CN105980354A - Method for producing harmful-organism control agent, and intermediate thereof - Google Patents

Abstract

The object of the present invention is to provide an intermediate suitable for the industrial scale production of the compound of general formula (4) having pest control activity and a production method thereof. The solution is: oxidize the mercaptophenol derivative, and then react with the general formula (a) in the presence of a base: R ³ -X (in the formula, R ³ is C1～C4 haloalkylthio C2～C10 alkyl, X is Halogen atom, etc.) to obtain the compound represented by the general formula (3) (in the formula, R ¹ and R ² are each independently a halogen atom or C1～C4 alkyl) represented by the compound, the general formula (3) The compound represented is reacted with the compound represented by general formula (b): R ⁴ -Y (in the formula, R ⁴ is C1～C4 haloalkyl, Y is a halogen atom, etc.) in the presence of a base to produce general formula (4) (wherein, R ¹ to R ⁴ have the same definitions as above).

Description

Production method and intermediate of pest control agent

technical field

The present invention relates to the manufacture method of the compound of general formula (4) and intermediate thereof,

(where,

R ¹ and R ² are each independently a halogen atom or a C1-C4 alkyl group,

R ³ is C1～C4 haloalkylthio C2～C10 alkyl,

R ⁴ is C1～C4 haloalkyl).

The present invention especially relates to the manufacture intermediate of the compound of above-mentioned general formula (4):

Compounds of general formula (2):

(wherein, R ¹ and R ² are as defined above); and

Compounds of general formula (3):

(wherein R ¹ and R ² and R ³ are as defined above); and

Compounds of general formula (5):

(In the formula, R ¹ and R ² and R ³ are as defined above).

Background technique

The compound of the above-mentioned general formula (4) is useful as a pest control agent in the form of an agricultural chemical or the like and an intermediate for its production (see Examples 12, 13, 17, 18, 26 and 27 of Patent Document 1).

As disclosed in Patent Document 1, for example, by making 6-thiocyanatohexyl-[2,4-dimethyl-5-(2,2,2-trifluoroethane) in the presence of tetra-n-butylammonium fluoride The product of Example 26 is obtained by reacting sulfanyl)phenyl]ether with trifluoromethyltrimethylsilane.

This method has problems in industrial production of 6-thiocyanatohexyl-[2,4-dimethyl-5-(2,2,2-trifluoroethylthio)phenyl]ether as a raw material. For example, problems such as the need for special equipment for the large amount of use of boric acid derivatives as raw materials, the need to use a large amount of expensive reagents, the need to use special reagents, and the need to use excessive amounts of reagents (see Examples 21 and 24 of Patent Document 1) and 25).

In addition, in the prior art, haloalkanes such as 1-iodo-2,2,2-trifluoroethane and 2,2,2-trifluoroethyl p-toluenesulfonate are used in the production of compounds of general formula (4). However, the haloalkylating agent is expensive, and the use of a large amount of the haloalkylating agent in the industrial production of the compound of the general formula (4) has become a major problem in terms of cost. For example, Patent Document 1 has specifically disclosed production methods 6 and 7 through examples. However, in the production method, at an early stage in the production route of the pest control agent as the final target compound, since the haloalkylation reaction using the haloalkylation agent is carried out, as a result, there is a need to use a large amount of high-priced Haloalkylating agent problem.

In addition, in general, sulfur-containing organic compounds often have characteristic odors, and it is necessary to consider the prevention of odors during industrial production.

Thus, various problems arise when the reaction is carried out on an industrial production scale.

In view of such a situation, it is desired to establish a simple, industrially inexpensive method for producing the compound of the general formula (4) that does not require special equipment or complicated operations.

prior art literature

patent documents

Patent Document 1: International Publication No. 2013/157229

Contents of the invention

The problem to be solved by the invention

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

Another object of the present invention is to provide an industrially preferable production method of the compound of the above general formula (4).

method used to solve the problem

In view of the above situation, the present inventors intensively studied the production method of the compound of the above-mentioned general formula (4). As a result, it has been surprisingly found that by providing a compound of the above general formula (2), a compound of the general formula (3) and/or a general formula (5), and by providing a compound of the above general formula (4) utilizing these compounds The manufacturing method can solve the above-mentioned problems. The present inventors thus completed the present invention based on the above knowledge.

That is, the present invention is as follows.

(1) A compound represented by general formula (2):

(In the formula, R ¹ and R ² are each independently a halogen atom or a C1-C4 alkyl group).

(2) The compound as described in (1) above, wherein each of R ¹ and R ² is independently a halogen atom; or each of R ¹ and R ² is independently a C1-C4 alkyl group.

(3) The compound as described in (1) above, wherein R ¹ is a fluorine atom, R ² is a chlorine atom; or R ¹ and R ² are each a methyl group.

(4) The compound as described in (1) above, wherein R ¹ and R ² are each independently a halogen atom.

(5) The compound as described in (1) above, wherein R ¹ is a fluorine atom, and R ² is a chlorine atom.

(6) The compound as described in (1) above, wherein R ¹ and R ² are each independently a C1-C4 alkyl group.

(7) The compound as described in (1) above, wherein R ¹ and R ² are each methyl.

(8) A compound represented by general formula (3):

(where,

R ¹ and R ² are each independently a halogen atom or a C1-C4 alkyl group,

R ³ is C1～C4 haloalkylthio (C2～C10 alkyl).

(9) The compound as described in (8) above, wherein R ¹ and R ² are each independently a halogen atom, R ³ is a C1-C4 haloalkylthio C2-C10 alkyl group; or R ¹ and R ² are each independently is a C1-C4 alkyl group, and R ³ is a C1-C4 haloalkylthio C2-C10 alkyl group.

(10) The compound as described in (8) above, 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.

(11) The compound as described in (8) above, wherein R ¹ and R ² are each independently a halogen atom, and R ³ is a C1-C4 haloalkylthio C2-C10 alkyl group.

(12) The compound as described in (8) above, wherein R ¹ is a fluorine atom, R ² is a chlorine atom, and R ³ is 5-trifluoromethylthiopentyl.

(13) The compound as described in (8) above, wherein R ¹ and R ² are each independently a C1-C4 alkyl group, and R ³ is a C1-C4 haloalkylthio C2-C10 alkyl group.

(14) The compound as described in (8) above, wherein R ¹ and R ² are each methyl, and R ³ is 6-trifluoromethylthiohexyl.

(15) A compound represented by general formula (5):

(where,

R ¹ and R ² are each independently a halogen atom or a C1-C4 alkyl group,

R ³ is C1～C4 haloalkylthio (C2～C10 alkyl).

(16) The compound as described in (15) above, wherein R ¹ and R ² are each independently a halogen atom, R ³ is a C1-C4 haloalkylthio C2-C10 alkyl group; or R ¹ and R ² are each independently is a C1-C4 alkyl group, and R ³ is a C1-C4 haloalkylthio C2-C10 alkyl group.

(17) The compound as described in (15) above, 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 methyl , R ³ is 6-trifluoromethylthiohexyl.

(18) The compound as described in (15) above, wherein R ¹ and R ² are each independently a halogen atom, and R ³ is a C1-C4 haloalkylthio C2-C10 alkyl group.

(19) The compound as described in (15) above, wherein R ¹ is a fluorine atom, R ² is a chlorine atom, and R ³ is 5-trifluoromethylthiopentyl.

(20) The compound as described in (15) above, wherein R ¹ and R ² are each independently a C1-C4 alkyl group, and R ³ is a C1-C4 haloalkylthio C2-C10 alkyl group.

(21) The compound as described in (15) above, wherein R ¹ and R ² are each methyl, and R ³ is 6-trifluoromethylthiohexyl.

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

(where,

R ¹ and R ² are each independently a halogen atom or a C1-C4 alkyl group,

R ³ is C1～C4 haloalkylthio C2～C10 alkyl,

R ⁴ is C1～C4 haloalkyl),

The method comprises the following steps:

(i) 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 as defined above),

(wherein, R ¹ and R ² are as defined above);

(ii) reacting the compound represented by the above general formula (2) with the compound represented by the general formula (a) in the presence of a base to produce the compound represented by the general formula (3),

R ³ -X (a)

(where,

^R3 is as defined above,

X is a halogen atom, a C1-C4 alkylsulfonyloxy group, a C1-C4 haloalkylsulfonyloxy group, or a phenylsulfonyloxy group that may be substituted by a C1-C4 alkyl group or a halogen atom),

(wherein, R ¹ , R ² and R ³ are as defined above); and

(iii) A step of converting the compound of the above general formula (3) into the compound of the above general formula (4).

(23) The method as described in (22) above, wherein step (iii) is a step of:

(iii-a) Converting the compound of the above general formula (3) into the above general formula (4) by reacting the compound represented by the general formula (3) with the compound represented by the general formula (b) in the presence of a base the compound step,

(where,

R ¹ and R ² are each independently a halogen atom or a C1-C4 alkyl group,

R ³ is C1～C4 haloalkylthio C2～C10 alkyl),

R ⁴ -Y (b)

(where,

R ⁴ is C1～C4 haloalkyl,

Y is a halogen atom, a C1-C4 alkylsulfonyloxy group, a C1-C4 haloalkylsulfonyloxy group, or a phenylsulfonyloxy group which may be substituted by a C1-C4 alkyl group or a halogen atom).

(24) The method as described in (22) above, wherein step (iii) comprises the following steps:

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

(where,

R ¹ and R ² are each independently a halogen atom or a C1-C4 alkyl group,

R ³ is C1～C4 haloalkylthio C2～C10 alkyl),

(wherein, R ¹ , R ² and R ³ are as defined above); and

(iii-c) Converting the compound of the above general formula (5) into the compound of the above general formula (4) by reacting the compound of the above general formula (5) with the compound represented by the general formula (b) in the presence of a base compound steps,

R ⁴ -Y (b)

(where,

R ⁴ is C1～C4 haloalkyl,

Y is a halogen atom, a C1-C4 alkylsulfonyloxy group, a C1-C4 haloalkylsulfonyloxy group, or a phenylsulfonyloxy group which may be substituted by a C1-C4 alkyl group or a halogen atom).

(25) The method as described in (23) or (24) above, wherein each of R ¹ and R ² is independently a halogen atom; or each of R ¹ and R ² is independently a C1-C4 alkyl group.

(26) The method as described in (23) or (24) above, 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 a chlorine atom, a bromine atom, an iodine atom, methanesulfonyloxy, benzenesulfonyloxy, p-toluenesulfonyloxy or p-chlorobenzenesulfonyloxy,

Y is a chlorine atom, a bromine atom, an iodine atom, methanesulfonyloxy, benzenesulfonyloxy, p-toluenesulfonyloxy or p-chlorobenzenesulfonyloxy; or

R ¹ and R ² are each methyl,

R ³ is 6-trifluoromethylthiohexyl,

R ⁴ is 2,2,2-trifluoroethyl,

X is a chlorine atom, a bromine atom, an iodine atom, methanesulfonyloxy, benzenesulfonyloxy, p-toluenesulfonyloxy or p-chlorobenzenesulfonyloxy,

Y is a chlorine atom, a bromine atom, an iodine atom, methanesulfonyloxy, benzenesulfonyloxy, p-toluenesulfonyloxy or p-chlorobenzenesulfonyloxy.

(27) The method as described in (23) or (24) above, wherein R ¹ and R ² are each independently a halogen atom.

