WO2015060402A1

WO2015060402A1 - Production method for trifluoromethanesulfonanilide compound

Info

Publication number: WO2015060402A1
Application number: PCT/JP2014/078254
Authority: WO
Inventors: 義之楠岡; 明星　知宏; 知明井尾; 中村　大輔
Original assignee: 日産化学工業株式会社
Priority date: 2013-10-25
Filing date: 2014-10-23
Publication date: 2015-04-30
Also published as: JP6512104B2; JPWO2015060402A1

Abstract

　Provided are a novel production method for trifluoromethanesulfonanilides, which are useful as herbicides, etc., and intermediates therefor.　Specifically provided are: an industrially-useful production method for producing a trifluoromethanesulfonanilide compound represented by formula (2) (therein, A represents -CH=CH- or a sulfur atom, R¹ represents a hydrogen atom or a C_1-12 alkoxycarbonyl, and Q represents an alkoxyalkyl, an alkoxycarbonyl, a cyano, an aminomethylene, etc.) using an oxidizing agent; a trifluoromethanesulfinyl compound useful as an intermediate therefor; and a production method for the trifluoromethanesulfinyl compound.

Description

Process for producing trifluoromethanesulfonanilide compound

The present invention relates to a method for producing a trifluoromethanesulfonanilide compound useful as an intermediate for producing pharmaceuticals and agricultural chemicals, a trifluoromethanesulfine anilide compound useful as an intermediate thereof, and a method for producing the same.

Certain trifluoromethanesulfonanilide compounds are known to have herbicidal activity (see, for example, Patent Documents 1 and 2), and some methods for producing trifluoromethanesulfonanilide are also known (for example, patents). Reference 1-7). On the other hand, some methods for producing a trifluoromethanesulfinanilide compound are also known (see, for example, Patent Document 3, Non-Patent Documents 1 and 2).
As a method for synthesizing an N-benzyl lactam compound that can be an intermediate of a trifluoromethanesulfonanilide compound, for example, a method of condensing a benzyl halide compound and a lactam compound as in Patent Documents 8 to 10 is known.

International Publication No. 2010/026989 International Publication No. 2010/119906 Japanese Unexamined Patent Publication No. 10-218857 Japanese Patent Laid-Open No. 9-286771 U.S. Pat. No. 4,380,464 U.S. Pat. No. 4,321,663 US Pat. No. 3,639,474 International Publication No. 2004/094375 International Publication No. 2003/078394 Japanese Unexamined Patent Publication No. 2011-037746

Regarding the method for producing a trifluoromethanesulfonanilide compound, Patent Documents 1, 2, 5, 6 and 7 disclose production methods using a trifluoromethanesulfonylating agent. However, an expensive trifluoromethanesulfonic acid anhydride, trifluoromethane is disclosed. Only a production method using sulfonyl chloride, trifluoromethanesulfonyl fluoride or the like as a trifluoromethanesulfonylating agent is disclosed. Patent Document 3 describes that magnesium monoperoxyphthalate or m-chloroperbenzoic acid is used as an oxidizing agent to produce a corresponding trifluoromethanesulfonanilide compound from a certain trifluoromethanesulfinanilide compound. However, there is no disclosure regarding the trifluoromethanesulfinanilide compound according to the present invention.

In addition, the method for producing the trifluoromethanesulfinanilide compound is described in Non-Patent Documents 1 and 2, but 2 equivalents of sodium trifluoromethanesulfinate are used for 1 equivalent of the starting aniline compound, Only examples in which sodium trifluoromethanesulfinate is used in an excessive amount relative to the starting aniline compound are known, and there is no disclosure regarding the trifluoromethanesulfinanilide compound according to the present invention.

As for the method for producing the N-benzyl lactam compound, when producing the N-benzyl lactam compound according to the methods described in Patent Documents 8 and 9, sodium hydride and hexamethyldisilazane lithium, which are water-absorbing reagents, are used. Since it needs to be used, there are problems in terms of handling method and safety as an industrial production method. In the case of producing an N-benzyl lactam compound according to Patent Document 10, since heating is performed in the presence of an acid, it cannot be applied to a raw material or product that is weak against an acid.

As a result of intensive studies to solve the above problems, the inventor of the present invention industrially relates to a trifluoromethanesulfonilide compound which is advantageous as an industrial production intermediate of a trifluoromethanesulfonanilide compound, a method for producing the compound, and a trifluoromethanesulfonanilide compound. I found a useful production method.

Further, the inventors have found a method for synthesizing an N-benzyl lactam compound by reacting a benzyl halide compound and a lactam compound, which are available as industrial raw materials, in the presence of a base that is easy to handle. In addition, the inventors have found a method of synthesizing an N-benzyl lactam compound by subjecting a benzyl halide compound and an amide compound to a condensation reaction under the same conditions, followed by an intramolecular cyclization reaction, thereby completing the present invention.

The gist of the present invention is the following [1] to [30].
[1] Formula (1):

[In the formula, A represents —CH═CH— or a sulfur atom,
R ¹ represents a hydrogen atom or C ₁ -C ₁₂ alkoxycarbonyl,
Q represents CH ₂ OR ² , C (═O) OR ² , cyano, or CH ₂ N (Q ¹ ) Q ² ,
R ² represents a hydrogen atom or C ₁ -C ₆ alkyl,
Q ¹ and Q ² are each independently a hydrogen atom, C ₁ -C ₁₂ alkyl, C ₁ -C ₁₂ alkoxy, halo (C ₁ -C ₁₂ ) alkyl, halo (C ₁ -C ₁₂ ) alkoxy, C ₃ -C ₈ cycloalkyl, C ₁ -C ₁₂ alkylcarbonyl, C ₁ -C ₁₂ alkoxycarbonyl, halo (C ₁ -C ₁₂ ) alkylcarbonyl, halo (C ₁ -C ₁₂ ) alkoxycarbonyl, C ₃ -C ₈ cyclo Alkylcarbonyl, phenyl, phenyl substituted by (Y) _n , phenylcarbonyl, phenylcarbonyl substituted by (Y) _m , C ₁ -C ₆ alkoxy (C ₁ -C ₆ ) alkyl, C ₁ -C ₆ alkylthio _{_(C} 1 ~ _C ₆₎ _alkyl, _C 1 ~ C ₆ alkylsulfinyl _{_(C} 1 ~ C ₆₎ _alkyl, _C 1 ~ C ₆ Alkylsulfonyl _{_(C} 1 ~ C ₆₎ _alkyl, _C 1 ~ C ₆ alkoxy _{_(C} 1 ~ C ₆₎ _{alkylcarbonyl,} _C 1 ~ C ₆ alkylthio _{_(C} 1 ~ C ₆₎ _{alkylcarbonyl,} _C 1 ~ C ₆ alkylsulfinyl Represents (C ₁ -C ₆ ) alkylcarbonyl or C ₁ -C ₆ alkylsulfonyl (C ₁ -C ₆ ) alkylcarbonyl,
Y represents a halogen atom,
n represents an integer of 1, 2, 3, 4 or 5;
m represents an integer of 1, 2, 3, 4 or 5. Wherein the trifluoromethanesulfinanilide compound represented by the formula (2) is reacted with an oxidizing agent:

[Wherein, A, R ¹ and Q represent the same meaning as described above] A method for producing a trifluoromethanesulfonanilide compound represented by the formula:

[2] A represents —CH═CH—,
R ¹ represents a hydrogen atom or C ₁ -C ₆ alkoxycarbonyl,
Q ¹ and Q ² are each independently a hydrogen atom, C ₁ -C ₁₂ alkyl, halo (C ₁ -C ₁₂ ) alkyl, C ₁ -C ₁₂ alkylcarbonyl, halo (C ₁ -C ₁₂ ) alkylcarbonyl, The method for producing a trifluoromethanesulfonanilide compound according to the above [1], which represents phenyl, phenyl substituted by (Y) _n , phenylcarbonyl or phenylcarbonyl substituted by (Y) _m .

[3] Production of the trifluoromethanesulfonanilide compound according to [1] or [2] above, wherein the oxidizing agent is one selected from the group consisting of peracids, iodine peroxides, persulfates, and hydroperoxides. Method.
[4] The trifluoromethanesulfone according to the above [3], wherein the oxidizing agent is one selected from the group consisting of m-chloroperbenzoic acid, magnesium monoperoxyphthalate, sodium periodate and hydrogen peroxide. A method for producing an anilide compound.
[5] The method for producing a trifluoromethanesulfonanilide compound according to the above [4], wherein the oxidizing agent is sodium periodate and the reaction is performed in the presence of ruthenium trichloride.
[6] The method for producing a trifluoromethanesulfonanilide compound according to the above [4], wherein the oxidizing agent is hydrogen peroxide solution and is performed in the presence of sodium tungstate and / or a phase transfer catalyst.
[7] The method for producing a trifluoromethanesulfonanilide compound according to [6] above, wherein the phase transfer catalyst is a quaternary ammonium salt.
[8] Formula (3):

[In the formula, A represents —CH═CH— or a sulfur atom,
R ¹ represents a hydrogen atom or C ₁ -C ₁₂ alkoxycarbonyl,
Q represents CH ₂ OR ² , C (═O) OR ² , cyano, or CH ₂ N (Q ¹ ) Q ² ,
R ² represents a hydrogen atom or C ₁ -C ₆ alkyl,
Q ¹ and Q ² are each independently a hydrogen atom, C ₁ -C ₁₂ alkyl, C ₁ -C ₁₂ alkoxy, halo (C ₁ -C ₁₂ ) alkyl, halo (C ₁ -C ₁₂ ) alkoxy, C ₃ -C ₈ cycloalkyl, C ₁ -C ₁₂ alkylcarbonyl, C ₁ -C ₁₂ alkoxycarbonyl, halo (C ₁ -C ₁₂ ) alkylcarbonyl, halo (C ₁ -C ₁₂ ) alkoxycarbonyl, C ₃ -C ₈ cyclo Alkylcarbonyl, phenyl, phenyl substituted by (Y) _n , phenylcarbonyl, phenylcarbonyl substituted by (Y) _m , C ₁ -C ₆ alkoxy (C ₁ -C ₆ ) alkyl, C ₁ -C ₆ alkylthio _{_(C} 1 ~ _C ₆₎ _alkyl, _C 1 ~ C ₆ alkylsulfinyl _{_(C} 1 ~ C ₆₎ _alkyl, _C 1 ~ C ₆ Alkylsulfonyl _{_(C} 1 ~ C ₆₎ _alkyl, _C 1 ~ C ₆ alkoxy _{_(C} 1 ~ C ₆₎ _{alkylcarbonyl,} _C 1 ~ C ₆ alkylthio _{_(C} 1 ~ C ₆₎ _{alkylcarbonyl,} _C 1 ~ C ₆ alkylsulfinyl Represents (C ₁ -C ₆ ) alkylcarbonyl or C ₁ -C ₆ alkylsulfonyl (C ₁ -C ₆ ) alkylcarbonyl,
Y represents a halogen atom,
n represents an integer of 1, 2, 3, 4 or 5;
m represents an integer of 1, 2, 3, 4 or 5, and an amine compound represented by the formula (4):

[Wherein X represents a halogen atom. A compound represented by formula (1):

[Wherein, A, R ¹ and Q represent the same meaning as described above] A method for producing a trifluoromethanesulfine anilide compound represented by the formula:

[9] A represents —CH═CH—,
R ¹ represents a hydrogen atom or C ₁ -C ₆ alkoxycarbonyl,
Q ¹ and Q ² are each independently a hydrogen atom, C ₁ -C ₁₂ alkyl, halo (C ₁ -C ₁₂ ) alkyl, C ₁ -C ₁₂ alkylcarbonyl, halo (C ₁ -C ₁₂ ) alkylcarbonyl, The method for producing a trifluoromethanesulfinanilide compound according to [8] above, which represents phenyl, phenyl substituted by (Y) _n , phenylcarbonyl or phenylcarbonyl substituted by (Y) _m .

[10] The method for producing a trifluoromethanesulfinanilide compound according to [8] or [9], wherein the reaction is performed in the presence of a base.

[11] Formula (5):

[Wherein M represents sodium or potassium. The compound represented by formula (4) is produced by reacting the compound represented by formula (4) with the halogenating agent, and the produced compound represented by formula (4) is used. Or the manufacturing method of the trifluoromethanesulfine anilide compound as described in [10].

[12] The process for producing a trifluoromethanesulfinanilide compound according to [11] above, wherein the halogenating agent is thionyl chloride.

