JP3491311B2 - Process for producing N-substituted-N-aryl cyanamide derivatives and N-substituted-N-arylthiourea derivatives - Google Patents

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION The present invention relates to a herbicide, especially as an intermediate for the production of medicines and agricultural chemicals (European patent application EP-A-
446802 published specification, U.S. Pat. No. 5,244,863, European patent application EP-A-529482 published specification, etc.) intermediates (described in Japanese Patent Application No. 4-325259)
The present invention relates to a process for producing a useful N-substituted-N-arylcyanamide derivative and N-substituted-N-arylthiourea derivative as an intermediate for producing a 2-iminothiazoline derivative.

[0002]

2. Description of the Related Art Conventionally, as a method for producing an N-substituted-N-arylcyanamide derivative, for example, the following reaction formula:

[Chemical 5] (In the formula, Et ₃ N represents triethylamine, and DMF
Represents N, N-dimethylformamide. ), J. Org. Chem., 29, 153-157 (196).
As described in 4), the yield was not always sufficient as described above.

[0003]

Means for Solving the Problems The present inventors
N-substituted-N-aryl cyanamide represented by the formula:
Derivatives and N-substituted-N represented by the following general formula
-For industrially advantageous production method of arylthiourea derivative
As a result of various examinations, the following general formula 6 is shown.
N-aryl cyanamide derivatives can be added to iodide salts and
In the presence of Lucari metal carbonate,
Derivation of allyl halide represented by the following general formula 7 in a medium
By reacting the body, the following general formula
N-substituted-aryl cyanamide derivative
Can be obtained well, in addition to this sulfide ion
Or chemistry that produces hydrogen sulfide ions
Species (eg, hydrogen sulfide; ammonium sulfide ((N
H_Four)₂Sn: NH₃And H ₂The molar ratio of S has various values.
For example, n = 1,3); sulfur (S₈) And
And ammonia; sulfur and organic amines)
And the N-substituted-N- represented by the following general formula 9
Aryl thiourea derivative was obtained in good yield and purity.
As a result, they have completed the present invention. That is, the present invention
Is the general formula

[Chemical 6] [In the formula, R ¹ represents an optionally substituted aryl group. ] The N-aryl cyanamide derivative shown by these, and General formula 7

[Chemical 7] [Wherein R ² represents a hydrogen atom, an optionally substituted alkyl group or an optionally substituted aryl group, and R 2
³ , R ⁴ and R ⁵ are the same or different and each is a hydrogen atom,
It represents a halogen atom, an optionally substituted alkyl group or an optionally substituted aryl group, and X represents a chlorine atom or a bromine atom. ] In the presence of an iodide salt and an alkali metal carbonate in an aprotic polar solvent, represented by the general formula 8

[Chemical 8] [In the formula, R ¹ , R ² , R ³ , R ⁴ and R ⁵ have the same meanings as described above. ] The manufacturing method of the N-substituted N-aryl cyanamide derivative shown by these, and making it react with the chemical species which generate | occur | produce a sulfide ion or a hydrogen sulfide ion, General formula 9