(28) The method as described in (23) or (24) above, 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 a chlorine atom, a bromine atom, an iodine atom, methanesulfonyloxy, benzenesulfonyloxy, p-toluenesulfonyloxy or p-chlorobenzenesulfonyloxy,

Y is a chlorine atom, a bromine atom, an iodine atom, methanesulfonyloxy, benzenesulfonyloxy, p-toluenesulfonyloxy or p-chlorobenzenesulfonyloxy.

(29) The method as described in (23) or (24) above, wherein R ¹ and R ² are each independently a C1-C4 alkyl group.

(30) The method as described in (23) or (24) above, wherein

R ¹ and R ² are each methyl,

R ³ is 6-trifluoromethylthiohexyl,

R ⁴ is 2,2,2-trifluoroethyl,

X is a chlorine atom, a bromine atom, an iodine atom, methanesulfonyloxy, benzenesulfonyloxy, p-toluenesulfonyloxy or p-chlorobenzenesulfonyloxy,

Y is a chlorine atom, a bromine atom, an iodine atom, methanesulfonyloxy, benzenesulfonyloxy, p-toluenesulfonyloxy or p-chlorobenzenesulfonyloxy.

(31) A method of producing a compound represented by general formula (2):

(wherein, R ¹ and R ² are as defined below),

It is characterized in that the compound represented by general formula (1) is oxidized,

(In the formula, R ¹ and R ² are each independently a halogen atom or a C1-C4 alkyl group).

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

(wherein, R ¹ , R ² and R ³ are as defined below),

It is characterized in that the compound represented by the general formula (2) is reacted with the compound represented by the general formula (a) in the presence of a base,

(wherein, R1 and R2 are each independently a halogen atom or a ^{C1 -} C4 alkyl group):

R ³ -X (a)

(where,

R3 is C1～C4 haloalkylthio C2～C10 alkyl,

X is a halogen atom, a C1-C4 alkylsulfonyloxy group, a C1-C4 haloalkylsulfonyloxy group, or a phenylsulfonyloxy group which may be substituted by a C1-C4 alkyl group or a halogen atom).

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

(wherein, R ¹ , R ² , R ³ and R ⁴ are as defined below),

It is characterized in that the compound represented by the general formula (3) is reacted with the compound represented by the general formula (b) in the presence of a base,

(where,

R ¹ and R ² are each independently a halogen atom or a C1-C4 alkyl group,

R ³ is C1～C4 haloalkylthio C2～C10 alkyl),

R ⁴ -Y (b)

(middle,,

R ⁴ is C1～C4 haloalkyl,

Y is a halogen atom, a C1-C4 alkylsulfonyloxy group, a C1-C4 haloalkylsulfonyloxy group, or a phenylsulfonyloxy group which may be substituted by a C1-C4 alkyl group or a halogen atom).

(34) A method for producing a compound represented by general formula (5),

(wherein, R ¹ , R ² and R ³ are as defined below),

It is characterized in that the compound represented by the general formula (3) is reduced,

(where,

R ¹ and R ² are each independently a halogen atom or a C1-C4 alkyl group,

R ³ is C1～C4 haloalkylthio (C2～C10 alkyl).

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

(wherein, R ¹ , R ² , RR ³ and R ⁴ are as defined below),

It is characterized in that the compound represented by the general formula (5) is reacted with the compound represented by the general formula (b) in the presence of a base,

(where,

R ¹ and R ² are each independently a halogen atom or a C1-C4 alkyl group,

R ³ is C1～C4 haloalkylthio C2～C10 alkyl),

R ⁴ -Y (b)

(where,

R ⁴ is C1～C4 haloalkyl,

Y is a halogen atom, a C1-C4 alkylsulfonyloxy group, a C1-C4 haloalkylsulfonyloxy group, or a phenylsulfonyloxy group which may be substituted by a C1-C4 alkyl group or a halogen atom).

Invention effect

According to the present invention, novel production intermediates of compounds of the general formula (4) useful as harmful organism control agents and production intermediates thereof can be provided.

In addition, according to the present invention, a novel production method of a compound of the general formula (4) useful as a pest control agent and its production intermediate can be provided.

In addition, according to the present invention, by using the compound of the general formula (2), (3) and/or (5) of the present invention, a haloalkylation reaction is carried out in a later stage of the pest control agent production route, whereby it is possible to Significantly reduce the usage of high-valent haloalkylating agents, and can significantly reduce manufacturing costs. Therefore, the invention has good economic efficiency and high industrial application value.

Furthermore, the bis(2,4-dimethyl-5-hydroxyphenyl) disulfide produced in Example 1 of the present invention had almost no bad odor. In addition, bis(2,4-dimethyl-5-hydroxyphenyl) disulfide is a solid with a very high melting point. A high melting point means that its compounds are satisfactory in terms of preservation, as well as offering the option of recrystallization as an isolation method and/or purification method. The present invention finds that bis(2,4-dimethyl-5-hydroxyphenyl) disulfide has so many 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. It can be seen from this that the general formula ( The compound of 2) is industrially useful.

According to the present invention, the compounds of the general formula (2), (3) and (5) which become the production intermediates of the compound of the general formula (4) can be produced in high yields without using special reaction conditions or special expensive reagents. Therefore, it is suitable for industrial production, and it can be seen that by using these intermediates, there are also great advantages in terms of cost and the like in the industrial production of compounds of the general formula (4).

In providing the present invention, compounds of the general formulas (2), (3) and (5) and production methods using these compounds have been realized for the first time. In addition, according to the present invention, the industrial utility value of compounds of general formulas (2), (3) and (5) and production methods using these compounds has also been realized for the first time.

detailed description

The present invention will be described in detail below.

The words and symbols used in this manual are explained as follows.

As a halogen atom, a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom are mentioned, for example. Preferable examples of the halogen atom include a fluorine atom and a chlorine atom from the viewpoint of product usefulness and the like.

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

The C1-C4 alkyl refers to a straight-chain or branched-chain alkyl group having 1 to 4 carbon atoms. C1-C4 alkyl group includes, for example, methyl group, ethyl group, propyl group, isopropyl group, butyl group, sec-butyl group, isobutyl group and tert-butyl group. Preferable examples of the C1-C4 alkyl group include a methyl group from the viewpoint of product usefulness and the like.

The C2-C10 alkyl group refers to a straight-chain or branched-chain alkyl group having 2 to 10 carbon atoms. For C2-C10 alkyl groups, for example, ethyl, propyl, isopropyl, butyl, sec-butyl, isobutyl, tert-butyl, pentyl, hexyl, heptyl, octyl, Nonyl, decyl, etc., but not limited thereto.

C1～C4 haloalkyl refers to a linear or branched alkyl group with 1 to 4 carbon atoms substituted by the same or different 1 to 9 halogen atoms (wherein, the halogen atom has the same meaning as above ). Examples of C1-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, etc., but not limited thereto.

The C1-C4 haloalkylthio group refers to a (C1-C4 haloalkyl)-S- group (wherein, the C1-C4 haloalkyl has the same meaning as above). As for the C1-C4 haloalkylthio group, for example, fluoromethylthio group, difluoromethylthio group, trifluoromethylthio group, chlorodifluoromethylthio group, 2,2,2 -Trifluoroethylthio, pentafluoroethylthio, 3-fluoropropylthio, 2,2,3,3,3-pentafluoropropylthio, heptafluoropropylthio, 2,2 , 2-trifluoro-1-trifluoromethylethylthio, 2,2,3,3,4,4,4-heptafluorobutylthio, etc., but not limited thereto.

C1～C4 haloalkylthio C2～C10 alkyl refers to C2～C10 alkyl substituted by C1～C4 haloalkylthio (among them, C1～C4 haloalkylthio and C2～C10 alkyl have the same same meaning as above). For C1～C4 haloalkylthio C2～C10 alkyl, for example, 2-trifluoromethylthioethyl, 3-trifluoromethylthiopropyl, 4-trifluoromethyl Thiobutyl, 5-difluoromethylthiopentyl, 5-trifluoromethylthiopentyl, 5-(2,2,2-trifluoroethylthio)pentyl, 5-pentafluoro Ethylthiopentyl, 5-(2,2,3,3,3-pentafluoropropylthio)pentyl, 5-(2,2,3,3,4,4,4-heptafluorobutyl thiol)pentyl, 6-difluoromethylthiohexyl, 6-trifluoromethylthiohexyl, 6-(2,2,2-trifluoroethylthio)hexyl, 6-pentafluoroethyl thiolhexyl, 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, etc., but not Not limited to this. From the viewpoint of usefulness of the product, etc., preferred examples of C1-C4 haloalkylthio C2-C10 alkyl groups include 5-trifluoromethylthiopentyl and 6-trifluoromethylthiopentyl Hexyl.

C1-C4 alkylsulfonyloxy refers to (C1-C4 alkyl)-SO ₂ -O- group (wherein, C1-C4 alkyl has the same meaning as above). C1-C4 alkylsulfonyloxy groups include, for example, methanesulfonyloxy and ethylsulfonyloxy groups, but are not limited thereto.

C1-C4 haloalkylsulfonyloxy means (C1-C4 haloalkyl)-SO ₂ -O- group (wherein, C1-C4 haloalkyl has the same meaning as above). C1-C4 alkylsulfonyloxy group includes, for example, trifluoromethanesulfonyloxy group and the like, but is not limited thereto.

The phenylsulfonyloxy group that can be substituted by C1～C4 alkyl or halogen atom refers to the phenyl-SO ₂ -O- group that can be substituted by C1～C4 alkyl or halogen atom (wherein, C1～C4 alkyl and A halogen atom has the same meaning as above). As for the phenylsulfonyloxy group which may be substituted by a C1-C4 alkyl group or a halogen atom, for example, benzenesulfonyloxy group, p-toluenesulfonyloxy group and p-chlorobenzenesulfonyloxy group etc. are mentioned, but Not limited to this.

R ¹ in the present invention includes, for example, a halogen atom and a C1-C4 alkyl group.

In one embodiment, preferred R ¹ in the present invention includes, for example, a halogen atom, more preferably a fluorine atom, from the viewpoint of product usefulness and the like.

From the same viewpoint as above, for other embodiments, preferred R ¹ in the present invention includes, for example, a C1-C4 alkyl group, more preferably a methyl group.

R ² in the present invention includes, for example, a halogen atom and a C1-C4 alkyl group.

^In one embodiment, preferred R in the present invention includes, for example, a halogen atom, more preferably a chlorine atom, from the viewpoint of product availability and the like.

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

R ³ in the present invention includes, for example, a C1-C4 haloalkylthio C2-C10 alkyl group.

From the viewpoint of product usefulness and the like, in one embodiment, preferred ^R in the present invention includes, for example, 5-trifluoromethylthiopentyl.

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

R ⁴ in the present invention includes, for example, a C1-C4 haloalkyl group.

Preferred R ⁴ in the present invention includes, for example, 2,2,2-trifluoroethyl from the viewpoint of product usefulness and the like.

In terms of X in the present invention, for example, a halogen atom, a C1-C4 alkylsulfonyloxy group, a C1-C4 haloalkylsulfonyloxy group, and a C1-C4 alkyl group or a halogen atom that may be substituted of phenylsulfonyloxy.

From the viewpoints of reactivity, yield, and economical efficiency, 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 The oxy group and the p-chlorobenzenesulfonyloxy group are more preferably a chlorine atom, a bromine atom, and an iodine atom, still more preferably a bromine atom and an iodine atom, and especially preferably a bromine atom.

