WO2001087864A1

WO2001087864A1 - Thiazolylethanone compounds and process for the preparation thereof

Info

Publication number: WO2001087864A1
Application number: PCT/JP2001/004169
Authority: WO
Inventors: Tomio Yagihara; Toshio Aihara; Tatsumi Suzuki; Tetsushi Ookuchi
Original assignee: Nippon Soda Co.,Ltd.
Priority date: 2000-05-19
Filing date: 2001-05-18
Publication date: 2001-11-22
Also published as: AU2001256774A1

Abstract

Compounds of the general formula (1) useful as intermediates in the preparation of agricultural chemicals and drugs; and a process for the preparation of the compounds: (1) wherein A is optionally substituted pyridyl, thienyl, phenyl, or the like; X is nitro, cyano, halogeno, C1-6 alkyl, C1-6 haloalkyl, or the like; and n is an integer of 0 to 5.

Description

Specification

Thiazolyl ethanone compound and method for producing the same

The present invention relates to a method for producing a thiazolyl ethanone compound useful as an intermediate for producing agrochemicals, in particular, an intermediate for producing insecticides and acaricides.

Background technology:

A method for producing a thiazolylethanone compound from 2-methylthiazol is described in Pharmaceutical Journal 113 (1) 32 1993 in the presence of a strong base such as n-butyllithium in the presence of 2,4-dimethylthiazole and carbohydrate. A method has been described in which an on is generated and reacted with benzamide to obtain 2-benzylmethyl-4-methylthiazole. However, this method is not only disadvantageous for mass synthesis using a lithium compound at cryogenic temperatures, but also hardly causes a lithiation reaction of the 2-position methyl group depending on the substituent at the 4-position of the thiazole ring. The disadvantage is that the rate is very low.

For example, in the methylation reaction of 4-aryl-2-methylthiazole with methyl iodide, lithiation with n-butyllithium occurs mainly at the 5-position on the thiazole ring, and the 5-methyl form is preferentially obtained. (J, Org. Chem. Vol. 39, No. 9, 1192 974)), because almost no 2-methyl group can be lithiated (for example, a 5-litho form: a 2-methyl litho form). = 9 1: 4), the desired product cannot be expected to be obtained by reaction with ester amide.

Japanese Patent Application Laid-Open No. 8-1577363 discloses a reaction between a 2-methylthiazole compound and a benzamide in the presence of n-butyllithium to give 2-benzoylmethylthiazol. A method for synthesizing is described.

Furthermore, a method is known in which 2-methylsulfonyl-4,5-diphenylthiazole is reacted with acetophenone to synthesize a 2-benzoylmethylthiazole compound. (Pharmaceutical Magazine 110 (2) 105-111 (199))

As a reaction similar to the present invention, a method of synthesizing benzoylmethylthiazoles by benzoylation of 2-methylbenzthiazole instead of 2-methylthiazole is known. (J. Prakt. Chemie Band 312, Heft 2, 1979, S. 320-322)

(In the formula, R "represents an alkyl group or the like.) DISCLOSURE OF THE INVENTION

An object of the present invention is to provide a thiazolylethanone compound having a substituent at the 4-position which is useful as an intermediate for the production of agrochemicals, particularly as an intermediate for the production of insecticides and acaricides, and its industrially advantageous production Is to provide a way.

The present invention provides: 1. Formula (1)

(In the formula, A, halogen atom, C _{2 6} alkyl group, a haloalkyl group, - 6 § alkoxy group, optionally substituted C _{3 6} cycloalkyl group, an optionally substituted pyridyl group G, with G Represents a phenyl group which may be substituted with a phenyl group which may be substituted with G or a phenyl group which may be substituted with G, and X represents a nitro group, a cyano group, a halogen atom, a C ₆ alkyl group, a C i— Represents a ₆ haloalkyl group, a C ₆ alkoxy group, an optionally substituted phenyl group or an optionally substituted phenoxy group, and n is 0 or 1 to 5 Represents an integer.

