfonyloxy.

[27] The method according to the above [23] or [24], wherein R ¹ and R ² are each independently a halogen atom.

[28] The method according to the above [23] or [24], wherein R ¹ is a fluorine atom; R ² is a chlorine atom; R ³ is 5-trifluoromethylthiopentyl; R ⁴ is 2, 2, 2-trifluoroethyl; X is chlorine atom, bromine atom, iodine atom, methanesulfonyloxy, benzenesulfonyloxy, p-toluenesulfonyloxy or p-chlorobenzenesulfonyloxy; Y is chlorine atom, Bromine atom, iodine atom, methanesulfonyloxy, benzenesulfonyloxy, p-toluenesulfonyloxy or p-chlorobenzenesulfonyloxy.

[29] The method according to the above [23] or [24], wherein R ¹ and R ² are each independently a C1 to C4 alkyl group.

[30] The method according to the above [23] or [24], wherein R ¹ and R ² are each methyl; R ³ is 6-trifluoromethylthiohexyl; R ⁴ is 2,2,2-tris Fluoroethyl; X is chlorine atom, bromine atom, iodine atom, methanesulfonyloxy group, benzenesulfonyloxy group, p-toluenesulfonyloxy group or p-chlorobenzenesulfonyloxy group; Y is chlorine atom, bromine atom, Iodine atom, methanesulfonyloxy, benzenesulfonyloxy, p-toluenesulfonyloxy or p-chlorobenzenesulfonyloxy.

[31] A method for producing a compound represented by the general formula (2):

(Wherein R ¹ and R ² are as defined below), which is characterized by oxidizing a compound represented by the general formula (1),

(Wherein R ¹ and R ² are each independently a halogen atom or a C1 to C4 alkyl group).

[32] A method for producing a compound represented by the general formula (3),

(Wherein R ¹ , R ² and R ³ are as defined below), which is characterized in that a compound represented by the general formula (2) is reacted with a compound represented by the general formula (a) in the presence of a base. ,

(Wherein R ¹ and R ² are each independently a halogen atom or a C1 to C4 alkyl group): R ³ -X (a)

(Wherein R ³ is a C1 to C4 haloalkylthio group C2 to C10 alkyl group; X is a halogen atom, C1 to C4 alkylsulfonyloxy group, C1 to C4 haloalkylsulfonyloxy group, or C1-C4 alkyl or halogen atom-substituted phenylsulfonyloxy).

[33] A method for producing a compound represented by the general formula (4),

(Wherein R ¹ , R ² , R ³ and R ⁴ are as defined below), which is characterized in that the compound represented by the general formula (3) and the compound represented by the general formula (b) in the presence of a base Compound reaction,

(Wherein R ¹ and R ² are each independently a halogen atom or a C1 to C4 alkyl group; R ³ is a C1 to C4 haloalkylthio group C2 to C10 alkyl group), R ⁴ -Y (b)

(Wherein R ⁴ is a C1 to C4 haloalkyl group; Y is a halogen atom, C1 to C4 alkylsulfonyloxy group, C1 to C4 haloalkylsulfonyloxy group, or C1 to C4 alkyl group or halogen Atom substituted phenylsulfonyloxy).

[34] a method for producing a compound represented by the general formula (5),

(Wherein R ¹ , R ² and R ³ are as defined below), which is characterized by reducing a compound represented by the general formula (3),

(Wherein R ¹ and R ² are each independently a halogen atom or a C1 to C4 alkyl group; R ³ is a C1 to C4 haloalkylthio group C2 to C10 alkyl group).

[35] A method for producing a compound represented by the general formula (4),

(Wherein R ¹ , R ² , R ³ and R ⁴ are as defined below), which is characterized in that the compound represented by the general formula (5) is represented by the general formula (b) in the presence of a base. Compound reaction,

(Wherein R ¹ and R ² are each independently a halogen atom or a C1 to C4 alkyl group; R ³ is a C1 to C4 haloalkylthio group C2 to C10 alkyl group), R ⁴ -Y (b)

(Wherein R ⁴ is a C1 to C4 haloalkyl group; Y is a halogen atom, C1 to C4 alkylsulfonyloxy group, C1 to C4 haloalkylsulfonyloxy group, or C1 to C4 alkyl group or halogen Atom substituted phenylsulfonyloxy).

According to the present invention, there can be provided a novel manufacturing intermediate for a compound of general formula (4) as a pest control agent and a manufacturing intermediate thereof.

Furthermore, according to the present invention, there can be provided a novel method for producing a compound of general formula (4) as a pest control agent and a production intermediate thereof.

Furthermore, according to the present invention, by using the compound of the general formulae (2), (3), and / or (5) of the present invention, the haloalkylation reaction can be performed at a later stage in the production path of the pest control agent, which can Significantly reduce the amount of expensive halogenated alkylating agents, and can significantly reduce manufacturing costs. Accordingly, the present invention is economical and has high industrial use value.

In addition, the bis (2,4-dimethyl-5-hydroxyl) produced in Example 1 of the present invention Phenyl) disulfide has almost no malodor. In addition, bis (2,4-dimethyl-5-hydroxyphenyl) disulfide is a solid having a very high melting point. A high melting point means that the compound is better on storage and offers the option of recrystallization as a method of isolation and / or purification. The present invention has discovered that bis (2,4-dimethyl-5-hydroxyphenyl) disulfide has such a plurality of advantages at the same time. The bis (2-chloro-4-fluoro-5-hydroxyphenyl) disulfide produced in Example 6 of the present invention also has the same properties and advantages. Accordingly, the general formula (2) represented by bis (2,4-dimethyl-5-hydroxyphenyl) disulfide and bis (2-chloro-4-fluoro-5-hydroxyphenyl) disulfide ) Compounds are industrially useful.

According to the present invention, the compounds of the general formulae (2), (3), and (5), which are intermediates for the production of the compounds of the general formula (4), have good yields because they do not use special reaction conditions or special expensive reagents. It is suitable for industrial production, and therefore, by using these intermediates, it is also a great advantage in terms of cost and the like in the industrial production of the compound of the general formula (4).

In providing the present invention, the compounds of the general formulae (2), (3), and (5) and the production methods using them are the first time to implement them. Furthermore, according to the present invention, the industrial use value of the compounds of the general formulae (2), (3), and (5) and the production method using them is realized for the first time.

[Form of Implementing Invention]

Hereinafter, the present invention will be described in detail.

The terms and symbols used in this manual are explained below.

Examples of the halogen atom include a fluorine atom and a chlorine atom. Atom, bromine atom and iodine atom. From the viewpoint of the usefulness of the product, etc., preferred examples of the halogen atom include a fluorine atom and a chlorine atom.

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

The C1-C4 alkyl group means a straight-chain or branched alkyl group having 1 to 4 carbon atoms. Examples of the C1-C4 alkyl group include a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, a second butyl group, an isobutyl group, and a third butyl group. From the viewpoint of the usefulness of the product and the like, a preferred example of the C1 to C4 alkyl group is a methyl group.

The C2 to C10 alkyl group means a straight-chain or branched alkyl group having 2 to 10 carbon atoms. Examples of the C2 to C10 alkyl group include ethyl, propyl, isopropyl, butyl, second butyl, isobutyl, third butyl, pentyl, hexyl, heptyl, and octyl , Nonyl, decyl, and the like, but are not limited thereto.

C1 ~ C4 haloalkyl means a linear or branched alkyl group having 1 to 4 carbon atoms substituted with the same or different 1 to 9 halogen atoms (wherein the halogen atom has The same meaning). Examples of C1 to C4 haloalkyl include fluoromethyl, difluoromethyl, trifluoromethyl, chlorodifluoromethyl, 2,2,2-trifluoroethyl, pentafluoroethyl, 3-fluoropropyl, 2,2,3,3,3-pentafluoropropyl, heptafluoropropyl, 2,2,2-trifluoro-1-trifluoromethylethyl, 2,2,3, 3,4,4,4-Heptafluorobutyl and the like are not limited thereto.

The C1 to C4 haloalkylthio group refers to a (C1 to C4 haloalkyl) -S- group (wherein the C1 to C4 haloalkyl group has the same meaning as described above). Just C1 ~ C4 Examples of the haloalkylthio group include fluoromethylthio, difluoromethylthio, trifluoromethylthio, chlorodifluoromethylthio, and 2,2,2-trifluoroethyl. Thio, pentafluoroethylthio, 3-fluoropropylthio, 2,2,3,3,3-pentafluoropropylthio, heptafluoropropylthio, 2,2,2-trifluoro 1-trifluoromethylethylthio, 2,2,3,3,4,4,4-heptafluorobutylthio, and the like are not limited thereto.

C1 ~ C4 haloalkylthio C2 ~ C10 alkyl means C2 ~ C10 alkyl substituted by C1 ~ C4 haloalkylthio (C1 ~ C4 haloalkylthio and C2 ~ C10 alkyl Has the same meaning as above). Examples of the C1-C4 haloalkylthio group and the C2-C10 alkyl group include 2-trifluoromethylthioethyl, 3-trifluoromethylthiopropyl, and 4-trifluoromethylthio. Butylbutyl, 5-difluoromethylthiopentyl, 5-trifluoromethylthiopentyl, 5- (2,2,2-trifluoroethylthio) pentyl, 5-pentafluoroethyl Pentylthiopentyl, 5- (2,2,3,3,3-pentafluoropropylthio) pentyl, 5- (2,2,3,3,4,4,4-heptafluorobutyl Thio) pentyl, 6-difluoromethylthiohexyl, 6-trifluoromethylthiohexyl, 6- (2,2,2-trifluoroethylthio) hexyl, 6-pentafluoroethyl Thiohexyl, 6- (2,2,3,3,3-pentafluoropropylthio) hexyl, 6- (2,2,3,3,4,4,4-heptafluorobutylthio) Hexyl, 7-trifluoromethylthioheptyl, 8-trifluoromethylthiooctyl, 9-trifluoromethylthiononyl, 10-trifluoromethylthiodecyl, and the like, but not limited And so on. From the viewpoint of the usefulness of the product, etc., preferred examples of the C1 to C4 haloalkylthio group and the C2 to C10 alkyl group include 5-trifluoromethylthiopentyl and 6-trifluoromethyl. Thiohexyl.

The C1 to C4 alkylsulfonyloxy group means a (C1 to C4 alkyl) -SO ₂ -O- group (wherein the C1 to C4 alkyl group has the same meaning as described above). Examples of the C1 to C4 alkylsulfonyloxy group include, but are not limited to, methanesulfonyloxy and ethanesulfonyloxy.

The C1-C4 haloalkylsulfonyloxy group means a (C1-Chaloalkyl) -SO ₂ -O- group (wherein the C1-C4 haloalkyl group has the same meaning as described above). Examples of the C1 to C4 alkylsulfonyloxy group include trifluoromethanesulfonyloxy group and the like, but are not limited thereto.

The phenylsulfonyloxy group which may be substituted with a C1 to C4 alkyl group or a halogen atom means a phenyl-SO ₂ -O- group (wherein the C1 to C4 alkyl group may be substituted with a C1 to C4 alkyl group or a halogen atom) And halogen atom system have the same meaning as above). Examples of the phenylsulfonyloxy group which may be substituted by a C1 to C4 alkyl group or a halogen atom include benzenesulfonyloxy group, p-toluenesulfonyloxy group, p-chlorobenzenesulfonyloxy group, and the like, but It is not limited to these.

Examples of R ¹ in the present invention include a halogen atom and a C1 to C4 alkyl group.

From the viewpoint of the usefulness of the product, etc., in one embodiment, the preferred R ¹ in the present invention includes, for example, a halogen atom, and more preferably a fluorine atom. From the same viewpoint as the above, in other embodiments, the preferred R ¹ in the present invention includes, for example, a C1 to C4 alkyl group, and more preferably a methyl group.

Examples of R ² in the present invention include a halogen atom and a C1 to C4 alkyl group.

From the viewpoint of the usefulness of the product, etc., in one embodiment, the preferred R ² in the present invention includes, for example, a halogen atom, and more preferably a chlorine atom.

From the same viewpoints as above, in other embodiments, the preferred R ² in the present invention includes, for example, a C1 to C4 alkyl group, and more preferably a methyl group.

Examples of R ³ in the present invention include a C1 to C4 haloalkylthio group and a C2 to C10 alkyl group.

From the viewpoint of the usefulness of the product and the like, in one embodiment, as a preferable R ³ in the present invention, for example, 5-trifluoromethylthiopentyl may be mentioned.

From the same viewpoint as above, in other embodiments, as a preferred R ³ in the present invention, for example, 6-trifluoromethylthiohexyl may be mentioned.

Examples of R ⁴ in the present invention include C1 to C4 haloalkyl.

From the viewpoint of usefulness of the product, etc., preferred R ⁴ in the present invention includes, for example, 2,2,2-trifluoroethyl.

As for X in the present invention, for example, a halogen atom, a C1 to C4 alkylsulfonyloxy group, a C1 to C4 haloalkylsulfonyloxy group, and a C1 to C4 alkyl group or a halogen atom that may be substituted Phenylsulfonyloxy.

From the viewpoints of reactivity, productivity, economic efficiency, etc., preferred X in the present invention includes, for example, a chlorine atom, a bromine atom, an iodine atom, a methanesulfonyloxy group, and a trifluoromethanesulfonyloxy group. , Benzenesulfonyloxy, p-toluenesulfonyloxy and p-chlorobenzenesulfonyloxy, more preferably chlorine atom, bromine atom, iodine atom, methanesulfonyloxy, benzenesulfonyloxy, p-toluenesulfonyl Oxygen and p-chlorobenzenesulfonyloxy are even more preferably a chlorine atom, a bromine atom, and an iodine atom, still more preferably a bromine atom and an iodine atom, and particularly preferably a bromine atom.

