KR20030085788A - Pyridine derivatives, process for the preparation thereof, and use as an intermediate of herbicides - Google Patents

Abstract

PURPOSE: A process for producing a new pyridine derivative is provided. The pyridine derivative can be effectively used in production of fluoroalkylpyridine-sulfonyl urea derivatives exhibiting excellent herbicidal activity as a herbicide intermediate. CONSTITUTION: A pyridine derivative of the formula(1) useful as an intermediate of fluoroalkylpyridine-sulfonyl urea derivatives of the formula(2) is obtained by reacting a compound of the formula(6) with a copper(II) salt of CuY'2 in the presence of a solvent to give a compound of the formula(1c), or reacting the compound of the formula(1c) with a compound(MF) in the presence of a solvent and optionally a phase transfer catalyst to give a compound of the formula(1b). In formula, R1 is H, cyano, C1-4 alkyl, C3-6 cycloalkyl, C1-4 alkylcarbonyl, C1-4 alkoxymethyl, or -C(=S)OEt, 1-5 substituted benzyl substituted with a substituent selected from halogen, C1-4 alkyl and C1-4 alkoxy or non-substituted benzyl, or SQ in which Q is pyridine radicals; R2 is H or C1-4 alkyl; and Y exhibits halogen.

Description

Pyridine derivatives, process for the preparation, and use as an intermediate of herbicides}

The present invention relates to a novel pyridine derivative of formula (1), a process for preparing the same, and a use as an intermediate of a fluoroalkylpyridine-sulfonylurea derivative of formula (2) exhibiting excellent herbicidal activity.

[Formula 1]

[Formula 2]

In the above formula,

R ¹ is hydrogen, cyano, C ₁ -C ₄ -alkyl, C ₃ -C ₆ -cycloalkyl, C ₁ -C ₄ -alkylcarbonyl, C ₁ -C ₄ -alkoxymethyl, or -C (= S Or benzyl unsubstituted or substituted 1 to 5 by a substituent selected from halogen, C ₁ -C ₄ -alkyl and C ₁ -C ₄ -alkoxy,

R ¹ represents SQ, where Q represents the following pyridine radical:

Q:

R ² represents hydrogen or C ₁ -C ₄ -alkyl,

Y represents a halogen atom,

R ³ represents hydrogen or C ₁ -C ₄ -alkylcarbonyl.

In particular, when R ¹ represents SQ, the compound of Formula 1 forms a disulfide compound having a symmetric structure of the following Formula (1a).

Compounds of formula (1) according to the invention are fluoroalkyls of formula (2) which are known to have excellent herbicidal activity in the prior art (see WO 92/14728, WO 96/12708, WO 97/31913). It can be usefully used as an intermediate for preparing pyridine-sulfonylurea derivatives.

[Formula 2]

Wherein R ² and R ³ are as defined above.

As known from WO 92/14728, WO 96/12708 and WO 97/31913, the fluoroalkylpyridine-sulfonylurea derivatives of formula (2) can be used as It is synthesized via.

Wherein R ² is as defined above.

However, some problems have been found in synthesizing the pyridyl ketone compound of formula (5) which is a key intermediate. That is, as shown in the following reaction formula (1), since n- BuLi is used in the process of introducing a carbon-carbon bond to the position 2 of the pyridine ring, it is required to have an extreme condition of -70 ° C. or less and an extreme anhydrous condition. Is:

Moreover, since sulfonamide has been introduced at position 3 of pyridine in advance, side reactions may occur due to dehydrogenation of amides, which requires attention.

Therefore, the present inventors conducted intensive research to devise a method for easily preparing a pyridyl ketone compound of formula (5), which is a key intermediate of an excellent herbicide compound, and in the process, developed a new compound of formula (1). The present invention has been completed as a result of discovering that the compound can be very useful for preparing the compound of formula (5).

It is therefore an object of the present invention to provide novel pyridine derivatives of formula (1).

It is also an object of the present invention to provide a process for preparing the compound of formula (1).

It is also an object of the present invention to provide a process for preparing a compound of formula (5) using a compound of formula (1).