[Chemical 9] [In the formula, R ¹ , R ² , R ³ , R ⁴ and R ⁵ have the same meanings as described above. ] The manufacturing method of the N-substituted N-aryl thiourea derivative shown by these is provided. In the present invention, as a specific example of R ^1, an aryl group which may be plurally substituted (as the substituent, an alkyl group having 1 to 8 carbon atoms which may be plurally substituted by a halogen atom, a plural halogen atom) And optionally substituted C 1-8 alkoxy groups, aryl groups, nitro groups, halogen atoms and the like). Specific examples of R ² include a hydrogen atom and an optionally substituted alkyl group having 1 to 8 carbon atoms (as a substituent, an alkoxy group having 1 to 8 carbon atoms, an aryl group, and an alkyl group having 3 to 8 carbon atoms). A cycloalkyl group and the like), an aryl group which may be substituted with a plurality of groups (as the substituent, an alkyl group having 1 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, an aryl group, a nitro group, a halogen atom, etc. Can be mentioned). Specific examples of R ³ , R ⁴ and R ⁵ include a hydrogen atom, a halogen atom and an optionally substituted alkyl group having 1 to 8 carbon atoms (as a substituent,
Alkoxy group having 1 to 8 carbon atoms, aryl group, and 3 to carbon atoms
8 cycloalkyl group, etc.), and an aryl group which may be substituted with a plurality of groups (as the substituent, an alkyl group having 1 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, an aryl group, a nitro group, a halogen). Atoms and the like) can be mentioned. In the above, "alkyl" means, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, hexyl,
Represents octyl, "alkoxy" represents, for example, methoxy, ethoxy, propyloxy, isopropyloxy, butoxy, isobutyloxy, sec-butyloxy, tert-butyloxy, hexyloxy, octyloxy, and "aryl" is, for example. Represents phenyl, α-naphthyl, β-naphthyl, and “cycloalkyl” includes, for example, cyclopropyl, cyclobutyl,
Represents cyclopentyl, cyclohexyl and cyclooctyl, examples of the “halogen atom” include a chlorine atom, a bromine atom, an iodine atom and a fluorine atom, and “may be plurally substituted” means, for example, 1 to 3 hydrogen atoms. It indicates that each may be substituted with a substituent.

A general formula, which is a raw material compound used in the present invention
Examples of the N-aryl cyanamide derivative represented by Chemical formula 6 include the following. 3- (trifluoromethyl) phenylcyanamide 3- (trifluoromethoxy) phenylcyanamide 4-fluoro-3- (trifluoromethyl) phenylcyanamide 3,5-dichlorophenylcyanamide 4-methoxyphenylanamido 2-chlorophenylcyanamide General formula Examples of the allyl halide derivative represented by 7 include the following. 2,3-dichloro-1-propene 1,3-dichloro-1-propene 2,3-dichloro-3-methyl-1-propene 1,2-dichloro-2-butene 1,2-dichloro-3-methyl- 2-Butene 2,3-dibromo-1-propene General Formula As the N-substituted-N-aryl cyanamide derivative represented by the following chemical formula 8, for example, the following ones can be mentioned. N- (3- (trifluoromethyl) phenyl) -N-
(2-chloro-2-propenyl) cyanamide N- (3- (trifluoromethyl) phenyl) -N-
(3-Chloro-2-propenyl) cyanamide N- (3- (trifluoromethyl) phenyl) -N-
(2-Chloro-1-methyl-2-propenyl) cyanamide N- (3- (trifluoromethyl) phenyl) -N-
(2-chloro-2-butenyl) cyanamide N- (3- (trifluoromethyl) phenyl) -N-
(2-Chloro-3-methyl-2-butenyl) cyanamide N- (3- (trifluoromethyl) phenyl) -N-
(2-Bromo-2-propenyl) cyanamide N- (3- (trifluoromethoxy) phenyl) -N-
(2-chloro-2-propenyl) cyanamide N- (3- (trifluoromethoxy) phenyl) -N-
(3-Chloro-2-propenyl) cyanamide N- (3- (trifluoromethoxy) phenyl) -N-
(2-Chloro-1-methyl-2-propenyl) cyanamide N- (3- (trifluoromethoxy) phenyl) -N-
(2-chloro-2-butenyl) cyanamide N- (3- (trifluoromethoxy) phenyl) -N-
(2-chloro-3-methyl-2-butenyl) cyanamide N- (4-fluoro-3- (trifluoromethyl) phenyl) -N- (2-chloro-2-propenyl) cyanamide N- (4-fluoro- 3- (trifluoromethyl) phenyl) -N- (3-chloro-2-propenyl) cyanamide N- (4-fluoro-3- (trifluoromethyl) phenyl) -N- (2-chloro-1-methyl- 2-Propenyl) cyanamide N- (4-fluoro-3- (trifluoromethyl) phenyl) -N- (2-chloro-2-butenyl) cyanamide N- (4-fluoro-3- (trifluoromethyl) phenyl) -N- (2-chloro-3-methyl-2-butenyl) cyanamide N- (3,5-dichlorophenyl) -N- (2-chloro-2-propenyl) cyanamide N- (4 Methoxyphenyl)-N-(2-chloro-2
-Propenyl) cyanamide N- (2-chlorophenyl) -N- (2-chloro-2-
Examples of the N-substituted-N-arylthiourea derivative represented by the general formula 9 include the following. N- (3- (trifluoromethyl) phenyl) -N-
(2-Chloro-2-propenyl) thiourea N- (3- (trifluoromethyl) phenyl) -N-
(3-Chloro-2-propenyl) thiourea N- (3- (trifluoromethyl) phenyl) -N-
(2-Chloro-1-methyl-2-propenyl) thiourea N- (3- (trifluoromethyl) phenyl) -N-
(2-Chloro-2-butenyl) thiourea N- (3- (trifluoromethyl) phenyl) -N-
(2-Chloro-3-methyl-2-butenyl) thiourea N- (3- (trifluoromethyl) phenyl) -N-
(2-Bromo-2-propenyl) thiourea N- (3- (trifluoromethoxy) phenyl) -N-
(2-Chloro-2-propenyl) thiourea N- (3- (trifluoromethoxy) phenyl) -N-
(3-Chloro-2-propenyl) thiourea N- (3- (trifluoromethoxy) phenyl) -N-
(2-Chloro-1-methyl-2-propenyl) thiourea N- (3- (trifluoromethoxy) phenyl) -N-
(2-Chloro-2-butenyl) thiourea N- (3- (trifluoromethoxy) phenyl) -N-
(2-Chloro-3-methyl-2-butenyl) thiourea N- (4-fluoro-3- (trifluoromethyl) phenyl) -N- (2-chloro-2-propenyl) thiourea N- (4-fluoro- 3- (trifluoromethyl) phenyl) -N- (3-chloro-2-propenyl) thiourea N- (4-fluoro-3- (trifluoromethyl) phenyl) -N- (2-chloro-1-methyl- 2-Propenyl) thiourea N- (4-fluoro-3- (trifluoromethyl) phenyl) -N- (2-chloro-2-butenyl) thiourea N- (4-fluoro-3- (trifluoromethyl) phenyl) -N- (2-chloro-3-methyl-2-butenyl) thiourea N- (3,5-dichlorophenyl) -N- (2-chloro-2-propenyl) thiourea N- (4 Methoxyphenyl)-N-(2-chloro-2
-Propenyl) thiourea N- (2-chlorophenyl) -N- (2-chloro-2-
Propenyl) thiourea

