WO1997000250A1

WO1997000250A1 - Process for producing 3-(3-fluoropropyl)-2-iminothiazoline

Info

Publication number: WO1997000250A1
Application number: PCT/JP1996/001633
Authority: WO
Inventors: Hideaki Suzuki; Toshio Niki; Yoshiyuki Kusuoka; Toshimasa Hamada; Takashi Mizukoshi; Jun Satow
Original assignee: Nissan Chemical Industries, Ltd.
Priority date: 1995-06-15
Filing date: 1996-06-14
Publication date: 1997-01-03

Abstract

A process for producing 3-(3-fluoropropyl)-2-iminothiazoline through the scheme (1) (wherein X represents halogeno) or scheme (2) (wherein R represents methyl, p-toluyl or trifluoromethyl) and intermediates therefor.

Description

Specification

Method for producing 3- (3-fluoropropyl) -2-iminothiazoline

The present invention relates to a method for producing an intermediate used for producing a fluoropropylthiazoline derivative (described in JP-A-7-242665) useful as a herbicide, and a synthetic intermediate thereof.

Background art

Prior art of the present invention includes 3- (3-fluoropropyl) -2-iminothiazoline via 3- (3-fluoropropyl) -2-iminothiazoline-hydrobromide described in JP-A-7-242665. There is a synthesis of However, the production method using 1-bromo-3-fluoropropane described in the literature is not always satisfactory as a production method of 3- (3-fluoropropyl) -2-iminothiazoline, It is desirable to expand the freedom of choice and to use an advantageous production method using industrially inexpensive raw materials.

U.S. Pat.Nos. 4,237,302 and WO9300336 disclose a method for synthesizing 3-alkyl-2-iminothiazolines using 2-aminothiazole and alkylhalide in Scheme 1 below, which is used in the literature. Alkyl halides are bromide or iodide, and there is no disclosure of alkyl chloride. Those skilled in the art will appreciate that these prior art disclosures suggest that highly reactive alkyl bromides or iodides are suitable for the alkylation reaction of 2-aminothiazole, and that the reaction using alkyl chloride is difficult. The suggestions can be easily analogized.

In addition, the intermediates shown in Scheme 2, 3- (3-fluoropropyl) -2-iminothiazoline disulfonic acid salts, and fluoropropyl ester trifluoromethanesulfonate have never been known before and are novel compounds. It is.

Disclosure of the invention

The present inventors have conducted intensive studies on a method for producing a 3-fluoropropylthiazoline derivative (described in JP-A-7-242665) useful as a herbicide. As a result, the following scheme using a less expensive raw material was obtained. The present inventors have found a method for producing 3- (3-fluoropropyl) -2-ylline represented by 1 and Scheme 2, and have completed the present invention. Scheme 1

(1) (6) (3)

(In the formula, X represents a halogen atom.)

That is, the method of Scheme 1 was obtained by reacting 2-aminothiazole (1) with 1-chloro-3-fluoropropane (2) in the presence of a metal bromide or metal iodide or a phase transfer catalyst. Intermediate 3- (3-fluoropropyl) -2-iminothiazoline. This is a method for obtaining 3- (3-fluoropropyl) -2-iminothiazoline (3) by reacting a hydrogen halide with a base.

(3)

(In the formula, R represents a methyl group, a paratolyl group, or a trifluoromethyl group.) In other words, the method of Scheme 2 uses a sulfonic acid fluoropropyl ester (4) and a 2-aminothiazole (1) To give 3- (3-fluoropropyl) -2-iminothiazoline-sulfonate (5), and this is further converted to 3- (3-fluoropropyl) -2-iminothiazoline ( 3).

According to the present invention, 3- (3-fluoropropyl) -2-iminothiazoline, which is useful as an intermediate of a highly active herbicide, can be efficiently produced from an industrially inexpensive raw material. BEST MODE FOR CARRYING OUT THE INVENTION The reaction between 2-aminothiazole (1) and 1-chloro-3-fluoropropane (2) in Scheme 1 is 1-chloro-3 to 1 mole of 2-aminothiazole (1). -Fluopropane (2) is used with 0.5 to 3 moles, more preferably from 0.75 to 2.0 moles. Examples of the additives include metal halides such as potassium iodide, sodium iodide, potassium bromide, and sodium bromide; Alternatively, a catalyst such as 18-crown-6-ether is added in an amount of 2.0 mole equivalents based on the amount of the catalyst to 1-kokuguchi-3-fluoropropane (2). These additives may be used alone or as a mixture. For example, metal halides such as potassium bromide and sodium bromide can be used by further adding chloroethers such as 18-crown-6-ether. The reaction temperature is a force that can be arbitrarily selected from the range of -30 ° C to 150 ° C, and is preferably in the range of 0 ° C to 100 ° C.