The present invention relates to novel pyridine derivatives of formula (1)

[Formula 1]

In the above formula,

R ¹ is hydrogen, cyano, C ₁ -C ₄ -alkyl, C ₃ -C ₆ -cycloalkyl, C ₁ -C ₄ -alkylcarbonyl, C ₁ -C ₄ -alkoxymethyl, or -C (= S Or benzyl unsubstituted or substituted 1 to 5 by a substituent selected from halogen, C ₁ -C ₄ -alkyl and C ₁ -C ₄ -alkoxy,

R ¹ represents SQ, where Q represents the following pyridine radical:

Q:

R ² represents hydrogen or C ₁ -C ₄ -alkyl,

Y represents a halogen atom.

In particular, when R ¹ represents SQ, the compound of Formula 1 forms a disulfide compound having a symmetric structure of the following Formula (1a).

[Formula 1a]

Substituents mentioned herein have the following meanings.

Halogen means fluorine, chlorine, bromine, iodine and preferably fluorine, chlorine, bromine.

Alkyl means a straight or branched chain saturated hydrocarbon such as methyl, ethyl, n -propyl, isopropyl, n -butyl, or various butyl isomers, preferably methyl, ethyl, n -propyl, isopropyl, or t- butyl Means.

Alkoxy are methoxy, ethoxy, n - it represents a butoxy, or straight or means a branched saturated hydrocarbon oxy, and preferably methoxy or ethoxy, such as the various butyl isomers-propoxy, isopropoxy, n.

Cycloalkyl means cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl, preferably cyclopropyl or cyclohexyl.

Alkylcarbonyl means acetyl, propionyl, n- butyroyl, isobutyroyl, s- butyroyl, or t- butyroyl and preferably means acetyl.

Alkoxymethyl means methoxymethyl, ethoxymethyl, n -propoxymethyl, isopropoxymethyl, n -butoxymethyl, isobutoxymethyl, s -butoxymethyl, or t -butoxymethyl, preferably Means methoxymethyl.

Preferred compounds among the compounds of formula (1) according to the present invention R ¹ is C ₁ -C ₄ - alkyl and C ₁ -C ₄ - substituted by 1 to 5 substituents selected from alkoxy, or represent or an unsubstituted benzyl , C ₁ -C ₄ -alkyl, C ₁ -C ₄ -alkoxymethyl, -C (= S) OEt, or SQ, wherein Q is as defined above and R ² represents hydrogen, methyl or ethyl , Y represents a fluorine, chlorine or bromo atom.

More preferred compounds are those in which R ¹ represents 4-methoxybenzyl, benzyl, isopropyl, t-butyl, methoxymethyl, -C (= S) OEt, or SQ, wherein Q is as defined above and R ² Is hydrogen, methyl or ethyl, and Y is a fluorine, chlorine or bromo atom.

The compound of formula (1) according to the present invention is prepared by reacting a compound of formula (6) with a copper (II) salt of formula (7) in a solvent to prepare a compound of formula (1c), The compound of formula (c) can be prepared by reacting the compound of formula (8) with a compound of formula (8), optionally in the presence of a phase transfer catalyst in a solvent. Accordingly, another object of the present invention is to provide a method for preparing such a compound of formula (1).

The reactions are shown in the respective reaction formulas and detailed reaction conditions are as follows.

In the above formula

R ¹ and R ² are as defined above,

Y 'represents a chlorine or bromo atom.

In the process of Scheme 2, the ketone compound of formula (6) is reacted with 2 to 3 equivalents of the corresponding copper (II) salt, ie CuCl ₂ if Y 'is chlorine, or CuBr if Y' is bromo Reaction with ₂ may be carried out to obtain a compound of the formula (1c).

In this reaction, a solvent may be used a conventional solvent that does not participate in the reaction by itself, preferably hydrocarbons such as chloroform, dichloromethane, dichloroethane, aromatic hydrocarbons such as toluene, benzene, xylene, methyl acetate, ethyl Acetates such as acetate and isopropyl acetate, alcohols such as methanol, ethanol and isopropanol, ethers such as dimethyl ether, diethyl ether, methyl t-butyl ether, dimethoxyethane, tetrahydrofuran and dioxane alone or Use by mixing.

The reaction temperature can be carried out in the range of -20 ° C to 150 ° C, preferably 10 ° C to 80 ° C.