[13] Formula (1):

[In the formula, A represents —CH═CH— or a sulfur atom,
R ¹ represents a hydrogen atom or C ₁ -C ₁₂ alkoxycarbonyl,
Q represents CH ₂ OR ² , C (═O) OR ² , cyano, or CH ₂ N (Q ¹ ) Q ² ,
R ² represents a hydrogen atom or C ₁ -C ₆ alkyl,
Q ¹ and Q ² are each independently a hydrogen atom, C ₁ -C ₁₂ alkyl, C ₁ -C ₁₂ alkoxy, halo (C ₁ -C ₁₂ ) alkyl, halo (C ₁ -C ₁₂ ) alkoxy, C ₃ -C ₈ cycloalkyl, C ₁ -C ₁₂ alkylcarbonyl, C ₁ -C ₁₂ alkoxycarbonyl, halo (C ₁ -C ₁₂ ) alkylcarbonyl, halo (C ₁ -C ₁₂ ) alkoxycarbonyl, C ₃ -C ₈ cyclo Alkylcarbonyl, phenyl, phenyl substituted by (Y) _n , phenylcarbonyl, phenylcarbonyl substituted by (Y) _m , C ₁ -C ₆ alkoxy (C ₁ -C ₆ ) alkyl, C ₁ -C ₆ alkylthio _{_(C} 1 ~ _C ₆₎ _alkyl, _C 1 ~ C ₆ alkylsulfinyl _{_(C} 1 ~ C ₆₎ _alkyl, _C 1 ~ C ₆ Alkylsulfonyl _{_(C} 1 ~ C ₆₎ _alkyl, _C 1 ~ C ₆ alkoxy _{_(C} 1 ~ C ₆₎ _{alkylcarbonyl,} _C 1 ~ C ₆ alkylthio _{_(C} 1 ~ C ₆₎ _{alkylcarbonyl,} _C 1 ~ C ₆ alkylsulfinyl Represents (C ₁ -C ₆ ) alkylcarbonyl or C ₁ -C ₆ alkylsulfonyl (C ₁ -C ₆ ) alkylcarbonyl,
Y represents a halogen atom,
n represents an integer of 1, 2, 3, 4 or 5;
m represents an integer of 1, 2, 3, 4 or 5.] A trifluoromethanesulfinanilide compound or a salt thereof.

[14] A represents —CH═CH—,
R ¹ represents a hydrogen atom or C ₁ -C ₆ alkoxycarbonyl,
Q ¹ and Q ² are each a hydrogen atom, C ₁ -C ₁₂ alkyl, halo (C ₁ -C ₁₂ ) alkyl, C ₁ -C ₁₂ alkylcarbonyl, halo (C ₁ -C ₁₂ ) alkylcarbonyl, phenyl, (Y The trifluoromethanesulfinanilide compound or a salt thereof according to the above [13], which represents phenyl substituted by _n , phenylcarbonyl, or phenylcarbonyl substituted by (Y) _m .

[15] Formula (6):

[R ¹ represents a hydrogen atom or C ₁ -C ₆ alkoxycarbonyl;
Q ¹ and Q ² are each independently halo (C ₁ -C ₁₂ ) alkylcarbonyl, halo (C ₁ -C ₁₂ ) alkoxycarbonyl, C ₁ -C ₆ alkoxy (C ₁ -C ₆ ) alkylcarbonyl, C It represents a ₁ ~ _{C 6} alkylthio _{_(C} 1 ~ C ₆₎ _{alkylcarbonyl,} _C 1 ~ C ₆ alkylsulfinyl _{_(C} 1 ~ C ₆₎ alkylcarbonyl or _C 1 ~ _{C 6} alkylsulfonyl _{_(C} 1 ~ C ₆₎ alkylcarbonyl ] The trifluoromethanesulfonamide compound represented by these, or its salt.

[16] Formula (7):

[R ¹ represents a hydrogen atom or C ₁ -C ₆ alkoxycarbonyl;
Q ¹ is halo (C ₁ -C ₁₂ ) alkylcarbonyl, halo (C ₁ -C ₁₂ ) alkoxycarbonyl, C ₁ -C ₆ alkoxy (C ₁ -C ₆ ) alkylcarbonyl, C ₁ -C ₆ alkylthio (C ₁ -C ₆ ) alkylcarbonyl, C ₁ -C ₆ alkylsulfinyl (C ₁ -C ₆ ) alkylcarbonyl or C ₁ -C ₆ alkylsulfonyl (C ₁ -C ₆ ) represents alkylcarbonyl] Amine compounds.

[17] Formula (8):

[In the formula, A represents —CH═CH— or a sulfur atom,
X ¹ represents a halogen atom, methanesulfonyloxy, trifluoromethanesulfonyloxy or p-toluenesulfonyloxy,
Y represents —NO ₂ , —NH ₂ , —NHCO ₂ R ¹ , —NHSOR ¹ or —NHSO ₂ R ¹ ;
R ¹ represents C ₁ -C ₆ haloalkyl or C ₁ -C ₆ alkyl. A benzyl compound represented by formula (9):

[Wherein R ² represents a hydrogen atom, a halogen atom, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ alkoxy or C ₁ -C ₆ alkyl,
R ³ represents a hydrogen atom, a halogen atom, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ alkoxy or C ₁ -C ₆ alkyl, and R ² and R ³ together with the carbon atom to which each is attached together with C ₃ -C ₆ cycloalkyl may be formed,
R ⁴ represents a hydrogen atom, a halogen atom, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ alkoxy or C ₁ -C ₆ alkyl,
R ⁵ represents a hydrogen atom, a halogen atom, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ alkoxy or C ₁ -C ₆ alkyl, and R ⁴ and R ⁵ together with the carbon atom to which each is bonded together, C ₃ -C ₆ cycloalkyl may be formed,
n represents an integer of 0, 1, 2, or 3. Wherein the lactam compound represented by the formula (10) is reacted in the presence of a base:

[Wherein, A, Y, R ¹ , R ² , R ³ , R ⁴ , R ⁵ and n represent the same meaning as described above. ] The manufacturing method of the N-benzyl lactam compound represented by this.

[18] Formula (8):

[In the formula, A represents —CH═CH— or a sulfur atom,
X ¹ represents a halogen atom, methanesulfonyloxy, trifluoromethanesulfonyloxy or p-toluenesulfonyloxy,
Y represents —NO ₂ , —NH ₂ , —NHCO ₂ R ¹ , —NHSOR ¹ or —NHSO ₂ R ¹ ;
R ¹ represents C ₁ -C ₆ haloalkyl or C ₁ -C ₆ alkyl. A benzyl compound represented by formula (11):

[Wherein R ² represents a hydrogen atom, a halogen atom, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ alkoxy or C ₁ -C ₆ alkyl,
R ³ represents a hydrogen atom, a halogen atom, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ alkoxy or C ₁ -C ₆ alkyl, and R ² and R ³ together with the carbon atom to which each is attached together with C ₃ -C ₆ cycloalkyl may be formed,
R ⁴ represents a hydrogen atom, a halogen atom, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ alkoxy or C ₁ -C ₆ alkyl,
R ⁵ represents a hydrogen atom, a halogen atom, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ alkoxy or C ₁ -C ₆ alkyl, and R ⁴ and R ⁵ together with the carbon atom to which each is bonded together, C ₃ -C ₆ cycloalkyl may be formed,
n represents an integer of 0, 1, 2, or 3;
X ² represents a halogen atom, methanesulfonyloxy, trifluoromethanesulfonyloxy or p-toluenesulfonyloxy. Wherein the amide compound represented by formula (12) is reacted in the presence of a base:

[Wherein, A, Y, R ¹ , R ² , R ³ , R ⁴ , R ⁵ , n, and X ² represent the same meaning as described above. ] The manufacturing method of the N-benzylamide compound represented by this.

[19] Formula (12):

[In the formula, A represents —CH═CH— or a sulfur atom,
Y represents —NO ₂ , —NH ₂ , —NHCO ₂ R ¹ , —NHSOR ¹ or —NHSO ₂ R ¹ ;
R ¹ represents C ₁ -C ₆ haloalkyl or C ₁ -C ₆ alkyl,
R ² represents a hydrogen atom, a halogen atom, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ alkoxy or C ₁ -C ₆ alkyl,
R ³ represents a hydrogen atom, a halogen atom, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ alkoxy or C ₁ -C ₆ alkyl, and R ² and R ³ together with the carbon atom to which each is attached together with C ₃ -C ₆ cycloalkyl may be formed,
R ⁴ represents a hydrogen atom, a halogen atom, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ alkoxy or C ₁ -C ₆ alkyl,
R ⁵ represents a hydrogen atom, a halogen atom, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ alkoxy or C ₁ -C ₆ alkyl, and R ⁴ and R ⁵ together with the carbon atom to which each is bonded together, C ₃ -C ₆ cycloalkyl may be formed,
n represents an integer of 0, 1, 2 or 3,
X ² represents a halogen atom, methanesulfonyloxy, trifluoromethanesulfonyloxy or p-toluenesulfonyloxy. Wherein the N-benzylamide compound represented by the formula (10) is reacted in the presence of a base:

[20] The production method according to the above [17] to [19], wherein a phase transfer catalyst is added as an additive.
[21] The production method according to [17] to [20], wherein n represents 0.
[22] The production method according to [17] to [20], wherein n represents an integer of 1.
[23] The production method according to [17] to [20], wherein n represents an integer of 2.
[24] The production method according to [17] to [20], wherein n represents an integer of 3.

[25] The base is lithium hydroxide, sodium hydroxide, potassium hydroxide, magnesium hydroxide, calcium hydroxide, barium hydroxide, sodium carbonate, potassium carbonate, cesium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, sodium phosphate, The production method according to the above [17] to [24], which is potassium phosphate, sodium monohydrogen phosphate or potassium monohydrogen phosphate.
[26] The production method of the above-mentioned [25], wherein the base is sodium hydroxide, potassium carbonate or potassium phosphate.
[27] Phase transfer catalyst is tetramethylammonium chloride, tetramethylammonium bromide, tetra-n-butylammonium fluoride, tetra-n-butylammonium chloride, tetra-n-butylammonium bromide, tetra-n-butylammonium iodide Tetra-n-butylammonium hydrogen sulfate, tetra-n-butylammonium hydroxide, benzyltrimethylammonium chloride, benzyltrimethylammonium bromide, benzyltri-n-butylammonium chloride, benzyltri-n-butylammonium bromide, tetraethylphosphonium bromide Tetra-n-butylphosphonium bromide, tetra-n-butylphosphonium chloride or tetraphenylphosphonium bromide Method for producing N- benzyl lactam compound according to [20] to [26].
[28] The production method of the above-mentioned [27], wherein the phase transfer catalyst is tetra-n-butylammonium bromide.
[29] The production method of the above-mentioned [17] to [28], wherein A represents —CH═CH—.
[30] The production method according to the above [17] to [28], wherein A represents a sulfur atom.

INDUSTRIAL APPLICABILITY According to the present invention, N-benzyl lactam compounds and trifluoromethanesulfonamide compounds that are industrially useful as intermediates for the production of medical and agricultural chemicals and various chemicals, and trifluoromethanesulfinyl compounds that are useful as intermediates thereof, and the production thereof A method is provided.

When the compound used as a raw material used in the production method of the present invention has one or more asymmetric carbon atoms, the present invention includes all optically active substances, racemates or diastereomers.

Next, specific examples of each substituent shown in the present specification are shown below. Here, n- means normal, i- means iso, s- means secondary and t- means tertiary, m- means meta and p- means para.

As a halogen atom in this invention, a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom are mentioned. In the present specification, the notation “halo” also represents these halogen atoms.
Among the compounds included in the present invention, those that can be converted into a salt according to a conventional method include, for example, salts of hydrogen halides such as hydrogen fluoride, hydrogen chloride, hydrogen bromide, hydrogen iodide, nitric acid, sulfuric acid , Inorganic acid salts such as phosphoric acid, chloric acid, perchloric acid, sulfonic acid salts such as methanesulfonic acid, ethanesulfonic acid, trifluoromethanesulfonic acid, formic acid, acetic acid, propionic acid, trifluoroacetic acid, fumaric acid, tartaric acid , Succinic acid, maleic acid, malic acid, succinic acid, benzoic acid, mandelic acid, ascorbic acid, carboxylic acid salts such as lactic acid, gluconic acid, citric acid, amino acid salts such as glutamic acid, aspartic acid, lithium, sodium, potassium Alkali metal salts such as alkaline earth metal salts such as calcium, barium and magnesium, aluminum salts, tetramethyla Moniumu salts, tetrabutylammonium salts, can be a quaternary ammonium salt such as benzyltrimethylammonium salts, salts of trifluoromethane sulfinic anilide compound in the present invention the term denotes these salts.

In the present specification, C _a -C _b alkyl represents a linear or branched hydrocarbon group having from a to b carbon atoms, for example, a methyl group, an ethyl group, or an n-propyl group. I-propyl group, n-butyl group, i-butyl group, t-butyl group, s-butyl group, n-pentyl group, 1-methylbutyl group, 2-methylbutyl group, 3-methylbutyl group, 1-ethylpropyl group Group, 1,1-dimethylpropyl group, 1,2-dimethylpropyl group, neopentyl group, n-hexyl group, 1-methylpentyl group, 2-methylpentyl group, 3-methylpentyl group, 4-methylpentyl group, 1-ethylbutyl group, 2-ethylbutyl group, 1,1-dimethylbutyl group, 1,2-dimethylbutyl group, 1,3-dimethylbutyl group, 2,2-dimethylbutyl group, 2,3-dimethylbutyl group, 3,3-di Tylbutyl group, 1,1,2-trimethylpropyl group, 1-ethyl-1-methylpropyl group, 1-ethyl-2-methylpropyl group, 1-heptyl group, 1-octyl group, 1-nonyl group, 1- Specific examples include a decyl group, a 1-undecyl group, a 1-dodecyl group, and the like, and each is selected within a range of each designated carbon number.