Examples of Y in the present invention include a halogen atom, a C1 to C4 alkylsulfonyloxy group, a C1 to C4 haloalkylsulfonyloxy group, and A phenylsulfonyloxy group which may be substituted by a C1-C4 alkyl group or a halogen atom.

From the viewpoints of reactivity, productivity, economic efficiency, etc., preferred Y in the present invention includes, for example, a chlorine atom, a bromine atom, an iodine atom, a methanesulfonyloxy group, and a trifluoromethanesulfonyloxy group. , Benzenesulfonyloxy, p-toluenesulfonyloxy and p-chlorobenzenesulfonyloxy, more preferably chlorine atom, bromine atom, iodine atom, methanesulfonyloxy, benzenesulfonyloxy, p-toluenesulfonyl Oxygen and p-chlorobenzenesulfonyloxy, still more preferably chlorine, bromine, iodine, methanesulfonyloxy, p-toluenesulfonyloxy, even more preferably bromine, iodine, methanesulfonyl Oxygen and p-toluenesulfonyloxy are still more preferably iodine atom, p-toluenesulfonyloxy, and particularly preferably p-toluenesulfonyloxy.

(Step (i))

First, step (i) will be described.

Step (i) is a step of producing a compound represented by General Formula (2) from a compound represented by General Formula (1),

(Wherein R ¹ and R ² are each independently a halogen atom or a C1 to C4 alkyl group),

(Wherein R ¹ and R ² are as defined above).

Among them, step (i) is a step of producing a compound of general formula (2) by oxidizing the compound of general formula (1). In other words, step (i) is a step of producing a compound of general formula (2) by reacting a compound of general formula (1) with an oxidizing agent.

(Raw material; compound of general formula (1))

A compound of the general formula (1) is used as a raw material for the method of the present invention. The compound of the general formula (1) is a known compound, or a compound that can be produced from a known compound by a known method. Specific examples of the compound of the general formula (1) include 2,4-difluoro-5-mercaptophenol, 2,4-dichloro-5-mercaptophenol, and 4-chloro-2-fluoro- 5-mercaptophenol, 2-chloro-5-mercapto-4-methylphenol, 2-fluoro-5-mercapto-4-methylphenol, 5-mercapto-2,4-dimethylphenol, etc., but not limited And so on.

(Step (i) oxidant)

The oxidizing agent used in the step (i) may be any type as long as the reaction can proceed. Examples of the oxidant usable in step (i) include, for example, hydrogen peroxide; organic peracids such as peracetic acid and m-chloroperbenzoic acid; oxygen and air; hypochlorous acid such as sodium hypochlorite Salts; chlorates such as sodium chlorate; halogens such as chlorine, bromine, and iodine; metal oxides such as manganese dioxide; potassium permanganate; potassium ferricyanide (potassium hexacyanoferrate (III)); Iron (III), dimethylsulfinium and the like, but not limited to these. From the viewpoints of reactivity, selectivity, economic efficiency, etc., preferred examples of the oxidizing agent in step (i) Specific examples include hydrogen peroxide and oxygen.

The oxidizing agent in step (i) may be used alone or in a combination of two or more kinds at any ratio. The form of the oxidant in step (i) is not limited as long as the reaction can proceed, and may be in any form. The form of the oxidizing agent in step (i) can be appropriately selected by those having ordinary knowledge in the art. The amount of the oxidant used in step (i) is any amount as long as the reaction can proceed. It can be exemplified by 0.5 to 5 mol, preferably 0.5 to 2 mol, and more preferably 0.5 to 1.5 mol relative to 1 mol of the compound of the general formula (1), but step (i) The amount of the oxidant to be used can be appropriately adjusted by those having ordinary knowledge in the technical field to which this item belongs.

When hydrogen peroxide is used as the oxidizing agent in step (i), the form of the hydrogen peroxide may be any form as long as the reaction can proceed. In consideration of the danger and economic efficiency, the form of hydrogen peroxide includes, for example, an aqueous solution having a concentration of 5% or more and less than 40%, and preferably an aqueous solution having a concentration of 10% to 35%.

When hydrogen peroxide is used as the oxidizing agent in step (i), the amount of hydrogen peroxide used may be any amount as long as the reaction can proceed. From the viewpoints of yield, suppression of by-products, and economic efficiency, for example, it is 0.5 to 1.5 mol, preferably 0.5 to 1.0 mol, more preferably 1 to mol of the compound of the general formula (1). It is preferably in the range of 0.5 to 0.6 mol.

When hydrogen peroxide is used as the oxidant in step (i), the reaction can be performed in the presence of a catalyst amount of iodide. No iodide can be used. Whether or not to use iodide can be appropriately determined by those having ordinary knowledge in the technical field. Examples of the iodide include sodium iodide and potassium iodide, and sodium iodide is preferred. As long as the iodide species react It can be carried out as long as it takes any form. The amount of iodide used may be any amount as long as the reaction proceeds. From the viewpoints of yield, by-product suppression, economic efficiency, etc., it may be exemplified by 0 (zero) to 0.1 mol, preferably 0 to 0.05 mol relative to 1 mol of the compound of the general formula (1). Ear, more preferably in the range of 0 to 0.03 moles. In the case of using iodide compounds, it can be exemplified by 0.001 to 0.1 mol, preferably 0.001 to 0.05 mol, and more preferably 0.005 to 0.03 mol relative to 1 mol of the compound of the general formula (1). range.

When oxygen is used as the oxidant in step (i), air may be used. That is, air oxidation can be used.

(Solvent of step (i))

From the viewpoint of smooth progress of the reaction, etc., it is preferred that the reaction in step (i) is carried out in the presence of a solvent. The solvent in step (i) is only required to be carried out in the reaction in step (i), and may be any solvent.

Examples of the solvent in step (i) include water, alcohols (for example, methanol, ethanol, 2-propanol, butanol, etc.), and ethers (for example, tetrahydrofuran (THF), 1,4-dihydrofuran). Alkane, diisopropyl ether, dibutyl ether, di-third butyl ether, cyclopentyl methyl ether (CPME), methyl-third butyl ether, 1,2-dimethoxyethane (DME), diglyme, triglyme, etc.), nitriles (e.g., acetonitrile, etc.), amidines (e.g., N, N-dimethylformamidine) Amine (DMF), N, N-dimethylacetamide (DMAC), N-methylpyrrolidone (NMP), etc.), alkyl ureas (for example, N, N'-dimethylimidazolidone (DMI), etc., fluorenes (e.g., dimethyl sulfene (DMSO), etc.), fluorenes (e.g., cyclobutane, etc.), ketones (e.g., acetone, isobutyl methyl ketone (MIBK), cyclic Hexanone, etc.), carboxylic acid esters (e.g., ethyl acetate, butyl acetate, etc.), carboxylic acids (e.g., acetic acid, etc.), carbonates (e.g., ethyl carbonate, propyl carbonate, etc.), aromatic Hydrocarbon derivatives (for example, benzene, toluene, xylene, chlorobenzene, dichlorobenzene, trichlorobenzene, nitrobenzene, etc.), halogenated aliphatic hydrocarbons (for example, methylene chloride, etc.), and any ratio Any arbitrary combination of them is not limited to these.

From the viewpoints of reactivity, economic efficiency, etc., as preferred examples of the solvent in step (i), water, alcohols, nitriles, amidines, fluorenes, ketones, carboxylic acid esters, Any combination of carboxylic acids, aromatic hydrocarbon derivatives, halogenated aliphatic hydrocarbons, and any ratio thereof. As specific examples of the solvent in step (i), water, methanol, ethanol, 2-propanol, acetonitrile, N, N-dimethylformamide (DMF), N, N-dimethyl Acetylacetamide (DMAC), dimethylmethylene sulfoxide, acetone, isobutyl methyl ketone (MIBK), cyclohexanone, ethyl acetate, butyl acetate, acetic acid, toluene, xylene, chlorobenzene, dichlorobenzene, Dichloromethane, and any combination thereof in any ratio.

The amount of the solvent used in step (i) may be any amount as long as the reaction system can be sufficiently stirred. From the viewpoints of yield, suppression of by-products, economic efficiency, etc., it may be exemplified by 0.01 to 10.0 L (liters), preferably 0.1 to 5.0 L relative to 1 mole of the compound of the general formula (1) Fan Around. When a combination of two or more solvents is used, the ratio of the two or more solvents may be any ratio as long as the reaction proceeds.

When hydrogen peroxide or oxygen is used as the oxidizing agent in step (i), for example, the compound of the general formula (1) is used as a sodium salt or potassium salt in an aqueous solution of an alkali metal hydroxide such as sodium hydroxide or potassium hydroxide. Alkali metal salts can be reacted in this aqueous solution.

(Reaction temperature of step (i))

The reaction temperature of step (i) is not particularly limited. From the viewpoints of yield, suppression of by-products, economic efficiency, and the like, a range of -30 ° C (minus 30 ° C) to 160 ° C, and preferably -10 ° C to 80 ° C is exemplified.

(Reaction time of step (i))

The reaction time of step (i) is not particularly limited. From the viewpoints of productivity, by-product suppression, and economic efficiency, for example, 0.5 hours to 48 hours, preferably 0.5 hours to 24 hours, and more preferably 1 hour to 12 hours.

Regarding step (i), if necessary, refer to the following documents.

(Compiled by the Japan Chemical Society, "New Experimental Chemistry Lecture 14 Synthesis and Reaction of Organic Compounds III", pages 1736 ~ 1738 (1978), issued by Iizumi Shingo, Maruzen Co., Ltd.

(Compiled by) The Chemical Society of Japan, "Experimental Chemistry Lecture 24 Organic Synthesis VI", 4th edition, pages 330-331 (1992), publisher Murata Seishiro, Maruzen Co., Ltd.

(Product of step (i); compound of general formula (2))

Specific examples of the compound of the general formula (2) obtained in step (i) include bis (2,4-difluoro-5-hydroxyphenyl) disulfide, Bis (2,4-dichloro-5-hydroxyphenyl) disulfide, bis (2-chloro-4-fluoro-5-hydroxyphenyl) disulfide, bis (4-fluoro-2-methyl- 5-hydroxyphenyl) disulfide, bis (4-chloro-2-methyl-5-hydroxyphenyl) disulfide, bis (2,4-dimethyl-5-hydroxyphenyl) disulfide Etc., but it is not limited to these.

The bis (2,4-difluoro-5-hydroxyphenyl) disulfide is also referred to as 5,5'-dithiobis (2,4-difluorophenol).

Bis (2,4-dichloro-5-hydroxyphenyl) disulfide is also called 5,5'-dithiobis (2,4-dichlorophenol).

Bis (2-chloro-4-fluoro-5-hydroxyphenyl) disulfide is also called 5,5'-dithiobis (4-chloro-2-fluorophenol).

Bis (4-fluoro-2-methyl-5-hydroxyphenyl) disulfide is also referred to as 5,5'-dithiobis (2-fluoro-4-methylphenol).

Bis (4-chloro-2-methyl-5-hydroxyphenyl) disulfide is also referred to as 5,5'-dithiobis (2-chloro-4-methylphenol).

Bis (2,4-dimethyl-5-hydroxyphenyl) disulfide is also known as 5,5'-dithiobis (2,4-dimethylphenol).

The compound of general formula (2), which is the product of step (i), can be used as a raw material of step (ii). The compound of the general formula (2) obtained in step (i) can be isolated and used in the next step, or can be purified and used in the next step, or can be used in the next step without being isolated.

(Step (ii))

Next, step (ii) will be described.

Step (ii) is a step of producing a compound represented by General Formula (3) by reacting a compound represented by General Formula (2) with a compound represented by General Formula (a) in the presence of a base,

(Wherein R ¹ and R ² are each independently a halogen atom or a C1 to C4 alkyl group), and R ³ -X (a)

(Wherein R ³ is a C1 to C4 haloalkylthio group C2 to C10 alkyl group; X is a halogen atom, C1 to C4 alkylsulfonyloxy group, C1 to C4 haloalkylsulfonyloxy group, or C1 ~ C4 alkyl or halogen atom substituted phenylsulfonyloxy),

(Wherein R ¹ , R ² and R ³ are as defined above).

(Compound of general formula (a))

The compound of the general formula (a) is a known compound, or a compound that can be produced from a known compound by a known method. Specific examples of the compound of the general formula (a) include 1-chloro-5-trifluoromethylthiopentane, 1-bromo-5-trifluoromethylthiopentane, 1 -Iodine-5-trifluoromethylsulfanylpentane, 1-methanesulfonyloxy-5-trifluoromethylsulfanylpentane, 1-trifluoromethanesulfonyloxy-5-trifluoromethylsulfan Pentyl, 1- (p-toluenesulfonyloxy) -5-trifluoromethylthiopentane, 1-chloro-6-trifluoromethylthiohexane, 1-bromo-6-trifluoromethylthiohexyl Alkanes, 1-iodo-6-trifluoromethylsulfanyl hexane, 1-methanesulfonyloxy-6-trifluoromethylsulfanyl hexane, 1-trifluoromethanesulfanyloxy-6-trifluoro Methylthiohexane, 1- (p-toluenesulfonyloxy) -6-trifluoromethylthiohexane, and the like are not limited thereto.

The amount of the compound of the general formula (a) may be any amount as long as the reaction proceeds. From the viewpoints of yield, by-product suppression, economic efficiency, etc., it may be exemplified by a range of 2.0 to 3.0 mol, and preferably a range of 2.0 to 2.4 mol relative to 1 mol of the compound of the general formula (2). .