G represents a halogen atom, a nitro group, an alkyl group, or a C-Is alkoxy group, and when having two or more substituents, G may be different. A compound represented by the formula: 2. Formula (2)

(Wherein X and n have the same meanings as described above), and a benzoylthioacetamide compound represented by the formula:

Equation (3) A, — CO— CH ₂ — Y (3)

(A wherein Y is a halogen atom, A 'is - 6 alkyl group, optionally substituted C ₃ one ₆ cyclo alkyl group, pyridyl group optionally substituted by G, may be substituted by G thienyl A group or a phenyl group which may be substituted with G, wherein G has the same meaning as in the above 1.), and a compound represented by the formula (1-1):

(Wherein, A ′, X and n have the same meanings as described above), and a method for producing a thiazolylethanenone derivative represented by the formula:

3. Equation (4)

(In the formula, A represents the same meaning as described above.)

Equation (5) or (6)

(5) (6)

(Wherein, X and n represent the same meanings as described above), and then a hydrolysis reaction is carried out, wherein the thiazolyl ester represented by the above formula (1) is reacted. This is a method for manufacturing a Tanon derivative.

Embodiment of the invention:

In the definition of the compound of the present invention represented by the formula (1), A is a halogen atom such as fluorine, chlorine, bromine, iodine, etc .; ethyl, propyl, isopropyl, butyl, sec-butyl, isobutyl, t-butyl, pentyl and its isomers, hexyl and C ₂ _ ₆ alkyl group isomers thereof, and the like; chloromethyl, triflumizole Ruo Russia methyl, Torifurufuruo Roechiru, C i-6 haloalkyl group such as a penta full O Roe chill; main butoxy, ethoxy , Propoxy, isopropoxy, butoxy, sec —butoxy, isobutoxy, t-butoxy and other C i-e alkoxy groups; cyclopropyl, 1-methylcyclopropyl, 2,2,3,3-tetramethylcyclopropyl, cyclobutyl , Cyclopentyl, 1-methylcyclopentyl, cyclohexyl, 1-methylcyclohexyl Sill, 4 Mechirushiku port to which it may be substituted cyclohexyl, etc. C ₃ - ₆ cycloalkyl group; optionally substituted by a G; which may thienyl group is substituted by G; optionally substituted pin lysyl group optionally in G Represents a good phenyl group or a phenoxy group which may be substituted by G, and m represents 0 or an integer of 1 to 5. G is a halogen atom such as fluorine, chlorine, bromine and iodine; nitro group, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, isoptyl, t-butyl, pentyl and its isomers, hexyl and A C ^ 6 alkyl group such as an isomer thereof; a C i- ₆ alkoxy group such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy, isobutoxy, t-butoxy or an optionally substituted phenyl group; . Examples of the substituent of the phenyl group which may be substituted include a halogen atom such as fluorine, chlorine, bromine and iodine; a C i-6 alkyl group such as methyl, ethyl, propyl, isopropyl, butyl and t-butyl; , triflumizole Ruo Russia methyl, tri furfur O Roe chill, Bae pointer full O Roe chill etc. C 1 _ ₆ C port alkyl group; main butoxy, etc. C 1-6 alkoxy group ethoxy, and the like. X is a nitro group; a cyano group; a halogen atom such as fluorine, chlorine, bromine and iodine; methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, isoptyl, t-butyl, pentyl and isomers thereof, hexyl And C i-6 alkyl groups such as isomers thereof; chill, CL- 6 Haroaru kill group such penta full O Roe chill; main butoxy, Etokishi, propoxy, Isopurobokishi, butoxy, sec - butoxy, isobutoxy, t - C 1- ₆ alkoxy group butoxy; substituted A good phenyl group or a phenyloxy which may be substituted Representing the. Examples of the substituent of the phenyl group or phenoxy group which may be substituted include halogen atoms such as fluorine, chlorine, bromine, and iodine; and carbon atoms such as methyl, ethyl, propyl, isopropyl, butyl, and t-butyl. ₆ alkyl group; chloromethyl, triflumizole Ruo Russia methyl, tri furfur O Roe chill, Bae pointer full O Roe chill like C _ ₆ haloalkyl group; main butoxy, etc. C _i-6 alkoxy groups ethoxy, and the like.

n represents 0 or an integer from 1 to 5; Hereinafter, the production method of the present invention will be described.

Manufacturing method A

(In the formula, A ′, X, Y and n represent the same meaning as described above.)

The production method of the present invention comprises reacting a benzoylthioacetamide compound represented by the formula (2) with a compound represented by the formula (3).

As a reaction solvent, a protic solvent such as water or ethyl alcohol, an ether solvent such as dioxane, a nitrile solvent such as acetonitrile, an aromatic hydrocarbon solvent such as toluene, or a mixed solvent thereof can be used.