In the present specification, the expression C _a -C _b alkoxy represents the C _a -C _b alkyl-O— group having the above-mentioned meaning, for example, methyl-O-group, ethyl-O-group, n-propyl- O-group, i-propyl-O-group, n-butyl-O-group, i-butyl-O-group, t-butyl-O-group, s-butyl-O-group, pentyl-O-group, 1-methylbutyl-O-group, 2-methylbutyl-O-group, 3-methylbutyl-O-group, 1-ethylpropyl-O-group, 1,1-dimethylpropyl-O-group, 1,2-dimethylpropyl -O- group, neopentyl-O- group, n-hexyl-O- group, 1-methylpentyl-O- group, 2-methylpentyl-O- group, 3-methylpentyl-O- group, 4-methylpentyl -O- group, 1-ethylbutyl-O- group, 2-ethylbutyl-O- group, 1,1-dimethylbutyl-O- group, 1,2-dimethylbutyl-O- group, 1,3-dimethylbutyl O-group, 2,2-dimethylbutyl-O-group, 2,3-dimethylbutyl-O-group, 3,3-dimethylbutyl-O-group, 1,1,2-trimethylpropyl-O-group, 1-ethyl-1-methylpropyl-O- group, 1-ethyl-2-methylpropyl-O- group, 1-heptyl-O- group, 1-octyl-O- group, 1-nonyl-O- group, Specific examples include a 1-decyl-O— group, a 1-undecyl-O— group, a 1-dodecyl-O— group, and the like, and each is selected within a range of each designated carbon number.

The notation of C _a -C _b alkoxy (C _a -C _b ) alkyl in the present specification means the above-mentioned meaning that a hydrogen atom bonded to a carbon atom is optionally substituted by C _a -C _b alkoxy as defined above. C _a -C _b alkyl, such as methyl-O-methyl group, ethyl-O-methyl group, n-propyl-O-methyl group, i-propyl-O-methyl group, n-butyl-O -Methyl group, i-butyl-O-methyl group, t-butyl-O-methyl group, s-butyl-O-methyl group, pentyl-O-methyl group, 1-methylbutyl-O-methyl group, 2-methylbutyl -O-methyl group, 3-methylbutyl-O-methyl group, 1-ethylpropyl-O-methyl group, 1,1-dimethylpropyl-O-methyl group, 1,2-dimethylpropyl-O-methyl group, neopentyl -O-methyl group, n-hexyl-O-methyl group, 1-methylpentyl-O-methyl Group, 2-methylpentyl-O-methyl group, 3-methylpentyl-O-methyl group, 4-methylpentyl-O-methyl group, 1-ethylbutyl-O-methyl group, 1- (methyl-O-) ethyl Group, 2- (methyl-O-) ethyl group, 3- (methyl-O-) propyl group, 4- (methyl-O-) butyl group, 5- (methyl-O-) pentyl group, 6- (methyl Specific examples include —O—) hexyl group and the like, and each is selected within a range of each designated carbon number.

In the present specification, the expression C _a -C _b alkoxycarbonyl represents a C _a -C _b alkyl-O—C (O) — group as defined above, for example, a methyl-O—C (O) — group. , Ethyl-O-C (O)-group, n-propyl-O-C (O)-group, i-propyl-O-C (O)-group, n-butyl-O-C (O)-group , I-butyl-O-C (O)-group, t-butyl-O-C (O)-group, s-butyl-O-C (O)-group, n-pentyl-O-C (O) -Group, 1-methylbutyl-O-C (O)-group, 2-methylbutyl-O-C (O)-group, 3-methylbutyl-O-C (O)-group, 1-ethylpropyl-O-C (O)-group, 1,1-dimethylpropyl-O-C (O)-group, 1,2-dimethylpropyl-O-C (O)-group, neopentyl-O-C (O)-group, n -Hexyl-O-C (O)-group, 1-methylpentyl-O-C (O)-group, 2-methylpentyl-O-C (O)-group, 3-methylpentyl-O-C (O ) -Group, 4-methylpen -O-C (O)-group, 1-ethylbutyl-O-C (O)-group, 2-ethylbutyl-O-C (O)-group, 1,1-dimethylbutyl-O-C (O) -Group, 1,2-dimethylbutyl-O-C (O)-group, 1,3-dimethylbutyl-O-C (O)-group, 2,2-dimethylbutyl-O-C (O)-group 2,3-dimethylbutyl-O—C (O) — group, 3,3-dimethylbutyl-O—C (O) — group, 1,1,2-trimethylpropyl-O—C (O) — group 1-ethyl-1-methylpropyl-O—C (O) — group, 1-ethyl-2-methylpropyl-O—C (O) — group, 1-heptyl-O—C (O) — group, 1-octyl-O—C (O) — group, 1-nonyl-O—C (O) — group, 1-decyl-O—C (O) — group, 1-undecyl-O—C (O) — group Specific examples include a group, 1-dodecyl-O—C (O) — group, and the like, and each is selected within the range of the designated number of carbon atoms.

Halo notation (C _a ~ C _b) alkyl in the present specification, the C _a ~ C _b alkyl by halogen atom is meant the meaning of the in which a hydrogen atom bonded to a carbon atom which is optionally substituted For example, fluoromethyl group, chloromethyl group, bromomethyl group, iodomethyl group, 2-fluoroethyl group, 2-chloroethyl group, 2-bromoethyl group, 3-fluoropropyl group, 3-chloropropyl group, difluoromethyl group, Trifluoromethyl group, dichloromethyl group, trichloromethyl group, 2,2-difluoroethyl group, 2,2,2-trifluoroethyl group, 2,2,2-trichloroethyl group, chlorodifluoromethyl group, bromodifluoromethyl Group, pentafluoroethyl group, heptafluoropropyl group, heptafluoroisopropyl group, 4- Rorobuchiru group, 4-fluoro butyl group as specific examples, may be selected from the range of the specified number of carbon.

The notation of C _a -C _b alkylcarbonyl in the present specification represents an alkyl-C (O) — group having the above-mentioned meaning consisting of a to b carbon atoms, for example, acetyl group, propionyl group, butyryl group. Specific examples thereof include isobutyryl group, valeryl group, isovaleryl group, 2-methylbutanoyl group, pivaloyl group, and the like, and each is selected within the range of each designated carbon number.

In the present specification, the notation of halo (C _a -C _b ) alkylcarbonyl represents a haloalkyl-C (O) -group having the above-mentioned meaning consisting of a to b carbon atoms, such as fluoroacetyl group, chloro Acetyl group, difluoroacetyl group, dichloroacetyl group, trifluoroacetyl group, chlorodifluoroacetyl group, bromodifluoroacetyl group, trichloroacetyl group, pentafluoropropionyl group, heptafluorobutanoyl group, 3-chloro-2,2-dimethyl Specific examples include a propanoyl group and the like, and each is selected within a range of each designated carbon number.

In the present specification, C _a -C _b cycloalkyl represents a cyclic hydrocarbon group having a to b carbon atoms, for example, cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl. Groups and the like are listed as specific examples, and each group is selected within the range of each designated carbon number.

Next, the manufacturing method of the trifluoromethanesulfine anilide compound represented by Formula (1) of this invention is demonstrated.
When R ¹ represents a substituent other than a hydrogen atom, the trifluoromethanesulfinanilide compound represented by the formula (1) can be produced, for example, by the following method.
Reaction formula 1

That is, Formula (13) [In the Formula, A and Q represent the same meaning as the above. And a trifluoromethanesulfinanilide compound represented by the formula (14): wherein R ¹ represents C ₁ -C ₁₂ alkoxycarbonyl, and T represents a halogen atom. Can be produced in the presence of a base to produce a trifluoromethanesulfine anilide compound represented by the formula (1).
The compound represented by the formula (14) can be used in an amount of 1 to 5 equivalents relative to 1 equivalent of the compound represented by the formula (13).

Examples of the base include alkali metal hydroxides such as sodium hydroxide and potassium hydroxide, alkali metal carbonates such as sodium carbonate, calcium carbonate and potassium carbonate, alkali metal bicarbonates such as sodium hydrogen carbonate and potassium hydrogen carbonate, An organic base such as triethylamine, tributylamine, pyridine, 4- (dimethylamino) pyridine, imidazole, 1,8-diazabicyclo [5,4,0] -7-undecene, etc. is converted into the compound represented by the formula (13). 1 to 5 equivalents can be used.

When using a solvent, the solvent used is not particularly limited as long as it does not inhibit the progress of the reaction. For example, hydrocarbons such as hexane, cyclohexane, methylcyclohexane, ethylcyclohexane, heptane, benzene, xylene, toluene, etc. Halogenated hydrocarbons such as dichloromethane, carbon tetrachloride, chloroform, 1,2-dichloroethane, chlorobenzene, trifluoromethylbenzene, alcohols such as methanol, ethanol, 2-propanol, acetone, methyl ethyl ketone, methyl isobutyl ketone, etc. Ketones, nitriles such as acetonitrile and propionitrile, carboxylic acid esters such as ethyl acetate and ethyl propionate, N, N-dimethylformamide, N, N-dimethylacetamide, N-methylpyrrolidone Examples thereof include nitrogen-containing aprotic polar solvents such as 1,3-dimethyl-2-imidazolidinone, water and the like, preferably hydrocarbons such as xylene and toluene, halogenated hydrocarbons such as dichloromethane and dichloroethane, water Can be used. These solvents can be used by mixing two or more kinds.
The reaction temperature is usually -90 to 200 ° C, preferably 0 to 150 ° C.
The reaction time varies depending on the concentration of the reaction substrate and the reaction temperature, but is usually 10 minutes to 100 hours, preferably 10 minutes to 24 hours.

In the production of the trifluoromethanesulfonanilide compound of the present invention, the trifluoromethanesulfine anilide compound represented by the formula (1) and the trifluoromethanesulfonanilide compound represented by the formula (2) obtained by oxidizing it are each substituted. Among them, trifluoromethanesulfine anilide and trifluoromethanesulfonanilide compounds in which the substituents are as follows are preferable.
A represents —CH═CH—,
R ¹ represents a hydrogen atom or C ₁ -C ₆ alkoxycarbonyl,
Q represents CH ₂ OR ² , C (═O) OR ² , cyano, or CH ₂ N (Q ¹ ) Q ² ,
R ² represents a hydrogen atom or C ₁ -C ₆ alkyl,
Q ¹ and Q ² are each independently a hydrogen atom, C ₁ -C ₁₂ alkyl, halo (C ₁ -C ₁₂ ) alkyl, C ₁ -C ₁₂ alkylcarbonyl, halo (C ₁ -C ₁₂ ) alkylcarbonyl, It represents phenyl, phenylcarbonyl substituted by the (Y) phenyl substituted by _n, phenylcarbonyl or (Y) _m,
Y represents a halogen atom,
n represents an integer of 1, 2, 3, 4 or 5;
m represents an integer of 1, 2, 3, 4 or 5.

For the method for producing the trifluoromethanesulfonanilide compound, a solvent can be used as necessary. The solvent used is not particularly limited as long as it does not inhibit the progress of the reaction. For example, hydrocarbons such as hexane, cyclohexane, methylcyclohexane, ethylcyclohexane, heptane, benzene, xylene, toluene, dichloromethane, tetrachloride Halogenated hydrocarbons such as carbon, chloroform, 1,2-dichloroethane, chlorobenzene and trifluoromethylbenzene, nitriles such as acetonitrile and propionitrile, alcohols such as methanol, ethanol and 2-propanol, formic acid and acetic acid Acid, water, etc., preferably hydrocarbons such as xylene, toluene, halogenated hydrocarbons such as dichloromethane, chloroform, dichloroethane, nitriles such as acetonitrile, propionitrile, methanol, ethanol Alcohols such as 2-propanol, water can be used. These solvents can be used in a mixture of two or more.

The method for producing the trifluoromethanesulfonanilide compound can be carried out by adding an acid as necessary. The acid used is not particularly limited, but for example, fatty acids such as formic acid, acetic acid and trifluoroacetic acid, sulfonic acids such as methanesulfonic acid, trifluoromethanesulfonic acid and 4-methylbenzenesulfonic acid, and carboxylic acids such as benzoic acid Phosphonic acids such as aminomethylphosphonic acid and phenylphosphonic acid, and inorganic acids such as hydrochloric acid, sulfuric acid and phosphoric acid. Preferably, acetic acid, hydrochloric acid, sulfuric acid, phosphoric acid, phenylphosphonic acid and the like are used. The acid is usually used in an amount of 100 equivalents or less, preferably 2 equivalents or less, more preferably 0.01 to 2 equivalents, relative to 1 equivalent of the compound represented by formula (1) or formula (3).

Specific examples of the oxidizing agent in the above method for producing a trifluoromethanesulfonanilide compound include m-chloroperbenzoic acid, magnesium monoperoxyphthalate, peracid such as peracetic acid, iodine peroxidation such as sodium periodate and iodosobenzene. Products, persulfates such as potassium hydrogen persulfate, hydroperoxides such as hydrogen peroxide, t-butyl hydroperoxide, cumene hydroperoxide.

The oxidizing agent is preferably one selected from the group consisting of peracids, iodine peroxides, persulfates and hydroperoxides. Specific examples thereof are preferably one selected from the group consisting of m-chloroperbenzoic acid, magnesium monoperoxyphthalate, sodium periodate, and aqueous hydrogen peroxide.