(Base of step (ii))

The base used in step (ii) may be any base as long as the reaction proceeds. Examples of the base used in step (ii) include alkali metal hydroxides (for example, lithium hydroxide, sodium hydroxide, and potassium hydroxide), and alkaline earth metal hydroxides (for example, magnesium hydroxide). , Calcium hydroxide, barium hydroxide, etc.), alkali metal carbonates (e.g., lithium carbonate, sodium carbonate, potassium carbonate, etc.), alkaline earth metal carbonates (e.g., magnesium carbonate, calcium carbonate, barium carbonate, etc.), alkali metals Bicarbonate (for example, lithium bicarbonate, sodium bicarbonate, potassium bicarbonate, etc.), alkaline earth metal bicarbonate (for example, magnesium bicarbonate, calcium bicarbonate, etc.), Phosphate (e.g., sodium phosphate, potassium phosphate, calcium phosphate, etc.), hydrogen phosphate (e.g., sodium hydrogen phosphate, potassium hydrogen phosphate, calcium hydrogen phosphate, etc.), metal hydride (e.g., sodium hydride, calcium hydride, etc.), Metal alkoxides (e.g., sodium methoxide, sodium ethoxide, potassium tert-butoxide, etc.) and amines (e.g., triethylamine, tributylamine, diisopropylethylamine, 1,8-diazine Bicyclic [5.4.0] -7-undec-7-ene (DBU), 1,4-diazine bicyclic [2.2.2] octane (DABCO), N, N-dimethylaniline, N, N- Diethylaniline, pyridine, 4- (dimethylamino) -pyridine, 2,6-dimethylpyridine, etc.) are not limited thereto.

From the viewpoints of reactivity, productivity, economic efficiency, etc., preferred examples of the base in step (ii) include alkali metal hydroxides, alkali metal carbonates, and alkali metal bicarbonates, and more preferred are alkalis. Metal hydroxides and alkali metal carbonates. Specific preferred examples of the base in step (ii) include sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, and potassium bicarbonate, and more preferably sodium hydroxide, potassium hydroxide, Sodium carbonate and potassium carbonate.

The base of step (ii) can be used alone or in a combination of two or more at any ratio. The form of the base in step (ii) may be any form as long as the reaction proceeds. The form of the base in step (ii) can be appropriately selected by those having ordinary knowledge in the technical field.

The amount of the base used in step (ii) is any amount as long as the reaction proceeds. From the viewpoints of yield, by-product suppression, economic efficiency, etc., it may be exemplified by 0.5 to 3.0 mol, preferably 0.5 to 2.4 mol relative to 1 mol of the compound of the general formula (2). .

(Phase transfer catalyst in step (ii))

The reaction of step (ii) can be performed in the presence of a phase transfer catalyst. It is not necessary to use a phase transfer catalyst. Whether or not to use a phase transfer catalyst can be appropriately determined by those having ordinary knowledge in this technical field. Examples of the phase transfer catalyst include, but are not limited to, quaternary ammonium salts, quaternary phosphonium salts, and crown ethers.

Examples of the quaternary ammonium salt include tetrabutylammonium chloride, tetrabutylammonium bromide, tetrabutylammonium iodide, tetrabutylammonium hydrogen sulfate, benzyltrimethylammonium chloride, and benzyl Trimethylammonium bromide, octyltrimethylammonium chloride, octyltrimethylammonium bromide, trioctylmethylammonium chloride, trioctylmethylammonium bromide, benzyllauryldimethyl Ammonium chloride (benzyldodecyldimethylammonium chloride), benzyllauryldimethylammonium bromide (benzyldodecyldimethylammonium bromide), myristyltrimethyl chloride Ammonium (tetradecyltrimethylammonium chloride), myristyltrimethylammonium bromide (tetradecyltrimethylammonium bromide), benzyldimethylstearylammonium chloride (benzylstearyl) Dimethyl ammonium chloride), benzyl dimethyl stearyl ammonium bromide (benzyl octadecyl dimethyl ammonium bromide), and the like.

Examples of the quaternary phosphonium salt include tetrabutylphosphonium bromide, tetraoctylphosphonium bromide, and tetraphenylphosphonium bromide.

Examples of the crown ethers include 12-crown-4, 15-crown-5, 18-crown-6, and the like.

From the viewpoints of reactivity, productivity, economic efficiency, etc., the phase transfer catalyst is preferably a quaternary ammonium salt, and more preferably tetrabutylammonium bromide or tetrabutylammonium iodide.

The phase transfer catalyst may be used alone or in a combination of two or more at any ratio. As long as the reaction of the phase transfer catalyst You can do it, and it can take any form. The form of the phase transfer catalyst can be appropriately selected by those having ordinary knowledge in the technical field.

The amount of the phase transfer catalyst used in step (ii) may be any amount as long as the reaction proceeds. From the viewpoints of yield, by-product suppression, economic efficiency, etc., the range of 0 (zero) to 0.3 mol relative to 1 mol of the compound of the general formula (2) can be exemplified, but step (ii) The amount of the phase transfer catalyst used can be appropriately adjusted by those having ordinary knowledge in the technical field.

(Solvent in step (ii))

From the viewpoint that the reaction proceeds smoothly, etc., the reaction in step (ii) is preferably carried out in the presence of a solvent. The solvent in step (ii) may be any solvent as long as the reaction in step (ii) proceeds. As the solvent of step (ii), for example, amidines (e.g., N, N-dimethylformamide (DMF), N, N-dimethylacetamide (DMAC), N- Methylpyrrolidone (NMP), etc.), alkyl ureas (e.g., N, N'-dimethylimidazolidone (DMI), etc.), fluorenes (e.g., dimethylsulfine (DMSO), etc. ), Amidines (e.g., cyclobutane, etc.), ethers (e.g., tetrahydrofuran (THF), 1,4-bis Alkane, diisopropyl ether, dibutyl ether, di-third butyl ether, cyclopentyl methyl ether (CPME), methyl-third butyl ether, 1,2-dimethoxyethane (DME), diglyme, triglyme, etc.), ketones (e.g., acetone, isobutyl methyl ketone (MIBK), cyclohexanone, etc.), carboxylic acid esters (E.g., ethyl acetate, butyl acetate, etc.), nitriles (e.g., acetonitrile, etc.), alcohols (e.g., methanol, ethanol, 2-propanol, butanol, etc.), aromatic hydrocarbon derivatives (e.g., , Benzene, toluene, xylene, chlorobenzene, dichlorobenzene, trichlorobenzene, nitrobenzene, etc.), halogenated aliphatic hydrocarbons (e.g., methylene chloride, etc.), water, and any ratio of any of them Combinations are not limited to these.

From the viewpoints of reactivity, economic efficiency, etc., as examples of the solvent of step (ii), amines, fluorenes, ethers, ketones, nitriles, alcohols, and aromatic hydrocarbon derivatives may be mentioned. Any combination of species, water, and any ratio. As specific examples of the solvent in step (ii), N, N-dimethylformamide (DMF), N, N-dimethylacetamide (DMAC), and N-methylpyrrole are mentioned. Pyridone (NMP), dimethyl sulfoxide (DMSO), tetrahydrofuran (THF), acetone, isobutyl methyl ketone (MIBK), acetonitrile, methanol, ethanol, 2-propanol, toluene, xylene, chlorobenzene, dioxin Any combination of chlorobenzene, water, and any ratio thereof.

The amount of the solvent used in step (ii) is sufficient as long as the stirring of the reaction system is sufficient, and may be any amount. From the viewpoints of yield, by-product suppression, economic efficiency, etc., it may be exemplified by 0.01 to 10.0 L (liters), preferably 0.1 to 5.0 L relative to 1 mol of the compound of the general formula (2). range. When a combination of two or more solvents is used, the ratio of the two or more solvents may be any ratio as long as the reaction proceeds.

(Reaction temperature of step (ii))

The reaction temperature of step (ii) is not particularly limited. From the viewpoints of yield, suppression of by-products, and economic efficiency, a range of -10 ° C (negative 10 ° C) to 160 ° C, preferably 10 ° C to 120 ° C is exemplified.

(Reaction time of step (ii))

The reaction time of step (ii) is not particularly limited. From the viewpoints of yield, suppression of by-products, and economic efficiency, the range of 0.5 to 48 hours is preferable, and the range of 1 to 24 hours is preferable.

(Product of step (ii); compound of general formula (3))

Specific examples of the compound of the general formula (3) obtained in step (ii) include bis [2,4-difluoro-5- (5-trifluoromethylthiopentyloxy) benzene Yl] disulfide, bis [2,4-difluoro-5- (6-trifluoromethylthiohexyloxy) phenyl] disulfide, bis [2,4-dichloro-5- (5 -Trifluoromethylthiopentyloxy) phenyl] disulfide, bis [2,4-dichloro-5- (6-trifluoromethylthiohexyloxy) phenyl] disulfide, Bis [2-chloro-4-fluoro-5- (5-trifluoromethylthiopentyloxy) phenyl] disulfide, bis [2-chloro-4-fluoro-5- (6-trifluoro Methylthiohexyloxy) phenyl] disulfide, bis [4-fluoro-2-methyl-5- (5-trifluoromethylthiopentyloxy) phenyl] disulfide, bis [4-fluoro-2-methyl-5- (6-trifluoromethylthiohexyloxy) phenyl] disulfide, bis [4-chloro-2-methyl-5- (5-trifluoro Methylthiopentyloxy) phenyl] disulfide, Bis [4-chloro-2-methyl-5- (6-trifluoromethylthiohexyloxy) phenyl] disulfide, bis [2,4-dimethyl-5- (5-trifluoro Methylthiopentyloxy) phenyl] disulfide, bis [2,4-dimethyl-5- (6-trifluoromethylthiohexyloxy) phenyl] disulfide, etc., but It is not limited to these.

The compound of general formula (3) which is the product of step (ii) can be used as a raw material of step (iii). That is, the compound of the general formula (3) which is a product of step (ii) can be used as a raw material of step (iii-a) and step (iii-b). The compound of the general formula (3) obtained in step (ii) may be isolated and used in the next step, or may be further purified and used in the next step, or may be used in the next step without being isolated.

(Step (iii))

Next, step (iii) will be described.

Step (iii) is a step of converting a compound represented by the general formula (3) into a compound represented by the general formula (4),

(Wherein R ¹ and R ² are each independently a halogen atom or a C1 to C4 alkyl group; R ³ is a C1 to C4 haloalkylthio group C2 to C10 alkyl group),

(Wherein R ¹ , R ² and R ³ are as defined above; R ⁴ is a C1 to C4 haloalkyl group).

Among them, step (iii) includes step (iii-a), or includes step (iii-b) and step (iii-c).

In one embodiment, step (iii) is the following step: (iii-a) by reacting a compound represented by general formula (3) with a compound represented by general formula (b) in the presence of a base And the step of converting the compound of the aforementioned general formula (3) into the compound of the aforementioned general formula (4),

(Wherein R ¹ and R ² are each independently a halogen atom or a C1 to C4 alkyl group; R ³ is a C1 to C4 haloalkylthio group C2 to C10 alkyl group), R ⁴ -Y (b)

(Wherein R ⁴ is a C1 to C4 haloalkyl group; Y is a halogen atom, C1 to C4 alkylsulfonyloxy group, C1 to C4 haloalkylsulfonyloxy group, or C1 to C4 alkyl group or halogen Atom substituted phenylsulfonyloxy).

In other embodiments, step (iii) includes the following steps: (iii-b) a step of converting a compound represented by general formula (3) into a compound represented by general formula (5),

(Wherein R ¹ and R ² are each independently a halogen atom or a C1 to C4 alkyl group; R ³ is a C1 to C4 haloalkylthio group C2 to C10 alkyl group),

(Wherein R ¹ , R ^2, and R ³ are as defined above); and (iii-c) by allowing the compound of the aforementioned general formula (5) in the presence of a base to react with the general formula (b) A step of reacting a compound represented by the formula (5) to convert the compound of the aforementioned general formula (5) to the compound of the aforementioned general formula (4), R ⁴ -Y (b)

(Wherein R ⁴ is a C1 to C4 haloalkyl group; Y is a halogen atom, C1 to C4 alkylsulfonyloxy group, C1 to C4 haloalkylsulfonyloxy group, or C1 to C4 alkyl group or halogen Atom substituted phenylsulfonyloxy).

Specifically, for example, after step (iii) and step (iii-b) are performed, step (iii-c) is performed.

(Step (iii-a))

Next, step (iii-a) will be described.

Step (iii-a) is to convert a compound represented by the general formula (3) into a compound represented by the general formula (3) by reacting the compound represented by the general formula (3) with a compound represented by the general formula (b) in the presence of a base. A step of a compound represented by the general formula (4),

(Wherein R ¹ and R ² are each independently a halogen atom or a C1 to C4 alkyl group; R ³ is a C1 to C4 haloalkylthio group C2 to C10 alkyl group), R ⁴ -Y (b)

(Wherein R ⁴ is a C1 to C4 haloalkyl group; Y is a halogen atom, C1 to C4 alkylsulfonyloxy group, C1 to C4 haloalkylsulfonyloxy group, or C1 to C4 alkyl group or halogen Atom substituted phenylsulfonyloxy),

(Wherein R ¹ , R ² , R ³ and R ⁴ are as defined above).

(Compound of general formula (b) in step (iii-a))

The compound of formula (b) in step (iii-a) is a known compound, or A compound produced by a known method from a known compound. As for the compound of the general formula (b) in step (iii-a), specifically, for example, 1-chloro-2,2,2-trifluoroethane, 1-bromo-2,2,2- Trifluoroethane, 1-iodo-2,2,2-trifluoroethane, methanesulfonic acid 2,2,2-trifluoroethyl, trifluoromethanesulfonic acid 2,2,2-trifluoroethyl, Para-toluenesulfonic acid 2,2,2-trifluoroethyl and the like are not limited thereto.

The amount of the compound of the general formula (b) in step (iii-a) may be any amount as long as the reaction proceeds. From the viewpoints of yield, suppression of by-products, economic efficiency, etc., it may be exemplified by the range of 2.0 to 3.0 moles, and preferably the range of 2.0 to 2.4 moles relative to the compound of the general formula (3) of 1 mole .