Pyridyl ketone compounds of formula (6) used as starting materials are described in Kevin A. Memoli, Tetrahedron Letters 37, 3617 (1996); DE 4304007 A1; or Blank, B. et al., J. Med. Chem. 1974, 17, pp 1065-1071) or readily prepared by the same method as disclosed herein.

On the other hand, among the compounds of the formula (1) according to the present invention Y = F, that is, a compound of the formula (1b) is a compound of the formula (1c) corresponding to the formula (8) It can obtain by substitution reaction with a nucleophile.

In the above formula

R ¹ and R ² are as defined above,

Y 'represents a chlorine or bromo atom,

M represents an alkali metal.

As the nucleophile of the formula (8), a fluoride compound of an alkali metal is used, and preferably sodium fluoride, potassium fluoride or lithium fluoride can be used. The nucleophile of the formula (8) is preferably reacted with 1 to 3 equivalents to the compound of the formula (1c).

It is preferable to use a polar solvent as the solvent. Preferably, amides such as formamide, dimethylformamide and dimethylacetamide, glycols such as ethylene glycol and polyethylene glycol, nitriles such as acetonitrile and propionitrile use.

The reaction can be promoted by using crown ethers or quaternary alkylammonium salts as phase transfer catalysts. As the quaternary alkylammonium salt, triethylbenzyl ammonium chloride, tetrabutylammonium fluoride, trioctylmethylammonium fluoride, tetrabutylammonium bromide and the like are preferably used.

The reaction temperature can be carried out in the range of 20 ° C to 150 ° C, preferably 20 ° C to 130 ° C.

To clarify the compounds of the formula (1) according to the present invention prepared according to the above-described method as shown in the individual compounds as shown in Table 1 below.

R ¹ R ² Y One Me Me Br 2 Me Me Cl 3 Me Me F 4 Et Me Br 5 Et Me Cl 6 i-Pr Me Br 7 i-Pr Me Cl 8 i-Pr Me F 9 t-Bu Me Br 10 t-Bu Me Cl 11 t-Bu Me F 12 Cyclopropyl Me Br 13 Cyclobutyl Me Br 14 Cyclopentyl Me Br 15 Cyclohexyl Me Br 16 Acetyl Me Br 17 Propionyl Me Br 18 Butyroyl Me Br 19 benzyl Me Br 20 benzyl Me Cl 21 benzyl Me F 22 4-methoxybenzyl Me Br 23 4-methoxybenzyl Me Cl 24 4-methoxybenzyl Me F 25 2-methylbenzyl Me Br 26 4-t-butylbenzyl Me Br 27 1,2-dimethylbenzyl Me Br 28 1,2,3,4,5-perchlorobenzyl Me Br 29 MeOCH ₂ Me F 30 MeOCH ₂ Me Cl 31 MeOCH ₂ Me Br 32 EtOCH ₂ Me Br 33 n-PrOCH ₂ Me Br

34 i-PrOCH ₂ Me Br 35 CN Me Br 36 C (= S) OEt Me Br 37 C (= S) OEt Me F 38 39 40 41 i-Pr Et Br 42 i-Pr Et Cl 43 i-Pr Et F 44 benzyl Et Br 45 benzyl Et Cl 46 benzyl Et F 47 i-Pr H Br 48 i-Pr H Cl 49 i-Pr H F 50 benzyl H Br 51 benzyl H Cl 52 benzyl H F

From pyridylketone compounds of formula (6), which are known compounds or readily obtainable from known compounds, the compounds of formula (1b) according to the invention prepared under much mild reaction conditions without the need to maintain extreme low temperature or anhydrous conditions are Very usefully used to prepare the compound of (5), the compound of formula (5) thus prepared is a key intermediate in the preparation of fluoroalkylpyridine-sulfonyl urea derivatives of formula (2) with excellent herbicidal activity Used as

That is, according to the present invention, a compound of formula (5) is prepared by reacting a compound of formula (1b) with chlorine gas in a mixture of water or an acetic acid aqueous solution and an organic solvent and then reacting it with t-butylamine in an organic solvent. A method is provided, which is shown in Scheme (4).

Wherein R ¹ and R ² are as defined above.

As the reaction is carried out, the mercaptoether group included in the compound of formula (1b) is converted into a sulfonamide group.