The reaction temperature can be usually from room temperature to the boiling point of the solvent used.

During the reaction, hydrogen halide is generated in the system, but the hydrogen halide adversely affects the reaction system. If so, an organic base such as triethylamine or an inorganic base such as sodium hydroxide or sodium bicarbonate may be used to remove hydrogen halide, if necessary. Manufacturing method B

(1)

(In the formula, A, X and n represent the same meaning as described above.)

The reaction between the compound represented by the formula (4) and the compound represented by the formula (5) or (6) is performed in a solvent in the presence of an organic base. As the organic base, aliphatic amines such as triethylamine, heterocycles such as pyridine, polycyclic amines such as DBU and the like can be used. The reaction solvent may be any as long as it allows the reaction to proceed smoothly, and the reaction can be carried out at room temperature to the boiling point of the solvent.

The compound represented by the above formula (7) obtained by this reaction can be isolated and purified by a usual post-treatment. However, by performing the following hydrolysis reaction without isolation, the compound of the above formula (7) can be obtained. The thiazole compound represented by 1) can be obtained. The hydrolysis can be carried out by hydrolysis with alkaline water, and any aluminum hydroxide can be used, and the product can be obtained almost quantitatively.

After completion of the reaction, the desired product can be obtained by performing isolation and purification according to ordinary synthetic organic chemistry techniques. The structure of the target object can be determined by measuring various spectra such as NME, IR, and MASS.

The thiazolyl ethanone compound represented by the formula (1) according to the present invention is structurally There exist isomers of the enol form due to migration, and the present invention includes both isomers. The compounds shown in the following examples were observed as a mixture of a keto form and an enol form under the measurement conditions of ME.

The compound of the present invention represented by the formula (1) and the formula (1-1) obtained as described above is a compound that can be a raw material of a compound expected to have a physiological activity. For example, WO 00/17 The insecticide and acaricide described in 174 etc. can be produced according to the following scheme.

Examples of the halogenating agent used in the halogenation reaction in the above scheme include chlorine, bromine, iodine, phosgene, sulfuryl chloride, thionyl chloride, N-chlorosuccinic imide (NCS :), N-bromosuccinic imide (NBS) And other common halogenating agents. In the case of fluorination, N-fluorobenzenesulfonamides and N-fluoropyridinium salts can be used. The amount of the halogenating agent to be used is generally 1 to 3 mol, per 1 mol of the compound represented by the formula (1).

The reaction solvent is not particularly limited as long as it is an inert solvent. For example, halogenated carbons such as methylene chloride, dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane, cyclobenzene, dichlorobenzene, etc. Hydrogen; saturated hydrocarbons such as pentane, hexane, heptane, and cyclohexane; aromatic hydrocarbons such as benzene, toluene, xylene, and ethylbenzene; and mixed solvents of two or more of these. these Among them, a halogen-based solvent such as chloroform-form-dichloromethane is preferable.

The reaction proceeds smoothly at a temperature in the range of from 11 ° C to the boiling point of the solvent, preferably from 0 ° C to room temperature.

Next, the cyanation reaction is carried out by reacting a cyanating agent in a suitable organic solvent. As the cyanating agent, sodium cyanide, potassium cyanide, calcium cyanide, cuprous cyanide, acetone cyanohydrin, and the like can be used. BEST MODE FOR CARRYING OUT THE INVENTION:

Next, the present invention will be described in detail with reference to examples, but the present invention is not limited to the following examples.

Example 1

2- [4- (2,6-difluorophenyl)-(1,3-thiazol-2-yl)]-1- [2- (trifluoromethyl) phenyl Xnyl] ethane-1-one Manufacturing of

To a solution of 2.2 g of 2-trifluoromethylbenzoylthioacetamide in 20 mL of ethyl alcohol was added 2.1 g of 2,6-difluorophenacyl bromide under ice-cooling. Heated at 60-70 ° C for 3 hours. Ethyl alcohol was distilled off and the remaining oil was purified by silica gel column chromatography (developing solvent: n-hexane / ethyl acetate = 4/1) to obtain 2.5 g of the desired product. Yield: 73.3% mp: 85.0—86.0 ° C Example 2

Production of 2- [4- (2,6-difluorophenyl)-(1,3-thiazol-2-yl)] —1— [2-methylphenyl] ethane