(Base of step (iii-a))

The base used in step (iii-a) may be any base as long as the reaction proceeds. Examples of the base usable in step (iii-a) include alkali metal hydroxides (for example, lithium hydroxide, sodium hydroxide, potassium hydroxide, etc.), and alkaline earth metal hydroxides (for example, hydrogen Magnesium oxide, calcium hydroxide, barium hydroxide, etc.), alkali metal carbonates (e.g., lithium carbonate, sodium carbonate, potassium carbonate, etc.), alkaline earth metal carbonates (e.g., magnesium carbonate, calcium carbonate, barium carbonate, etc.), Alkali metal bicarbonates (for example, lithium bicarbonate, sodium bicarbonate, potassium bicarbonate, etc.), alkaline earth metal bicarbonates (for example, magnesium bicarbonate, calcium bicarbonate, etc.), phosphates (for example, sodium phosphate, phosphoric acid Potassium, calcium phosphate, etc.), hydrogen phosphate (e.g., sodium hydrogen phosphate, potassium hydrogen phosphate, calcium hydrogen phosphate, etc.), metal hydrides (e.g., sodium hydride, calcium hydride, etc.), metal alkoxides (e.g., sodium methoxide , Sodium ethoxide, potassium tert-butoxide, etc.), amines (for example, triethylamine, tributylamine, diisopropylethylamine, 1,8-diazinebicyclo [5.4.0] -7- Undec-7-ene (DBU), 1,4-diazinebicyclo [2.2.2] octane (DABCO), N, N-dimethylaniline, N, N-diethylaniline, pyridine, 4- (Secondary Aminoamino) -pyridine, 2,6-dimethylpyridine, etc.) and the radical initiators described below are also suitable as base radical initiators (e.g., sodium bisulfite, potassium bisulfite, hanging white Block (trade name Ron galite) (sodium formaldehyde sulfoxylate 2H ₂ O, etc.), but is not limited to these.

From the viewpoints of reactivity, productivity, economic efficiency, etc., preferred examples of the base in step (iii-a) include alkali metal hydroxides, alkali metal carbonates, and alkali metal bicarbonates. Specific preferred examples of the base in step (iii-a) include sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, and potassium bicarbonate.

The base of step (iii-a) can be used alone or in a combination of two or more at any ratio. As long as the base morphology of step (iii-a) is reacted It can be performed as long as it takes, and it can take any form. The form of the base in step (iii-a) can be appropriately selected by those having ordinary knowledge in the technical field.

The amount of the base to be used in step (iii-a) is sufficient for the reaction to proceed, and may be any amount. From the viewpoints of yield, by-product suppression, and economic efficiency, for example, it is 0.5 to 3.0 moles, preferably 0.5 to 2.4 moles, more preferably 1 to 2.5 moles of the compound of the general formula (3). It is preferably in the range of 1.0 to 2.4 moles.

(Free radical initiator of step (iii-a))

The reaction of step (iii-a) is performed in the presence or absence of a radical initiator, preferably in the presence of a radical initiator. However, whether to use a radical initiator in step (iii-a) can be appropriately determined by a person having ordinary knowledge in the art. The radical initiator used in step (iii-a) may be any radical initiator as long as the reaction proceeds. Examples of the radical initiator that can be used in step (iii-a) include, for example, sulfurous acid, sodium bisulfite, potassium bisulfite, sodium sulfite, potassium sulfite, hanging white block (trade name) (formaldehyde) Sodium bisulfite dihydrate) and the like are not limited thereto. Herein, the radical initiator is understood as a reducing agent. Sodium formaldehyde sulfoxylate dihydrate has the same meaning as sodium hydroxymethylsulfinate dihydrate. From the viewpoints of yield, reactivity, availability, price, and ease of handling, as a preferred example of the radical initiator used in step (iii-a), a white block can be cited.

The radical initiator in step (iii-a) can be used alone or in a combination of two or more at any ratio. The form of the radical initiator in step (iii-a) is any form as long as it can react. The morphology of the radical initiator in step (iii-a) can be obtained by this technology. Those with ordinary knowledge in the domain choose appropriately. The amount of the radical initiator used in step (iii-a) is any amount as long as the reaction can be performed. From the viewpoints of yield, by-product suppression, economic efficiency, etc., it may be exemplified by 0 (zero) to 6.0 mol, preferably 0.01 to 6.0 mol relative to 1 mol of the compound of the general formula (3). More preferably, it is in the range of 0.1 to 4.0 moles, and more preferably in the range of 1.0 to 4.0 moles, but the amount of the radical initiator used in step (iii-a) can be appropriately adjusted by those having ordinary knowledge in the technical field. . The appropriate radical initiator as described above in step (iii-a) can also be used as the base in step (iii-a) described above. The radical initiator of step (iii-a) and the base of step (iii-a) described above may also be used in combination.

(Solvent of step (iii-a))

From the viewpoint of smooth progress of the reaction, etc., it is preferred that the reaction in step (iii-a) is carried out in the presence of a solvent. The solvent in step (iii-a) is any solvent as long as the reaction in step (iii-a) proceeds. As the solvent of step (iii-a), for example, amidines (for example, N, N-dimethylformamide (DMF), N, N-dimethylacetamide (DMAC), N-methylpyrrolidone (NMP), etc.), alkyl ureas (e.g., N, N'-dimethylimidazolidone (DMI), etc.), fluorenes (e.g., dimethylsulfinium (DMSO) ), Etc.), amidines (for example, cyclobutane, etc.), ethers (for example, tetrahydrofuran (THF), 1,4-bis Alkane, diisopropyl ether, dibutyl ether, di-third butyl ether, cyclopentyl methyl ether (CPME), methyl-third butyl ether, 1,2-dimethoxyethane (DME), diglyme, triglyme, etc.), ketones (e.g., acetone, isobutyl methyl ketone (MIBK), cyclohexanone, etc.), carboxylic acid esters (E.g., ethyl acetate, butyl acetate, etc.), nitriles (e.g., acetonitrile, etc.), alcohols (e.g., methanol, ethanol, 2-propanol, butanol, etc.), aromatic hydrocarbon derivatives (e.g., , Benzene, toluene, xylene, chlorobenzene, dichlorobenzene, trichlorobenzene, nitrobenzene, etc.), halogenated aliphatic hydrocarbons (for example, dichloromethane, etc.), water, and any ratio of any of them The combination is not limited to these.

From the viewpoints of reactivity, economic efficiency, etc., preferred examples of the solvent in step (iii-a) include amidoamines, fluorenes, ethers, ketones, nitriles, alcohols, aromatic Any combination of hydrocarbon derivatives, water, and any ratio. As specific examples of the solvent of step (iii-a), N, N-dimethylformamide (DMF), N, N-dimethylacetamide (DMAC), N-formaldehyde N-pyrrolidone (NMP), dimethylsulfine (DMSO), tetrahydrofuran (THF), acetone, isobutyl methyl ketone (MIBK), acetonitrile, methanol, ethanol, 2-propanol, toluene, xylene, chlorobenzene , Dichlorobenzene, water, and any combination thereof at any ratio.

The amount of the solvent used in step (iii-a) may be any amount as long as the stirring of the reaction system can be sufficiently performed. From the viewpoints of yield, suppression of by-products, economic efficiency, etc., it may be exemplified by 0.01 to 10.0 L (liters), preferably 0.1 to 5.0 L relative to 1 mol of the compound of the general formula (3). range. When a combination of two or more solvents is used, the ratio of the two or more solvents may be any ratio as long as the reaction proceeds.

(Reaction temperature of step (iii-a))

The reaction temperature of step (iii-a) is not particularly limited. From the viewpoints of yield, suppression of by-products, economic efficiency, etc., a range of -10 ° C (negative 10 ° C) to 160 ° C, and preferably 10 ° C to 120 ° C is exemplified.

(Reaction time of step (iii-a))

The reaction time of step (iii-a) is not particularly limited. From the viewpoints of yield, suppression of by-products, and economic efficiency, the range of 0.5 to 48 hours is preferable, and the range of 1 to 24 hours is preferable.

(Product of step (iii-a); compound of general formula (4))

Specific examples of the compound of the general formula (4) obtained in step (iii-a) include 5-trifluoromethylthiopentyl- [2,4-difluoro-5- (2, 2,2-trifluoroethylthio) phenyl] ether, 6-trifluoromethylthiohexyl- [2,4-difluoro-5- (2,2,2-trifluoroethylthio) Phenyl] ether, 5-trifluoromethylthiopentyl- [2,4-dichloro-5- (2,2,2-trifluoroethylthio) phenyl] ether, 6-trifluoromethyl Methylthiohexyl- [2,4-dichloro-5- (2,2,2-trifluoroethylthio) phenyl] ether, 5-trifluoromethylthiopentyl- [4-chloro- 2-fluoro-5- (2,2,2-trifluoroethylthio) phenyl] ether, 6-trifluoromethylthiohexyl- [4-chloro-2-fluoro-5- (2,2 , 2-trifluoroethylthio) phenyl] ether, 5-trifluoromethylthiopentyl- [2-fluoro-4-methyl-5- (2,2,2-trifluoroethylthio) (Phenyl) phenyl] ether, 6-trifluoromethylthiohexyl- [2-fluoro-4-methyl-5- (2,2,2-trifluoroethyl Methylthio) phenyl] ether, 5-trifluoromethylthiopentyl- [2-chloro-4-methyl-5- (2,2,2-trifluoroethylthio) phenyl] ether 6-trifluoromethylthiohexyl- [2-chloro-4-methyl-5- (2,2,2-trifluoroethylthio) phenyl] ether, 5-trifluoromethylthio Amyl- [2,4-dimethyl-5- (2,2,2-trifluoroethylthio) phenyl] ether, 6-trifluoromethylthiohexyl- [2,4-dimethyl Butyl-5- (2,2,2-trifluoroethylthio) phenyl] ether and the like are not limited thereto.

(Step (iii-b))

Next, step (iii-b) will be described.

Step (iii-b) is a step of converting a compound represented by the general formula (3) into a compound represented by the general formula (5),

(Wherein R ¹ and R ² are each independently a halogen atom or a C1 to C4 alkyl group; R ³ is a C1 to C4 haloalkylthio group C2 to C10 alkyl group),

(Wherein R ¹ , R ² and R ³ are as defined above).

Herein, step (iii-b) is performed by combining the general formula (3) A step of reducing a substance to produce a compound of the general formula (5). In other words, step (iii-b) is a step of producing a compound of general formula (5) by reacting a compound of general formula (3) with a reducing agent.

(Reducing agent of step (iii-b))

The reducing agent used in step (iii-b) may be any reducing agent as long as it can react. Examples of the reducing agent that can be used in step (iii-b) include, for example, metals (for example, zinc, iron, tin, etc.); boron hydride compounds (for example, sodium borohydride, potassium borohydride, sodium borohydride, Borane‧tetrahydrofuran complex, etc.); aluminum hydride compounds (e.g., lithium aluminum hydride, diisobutyl aluminum hydride, etc.); triphenylphosphine-hydroalcohol; tertiary phosphites (e.g., triphenyl phosphite) , Trimethyl phosphite, triethyl phosphite, etc.); hydrazine hydrate and the like, but are not limited thereto. From the viewpoints of yield, reactivity, availability, price, ease of handling, etc., preferred examples of the reducing agent in step (iii-b) include metals and boron hydride compounds, and more preferably metals. Specific examples of the reducing agent in step (iii-b) include zinc, iron, tin, and sodium borohydride, and more preferably zinc, iron, and tin.

The reducing agents in step (iii-b) can be used alone or in a combination of two or more at any ratio. The form of the reducing agent in step (iii-b) may be any form as long as the reaction proceeds. The form of the reducing agent in step (iii-b) can be appropriately selected by those having ordinary knowledge in the technical field. The amount of the reducing agent used in step (iii-b) may be any amount as long as the reaction proceeds. For example, it is 0.25 to 10 mol, preferably 0.25 to 2 mol, and preferably 0.5 to 1.5 mol relative to 1 mol of the compound of the general formula (3), but step (iii- The amount of the reducing agent used in b) can be appropriately adjusted by those having ordinary knowledge in the technical field.

When a metal (for example, zinc, iron, tin, etc.) is used as the reducing agent in step (iii-b), the form of the metal may be any form as long as the reaction proceeds. However, from the viewpoints of reactivity, availability, and ease of handling, powdered metals are preferred. Therefore, as a preferable specific example of the metal as the reducing agent in step (iii-b), zinc powder, iron powder, tin powder, and the like can be mentioned. When a metal (for example, zinc, iron, tin, etc.) is used as the reducing agent in step (iii-b), the amount of metal used may be any amount as long as the reaction proceeds. From the viewpoints of yield, by-product suppression, economic efficiency, etc., it may be exemplified by 1.0 to 10 mol, more preferably 1.0 to 3.0 mol, and more preferably 1 to 3.0 mol relative to 1 mol of the compound of the general formula (3). It is preferably in the range of 1.0 to 2.0 mol.

When a metal (for example, zinc, iron, tin, etc.) is used as the reducing agent in step (iii-b), the reaction is preferably performed in the presence of an acid. Examples of the acid include, but are not limited to, hydrochloric acid, sulfuric acid, and acetic acid. From the viewpoints of yield, reactivity, availability, price, and ease of handling, examples of preferred acids include hydrochloric acid and sulfuric acid, and more preferred is hydrochloric acid. The form of the acid may be any form as long as the reaction proceeds. Examples of the form of the acid include, for example, only a liquid or solid of the acid, or a solution of a solvent other than the step (iii-b) described later, other than an aqueous solution or water. From the viewpoints of availability, price, ease of handling, etc., as a preferred example of the form of the acid, an acid-only liquid (for example, concentrated sulfuric acid, etc.) or a 5 to 50% aqueous solution (for example, concentrated hydrochloric acid) (Ie, 35% hydrochloric acid), etc.), but the form of the acid can be appropriately selected by those having ordinary knowledge in the technical field. The amount of the acid used may be any amount as long as the reaction proceeds. Examples from the viewpoints of productivity, by-product suppression, and economic efficiency For the compound of the formula (3) of 1 mole, it is in the range of 1 to 100 moles, preferably 1 to 30 moles, but the amount of acid used can be appropriately determined by those having ordinary knowledge in the technical field. To adjust.