When hydrogen peroxide is used as the oxidizing agent, preferably 1 to 50% by mass hydrogen peroxide solution, urea hydrogen peroxide, etc. can be used, more preferably 30 to 36% by mass hydrogen peroxide solution. Can be used. The oxidizing agent is generally used in an amount of 0.5 to 100 equivalents, preferably 1 to 5 equivalents, relative to 1 equivalent of the compound represented by the formula (1).
When using sodium periodate as the oxidizing agent, it is desirable to carry out the reaction in the presence of ruthenium trichloride. Ruthenium trichloride is usually used in an amount of 0.001 to 100 equivalents, preferably 0.01 to 2 equivalents, per 1 equivalent of the compound represented by the formula (1).

When using hydrogen peroxide as an oxidizing agent, it is desirable to carry out the reaction in the presence of sodium tungstate and / or a phase transfer catalyst.
When the reaction is carried out in the presence of sodium tungstate, sodium tungstate is usually used in an amount of 0.001 to 100 equivalents, preferably 0.01 to 2 equivalents, relative to 1 equivalent of the compound represented by formula (1). .

When the reaction is performed in the presence of the phase transfer catalyst, specific examples of the phase transfer catalyst include tetrabutylammonium chloride, tetrabutylammonium bromide, tetramethylammonium hydrogensulfate, tetraethylammonium hydrogensulfate, tetrapropylammonium hydrogensulfate. , Quaternary ammonium salts such as tetrabutylammonium hydrogensulfate, tetrahexylammonium hydrogensulfate, methyltrioctylammonium hydrogensulfate, methyltrioctylammonium chloride, pyridinium salts such as cetylpyridinium chloride, tetrabutylphosphonium bromide, tributylhexa Examples thereof include phosphonium salts such as decylphosphonium chloride and tetraphenylphosphonium chloride. Use quaternary ammonium salts such as tetramethylammonium hydrogensulfate, tetraethylammonium hydrogensulfate, tetrapropylammonium hydrogensulfate, tetrabutylammonium hydrogensulfate, tetrahexylammonium hydrogensulfate, methyltrioctylammonium hydrogensulfate It is preferable to use tetrabutylammonium hydrogen sulfate. The phase transfer catalyst is generally used in an amount of 100 equivalents or less, preferably 2 equivalents or less, more preferably 0.01 to 1 equivalent, per 1 equivalent of the compound represented by the formula (1).

The reaction in the above method for producing a trifluoromethanesulfonanilide compound can be carried out in a pressure range of 0.001 to 100 MPa, preferably 0.1 to 10 MPa. The reaction temperature is usually −20 to 100 ° C., preferably 0 to 80 ° C. The reaction time is usually 10 minutes to 100 hours, preferably 10 minutes to 24 hours. If necessary, it can be carried out in an inert gas atmosphere such as nitrogen or argon.

The treatment method after the reaction is not particularly limited, but the reaction mixture after completion of the reaction is directly concentrated or dissolved in an organic solvent, and then poured into water, separated, concentrated as necessary, or poured into water. The post-treatment such as extraction and concentration as necessary can be carried out to obtain the produced compound. If necessary, the reaction mixture and the solution obtained by the reaction treatment can be treated with a reducing agent, an acid, a base and the like. Moreover, the reaction mixture after completion | finish of reaction can be used for the following process as it is. Moreover, the manufactured compound can also be used for the following process with the solution obtained by the post-process. When the need for purification arises, it can be separated and purified by any purification method such as distillation, recrystallization, column chromatograph, thin layer chromatograph, liquid chromatographic fractionation and the like.

Next, a method for producing the trifluoromethanesulfinanilide compound represented by the formula (1) using the amine compound represented by the formula (3) in the present invention as a starting material will be described.

In the amine compound represented by the formula (3) used in the method for producing the trifluoromethanesulfine anilide compound, each substituent is as described above, and among these, the following amine compounds are preferable.
This production method can be applied not only to the amino group on the benzene ring where A is —CH═CH— but also to the amino group on the heterocycle where A is a sulfur atom.
A represents —CH═CH—,
R ¹ represents a hydrogen atom or C ₁ -C ₆ alkoxycarbonyl,
Q represents CH ₂ OR ² , C (═O) OR ² , cyano or CH ₂ NHQ ¹ ,
R ² represents a hydrogen atom or C ₁ -C ₆ alkyl,
Q ¹ is a hydrogen atom, C ₁ -C ₁₂ alkyl, halo (C ₁ -C ₁₂ ) alkyl, C ₁ -C ₁₂ alkylcarbonyl, halo (C ₁ -C ₁₂ ) alkylcarbonyl, phenyl, (Y) _n Represents substituted phenyl, phenylcarbonyl or phenylcarbonyl substituted by (Y) _m ;
Y represents a halogen atom,
n represents an integer of 1, 2, 3, 4 or 5;
m represents an integer of 1, 2, 3, 4 or 5.

Examples of the compound represented by the formula (4) used in the method for producing the trifluoromethanesulfinylide compound include trifluoromethanesulfinyl fluoride, trifluoromethanesulfinyl chloride, trifluoromethanesulfinyl bromide, and trifluoromethanesulfinyl iodide. Trifluoromethanesulfinyl chloride can be synthesized according to a general synthesis method described in the literature. For example, it can be produced by the method described in JP-A-10-218857, Chemiche Beirichte 1974, 107, 508, Tetrahedron 1999, Vol. 55, Vol. 7243, or Tetrahedron, 1976, Vol. 32, 1627. is there. The compound represented by the formula (4) is usually used in an amount of 0.5 to 2 equivalents with respect to 1 equivalent of the compound represented by the formula (3).

Examples of the salt of trifluoromethanesulfinic acid represented by the formula (5) in the method for producing the trifluoromethanesulfinanilide compound include alkali metal salts such as lithium, sodium, and potassium. Of these, sodium trifluoromethanesulfinate, which is a sodium salt of trifluoromethanesulfinic acid, is commercially available, and potassium trifluoromethanesulfinate, which is a potassium salt of trifluoromethanesulfinic acid, is generally described in the literature. It can be synthesized according to a typical synthesis method. For example, it can be manufactured by the method described in Journal of the American Chemical Society, 1974, Vol. 96, page 2275. The salt of trifluoromethanesulfinic acid represented by the formula (5) is usually used in an amount of 0.5 to 2 equivalents per 1 equivalent of the compound represented by the formula (3).

As for the method for producing the trifluoromethanesulfinanilide compound, a solvent can be used as necessary. The solvent used is not particularly limited as long as it does not inhibit the progress of the reaction. For example, hydrocarbons such as n-hexane, cyclohexane, methylcyclohexane, ethylcyclohexane, n-heptane, benzene, xylene, and toluene, Halogenated hydrocarbons such as dichloromethane, carbon tetrachloride, chloroform, 1,2-dichloroethane, chlorobenzene, trifluoromethylbenzene, ethers such as diethyl ether, diisopropyl ether, 1,4-dioxane, tetrahydrofuran, acetone, methyl ethyl ketone, Ketones such as methyl isobutyl ketone, nitriles such as acetonitrile and propionitrile, carboxylic acid esters such as ethyl acetate and ethyl propionate, N, N-dimethylformamide, N, N-dimethylacetoa Nitrogen, aprotic polar solvents such as N-methylpyrrolidone and 1,3-dimethyl-2-imidazolidinone, water, etc., preferably hydrocarbons such as benzene, xylene and toluene, dichloromethane, Halogenated hydrocarbons such as dichloroethane, alcohols such as methanol, ethanol and 2-propanol, and water can be used. These solvents can be used in a mixture of two or more.

In the above method for producing a trifluoromethanesulfinanilide compound, the reaction between the amine compound represented by the formula (3) and the compound represented by the formula (4) can be performed in the presence of a base.

The base to be used is not particularly limited, but examples thereof include inorganic bases such as sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, sodium hydride, potassium phosphate, pyridine, 4 -Dimethylaminopyridine, triethylamine, tributylamine, 5-ethyl-2-methylpyridine, 2-methylpyridine, 4-methylpyridine, 2,6-dimethylpyridine, N, N-dimethylaniline, N, N-diethylaniline, Organic bases such as 1,8-diazabicyclo [5.4.0] -7-undecene, organic lithium compounds such as n-butyllithium and s-butyllithium, lithium diisopropylamide, lithium bis (trimethylsilyl) amide, etc. Lithium amides, sodium methoxide, sodium And metal alkoxides such as muethoxide, sodium i-propoxide and potassium t-butoxide. Preferably, triethylamine, tributylamine, 5-ethyl-2-methylpyridine, 2-methylpyridine, 4-methylpyridine, 2,6-dimethylpyridine and pyridine are used. The base is generally used in an amount of 10 equivalents or less, preferably 4 equivalents or less, more preferably 0.01 to 2 equivalents, relative to 1 equivalent of the compound represented by Formula (1) or Formula (3).

The compound represented by the above formula (4) can be produced by reacting the compound represented by the above formula (5) with a halogenating agent.
Examples of the halogenating agent used include thionyl chloride, oxalyl chloride, phosphorus trichloride, phosphorus pentachloride, and phosphorus oxychloride. Preferably, thionyl chloride is used. The halogenating agent is generally used in an amount of 0.5 to 100 equivalents, preferably 1 to 10 equivalents, relative to the compound represented by the formula (3).

In the above method for producing a trifluoromethanesulfinanilide compound, when the compound represented by the formula (4) is produced from the compound represented by the formula (5), N, N-dimethylformamide, N, N— Amide compounds such as dimethylacetamide and amine compounds such as triethylamine can be added. The additive is generally used in an amount of 100 equivalents or less, preferably 10 equivalents or less, particularly preferably 0.001 to 1 equivalent, based on the compound represented by the formula (3).

The reaction in the above method for producing a trifluoromethanesulfinanilide compound can be carried out in a pressure range of 0.001 to 100 MPa, preferably 0.1 to 10 MPa. The reaction temperature is usually −90 to 200 ° C., preferably −50 to 50 ° C. The reaction time is usually 10 minutes to 100 hours, preferably 10 minutes to 24 hours. If necessary, it can be carried out in an inert gas atmosphere such as nitrogen or argon.

In addition, the acid, base, additive, oxidizing agent, halogenating agent, sodium tungstate, ruthenium trichloride, and phase transfer catalyst related to the production method of the present invention are diluted in solvates such as hydrates and solvents. Can also be used.
As used herein, a compound represented by the formula (3) (where Q is C (═O) OR ² or cyano, and R ¹ represents the same meaning as described above) is a known compound, and a part thereof Also available as a commercial product. Others can also be synthesized according to general synthesis methods described in literatures relating to known compounds.

The present invention is also a trifluoromethanesulfinanilide compound represented by the above formula (1) or a salt thereof. The preferable substituents in the trifluoromethanesulfinanilide compound represented by the formula (1) are also as described above.
Examples of the salt of the trifluoromethanesulfinanilide compound represented by the formula (1) include sodium salts and potassium salts.
The aminobenzylamine compound represented by the above formula (7) is produced, for example, by the method represented by the following reaction formula 2.
Reaction formula 2

That is, Formula (15) [wherein Q ¹ represents the same meaning as described above. In the formula (7), R ¹ represents a hydrogen atom, and Q ¹ represents the same meaning as described above. The aminobenzylamine compound represented by this can be manufactured.

Examples of the reduction method used in Step 2 include a method using a metal hydride such as sodium borohydride, lithium borohydride, and lithium aluminum hydride, a method using hydrogenation in the presence of a palladium catalyst, iron, zinc chloride, tin chloride, and the like. The metal reduction method can be used.
The amount of the reducing agent used can be 0.01 to 5 equivalents per 1 equivalent of the compound represented by the formula (15).

When using a solvent, the solvent used is not particularly limited as long as it does not inhibit the progress of the reaction. For example, hydrocarbons such as hexane, cyclohexane, methylcyclohexane, ethylcyclohexane, heptane, benzene, xylene, toluene, etc. Halogenated hydrocarbons such as dichloromethane, carbon tetrachloride, chloroform, 1,2-dichloroethane, chlorobenzene, trifluoromethylbenzene, alcohols such as methanol, ethanol, 2-propanol, diethyl ether, tetrahydrofuran, cyclopentyl methyl ether, Examples include ethers such as tertiary butyl methyl ether, water, and the like. Preferably, alcohols such as methanol and ethanol, ethers such as tetrahydrofuran and cyclopentyl methyl ether, and water can be used. These solvents can be used in a mixture of two or more.
The reaction temperature is usually -90 to 200 ° C, preferably 0 to 150 ° C.
The reaction time varies depending on the concentration of the reaction substrate and the reaction temperature, but is usually 10 minutes to 100 hours, preferably 10 minutes to 24 hours.

The reaction in the above method for producing an aminobenzylamine compound can be carried out in a pressure range of 0.001 to 100 MPa, preferably 0.1 to 10 MPa. The reaction temperature is usually −20 to 100 ° C., preferably 0 to 80 ° C. The reaction time is usually 10 minutes to 100 hours, preferably 10 minutes to 24 hours. If necessary, it can be carried out in an inert gas atmosphere such as nitrogen or argon.