Solvents used in this reaction include solvents inert to this reaction, for example, aromatic hydrocarbons such as benzene, toluene and xylene, halogenated aromatic hydrocarbons such as benzene and dichlorobenzene, dichloromethane, and chloroform. Halogenated hydrocarbons such as form, ethylene dichloride and carbon tetrachloride, ethers such as ethyl ether, isopropyl ether, dioxane, and tetrahydrofuran; alcohols such as methanol, ethanol, normal propyl alcohol, and isopropyl alcohol; Nitriles such as acetonitrile and propionitrile; amides such as dimethylformamide, dimethylacetamide, N-methylpyrrolidone and hexamethylphosphoric acid trimid; 1,3-dimethyl-2-imidazolidinone; 3-dimethyl-1,3-diazacyclohexyl Cyclic ureas such as san-2-one, sulfoxides such as dimethyl sulfoxide, sulfones such as sulfolane, ketones such as acetone and methyl ethyl ketone, esters such as ethyl acetate, petroleum ether, petroleum benzine , Hexane, heptane and other hydrocarbons, and aqueous solvents.

These solvents may be used alone or as a mixture. After completion of the reaction, an ordinary post-treatment is carried out, whereby an intermediate 3- (3-fluoromethylpropyl) -2-iminothiazoline-no-hydrogen gentate (6) can be obtained. This reaction can also be performed under pressurized conditions using an autoclave or the like. 3- (3-Fluoropropyl) -2-iminothiazoline'hydrogen halide (4) is reacted with a base to give 3- (3-fluoropropyl) -2-iminothiazoline; hydrogen halide (6) 1 mol The reaction is carried out using from 0.2 to 3.0 molar amounts of base. Preferably, it is carried out in the range of 0.5 to 1.5 mol.

Examples of the base include inorganic bases such as potassium carbonate, sodium carbonate, potassium hydroxide, sodium hydroxide, potassium hydrogen carbonate, and sodium hydrogen carbonate; organic bases such as triethylamine, pyridine, and DBU; sodium methoxide; Metal alkoxides such as methoxide; and metal hydrides such as sodium hydride. Preferably, inorganic bases and organic bases are used.

The reaction temperature is a force that can be arbitrarily selected from the range of -30 ° C to 100 ° C, preferably the range of -20 ° C to 40 ° C.

Solvents for this reaction include solvents inert to this reaction, for example, alcohols such as methanol, ethanol, normal propyl alcohol, and isopropyl alcohol, dimethylformamide, dimethylacetamide, N-methylpyrrolidone, and hexamethylphosphine. Examples include amides such as acid triamide, aromatic hydrocarbons such as benzene, toluene, and xylene; ethers such as ethyl ether, isopropyl ether, dioxane, and tetrahydrofuran; and water solvents.

These solvents may be used alone or as a mixture. Preferably, an aqueous solvent and an alcohol are used. After completion of the reaction, 3- (3-fluoropropyl) -2-iminothiazoline (3) can be obtained by performing a usual treatment. The structure can be confirmed by IR, NMR, MS spectrum and the like.

In this production method, the desired 3- (3-fluoropropyl) -2-iminothiazoline (3) is obtained by reacting the intermediate (6) with a base without isolation and purification. It is also possible.

The reaction of 2-aminothiazole (1) with sulfonic acid fluoropropyl ester (4) in Scheme 2 is based on 1 mole of 2-aminothiazole (1) The reaction is carried out using 0.5 to 3.0 moles of the pillester (4), more preferably 0.75 to 2.0 moles.

The reaction temperature is a force that can be arbitrarily selected from the range of -30 ° C to 150 ° C, and is preferably in the range of O'C to 100 ° C.