When a metal (for example, zinc, iron, tin, etc.) is used as the reducing agent in step (iii-b), water and / or alcohol is preferably used. Examples of the alcohol include, but are not limited to, methanol, ethanol, and 2-propanol. Water and / or alcohol can be used individually or in combination of 2 or more types by arbitrary ratios. The amount of water and / or alcohol used may be any amount as long as the reaction proceeds. From the viewpoints of yield, suppression of by-products, economic efficiency, etc., the range of 1 to 50 mol is exemplified with respect to 1 mol of the compound of the general formula (3), but the use of water and / or alcohol The amount system can be appropriately adjusted by those having ordinary knowledge in the technical field. In addition, when water and / or alcohol is used as a solvent to be described later, there is no relation with the range exemplified herein, and a large excess of water and / or alcohol can be used.

When sodium borohydride or the like is used as the reducing agent in step (iii-b), an alcohol or the like is preferably used. Examples of the alcohol include, but are not limited to, methanol, ethanol, and 2-propanol. The alcohol may be used alone or in a combination of two or more at any ratio. The amount of the alcohol used may be any amount as long as the reaction proceeds. From the viewpoints of yield, suppression of by-products, economic efficiency, etc., it can be exemplified by the range of 1 to 10 moles relative to 1 mole of the compound of the general formula (3). Those with ordinary knowledge in the technical field adjust appropriately. In addition, when an alcohol is used as a solvent to be described later, it does not matter the range exemplified herein, and a large excess of alcohol can be used.

(Solvent of step (iii-b))

From the viewpoint of smooth progress of the reaction, etc., it is preferable that the reaction in step (iii-b) is carried out in the presence of a solvent. The solvent of step (iii-b) may be any solvent as long as the reaction of step (iii-b) proceeds. Examples of the solvent in step (iii-b) include water, alcohols (for example, methanol, ethanol, 2-propanol, butanol, etc.), and ethers (for example, tetrahydrofuran (THF), 1,4 -two Alkane, diisopropyl ether, dibutyl ether, di-third butyl ether, cyclopentyl methyl ether (CPME), methyl-third butyl ether, 1,2-dimethoxyethane (DME), diglyme, triglyme, etc.), nitriles (e.g., acetonitrile, etc.), amidines (e.g., N, N-dimethylformamidine) Amine (DMF), N, N-dimethylacetamide (DMAC), N-methylpyrrolidone (NMP), etc.), alkyl ureas (for example, N, N'-dimethylimidazolidone (DMI), etc.), fluorenes (e.g., dimethyl sulfene (DMSO), etc.), fluorenes (e.g., cyclobutane, etc.), ketones (e.g., acetone, isobutyl methyl ketone (MIBK), cyclic Hexanone, etc.), carboxylic acid esters (e.g., ethyl acetate, butyl acetate, etc.), carboxylic acids (e.g., acetic acid, etc.), carbonates (e.g., ethyl carbonate, propyl carbonate, etc.), aromatic Hydrocarbons (e.g., benzene, toluene, xylene, etc.), halogenated aromatic hydrocarbons (e.g., chlorobenzene, dichlorobenzene, trichlorobenzene, etc.), halogenated aliphatic hydrocarbons (e.g., methylene chloride, etc.) ), And any combination of them at any ratio, but is not limited to these.

From the viewpoints of reactivity and economic efficiency, etc., regarding step (iii-b) Preferred examples of the solvent include water, alcohols, ethers, nitriles, amidines, carboxylic acid esters, carboxylic acids, aromatic hydrocarbons, halogenated aromatic hydrocarbons, and halogenated aliphatics. Any combination of hydrocarbons and any ratio thereof. As specific examples of the solvent in step (iii-b), water, methanol, ethanol, 2-propanol, tetrahydrofuran, acetonitrile, N, N-dimethylformamide (DMF), N, N-dimethylacetamide (DMAC), ethyl acetate, butyl acetate, acetic acid, toluene, xylene, chlorobenzene, dichlorobenzene, dichloromethane, and any combination thereof in any ratio.

The amount of the solvent used in step (iii-b) may be sufficient for the stirring of the reaction system, and may be any amount. From the viewpoints of yield, suppression of by-products, economic efficiency, etc., it may be exemplified by 0.01 to 10.0 L (liters), preferably 0.1 to 5.0 L relative to 1 mol of the compound of the general formula (3). range. When a combination of two or more solvents is used, the ratio of the two or more solvents may be any ratio as long as the reaction proceeds.

(Reaction temperature of step (iii-b))

The reaction temperature of step (iii-b) is not particularly limited. From the viewpoints of yield, suppression of by-products, economic efficiency, etc., a range of -10 ° C (negative 10 ° C) to 160 ° C, and preferably 10 ° C to 120 ° C is exemplified.

(Reaction time of step (iii-b))

The reaction time of step (iii-b) is not particularly limited. From the viewpoints of productivity, by-product suppression, and economic efficiency, for example, 0.5 hours to 48 hours, preferably 0.5 hours to 24 hours, and more preferably 1 hour to 12 hours.

Regarding step (iii-b), if necessary, refer to the following documents.

(Company) The Japanese Chemical Society, "New Experimental Chemistry Lecture 14 Organic Chemicals Synthesis and Reactions of Matter III ", pages 1699 ~ 1700 (1978), issued by Shingo Iizumi, Maruzen Co., Ltd.

(Compiled by) The Japan Chemical Society, "Experimental Chemistry Lecture 24 Organic Synthesis VI", 4th edition, page 325 (1992), issued by Masaru Murata, Maruzen Corporation

(Product of step (iii-b); compound of general formula (5))

Specific examples of the compound of the general formula (5) obtained in step (iii-b) include 2,4-difluoro-5- (5-trifluoromethylthiopentyloxy) benzene. Thiol, 2,4-difluoro-5- (6-trifluoromethylthiohexyloxy) benzenethiol, 2,4-dichloro-5- (5-trifluoromethylthiopentyloxy) ) Thiophenol, 2,4-dichloro-5- (6-trifluoromethylthiohexyloxy) thiophenol, 2-chloro-4-fluoro-5- (5-trifluoromethylsulfide Pentyloxy) thiophenol, 2-chloro-4-fluoro-5- (6-trifluoromethylthiohexyloxy) thiophenol, 4-fluoro-2-methyl-5- (5 -Trifluoromethylthiopentyloxy) thiophenol, 4-fluoro-2-methyl-5- (6-trifluoromethylthiohexyloxy) thiophenol, 4-chloro-2- Methyl-5- (5-trifluoromethylthiopentyloxy) thiophenol, 4-chloro-2-methyl-5- (6-trifluoromethylthiohexyloxy) thiophenol , 2,4-dimethyl-5- (5-trifluoromethylthiopentyloxy) thiophenol, 2,4-dimethyl-5- (6-trifluoromethylthiohexyloxy) Phenylthiophenol and the like, but are not limited thereto.

The compound of general formula (5), which is the product of step (iii-b), can be used as a raw material of step (iii-c). The compound of the general formula (5) obtained in step (iii-b) may be isolated and used in the next step, may be further purified and used in the next step, or may be used in the next step without being isolated.

(Step (iii-c))

Next, step (iii-c) will be described.

Step (iii-c) is to convert a compound represented by the general formula (5) into a compound represented by the general formula (5) by reacting the compound represented by the general formula (5) with a compound represented by the general formula (b) in the presence of a base. A step of a compound represented by the general formula (4),

(Wherein R ¹ and R ² are each independently a halogen atom or a C1 to C4 alkyl group; R ³ is a C1 to C4 haloalkylthio group C2 to C10 alkyl group), R ⁴ -Y (b)

(Wherein R ⁴ is a C1 to C4 haloalkyl group; Y is a halogen atom, C1 to C4 alkylsulfonyloxy group, C1 to C4 haloalkylsulfonyloxy group, or C1 to C4 alkyl group or halogen Atom substituted phenylsulfonyloxy),

(Wherein R ¹ , R ² , R ³ and R ⁴ are as defined above).

(Compound of general formula (b) in step (iii-c))

The compound of formula (b) in step (iii-c) is a well-known compound, or A compound that can be produced from a known compound by a known method. As for the compound of the general formula (b) in step (iii-c), specifically, as described in step (iii-a).

The amount of the compound of the general formula (b) in step (iii-c) may be any amount as long as the reaction proceeds. From the viewpoints of yield, suppression of by-products, economic efficiency, etc., it is exemplified that it is in the range of 1.0 to 1.5 mol, preferably 1.0 to 1.2 mol relative to 1 mol of the compound of general formula (5) .

(Base of step (iii-c))

The base used in step (iii-c) may be any base as long as the reaction proceeds. Examples of the base usable in step (iii-c) include alkali metal hydroxides (for example, lithium hydroxide, sodium hydroxide, potassium hydroxide, etc.) and alkaline earth metal hydroxides (for example, Magnesium hydroxide, calcium hydroxide, barium hydroxide, etc.), alkali metal carbonates (for example, lithium carbonate, sodium carbonate, potassium carbonate, etc.), alkaline earth metal carbonates (for example, magnesium carbonate, calcium carbonate, barium carbonate, etc.) , Alkali metal bicarbonate (for example, lithium bicarbonate, sodium bicarbonate, potassium bicarbonate, etc.), alkaline earth metal bicarbonate (for example, magnesium bicarbonate, calcium bicarbonate, etc.), phosphate (for example, sodium phosphate, Potassium phosphate, calcium phosphate, etc.), hydrogen phosphate salts (e.g., sodium hydrogen phosphate, potassium hydrogen phosphate, calcium hydrogen phosphate, etc.), metal hydrides (e.g., sodium hydride, calcium hydride, etc.), Metal alkoxides (e.g., sodium methoxide, sodium ethoxide, potassium tert-butoxide, etc.), amines (e.g., triethylamine, tributylamine, diisopropylethylamine, 1,8-diazine Bicyclic [5.4.0] -7-undec-7-ene (DBU), 1,4-diazine bicyclic [2.2.2] octane (DABCO), N, N-dimethylaniline, N, N- Diethylaniline, pyridine, 4- (dimethylamino) -pyridine, 2,6-dimethylpyridine, etc.) and radical initiators described below are also suitable as base radical initiators (for example, Sodium bisulfite, potassium bisulfite, hanging white block (trade name) (sodium formaldehyde sulfoxylate dihydrate), etc.).

From the viewpoints of reactivity, yield, economic efficiency, etc., preferred examples of the base in step (iii-c) include alkali metal hydroxides, alkali metal carbonates, and alkali metal bicarbonates. Specific preferred examples of the base in step (iii-c) include sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, and potassium bicarbonate.

The base of step (iii-c) can be used alone or in a combination of two or more at any ratio. The form of the base in step (iii-c) may be any form as long as the reaction proceeds. The form of the base in step (iii-c) can be appropriately selected by those having ordinary knowledge in the technical field.

The amount of the base used in step (iii-c) is any amount as long as the reaction proceeds. From the viewpoints of yield, by-product suppression, and economic efficiency, for example, it is 0.5 to 1.5 mol, preferably 0.5 to 1.2 mol relative to 1 mol of the compound of the general formula (5). .

(Free radical initiator of step (iii-c))

The reaction of step (iii-c) is in the presence or absence of a free radical initiator It is preferably carried out in the presence of a radical initiator. However, whether to use a radical initiator in step (iii-c) can be appropriately determined by a person having ordinary skill in the art. The radical initiator used in step (iii-c) may be any radical initiator as long as the reaction proceeds. Examples of the free radical initiator that can be used in step (iii-c) include, for example, sulfurous acid, sodium hydrogen sulfite, potassium hydrogen sulfite, sodium sulfite, potassium sulfite, hanging white block (trade name) (formaldehyde) Sodium bisulfite dihydrate) and the like are not limited thereto. Herein, the radical initiator is understood as a reducing agent. Sodium formaldehyde sulfoxylate dihydrate has the same meaning as sodium hydroxymethylsulfinate dihydrate. From the viewpoints of yield, reactivity, availability, price, ease of handling, etc., as a preferred example of the radical initiator used in step (iii-c), a white block can be cited.

The radical initiators in step (iii-c) can be used alone or in a combination of two or more at any ratio. The form of the radical initiator in step (iii-c) may be any form as long as the reaction proceeds. The form of the radical initiator in step (iii-c) can be appropriately selected by those having ordinary knowledge in the art. The amount of the radical initiator used in step (iii-c) is any amount as long as the reaction proceeds. From the viewpoints of yield, by-product suppression, economic efficiency, etc., it may be exemplified by 0 (zero) to 2.0 mol, preferably 0.01 to 2.0 mol, relative to 1 mol of the compound of the general formula (5). Ears, more preferably in the range of 0.1 to 1.5 moles, but the amount of the radical initiator used in step (iii-c) can be appropriately adjusted by those having ordinary knowledge in the technical field. The appropriate radical initiator as described in step (iii-c) can also be used as the base of step (iii-c). The radical initiator of step (iii-c) and the base of step (iii-c) described above may be And use.