Carbonic acid of an alkali metal used when the N-aryl cyanamide derivative of the general formula 6 is reacted with the allyl halide derivative of the general formula 7 to obtain the N-substituted-N-aryl cyanamide derivative of the general formula 8. Specific examples of the salt include sodium carbonate and potassium carbonate. The alkali metal carbonate is usually used in the form of powder, but if a fine powder having a large surface area per constant weight (for example, a particle size of 300 mesh or less) is used, the reaction is further accelerated. Examples of the iodide salt used include alkali metal iodide salts such as sodium iodide and potassium iodide, and alkaline earth metal iodide salts such as calcium iodide and barium iodide. Sodium iodide or potassium iodide is used. The aprotic polar solvent used is preferably one having a relative dielectric constant of 22 or more, and specifically,
N, N-dimethylformamide (DMF), dimethylsulfoxide (DMSO), hexamethylphosphoric triamide (HMPA), sulfolane, N-methylpyrrolidone (NMP), N, N'-dimethylpropyleneurea (DMPU), 1 , 3-dimethyl-2-imidazolidinone (DMI), nitromethane, acetonitrile, N, N
-Dimethylacetamide (DMA) and the like, or a mixture thereof, but from an industrial viewpoint, DMF,
DMSO and NMP are particularly preferable. As an allyl halide derivative represented by the general formula 7, when X is a bromine atom, the reactivity is higher and the reaction time is shorter, but when X is a chlorine atom, the availability and the price are lower. Therefore, it is more practical. The reaction is usually carried out at a temperature in the range of 0 to 150 ° C. for 0.5 to 24 hours, preferably 2
It is performed at a temperature in the range of 0 to 80 ° C. The amount ratio of the reagent used is such that the alkali metal carbonate is usually 0.5 to 3 mol per 1 mol of the compound represented by the general formula:
The iodide salt is usually contained in a proportion of 0.01 to 1.0 mol. As a post-treatment method for the reaction, the reaction solution after completion of the reaction is concentrated as necessary, water is added, and if necessary, an acid such as dilute hydrochloric acid is added for neutralization, followed by extraction with an organic solvent and concentration. The N-substituted-N-arylcyanamide derivative represented by the general formula (8) can be obtained by performing ordinary treatment and, if necessary, further purifying by an operation such as chromatography.