Solvents used in this reaction include solvents inert to this reaction, for example, aromatic hydrocarbons such as benzene, toluene and xylene, halogenated aromatic hydrocarbons such as benzene and dichlorobenzene, dichloromethane, and chloroform. Halogenated hydrocarbons such as form, ethylene dichloride and carbon tetrachloride, ethers such as ethyl ether, isopropyl ether, dioxane and tetrahydrofuran, alcohols such as methanol, ethanol, normal propyl alcohol and isopropyl alcohol; Nitriles such as acetonitrile and propionitrile; amides such as dimethylformamide, dimethylacetamide, N-methylpyrrolidone and hexamethylphosphoric acid triamide; 1,3-dimethyl-2-imidazolidinone; 3-dimethyl-1,3-diazacyclo Cyclic ureas such as xan-2-one; sulfoxides such as dimethyl sulfoxide; sulfones such as sulfolane; ketones such as acetone and methyl ethyl ketone; esters such as ethyl acetate; petroleum ether; petroleum benzine , Hexane, heptane and other hydrocarbons, and aqueous solvents.

These solvents may be used alone or as a mixture. After completion of the reaction, the compound (5) of the present invention can be obtained by performing ordinary post-treatment.

The reaction of 3- (3-fluoropropyl) -2-iminothiazoline-sulfonate (5) with a base is based on 1 mol of 3- (3-fluoropropyl) -2-iminothiazoline'sulfonate (5) The reaction is carried out using 0.5 to 3.0 moles of base. It is preferably carried out in the range of 0.9 to 1.2 molar amount.

Examples of the base include inorganic bases such as potassium carbonate, sodium carbonate, potassium hydroxide, sodium hydroxide, potassium hydrogen carbonate, and sodium hydrogen carbonate; organic bases such as triethylamine, pyridine, and DBU; sodium methoxide; Metal alkoxides such as methoxide; and metal hydrides such as sodium hydride. Preferred are inorganic bases and organic bases. The reaction temperature can be arbitrarily selected from the range of -30 ° C to 100 ° C, but is preferably in the range of -20 ° C to 40 ° C.

Solvents for this reaction include solvents inert to this reaction, for example, alcohols such as methanol, ethanol, normal propyl alcohol, and isopropyl alcohol, dimethylformamide, dimethylacetamide, N-methylpyrrolidone, and hexamethylphosphoric triamide. And the like, aromatic hydrocarbons such as benzene, toluene, and xylene; ethers such as ethyl ether, isopropyl ether, dioxane, and tetrahydrofuran; and water solvents.

These solvents may be used alone or as a mixture. Preferably, an aqueous solvent and an alcohol are used. After completion of the reaction, 3- (3-fluoropropyl) -2-iminothiazoline (3) can be obtained by performing a usual treatment. The structure can be confirmed by IR, NMR and MS spectra.

3-Fluoropropyl trifluoromethanesulfonate used in this reaction is also a novel compound.

The intermediate sulfonic acid 3-fluoromethyl propyl ester (4) used in this reaction can be produced by a method known from the literature or a method used per se. Known techniques include U.S. Pat. No. 5,035,740, U.S. Pat. No. 4,913,724, Journal-of'Medical 'Chemistry GJ.Med.Chem) 35, 2221 (1992), Journal of Ob. Chemical 'Society' (J.Chem.Soc.) 2574 (1957), Angew.Chem. (98), 264 (1986), Hemitsche Berichte (Chem.Ber.) 126, 779 (1993), Tetrahedron Le. 21, 21, 2991 (1980).

3-fluoropropyl methanesulfonate (4: R = Me), 3-fluoropropyl P-toluenesulfonate (4: R = p-MeC6H4) and 3-fluoropropyl trifluoromethanesulfonate (4: R = CF3) Are shown in Reaction Schemes 1, 2 and 3. (Reaction formula 1)

MeSO CI

OH OS0 ₂ Me (4: R = Me)

(Reaction formula 2)

(Reaction formula 3)

(CF ₃ SO) ₂ 0

or

CF ₃ S0 ₂ CI

F OH F ^v OS0 ₂ CF ₃

(4: R = CF ₃ ) Also, the starting material used in this reaction, 1-chloro-3-fluoropropane, is journalile 'ob''organic' chemistry (J.0rg.Chem.) Volume 15, page 425

(1950), and can be easily synthesized from 1-bromo-3-chloropropane with reference to literatures such as JP-A 64-45321. 3-Fluoro-1-propanol is described in Journal-Ob 'Organic' Chemistry (J.0rg.Chem.), Vol. 15, p. 425 (1950), etc. -Can be easily synthesized from 1-propanol.