(Solvent of step (iii-c))

From the viewpoint of smooth progress of the reaction, etc., it is preferable that the reaction in step (iii-c) is carried out in the presence of a solvent. The solvent in step (iii-c) is any solvent as long as the reaction in step (iii-c) proceeds. As the solvent of step (iii-c), for example, amidoamines (for example, N, N-dimethylformamide (DMF), N, N-dimethylacetamide (DMAC) , N-methylpyrrolidone (NMP), etc.), alkyl ureas (e.g., N, N'-dimethylimidazolidone (DMI), etc.), fluorenes (e.g., dimethylsulfine ( DMSO), etc.), amidines (e.g., cyclobutane, etc.), ethers (e.g., tetrahydrofuran (THF), 1,4-bis Alkane, diisopropyl ether, dibutyl ether, di-third butyl ether, cyclopentyl methyl ether (CPME), methyl-third butyl ether, 1,2-dimethoxyethane (DME), diglyme, triglyme, etc.), ketones (e.g., acetone, isobutyl methyl ketone (MIBK), cyclohexanone, etc.), carboxylic acid esters (E.g., ethyl acetate, butyl acetate, etc.), nitriles (e.g., acetonitrile, etc.), alcohols (e.g., methanol, ethanol, 2-propanol, butanol, etc.), aromatic hydrocarbon derivatives (e.g., , Benzene, toluene, xylene, chlorobenzene, dichlorobenzene, trichlorobenzene, nitrobenzene, etc.), halogenated aliphatic hydrocarbons (e.g., methylene chloride, etc.), water, and any ratio of any of them Combinations are not limited to these.

From the viewpoints of reactivity and economic efficiency, etc., regarding step (iii-c) Preferable examples of the solvent include amines, fluorenes, ethers, ketones, nitriles, alcohols, aromatic hydrocarbon derivatives, water, and any combination thereof at any ratio. As specific examples of the solvent of step (iii-c), N, N-dimethylformamide (DMF), N, N-dimethylacetamide (DMAC), N-formaldehyde N-pyrrolidone (NMP), dimethylsulfine (DMSO), tetrahydrofuran (THF), acetone, isobutyl methyl ketone (MIBK), acetonitrile, methanol, ethanol, 2-propanol, toluene, xylene, chlorobenzene , Dichlorobenzene, water, and any combination thereof at any ratio.

The amount of the solvent used in step (iii-c) is sufficient that the stirring of the reaction system is sufficiently performed, and may be any amount. From the viewpoints of yield, by-product suppression, economic efficiency, etc., it may be exemplified by 0.01 to 10.0 L (liters), preferably 0.1 to 5.0 L relative to 1 mol of the compound of the general formula (5). range. When a combination of two or more solvents is used, the ratio of the two or more solvents may be any ratio as long as the reaction proceeds.

(Reaction temperature of step (iii-c))

The reaction temperature of step (iii-c) is not particularly limited. From the viewpoints of yield, suppression of by-products, economic efficiency, etc., a range of -10 ° C (negative 10 ° C) to 160 ° C, and preferably 10 ° C to 120 ° C is exemplified.

(Reaction time of step (iii-c))

The reaction time of step (iii-c) is not particularly limited. From the viewpoints of yield, suppression of by-products, and economic efficiency, the range of 0.5 to 48 hours is preferable, and the range of 1 to 24 hours is preferable.

(Product of step (iii-c); compound of general formula (4))

As the compound of the general formula (4) obtained in the step (iii-c), specifically, for example, the compound of the general formula (4) obtained in the above step (iii-a) can be cited. Specific examples of the compound are not limited thereto.

[Example]

Next, the present invention will be specifically described by citing examples, but the present invention is not limited to these examples.

Example 1

Production of bis (2,4-dimethyl-5-hydroxyphenyl) disulfide

In a reaction flask, 4.32 g (28.0 mmol) of 5-mercapto-2,4-dimethylphenol, 42 mg (0.28 mmol) of sodium iodide, and 80 mL of ethyl acetate were added. While the mixture was stirred at room temperature, 1.59 g (14 mmol) of 30% hydrogen peroxide water was slowly added dropwise thereto. The mixture was stirred at room temperature for 1 hour. 5 mL of a saturated aqueous sodium sulfite solution was added to the reaction mixture, and the mixture was stirred at room temperature for 10 minutes. The pH of the aqueous layer was adjusted to about 1 to 2 by adding concentrated hydrochloric acid thereto. The obtained mixture was partitioned into an organic layer and an aqueous layer, and the organic layer was separated. The organic layer was dried over anhydrous magnesium sulfate, and after filtration, the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography to obtain 3.03 g of bis (2,4-dimethyl-5-hydroxyphenyl) disulfide in a yield of 71%.

¹ H-NMR (300 MHz, CDCl ₃ ) δ (ppm): 6.94 (s, 2H), 6.90 (s, 2H), 4.87 (s, 2H), 2.30 (s, 6H), 2.17 (s, 6H).

Melting point: 125-127 ° C

Example 2

Bis [2,4-dimethyl-5- (6-trifluoromethylthiohexyloxy) phenyl] Manufacture of disulfide

In a reaction flask, 2.60 g (8.5 mmol) of bis (2,4-dimethyl-5-hydroxyphenyl) disulfide and 1.73 g of 1-bromo-6-trifluoromethylthiohexane (17.9) were added. mmol), potassium carbonate 2.58 g (18.7 mmol), tetrabutylammonium iodide 0.63 g (1.7 mmol), and 17 mL of N, N-dimethylformamide. The mixture was stirred under a nitrogen atmosphere at 80 ° C for 20 hours. Dilute hydrochloric acid, water, and diethyl ether were added to the reaction mixture, and the mixture was partitioned into an organic layer and an aqueous layer, and the organic layer was separated. The organic layer was dried over anhydrous magnesium sulfate, and after filtration, the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography to obtain 4.95 g of bis [2,4-dimethyl-5- (6-trifluoromethylthiohexyloxy) phenyl] disulfide. The rate is 86%.

¹ H-NMR (300 MHz, CDCl ₃ ) δ (ppm): 6.92 (s, 2H), 6.90 (s, 2H), 3.78 (t, 4H), 2.88 (t, 4H), 2.30 (s, 6H), 2.14 (s, 6H), 1.72 (m, 8H), 1.45 (m, 8H).

Example 3

Production of 6-trifluoromethylthiohexyl- [2,4-dimethyl-5- (2,2,2-trifluoroethylthio) phenyl] ether

In a reaction flask, 337.4 mg (0.50 mmol) of bis [2,4-dimethyl-5- (6-trifluoromethylthiohexyloxy) phenyl] disulfide and p-toluenesulfonic acid 2,2 were added. 266.9 mg (1.05 mmol) of 2-trifluoroethyl, 152.0 mg (1.10 mmol) of potassium carbonate, white block (trade name) (sodium formaldehyde sulfoxylate dihydrate) 231.2 mg (1.50 mmol) and N, N -2 mL of dimethylformamide. The mixture was stirred under a nitrogen atmosphere at 50 ° C for 16 hours. Dilute hydrochloric acid, water, and diethyl ether were added to the reaction mixture, and the mixture was partitioned into an organic layer and an aqueous layer, and the organic layer was separated. The organic layer was dried over anhydrous magnesium sulfate, and after filtration, the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography to obtain 242.0 mg of 6-trifluoromethylthiohexyl- [2,4-dimethyl-5- (2,2,2-trifluoroethylsulfide). (Yl) phenyl] ether, yield 58%.

¹ H-NMR (300MHz, CDCl ₃ ) δ (ppm): 6.96 (s, 1H), 6.70 (s, 1H), 3.94 (t, 2H), 3.30 (q, 2H), 2.90 (t, 2H), 2.38 (s, 3H), 2.17 (s, 3H), 1.71-1.82 (m, 4H), 1.49-1.53 (m, 4H).

Example 4

Production of 2,4-dimethyl-5- (6-trifluoromethylthiohexyloxy) thiophenol

In a reaction flask, 337.4 mg (0.50 mmol) of bis [2,4-dimethyl-5- (6-trifluoromethylthiohexyloxy) phenyl] disulfide, 1 mL of concentrated hydrochloric acid and 2 mL of methanol were added. While stirring the mixture at room temperature, 32.7 mg (0.50 mmol) of zinc powder was added thereto. The mixture was stirred at 80 ° C for 2 hours. Water and diethyl ether were added to the reaction mixture, the mixture was partitioned into an organic layer and an aqueous layer, and the organic layer was separated. The organic layer was dried over anhydrous magnesium sulfate, and after filtration, the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography to obtain 176.0 mg of 2,4-dimethyl-5- (6-trifluoromethylthiohexyloxy) benzenethiol in a yield of 52%.

¹ H-NMR (300 MHz, CDCl ₃ ) δ (ppm): 6.92 (s, 1H), 6.74 (s, 1H), 3.90 (t, 2H), 3.22 (s, 1H), 2.89 (t, 2H), 2.24 (s, 3H), 2.13 (s, 3H), 1.76 (m, 4H), 1.49 (m, 4H).

Example 5

Production of 6-trifluoromethylthiohexyl- [2,4-dimethyl-5- (2,2,2-trifluoroethylthio) phenyl] ether

176.0 mg (0.52 mmol) of 2,4-dimethyl-5- (6-trifluoromethylthiohexyloxy) thiophenol and 2,2,2-trifluoro p-toluenesulfonic acid were added to the reaction flask. 138.8 mg (0.55 mmol) of ethyl, 79.1 mg (0.57 mmol) of potassium carbonate, white block (trade name) (sodium formaldehyde sulfoxylate dihydrate) 40.1 mg (0.26 mmol), and N, N-dimethylformamide Amidine 2mL. The mixture was stirred under a nitrogen atmosphere at 50 ° C for 15 hours. Dilute hydrochloric acid, water, and diethyl ether were added to the reaction mixture, the mixture was partitioned into an organic layer and an aqueous layer, and the organic layer was separated. The organic layer was dried over anhydrous magnesium sulfate, and after filtration, the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography to obtain 188.0 mg of 6-trifluoromethylthiohexyl- [2,4-dimethyl-5- (2,2,2-trifluoroethylsulfide). (Yl) phenyl] ether, 86% yield.

¹ H-NMR (300MHz, CDCl ₃ ) δ (ppm): 6.96 (s, 1H), 6.70 (s, 1H), 3.94 (t, 2H), 3.30 (q, 2H), 2.90 (t, 2H), 2.38 (s, 3H), 2.17 (s, 3H), 1.71-1.82 (m, 4H), 1.49-1.53 (m, 4H).

Example 6

Manufacture of bis (2-chloro-4-fluoro-5-hydroxyphenyl) disulfide

44.7 mg (0.25 mmol) of 4-chloro-2-fluoro-5-mercaptophenol and 1 mL of water were added to the reaction flask. While stirring the mixture at room temperature, 26.7 mg (0.28 mmol) of 35% hydrogen peroxide water was slowly added dropwise thereto. The mixture was stirred at room temperature for 1 hour. After the reaction mixture was filtered, the filtrate was washed with water and dried to obtain 39.9 mg of bis (2-chloro-4-fluoro-5-hydroxyphenyl) disulfide in a yield of 90%.

¹ H-NMR (300 MHz, CDCl ₃ ) δ (ppm): 7.22 (d, J = 8.7 Hz, 2H), 7.16 (d, J = 9.6 Hz, 2H).

Melting point: 160 ° C

Example 7

Production of bis [2-chloro-4-fluoro-5- (5-trifluoromethylthiopentyloxy) phenyl] disulfide

177.6 mg (0.50 mmol) of bis (2-chloro-4-fluoro-5-hydroxyphenyl) disulfide and 1-bromo-5-trifluoromethylthiopentane were added to the reaction flask. 263.7 mg (1.05 mmol), potassium carbonate 152.0 mg (1.10 mmol), and 1 mL of N, N-dimethylformamide. The mixture was stirred under a nitrogen atmosphere at 50 ° C for 15 hours. Dilute hydrochloric acid, water, and diethyl ether were added to the reaction mixture, and the mixture was partitioned into an organic layer and an aqueous layer, and the organic layer was separated. The organic layer was dried over anhydrous magnesium sulfate, and after filtration, the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography to obtain 277.0 mg of bis [2-chloro-4-fluoro-5- (5-trifluoromethylthiopentyloxy) phenyl] disulfide, Yield 80%.

¹ H-NMR (300MHz, CDCl ₃ ) δ (ppm): 7.21 (d, J = 8.4Hz, 2H), 7.12 (d, J = 10.2Hz, 2H), 3.97 (t, J = 6.3Hz, 4H) , 2.90 (t, J = 7.2 Hz, 4H), 1.78 (m, 8H), 1.56 (m, 4H).

Example 8

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

In a reaction flask, bis [2-chloro-4-fluoro-5- (5-trifluoromethylthiopentyloxy) phenyl] disulfide 277.0 mg (0.40 mmol) and p-toluenesulfonic acid were added. 213.5 mg (0.84 mmol) of 2,2,2-trifluoroethyl acid, 121.6 mg (0.88 mmol) of potassium carbonate, white block (brand name) (sodium formaldehyde sulfoxylate dihydrate) 184.9 mg (1.20 mmol) , 72.0 mg (4.0 mmol) of water and 1 mL of N, N-dimethylformamide. The mixture was stirred under a nitrogen atmosphere at 50 ° C for 12 hours. Dilute hydrochloric acid, water, and diethyl ether were added to the reaction mixture, and the mixture was partitioned into an organic layer and an aqueous layer, and the organic layer was separated. The organic layer was dried over anhydrous magnesium sulfate, and after filtration, the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography to obtain 306.0 mg of 5-trifluoromethylthiopentyl- [4-chloro-2-fluoro-5- (2,2,2-trifluoroethyl) Thio) phenyl] ether, yield 89%.

¹ H-NMR (300MHz, CDCl ₃ ) δ (ppm): 7.23 (d, J = 8.4Hz, 1H), 7.21 (d, J = 10.8Hz, 1H), 4.03 (t, J = 6.3Hz, 2H) , 3.41 (d, J = 9.6Hz, 2H), 2.92 (t, J = 7.5Hz, 2H), 1.82 (m, 4H), 1.61 (m, 2H).