In terms of Y in the present invention, for example, a halogen atom, a C1-C4 alkylsulfonyloxy group, a C1-C4 haloalkylsulfonyloxy group, and a C1-C4 alkyl group or a halogen atom that may be substituted of phenylsulfonyloxy.

From the viewpoints of reactivity, yield, and economical efficiency, examples of preferred Y in the present invention include 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, more preferably chlorine atom, bromine atom, iodine atom, methanesulfonyloxy, p-toluenesulfonyloxy, more preferably bromine atom, iodine atom, methanesulfonyloxy group, p-toluenesulfonyloxy group, more preferably iodine atom, p-toluenesulfonyloxy group, particularly preferably p-toluenesulfonyloxy group.

(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-C4 alkyl group),

(wherein, R ¹ R ² is as defined above).

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

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

The compounds of the general formula (1) are used as starting materials for the process according to the 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. As for the compound of general formula (1), specifically, for example,

2,4-difluoro-5-mercaptophenol,

2,4-dichloro-5-mercaptophenol,

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 thereto.

(oxidizing agent of step (i))

As for the oxidizing agent used in the step (i), any oxidizing agent may be used as long as the reaction proceeds. The oxidizing agent usable in the step (i) includes, for example, hydrogen peroxide; organic peracids such as peracetic acid and m-chloroperbenzoic acid; oxygen and air; hypochlorites such as sodium hypochlorite Chlorates such as sodium chlorate; Halogen such as chlorine, bromine, iodine; Metal oxides such as manganese dioxide; Potassium permanganate; Potassium ferricyanide (potassium hexacyanoferrate (III)); Ferric chloride ( III); dimethyl sulfoxide, etc., but not limited thereto. Preferred examples of the oxidizing agent in the step (i) include hydrogen peroxide and oxygen from the viewpoints of reactivity, selectivity, and economical efficiency.

The oxidizing agents in the step (i) may be used alone or in combination of two or more in any ratio. The form of the oxidizing agent in the step (i) may be any form as long as the reaction proceeds. The form of the oxidizing agent in step (i) can be appropriately selected by those skilled in the art. The amount of the oxidizing agent used in the step (i) may be any amount as long as the reaction proceeds. Can exemplify the range of 0.5 to 5 moles, preferably 0.5 to 2 moles, more preferably 0.5 to 1.5 moles relative to 1 mole of the compound of the general formula (1), but the amount of the oxidizing agent used in step (i) can be determined by those skilled in the art Technicians make appropriate adjustments.

When hydrogen peroxide is used as the oxidizing agent in the step (i), any form of hydrogen peroxide may be used as long as the reaction proceeds. In consideration of risk 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%, preferably an aqueous solution having a concentration of 10% or more and 35% or less.

When hydrogen peroxide is used as the oxidizing agent in the step (i), the amount of hydrogen peroxide used may be any amount as long as the reaction proceeds. From the viewpoints of yield, suppression of by-products, and economical efficiency, the range of 0.5 to 1.5 moles, preferably 0.5 to 1.0 moles, and more preferably 0.5 to 0.6 moles can be illustrated with respect to 1 mole of the compound of the general formula (1). .

When hydrogen peroxide is used as the oxidizing agent in step (i), the reaction may be carried out in the presence of catalytic amounts of iodides. It is also possible not to use iodides. Whether to use iodides can be appropriately determined by those skilled in the art. Examples of iodides include sodium iodide and potassium iodide, preferably sodium iodide. As for the form of iodides, any form may be used as long as the reaction proceeds. Any amount may be used as long as the reaction proceeds as to the amount of iodides used. From the viewpoints of yield, suppression of by-products, and economic efficiency, 0 (zero) to 0.1 mol, preferably 0 to 0.05 mol, more preferably 0 to 0.03 molar range. When using iodides, it is 0.001-0.1 mol with respect to 1 mol of the compound of general formula (1), Preferably it is 0.001-0.05 mol, More preferably, it is the range of 0.005-0.03 mol.

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

(solvent for step (i))

The reaction in step (i) is preferably carried out in the presence of a solvent from the viewpoint of smooth progress of the reaction. As the solvent of the step (i), any solvent may be used as long as the reaction of the step (i) proceeds.

As the solvent of step (i), for example:

water,

Alcohols (for example, methanol, ethanol, 2-propanol, butanol, etc.),

Ethers (for example, tetrahydrofuran (THF), 1,4-dioxane, diisopropyl ether, dibutyl ether, di-tert-butyl ether, cyclopentyl methyl ether (CPME), methyl base-tert-butyl ether, 1,2-dimethoxyethane (DME), diglyme, triglyme, etc.),

Nitriles (for example, acetonitrile, etc.),

Amides (for example, N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAC), N-methylpyrrolidone (NMP), etc.),

Alkylureas (e.g., N,N'-dimethylimidazolidinone (DMI), etc.),

Sulfoxides (for example, dimethylsulfoxide (DMSO) etc.),

Sulfones (for example, sulfolane, etc.),

Ketones (for example, acetone, isobutyl methyl ketone (MIBK), cyclohexanone, etc.),

Carboxylate esters (for example, ethyl acetate, butyl acetate, etc.),

Carboxylic acids (for example, acetic acid, etc.),

Carbonates (for example, ethylene carbonate, propylene carbonate, etc.),

Aromatic hydrocarbon derivatives (for example, benzene, toluene, xylene, chlorobenzene, dichlorobenzene, trichlorobenzene, nitrobenzene, etc.),

Halogenated aliphatic hydrocarbons (for example, dichloromethane, etc.),

And any combination of them in any proportion, but not limited thereto.

From the viewpoints of reactivity and economical efficiency, preferred examples of solvents in step (i) include water, alcohols, nitriles, amides, sulfoxides, ketones, carboxylic acid esters, carboxylic acids Classes, aromatic hydrocarbon derivatives, halogenated aliphatic hydrocarbons, and any combination thereof in any proportion. In terms of preferred specific examples of the solvent in step (i), water, methanol, ethanol, 2-propanol, acetonitrile, N,N-dimethylformamide (DMF), N,N-dimethylethyl Amide (DMAC), Dimethyl Sulfoxide, Acetone, Isobutyl Methyl Ketone (MIBK), Cyclohexanone, Ethyl Acetate, Butyl Acetate, Acetic Acid, Toluene, Xylene, Chlorobenzene, Dichlorobenzene, Dichloromethane , and any combination of them in any proportion.

The amount of the solvent used in the 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, and economical efficiency, the range of 0.01 to 10.0 L (liter), preferably 0.1 to 5.0 L can be exemplified with respect to 1 mol of the compound of the general formula (1). When using a combination of two or more solvents, the ratio of the two or more solvents may be any ratio as long as the reaction proceeds.

When using hydrogen peroxide or oxygen etc. as the oxidizing agent of step (i), for example, in the aqueous solution of alkali metal hydroxides such as sodium hydroxide, potassium hydroxide, make the compound of general formula (1) into sodium salt, potassium salt etc. 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, economical efficiency, etc., -30°C (minus 30°C) to 160°C can be exemplified, preferably -10°C to 80°C.

(reaction time of step (i))

The reaction time of step (i) is not particularly limited. From the viewpoints of yield, suppression of by-products, economic efficiency, etc., 0.5 hours to 48 hours are exemplified, preferably 0.5 hours to 24 hours, and more preferably 1 hour to 12 hours.

Regarding step (i), the following documents can be referred to as necessary.

(Company) Edited by the Chemical Society of Japan, "New Experimental Chemistry Lecture 14 Synthesis and Reaction of Organic Compounds III", pp. 1736-1738 (1978), publisher Shingo Iizumi, Maruzen Co., Ltd.

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

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

In terms of the compound of general formula (2) obtained in step (i), specifically, for example:

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 not limited thereto.

In addition, bis(2,4-difluoro-5-hydroxyphenyl) disulfide is also called 5,5'-dithiobis(2,4-difluorophenol).

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

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

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

Bis(4-chloro-2-methyl-5-hydroxyphenyl) disulfide is also known 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 starting material for step (ii). The compound of general formula (2) obtained in step (i) may be used in the next step after isolation, may be further purified and used in the next step, or may be used in the next step without isolation.

(step (ii))

Next, step (ii) will be described.

The step (ii) is a step in which the compound represented by the general formula (2) is reacted with the compound represented by the general formula (a) in the presence of a base to produce the compound represented by the general formula (3),

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

R ³ -X (a)

(wherein, R ³ is C1～C4 haloalkylthio C2～C10 alkyl,

X is a halogen atom, a C1-C4 alkylsulfonyloxy group, a C1-C4 haloalkylsulfonyloxy group, or a phenylsulfonyloxy group that may be substituted by a C1-C4 alkyl group or a halogen atom),

(In the formula, 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. As far as the compound of general formula (a) is concerned, specifically, for example:

1-Chloro-5-trifluoromethylthiopentane,

1-Bromo-5-trifluoromethylthiopentane,

1-iodo-5-trifluoromethylthiopentane,

1-Methanesulfonyloxy-5-trifluoromethylthiopentane,

1-Trifluoromethanesulfonyloxy-5-trifluoromethylthiopentane,

1-(p-toluenesulfonyloxy)-5-trifluoromethylthiopentane,

1-Chloro-6-trifluoromethylthiohexane,

1-Bromo-6-trifluoromethylthiohexane,

1-iodo-6-trifluoromethylthiohexane,

1-Methanesulfonyloxy-6-trifluoromethylthiohexane,

1-Trifluoromethanesulfonyloxy-6-trifluoromethylthiohexane,

1-(p-toluenesulfonyloxy)-6-trifluoromethylthiohexane, etc., but not limited thereto.

The amount of the compound of the general formula (a) used may be any amount as long as the reaction proceeds. The range of 2.0-3.0 mol, preferably 2.0-2.4 mol is exemplified with respect to 1 mol of the compound of general formula (2) from viewpoints, such as yield, by-product suppression, and economical efficiency.

(base of step (ii))

As for the base used in the step (ii), any base may be used as long as the reaction proceeds. In terms of the base used in step (ii), for example:

Alkali metal hydroxides (for example, lithium hydroxide, sodium hydroxide, potassium hydroxide, etc.),

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 bicarbonates (for example, lithium bicarbonate, sodium bicarbonate, potassium bicarbonate, etc.),

Alkaline earth metal bicarbonates (for example, magnesium bicarbonate, calcium bicarbonate, etc.),

Phosphates (e.g., sodium phosphate, potassium phosphate, calcium phosphate, etc.),

Hydrogen phosphate (for example, sodium hydrogen phosphate, potassium hydrogen phosphate, calcium hydrogen phosphate, etc.),

Metal hydrides (e.g., sodium hydride, calcium hydride, etc.),

Metal alkoxides (for example, sodium methoxide, sodium ethoxide, potassium tert-butoxide, etc.) and

Amines (for example, triethylamine, tributylamine, diisopropylethylamine, 1,8-diazabicyclo[5.4.0]-7-undec-7-ene (DBU), 1 ,4-diazabicyclo[2.2.2]octane (DABCO), N,N‐dimethylaniline, N,N‐diethylaniline, pyridine, 4-(dimethylamino)-pyridine, 2,6-Lutidine, etc.), but not limited thereto.

From the viewpoints of reactivity, yield, and economic efficiency, etc., preferred examples of the base in step (ii) include alkali metal hydroxides, alkali metal carbonates, and alkali metal bicarbonates, and more preferably alkali Metal hydroxides and alkali metal carbonates. In terms of preferred specific examples of the base in step (ii), sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate and potassium bicarbonate can be cited, more preferably sodium hydroxide, potassium hydroxide, carbonic acid Sodium and Potassium Carbonate.

The base of step (ii) can be used alone or in combination of two or more in any ratio. The form of the base in the 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 skilled in the art.

The amount of the base used in the step (ii) may be any amount as long as the reaction proceeds. The range of 0.5-3.0 mol, preferably 0.5-2.4 mol is exemplified with respect to 1 mol of the compound of general formula (2) from viewpoints, such as yield, by-product suppression, and economical efficiency.

(phase transfer catalyst of step (ii))

The reaction of step (ii) can be carried out in the presence of a phase transfer catalyst. It is also possible not to use a phase transfer catalyst. Whether to use a phase transfer catalyst can be appropriately determined by those skilled in the art. In terms of phase transfer catalysts, for example, quaternary ammonium salts, quaternary Salts, crown ethers, etc., but not limited thereto.

In terms of quaternary ammonium salts, for example, tetrabutylammonium chloride, tetrabutylammonium bromide, tetrabutylammonium iodide, tetrabutylammonium hydrogensulfate, benzyltrimethylammonium chloride, benzyl Trimethyl ammonium bromide, octyl trimethyl ammonium chloride, octyl trimethyl ammonium bromide, trioctyl methyl ammonium chloride, trioctyl methyl ammonium bromide, benzyl lauryl dimethyl Ammonium chloride (benzyl dodecyl dimethyl ammonium chloride), benzyl lauryl dimethyl ammonium bromide (benzyl dodecyl dimethyl ammonium bromide), myristyl trimethyl ammonium chloride Ammonium (tetradecyltrimethylammonium chloride), myristyltrimethylammonium bromide (tetradecyltrimethylammonium bromide), benzyldimethylstearylammonium chloride (benzyloctadecyl dimethyl ammonium chloride), benzyl dimethyl stearyl ammonium bromide (benzyl octadecyl dimethyl ammonium bromide), etc.

season For salts, for example, tetrabutyl bromide tetraoctyl bromide tetraphenyl bromide Wait.

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

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

The phase transfer catalysts may be used alone or in combination of two or more in arbitrary ratios. The form of the phase transfer catalyst may be any form as long as the reaction proceeds. The form of the phase transfer catalyst can be appropriately selected by those skilled in the art.

The amount of the phase transfer catalyst used in the step (ii) 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 0 (zero) to 0.3 moles can be illustrated relative to 1 mole of the compound of the general formula (2), but the use of the phase transfer catalyst in step (ii) The amount can be appropriately adjusted by those skilled in the art.

(solvent for step (ii))

The reaction of step (ii) is preferably carried out in the presence of a solvent from the viewpoint of smooth progress of the reaction. As the solvent of the step (ii), any solvent may be used as long as the reaction of the step (ii) proceeds. As the solvent of step (ii), for example,

Amides (for example, N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAC), N-methylpyrrolidone (NMP), etc.),

Alkylureas (e.g., N,N'-dimethylimidazolidinone (DMI), etc.),

Sulfoxides (for example, dimethylsulfoxide (DMSO) etc.),

Sulfones (for example, sulfolane, etc.),

Ethers (for example, tetrahydrofuran (THF), 1,4-dioxane, diisopropyl ether, dibutyl ether, di-tert-butyl ether, cyclopentyl methyl ether (CPME), methyl base-tert-butyl ether, 1,2-dimethoxyethane (DME), diglyme, triglyme, etc.),

Ketones (for example, acetone, isobutyl methyl ketone (MIBK), cyclohexanone, etc.),

Carboxylate esters (for example, ethyl acetate, butyl acetate, etc.),

Nitriles (for example, acetonitrile, etc.),

Alcohols (for example, methanol, ethanol, 2-propanol, butanol, etc.),

Aromatic hydrocarbon derivatives (for example, benzene, toluene, xylene, chlorobenzene, dichlorobenzene, trichlorobenzene, nitrobenzene, etc.),

Halogenated aliphatic hydrocarbons (for example, dichloromethane, etc.), water and any combination thereof in any proportion, but not limited thereto.

From the viewpoint of reactivity, economical efficiency, etc., preferred examples of solvents in step (ii) include amides, sulfoxides, ethers, ketones, nitriles, alcohols, and aromatic hydrocarbon derivatives. , water, and any combination of them in any proportion. Preferred specific examples of the solvent in step (ii) include N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAC), N-methylpyrrolidone (NMP) , dimethyl sulfoxide (DMSO), tetrahydrofuran (THF), acetone, isobutyl methyl ketone (MIBK), acetonitrile, methanol, ethanol, 2-propanol, toluene, xylene, chlorobenzene, dichlorobenzene, water, and any combination of them in any proportion.

The amount of the solvent used in the step (ii) may be any amount as long as the reaction system can be sufficiently stirred. From the viewpoints of yield, suppression of by-products, and economical efficiency, the range of 0.01 to 10.0 L (liter), preferably 0.1 to 5.0 L can be exemplified with respect to 1 mol of the compound of the general formula (2). When using a combination of two or more solvents, 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, economic efficiency, etc., the range of -10°C (minus 10°C) to 160°C, preferably 10°C to 120°C can be 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, economical efficiency, etc., 0.5 hours to 48 hours can be exemplified, and the range of 1 hour to 24 hours is preferable.

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

As the compound of the general formula (3) obtained in step (ii), specifically, for example,

Bis[2,4-difluoro-5-(5-trifluoromethylthiopentyloxy)phenyl] 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-trifluoromethylthiohexyloxy)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-trifluoromethylthiopentyloxy)phenyl] disulfide,

Bis[4-chloro-2-methyl-5-(6-trifluoromethylthiohexyloxy)phenyl] disulfide,

Bis[2,4-dimethyl-5-(5-trifluoromethylthiopentyloxy)phenyl] disulfide,

Bis[2,4-dimethyl-5-(6-trifluoromethylthiohexyloxy)phenyl]disulfide, etc., but not limited thereto.

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

(step (iii))

Next, step (iii) will be described.

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

(where,

R ¹ and R ² are each independently a halogen atom or a C1-C4 alkyl group,

R ³ is C1～C4 haloalkylthio C2～C10 alkyl),

(where,

R ¹ , R ² and R ³ are as defined above;

R ⁴ is C1～C4 haloalkyl).

Wherein, step (iii) is step (iii-a), or step (iii) includes step (iii-b) and step (iii-c).

In one embodiment, step (iii) is the step of:

(iii-a) Converting the compound of the above general formula (3) into the above general formula (4) by reacting the compound represented by the general formula (3) with the compound represented by the general formula (b) in the presence of a base the compound step,

(where,

R ¹ and R ² are each independently a halogen atom or a C1-C4 alkyl group,

R ³ is C1～C4 haloalkylthio C2～C10 alkyl),

R ⁴ -Y (b)

(where,

R ⁴ is C1～C4 haloalkyl,

Y is a halogen atom, a C1-C4 alkylsulfonyloxy group, a C1-C4 haloalkylsulfonyloxy group, or a phenylsulfonyloxy group which may be substituted by a C1-C4 alkyl group or a halogen atom).

For other embodiments, step (iii) comprises the following steps:

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

(where,

R ¹ and R ² are each independently a halogen atom or a C1-C4 alkyl group,

R ³ is C1～C4 haloalkylthio C2～C10 alkyl),

(wherein, R ¹ , R ² and R ³ are as defined above); and

(iii-c) Converting the compound of the above general formula (5) into the compound of the above general formula (4) by reacting the compound of the above general formula (5) with the compound represented by the general formula (b) in the presence of a base compound steps,

R ⁴ -Y (b)

(where,

R ⁴ is C1～C4 haloalkyl,

Y is a halogen atom, a C1-C4 alkylsulfonyloxy group, a C1-C4 haloalkylsulfonyloxy group, or a phenylsulfonyloxy group which may be substituted by a C1-C4 alkyl group or a halogen atom).

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

(step (iii-a))

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

Step (iii-a) is by making the compound represented by the general formula (3) react with the compound represented by the general formula (b) in the presence of a base, and the compound of the above general formula (3) is converted into the compound of the general formula (4 ) the step of the compound represented,

(where,

R ¹ and R ² are each independently a halogen atom or a C1-C4 alkyl group;

R ³ is C1～C4 haloalkylthio C2～C10 alkyl),

R ⁴ -Y (b)

(where,

R ⁴ is C1～C4 haloalkyl;

Y is a halogen atom, a C1-C4 alkylsulfonyloxy group, a C1-C4 haloalkylsulfonyloxy group, or a phenylsulfonyloxy group that may be substituted by a C1-C4 alkyl group or a halogen atom),

(In the formula, R ¹ , R ² , R ³ and R ⁴ are as defined above).

(compound of general formula (b) of step (iii-a))

The compound of the general formula (b) in the step (iii-a) is a known compound, or a compound that can be produced from a known compound by a known method. In terms of the compound of 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,

2,2,2-trifluoroethyl methanesulfonate,

2,2,2-trifluoroethyl trifluoromethanesulfonate,

2,2,2-trifluoroethyl p-toluenesulfonate, etc., but not limited thereto.

The amount of the compound of the general formula (b) used in the step (iii-a) may be any amount as long as the reaction proceeds. The range of 2.0-3.0 mol, preferably 2.0-2.4 mol is exemplified with respect to 1 mol of the compound of general formula (3) from viewpoints, such as yield, by-product suppression, and economical efficiency.

(base of step (iii-a))

As the base used in the step (iii-a), any base may be used as long as the reaction proceeds. In terms of bases that can be used in step (iii-a), for example,

Alkali metal hydroxides (for example, lithium hydroxide, sodium hydroxide, potassium hydroxide, etc.),

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 bicarbonates (for example, lithium bicarbonate, sodium bicarbonate, potassium bicarbonate, etc.),

Alkaline earth metal bicarbonates (for example, magnesium bicarbonate, calcium bicarbonate, etc.),

Phosphates (e.g., sodium phosphate, potassium phosphate, calcium phosphate, etc.),

Hydrogen phosphate (for example, sodium hydrogen phosphate, potassium hydrogen phosphate, calcium hydrogen phosphate, etc.),

Metal hydrides (e.g., sodium hydride, calcium hydride, etc.),

Metal alkoxides (for example, sodium methoxide, sodium ethoxide, potassium tert-butoxide, etc.),

Amines (for example, triethylamine, tributylamine, diisopropylethylamine, 1,8-diazabicyclo[5.4.0]-7-undec-7-ene (DBU), 1 ,4-diazabicyclo[2.2.2]octane (DABCO), N,N‐dimethylaniline, N,N‐diethylaniline, pyridine, 4-(dimethylamino)-pyridine, 2,6-lutidine, etc.) and

Among the free radical initiators described later, those suitable as bases (for example, _sodium hydrogensulfite, potassium hydrogensulfite, Rongalite (trade name) (sodium formaldehyde sulfoxylate2H2O ) etc.), but is not limited to this.

Preferable examples of the base in the step (iii-a) include alkali metal hydroxides, alkali metal carbonates, and alkali metal bicarbonates from the viewpoints of reactivity, yield, and economical efficiency. Preferable specific examples of the base in step (iii-a) include sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, and potassium bicarbonate.

The bases of the step (iii-a) may be used alone or in combination of two or more in any ratio. The form of the base in the step (iii-a) may be any form as long as the reaction proceeds. The form of the base in step (iii-a) can be appropriately selected by those skilled in the art.

The amount of the base used in the step (iii-a) may be any amount as long as the reaction proceeds. From the viewpoints of yield, suppression of by-products, and economical efficiency, the range of 0.5 to 3.0 moles, preferably 0.5 to 2.4 moles, and more preferably 1.0 to 2.4 moles can be illustrated with respect to 1 mole of the compound of the general formula (3). .

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

The reaction of step (iii-a) is carried out in the presence or absence of a free radical initiator, preferably in the presence of a free radical initiator. However, whether to use a radical initiator in step (iii-a) can be appropriately determined by those skilled in the art. As the radical initiator used in the step (iii-a), any radical initiator may be used as long as the reaction proceeds. In terms of free radical initiators that can be used in step (iii-a), for example, sulfurous acid, sodium hydrogensulfite, potassium hydrogensulfite, sodium sulfite, potassium sulfite, Rongalite (trade name) (formaldehyde sulfoxylate) sodium hydrogen dihydrate), etc., but not limited thereto. In this context, the radical initiator is understood to be a reducing agent. Sodium formaldehyde sulfoxylate dihydrate has the same meaning as sodium hydroxymethanesulfinate dihydrate. From the viewpoints of yield, reactivity, availability, price, and ease of handling, Rongalite is a preferred example of the radical generator used in the step (iii-a).

The radical initiators of the step (iii-a) may be used alone or in combination of two or more in any ratio. The form of the radical generator in step (iii-a) may be any form as long as the reaction proceeds. The form of the radical initiator in step (iii-a) can be appropriately selected by those skilled in the art. The amount of the radical initiator used in the step (iii-a) may be any amount as long as the reaction proceeds. From the viewpoints of yield, suppression of by-products, and economic efficiency, 0 (zero) to 6.0 moles, preferably 0.01 to 6.0 moles, more preferably 0.1 to 4.0 moles can be exemplified relative to 1 mole of the compound of the general formula (3). moles, more preferably in the range of 1.0 to 4.0 moles, but the usage-amount of the radical initiator in the step (iii-a) can be appropriately adjusted by those skilled in the art. An appropriate radical initiator as described above for step (iii-a) may also be used as a base for step (iii-a) above. The radical initiator of the step (iii-a) and the base of the above-mentioned step (iii-a) may also be used in combination.

(solvent for step (iii-a))

The reaction of step (iii-a) is preferably carried out in the presence of a solvent from the viewpoint of smooth progress of the reaction. As the solvent of the step (iii-a), any solvent may be used as long as the reaction of the step (iii-a) proceeds. As the solvent of step (iii-a), for example,

Amides (for example, N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAC), N-methylpyrrolidone (NMP), etc.),

Alkylureas (e.g., N,N'-dimethylimidazolidinone (DMI), etc.),

Sulfoxides (for example, dimethylsulfoxide (DMSO) etc.),

Sulfones (for example, sulfolane, etc.),

Ethers (for example, tetrahydrofuran (THF), 1,4-dioxane, diisopropyl ether, dibutyl ether, di-tert-butyl ether, cyclopentyl methyl ether (CPME), methyl base-tert-butyl ether, 1,2-dimethoxyethane (DME), diglyme, triglyme, etc.),

Ketones (for example, acetone, isobutyl methyl ketone (MIBK), cyclohexanone, etc.),

Carboxylate esters (for example, ethyl acetate, butyl acetate, etc.),

Nitriles (for example, acetonitrile, etc.),

Alcohols (for example, methanol, ethanol, 2-propanol, butanol, etc.),

Aromatic hydrocarbon derivatives (for example, benzene, toluene, xylene, chlorobenzene, dichlorobenzene, trichlorobenzene, nitrobenzene, etc.),

Halogenated aliphatic hydrocarbons (for example, dichloromethane, etc.),

water,

And any combination of them in any proportion, but not limited thereto.

From the viewpoint of reactivity and economical efficiency, preferred examples of solvents in step (iii-a) include amides, sulfoxides, ethers, ketones, nitriles, alcohols, aromatic hydrocarbon derivatives Species, water, and any combination of them in any proportion. In terms of preferred specific examples of the solvent of step (iii-a), N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAC), N-methylpyrrolidone ( NMP), dimethyl sulfoxide (DMSO), tetrahydrofuran (THF), acetone, isobutyl methyl ketone (MIBK), acetonitrile, methanol, ethanol, 2-propanol, toluene, xylene, chlorobenzene, dichlorobenzene, Water, and any combination of them in any proportion.

The amount of the solvent used in the step (iii-a) may be any amount as long as the reaction system can be sufficiently stirred. From the viewpoints of yield, suppression of by-products, and economical efficiency, the range of 0.01 to 10.0 L (liter), preferably 0.1 to 5.0 L can be exemplified with respect to 1 mol of the compound of the general formula (3). When using a combination of two or more solvents, 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, economical efficiency, etc., -10°C (minus 10°C) to 160°C can be exemplified, preferably 10°C to 120°C.

(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, economical efficiency, etc., 0.5 hours to 48 hours can be exemplified, and the range of 1 hour to 24 hours is preferable.

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

As the compound of the general formula (4) obtained in step (iii-a), specifically, for example,

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-trifluoromethylthiohexyl-[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]ether,

6-trifluoromethylthiohexyl-[2-fluoro-4-methyl-5-(2,2,2-trifluoroethylthio)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-trifluoromethylthiopentyl-[2,4-dimethyl-5-(2,2,2-trifluoroethylthio)phenyl]ether,

6-trifluoromethylthiohexyl-[2,4-dimethyl-5-(2,2,2-trifluoroethylthio)phenyl]ether, etc., but not limited thereto.

(step (iii-b))

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

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

(where,

R ¹ and R ² are each independently a halogen atom or a C1-C4 alkyl group,

R ³ is C1～C4 haloalkylthio C2～C10 alkyl),

(In the formula, R ¹ , R ² and R ³ are as defined above).

Here, the step (iii-b) is a step of producing the compound of the general formula (5) by reducing the compound of the general formula (3). In other words, the step (iii-b) is a step of producing the compound of the general formula (5) by reacting the compound of the general formula (3) with a reducing agent.

(reducing agent of step (iii-b))

As the reducing agent used in the step (iii-b), any reducing agent may be used as long as the reaction proceeds. As for the reducing agent usable in step (iii-b), for example, metals (for example, zinc, iron, tin, etc.); borohydrides (for example, sodium borohydride, potassium borohydride, sodium cyanoborohydride , borane tetrahydrofuran complexes, etc.); aluminum hydride compounds (for example, lithium aluminum hydride, diisobutylaluminum hydride, etc.); triphenylphosphine-hydrous alcohols; tertiary phosphate esters (for example, triphenyl phosphate, methyl ester, triethyl phosphate, etc.); hydrazine hydrate, etc., but are not limited thereto. Preferred examples of the reducing agent in step (iii-b) include metals and borohydrides, more preferably metals, from the viewpoints of yield, reactivity, availability, price, and ease of handling. Preferable specific examples of the reducing agent in step (iii-b) include zinc, iron, tin, and sodium borohydride, more preferably zinc, iron, and tin.

The reducing agent of step (iii-b) may be used alone or in combination of two or more in any ratio. As for the form of the reducing agent in the step (iii-b), any form may be used as long as the reaction proceeds. The form of the reducing agent in step (iii-b) can be appropriately selected by those skilled in the art. The amount of the reducing agent used in the step (iii-b) may be any amount as long as the reaction proceeds. Can exemplify the range of 0.25 to 10 moles, preferably 0.25 to 2 moles, preferably 0.5 to 1.5 moles relative to 1 mole of the compound of the general formula (3), but the amount of the reducing agent used in step (iii-b), It can be appropriately adjusted by those skilled in the art.

When a metal (eg, zinc, iron, tin, etc.) is used as the reducing agent in step (iii-b), the form of the metal can be any form as long as the reaction proceeds. However, from the viewpoints of reactivity, availability, ease of handling, and the like, powdery metals are preferable. Therefore, preferred specific examples of the metal used as the reducing agent in the step (iii-b) include zinc powder, iron powder, tin powder, and the like. When a metal (for example, zinc, iron, tin, etc.) is used as the reducing agent in the step (iii-b), the amount of the metal used can be any amount as long as the reaction proceeds. From the viewpoints of yield, suppression of by-products, and economical efficiency, the range of 1.0 to 10 moles, preferably 1.0 to 3.0 moles, and more preferably 1.0 to 2.0 moles can be exemplified with respect to 1 mole of the compound of the general formula (3). .

When using a metal (eg, zinc, iron, tin, etc.) as the reducing agent in step (iii-b), it is preferable to conduct the reaction in the presence of an acid. Examples of acids 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, hydrochloric acid and sulfuric acid are examples of preferable acids, and hydrochloric acid is more preferable. The form of the acid may be any form as long as the reaction proceeds. The form of the acid includes, for example, only the liquid or solid of the acid, or an aqueous solution or a solution of a solvent in the later-described step (iii-b) other than water, and the like. From the viewpoints of availability, price, and ease of handling, etc., preferred examples of the acid form include only acidic liquids (for example, concentrated sulfuric acid, etc.) or 5-50% aqueous solutions (for example, concentrated hydrochloric acid ( That is, 35% hydrochloric acid), etc.), but the acid form can be appropriately selected by those skilled in the art. The amount of the acid used may be any amount as long as the reaction proceeds. From the viewpoints of yield, suppression of by-products, and economical efficiency, the range of 1 to 100 moles, preferably 1 to 30 moles can be exemplified relative to 1 mole of the compound of the general formula (3), but the amount of the acid used can be determined from the present invention. appropriate adjustments by those skilled in the art.

When using a metal (eg, zinc, iron, tin, etc.) as the reducing agent in step (iii-b), water and/or alcohol are preferably used. Examples of alcohols include methanol, ethanol, and 2-propanol, but are not limited thereto. Water and/or alcohol may be used alone or in combination of two or more in any ratio. 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, and economic efficiency, the range of 1 to 50 moles relative to 1 mole of the compound of general formula (3) can be exemplified, but the amount of water and/or alcohol used can be determined by those skilled in the art. Appropriate adjustments. In addition, when water and/or alcohol are used as the solvent described later, a large excess amount of water and/or alcohol may be used regardless of the range exemplified here.

When sodium borohydride or the like is used as the reducing agent in step (iii-b), alcohol or the like is preferably used. Examples of alcohols include methanol, ethanol, and 2-propanol, but are not limited thereto. Alcohols may be used alone or in combination of two or more in arbitrary ratios. The amount of alcohol used may be any amount as long as the reaction proceeds. From the viewpoints of yield, suppression of by-products, economical efficiency, etc., the range of 1 to 10 moles can be exemplified relative to 1 mole of the compound of the general formula (3), but the amount of alcohol used can be appropriately adjusted by those skilled in the art. Moreover, when alcohol is used also as a solvent mentioned later, regardless of the range illustrated here, a large excess amount of alcohol can be used.

(solvent for step (iii-b))

The reaction of step (iii-b) is preferably carried out in the presence of a solvent from the viewpoint of smooth progress of the reaction. As the solvent of the step (iii-b), any solvent may be used as long as the reaction of the step (iii-b) proceeds. As the solvent of the step (iii-b), for example,

water,

Alcohols (for example, methanol, ethanol, 2-propanol, butanol, etc.),

Ethers (for example, tetrahydrofuran (THF), 1,4-dioxane, diisopropyl ether, dibutyl ether, di-tert-butyl ether, cyclopentyl methyl ether (CPME), methyl base-tert-butyl ether, 1,2-dimethoxyethane (DME), diglyme, triglyme, etc.),

Nitriles (for example, acetonitrile, etc.),

Amides (for example, N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAC), N-methylpyrrolidone (NMP), etc.),

Alkyl urea (such as N,N'-dimethylimidazolidinone (DMI), etc.),

Sulfoxides (for example, dimethylsulfoxide (DMSO) etc.),

Sulfones (for example, sulfolane, etc.),

Ketones (for example, acetone, isobutyl methyl ketone (MIBK), cyclohexanone, etc.),

Carboxylate esters (for example, ethyl acetate, butyl acetate, etc.),

Carboxylic acids (for example, acetic acid, etc.),

Carbonates (for example, ethylene carbonate, propylene carbonate, etc.),

Aromatic hydrocarbons (for example, benzene, toluene, xylene, etc.),

Halogenated aromatic hydrocarbons (for example, chlorobenzene, dichlorobenzene, trichlorobenzene, etc.),

Halogenated aliphatic hydrocarbons (for example, dichloromethane, etc.) and any combination thereof in any proportion, but not limited thereto.

From the viewpoints of reactivity and economic efficiency, etc., preferred examples of the solvent in step (iii-b) include water, alcohols, ethers, nitriles, amides, carboxylic acid esters, carboxylic acids, Aromatic hydrocarbons, halogenated aromatic hydrocarbons, halogenated aliphatic hydrocarbons, and any combination thereof in any proportion. Preferable specific examples of the solvent in step (iii-b) include 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 proportion.

The amount of the solvent used in the step (iii-b) may be any amount as long as the reaction system can be sufficiently stirred. From the viewpoints of yield, suppression of by-products, and economical efficiency, the range of 0.01 to 10.0 L (liter), preferably 0.1 to 5.0 L can be exemplified with respect to 1 mol of the compound of the general formula (3). When using a combination of two or more solvents, as long as the reaction proceeds, the ratio of the two or more solvents may be any ratio.

(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, economical efficiency, etc., -10°C (minus 10°C) to 160°C can be exemplified, preferably 10°C to 120°C.

(reaction time of step (iii-b))

The reaction time of step (iii-b) is not particularly limited. From the viewpoints of yield, suppression of by-products, economic efficiency, etc., 0.5 hours to 48 hours are exemplified, preferably 0.5 hours to 24 hours, and more preferably 1 hour to 12 hours.

Regarding the step (iii-b), the following documents can be referred to as necessary.

(Company) Edited by the Chemical Society of Japan, "New Experimental Chemistry Lecture 14 Synthesis and Reaction of Organic Compounds III", pp. 1699-1700 (1978), published by Shingo Iizumi and Maruzen Co., Ltd.

(Company) Edited by the Chemical Society of Japan, "Experimental Chemistry Lecture 24 Organic Synthesis VI" 4th edition, p. 325 (1992), publisher Seishiro Murata, Maruzen Co., Ltd.

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

As the compound of the general formula (5) obtained in step (iii-b), specifically, for example,

2,4-Difluoro-5-(5-trifluoromethylthiopentyloxy)thiophenol,

2,4-difluoro-5-(6-trifluoromethylthiohexyloxy)thiophenol,

2,4-Dichloro-5-(5-trifluoromethylthiopentyloxy)thiophenol,

2,4-Dichloro-5-(6-trifluoromethylthiohexyloxy)thiophenol,

2-Chloro-4-fluoro-5-(5-trifluoromethylthiopentyloxy)benzenethiophenol,

2-Chloro-4-fluoro-5-(6-trifluoromethylthiohexyloxy)benzenethiophenol,

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)benzenethiophenol,

2,4-Dimethyl-5-(5-trifluoromethylthiopentyloxy)thiophenol,

2,4-Dimethyl-5-(6-trifluoromethylthiohexyloxy)thiophenol, etc., but not limited thereto.

A compound of general formula (5) as a product of step (iii-b) can be used as a starting material for step (iii-c). The compound of general formula (5) obtained in step (iii-b) can be used in the next step after isolation, can also be further purified and used in the next step, or can be used in the next step without isolation.

(step (iii-c))

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

Step (iii-c) is by making the compound represented by general formula (5) react with the compound represented by general formula (b) in the presence of a base, and the compound of above-mentioned general formula (5) is converted into general formula (4 ) the step of the compound represented,

(where,

R ¹ and R ² are each independently a halogen atom or a C1-C4 alkyl group,

R ³ is C1～C4 haloalkylthio C2～C10 alkyl),

R ⁴ -Y (b)

(where,

R ⁴ is C1～C4 haloalkyl,

Y is a halogen atom, a C1-C4 alkylsulfonyloxy group, a C1-C4 haloalkylsulfonyloxy group, or a phenylsulfonyloxy group that may be substituted by a C1-C4 alkyl group or a halogen atom),

(In the formula, R ¹ , R ² , R ³ and R ⁴ are as defined above).

(compound of general formula (b) of step (iii-c))

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

The amount of the compound of the general formula (b) used in the step (iii-c) may be any amount as long as the reaction proceeds. The range of 1.0-1.5 mol, preferably 1.0-1.2 mol is exemplified with respect to 1 mol of the compound of general formula (5) from viewpoints, such as yield, by-product suppression, and economical efficiency.

(base of step (iii-c))

As the base used in the step (iii-c), any base may be used as long as the reaction proceeds. In terms of bases that can be used in step (iii-c), for example:

Alkali metal hydroxides (for example, lithium hydroxide, sodium hydroxide, potassium hydroxide, etc.),

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 bicarbonates (for example, lithium bicarbonate, sodium bicarbonate, potassium bicarbonate, etc.),

Alkaline earth metal bicarbonates (for example, magnesium bicarbonate, calcium bicarbonate, etc.),

Phosphates (e.g., sodium phosphate, potassium phosphate, calcium phosphate, etc.),

Hydrogen phosphate (for example, sodium hydrogen phosphate, potassium hydrogen phosphate, calcium hydrogen phosphate, etc.),

Metal hydrides (e.g., sodium hydride, calcium hydride, etc.),

Metal alkoxides (for example, sodium methoxide, sodium ethoxide, potassium tert-butoxide, etc.),

Amines (for example, triethylamine, tributylamine, diisopropylethylamine, 1,8-diazabicyclo[5.4.0]-7-undec-7-ene (DBU), 1 ,4-diazabicyclo[2.2.2]octane (DABCO), N,N‐dimethylaniline, N,N‐diethylaniline, pyridine, 4-(dimethylamino)-pyridine, 2,6-lutidine, etc.) and

Among the free radical initiators described later, those suitable as bases (for example, sodium bisulfite, potassium hydrogen sulfite, Rongalite (trade name) (formaldehyde sodium sulfoxylate dihydrate) etc.) Not limited to this.

Preferable examples of the base in the step (iii-c) include alkali metal hydroxides, alkali metal carbonates, and alkali metal bicarbonates from the viewpoints of reactivity, yield, and economical efficiency. Preferable specific examples of the base in step (iii-c) include sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, and potassium bicarbonate.

The bases in step (iii-c) can be used alone or in combination of two or more in any ratio. The form of the base in the step (iii-c) may be in any form as long as the reaction proceeds. The form of the base in step (iii-c) can be appropriately selected by those skilled in the art.

The amount of the base used in the step (iii-c) may be any amount as long as the reaction proceeds. The range of 0.5-1.5 mol, preferably 0.5-1.2 mol is exemplified with respect to 1 mol of the compound of general formula (5) from viewpoints, such as yield, by-product suppression, and economical efficiency.

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

The reaction of step (iii-c) is carried out in the presence or absence of a free radical initiator, preferably in the presence of a free radical initiator. However, whether to use a free radical initiator in step (iii-c) can be appropriately determined by those skilled in the art. The radical initiator used in step (iii-c) may be any radical initiator as long as the reaction proceeds. In terms of free radical initiators that can be used in the step (iii-c), for example, sulfurous acid, sodium bisulfite, potassium bisulfite, sodium sulfite, potassium sulfite, Rongalite (trade name) (formaldehyde sulfoxylate) sodium dihydrate), etc., but not limited thereto. In this context, the radical initiator is understood to be a reducing agent. Sodium formaldehyde sulfoxylate dihydrate has the same meaning as sodium hydroxymethanesulfinate dihydrate. From the viewpoints of yield, reactivity, availability, price, and ease of handling, Rongalite is a preferred example of the radical generator used in step (iii-c).

The radical initiators of step (iii-c) may be used alone or in combination of two or more in any ratio. The form of the radical generator in step (iii-c) may be any form as long as the reaction proceeds. The form of the free radical initiator in step (iii-c) can be appropriately selected by those skilled in the art. The amount of the radical initiator used in the step (iii-c) may be any amount as long as the reaction proceeds. From the viewpoints of yield, suppression of by-products, and economical efficiency, 0 (zero) to 2.0 moles, preferably 0.01 to 2.0 moles, more preferably 0.1 to 1.5 moles can be exemplified relative to 1 mole of the compound of the general formula (5). Mole range, but the usage amount of the free radical initiator in step (iii-c) can be adjusted appropriately by those skilled in the art. An appropriate radical initiator as described above in the step (iii-c) may also be used as the base in the above-mentioned step (iii-c). The radical initiator of the step (iii-c) and the base of the above-mentioned step (iii-c) may be used in combination.

(solvent for step (iii-c))

The reaction of step (iii-c) is preferably carried out in the presence of a solvent from the viewpoint of smooth progress of the reaction. As the solvent of the step (iii-c), any solvent may be used as long as the reaction of the step (iii-c) proceeds. With regard to the solvent of step (iii-c), for example:

Amides (for example, N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAC), N-methylpyrrolidone (NMP), etc.),

Alkylureas (e.g., N,N'-dimethylimidazolidinone (DMI), etc.),

Sulfoxides (for example, dimethylsulfoxide (DMSO) etc.),

Sulfones (for example, sulfolane, etc.),

Ethers (for example, tetrahydrofuran (THF), 1,4-dioxane, diisopropyl ether, dibutyl ether, di-tert-butyl ether, cyclopentyl methyl ether (CPME), methyl base-tert-butyl ether, 1,2-dimethoxyethane (DME), diglyme, triglyme, etc.),

Ketones (for example, acetone, isobutyl methyl ketone (MIBK), cyclohexanone, etc.),

Carboxylate esters (for example, ethyl acetate, butyl acetate, etc.),

Nitriles (for example, acetonitrile, etc.),

Alcohols (for example, methanol, ethanol, 2-propanol, butanol, etc.),

Aromatic hydrocarbon derivatives (for example, benzene, toluene, xylene, chlorobenzene, dichlorobenzene, trichlorobenzene, nitrobenzene, etc.),

Halogenated aliphatic hydrocarbons (for example, dichloromethane, etc.),

Water and any combination thereof in any proportion, but not limited thereto.

From the viewpoints of reactivity and economical efficiency, preferred examples of solvents in step (iii-c) include amides, sulfoxides, ethers, ketones, nitriles, alcohols, aromatic hydrocarbon derivatives, Species, water, and any combination of them in any proportion. In terms of preferred specific examples of the solvent of step (iii-c), N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAC), N-methylpyrrolidone ( NMP), dimethyl sulfoxide (DMSO), tetrahydrofuran (THF), acetone, isobutyl methyl ketone (MIBK), acetonitrile, methanol, ethanol, 2-propanol, toluene, xylene, chlorobenzene, dichlorobenzene, Water, and any combination of them in any proportion.

The amount of the solvent used in the step (iii-c) 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., the range of 0.01 to 10.0 L (liter), preferably 0.1 to 5.0 L can be exemplified with respect to 1 mol of the compound of the general formula (5). When using a combination of two or more solvents, 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, economical efficiency, etc., -10°C (minus 10°C) to 160°C can be exemplified, preferably 10°C to 120°C.

(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, economical efficiency, etc., 0.5 hours to 48 hours can be exemplified, and the range of 1 hour 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, specific examples of the compound of the general formula (4) obtained in the above-mentioned step (iii-a) can be cited, but not Limited to this.

Example

Next, although an Example is given and this invention is demonstrated concretely, this invention is not limited at all by the said Example.

Example 1

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

To the reaction flask were added 44.32 g (28.0 mmol) of 5-mercapto-2,4-dimethylphenol, 42 mg (0.28 mmol) of sodium iodide, and 80 mL of ethyl acetate. While stirring the mixture at room temperature, 1.59 g (14 mmol) of 30% aqueous hydrogen peroxide was slowly added dropwise thereto. The mixture was stirred at room temperature for 1 hour. 5 mL of saturated aqueous sodium sulfite solution was added to the reaction mixture, and the mixture was stirred at room temperature for 10 minutes, then concentrated hydrochloric acid was added thereto to adjust the pH of the aqueous layer to about pH 1-2. 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, yield 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

Production of bis[2,4-dimethyl-5-(6-trifluoromethylthiohexyloxy)phenyl]disulfide

In the reaction flask, add bis(2,4-dimethyl-5-hydroxyphenyl) disulfide 2.60g (8.5mmol), 1-bromo-6-trifluoromethylthiohexane 4.73g (17.9 mmol), potassium carbonate 2.58g (18.7mmol), tetrabutylammonium iodide 0.63g (1.7mmol) and N,N-dimethylformamide 17mL. The mixture was stirred at 80° C. for 20 hours under nitrogen atmosphere. 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, filtered, and 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, yield 86 %.

¹ H‐NMR (300MHz, 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

Add bis[2,4-dimethyl-5-(6-trifluoromethylthiohexyloxy)phenyl]disulfide 337.4mg (0.50mmol), p-toluenesulfonic acid 2,2, 266.9 mg (1.05 mmol) of 2-trifluoroethyl ester, 152.0 mg (1.10 mmol) of potassium carbonate, 231.2 mg (1.50 mmol) of Rongalite (trade name) (sodium formaldehyde sulfoxylate dihydrate) and N,N-dimethyl 2 mL of methyl formamide. The mixture was stirred at 50 °C under nitrogen atmosphere for 16 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 242.0 mg of 6-trifluoromethylthiohexyl-[2,4-dimethyl-5-(2,2,2-trifluoroethylthio) 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

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 to the reaction flask. 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)thiophenol, yield 52%.

¹ H‐NMR (300MHz, 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, 2,2,2-trifluoro-toluenesulfonic acid were added to the reaction flask Ethyl ester 138.8mg (0.55mmol), potassium carbonate 79.1mg (0.57mmol), Rongalite (trade name) (sodium formaldehyde sulfoxylate dihydrate) 40.1mg (0.26mmol) and N,N-dimethylformamide 2mL . The mixture was stirred at 50° C. for 15 hours under nitrogen atmosphere. 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-trifluoroethylthio) Phenyl] ether, yield 86%.

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

Production 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% aqueous hydrogen peroxide was slowly added dropwise thereto. The mixture was stirred at room temperature for 1 hour. After filtering the reaction mixture, the filtrate was washed with water and dried to obtain 39.9 mg of bis(2-chloro-4-fluoro-5-hydroxyphenyl) disulfide, a yield of 90%.

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

Melting point: 160°C

Example 7

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

Add 177.6 mg (0.50 mmol) of bis(2-chloro-4-fluoro-5-hydroxyphenyl) disulfide, 263.7 mg (1.05 mmol) of 1-bromo-5-trifluoromethylthiopentane into the reaction flask ), potassium carbonate 152.0mg (1.10mmol), and N,N-dimethylformamide 1mL. The mixture was stirred at 50° C. for 15 hours under nitrogen atmosphere. 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=7.2Hz,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

Add bis[2-chloro-4-fluoro-5-(5-trifluoromethylthiopentyloxy)phenyl] disulfide 277.0mg (0.40mmol), p-toluenesulfonic acid 2, 2,2-trifluoroethyl ester 213.5mg (0.84mmol), potassium carbonate 121.6mg (0.88mmol), Rongalite (trade name) (sodium formaldehyde sulfoxylate dihydrate) 184.9mg (1.20mmol), water 72.0mg ( 4.0mmol) and N,N-dimethylformamide 1mL. The mixture was stirred at 50° C. for 12 hours under nitrogen atmosphere. 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 306.0 mg of 5-trifluoromethylthiopentyl-[4-chloro-2-fluoro-5-(2,2,2-trifluoroethylthio ) 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

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 flask. 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. Then, the mixture was stirred under ice cooling for 3 hours. Diluted hydrochloric acid and water were added to the obtained reaction mixture, and it was partitioned into toluene and water to obtain a toluene layer containing 6-bromohexyl acetate. The obtained toluene layer containing 6-bromohexyl acetate was used for the next reaction.

(2) Manufacture of 6-cyanthiohexyl acetate

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 to the reaction flask . Then, 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, the toluene was distilled off under reduced pressure to obtain 6-thiocyanatohexyl acetate. The obtained 6-thiocyanatohexyl acetate was used in the next reaction without purification.

¹ H-NMR (300MHz, CDCl ₃ ) δ (ppm): 4.07(t, J=6.6Hz, 2H), 2.96(t, J=6.9Hz, 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

The entire amount of 6-thiocyanatohexyl acetate obtained in (2), 25.60 g (180 mmol) of trifluoromethyltrimethylsilane, and 90 mL of tetrahydrofuran were added to the reaction flask. Next, 9 mL of tetrabutylammonium fluoride (1 mol/L tetrahydrofuran solution) was added dropwise to the mixture while stirring under ice-cooling. Then, 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, the diethyl ether layer was dried over anhydrous magnesium sulfate, and after filtration, the 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 (300MHz, CDCl ₃ )δ(ppm): 4.06(t, J=6.6Hz, 2H), 2.88(t, J=7.2Hz, 2H), 2.05(s, 3H), 1.67(m, 4H),1.41(m,4H).

(4) Production of 6-trifluoromethylthiohexan-1-ol

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 to the reaction flask. Then, 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, partitioned into diethyl ether and water, and the diethyl ether layer was separated. Next, the diethyl ether layer was dried over anhydrous magnesium sulfate, filtered, and diethyl ether was distilled off under reduced pressure to obtain 6-trifluoromethylthiohexan-1-ol. The obtained 6-trifluoromethylthiohexan-1-ol 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) Production of 1-bromo-6-trifluoromethylthiohexane

Add the whole amount of 6-trifluoromethylthiohexan-1-alcohol obtained in (4), 45.51 g (270 mmol) of 48% hydrogen bromide and 2.90 g (9.0 mmol) of tetrabutylammonium bromide in the flask. mmol). Then, the mixture was stirred at 130°C for 4 hours. Dichloromethane and water were added to the obtained reaction mixture, 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-trifluoromethylthiohexane. The yield for 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

Manufacture of 5-mercapto-2,4-dimethylphenol

(1) Production of 2,4-dimethylphenyl methanesulfonate

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 to the reaction flask. 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 complete, the mixture was stirred at room temperature for 1 hour. Water was added to the obtained reaction mixture, partitioned into dichloromethane and water, and the dichloromethane layer was separated. Next, the dichloromethane layer was dried with anhydrous magnesium sulfate, and after filtration, the dichloromethane was distilled off under reduced pressure to obtain 19.78 g of 2,4-dimethylphenyl mesylate, yield 99%.

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

(2) Production of 5-chlorosulfonyl-2,4-dimethylphenyl methanesulfonate

5.91 g (22.2 mmol) of 30% oleum and 10 mL of dichloromethane were added to the reaction flask. Next, a solution obtained by dissolving 4.35 g (21.7 mmol) of 2,4-dimethylphenylmethanesulfonate in 12 mL of dichloromethane was added dropwise to the mixture while stirring in an ice-cooled state. After the dropwise addition was completed, 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. Next, the mixture was stirred at 50°C for 3 hours. The obtained reaction mixture was added dropwise to ice water, 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-dimethylphenyl methanesulfonate, a yield of 87%.

¹ H-NMR (300MHz, 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) Production of 5-mercapto-2,4-dimethylphenyl methanesulfonate

610.0 mg (2.0 mmol) of 5-chlorosulfonyl-2,4-dimethylphenyl mesylate, 2 mL of 18% hydrochloric acid, and 2 mL of methanol were added to the reaction flask. Next, 484.8 mg (4.1 mmol) of tin powder was added while stirring the mixture at room temperature. Then, 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, 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-dimethylphenyl methanesulfonate in a yield of 84%.

¹ H-NMR (300MHz, 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) Production of 5-mercapto-2,4-dimethylphenol

2.32 g (10.0 mmol) of 5-mercapto-2,4-dimethylphenyl mesylate, 4.00 g (100.0 mmol) of sodium hydroxide, and 15 mL of water were added to the reaction flask. Then, 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, dichloromethane was added there, 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 1.48 g of 5-mercapto-2,4-dimethylphenol (yield: 96%).

¹ H-NMR (300MHz, 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

Production of 1-bromo-5-trifluoromethylthiopentane

(1) Manufacture of 5-bromopentyl acetate

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 to the reaction flask. To 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. Then, the mixture was stirred under ice cooling for 2 hours. Diluted hydrochloric acid and water were added to the obtained reaction mixture, and it was partitioned into toluene and water to obtain a toluene layer containing 5-bromopentyl acetate. The toluene layer containing the obtained 5-bromopentyl acetate was used for the next reaction.

(2) Manufacture of 5-cyanothiopentyl acetate

The entire amount of the 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 to the reaction flask. Then, 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, the toluene was distilled off under reduced pressure to obtain 5-thiocyanatopentyl acetate. The obtained 5-thiocyanatopentyl acetate was used in the next reaction without purification.

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

(3) Manufacture of 5-trifluoromethylthiopentyl acetate

The entire amount of 5-thiocyanatopentyl acetate obtained in (2), 25.81 g (181.5 mmol) of trifluoromethyltrimethylsilane, and 100 mL of tetrahydrofuran were added to the reaction flask. Next, 12 mL of tetrabutylammonium fluoride (1 mol/L tetrahydrofuran solution) was added dropwise to the mixture while stirring under ice-cooling. Then, 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, 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, the diethyl ether was distilled off under reduced pressure to obtain 5-trifluoromethylthiopentyl acetate. The obtained 5-trifluoromethylthiopentyl 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) Production of 5-trifluoromethylthiopentan-1-ol

The entire amount of 5-trifluoromethylthiopentyl acetate obtained in (3), 15.93 g (115.3 mmol) of potassium carbonate, and 100 mL of methanol were added to the reaction flask. Then, 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, 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, the diethyl ether was distilled off under reduced pressure to obtain 5-trifluoromethylthiopentan-1-ol. The obtained 5-trifluoromethylthiopentan-1-ol was used in the next reaction without purification.

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

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

The entire amount of 5-trifluoromethylthiopentan-1-ol obtained in (4) and 53.12 g (315 mmol) of 48% hydrobromic acid were added to the reaction flask. Then, the mixture was stirred at 140°C for 6 hours. Dichloromethane and water were added to the obtained reaction mixture, 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 for 5 steps was 46%.

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

Reference example 4

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

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

6.67 g (25.0 mmol) of 30% oleum and 2.5 mL of dichloromethane were added to the reaction flask. Next, a solution in which 732.8 mg (5.0 mmol) of 4-chloro-2-fluorophenol was dissolved in 2.5 mL of dichloromethane was added dropwise to the mixture while stirring at room temperature. After the dropwise addition was complete, the mixture was stirred at room temperature for 1 hour. Then, 5.95 g (50.0 mmol) of thionyl chloride was added to the mixture. Next, the mixture was stirred at 50°C for 1 hour. The obtained reaction mixture was dropped into ice water, and 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 (yield 77%).

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

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

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 to the reaction flask. Next, 237.4 mg (2.0 mmol) of tin powder was added while stirring the mixture at room temperature. Then, 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, 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 (yield 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-trifluoroethylsulfinyl)phenyl]ether

86.2mg (0.20mmol ) and dichloromethane 2mL. 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. 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-trifluoroethylsulfinyl Acyl) phenyl] ether, yield 76%.

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).

The measurement of each physical property in this specification, an Example, and a reference example used 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 standard substance: tetramethylsilane

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

(High performance liquid chromatography (HPLC) analysis method)

Regarding the HPLC analysis method, the following literature can be referred to as necessary.

(Company) The Chemical Society of Japan, "New Experimental Chemistry Lecture 9 Analytical Chemistry II", pp. 86-112 (1977), publisher Shingo Iizumi, Maruzen Co., Ltd. (for example, about packing agents that can be used in columns - For the combination of mobile phases, please refer to pages 93-96).

(Company) Edited by the Chemical Society of Japan, "Experimental Chemistry Lecture 20-1 Analytical Chemistry" 5th edition, pp. 130-151 (2007), publisher Seishiro Murata, Maruzen Co., Ltd. (for example, about reversed-phase chromatography Please refer to pages 135-137 for the specific usage methods and conditions of the analysis).

(Gas chromatography (GC) analysis method)

Regarding the GC analysis method, the following literature can be referred to as necessary.

(Company) The Chemical Society of Japan, "New Experimental Chemistry Lecture 9 Analytical Chemistry II", pp. 60-86 (1977), publisher Shingo Iizumi, Maruzen Co., Ltd. (for example, about stationary phases that can be used in columns liquid, see page 66).

(Company) Edited by the Chemical Society of Japan, "Experimental Chemistry Lecture 20-1 Analytical Chemistry" 5th edition, pp. 121-129 (2007), publisher Seishiro Murata, Maruzen Co., Ltd. (for example, about hollow capillary separation tubes For the specific usage of the column, please refer to pages 124-125).

(measurement method of pH)

pH is measured by a glass electrode hydrogen ion concentration indicator. As the glass electrode type hydrogen ion concentration indicator, for example, DKK-TOA Co., Ltd. product, format: HM-20P can be used.

Industrial availability

According to the present invention, a novel production method and a novel production intermediate of the general formula (4) used as pest control agents such as pesticides and production intermediates thereof can be provided.

Therefore, the present invention is economical, beneficial to environmental protection, and has high industrial application value.

Claims (30)

1. A compound represented by general formula (2), In the formula, R ¹ and R ² are each independently a halogen atom or a C1-C4 alkyl group. 2. The compound according to 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. 3. The compound according to claim 1, wherein, R1 is ^a fluorine atom, R2 is a chlorine atom ^; or R ¹ and R ² are each methyl. 4. The compound according to claim 1, wherein R ¹ and R ² are each independently a halogen atom. 5. The compound according to claim 1, wherein R ¹ is a fluorine atom, and R ² is a chlorine atom. 6. The compound according to claim 1, wherein R ¹ and R ² are each independently C1-C4 alkyl. 7. The compound of claim 1, wherein R ¹ and R ² are each methyl. 8. A compound represented by general formula (3), 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 C2-C10 alkyl group. 9. The compound according to claim 8, wherein, R ¹ and R ² are each independently a halogen atom, R ³ is C1～C4 haloalkylthio C2～C10 alkyl; or R ¹ and R ² are each independently a C1-C4 alkyl group, R ³ is a C1-C4 haloalkylthio C2-C10 alkyl group. 10. The compound according to claim 8, 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 methyl, R ³ is 6-trifluoromethylthiohexyl. 11. The compound according to claim 8, wherein, R ¹ and R ² are each independently a halogen atom, R ³ is a C1-C4 haloalkylthio C2-C10 alkyl group. 12. The compound according to claim 8, wherein, R ¹ is a fluorine atom, R ² is a chlorine atom, R ³ is 5-trifluoromethylthiopentyl. 13. The compound according to claim 8, wherein, R ¹ and R ² are each independently a C1-C4 alkyl group, R ³ is a C1-C4 haloalkylthio C2-C10 alkyl group. 14. The compound according to claim 8, wherein, R ¹ and R ² are each methyl, R ³ is 6-trifluoromethylthiohexyl. 15. A compound represented by general formula (5), 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 C2-C10 alkyl group. 16. The compound according to claim 15, wherein R ¹ and R ² are each independently a halogen atom, R ³ is C1～C4 haloalkylthio C2～C10 alkyl; or R ¹ and R ² are each independently a C1-C4 alkyl group, R ³ is a C1-C4 haloalkylthio C2-C10 alkyl group. 17. The compound according to claim 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 methyl, R ³ is 6-trifluoromethylthiohexyl. 18. The compound of claim 15, wherein, R ¹ and R ² are each independently a halogen atom, R ³ is a C1-C4 haloalkylthio C2-C10 alkyl group. 19. The compound of claim 15, wherein, R ¹ is a fluorine atom, R ² is a chlorine atom, R ³ is 5-trifluoromethylthiopentyl. 20. The compound of claim 15, wherein, R ¹ and R ² are each independently a C1-C4 alkyl group, R ³ is a C1-C4 haloalkylthio C2-C10 alkyl group. 21. The compound of claim 15, wherein, R ¹ and R ² are each methyl, R ³ is 6-trifluoromethylthiohexyl. 22. A method for producing a compound represented by 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 C1～C4 haloalkylthio C2～C10 alkyl, R ⁴ is C1～C4 haloalkyl, The method comprises the following steps: (i) a step of producing a compound represented by general formula (2) from a compound represented by 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) reacting the compound represented by the general formula (2) with the compound represented by the general formula (a) in the presence of a base to produce a compound represented by the general formula (3), R ³ -X (a) In the formula, ^R3 is as defined above, X is a halogen atom, a C1-C4 alkylsulfonyloxy group, a C1-C4 haloalkylsulfonyloxy group, or a phenylsulfonyloxy group that may be substituted by a C1-C4 alkyl group or a halogen atom, In the formula, R ¹ and 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 general formula (4). 23. The method of claim 22, wherein, Step (iii) is the following steps: (iii-a) By reacting the compound represented by the general formula (3) with the compound represented by the general formula (b) in the presence of a base, the compound of the general formula (3) is converted into the compound of the general formula (4) the compound step, In the formula, R ¹ and R ² are each independently a halogen atom or a C1-C4 alkyl group, R ³ is C1～C4 haloalkylthio C2～C10 alkyl, R ⁴ -Y (b) In the formula, R ⁴ is C1～C4 haloalkyl, Y is a halogen atom, a C1-C4 alkylsulfonyloxy group, a C1-C4 haloalkylsulfonyloxy group, or a phenylsulfonyloxy group which may be substituted by a C1-C4 alkyl group or a halogen atom. 24. The method of claim 22, wherein step (iii) comprises the steps of: (iii-b) a step of converting the 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-C4 alkyl group, R ³ is C1～C4 haloalkylthio C2～C10 alkyl, In the formula, R ¹ , R ² and R ³ are as defined above; and (iii-c) converting the compound of the general formula (5) into the compound of the general formula (4) by reacting the compound of the general formula (5) with a compound represented by the general formula (b) in the presence of a base the compound step, R ⁴ -Y (b) In the formula, R ⁴ is C1～C4 haloalkyl, Y is a halogen atom, a C1-C4 alkylsulfonyloxy group, a C1-C4 haloalkylsulfonyloxy group, or a phenylsulfonyloxy group which may be substituted by a C1-C4 alkyl group or a halogen atom. 25. The method of claim 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-C4 alkyl group. 26. The method of claim 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 a chlorine atom, a bromine atom, an iodine atom, methanesulfonyloxy, benzenesulfonyloxy, p-toluenesulfonyloxy or p-chlorobenzenesulfonyloxy, Y is a chlorine atom, a bromine atom, an iodine atom, methanesulfonyloxy, benzenesulfonyloxy, p-toluenesulfonyloxy or p-chlorobenzenesulfonyloxy; or R ¹ and R ² are each methyl, R ³ is 6-trifluoromethylthiohexyl, R ⁴ is 2,2,2-trifluoroethyl, X is a chlorine atom, a bromine atom, an iodine atom, methanesulfonyloxy, benzenesulfonyloxy, p-toluenesulfonyloxy or p-chlorobenzenesulfonyloxy, Y is a chlorine atom, a bromine atom, an iodine atom, methanesulfonyloxy, benzenesulfonyloxy, p-toluenesulfonyloxy or p-chlorobenzenesulfonyloxy. 27. The method according to claim 23 or 24, wherein R ¹ and R ² are each independently a halogen atom. 28. The method of claim 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 a chlorine atom, a bromine atom, an iodine atom, methanesulfonyloxy, benzenesulfonyloxy, p-toluenesulfonyloxy or p-chlorobenzenesulfonyloxy, Y is a chlorine atom, a bromine atom, an iodine atom, methanesulfonyloxy, benzenesulfonyloxy, p-toluenesulfonyloxy or p-chlorobenzenesulfonyloxy. 29. The method according to claim 23 or 24, wherein R ¹ and R ² are each independently C1-C4 alkyl. 30. The method of claim 23 or 24, wherein, R ¹ and R ² are each methyl, R ³ is 6-trifluoromethylthiohexyl, R ⁴ is 2,2,2-trifluoroethyl, X is a chlorine atom, a bromine atom, an iodine atom, methanesulfonyloxy, benzenesulfonyloxy, p-toluenesulfonyloxy or p-chlorobenzenesulfonyloxy, Y is a chlorine atom, a bromine atom, an iodine atom, methanesulfonyloxy, benzenesulfonyloxy, p-toluenesulfonyloxy or p-chlorobenzenesulfonyloxy.