Example

Hereinafter, in the present invention, the intermediates and the production method shown in Scheme 1 are used as examples, and the production methods of various starting materials used in the production method of the present invention, and 3- (3-fluoropropyl) -2-iminothiazoline are described. The production of the used herbicides will be specifically described as reference examples, but the present invention is not limited thereto.

[Reference Example 1] Synthesis of 1-chloro-3-3-fluoropropane

F-^^ CI ( ² ) A mixture of 157 g (lmol) of 1-bromo-3-chloropropane, 206 g (2.7 mol) of propylene glycol and 36 ml of water was heated to 100 ° C, and 87 g (1.5 mol) of fluorinated rim and 78 ml of water were added. Was added dropwise. The reaction mixture was heated to 120 ° C., and 114.65 g of the obtained fraction was dried over anhydrous sodium sulfate and distilled again to obtain 15.24 g of 1-chloro-3-fluoropropane. Boiling point 73-75 ° C.

Example 1 Synthesis of 3- (3-fluoropropyl) -2-iminothiazoline (3)

A) 2-aminothiazole lg (10 mmol), 1-chloro-3-fluoropropane

A mixture of 0.97 g (10 mmol), sodium iodide 1.5 g (10 mmol) and DMF 1.2 ml was stirred at 80 ° C for 10 hours. The reaction mixture was washed three times with 50 ml of ethyl acetate, and 2.14 g of precipitated crystals were collected by filtration.

2.14 g of these crystals were dissolved in 14 ml of water, and 1.02 g (7.4 mmol) of potassium carbonate was added. After stirring for 10 minutes, the mixture was extracted three times with 20 ml of chloroform, and the organic layer was washed with saturated saline and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to obtain 0.84 g of pale yellow oily 3- (3-fluoropropyl) -2-iminothiazoline.

B) 2-aminothiazol 0.5 g (5 mmol), 1-chloro-3-fluoropropane

A mixture of 0.48 g (5 mmol), 0.83 g (5 mmol) of potassium iodide and 0.6 ml of DMF was stirred at 80 ° C. for 8 hours. The reaction mixture was washed three times with 50 ml of ethyl acetate, and 1.31 _{g of} precipitated crystals were collected by filtration.

1.31 g of these crystals was dissolved in 11 ml of water, and 0.63 g (4.6 nmol) of potassium carbonate was added. After stirring for 10 minutes, the mixture was extracted three times with 20 ml of chloroform. The organic layer was washed with brine and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to obtain 0.46 g of 3- (3-fluoropropyl) -2-iminothiazoline as a pale yellow oil.

C) 2-aminothiazole lg (10 mmol), 1-chloro-3-fluoropropane

A mixture of 0.97 g (10 mmol), 1.03 g (10 mmol) of sodium bromide and 1.2 ml of DMF was stirred at 80 ° C for 16 hours. The reaction mixture was washed three times with 50 ml of ethyl acetate, and 1.34 g of precipitated crystals were collected by filtration. 1.34 g of these crystals was dissolved in 14 ml of water, and 0.77 g (5.6 mmol) of potassium carbonate was added. After stirring for 10 minutes, the mixture was extracted three times with 20 ml of chloroform. The organic layer was washed with brine and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to obtain 0.28 g of 3- (3-fluoropropyl) -2-iminothiazoline as a pale yellow oil.

D) 2-Aminothiazol 0.5g (5mmol), 1-chloro-3-fluoropropane

A mixture of 0.48 g (5 mmol), 0.6 g (5 mmol) of potassium bromide and 0.6 ml of DMF was stirred at 80 ° C. for 19 hours. The reaction mixture was washed three times with 50 ml of ethyl acetate. The resulting crude product was dissolved in 13 ml of water, and 0.69 g (5 mmol) of potassium carbonate was added. After stirring for 10 minutes, the mixture was extracted three times with 20 ml of chloroform, and the organic layer was washed with saturated saline and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to obtain 3- (3-fluoropropyl) -2-iminothiazoline O.llg as a pale yellow oil.