Reference example 1

Manufacture of 1-bromo-6-trifluoromethylthiohexane

(1) Manufacture of 6-bromohexyl acetate

In a reaction flask, 16.27 g (89.9 mmol) of 6-bromo-1-hexanol, 9.63 g (94.3 mmol) of acetic anhydride, and 180 mL of toluene were added. To the reaction mixture, 10.48 g (98.9 mmol) of anhydrous sodium carbonate and 0.55 g (4.5 mmol) of N, N-dimethyl-4-aminopyridine were added while stirring under ice-cooling. After that, the mixture was stirred under ice-cooling for 3 hours. Dilute hydrochloric acid and water were added to the obtained reaction mixture, and the mixture was partitioned into toluene and water to obtain 6-bromohexyl acetate. Toluene layer. The obtained toluene layer containing 6-bromohexyl acetate was used for the next reaction.

(2) Manufacture of 6-cyanothiohexyl acetate

In the reaction flask, the entire amount of the toluene layer containing 6-bromohexyl acetate obtained in (1), 8.75 g (107.9 mmol) of sodium thiocyanate, 2.90 g (9.0 mmol) of tetrabutylammonium bromide, and 100 mL of water were added. . After that, the mixture was stirred at 80 ° C for 5 hours. The obtained reaction mixture was partitioned into toluene and water, and the toluene layer was separated. Next, the toluene layer was dried over anhydrous magnesium sulfate, and after filtration, toluene was distilled off under reduced pressure to obtain 6-cyanothiohexyl acetate. The obtained 6-cyanothiohexyl acetate was used in the next reaction without purification.

¹ H-NMR (300 MHz, CDCl ₃ ) δ (ppm): 4.07 (t, J = 6.6 Hz, 2H), 2.96 (t, J = 6.9 Hz, 2H), 2.06 (s, 3H), 1.85 (quin, J = 6.6Hz, 2H), 1.66 (quin, J = 6.9Hz, 2H), 1.43 (m, 4H).

(3) Manufacture of 6-trifluoromethylthiohexyl acetate

In the reaction flask, the entire amount of 6-cyanothiohexyl acetate obtained in (2), 25.60 g (180 mmol) of trifluoromethyltrimethylsilane, and 90 mL of tetrahydrofuran were added. Next, 9 mL of tetrabutylammonium fluoride (1 mol / L tetrahydrofuran solution) was added dropwise to the mixture while stirring under ice-cooling. After that, the mixture was stirred under ice-cooling for 1 hour. From the obtained reaction mixture, tetrahydrofuran was distilled off under reduced pressure. Diethyl ether and water were added to the obtained residue, and the mixture was partitioned into diethyl ether and water, and the diethyl ether layer was separated. Next, diethyl ether The layer was dried over anhydrous magnesium sulfate, and after filtration, diethyl ether was distilled off under reduced pressure to obtain 6-trifluoromethylthiohexyl acetate. The obtained 6-trifluoromethylthiohexyl acetate was used in the next reaction without purification.

¹ H-NMR (300 MHz, CDCl ₃ ) δ (ppm): 4.06 (t, J = 6.6 Hz, 2H), 2.88 (t, J = 7.2 Hz, 2H), 2.05 (s, 3H), 1.67 (m, 4H), 1.41 (m, 4H).

(4) Manufacture of 6-trifluoromethylsulfanyl-1-ol

In the reaction flask, the entire amount of 6-trifluoromethylthiohexyl acetate obtained in (3), 13.68 g (99 mmol) of potassium carbonate, and 90 mL of methanol were added. After that, the mixture was stirred at room temperature for 14 hours. From the obtained reaction mixture, methanol was distilled off under reduced pressure. Diethyl ether and water were added to the obtained residue, and the mixture was partitioned into diethyl ether and water, and the diethyl ether layer was separated. Next, the diethyl ether layer was dried over anhydrous magnesium sulfate, and after filtration, diethyl ether was distilled off under reduced pressure to obtain 6-trifluoromethylthiohexane-1-ol. The obtained 6-trifluoromethylthiohexane-1-ol system was used in the next reaction without purification.

¹ H-NMR (300MHz, CDCl ₃ ) δ (ppm): 3.66 (t, J = 6.6Hz, 2H), 2.89 (t, J = 7.5Hz, 2H), 1.72 (quin, J = 7.5Hz, 2H) , 1.59 (quin, J = 6.6Hz, 2H), 1.43 (m, 4H).

(5) Manufacture of 1-bromo-6-trifluoromethylthiohexane

In the reaction flask, the entire amount of 6-trifluoromethylthiohexane-1-ol obtained in (4), 45.51 g (270 mmol) of 48% hydrogen bromide, and 2.90 g of tetrabutylammonium bromide (9.0 mmol). After that, the mixture was stirred at 130 ° C for 4 hours. . Dichloromethane and water were added to the obtained reaction mixture, and the mixture was partitioned into dichloromethane and water, and the dichloromethane layer was separated. Next, the dichloromethane layer was dried over anhydrous magnesium sulfate, and after filtration, the dichloromethane was distilled off under reduced pressure. The obtained residue was purified by distillation under reduced pressure to obtain 20.51 g of 1-bromo-6-trifluoromethylsulfanylhexane. The yield in 5 steps was 86%.

¹ H-NMR (300MHz, CDCl ₃ ) δ (ppm): 3.41 (t, J = 6.9Hz, 2H), 2.89 (t, J = 7.2Hz, 2H), 1.87 (quin, J = 7.2Hz, 2H) , 1.72 (quin, J = 6.9Hz, 2H), 1.47 (m, 4H).

Reference example 2

Production of 5-mercapto-2,4-dimethylphenol

(1) Manufacturing of 2,4-dimethylphenylmethane sulfonate

In a reaction flask, 12.22 g (100.0 mmol) of 2,4-dimethylphenol, 11.68 g (102.0 mmol) of methanesulfonyl chloride and 100 mL of dichloromethane were added. Next, while stirring the mixture under ice-cooling, a solution of 11.13 g (110.0 mmol) of triethylamine in 50 mL of dichloromethane was slowly added dropwise. After the dropwise addition was completed, the mixture was stirred at room temperature for 1 hour. Water was added to the obtained reaction mixture, and the mixture was partitioned into dichloromethane and water, and the dichloromethane layer was separated. Next, the dichloromethane layer was dried over anhydrous magnesium sulfate, and after filtration, the dichloromethane was distilled off under reduced pressure to obtain 19.78 g of 2,4-dimethylphenylmethanesulfonate in a 99% yield.

¹ H-NMR (300 MHz, CDCl ₃ ) δ (ppm): 7.16 (d, J = 8.1 Hz, 1 H), 7.07 (d, J = 0.6 Hz, 1 H), 7.01 (dd, J = 8.1, 0.6 Hz, 1H), 3.17 (s, 3H), 2.32 (s, 3H), 2.31 (s, 3H).

(2) Manufacture of 5-chlorosulfonyl-2,4-dimethylphenylmethanesulfonate

In a reaction flask, 5.91 g (22.2 mmol) of 30% oleum and 10 mL of dichloromethane were added. Next, a solution of 4.35 g (21.7 mmol) of 2,4-dimethylphenylmethanesulfonate in 12 mL of dichloromethane was added dropwise to the mixture while stirring under ice-cooling. After completion of the dropwise addition, the mixture was stirred under ice-cooling for 1 hour. Then, 6.45 g (54.3 mmol) of thionyl chloride was added to the mixture. Then, the mixture was stirred at 50 ° C for 3 hours. The obtained reaction mixture was dropped into ice water, and then partitioned into dichloromethane and water, and the dichloromethane layer was separated. Next, the dichloromethane layer was dried over anhydrous magnesium sulfate, and after filtration, the dichloromethane was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography to obtain 5.65 g of 5-chlorosulfonyl-2,4-dimethylphenylmethanesulfonate in a yield of 87%.

¹ H-NMR (300 MHz, CDCl ₃ ) δ (ppm): 7.93 (s, 1H), 7.35 (s, 1H), 3.30 (s, 3H), 2.75 (s, 3H), 2.45 (s, 3H).

(3) Manufacturing of 5-mercapto-2,4-dimethylphenylmethanesulfonate

610.0 mg (2.0 mmol) of 5-chlorosulfonyl-2,4-dimethylphenylmethanesulfonate, 2 mL of 18% hydrochloric acid, and 2 mL of methanol were added to a reaction flask. Next, 484.8 mg (4.1 mmol) of tin powder was added to the mixture while stirring at room temperature. After that, the mixture was stirred at 80 ° C for 1 hour. From the obtained reaction mixture, methanol was distilled off under reduced pressure. Dichloromethane and water were added to the obtained residue, and the mixture was partitioned into dichloromethane and water, and the dichloromethane layer was separated. Next, the dichloromethane layer was dried over anhydrous magnesium sulfate, and after filtration, the dichloromethane was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography to obtain 400.0 mg of 5-mercapto-2,4-dimethylphenylmethanesulfonate in a yield of 84%.

¹ H-NMR (300 MHz, CDCl ₃ ) δ (ppm): 7.22 (s, 1H), 7.06 (s, 1H), 3.18 (s, 3H), 2.28 (s, 3H), 2.27 (s, 3H).

(4) Manufacture of 5-mercapto-2,4-dimethylphenol

In a reaction flask, 2.32 g (10.0 mmol) of 5-mercapto-2,4-dimethylphenylmethanesulfonate, 4.00 g (100.0 mmol) of sodium hydroxide, and 15 mL of water were added. After that, the mixture was stirred at 80 ° C for 1 hour. Hydrochloric acid was added to the obtained reaction mixture to adjust the pH to about 1. Next, methylene chloride was added thereto, and the mixture was partitioned into methylene chloride and water, and the methylene chloride layer was separated. Next, the dichloromethane layer was dried over anhydrous magnesium sulfate, and after filtration, the dichloromethane was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography to obtain 1.48 g of 5-mercapto-2,4-dimethylphenol in a yield of 96%.

¹ H-NMR (300 MHz, CDCl ₃ ) δ (ppm): 6.90 (s, 1H), 6.74 (s, 1H), 3.19 (s, 1H), 2.22 (s, 1H), 2.17 (s, 1H).

Reference example 3

Manufacture of 1-bromo-5-trifluoromethylthiopentane

(1) Manufacturing of 5-bromopentyl acetate

In a reaction flask, 20.30 g (121.5 mmol) of 5-bromo-1-pentanol, 13.03 g (127.6 mmol) of acetic anhydride, and 120 mL of toluene were added. In the reaction mixture, 14.17 g (133.7 mmol) of anhydrous sodium carbonate and 0.74 g (6.1 mmol) of N, N-dimethyl-4-aminopyridine were added while stirring under ice-cooling. After that, the mixture was stirred under ice-cooling for 2 hours. Dilute hydrochloric acid and water were added to the obtained reaction mixture, and the mixture was partitioned into toluene and water to obtain a toluene layer containing 5-bromopentyl acetate. The toluene layer containing the 5-bromopentyl acetate obtained was used in the next reaction.

(2) Manufacturing of 5-cyanothiopentyl acetate

In the reaction flask, the total amount of a toluene layer containing 5-bromopentyl acetate obtained in (1), 14.78 g (182.3 mmol) of sodium thiocyanate, 3.92 g (12.2 mmol) of tetrabutylammonium bromide, and 120 mL of water were added. After that, the mixture was stirred at 80 ° C for 3 hours. The obtained reaction mixture was partitioned into toluene and water, and the toluene layer was separated. Next, the toluene layer was dried over anhydrous magnesium sulfate, and after filtration, toluene was distilled off under reduced pressure to obtain 5-cyanothiopentyl acetate. The obtained 5-cyanothiopentyl acetate was used in the next reaction without purification.

¹ H-NMR (300 MHz, CDCl ₃ ) δ (ppm): 4.09 (t, J = 6.3 Hz, 2H), 2.96 (t, J = 7.2 Hz, 2H), 2.06 (s, 3H), 1.88 (m, 2H), 1.71 (m, 2H), 1.53 (m, 2H).

(3) Manufacturing of 5-cyanothiopentyl acetate

Add 5-cyanothiopentyl acetate obtained in (2) to the reaction flask. Full amount, 25.81 g (181.5 mmol) of trifluoromethyltrimethylsilane and 100 mL of tetrahydrofuran. Next, 12 mL of tetrabutylammonium fluoride (1 mol / L tetrahydrofuran solution) was added dropwise while stirring the mixture under ice-cooling. After that, the mixture was stirred under ice-cooling for 2 hours. From the obtained reaction mixture, tetrahydrofuran was distilled off under reduced pressure. Diethyl ether and water were added to the obtained residue, and the mixture was partitioned into diethyl ether and water, and the diethyl ether layer was separated. Next, the diethyl ether layer was dried over anhydrous magnesium sulfate, and after filtration, diethyl ether was distilled off under reduced pressure to obtain 5-cyanothiopentyl acetate. The obtained 5-cyanothiopentyl acetate was used in the next reaction without purification.

¹ H-NMR (300MHz, CDCl ₃ ) δ (ppm): 4.07 (t, J = 6.3Hz, 2H), 2.89 (t, J = 7.5Hz, 2H), 2.05 (s, 3H), 1.70 (m, 4H), 1.48 (m, 2H).

(4) Manufacturing of 5-trifluoromethylthiopentane-1-ol

In the reaction flask, the entire amount of 5-cyanothiopentyl acetate obtained in (3), 15.93 g (115.3 mmol) of potassium carbonate, and 100 mL of methanol were added. After that, the mixture was stirred at room temperature for 5 hours. From the obtained reaction mixture, methanol was distilled off under reduced pressure. Diethyl ether and water were added to the obtained residue, and the mixture was partitioned into diethyl ether and water, and the diethyl ether layer was separated. Next, the diethyl ether layer was dried over anhydrous magnesium sulfate, and after filtration, diethyl ether was distilled off under reduced pressure to obtain 5-trifluoromethylthiopentane-1-ol. The obtained 5-trifluoromethylthiopentane-1-ol was used in the next reaction without purification.