As a specific operation method in the reaction for converting the N-substituted-N-arylcyanamide derivative of the general formula 8 into the N-substituted-N-arylthiourea derivative of the general formula 9, for example, the following methods are mentioned. Can be used. (A) A method in which hydrogen sulfide gas and ammonia gas are blown into a solution of the N-substituted-N-arylcyanamide derivative represented by the general formula (8) at a similar rate to react. (B) A method of blowing hydrogen sulfide gas or adding sulfur to a solution of the N-substituted-N-arylcyanamide derivative represented by the general formula 8 and ammonia water to react them. (C) N-substituted-N-aryl cyanamide derivative of general formula 8 and an organic amine (triethylamine, pyridine,
(Aniline, morpholine, etc.) A method in which hydrogen sulfide gas is blown into the solution or sulfur is added to react. (D) A method of reacting a solution of the N-substituted-N-aryl cyanamide derivative represented by the general formula 8 with a solution of ammonium sulfide. The above reactions (a) to (d) are usually carried out in a solvent,
The solvent used in the reaction is not particularly limited, but for example, aromatic hydrocarbon solvents such as benzene, toluene, xylene, halogenated hydrocarbon solvents such as monochlorobenzene, chloroform, ethylene dichloride, dimethoxyethane, tetrahydrofuran, dioxane, etc. Examples thereof include ether solvents, carbonyl solvents such as acetone and methyl isobutyl ketone, alcohol solvents such as methanol and ethanol, N, N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), water, and a mixture thereof. The reaction is usually carried out at a temperature within the range of 0 to 150 ° C. for 0.2 to 24 hours. The amount ratio of the reagents used is usually 1 mol of the N-substituted-N-aryl cyanamide derivative represented by the general formula: hydrogen sulfide, sulfur, or ammonium sulfide as an S content.
The amount is 1.0 to 5 mol, preferably 1.2 to 2 mol.
In the methods (a) to (c), ammonia or organic amine is usually used in a proportion of 0.1 to 1.2 mol with respect to 1 mol of hydrogen sulfide, sulfur or ammonium sulfide. When the above reaction is carried out, the reaction may be carried out using the isolated N-substituted-N-arylcyanamide derivative represented by the general formula (8), or the N-arylcyanamide derivative represented by the general formula (6) and the general formula The reaction may be carried out using the reaction solution after completion of the reaction in which the N-substituted-N-arylcyanamide derivative of the general formula 10 was synthesized by reacting the allyl halide derivative of 7 As a post-treatment method for the reaction, the reaction solution after completion of the reaction is concentrated as necessary, water is added, and if necessary, an acid such as dilute hydrochloric acid is added for neutralization,
The compound is subjected to usual treatments such as extraction and concentration with an organic solvent, and if necessary, further purified by an operation such as chromatography to obtain the N-substituted-N- of the general formula 9
An aryl thiourea derivative can be obtained. N of the general formula 6 used as a starting compound in the present invention
The -aryl cyanamide derivative can be obtained by a conventional method. Further, as the allyl halide derivative represented by the general formula 7, a commercially available one can be used, or one obtained by a conventional method can be used.

[0007]

EXAMPLES The present invention will now be described in more detail with reference to examples, but the present invention is not limited to these examples. The purity of the obtained product was determined from the results of NMR spectrum and gas chromatography and / or liquid chromatography. In the gas chromatography, a wide-bore capillary column DB-1 (manufactured by J & W Scientific Co., Ltd.) was used as a column, and a flame ionization detector was used for detection.
For liquid chromatography, the column is reverse-phase ODS.
A-212 (manufactured by Sumika Chemical Analysis Service Co., Ltd.) was used as the developing solvent, and pH 7.2 phosphate buffer aqueous solution: methanol: tetrahydrofuran = 40: 55: 5 was used. Used 254 nm. Example 1 18.6 g of N- (3- (trifluoromethyl) phenyl) cyanamide was dissolved in 93.0 g of DMF, and 20.7 g of finely powdered potassium carbonate and 1.7 g of potassium iodide were added thereto with stirring at room temperature. Furthermore, 13.3-g of 2,3-dichloro-1-propene
Was added dropwise with stirring at room temperature, then the temperature was raised to 50 ° C and 1
Stir for hours. After cooling to room temperature, water was added, the mixture was extracted with ethyl acetate, and the organic layer was washed with water. The solvent was distilled off under reduced pressure, and oily N- (3- (trifluoromethyl) phenyl) was obtained.
-N- (2-chloro-2-propenyl) cyanamide 25.8
g (apparent yield 99%) was obtained. The area percentage of gas chromatography and liquid chromatography is 9 each.
8% and 99%. ¹ H-NMR (CDCl ₃ / TMS) δ (ppm):
7.8 to 7.3 (4H, m), 5.6 (2H, s), 4.4 (2
H, s) mass (EI): m / e parent peak 260 N- (3- (trifluoromethyl) thus obtained
23.2 g of phenyl-N- (2-chloro-2-propenyl) cyanamide was dissolved in 380 ml of ethanol, and 460.8 g of ammonium sulfide solution (colorless) with S content of 0.6% was added dropwise to the solution at room temperature with stirring. The temperature was raised and the mixture was stirred at the same temperature for 8 hours. After cooling to room temperature, ethanol was distilled off under reduced pressure, extraction was performed with ethyl acetate, and the organic layer was washed with water. The solvent was distilled off under reduced pressure to give solid N- (3- (trifluoromethyl) phenyl) -N- (2-chloro-2-propenyl).
25.2 g (apparent yield 96%) of thiourea was obtained. The area percentages of gas chromatography and liquid chromatography were 99% and 100%, respectively. ¹ H-NMR (CDCl ₃ / TMS) δ (ppm):
7.8-7.6 (4H, m), 5.9 (2H, br), 5.4
(1H, s), 5.4 (1H, s), 5.1 (2H, s) mass (FD): m / e parent peak 294 Example 2 16.3 g of N- (3- (trifluoromethyl) phenyl) cyanamide was added to DMF. It was dissolved in 108.6 g, and 18.4 g of powdered potassium carbonate was added thereto while stirring at room temperature. Further, 11.8 g of 2,3-dichloro-1-propene was added dropwise with stirring at room temperature, the temperature was raised to 50 ° C., and the mixture was stirred at the same temperature for 1.5 hours. [In the liquid chromatography of the reaction solution for 1 hour after the temperature rise,
N- (3- (trifluoromethyl) phenyl) cyanamide and N- (3- (trifluoromethyl) phenyl) -N
The area percentage ratio of-(2-chloro-2-propenyl) cyanamide was 81:19. ] Then, 1.7 g of potassium iodide was added with stirring at 50 ° C, and the mixture was further stirred at the same temperature for 1.5
Stir for hours. [N- (3- (trifluoromethyl) phenyl) cyanamide and N- (3- (trifluoromethyl) phenyl) -N- (2-chloro in the liquid chromatography of the reaction solution 1 hour after the addition of iodide salt -2-
The area percentage ratio of propenyl) cyanamide is 1:99.
Met. After cooling to room temperature, water was added, the mixture was extracted with ethyl acetate, and the organic layer was washed with water. The solvent was distilled off under reduced pressure, and oily N- (3- (trifluoromethyl) phenyl)-
N- (2-chloro-2-propenyl) cyanamide 23.3g
(Apparent yield 100%) was obtained. The area percentage of gas chromatography was 92%. Thus obtained N- (3- (trifluoromethyl) phenyl-N- (2
2.62 g of -chloro-2-propenyl) cyanamide was dissolved in 13.25 g of methanol, and 8.17 g of ammonium sulfide solution (yellow) having an S content of 6% was added dropwise thereto at room temperature with stirring.
It heated up at 50 degreeC and stirred at the same temperature for 7 hours. After cooling to room temperature, water was added, the mixture was extracted with ethyl acetate, and the organic layer was washed with water. The solvent was distilled off under reduced pressure to obtain 2.82 g of solid N- (3- (trifluoromethyl) phenyl) -N- (2-chloro-2-propenyl) thiourea (apparent yield 95%). The area percentage of gas chromatography was 86%. Further, the above N- (3- (trifluoromethyl) phenyl) -N- (2-chloro-2-propenyl)
Cyanamide (2.61 g) was dissolved in methyl isobutyl ketone (13.01 g), and an ammonium sulfide solution (yellow) having an S content of 6% (8.12 g) was added dropwise to the solution at room temperature with stirring. . After cooling to room temperature, water was added, the mixture was extracted with ethyl acetate, and the organic layer was washed with water. The solvent was distilled off under reduced pressure to obtain 2.67 g (apparent yield 90%) of solid N- (3- (trifluoromethyl) phenyl) -N- (2-chloro-2-propenyl) thiourea. The area percentage of gas chromatography was 85%. Further, the above N- (3- (trifluoromethyl) phenyl) -N-
0.8 g of (2-chloro-2-propenyl) cyanamide,
Sulfur (S ₈ ) 0.15 g, MIK (methyl isobutyl ketone) 5 ml and ammonium water (about 30%) 4 ml
Were mixed and stirred at 50 ° C. for 6 hours. 20m water in the reaction solution
1 was added, and the mixture was extracted twice with 30 ml of ethyl acetate. The solvent was distilled off under reduced pressure, and the obtained crystals were washed with hexane to give 0.77 g of N- (3- (trifluoromethyl) phenyl) -N- (2-chloro-2-propenyl) thiourea ( Yield 85%) was obtained. Example 3 N- (3- (trifluoromethyl) phenyl) cyanamide (2.00 g) was dissolved in DMF (15.0 g), and powdered potassium carbonate (2.23 g) and potassium iodide (0.19 g) were added thereto with stirring at room temperature. Furthermore, 1,3-dichloro-1-propene (E form, Z
1.44 g of body mixture) was added dropwise with stirring at room temperature, then at 50 ° C.
The temperature was raised to and the mixture was stirred at the same temperature for 4.5 hours. After cooling to room temperature, an ammonium sulfide solution containing 6% S (yellow)
8.17 g was added dropwise with stirring at room temperature, the temperature was raised to 50 ° C., and the mixture was stirred at the same temperature for 1 hour. After cooling to room temperature, water was added, the mixture was extracted with ethyl acetate, and the organic layer was washed with water. The solvent was distilled off under reduced pressure,
3.47 g of a dark red solid was obtained. ^From the result of ¹ H-NMR,
It contained 6% (weight ratio) of DMF. N- (3-
(Trifluoromethyl) phenyl) -N- (3-chloro-2-propenyl) thiourea (mixture of E-form and Z-form)
The yield was 99% (value corrected for DMF content).
The area percentage of liquid chromatography is 95% (DM
Except F). E form; ¹ H-NMR (CDCl ₃ / TMS) δ (ppm):
7.8 to 7.4 (4H, m), 6.2 (1H, m), 6.1 (1
H, m), 5.8 (2H, br), 5.0 (2H, s) mass (FD): m / e parent peak 294 Z-form; ¹ H-NMR (CDCl ₃ / TMS) δ (ppm):
7.8 to 7.4 (4H, m), 6.2 (1H, m), 6.1 (1
H, m), 5.8 (2H, br), 4.8 (2H, s) mass (FD): m / e parent peak 294 Example 4 Dissolve 2.81 g of N- (3,5-dichlorophenyl) cyanamide in 14.03 g of DMF. Powdered potassium carbonate 3.
11 g and 0.26 g of potassium iodide were added with stirring at room temperature. Further, 2.00 g of 2,3-dichloro-1-propene was added dropwise with stirring at room temperature, the temperature was raised to 50 ° C., and the mixture was stirred at the same temperature for 2.5 hours. After cooling to room temperature, 9.00 g of DMF and 8.00 g of ammonium sulfide solution with 6% S content (yellow) were added dropwise to the mixture at room temperature with stirring, then the temperature was raised to 50 ° C and the mixture was stirred at the same temperature for 4 hours.
After cooling to room temperature, water was added, the mixture was extracted with ethyl acetate, and the organic layer was washed with water. The solvent was distilled off under reduced pressure to obtain 4.00 g (apparent yield 90%) of N- (3,5-dichlorophenyl) -N- (2-chloro-2-propenyl) thiourea as a dark red solid. The area percentage of liquid chromatography was 94%. ¹ H-NMR (CDCl ₃ / TMS) δ (ppm):
7.5 (1H, t), 7.3 (2H, d), 5.8 (2H, b
r), 5.4 (1H, s), 5.3 (1H, s), 5.1 (2
H, s) Example 5 N- (4-methoxyphenyl) cyanamide 2.22 g was DM
F dissolved in 11.10g, powdered potassium carbonate 3.11g
And 0.26 g of potassium iodide were added with stirring at room temperature. Further, 2.00 g of 2,3-dichloro-1-propene was added dropwise with stirring at room temperature, the temperature was raised to 50 ° C., and the mixture was stirred at the same temperature for 1.5 hours. After cooling to room temperature, 8.00 g of ammonium sulfide solution with 6% S content (yellow) was added dropwise to the solution under stirring at room temperature, and then 5
The temperature was raised to 0 ° C. and the mixture was stirred at the same temperature for 3 hours. After cooling to room temperature,
Water was added, the mixture was extracted with ethyl acetate, and the organic layer was washed with water. The solvent was distilled off under reduced pressure, and N- (4-methoxyphenyl)-
N- (2-chloro-2-propenyl) thiourea 3.63 g
(Apparent yield 94%) was obtained as a dark red solid. The area percentage of liquid chromatography was 94%. ¹ H-NMR (CDCl ₃ / TMS) δ (ppm):
7.2 (2H, d), 7.0 (2H, d), 5.7 (2H, b
r), 5.3 (1H, s), 5.3 (1H, s), 5.1 (2
H, s), 3.9 (3H, s)

Comparative Example 1 5.58 g of N- (3- (trifluoromethyl) phenyl) cyanamide was dissolved in 90.0 g of toluene, and 6.22 g of finely powdered potassium carbonate, 0.50 g of potassium iodide and tetrabutylammonium bromide were dissolved therein. 0.97 g was added with stirring at room temperature. Further, 4.00 g of 2,3-dichloro-1-propene was added dropwise with stirring at room temperature, the temperature was raised to 80 ° C., and the mixture was stirred at the same temperature for 7 hours. After confirming the disappearance of N- (3- (trifluoromethyl) phenyl) cyanamide, the mixture was cooled to room temperature, water was added, the mixture was extracted with ethyl acetate, and the organic layer was washed with water. The solvent was distilled off under reduced pressure, and crude oily N- (3-trifluoromethyl) phenyl) -N- (2-chloro-2 was used.
-Propenyl) cyanamide 7.44 g (apparent yield 95%)
Got Area percentage of liquid chromatography is 55%
Met. Comparative Example 2 N- (3- (trifluoromethyl) phenyl) cyanamide (5.58 g) was dissolved in methyl isobutyl ketone (90.0 g), and fine powdery potassium carbonate (6.22 g) and potassium iodide (0.20 g) were added thereto.
50g and tetrabutylammonium bromide 0.97g
Was added with stirring at room temperature. Further, 4.00 g of 2,3-dichloro-1-propene was added dropwise with stirring at room temperature, the temperature was raised to 80 ° C., and the mixture was stirred at the same temperature for 7 hours. After confirming the disappearance of N- (3- (trifluoromethyl) phenyl) cyanamide, the mixture was cooled to room temperature, water was added, and the mixture was extracted with ethyl acetate.
The organic layer was washed with water. The solvent was distilled off under reduced pressure, and oily crude N- (3-trifluoromethyl) phenyl) -N-
8.21 g (apparent yield 105%) of (2-chloro-2-propenyl) cyanamide was obtained. The area percentage by liquid chromatography was 42%. Comparative Example 3 2.79 g of N- (3- (trifluoromethyl) phenyl) cyanamide was dissolved in 45.0 g of acetone, and 3.11 g of finely powdered potassium carbonate, 0.25 g of potassium iodide and 0.34 g of benzyltriethylammonium chloride were added. It was added with stirring at room temperature. Further 2,3-dichloro-1-propene 2.
After adding 00 g dropwise at room temperature with stirring, the temperature was raised to 50 ° C. and the mixture was stirred at the same temperature for 6 hours. N- (3- (trifluoromethyl)
After confirming that (phenyl) cyanamide disappeared, the mixture was cooled to room temperature, water was added, the mixture was extracted with ethyl acetate, the organic layer was washed with water, and crude N- (3-trifluoromethyl) phenyl) was added.
A -N- (2-chloro-2-propenyl) cyanamide solution was obtained. Area percentage of liquid chromatography is 35%
Met.

As described in the first half of the second embodiment,
The N-aryl cyanamide derivative represented by the general formula 6 is reacted with the allyl halide derivative represented by the general formula 7
In the reaction of the N-substituted-N-aryl cyanamide derivative of Chemical formula 8, the reaction rate was significantly reduced when the iodide salt was not added. Further, as described in Comparative Examples 1, 2 and 3, when the reaction is carried out in toluene, methyl isobutyl ketone or acetone, the reaction rate is lowered, and the N-substituted- The purity of the N-aryl cyanamide derivative also decreased.

[0010]

According to the method of the present invention, the above-mentioned general formula
The N-substituted-N-aryl cyanamide derivative represented by and the N-substituted-N-aryl thiourea derivative represented by the general formula 9 above can be easily produced in good yield and purity.

Continuation of the front page (72) Inventor Toshio Nagatomi 4-2-1 Takashi, Takarazuka-shi, Hyogo Within Sumitomo Chemical Co., Ltd. (56) Reference US Patent 4018917 (US, A) Periodica Polytechnica, Engineering, 1968 , Vol. 12, No. 2, p. 123-146 (58) Fields surveyed (Int.Cl. ⁷ , DB name) CA (STN) REGISTRY (STN)

Claims (5)

(57) [Claims] 1. A general formula: ## STR1 ## [In the formula, R ¹ represents an optionally substituted aryl group. ] And an N-aryl cyanamide derivative represented by the following general formula: [Wherein R ² represents a hydrogen atom, an optionally substituted alkyl group or an optionally substituted aryl group, and R 2
³ , R ⁴ and R ⁵ are the same or different and each represents a hydrogen atom, a halogen atom, an optionally substituted alkyl group or an optionally substituted aryl group, and X represents a chlorine atom or a bromine atom. ] In the presence of an iodide salt and an alkali metal carbonate in an aprotic polar solvent, represented by the general formula: [In the formula, R ¹ , R ² , R ³ , R ⁴ and R ⁵ have the same meanings as described above. ] The manufacturing method of the N-substitution N-aryl cyanamide derivative shown by these. 2. N represented by the general formula (1 ) according to claim 1.
- and arylene cyanamide derivative, an allyl halide derivative of the formula of 2 according to claim 1, wherein the presence of an iodide salt and an alkali metal carbonate, is reacted with an aprotic polar solvent, wherein Item 1. An N-substituted-N-arylcyanamide derivative represented by the general formula (3 ) is obtained, and the N-substituted-N-arylcyanamide derivative is then reacted with a chemical species that produces a sulfide ion or a hydrogen sulfide ion. Chemical formula 4 [In the formula, R ¹ , R ² , R ³ , R ⁴ and R ⁵ have the same meanings as described above. ] The manufacturing method of the N-substituted N-aryl thiourea derivative shown by these. 3. The method according to claim 2, wherein the chemical species that generate sulfide ions or hydrogen sulfide ions are hydrogen sulfide; ammonium sulfide; sulfur and ammonium; or sulfur and organic amine. 4. N represented by the general formula (3) according to claim 1.
-Substituted-N -aryl cyanamide derivative (provided that N-phenyl-N- (2-bromo-2-propenyl) cyanamide and N-phenyl-N- (2-propenyl) cyanamide
Excluding de . ). 5. N- (3- (trifluoromethyl) phenyl) -N- (2-chloro-2-propenyl) cyanamide.