E) 0.5 g (5 mmol) of 2-aminothiazole, 1-chloro-3-fluoropropane

A mixture of 0.48 g (5 mmol), 1.61 g (5 mmol) of tetranormal butylammonium bromide and 0.6 ml of DMF was stirred at 80 ° C for 14 hours. The reaction mixture was washed three times with 50 ml of ethyl acetate, and the resulting crude product was dissolved in 13 ml of water, and 0.69 _g (5 mmol) of potassium carbonate was added. After stirring for 10 minutes, the mixture was extracted three times with 20 ml of chloroform, and the organic layer was washed with saturated saline and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to obtain 0.21 g of 3- (3-fluoropropyl) -2-iminothiazoline as a pale yellow oil.

F) 2-Aminothiazole 0.5g ( ⁵ mmol), 1-chloro-3-fluoropropane

0.48 g (5 mmol), potassium bromide 0.6 g (5 mmol), 18-crown-6 (catalytic amount) and

The mixture of 0.6 ml of DMF was stirred at 80 ° C for 19 hours. The reaction mixture was washed three times with 50 ml of ethyl acetate. The resulting crude product was dissolved in 13 ml of water, and 0.69 g (5 mmol) of potassium carbonate was added. After stirring for 10 minutes, the mixture was extracted three times with 20 ml of chloroform, and the organic layer was washed with saturated saline and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to obtain 0.18 g of 3- (3-fluoropropyl) -2-iminothiazoline as a pale yellow oil.

Reference Example 2 Synthesis of 1- {3- (3-fluoropropyl) thiazoline-2-imino-sulfonysole}-(4,6-dimethoxytriazin-2-yl) urea

0.62 g (4imnol) of 2-amino-4,6-dimethoxytriazine was suspended in 40 ml of dry tetrahydrofuran, and 0.57 g (4 mmol) of chlorosulfonyl isocyanate was added dropwise at room temperature. After stirring at room temperature for 30 minutes, 3- (3-fluoropropyl) -2-iminothiazoline

A mixture of 0.64 g (4 mmol), triethylamine 0.45 g (4.4 mmol) and 4 ml of tetrahydrofuran was added dropwise. After stirring at room temperature for 30 minutes, the solvent was distilled off under reduced pressure, 200 ml of water was added to the obtained residue, and the precipitated crystals were collected by filtration to obtain the desired 1- {3- (3-fluoropropifle) thiazoline. 0.7 g of -2-iminosulfonyl} -3- (4,6-dimethoxytriazin-2-yl) urea was obtained.

Then, in the present invention, the intermediates and the production method shown in Scheme 2 are used as examples, and the production methods of various starting materials used in the production method of the present invention, and 3- (3-fluoropropyl) -2-iminothiazoline are used. The production of herbicides was specifically described as a reference example, but the present invention is not limited to these.

Reference Example 3 Synthesis of 3-Fluoro-1-propanol

A mixture of 18.9 g (0.2 mol) of 3-propanol, 18.9 g (0.2 mol), 17.4 g (0.3 mol) of potassium fluoride, and 25 g of ethylene glycol was heated to 175 to 180 ° C with vigorous stirring to give a boiling point of 125 to 180 ° C. 8.31 g of a fraction at 135 ° C was obtained. This was distilled again to obtain 3.28 g of 3-fluoro-1-propanol. Boiling point 126-130t :.

[Reference Example 4] Synthesis of 3-fluoropropyl methanesulfonate

0S0 ₂ Me (4: R = Me)

1.95 g (25 mmol) of 3-fluoro-1-propanol, triethylamine

A mixture of 3.83 g (37.9 mmol) and 25 ml of methylene chloride was cooled to -40 ° C, and 3.15 g (27.5 mmol) of methanesulfonyl chloride was added thereto. After the reaction solution was returned to room temperature over 30 minutes, 20 ml of water was added, the organic layer was separated, and the aqueous layer was extracted three times with 50 ml of methylene chloride. The organic layers are combined, washed sequentially with diluted hydrochloric acid, saturated aqueous sodium hydrogen carbonate, and saturated saline, and then dried over anhydrous sodium sulfate. Dried with lium. After distilling off the solvent under reduced pressure, methanesulfonic acid

2.90 g of 3-fluoropropyl were obtained. Boiling point 73-74 ° C / 0.60 Torr.