¹ H-NMR (300 MHz, CDCl ₃ ) δ (ppm): 3.67 (t, J = 6.0 Hz, 2 H), 2.90 (t, J = 7.2 Hz, 2H), 1.74 (m, 2H), 1.54 (m , 4H).

(5) Manufacture of 1-bromo-5-trifluoromethylthiopentane

In the reaction flask, the entire amount of 5-trifluoromethylthiopentane-1-ol obtained in (4) and 53.12 g (315 mmol) of 48% hydrogen bromide were added. After that, the mixture was stirred at 140 ° C for 6 hours. Dichloromethane and water were added to the obtained reaction mixture, and the mixture was partitioned into dichloromethane and water, and the dichloromethane layer was separated. Next, the dichloromethane layer was dried over anhydrous magnesium sulfate, and after filtration, the dichloromethane was distilled off under reduced pressure. The obtained residue was purified by distillation under reduced pressure to obtain 14.11 g of 1-bromo-5-trifluoromethylthiopentane. The yield in 5 steps was 46%.

¹ H-NMR (300MHz, CDCl ₃ ) δ (ppm): 3.42 (t, J = 6.9 Hz, 2H), 2.90 (t, J = 7.2 Hz, 2H), 1.90 (m, 2H), 1.74 (m, 2H), 1.57 (m, 2H).

Reference example 4

Production of 4-chloro-2-fluoro-5-mercaptophenol

(1) Manufacture of 4-chloro-5-chlorosulfonyl-2-fluorophenol

In a reaction flask, 6.67 g (25.0 mmol) of 30% oleum and 2.5 mL of dichloromethane were added. Then, 2.5 mL of dichloromethane was dissolved in 732.8 mg (5.0 mmol) of 4-chloro-2-fluorophenol while the mixture was dropped at room temperature while stirring. After the dropwise addition was completed, the mixture was stirred at room temperature for 1 hour. after that 5.95 g (50.0 mmol) of thionyl chloride was added to the mixture. Then, the mixture was stirred at 50 ° C for 1 hour. The obtained reaction mixture was dropped into ice water, and then partitioned into dichloromethane and water, and the dichloromethane layer was separated. Next, the dichloromethane layer was dried over anhydrous magnesium sulfate, and after filtration, the dichloromethane was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography to obtain 941.0 mg of 4-chloro-5-chlorosulfonyl-2-fluorophenol with a yield of 77%.

¹ H-NMR (300MHz, CDCl ₃ ) δ (ppm): 7.83 (d, J = 8.4Hz, 1H), 7.38 (d, J = 9.9Hz, 1H).

(2) Manufacture of 4-chloro-2-fluoro-5-mercaptophenol

In a reaction flask, 245.1 mg (1.0 mmol) of 4-chloro-5-chlorosulfonyl-2-fluorophenol, 1 mL of 18% hydrochloric acid, and 1 mL of methanol were added. Next, 237.4 mg (2.0 mmol) of tin powder was added to the mixture while stirring at room temperature. After that, the mixture was stirred at 80 ° C for 1 hour. From the obtained reaction mixture, methanol was distilled off under reduced pressure. Dichloromethane and water were added to the obtained residue, and the mixture was partitioned into dichloromethane and water, and the dichloromethane layer was separated. Next, the dichloromethane layer was dried over anhydrous magnesium sulfate, and after filtration, the dichloromethane was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography to obtain 152.0 mg of 4-chloro-2-fluoro-5-mercaptophenol in a yield of 85%.

¹ H-NMR (300MHz, CDCl ₃ ) δ (ppm): 7.14 (d, J = 10.2Hz, 1H), 7.01 (d, J = 8.7Hz, 1H), 3.82 (s, 1H).

Reference example 5

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

To a reaction flask was added 5-trifluoromethylthiopentyl- [4-chloro-2-fluoro-5- (2,2,2-trifluoroethylthio) phenyl] ether 86.2 mg (0.20 mmol ) And 2 mL of dichloromethane. While stirring the mixture at room temperature, 50.6 mg (0.22 mmol) of m-chloroperbenzoic acid was added thereto. The mixture was stirred at room temperature for 2 hours. An aqueous sodium sulfite solution, water and dichloromethane were added to the reaction mixture, the mixture was partitioned into an organic layer and an aqueous layer, and the organic layer was separated. The organic layer was dried over anhydrous magnesium sulfate, and after filtration, the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography to obtain 68.0 mg of 5-trifluoromethylthiopentyl- [4-chloro-2-fluoro-5- (2,2,2-trifluoroethyl). Sulfinylene) phenyl] ether, 76% yield.

¹ H-NMR (300MHz, CDCl ₃ ) δ (ppm): 7.54 (d, J = 8.1Hz, 1H), 7.21 (d, J = 9.9Hz, 1H), 4.13 (t, J = 6.3Hz, 2H) , 3.72 (m, 1H), 3.37 (m, 1H), 2.92 (t, J = 7.2Hz, 2H), 1.84 (m, 4H), 1.62 (m, 2H).

In this specification, the measurement of each physical property of an Example and a reference example uses the following equipment.

¹ H nuclear magnetic resonance spectrum ( ¹ H-NMR); JEOL JMN-Lambda 300 or JEOL JMN-Lambda-400 (manufactured by Japan Electronics Co., Ltd.), internal reference substance: tetramethylsilane

Melting point; MP-500V (manufactured by Anatec Yanaco Co., Ltd.).

(High-speed liquid chromatography (HPLC) analysis method)

Regarding the HPLC analysis method, if necessary, reference can be made to the following documents.

(Institute of Chemical Engineering of Japan, "New Experimental Chemistry Lecture 9 Analytical Chemistry II", pages 86 to 112 (1977), publisher Iizumi Shingo, Maruzen Co., Ltd. (for example, about fillers that can be used in column- (For combinations of mobile phases, see pages 93-96).

(Company) The Japanese Chemical Society, "Experimental Chemistry Lecture 20-1 Analytical Chemistry", 5th edition, pages 130 to 151 (2007), publishers Masaru Murata, Maruzen Co., Ltd. (for example, about reversed phase chromatography (For specific methods and conditions of analysis, please refer to pages 135 ~ 137).

(Gas Chromatography (GC) Analysis Method)

Regarding the GC analysis method, if necessary, refer to the following documents.

(Institute of Chemical Engineering of Japan, "New Experimental Chemistry Lecture 9 Analytical Chemistry II", pages 60 to 86 (1977), publisher Iizumi Shingo, Maruzen Co., Ltd. (for example, stationary phase liquids that can be used in column , See page 66).

(Company) The Japanese Chemical Society, "Experimental Chemistry Lecture 20-1 Analytical Chemistry", 5th edition, pages 121 to 129 (2007), publishers Masaru Murata, Maruzen Co., Ltd. Column specific (Please refer to pages 124 ~ 125).

(Method for measuring pH)

The pH is measured by a glass electrode type hydrogen ion concentration indicator. For the glass electrode type hydrogen ion concentration indicator, for example, DKK-TOA Co., Ltd. can be used in the form of HM-20P.

[Industrial availability]

According to the present invention, there can be provided a novel manufacturing method of the general formula (4) used as a pest control agent for pesticides and the like and a manufacturing intermediate thereof, and a novel manufacturing intermediate thereof.

Accordingly, the present invention is economical, environmentally friendly, and has high industrial use value.

Claims (16)

A compound represented by the general formula (2), In the formula, R ¹ and R ² are each independently a halogen atom or a C1 to C4 alkyl group. For example, the compound of claim 1, wherein R ¹ and R ² are each independently a halogen atom; or R ¹ and R ² are each independently a C1-C4 alkyl group. The compound of claim 1, wherein R ¹ is a fluorine atom; R ² is a chlorine atom; or R ¹ and R ² are each a methyl group. The compound as claimed in claim 1, wherein R ¹ and R ² are each independently a halogen atom. A compound as claimed in claim 1, wherein R ¹ is a fluorine atom; R ² is a chlorine atom. For example, the compound of claim 1, wherein R ¹ and R ² are each independently a C1-C4 alkyl group. A compound as claimed in claim 1, wherein R ¹ and R ² are each methyl. A method for producing a compound represented by the general formula (4): In the formula, R ¹ and R ² are each independently a halogen atom or a C1 to C4 alkyl group; R ³ is a C1 to C4 haloalkylthio group C2 to C10 alkyl group; R ⁴ is a C1 to C4 haloalkyl group; it includes the following Step: (i) a step of producing a compound represented by the general formula (2) from a compound represented by the general formula (1), In the formula, R ¹ and R ² are as defined above, In the formula, R ¹ and R ² are as defined above; (ii) the compound of the general formula (2) is reacted with a compound represented by the general formula (a) in the presence of a base to produce the general formula ( 3) A step of the compound represented by R ³ -X (a) wherein R ³ is as defined above; X is a halogen atom, C1 to C4 alkylsulfonyloxy, C1 to C4 haloalkylsulfonyl Oxygen, or phenylsulfonyloxy which may be substituted by C1 ~ C4 alkyl or halogen atom, In the formula, R ¹ , R ² and R ³ are as defined above; and (iii) a step of converting the compound of the general formula (3) into the compound of the aforementioned general formula (4). The method as claimed in claim 8, wherein step (iii) is the following step: (iii-a) by making the compound represented by the general formula (3) in the presence of a base and the compound represented by the general formula (b) A step of reacting a compound to convert the compound of the general formula (3) into the compound of the general formula (4), In the formula, R ¹ and R ² are each independently a halogen atom or a C1-C4 alkyl group; R ³ is a C1-C4 haloalkylthio group C2-C10 alkyl group, and R ⁴ -Y (b) In the formula, R ⁴ is C1 ~ C4 haloalkyl; Y is a halogen atom, C1 ~ C4 alkylsulfonyloxy, C1 ~ C4 haloalkylsulfonyloxy, or phenylsulfonium which may be substituted by C1 ~ C4 alkyl or halogen atom Oxygen. The method of claim 8, wherein step (iii) includes the following steps: (iii-b) a step of converting a compound represented by the general formula (3) into a compound represented by the general formula (5), In the formula, R ¹ and R ² are each independently a halogen atom or a C1 to C4 alkyl group; R ³ is a C1 to C4 haloalkylthio group C2 to C10 alkyl group, In the formula, R ¹ , R ² and R ³ are as defined above; and (iii-c) the compound represented by the general formula (5) is represented by the general formula (b) in the presence of a base. A step of converting a compound of the general formula (5) to a compound of the aforementioned general formula (4) by reacting a compound, wherein R ⁴ -Y (b) wherein R ⁴ is a C1-C4 haloalkyl group; Y is a halogen atom , C1 ~ C4 alkylsulfonyloxy, C1 ~ C4 haloalkylsulfonyloxy, or phenylsulfonyloxy which may be substituted by C1 ~ C4 alkyl or halogen atom. The method of claim 9 or 10, wherein R ¹ and R ² are each independently a halogen atom, or R ¹ and R ² are each independently a C1 to C4 alkyl group. The method of claim 9 or 10, wherein R ¹ is a fluorine atom; R ² is a chlorine atom; R ³ is 5-trifluoromethylthiopentyl; R ⁴ is 2,2,2-trifluoroethyl; X is chlorine atom, bromine atom, iodine atom, methanesulfonyloxy group, benzenesulfonyloxy group, p-toluenesulfonyloxy group or p-chlorobenzenesulfonyloxy group; Y is chlorine atom, bromine atom, iodine atom, methane sulfonic group, acyl group benzenesulfonamide, toluenesulfonamide acyl group or p-chlorophenyl sulfonylurea group; or R ¹ and R ² are each methyl; R ³ is 6-trifluoromethylthio-hexyl; R ⁴ is 2,2,2-trifluoroethyl; X is chlorine atom, bromine atom, iodine atom, methanesulfonyloxy, benzenesulfonyloxy, p-toluenesulfonyloxy or p-chlorobenzenesulfonyloxy Y is a chlorine atom, a bromine atom, an iodine atom, a methanesulfonyloxy group, a benzenesulfonyloxy group, a p-toluenesulfonyloxy group, or a p-chlorobenzenesulfonyloxy group. The method of claim 9 or 10, wherein R ¹ and R ² are each independently a halogen atom. The method of claim 9 or 10, wherein R ¹ is a fluorine atom; R ² is a chlorine atom; R ³ is 5-trifluoromethylthiopentyl; R ⁴ is 2,2,2-trifluoroethyl; X is chlorine atom, bromine atom, iodine atom, methanesulfonyloxy, benzenesulfonyloxy, p-toluenesulfonyloxy or p-chlorobenzenesulfonyloxy; Y is chlorine atom, bromine atom, iodine atom, methane Sulfonyloxy, benzenesulfonyloxy, p-toluenesulfonyloxy or p-chlorobenzenesulfonyloxy. The method of claim 9 or 10, wherein R ¹ and R ² are each independently a C1 to C4 alkyl group. The method of claim 9 or 10, wherein R ¹ and R ² are each methyl; R ³ is 6-trifluoromethylthiohexyl; R ⁴ is 2,2,2-trifluoroethyl; X is chlorine Atom, bromine atom, iodine atom, methanesulfonyloxy, benzenesulfonyloxy, p-toluenesulfonyloxy or p-chlorobenzenesulfonyloxy; Y is chlorine atom, bromine atom, iodine atom, methanesulfonyloxy Group, benzenesulfonyloxy, p-toluenesulfonyloxy or p-chlorobenzenesulfonyloxy.