First, in the first step of reacting with chlorine gas, a conventional solvent that does not participate in the reaction itself may be used. Specifically, water or acetic acid aqueous solution and an organic solvent are mixed in a volume ratio of 1: 1 to 1: 3. Use what you have. At this time, as the organic solvent, aromatic hydrocarbons such as toluene, benzene, xylene, chlorinated hydrocarbons such as chloroform, dichloromethane, 1,2-ethylenedichloride, dimethyl ether, diethyl ether, methyl t-butyl ether, dimethoxy Ethers, such as ethane, tetrahydrofuran, and dioxane, are used preferably. The reaction can be promoted by using 10-30% dilute acetic acid in place of water. The reaction temperature is in the range of -20 deg. C to 80 deg. C with a preferred range of 0 deg. C to 40 deg.

In the second step of reacting with t-butylamine, as the solvent, chlorinated hydrocarbons such as chloroform, dichloromethane and dichloroethane or aromatic hydrocarbons such as toluene, benzene and xylene are preferably used. Alternatively, the organic solvent layer may be used as it is without any further purification after the first step reaction. t-butylamine is slowly added dropwise in an amount of 1 to 2 equivalents. The reaction temperature is in the range of -20 ° C to 100 ° C, preferably in the range of -20 ° C to 30 ° C.

Hereinafter, the present invention will be described in more detail based on the following Preparation Examples and Examples. However, these preparation examples and examples are only for the understanding of the present invention, and the scope of the present invention in any sense is not limited thereto.

Preparation Example 1

Synthesis of 1- (3-isopropylsulfanylpyridin-2-yl) -propan-1-one

2-cyano-3-isopropylsulfanylpyridine (3.56 g, 20 mmol) was dissolved in tetrahydrofuran (40 mL) and an ether solution (8 mL) of 3M ethylmagnesium bromide was added dropwise at 0 ° C. When the starting material was completely consumed, the mixture was stirred at room temperature for 1 hour, and then the pH of the reaction solution was adjusted to 2 by adding 2N hydrochloric acid. The reaction solution was extracted twice with dichloromethane (200 mL), the organic layer was concentrated and separated and purified by silica gel column chromatography to obtain a white title compound (3.76 g, 18 mmol, 90% yield).

¹ H NMR (CDCl ₃ , δ): 8.38 (d, 1H), 7.75 (d, 1H), 7.40-7.32 (m, 1H), 3.49 (quin, 1H), 3.18 (q, 2H), 1.38 (d , 6H), 1.21 (t, 3H)

Example 1

Synthesis of 1- (3-isopropylsulfanylpyridin-2-yl) -2-chloropropan-1-one

Dissolve 1- (3-isopropylsulfanylpyridin-2-yl) -propan-1-one (1.88 g, 9 mmol) in toluene (20 mL), followed by 2.2 equivalents of copper (II) chloride (2.66 g, 19.8 mmol). ) Was added and stirred at room temperature for 5 hours. Water (25 mL) was added dropwise to the reaction solution, and the resulting solid was filtered through celite. The filtrate was separated and the aqueous layer was extracted twice with toluene (10 mL). The combined organic layers were concentrated and separated and purified by silica gel column chromatography to obtain a white title compound (1.76 g, 7.2 mmol, yield 80%).

¹ H NMR (CDCl ₃ , δ): 8.43 (d, 1H), 7.77 (d, 1H), 7.43-7.37 (m, 1H), 6.01 (q, 1H), 3.51 (quin, 1H), 1.73 (d , 3H), 1.45-1.37 (m, 6H)

Example 2

Synthesis of 1- (3-benzylsulfanylpyridin-2-yl) -2-chloropropan-1-one

1- (3-benzylsulfanylpyridin-2-yl) -propan-1-one (2.57 g, 10 mmol) was reacted with copper (II) chloride (2.96 g, 22 mmol) in the same manner as in Example 1 to give the title Compound (2.62 g, 9 mmol, yield 90%) was obtained.

¹ H NMR (CDCl ₃ , δ): 8.42 (d, 1H), 7.74 (d, 1H), 7.48-7.27 (m, 6H), 6.01 (q, 1H), 4.17 (s, 2H), 1.73 (d , 3H)

Example 3

Synthesis of 1- (3-isopropylsulfanylpyridin-2-yl) -2-bromopropan-1-one

Dissolve 1- (3-isopropylsulfanylpyridin-2-yl) -propan-1-one (1.88 g, 9 mmol) in toluene (20 mL), followed by 2.2 equivalents of copper bromide (II) (4.42 g, 19.8 mmol). ) Was added and stirred at room temperature for 5 hours. Water (25 mL) was added dropwise to the reaction solution, and the resulting solid was filtered through celite. The filtrate was separated and the aqueous layer was extracted twice with toluene (10 mL). The combined organic layers were concentrated and separated and purified by silica gel column chromatography to obtain a white title compound (2.20 g, 7.65 mmol, yield 85%).

¹ H NMR (CDCl ₃ , δ): 8.43 (d, 1H), 7.79 (d, 1H), 7.44-7.37 (m, 1H), 6.06 (q, 1H), 3.53 (quin, 1H), 1.91 (d , 3H), 1.42 (dd, 6H)

Example 4

Synthesis of Dithiocarboxylic Acid O-ethyl, S- [2- (2-bromopropionyl) pyridin-3-yl] Ester

Dithiocarboxylic acid O-ethyl, S- [2- (propionyl) pyridin-3-yl] ester (2.55 g, 10 mmol) was prepared in the same manner as in Example 3 with copper (II) bromide (4.91 g, 22 mmol). Reaction gave the title compound (3.00 g, 9 mmol, yield 90%).

¹ H NMR (CDCl ₃ , δ): 8.41 (d, 1H), 7.72 (d, 1H), 7.40-7.37 (m, 1H), 6.07 (q, 1H), 2.92 (q, 2H), 1.89 (d , 3H), 1.38 (t, 3H)

Example 5

Synthesis of 1- (3-benzylsulfanylpyridin-2-yl) -2-bromopropan-1-one

Reacting 1- (3-benzylsulfanylpyridin-2-yl) -propan-1-one (2.57 g, 10 mmol) with copper (II) bromide (4.91 g, 22 mmol) in the same manner as in Example 3 Compound (3.03 g, 9 mmol, yield 90%) was obtained.

¹ H NMR (CDCl ₃ , δ): 8.41 (d, 1H), 7.73 (d, 1H), 7.44-7.29 (m, 6H), 6.05 (q, 1H), 4.17 (s, 2H), 1.90 (d , 3H)

Example 6

Synthesis of 1- (3-t-butylsulfanylpyridin-2-yl) -2-bromopropan-1-one

Reaction of 1- (3-t-butylsulfanylpyridin-2-yl) -propan-1-one (2.57 g, 10 mmol) with copper (II) bromide (4.91 g, 22 mmol) in the same manner as in Example 3 To give the title compound (2.11 g, 7 mmol, yield 70%).

¹ H NMR (CDCl ₃ , δ): 8.57 (d, 1H), 7.90 (d, 1H), 7.36-7.30 (m, 1H), 6.07 (q, 1H), 3.10 (q, 1H), 1.24 (s , 9H), 1.15 (t, 3H)

Example 7

Synthesis of Bis ((2- (2-bromopropionyl) pyridin-3-yl) -disulfide

Bis ((2-propionyl) pyridin-3-yl) -disulfide (3.32 g, 10 mmol) was reacted with copper (II) bromide (9.82 g, 44 mmol) in the same manner as in Example 3 to give the title compound (3.43 g , 7 mmol, yield 70%) was obtained.

¹ H NMR (CDCl ₃ , δ): 8.45 (d, 1H), 8.10 (d, 1H), 7.42-7.35 (m, 1H), 6.08 (q, 1H), 1.98 (d, 3H)

Example 8

Synthesis of 1- (3-benzylsulfanylpyridin-2-yl) -2-fluoropropane-1-one

1- (3-benzylsulfanylpyridin-2-yl) -2-chloropropan-1-one (1.46 g, 5 mmol) was dissolved in polyethylene glycol 300 (3 mL), followed by potassium fluoride (0.51 g, 8.75). mmol) was added. It was heated to 70 ° C. for 5 hours and then cooled. Toluene (5 mL) and water (5 mL) were added, and the layers were separated. The organic layer was washed with 30% aqueous sulfuric acid solution (1 ml) and filtered through acidic clay. The filtrate was concentrated and separated and purified by silica gel column chromatography to obtain a white title compound (1.10g, 4mmol, yield 80%).

¹ H NMR (CDCl ₃ , δ): 8.38 (d, 1H), 7.75 (d, 1H), 7.48-7.29 (m, 6H), 6.28 (dq, 1H, J 1 = 51 Hz), 4.16 (s, 2H) , 1.67 (dd, 3H, J1 = 27 Hz)

Example 9

Synthesis of 1- (3-isopropylsulfanylpyridin-2-yl) -2-fluoropropane-1-one

1- (3-isopropylsulfanylpyridin-2-yl) -2-bromopropane-1-one (1.44 g, 5 mmol) was dissolved in polyethylene glycol 300 (3 mL), and the same procedure as in Example 8 was performed. Reaction with potassium fluoride (0.51 g, 8.75 mmol) gave the title compound (0.91 g, 4 mmol, yield 80%).

¹ H NMR (CDCl ₃ , δ): 8.37 (d, 1H), 7.77 (d, 1H), 7.42-7.37 (m, 1H), 6.23 (dq, 1H, J 1 = 62 Hz), 3.52 (quin, 1H) , 1.70 (d, 3H), 1.50 (dd, 6H, J1 = 65 Hz)

Example 10

Synthesis of Dithiocarboxylic Acid O-ethyl, S- [2- (2-fluoropropionyl) pyridin-3-yl] Ester

Dithiocarboxylic acid O-ethyl, S- [2- (2-bromopropionyl) pyridin-3-yl] ester (1.67 g, 5 mmol) was dissolved in polyethylene glycol 300 (3 mL) and then the same as in Example 8 Reaction with potassium fluoride (0.51 g, 8.75 mmol) gave the title compound (0.98 g, 3.6 mmol, yield 72%).

¹ H NMR (CDCl ₃ , δ): 8.37 (d, 1H), 7.73 (d, 1H), 7.43-7.37 (m, 1H), 6.29 (dq, 1H, J 1 = 65 Hz), 2.94 (q, 2H) , 1.70 (dd, 3H, J1 = 49 Hz), 1.42 (t, 3H)

Example 11

Synthesis of N-t-butyl- [2- (2-fluoropropionyl) -pyridin-3-yl] sulfonamide

Dilute 1- (3-benzylsulfanylpyridin-2-yl) -2-fluoropropane-1-one (2.75 g, 10 mmol) in dichloromethane (10 mL) and acetic acid (10 mL), and then chlorine at 0 ° C. (Gas) was bubbled for 30 minutes. When the reaction solution turned transparent yellow, the chlorine was stopped and nitrogen was bubbled into the reaction solution for 1 hour to remove excess chlorine. The reaction solution was left to stand and the layers were separated, and then the organic layer was cooled to 0 ° C. T-butylamine (11 mmol) was added dropwise to the cooled organic layer. Water (10 mL) was added to the reaction mixture, followed by concentration. The organic layer was concentrated and separated and purified by silica gel column chromatography to obtain a white title compound (2.33 g, 8.1 mmol, 81% yield).

As described above, the use of the novel compounds of formula (1) according to the present invention makes it very efficient to prepare compounds of formula (5) which serve as key intermediates for the preparation of compounds of formula (2) having excellent herbicidal activity. can do.

Claims (15)

Pyridine Derivatives of Formula (1) [Formula 1] In the above formula, R ¹ is hydrogen, cyano, C ₁ -C ₄ -alkyl, C ₃ -C ₆ -cycloalkyl, C ₁ -C ₄ -alkylcarbonyl, C ₁ -C ₄ -alkoxymethyl, or -C (= S Or benzyl unsubstituted or substituted 1 to 5 by a substituent selected from halogen, C ₁ -C ₄ -alkyl and C ₁ -C ₄ -alkoxy, R ¹ represents SQ, where Q represents the following pyridine radical: Q: R ² represents hydrogen or C ₁ -C ₄ -alkyl, Y represents a halogen atom. The method of claim 1, wherein, R ¹ is C ₁ -C ₄ - alkyl and C ₁ -C ₄ - by a substituent selected from alkoxy of 1 to 5, or a substituted or represent unsubstituted benzyl, C ₁ -C ₄ - alkyl, C ₁ -C ₄ -alkoxymethyl, -C (= S) OEt, or SQ, wherein Q is as defined in claim 1, R ² represents hydrogen, methyl or ethyl, Y represents fluorine, chlorine Or a compound representing a bromo atom. 3. The compound of claim 1, wherein R ¹ represents 4-methoxybenzyl, benzyl, isopropyl, t-butyl, methoxymethyl, —C (═S) OEt, or SQ, wherein Q is the first A compound as defined in the above, wherein R ² represents hydrogen, methyl or ethyl and Y represents a fluorine, chlorine or bromo atom. The method according to claim 1 or 2, 1- (3-isopropylsulfanylpyridin-2-yl) -2-chloropropan-1-one; 1- (3-benzylsulfanylpyridin-2-yl) -2-chloropropan-1-one; 1- (3-isopropylsulfanylpyridin-2-yl) -2-bromopropan-1-one; Dithiocarboxylic acid O-ethyl, S- [2- (2-bromopropionyl) pyridin-3-yl] ester; 1- (3-benzylsulfanylpyridin-2-yl) -2-bromopropan-1-one; 1- (3-t-butylsulfanylpyridin-2-yl) -2-bromopropan-1-one; Bis ((2- (2-bromopropionyl) pyridin-3-yl) -disulfide; 1- (3-benzylsulfanylpyridin-2-yl) -2-fluoropropan-1-one; 1- (3-isopropylsulfanylpyridin-2-yl) -2-fluoropropan-1-one; And Dithiocarboxylic acid O-ethyl, S- [2- (2-fluoropropionyl) pyridin-3-yl] ester. The compound of formula (6) is reacted with a copper (II) salt of formula (7) in a solvent to prepare a compound of formula (1c), or the obtained compound of formula (1c) is optionally A process for preparing the compound of formula (1) as defined in claim 1, characterized by reacting with a compound of formula (8) in the presence to produce a compound of formula (1b): [Formula 6] [Formula 7] [Formula 1c] [Formula 8] [Formula 1b] In the above formula R ¹ and R ² are as defined in claim 1, Y 'represents a chlorine or bromo atom, M represents an alkali metal. The method of claim 5, wherein the solvent in the preparation of the compound of formula (1c) is chloroform, dichloromethane, dichloroethane, toluene, benzene, xylene, methyl acetate, ethyl acetate, isopropyl acetate, methanol, ethanol, isopropanol, dimethyl At least one selected from ether, diethyl ether, methyl t-butyl ether, dimethoxyethane, tetrahydrofuran and dioxane. The process of claim 5 wherein the reaction temperature is in the range of −20 ° C. to 150 ° C. in the course of preparing the compound of formula (1c). The process according to claim 5, wherein the solvent in the preparation of the compound of formula (1b) is at least one selected from formamide, dimethylformamide, dimethylacetamide, ethylene glycol, polyethylene glycol, acetonitrile and propionitrile. The process according to claim 5, wherein the reaction temperature is in the range of 20 ° C to 150 ° C in the preparation of the compound of formula (1b). A method of preparing the compound of formula (5), wherein the compound of formula (1b) is reacted with chlorine gas in a mixture of water or an acetic acid aqueous solution and an organic solvent and then reacted with t-butylamine in an organic solvent. : [Formula 1b] [Formula 5] In the above formula R ¹ and R ² are as defined in claim 1. The method of claim 10, wherein in the first step of reacting with chlorine gas, the solvent is a water or acetic acid aqueous solution mixed with an organic solvent in a volume ratio of 1: 1 to 1: 3. The method of claim 11, wherein the organic solvent is toluene, benzene, xylene, chloroform, dichloromethane, 1,2-ethylenedichloride, dimethylether, diethylether, methyl t-butylether, dimethoxyethane, tetrahydrofuran and di At least one selected from oxane. The process of claim 10, wherein the reaction temperature of the first step of reacting with chlorine gas ranges from -20 ° C to 80 ° C. The process of claim 10, wherein the organic solvent in the second step of reacting with t-butylamine is at least one selected from chloroform, dichloromethane, dichloroethane, toluene, benzene and xylene. The process of claim 10, wherein the reaction temperature of the second step of reacting with t-butylamine is in the range of −20 ° C. to 100 ° C. 12.