2.5 g of the title compound was obtained in the same manner as in Example 1, except that 1.7 g of 2-methylbenzoylthioacetamide and 2.1 g of 2,6-difluorophenacyl promide were used. . Yield: 86.2% mp: 52.0—54.0 ° C Example 3

2 -— [4— (2,6-difluorophenyl)-(1,3-thiazole-1-yl)] — 1- [4-chlorophenyl] -ethane

1.9 g of the title compound was obtained in the same manner as in Example 1 using 1.9 g of 4-chlorobenzoylthioacetamide and 2.1 g of 2,6-difluorophenacyl bromide. Yield: 92.3% mp: 127.0-129.0 ° C Example 4

2- [4- (2,6-difluorophenyl) -1- (1,3-thiazol-2-yl)] — production of 1- [2- (trifluoromethyl) phenyl] ethane-1-one

4-(2,6-difluorophenyl) 1- 2-methyl-1,3-thiazole 2.0 g was dissolved in 15 ml of acetonitrile, 1.9 g of tridiethylamine and 4.O g of 2- (trifluoromethyl) benzoyl chloride were added, and the mixture was heated under reflux for 48 hours, and the reaction solution was poured into water. Extracted with black-mouthed form. After dehydrating the form layer of the gel with anhydrous magnesium sulfate, the residue obtained by concentration under reduced pressure is purified by silica gel chromatography to obtain 2- [4-1-1 (2,6). —Difluorophenyl) 1 (1,3-thiazol-1-yl)]-1-[2- (trifluoromethyl) phenyl] vinyl 2— (trifluoromethyl) benzoate 3 42 g were obtained. Yield 65.

0% mp 93. 0-95. 0 ° C

2- [4- (2,6-difluorophenyl) -1- (1,3-thiazol-1-yl)] — 1- [2- (trifluoromethyl) phenyl] vinyl 2- (trifluoromethyl) benzo Dissolve 2.2 g of ethyl acetate in 20 ml of ethyl alcohol, add 10 ml of an aqueous solution of 1N sodium hydroxide, stir at 50 to 60 ° C for 3 hours, and pour the reaction solution into ice water. — Acidified with N hydrochloric acid and extracted with black form. The port-form layer was washed with an aqueous sodium hydrogen carbonate solution and then with water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure.

The obtained crystals were washed with n-hexane to obtain 1.29 g of the desired product. Yield 85.0% mp 85.0-86.0 ° C Example 5

Production of 2- [4-phenyl- (1,3-thiazo-lu-2-yl)]-1- [2- (trifluoromethyl) phenyl] ethane-1-one

The same procedure as in Example 4 was carried out using 2.0 g of 4-phenyl-2-methyl-1,3-thiazole 2.0 g and 4.8 g of 2- (trifluoromethyl) benzoyl chloride to give 2- [4-phenylyl]. (1,3-thiazo-1-yl-2-yl)] 1-11 [2- (trifluoromethyl) phenyl] pinyl 2_ (trifluoromethyl) benzoate 3.42 g was obtained. Yield 30.0% mp 127.0—128.0 ° C

Then, 2- [4-phenyl- (1,3-thiazol-2-yl)] — 1— [2- (trifluoromethyl) phenyl] vinyl 2- (trifluoromethyl) benzoate The procedure of Example 4 was repeated using 0.35 g to obtain 0.20 g of the desired product. Yield 87.0% mp 115.0-116.0. C. Example 6

2 -— [4-Methyl- (1,3-thiazol-2-yl)] — 1— [2 -— (Trifluoromethyl) phenyl 1-one

The same procedure as in Example 4 was carried out using 2.0 g of 2,4-dimethyl-1,3-thiazole and 7.4 g of 2- (trifluoromethyl) benzoyl alcohol, to give 2- [4-methyl- (1,1).

3-thiazole-1-yl)]-1- [2- (trifluoromethyl) phenyl] vinyl 2- (trifluoromethyl) benzoate (6.5 g) was obtained. Yield 80.0% m P ll 2.0-113.0 ° C

Then, 1.5 g of 2- [4-methyl- (1,3-thiazoyl-2-yl)]-1— [2- (trifluoromethyl) phenyl] vinyl 2- (trifluoromethyl) benzoate was added. The same procedures used in Example 4 were carried out to obtain 0.79 g of the desired product. Yield 85.0% mp 137.0-138.0. C. Example 7

Preparation of 2- [4- (2,6-difluorophenyl) -1- (1,3-thiazol-2-yl)]-1- [2- (trifluoromethyl) phenyl] ethane-one

Dissolve 2.0 g of 4- (2,6-difluorophenyl) -12-methyl-1,3-thiazole in 15 ml of acetonitrile, and add 1.9 g of tridiethylamine and 2- (trifluoromethyl) benzoyl chloride 4.0 g, heated to reflux for 48 hours, returned to room temperature, added 20 ml of 1N aqueous sodium hydroxide solution, stirred at 50-60 ° C for 2 hours, poured the reaction solution into ice water, — Acidified with N hydrochloric acid and extracted with black form. The chromate-form layer was washed with aqueous sodium hydrogen carbonate solution and then with water, dried over anhydrous magnesium sulfate, concentrated under reduced pressure, and the residue obtained was purified by silica gel column chromatography. 1.62 g were obtained. Yield 45.0%

mp 85.0-86.0. C Comparative Example Application example of the known method to the compound of the present invention

2— [4 -— (2,6-difluorophenyl) -1- (1,3-thiazo-1-yl-2-yl)] — 1-1- [2- (trifluoromethyl) phenyl] ethane-1-one Manufacture

4 Dissolve 9.5 g of 1,2- (1,6-difluorophenyl) 1-2-methyl-1,3-thiazol in 10 Om 1 of anhydrous tetrahydrofuran, and add 1.6 mol / ln-butyllithium hexane solution. 3 ml was added dropwise at 1 78 ° C. After stirring for 30 minutes as it was, 9.2 g of methyl 2- (trifluoromethyl) benzoate was diluted with 20 ml of anhydrous tetrahydrofuran. After stirring at 178 ° C for 30 minutes, the mixture was stirred at room temperature for 2 hours. The reaction solution was poured into 2-N hydrochloric acid, and extracted with ethyl acetate. The ethyl acetate layer was washed with an aqueous solution of sodium hydrogen carbonate and then with water, dehydrated with anhydrous magnesium sulfate, concentrated under reduced pressure, and the residue obtained was purified by silica gel column chromatography to obtain the desired product. 2.6 g were obtained. Yield 15.0% Reference Example 1

2-Bromo-1- [4- (2,6-difluorophenyl)-(1,3-thiazo-ru-2-yl)]-] 1- [2- (Trifluoromethyl) phenyl] ethane-1-one Manufacturing of

2— [4— (2,6-difluorophenyl) one (1,3-thiazolu-2-yl)]

— 1— [2- (Trifluoromethyl) phenyl] ethane-1-one 0.5 g (1.3 mmo 1) is dissolved in 10 ml of chloroform and dissolved in 0.2 ml of bromine under stirring. 4 mmo 1) was added dropwise under ice cooling. After stirring at room temperature for 3 hours, the reaction solution was washed with an aqueous solution of sodium hydrogen sulfite and then with water, dehydrated with anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained crystals were washed with n-hexane to obtain 0.4 g of the desired product. mp. 125. 0 27.0. C Reference example 2

2-Chloro-2- [4- (2,6-difluorophenyl) -1- (1,3-thiazol-1-yl)] ―]-[2- (Trifluoromethyl) phenyl] ethane-1-one

2— [4— (2,6-difluorophenyl) — (1,3-thiazol-2-yl)] — 1- [2— (trifluoromethyl) phenyl] ethane-1-one 0.5 g (1.3 mmol) and 0.2 g of NCS were dissolved in 10 ml of black-mouthed form and stirred at room temperature for 1 hour. Water and ethyl acetate were added to the reaction mixture, water and ethyl acetate were added, the ethyl acetate layer was separated, anhydrous magnesium sulfate was added thereto, followed by dehydration and concentration. The obtained crystals were washed with n-hexane-ethyl acetate (small amount) to obtain 0.4 g of the desired product. mp. 143-1 45 ° C (decomposition) Reference example 3

2-Fluoro-2--1- [4-(2,6-difluorophenyl) -1- (1,3-thiazo-1-yl-2-yl)] — 1- [2- (Trifluoromethyl) phenyl] ethane-1 Production

A solution of 0.26 ml (1.7 mmol) of diisopropylamine in 8 ml of anhydrous tetrahydrofuran was stirred with stirring. 1.6 ml / ln-butyllithium hexane solution 1.1 ml (1.7 mmo 1) was added dropwise at C. — After stirring at 78 ° C for 30 minutes, 2- [4– (2,6-difluoro Phenyl) (1,3-thiazol-2-yl)] —1— [2—

(Trifluoromethyl) phenyl] ethane-oneone 0.6 g (l. 6 mmol) of anhydrous tetrahydrofuran solution (5 ml) was added dropwise, and the mixture was stirred at 178 ° C for 30 minutes, and N-fluorobenzene was added. A solution of 0.64 g (2. Ommo 1) of sulfonamide in anhydrous tetrahydrofuran (15 ml) was added dropwise. After gradually returning to room temperature and stirring at room temperature for 2 hours, the reaction solution was poured into an aqueous solution of ammonium chloride and extracted with ethyl acetate. The ethyl acetate layer was washed with water, dehydrated with anhydrous magnesium sulfate, and concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography to obtain 0.19 g of the desired product.

NM

= 6.52 (s, CH), 6.67 (s, CH), 6.95—7.9 (m), 7.27-7.40 (m), 7.61-7.85 ( m) Reference example 4

2-Cyano-2- [4- (2,6-difluorophenyl) -1- (1,3-thiazolu-2-yl)]-1-[2- (trifluoromethyl) phenyl] ethane-1-one

2-bromo-1- [4-(2,6-difluorophenyl) -1- (1,3-thiazole

—2—yl)] 1 1 1 [2— (trifluoromethyl) phenyl] ethane 1 1 1 0

46 g (1. Ommo 1) was dissolved in 8 ml of ethyl alcohol, and 0.14 g (2.9 mmol) of sodium cyanide was dissolved in 2 ml of water with stirring, and added dropwise at room temperature. After stirring at 50 ° C for 5 hours, the reaction solution was poured into ice water and extracted with a black hole form. The mouth layer was washed with water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained crystals were washed with n-hexane to obtain 0.27 g of the desired product. mp. 170. 0-1 0 ° C

Including the examples, Table 1 _c of the representative examples of the compounds of the present invention shown in Table 1 of formula (1)

34 _2-pyridyl 2,6- F 2 industrial availability:

ADVANTAGE OF THE INVENTION According to the manufacturing method of this invention, the thiazolyletanone derivative useful as an intermediate for agrochemical manufacturing, particularly an intermediate for manufacturing insecticides and acaricides, can be industrially advantageously manufactured. According to the production method B of the present invention, by using an inexpensive and easily available 2-methylthiazole compound as a raw material and using an organic base such as triethylamine which is safe to handle instead of n-butyllithium as a base, The desired compound can be easily produced via the enol ester.

Claims

The scope of the claims

Equation (1)

(In the formula, A, halogen atom, C ₂ _ ₆ alkyl groups, C ₆ haloalkyl group, - 6 § alkoxy group, optionally substituted C ₃ _ ₆ cycloalkyl group, optionally pyridyl substituted with G X represents a nitro group, a cyano group, a halogen atom, d-6 alkyl, a phenyl group optionally substituted with G, a phenyl group optionally substituted with G, or a phenyl group optionally substituted with G. group, - ₆ haloalkyl group, C i-s alkoxy groups, which are also good Fuweniru group or substituted substituted represents also good Fuwenokishi radical, n is an integer from 0 or 1 to 5.

G represents a halogen atom, a nitro group, a Ci ₆ alkyl group, or a C ₆ alkoxy group. When two or more substituents are present, G may be different. ) The compound represented by these. 2. Equation (2)

(Wherein X and n have the same meanings as in claim 1), and a benzoylthioacetamide compound represented by the formula:

Formula (3) A '-CO-CH ₂ — Y (3)

(A wherein Y is a halogen atom, A 'is an alkyl group, optionally substituted C _{3 6} cyclo alkyl group, an optionally substituted pyridyl group G, which may be thienyl group or G substituted by G Wherein G represents the same meaning as defined in claim 1). A compound represented by the following formula (1-1):

(Wherein, A ′, X and n have the same meanings as described above).

3. Equation (4)

(Wherein, A represents the same meaning as in claim 1).

Equation (5) or (6)

(5) (6)

(Wherein, X and n have the same meanings as in claim 1), and then a hydrolysis reaction is carried out after the reaction with the compound represented by the formula (1).

(Wherein, Α, X and η have the same meanings as described above.) C