The aminobenzylamine compound represented by the above formula (7) is also produced, for example, by the method represented by the following reaction formula 3.
Reaction formula 3

That is, formula (16) [wherein R ¹ represents a hydrogen atom or C ₁ -C ₆ alkoxycarbonyl. And an aminobenzylamine compound represented by the formula (17): wherein L represents a leaving group such as a halogen atom, and Q ¹ represents the same meaning as described above. By reacting the compound represented by formula (7), R ^{1 and} Q ¹ represent the same meaning as described above. The aminobenzylamine compound represented by this can be manufactured.

In the method for producing an aminobenzylamine compound, the reaction between the aminobenzylamine compound represented by the formula (16) and the compound represented by the formula (17) is preferably performed in the presence of a base.

The base to be used is not particularly limited, but examples thereof include inorganic bases such as sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, sodium hydride, potassium phosphate, pyridine, 4 -Dimethylaminopyridine, triethylamine, tributylamine, 5-ethyl-2-methylpyridine, 2-methylpyridine, 4-methylpyridine, 2,6-dimethylpyridine, N, N-dimethylaniline, N, N-diethylaniline, Organic bases such as 1,8-diazabicyclo [5.4.0] -7-undecene, organic lithium compounds such as n-butyllithium and s-butyllithium, lithium diisopropylamide, lithium bis (trimethylsilyl) amide, etc. Lithium amides, sodium methoxide, sodium And metal alkoxides such as muethoxide, sodium i-propoxide and potassium t-butoxide. Preferably, triethylamine, tributylamine, 5-ethyl-2-methylpyridine, 2-methylpyridine, 4-methylpyridine, 2,6-dimethylpyridine and pyridine are used. The base is generally used in an amount of 10 equivalents or less, preferably 4 equivalents or less, more preferably 0.01 to 2 equivalents, relative to 1 equivalent of the compound represented by Formula (16).

In the method for producing the aminobenzylamine compound, a solvent can be used as necessary. When using a solvent, the solvent used is not particularly limited as long as it does not inhibit the progress of the reaction. For example, hydrocarbons such as hexane, cyclohexane, methylcyclohexane, ethylcyclohexane, heptane, benzene, xylene, toluene, and halogen-based carbonization such as dichloromethane, carbon tetrachloride, chloroform, 1,2-dichloroethane, chlorobenzene, trifluoromethylbenzene, etc. Examples thereof include hydrogens, alcohols such as methanol, ethanol and 2-propanol, ethers such as diethyl ether, tetrahydrofuran, cyclopentyl methyl ether and tertiary butyl methyl ether, and water. Preferably, alcohols such as methanol and ethanol, ethers such as tetrahydrofuran and cyclopentyl methyl ether, and water can be used. These solvents can be used in a mixture of two or more.

The reaction temperature is usually -90 to 200 ° C, preferably 0 to 150 ° C.
The reaction time varies depending on the concentration of the reaction substrate and the reaction temperature, but is usually 10 minutes to 100 hours, preferably 10 minutes to 24 hours.
The reaction in the method for producing an aminobenzylamine compound can be carried out in a pressure range of 0.001 to 100 MPa, preferably 0.1 to 10 MPa. The reaction temperature is usually −20 to 100 ° C., preferably 0 to 80 ° C. The reaction time is usually 10 minutes to 100 hours, preferably 10 minutes to 24 hours. If necessary, it can be carried out in an inert gas atmosphere such as nitrogen or argon.

The production method of the N-benzyllactam compound represented by the formula (10) by reacting the compound represented by the formula (8) and the compound represented by (9) according to the present invention will be described below. .

A represents —CH═CH— or a sulfur atom,
X ¹ represents a halogen atom, methanesulfonyloxy, trifluoromethanesulfonyloxy or p-toluenesulfonyloxy,
Y represents —NO ₂ , —NH ₂ , —NHCO ₂ R ¹ , —NHSOR ¹ or —NHSO ₂ R ¹ ;
R ¹ represents C ₁ -C ₆ haloalkyl or C ₁ -C ₆ alkyl.
R ² represents a hydrogen atom, a halogen atom, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ alkoxy or C ₁ -C ₆ alkyl,
R ³ represents a hydrogen atom, a halogen atom, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ alkoxy or C ₁ -C ₆ alkyl, and R ² and R ³ together with the carbon atom to which each is attached together with C ₃ -C ₆ cycloalkyl may be formed,
R ⁴ represents a hydrogen atom, a halogen atom, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ alkoxy or C ₁ -C ₆ alkyl,
R ⁵ represents a hydrogen atom, a halogen atom, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ alkoxy or C ₁ -C ₆ alkyl, and R ⁴ and R ⁵ together with the carbon atom to which each is bonded together, C ₃ -C ₆ cycloalkyl may be formed,
n represents an integer of 0, 1, 2, or 3.

Solvents that can be used in the present invention include aromatic solvents such as toluene, benzene, chlorobenzene, orthodichlorobenzene, nitrobenzene, and trifluoromethylbenzene, hydrocarbon solvents such as hexane, heptane, octane, and nonane, acetonitrile, N, Polar solvents such as N-dimethylformamide, N, N-dimethylacetamide, N-methylpyrrolidone, dimethyl sulfoxide, water, alcohols such as methanol, ethanol, n-propanol, i-propanol, n-butanol, ethylene glycol, propylene glycol Solvents, halogen solvents such as dichloromethane, chloroform, 1,2-dichloroethane, tetrahydrofuran, diethyl ether, 1,2-dimethoxyethane, cyclopentyl methyl ether, methyl-t-butyl Examples include ether solvents such as tilether, and ester solvents such as methyl acetate, ethyl acetate, and butyl acetate, and mixed solvents thereof can also be used. Of these, toluene, tetrahydrofuran, and acetonitrile are preferable.

The amount of the solvent to be used is used in the range of 0.1 to 100 parts by weight, preferably in the range of 1 to 30 parts by weight with respect to 1 part by weight of the compound represented by the formula (8) as the raw material. To do.

Bases that can be used in this production method include calcium hydride, sodium hydride, potassium-t-butoxide, sodium-t-butoxide, sodium methoxide, lithium hydroxide, sodium hydroxide, potassium hydroxide, magnesium hydroxide, Calcium hydroxide, barium hydroxide, sodium carbonate, potassium carbonate, cesium carbonate, sodium bicarbonate, potassium bicarbonate, sodium phosphate, potassium phosphate, potassium phosphate monobasic, potassium monohydrogen phosphate, triethylamine, tributylamine, And organic bases such as pyridine, 4- (dimethylamino) pyridine, imidazole, and 1,8-diazabicyclo [5,4,0] -7-undecene. Of these, lithium hydroxide, sodium hydroxide, potassium hydroxide, magnesium hydroxide, calcium hydroxide, barium hydroxide, sodium carbonate, potassium carbonate, cesium carbonate, sodium bicarbonate, potassium bicarbonate, sodium phosphate, potassium phosphate , Sodium monohydrogen phosphate, or potassium monohydrogen phosphate. In particular, sodium hydroxide, potassium carbonate, or potassium phosphate is preferable.
The amount of the base that can be used in this production method is in the range of 1 to 100 mol, preferably in the range of 1 to 10 mol, relative to 1 mol of the compound represented by the formula (8) as the raw material.

In this production method, a phase transfer catalyst can be added. Examples of phase transfer catalysts that can be used include tetramethylammonium chloride, tetramethylammonium bromide, tetra-n-butylammonium fluoride, tetra-n-butylammonium chloride, tetra-n-butylammonium bromide, and tetra-n-butylammonium iodide. Quaternary such as tetra-n-butylammonium hydrogen sulfate, tetra-n-butylammonium hydroxide, benzyltrimethylammonium chloride, benzyltrimethylammonium bromide, benzyltri-n-butylammonium chloride, benzyltri-n-butylammonium bromide Ammonium salts and tetraethylphosphonium bromide, tetra-n-butylphosphonium bromide, tetra-n-butylphosphonium chloride, tetra Quaternary phosphonium salts such as E sulfonyl bromide and the like. Of these, tetra-n-butylammonium bromide is preferred.
The amount of the phase transfer catalyst that can be used in the present production method is in the range of 0.01 to 1 mol, preferably 0.01 to 0.1 mol, relative to 1 mol of the compound represented by the formula (8) as the raw material. Used in the range of 5 moles.

In this production method, the reaction is preferably performed at −50 ° C. or more and 200 ° C. or less, more preferably 0 ° C. or more and 150 ° C. or less. In this production method, the reaction is preferably carried out in an atmosphere of an inert gas such as nitrogen, argon or xenon.

Next, a method for producing an N-benzylamide compound represented by formula (12) by reacting a compound represented by formula (8) according to the present invention with a compound represented by formula (11) This will be described below.

A, X ¹ and Y are the same as those in the above compound (8).
R ² represents a hydrogen atom, a halogen atom, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ alkoxy or C ₁ -C ₆ alkyl,
R ³ represents a hydrogen atom, a halogen atom, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ alkoxy or C ₁ -C ₆ alkyl, and R ² and R ³ together with the carbon atom to which each is attached together with C ₃ -C ₆ cycloalkyl may be formed,
R ⁴ represents a hydrogen atom, a halogen atom, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ alkoxy or C ₁ -C ₆ alkyl,
R ⁵ represents a hydrogen atom, a halogen atom, C ₁ -C ₆ haloalkyl, C ₁ -C ₆ alkoxy or C ₁ -C ₆ alkyl, and R ⁴ and R ⁵ together with the carbon atom to which each is bonded together, C ₃ -C ₆ cycloalkyl may be formed,
n represents an integer of 0, 1, 2, or 3;
X ² represents a halogen atom, methanesulfonyloxy, trifluoromethanesulfonyloxy or p-toluenesulfonyloxy.

The solvent, base, phase transfer catalyst, and the like that can be used in this production method are the same as the production method of the N-benzyllactam compound represented by formula (10) from the compound represented by formula (8).

Next, a method for producing the N-benzyl lactam compound represented by the formula (10) from the compound represented by the formula (12) will be described below.

A, Y, R ¹ , R ² , R ³ , R ⁴ , R ⁵ , n and X ² are the same as in the above compound (12).

The solvent, base, phase transfer catalyst and the like that can be used in this production method are the same as those in the production method of the N-benzyllactam compound represented by the formula (10) from the compound represented by the formula (8).

The present invention will be described more specifically with reference to examples of the present invention. However, the present invention is not limited to these examples.
The proton nuclear magnetic resonance chemical shift values of the examples were measured at 300 MHz in deuterated chloroform solvent using Me ₄ Si (tetramethylsilane) as a reference substance.

[Example 1]
Synthesis of 2- (N-trifluoromethanesulfinyl) aminobenzyl alcohol To a slurry of 7 g of sodium trifluoromethanesulfinate 7 g of dichloromethane, 580 mg of thionyl chloride and 50 mg of N, N-dimethylformamide were added dropwise under ice cooling. After completion of dropping, the temperature was raised to room temperature and stirred for 1 hour. This slurry was added dropwise to a solution of 5 g of 2-aminobenzyl alcohol in 50 g of dichloromethane under ice cooling, and the mixture was stirred for 2 hours under ice cooling. After completion of the reaction, ethyl acetate and water were added to the reaction mixture, and the organic layer was separated. The obtained organic layer was washed with water and saturated brine in this order, dehydrated with anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography {n-hexane / ethyl acetate = 9/1 to 2/1 (volume ratio, the same shall apply hereinafter)} to obtain 1.69 g of the desired product as a red oil. It was.
¹ H NMR: δ 7.45-7.12 (m, 4H), 4.90 -4.55 (m, 2H), 3.40-2.70 (brs, 2H)

[Example 2]
Synthesis of 2- (N-trifluoromethanesulfonyl) aminobenzyl alcohol 2- (N-trifluoromethanesulfinyl) aminobenzyl alcohol 280 mg in toluene 5 g solution, 30% by mass hydrogen peroxide 400 mg, sodium tungstate dihydrate 39 mg Then, 40 mg of tetrabutylammonium hydrogen sulfate was added and stirred at 50 ° C. for 1 hour. After completion of the reaction, an aqueous sodium hydrogen sulfite solution and ethyl acetate were added to the reaction mixture, and the organic layer was separated. The obtained organic layer was washed with water and saturated brine in this order, dehydrated with anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (n-hexane / ethyl acetate = 3/1) to obtain 170 mg of the desired product as yellow crystals. Melting point: 48-48.5 ° C

[Example 3]
Synthesis of 2- (N-trifluoromethanesulfinyl) aminobenzonitrile Part 1
To 4.2 g of sodium trifluoromethanesulfinate, 30 g of toluene, 15 g of dichloromethane and 0.3 g of N, N-dimethylformamide were added and cooled to 0 ° C., and 3.6 g of thionyl chloride was added dropwise. After stirring at 0 ° C. for 2 hours, the mixture was cooled to −15 ° C. A mixed solution of 6 g of toluene in 3.0 g of 2-aminobenzonitrile and 3 g of dichloromethane was added dropwise, and the mixture was stirred for 30 minutes. Subsequently, a mixed solution of 4.6 g of N, N-dimethylaniline in 6 g of toluene and 3 g of dichloromethane was added dropwise over 2 hours. After stirring for an additional hour, water was added to the reaction mixture. The organic layer obtained by extracting this mixed solution twice with ethyl acetate was washed with saturated brine, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (n-hexane / ethyl acetate = 95/5 to 2/1) to obtain 4.8 g of the desired product as a yellow oil. The resulting oil was dissolved in toluene and extracted with aqueous sodium hydroxide. The aqueous layer was washed twice with toluene, acidified with 1 mol / L hydrochloric acid aqueous solution, and extracted twice with toluene. The organic layers were combined and washed twice with saturated brine, and the solvent was distilled off under reduced pressure to obtain 2.0 g of the desired product as a white solid. Melting point: 98-101 ° C

[Example 4]
Synthesis of 2- (N-trifluoromethanesulfinyl) aminobenzonitrile Part 2
To 4.0 g of sodium trifluoromethanesulfinate were added 35 g of toluene and 9.4 g of N, N-dimethylacetamide. After cooling to 0 ° C., 3.3 g of thionyl chloride was added dropwise. After stirring at 0 ° C. for 0.5 hour, the mixture was cooled to −15 ° C. A mixed solution of 3.0 g of 2-aminobenzonitrile in 6.9 g of toluene and 1.9 g of N, N-dimethylacetamide was added dropwise over 0.5 hours. After further stirring for 3 hours, 30 g of brine was added to the reaction mixture. The mixed solution was separated, and the aqueous layer was extracted with 26 g of toluene. The obtained organic layer was mixed and then subjected to high performance liquid chromatography [analysis conditions; column: XBridge C18, 4.6 × 150 mm, particle size 3.5 μm, eluent: acetonitrile / 20 mM ammonium formate aqueous solution = 40/60 (v / V), column temperature: 40 ° C., flow rate: 1.00 mL / min, observation wavelength: 254 nm], it was confirmed that the target product was produced at a relative area ratio of 91.5%.