[Reference Example 5] Synthesis of 3-fluoropropyl P-toluenesulfonate

F ', OS0 ₂ ~~ Me (4: R =)

To a mixture of 2.34 g (30 mmol) of 3-fluo-1-propanol, 4.55 g (45 mmol) of triethylamine and 30 ml of methylene chloride, at room temperature, was added P-toluenesulfonyl chloride

6.29 g (33 mmol) was added, and the mixture was stirred for 4 hours. 30 ml of water was added to the reaction solution, the organic layer was separated, and the aqueous layer was extracted three times with 50 ml of methylene chloride. The organic layers were combined, washed sequentially with dilute hydrochloric acid, saturated aqueous sodium bicarbonate, and saturated saline, and then dried over anhydrous sodium sulfate. After evaporating the solvent under reduced pressure, the residue was purified by silica gel column chromatography (chloroform) to obtain 3-fluoropropyl P-toluenesulfonate 3. n _D ^{2 () 3} 1.5043.

Example 2 Synthesis of 3-fluoropropyl trifluoromethanesulfonate

r V, oso ゥ CF ₃ (4: R = CF ₃ )

2.34 g (30 mmol) of 3-fluoro-1-propanol, 2,4,6-trimethylpyridine

A mixture of 4 _g (33 mmol) and 30 ml of methylene chloride was cooled to −40 ° C., and 9.31 _g (33 mmol) of trifluoromethanesulfonic anhydride was added thereto. After the reaction solution was returned to room temperature over 30 minutes, 30π of water was added, the organic layer was separated, and the aqueous layer was extracted three times with 50 ml of methylene chloride. The organic layers were combined, washed sequentially with saturated aqueous sodium hydrogen carbonate, diluted hydrochloric acid, and saturated saline, and dried over anhydrous sodium sulfate. After evaporating the solvent under reduced pressure, 3.29 g of 3-fluoropropyl trifluoromethanesulfonate was obtained by distillation under reduced pressure. Boiling point 62 ~ 63 ° C / 19Torr.

Example 3 Synthesis of 3- (3-fluoropropyl) -2-iminothiazoline'methanesulfonate

A mixture of 2.57 g (16.5 mmol) of 3-fluoropropyl methanesulfonate, 1.5 g (15 mmol) of 2-aminothiazole and 30 ml of isopropyl alcohol was heated under reflux for 72 hours. The solvent was distilled off under reduced pressure, ethyl ether and ethanol were poured, and the insoluble matter was separated by filtration. The filtrate was concentrated, ethyl acetate was added, and the precipitated crystals were collected by filtration to obtain 2.22 g of 3- (3-fluoropropyl) -2-iminothiazoline methanesulfonate. 81-83 ° C.

Example 4 Synthesis of 3- (3-fluoromethylpropyl) -2-iminothiazoline · ρ-toluenesulfonic acid salt

, NH, HOS0 ₂ ~ (〇 Me (5: R = ~ <to Me) p-toluenesulfonic acid 3- Furuoropuropiru 3.05g (16mmol), 2- Aminochiazo one Le 1.28 g (12.8 mmol) and Ν, Ν- dimethyl A mixture of 7.5 ml of formamide was heated for 32.5 hours at 80 ° C. After washing the reaction mixture with ethyl acetate and ethyl ether, the solvent was distilled off under reduced pressure to give 3- (3-fluoropropyl) -2-imino. 1.49 g of thiazoline / ρ-toluenesulfonate (brown viscous oil)

Example 5 3- (3-fluoropropyl) -2-iminothiazoline.trifluoromethanesulfonate

(5: R = CF ₃ )

, _S entering NH «HOS0 ₂ CF ₃

A mixture of 1,12 g (11.2 mmol) of 2-aminothiazole and 1.7 ml of N, N-dimethylformamide was cooled on ice, and 2.94 g (14 mmol) of 3-fluoropropyl trifluoromethanesulfonate was added thereto. After stirring at room temperature for 1.5 hours, the reaction solution was washed with ethyl ether, and the solvent was distilled off under reduced pressure to obtain 3.42 g of 3- (3-fluoropropyl) -2-iminothiazoline'trifluoromethanesulfonate. Was. (Pale yellow oil) Example 6 Synthesis of 3- (3-fluoropropyl) -2-iminothiazoline

A) 3- (3-fluoropropyl) -2-iminothiazoline 'methanesulfonate

1.02 g (4 mmol) was dissolved in 10 ml of water, and 0.55 g (4 mmol) of potassium carbonate was added. After stirring for 10 minutes, the reaction solution was extracted three times with 10 ml of chloroform, and the organic layer was washed with saturated saline and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to obtain 0.56 g of 3- (3-fluoropropyl) -2-iminothiazoline as a pale yellow oil. Boiling point 77 ° C / 0.52 Torr.