[Example 5]
Synthesis of 2- (N-trifluoromethanesulfonyl) aminobenzonitrile 2-1.8N toluene solution of 0.21 g of 2- (N-trifluoromethanesulfinyl) aminobenzonitrile, 0.31 g of 30% by mass hydrogen peroxide, tungstic acid Sodium dihydrate (38 mg) and tetrabutylammonium hydrogensulfate (42 mg) were added, and the mixture was stirred at 50 ° C. for 6 hours. After completion of the reaction, an aqueous sodium hydrogen sulfite solution and ethyl acetate were added to the reaction mixture, and the organic layer was separated. The obtained organic layer was washed 3 times with saturated brine, and the solvent was distilled off under reduced pressure to obtain 0.24 g of the desired product as a brown solid. Melting point: 78-81 ° C
¹ H NMR: δ 7.61-7.71 (m, 3H), 7.38 (t, 1H), 5.3-5.6 (brs, 1H)

The analysis by high performance liquid chromatography described in Examples 6 to 16 and Reference Examples 4 to 11 below was performed according to the conditions described below.
Column: Inertsil-Ph-3 4.6 × 50 mm, 3 μm (GL Science Co., Ltd.)
Eluent: acetonitrile / water / acetic acid = 30/70 / 0.07 to 85/15 / 0.015 (volume ratio), oven temperature: 45 ° C., flow rate: 1 ml / min., Detection wavelength: 220 nm
The quantitative yield was measured according to the above-mentioned high performance liquid chromatography conditions, and the internal standard was calculated using 2-ethoxynaphthalene.
Analysis by gas chromatography was performed according to the conditions described below.
Column: DB-1 30 m × 0.25 mm, film 0.25 μm (manufactured by Agilent Technologies), carrier gas: helium, control mode: pressure (100 kPa, constant),
Injection volume: 1 μL, vaporization chamber temperature: 150 ° C., injection method: split (30/1), detector temperature: FID 250 ° C., oven temperature: 50 ° C. (1 min) −10 ° C./min−300° C. (15 min)

Example 6
Synthesis of 3,3-dimethyl-1- (2-nitrobenzyl) azetidin-2-one Part 1
To a solution of 1.00 g (4.63 mmol) of 1- (bromomethyl) -2-nitrobenzene in 10.0 g of acetonitrile, 1.38 g (13.9 mmol) of 3,3-dimethylazetidin-2-one and potassium phosphate 1 .47 g (6.94 mmol) was added. After completion of the addition, the reaction mixture was stirred for 3 hours under heating and refluxing under a nitrogen atmosphere. After completion of the reaction, the reaction mixture was cooled to room temperature, and the precipitated solid was separated by filtration. As a result of analyzing the obtained filtrate by high performance liquid chromatography, the relative area value of the target product was 83% (quantitative yield 81%).

Example 7
Synthesis of 3,3-dimethyl-1- (2-nitrobenzyl) azetidin-2-one Part 2
To a solution of 1.00 g (4.63 mmol) of 1- (bromomethyl) -2-nitrobenzene in 10.0 g of toluene, 1.38 g (13.9 mmol) of 3,3-dimethylazetidin-2-one, tetra-n -0.149 g (0.463 mmol) of butylammonium bromide and 0.926 g (6.94 mmol) of 30 wt% aqueous sodium hydroxide solution were added. After completion of the addition, the reaction mixture was stirred at 70 ° C. for 5 hours under a nitrogen atmosphere. After completion of the reaction, the reaction mixture was cooled to room temperature and washed with 5 g of 1M hydrochloric acid. As a result of analyzing the obtained solution by high performance liquid chromatography, the relative area value of the target product was 81% (quantitative yield: 63%).

Example 8
Synthesis of 3,3-dimethyl-1- (2-nitrobenzyl) azetidin-2-one Part 3
To a solution of 2.00 g (9.26 mmol) of 1- (bromomethyl) -2-nitrobenzene in 20.0 g of toluene, 1.84 g (18.5 mmol) of 3,3-dimethylazetidin-2-one, tetra-n -0.298 g (0.926 mmol) of butylammonium bromide and 3.84 g (27.8 mmol) of potassium carbonate were added. After completion of the addition, the reaction mixture was stirred at 80 ° C. for 4 hours under a nitrogen atmosphere. After completion of the reaction, the reaction mixture was cooled to room temperature and washed with 20 g of 1M hydrochloric acid. As a result of analyzing the obtained solution by high performance liquid chromatography, the relative area value of the target product was 84% (quantitative yield: 87%).

Example 9
Synthesis of 1- (2-nitrobenzyl) pyrrolidin-2-one 1
To a solution of 0.200 g (0.930 mmol) of 1- (bromomethyl) -2-nitrobenzene in 2.00 g of acetonitrile was added 0.236 g (2.78 mmol) of pyrrolidin-2-one and 0.295 g (1.39 mmol) of potassium phosphate. Mmol) was added. After completion of the addition, the reaction mixture was stirred for 4 hours under heating and refluxing under a nitrogen atmosphere. After completion of the reaction, the reaction mixture was cooled to room temperature, and the precipitated solid was separated by filtration. As a result of analyzing the obtained filtrate by high performance liquid chromatography, the relative area value of the target product was 65%.

Example 10
Synthesis of 1- (2-nitrobenzyl) pyrrolidin-2-one 2
To a solution of 0.500 g (2.31 mmol) of 1- (bromomethyl) -2-nitrobenzene in 5.00 g of toluene, 0.591 g (6.94 mmol) of pyrrolidin-2-one, 0.4% of tetra-n-butylammonium bromide. 0746 g (0.231 mmol) and 30 wt% aqueous sodium hydroxide solution 0.463 g (3.47 mmol) were added. After completion of the addition, the reaction mixture was stirred at 70 ° C. for 1 hour under a nitrogen atmosphere. After completion of the reaction, the reaction mixture was cooled to room temperature and washed with 5 g of 1M hydrochloric acid. As a result of analyzing the obtained solution by high performance liquid chromatography, the relative area value of the target product was 76%.

Example 11
Synthesis of 1- (2-nitrobenzyl) pyrrolidin-2-one 3
To a solution of 0.500 g (2.31 mmol) of 1- (bromomethyl) -2-nitrobenzene in 5.00 g of toluene, 0.394 g (4.63 mmol) of pyrrolidin-2-one, 0.4% of tetra-n-butylammonium bromide. 0746 g (0.230 mmol) and 0.960 g (6.94 mmol) potassium carbonate were added. After completion of the addition, the reaction mixture was stirred at 80 ° C. for 7 hours under a nitrogen atmosphere. After completion of the reaction, the reaction mixture was cooled to room temperature and washed with 5 g of 1M hydrochloric acid. As a result of analyzing the obtained solution by high performance liquid chromatography, the relative area value of the target product was 67%.

Example 12
Synthesis of 4,4-dimethyl-1- (2-nitrobenzyl) pyrrolidin-2-one To a solution of 0.216 g (1.00 mmol) of 1- (bromomethyl) -2-nitrobenzene in a 3.00 g acetonitrile solution, WO2006 / 072953 0.678 g (3.00 mmol) of synthesized 4,4-dimethylpyrrolidin-2-one and 0.318 g (1.50 mmol) of potassium phosphate synthesized according to the method described in 1) were added. After completion of the addition, the reaction mixture was stirred at 50 ° C. for 2 hours under a nitrogen atmosphere. After completion of the reaction, the reaction mixture was cooled to room temperature and extracted with 5 g of ethyl acetate. The obtained organic layer was washed with 5 g of diluted hydrochloric acid, 5 g of an aqueous sodium hydrogen sulfite solution, and 5 g of saturated brine in that order, and then dried over anhydrous sodium sulfate, and acetonitrile was distilled off under reduced pressure. Purification by silica gel column chromatography (hexane: ethyl acetate = 3: 1) gave 0.185 g of the desired product as a pale yellow solid (yield 75%).
Melting point: 91-92 ° C

Example 13
Synthesis of 4,4-dimethyl-1- (2-nitrobenzyl) piperidin-2-one To a solution of 0.432 g (2.00 mmol) of 1- (bromomethyl) -2-nitrobenzene in 5.00 g of acetonitrile, WO2010 / 026989 4,62-dimethylpiperidin-2-one synthesized according to the method described in 1) (0.762 g (6.00 mmol)) and 1.27 g (6.00 mmol) of potassium phosphate were added. After completion of the addition, the reaction mixture was stirred at 80 ° C. for 4 hours under a nitrogen atmosphere. After completion of the reaction, the reaction mixture was cooled to room temperature and extracted with 10 g of ethyl acetate. The obtained organic layer was washed with 10 g of water, 10 g of dilute hydrochloric acid and 10 g of saturated saline in this order, and then dried over anhydrous sodium sulfate, and acetonitrile was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane: ethyl acetate = 3: 1) to obtain 0.203 g of the desired product as a light brown solid (yield 39%).
Melting point: 90-92 ° C

Example 14
Synthesis of N- [2-{(3,3-dimethyl-2-oxoazetidin-1-yl) methyl} phenyl] -1,1,1-trifluoromethanesulfonamide Part 1
To 0.186 g (0.50 mmol) of 3-chloro-2,2-dimethyl-N- {2- (trifluoromethanesulfonamido) benzyl} propanamide, 2.00 g (1 wt. .25 mmol) was added. After completion of the addition, the reaction mixture was stirred at 80 ° C. for 3 hours. After completion of the reaction, the reaction mixture was cooled to room temperature, 3 g of diluted hydrochloric acid was added, and the mixture was extracted with 10 g of ethyl acetate. As a result of analyzing the obtained ethyl acetate solution by high performance liquid chromatography, the relative area value of the target product was 97% (quantitative yield 97%).

Example 15
Synthesis of N- [2-{(3,3-dimethyl-2-oxoazetidin-1-yl) methyl} phenyl] -1,1,1-trifluoromethanesulfonamide Part 2
To a solution of 0.186 g (0.50 mmol) of 3-chloro-2,2-dimethyl-N- {2- (trifluoromethanesulfonamido) benzyl} propanamide in 3 ml of acetonitrile was added 0.318 g (1.50 mmol) of potassium phosphate. ) Was added. After completion of the addition, the reaction mixture was stirred at 80 ° C. for 9 hours. As a result of analyzing the reaction mixture by high performance liquid chromatography, the relative area value of the target product was 88%.

Example 16
Synthesis of N- [2-{(3,3-dimethyl-2-oxoazetidin-1-yl) methyl} phenyl] -1,1,1-trifluoromethanesulfonamide Part 3
N- {2- (aminomethyl) phenyl} -1,1,1-trifluoromethanesulfonamide 1.02 g (4.00 mmol) in a 7.00 g toluene solution 7.00 g 5% by weight aqueous sodium hydroxide solution ( 8.80 mmol) was added. After completion of the addition, the reaction mixture was stirred at 30 ° C. for 30 minutes, and then 0.684 g (4.40 mmol) of 3-chloropivaloyl chloride was added, followed by stirring at 30 ° C. for 5 hours. After completion of the stirring, 6.40 g (8.00 mmol) of 5 mass% aqueous sodium hydroxide solution was added to the reaction mixture, and the mixture was stirred at 80 ° C. for 3 hours. After completion of the reaction, 1.29 g (12.4 mmol) of 35 mass% hydrochloric acid was added to the reaction mixture, and the aqueous layer was separated. The obtained organic layer was washed with 3 g of water. The obtained solution was dried over anhydrous sodium sulfate, and toluene was distilled off under reduced pressure to obtain 1.13 g of the desired product as white crystals.
Melting point: 114-116 ° C

[Reference Example 1]
Synthesis of methyl 2- (N-trifluoromethanesulfonyl) aminobenzoate To a solution of 3.02 g of 2-aminobenzoic acid in 20 g of dichloromethane, 2.82 g of trifluoromethanesulfonic anhydride, 2.02 g of triethylamine, trifluoromethanesulfonic anhydride 2 .82 g and triethylamine 0.40 g were continuously added under ice cooling, followed by stirring for 1 hour under ice cooling. After completion of the reaction, water was added to the reaction mixture, and the organic layer was separated. The obtained organic layer was washed with water and saturated brine in this order, and dehydrated with anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to obtain 3.51 g of the desired product as a pale yellow solid. Melting point: 33-35 ° C

[Reference Example 2]
Synthesis of 2- (N-trifluoromethanesulfonyl) benzyl alcohol 114 mg of sodium borohydride was added to 10 ml of tetrahydrofuran solution of 566 mg of methyl 2- (N-trifluoromethanesulfonyl) aminobenzoate and heated to 50 ° C. 0.1 ml of methanol was slowly added dropwise to the reaction solution, and the mixture was heated and stirred at 50 ° C. for 2 hours. The reaction solution was subjected to high performance liquid chromatography [analysis conditions; column: Inertsil ODS-4, 4.6 × 250 mm, particle size 5 μm, eluent: acetonitrile / water / trifluoroacetic acid = 600/400 / 0.1 (v / v / V), column temperature: 40 ° C., flow rate: 1.00 mL / min, observation wavelength: 220 nm], it was confirmed that the target product was produced at a relative area ratio of 73.5%.

[Reference Example 3]
Synthesis of 2- (N-trifluoromethanesulfonyl) aminobenzonitrile To a solution of 3.0 g of 2-aminobenzonitrile in 20 g of dichloromethane, 3.6 g of trifluoromethanesulfonic acid anhydride, 2.6 g of triethylamine, trifluoromethanesulfonic acid anhydride; 6 g and 0.51 g of triethylamine were continuously added under ice cooling, followed by stirring for 1 hour under ice cooling. After completion of the reaction, the reaction solution was separated twice with a 5 mass% aqueous sodium hydroxide solution. The aqueous layer was mixed, washed with dichloromethane, acidified with 1 mol / L aqueous hydrochloric acid solution, and extracted with dichloromethane. The organic layer was washed twice with water and the solvent was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (n-hexane / ethyl acetate = 95/5 to 2/1) to obtain 3.4 g of the desired product as a white solid. Melting point: 78-81 ° C

[Reference Example 4]
Synthesis of 3-chloropivalic acid amide To 39.2 g (645 mmol) of 28% by mass aqueous ammonia, 200 g of ethyl acetate and 20.0 g (129 mmol) of 3-chloropivalic acid chloride were added dropwise at room temperature. After completion of the dropwise addition, the reaction mixture was stirred at room temperature for 4 hours. After completion of the reaction, 60 g of a saturated aqueous ammonium chloride solution was added little by little to the reaction mixture at room temperature, and then the aqueous layer was separated. The aqueous layer was extracted with 60 g of ethyl acetate, combined with the previous organic layer, and dried over anhydrous sodium sulfate. The obtained organic layer was distilled off under reduced pressure to obtain 16.1 g of the desired product as a white solid (yield 92%). Melting point: 100-102 ° C

[Reference Example 5]
Synthesis of 3,3-dimethyl-2-azetidinone-1
To a solution of 40.7 g (300 mmol) of 3-chloropivalic acid amide in 410 g of acetonitrile, 127 g (600 mmol) of potassium phosphate was added. After completion of the addition, the mixture was stirred for 9 hours under reflux with heating, and then cooled to room temperature, and then the solid matter precipitated in the reaction mixture was filtered off. Acetonitrile was distilled off under reduced pressure from the obtained filtrate, and then the obtained residue was distilled under reduced pressure to obtain 26.0 g of the objective product distilled at 110 to 118 ° C. at 3 kPa as a colorless liquid. . As a result of analysis by gas chromatography, the relative area value of the target product was 96%.

[Reference Example 6]
Synthesis of 3,3-dimethyl-2-azetidinone-2
To a solution of 10.0 g (73.8 mmol) of 3-chloropivalic acid amide in 300 g of tetrahydrofuran was added 16.6 g (148 mmol) of potassium tert-butoxide. After completion of the addition, the reaction mixture was stirred at room temperature for 4 hours. After completion of the reaction, the reaction mixture was washed with 80 g of a saturated aqueous ammonium chloride solution and dried over anhydrous sodium sulfate, and acetonitrile was distilled off under reduced pressure to obtain 6.82 g of the desired product as a colorless liquid. As a result of analysis by gas chromatography, the relative area value of the target product was 92%.

[Reference Example 7]
Synthesis of N- {2- (aminomethyl) phenyl} -1,1,1-trifluoromethanesulfonamide-Part 1
To a solution of N- (2-cyanophenyl) -1,1,1-trifluoromethanesulfonamide (615 mg, 2.46 mmol) in 6.15 g of methanol was added 57.7 mg of Raney nickel. After completion of the addition, the reaction mixture was stirred at 50 ° C. for 16 hours under a hydrogen atmosphere. After completion of the reaction, Raney nickel was removed from the reaction mixture by Celite filtration. As a result of analyzing the obtained solution by high performance liquid chromatography, the relative area value of the target product was 77%.

[Reference Example 8]
Synthesis of N- {2- (aminomethyl) phenyl} -1,1,1-trifluoromethanesulfonamide-Part 2
To a solution of 1.00 g (4.00 mmol) of N- (2-cyanophenyl) -1,1,1-trifluoromethanesulfonamide in 20.0 g of methanol was added 10% palladium on carbon (manufactured by NE Chemcat, NX Type) 200 mg was added. After completion of the addition, the reaction mixture was stirred at room temperature for 3 hours under a hydrogen atmosphere. After completion of the reaction, palladium carbon was removed from the reaction mixture by Celite filtration. As a result of analyzing the obtained solution by high performance liquid chromatography, the relative area value of the target product was 88%.

[Reference Example 9]
Synthesis of N- {2- (aminomethyl) phenyl} -1,1,1-trifluoromethanesulfonamide sulfate 1.00 g of N- (2-cyanophenyl) -1,1,1-trifluoromethanesulfonamide (4 0.001 g (4.00 mmol) of concentrated sulfuric acid and 50 mg of 5 mass% palladium carbon (manufactured by N.E. Chemcat, STD type) were added to a 10.0 g methanol solution. After completion of the addition, the reaction mixture was stirred at room temperature for 7 hours under a hydrogen gas atmosphere. After completion of the reaction, palladium carbon was removed from the reaction mixture by Celite filtration. As a result of analyzing the obtained solution by liquid chromatography, the relative area value of the target product was 99%.

[Reference Example 10]
Synthesis of 3-chloro-2,2-dimethyl-N- {2- (trifluoromethanesulfonamido) benzyl} propanamide Part 1
To a solution of 500 mg (1.97 mmol) of N- {2- (aminomethyl) phenyl} -1,1,1-trifluoromethanesulfonamide in 5.00 g of toluene, 574 mg (4.15 mmol) of potassium carbonate, 3-chloro 322 mg (2.08 mmol) of pivaloyl chloride was added. After the addition was complete, the reaction mixture was stirred at 70 ° C. for 3 hours. After completion of the reaction, the reaction mixture was cooled to room temperature and extracted twice with 5 g of a 5 mass% aqueous sodium hydroxide solution. The obtained aqueous sodium hydroxide solution was acidified with 2 g of 35% by mass hydrochloric acid and then extracted twice with 5 g of toluene. The obtained organic layer was dried over anhydrous sodium sulfate, and toluene was distilled off under reduced pressure to obtain 662 mg of the desired product as white crystals (yield 94%).
Melting point: 92-93 ° C

[Reference Example 11]
Synthesis of 3-chloro-2,2-dimethyl-N- {2- (trifluoromethanesulfonamido) benzyl} propanamide Part 2
To a solution of N- {2- (aminomethyl) phenyl} -1,1,1-trifluoromethanesulfonamide (258 mg, 1.01 mmol) in toluene (8.77 g) and ethyl acetate (4.49 g), triethylamine (307 mg, 3.03 mmol). ) And 3-chloropivaloyl chloride 167 mg (1.08 mmol). After completion of the addition, the reaction mixture was stirred at 20 ° C. for 1 hour. After completion of the reaction, 5 g of water and 7 g of dilute hydrochloric acid were added to the reaction mixture for liquid separation, and the aqueous layer was extracted with 18 g of toluene. The obtained organic layers were combined and washed with 5 g of saturated brine. As a result of analyzing the obtained solution by high performance liquid chromatography, the relative area value of the target product was 94%.

The trifluoromethanesulfinanilide compound according to the present invention is extremely useful as a novel production intermediate of a trifluoromethanesulfonanilide compound having high selectivity for rice, corn, wheat, beet and soybean and having an excellent herbicidal effect.
Japanese Patent Application No. 2013-221858 filed on October 25, 2013, Japanese Patent Application No. 2014-012677 filed on January 27, 2014, Japanese Patent Application filed on February 26, 2014 Application No. 2014-034902, Japanese Patent Application No. 2014-111609 filed on May 29, 2014, and Japanese Patent Application No. 2014-180886 filed on September 5, 2014 The entire contents of the scope, drawings and abstract are hereby incorporated by reference as disclosure of the specification of the present invention.

Claims

Formula (1):

[In the formula, A represents —CH═CH— or a sulfur atom,
R 1 represents a hydrogen atom or C 1 -C 12 alkoxycarbonyl,
Q represents CH 2 OR 2 , C (═O) OR 2 , cyano, or CH 2 N (Q 1 ) Q 2 ,
R 2 represents a hydrogen atom or C 1 -C 6 alkyl,
Q 1 and Q 2 are each independently a hydrogen atom, C 1 -C 12 alkyl, C 1 -C 12 alkoxy, halo (C 1 -C 12 ) alkyl, halo (C 1 -C 12 ) alkoxy, C 3 -C 8 cycloalkyl, C 1 -C 12 alkylcarbonyl, C 1 -C 12 alkoxycarbonyl, halo (C 1 -C 12 ) alkylcarbonyl, halo (C 1 -C 12 ) alkoxycarbonyl, C 3 -C 8 cyclo Alkylcarbonyl, phenyl, phenyl substituted by (Y) n , phenylcarbonyl, phenylcarbonyl substituted by (Y) m , C 1 -C 6 alkoxy (C 1 -C 6 ) alkyl, C 1 -C 6 alkylthio (C 1 ~ C 6) alkyl, C 1 ~ C 6 alkylsulfinyl (C 1 ~ C 6) alkyl, C 1 ~ C 6 Alkylsulfonyl (C 1 ~ C 6) alkyl, C 1 ~ C 6 alkoxy (C 1 ~ C 6) alkylcarbonyl, C 1 ~ C 6 alkylthio (C 1 ~ C 6) alkylcarbonyl, C 1 ~ C 6 alkylsulfinyl Represents (C 1 -C 6 ) alkylcarbonyl or C 1 -C 6 alkylsulfonyl (C 1 -C 6 ) alkylcarbonyl,
Y represents a halogen atom,
n represents an integer of 1, 2, 3, 4 or 5;
m represents an integer of 1, 2, 3, 4 or 5. Wherein the trifluoromethanesulfinanilide compound represented by the formula (2) is reacted with an oxidizing agent:

[Wherein, A, R 1 and Q represent the same meaning as described above] A method for producing a trifluoromethanesulfonanilide compound represented by the formula:
A represents —CH═CH—,
R 1 represents a hydrogen atom or C 1 -C 6 alkoxycarbonyl,
Q 1 and Q 2 are each independently a hydrogen atom, C 1 -C 12 alkyl, halo (C 1 -C 12 ) alkyl, C 1 -C 12 alkylcarbonyl, halo (C 1 -C 12 ) alkylcarbonyl, The method for producing a trifluoromethanesulfonanilide compound according to claim 1, which represents phenyl, phenyl substituted by (Y) n , phenylcarbonyl or phenylcarbonyl substituted by (Y) m .
The method for producing a trifluoromethanesulfonanilide compound according to claim 1 or 2, wherein the oxidizing agent is one selected from the group consisting of peracids, iodine peroxides, persulfates and hydroperoxides.
The production of a trifluoromethanesulfonanilide compound according to claim 3, wherein the oxidizing agent is one selected from the group consisting of m-chloroperbenzoic acid, magnesium monoperoxyphthalate, sodium periodate and hydrogen peroxide. Method.
The method for producing a trifluoromethanesulfonanilide compound according to claim 4, wherein the oxidizing agent is sodium periodate and the reaction is performed in the presence of ruthenium trichloride.
The method for producing a trifluoromethanesulfonanilide compound according to claim 4, wherein the oxidizing agent is hydrogen peroxide water, and is performed in the presence of sodium tungstate and / or a phase transfer catalyst.
The method for producing a trifluoromethanesulfonanilide compound according to claim 6, wherein the phase transfer catalyst is a quaternary ammonium salt.
Formula (3):

[In the formula, A represents —CH═CH— or a sulfur atom,
R 1 represents a hydrogen atom or C 1 -C 12 alkoxycarbonyl,
Q represents CH 2 OR 2 , C (═O) OR 2 , cyano, or CH 2 N (Q 1 ) Q 2 ,
R 2 represents a hydrogen atom or C 1 -C 6 alkyl,
Q 1 and Q 2 are each independently a hydrogen atom, C 1 -C 12 alkyl, C 1 -C 12 alkoxy, halo (C 1 -C 12 ) alkyl, halo (C 1 -C 12 ) alkoxy, C 3 -C 8 cycloalkyl, C 1 -C 12 alkylcarbonyl, C 1 -C 12 alkoxycarbonyl, halo (C 1 -C 12 ) alkylcarbonyl, halo (C 1 -C 12 ) alkoxycarbonyl, C 3 -C 8 cyclo Alkylcarbonyl, phenyl, phenyl substituted by (Y) n , phenylcarbonyl, phenylcarbonyl substituted by (Y) m , C 1 -C 6 alkoxy (C 1 -C 6 ) alkyl, C 1 -C 6 alkylthio (C 1 ~ C 6) alkyl, C 1 ~ C 6 alkylsulfinyl (C 1 ~ C 6) alkyl, C 1 ~ C 6 Alkylsulfonyl (C 1 ~ C 6) alkyl, C 1 ~ C 6 alkoxy (C 1 ~ C 6) alkylcarbonyl, C 1 ~ C 6 alkylthio (C 1 ~ C 6) alkylcarbonyl, C 1 ~ C 6 alkylsulfinyl Represents (C 1 -C 6 ) alkylcarbonyl or C 1 -C 6 alkylsulfonyl (C 1 -C 6 ) alkylcarbonyl,
Y represents a halogen atom,
n represents an integer of 1, 2, 3, 4 or 5;
m represents an integer of 1, 2, 3, 4 or 5, and an amine compound represented by the formula (4):

[Wherein X represents a halogen atom. A compound represented by formula (1):

[Wherein, A, R 1 and Q represent the same meaning as described above] A method for producing a trifluoromethanesulfine anilide compound represented by the formula:
A represents —CH═CH—,
R 1 represents a hydrogen atom or C 1 -C 6 alkoxycarbonyl,
Q 1 and Q 2 are each independently a hydrogen atom, C 1 -C 12 alkyl, halo (C 1 -C 12 ) alkyl, C 1 -C 12 alkylcarbonyl, halo (C 1 -C 12 ) alkylcarbonyl, The method for producing a trifluoromethanesulfinanilide compound according to claim 8, which represents phenyl, phenyl substituted by (Y) n , phenylcarbonyl, or phenylcarbonyl substituted by (Y) m .
The method for producing a trifluoromethanesulfinanilide compound according to claim 8 or 9, wherein the reaction is carried out in the presence of a base.
Formula (5):

[Wherein M represents sodium or potassium. The compound represented by formula (4) is produced by reacting the compound represented by formula (4) with a halogenating agent, and the produced compound represented by formula (4) is used. A process for producing the trifluoromethanesulfinanilide compound described.
The method for producing a trifluoromethanesulfinanilide compound according to claim 11, wherein the halogenating agent is thionyl chloride.
Formula (1):

[In the formula, A represents —CH═CH— or a sulfur atom,
R 1 represents a hydrogen atom or C 1 -C 12 alkoxycarbonyl,
Q represents CH 2 OR 2 , C (═O) OR 2 , cyano, or CH 2 N (Q 1 ) Q 2 ,
R 2 represents a hydrogen atom or C 1 -C 6 alkyl,
Q 1 and Q 2 are each independently a hydrogen atom, C 1 -C 12 alkyl, C 1 -C 12 alkoxy, halo (C 1 -C 12 ) alkyl, halo (C 1 -C 12 ) alkoxy, C 3 -C 8 cycloalkyl, C 1 -C 12 alkylcarbonyl, C 1 -C 12 alkoxycarbonyl, halo (C 1 -C 12 ) alkylcarbonyl, halo (C 1 -C 12 ) alkoxycarbonyl, C 3 -C 8 cyclo Alkylcarbonyl, phenyl, phenyl substituted by (Y) n , phenylcarbonyl, phenylcarbonyl substituted by (Y) m , C 1 -C 6 alkoxy (C 1 -C 6 ) alkyl, C 1 -C 6 alkylthio (C 1 ~ C 6) alkyl, C 1 ~ C 6 alkylsulfinyl (C 1 ~ C 6) alkyl, C 1 ~ C 6 Alkylsulfonyl (C 1 ~ C 6) alkyl, C 1 ~ C 6 alkoxy (C 1 ~ C 6) alkylcarbonyl, C 1 ~ C 6 alkylthio (C 1 ~ C 6) alkylcarbonyl, C 1 ~ C 6 alkylsulfinyl Represents (C 1 -C 6 ) alkylcarbonyl or C 1 -C 6 alkylsulfonyl (C 1 -C 6 ) alkylcarbonyl,
Y represents a halogen atom,
n represents an integer of 1, 2, 3, 4 or 5;
m represents an integer of 1, 2, 3, 4 or 5.] A trifluoromethanesulfinanilide compound or a salt thereof.
A represents —CH═CH—,
R 1 represents a hydrogen atom or C 1 -C 6 alkoxycarbonyl,
Q 1 and Q 2 are each a hydrogen atom, C 1 -C 12 alkyl, halo (C 1 -C 12 ) alkyl, C 1 -C 12 alkylcarbonyl, halo (C 1 -C 12 ) alkylcarbonyl, phenyl, (Y The trifluoromethanesulfinanilide compound or a salt thereof according to claim 13, which represents phenyl substituted by n , phenylcarbonyl or phenylcarbonyl substituted by (Y) m .
Formula (6):

[R 1 represents a hydrogen atom or C 1 -C 6 alkoxycarbonyl;
Q 1 and Q 2 are each independently halo (C 1 -C 12 ) alkylcarbonyl, halo (C 1 -C 12 ) alkoxycarbonyl, C 1 -C 6 alkoxy (C 1 -C 6 ) alkylcarbonyl, C It represents a 1 ~ C 6 alkylthio (C 1 ~ C 6) alkylcarbonyl, C 1 ~ C 6 alkylsulfinyl (C 1 ~ C 6) alkylcarbonyl or C 1 ~ C 6 alkylsulfonyl (C 1 ~ C 6) alkylcarbonyl ] The trifluoromethanesulfonamide compound represented by these, or its salt.
Formula (7):

[R 1 represents a hydrogen atom or C 1 -C 6 alkoxycarbonyl;
Q 1 is halo (C 1 -C 12 ) alkylcarbonyl, halo (C 1 -C 12 ) alkoxycarbonyl, C 1 -C 6 alkoxy (C 1 -C 6 ) alkylcarbonyl, C 1 -C 6 alkylthio (C 1 -C 6 ) alkylcarbonyl, C 1 -C 6 alkylsulfinyl (C 1 -C 6 ) alkylcarbonyl or C 1 -C 6 alkylsulfonyl (C 1 -C 6 ) represents alkylcarbonyl] Amine compounds.
Formula (8):

[In the formula, A represents —CH═CH— or a sulfur atom,
X 1 represents a halogen atom, methanesulfonyloxy, trifluoromethanesulfonyloxy or p-toluenesulfonyloxy,
Y represents —NO 2 , —NH 2 , —NHCO 2 R 1 , —NHSOR 1 or —NHSO 2 R 1 ;
R 1 represents C 1 -C 6 haloalkyl or C 1 -C 6 alkyl. A benzyl compound represented by formula (9):

[Wherein R 2 represents a hydrogen atom, a halogen atom, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy or C 1 -C 6 alkyl,
R 3 represents a hydrogen atom, a halogen atom, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy or C 1 -C 6 alkyl, and R 2 and R 3 together with the carbon atom to which each is attached together with C 3 -C 6 cycloalkyl may be formed,
R 4 represents a hydrogen atom, a halogen atom, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy or C 1 -C 6 alkyl,
R 5 represents a hydrogen atom, a halogen atom, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy or C 1 -C 6 alkyl, and R 4 and R 5 together with the carbon atom to which each is bonded together, C 3 -C 6 cycloalkyl may be formed,
n represents an integer of 0, 1, 2, or 3. Wherein the lactam compound represented by the formula (10) is reacted in the presence of a base:

[Wherein, A, Y, R 1 , R 2 , R 3 , R 4 , R 5 and n represent the same meaning as described above. ] The manufacturing method of the N-benzyl lactam compound represented by this.
Formula (8):

[In the formula, A represents —CH═CH— or a sulfur atom,
X 1 represents a halogen atom, methanesulfonyloxy, trifluoromethanesulfonyloxy or p-toluenesulfonyloxy,
Y represents —NO 2 , —NH 2 , —NHCO 2 R 1 , —NHSOR 1 or —NHSO 2 R 1 ;
R 1 represents C 1 -C 6 haloalkyl or C 1 -C 6 alkyl. A benzyl compound represented by formula (11):

[Wherein R 2 represents a hydrogen atom, a halogen atom, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy or C 1 -C 6 alkyl,
R 3 represents a hydrogen atom, a halogen atom, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy or C 1 -C 6 alkyl, and R 2 and R 3 together with the carbon atom to which each is attached together with C 3 -C 6 cycloalkyl may be formed,
R 4 represents a hydrogen atom, a halogen atom, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy or C 1 -C 6 alkyl,
R 5 represents a hydrogen atom, a halogen atom, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy or C 1 -C 6 alkyl, and R 4 and R 5 together with the carbon atom to which each is bonded together, C 3 -C 6 cycloalkyl may be formed,
n represents an integer of 0, 1, 2, or 3;
X 2 represents a halogen atom, methanesulfonyloxy, trifluoromethanesulfonyloxy or p-toluenesulfonyloxy. Wherein the amide compound represented by formula (12) is reacted in the presence of a base:

[Wherein, A, Y, R 1 , R 2 , R 3 , R 4 , R 5 , n, and X 2 represent the same meaning as described above. ] The manufacturing method of the N-benzylamide compound represented by this.
Formula (12):

[In the formula, A represents —CH═CH— or a sulfur atom,
Y represents —NO 2 , —NH 2 , —NHCO 2 R 1 , —NHSOR 1 or —NHSO 2 R 1 ;
R 1 represents C 1 -C 6 haloalkyl or C 1 -C 6 alkyl,
R 2 represents a hydrogen atom, a halogen atom, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy or C 1 -C 6 alkyl,
R 3 represents a hydrogen atom, a halogen atom, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy or C 1 -C 6 alkyl, and R 2 and R 3 together with the carbon atom to which each is attached together with C 3 -C 6 cycloalkyl may be formed,
R 4 represents a hydrogen atom, a halogen atom, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy or C 1 -C 6 alkyl,
R 5 represents a hydrogen atom, a halogen atom, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy or C 1 -C 6 alkyl, and R 4 and R 5 together with the carbon atom to which each is bonded together, C 3 -C 6 cycloalkyl may be formed,
n represents an integer of 0, 1, 2 or 3,
X 2 represents a halogen atom, methanesulfonyloxy, trifluoromethanesulfonyloxy or p-toluenesulfonyloxy. Wherein the N-benzylamide compound represented by the formula (10) is reacted in the presence of a base:

[Wherein, A, Y, R 1 , R 2 , R 3 , R 4 , R 5 and n represent the same meaning as described above. ] The manufacturing method of the N-benzyl lactam compound represented by this.
20. The production method according to claim 17, wherein a phase transfer catalyst is added as an additive.
21. The manufacturing method according to claim 17, wherein n represents 0.
21. The manufacturing method according to claim 17, wherein n represents an integer of 1.
21. The manufacturing method according to claim 17, wherein n represents an integer of 2.
21. The manufacturing method according to claim 17, wherein n represents an integer of 3.
The base is lithium hydroxide, sodium hydroxide, potassium hydroxide, magnesium hydroxide, calcium hydroxide, barium hydroxide, sodium carbonate, potassium carbonate, cesium carbonate, sodium bicarbonate, potassium bicarbonate, sodium phosphate, potassium phosphate, The production method according to any one of claims 17 to 24, which is sodium monohydrogen phosphate or potassium monohydrogen phosphate.
The production method according to claim 25, wherein the base is sodium hydroxide, potassium carbonate or potassium phosphate.
Phase transfer catalysts are tetramethylammonium chloride, tetramethylammonium bromide, tetra-n-butylammonium fluoride, tetra-n-butylammonium chloride, tetra-n-butylammonium bromide, tetra-n-butylammonium iodide, tetra -N-butylammonium hydrogen sulfate, tetra-n-butylammonium hydroxide, benzyltrimethylammonium chloride, benzyltrimethylammonium bromide, benzyltri-n-butylammonium chloride, benzyltri-n-butylammonium bromide, tetraethylphosphonium bromide, tetra- n-butylphosphonium bromide, tetra-n-butylphosphonium chloride or tetraphenylphosphonium bromide Method for producing N- benzyl lactam compound according to 20-26.
The production method according to claim 27, wherein the phase transfer catalyst is tetra-n-butylammonium bromide.
29. The production method according to claim 17, wherein A represents —CH═CH—.
In the above formula, A represents a sulfur atom.