B) 3- (3-Fluoropropyl) -2-iminothiazolinep-toluenesulfonate

0.87 g (3 nmol) was dissolved in 7.5 ml of water, and 0.41 g (3 mmol) of potassium carbonate was added. After stirring for 10 minutes, the reaction solution was extracted three times with 10 ml of chloroform, and the organic layer was washed with saturated saline and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to obtain 0.26 g of 3- (3-fluoropropyl) -2-iminothiazoline as a pale yellow oil.

C) 3- (3-Fluoropropyl) -2-iminothiazoline'trifluoromethanesulfonate (2.49 g, 8 mmol) was dissolved in water (20 ml), and potassium carbonate (1.llg (8imnol)) was added.

After stirring for 10 minutes, the reaction solution was extracted three times with 20 ml of chloroform and the organic layer was washed with saturated saline and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to obtain 0.84 g of 3- (3-fluoropropyl) -2-iminothiazoline as a pale yellow oil.

Reference Example 6 Synthesis of 1- {3- (3-fluoropropyl) thiazoline-2-imino-sulfonyl}-(4,6-dimethoxytriazin-2-yl) urea

312 mg (2 inniol) of 2-amino-4,6-dimethoxytriazine was suspended in 20 ml of dry tetrahydrofuran, and 284 mg (2 mmol) of chlorosulfonyl isocyanate was added dropwise at room temperature. After stirring at room temperature for 30 minutes, 3- (3-fluoropropyl) -2-iminothiazoline

A mixture of 320 mg (2 mmol), triethylamine 222 mg (2.2 mmol) and tetrahydrofuran 2 ml was added dropwise. After stirring at room temperature for 30 minutes, the solvent was distilled off under reduced pressure, 100 ml of water was added to the obtained residue, and the precipitated crystals were collected by filtration to obtain the desired 1- {3- (3-f 566 mg of (fluoropropyl) thiazoline-2-iminosulfonyl} -3- (4,6-dimethoxytriazine-2-isole) urea were obtained.

Claims

Claim formula (1): N

(1)

2 Aminochiazoru the formula represented by S 'H _{2 (2):}

Formula (3) characterized by reacting 1-chloro-3-fluoropropane represented by CI (2) with a metal bromide, metal iodide, or a phase transfer catalyst and then reacting with a base. :

(3)

, S NH

A method for producing 3- (3-fluoropropyl) -2-iminothiazoline represented by the formula:

2. Equation (4):

V ヽ〇S0 ₂ R (4)

(In the formula, R represents a methyl group, a paratoluisole group or a trifluoromethisole group.) A sulfonic acid fluoropropyl ester represented by the following formula (1):

Formula (5) characterized by reacting with 2-aminothiazole represented by:

( ₅ )

(In the formula, R represents a methyl group, a paratolyl group or a trifluoromethyl group.) A method for producing 3- (3-fluoropropyl) -2-iminothiazoline'sulfonic acid salt represented by the formula:

3. Equation (5):

• ^F (5)

, E NHHOS0 ₂ R

(Wherein R represents a methyl group, a paratolyl group or a trifluoromethyl group.) 3- (3-fluoropropynole) -2-iminothiazoline ' Equation (3) characterized by reacting: (3)

Method for producing 3- (3-fluoropropyl) -2 iminothiazoline represented by NH to S.

4. formula (5): S ON NH * HOS0 ₂ R

(Wherein, R represents a methyl group, a paratolyl group or a trifluoromethyl group.) 3- (3-fluoropropyl) -2-iminothiazoline sulfonic acid salt represented by the formula:

5. Below formula:

F '^ OS0 ₂ CF ₃ (4: R = CF ₃ )

Trifluoromethanesulfonic acid 3-fluoropropyl ester represented by the formula: