JPS6314718B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel method for producing phosphoric acid anilide derivatives having bactericidal activity.

The inventors previously calculated the formula O-methyl S-phenyl N-n-propyl-N-phenylthiophosphoramidate and its similar compounds are particularly effective against rice blast and rice sheath blight, and are phytotoxic to rice. He discovered that it had low toxicity even to warm-blooded animals, and completed the invention of an agricultural and horticultural fungicide containing these as active ingredients (see Japanese Patent Laid-Open Publication No. 160344/1983). The compound of formula () is disclosed in JP-A-54-160344, and is particularly excellent as a fungicide for agriculture and horticulture among a series of compounds.

The present inventors have conducted various studies on methods for producing such useful compounds () with simple operations and high yields. As a result, as shown in the following reaction formula, by using a new compound represented by the general formula ( The present inventors have discovered that the compound () can be obtained in a higher yield and in a shorter time than the known production methods, ie, the following methods [A], [B], and [C], leading to the present invention.

Method of the invention (In the formula, X represents a halogen atom) The method described in JP-A-54-160344 (In the formula, X represents a halogen atom, and Y represents a halogen atom, an -OSO ₃ C ₃ H ₇ (n) group, etc.) The present invention will be explained in more detail below.

Compound () has a methoxy group and an anilino group substituted with a bulky n-propyl group in its steric structure. Due to this chemical structure, in the methods [A] to [C] above, side reactions such as demethylation, which are specific to organic compounds, occur, and compound () cannot be obtained in high yield (see Comparative Example below). reference).
However, when the present inventors produced compound () by a method in which a methoxy group was introduced at the end, it was surprisingly possible to produce compound () without causing any problematic side reactions using methods [A] to [C]. It was possible to obtain it in high yield.

Methanol may be used as a solvent in the reaction to replace halogen in compound () with methoxy, but other solvents such as hexane,
Hydrocarbons such as benzene and toluene, halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, and chlorobenzene, ethers such as diethyl ether, tetrahydrofuran, and dioxane, and ketones such as acetone, methyl ethyl ketone, and methyl isobutyl ketone. It is preferable to carry out the reaction using nitriles such as , acetonitrile, and propionitrile. To make the reaction proceed smoothly, metallic sodium, metallic potassium,
It is appropriate to use methanol in its activated form, ie, as its alkali metal salt, with sodium hydride, sodium amide, etc. In addition, depending on the case, the reaction can be carried out using organic amines such as triethylamine and pyridine, and inorganic bases such as sodium carbonate and potassium carbonate as acid binders. The reaction proceeds smoothly at or below room temperature. In some cases, the reaction may be carried out by heating to any temperature from room temperature to the boiling point of the solvent. After the reaction is completed, the salts of the acid binder and the like are separated and the solvent is distilled off to obtain the compound (). Compound () can also be obtained by adding a solvent such as benzene and water, separating the organic layer, and distilling off the solvent.

Next, examples according to the present invention and JP-A-54-
Comparative examples using methods [A] to [C] described in No. 160344 are shown below.

Example 1 32.6 g of S-phenyl-N-n-propyl-N-phenylthiophosphoroamide chloridate was dissolved in 100 ml of dry tetrahydrofuran, and 6.5 g of powdered sodium methoxide was added to the resulting solution with stirring under ice cooling. The mixture was added little by little at the same time, and the reaction was then allowed to proceed at room temperature for 10 minutes. Next, the reaction solution is shaken with benzene and water, and the benzene layer is separated. After washing the benzene layer with water, it was dried over anhydrous sodium sulfate, and the benzene was distilled off under reduced pressure to obtain the desired compound (O-methyl S-phenyl N-n-propyl-N-phenylthiophosphoroamidate) as a yellow oil. 31.2 g (yield 97%) of the product was obtained. When this substance is purified by silica gel column chromatography, it becomes a colorless oil with a refractive index n ²³ _D =
It showed 1.5746. Its elemental analysis values are as follows.

N (%) P (%) S (%) Calculated value: 4.78 10.56 10.93 Actual value: 4.78 10.54 10.95 Example 2 32.6 g of S-phenyl N-n-propyl N-phenylthiophosphoroamide chloridate was added to benzene
21.2 g of a 28% methanol solution of sodium methoxide was added to the resulting solution while stirring under ice cooling. The resulting mixture was allowed to react for 5 minutes at room temperature. Next, water was added to the reaction solution to dissolve the precipitated salt, and the benzene layer that separated at this time was collected. The benzene layer was washed with water, dried over anhydrous sodium sulfate, and the benzene was distilled off under reduced pressure to obtain the desired compound as a yellow oil with 31.5
g (yield 98%). When purified by silica gel column chromatography, this product became a colorless oil with a refractive index n ²³ _D =1.5745.
Its elemental analysis values are as follows.

N (%) P (%) S (%) Calculated value: 4.78 10.56 10.93 Actual value: 4.76 10.56 10.94 Example 3 37.0 g of S-phenyl N-n-propyl N-phenylthiophosphoramidobromidate was added to benzene
The solution was dissolved in 100 ml, and 21.2 g of a 28% methanol solution of sodium methoxide was added thereto while stirring under ice cooling. The mixture was allowed to react for 5 minutes at room temperature. Next, water was added to the reaction solution to dissolve the precipitated salt, and the benzene layer that separated at this time was collected. The benzene layer was washed with water, dried over anhydrous sodium sulfate, and benzene was distilled off under reduced pressure to obtain 31.2 g (yield 97%) of the desired compound as a yellow oil. When purified by silica gel column chromatography, this product became a colorless oil with a refractive index n ²³ _D =1.5743. Its elemental analysis values are as follows.

N (%) P (%) S (%) Calculated value: 4.78 10.56 10.93 Actual value: 4.77 10.54 10.92 Comparative example 1 (according to method [A] described in JP-A-54-160344) O-methyl S-phene After adding 29.7 g of N-n-propylaniline to 22.3 g of nylthiophosphorochloridate with stirring at room temperature, the mixture was reacted at 50 to 60°C for 2 hours. After the reaction is completed, benzene and water are added, the resulting benzene layer is separated, and it is
% hydrochloric acid, 5% sodium hydroxide solution and water. After washing with water and drying over anhydrous sodium sulfate, the benzene was distilled off under reduced pressure to obtain 5.8 g (yield 18%) of the desired compound as a brown oil.
When this product was purified by silica gel column chromatography in the same manner as in Examples 1 to 3, it became a colorless oil with a refractive index n ²³ _D =1.5745.

Comparative Example 2 (By method [B] described in JP-A-54-160344) Thiophenol 11.6g and triethylamine
11.1 g was dissolved in 100 ml of benzene, and 24.8 g of O-methyl N-n-propyl N-phenyl phosphoroamide chloridate was added thereto while stirring under water cooling. The mixture was reacted for 2 hours at the reflux temperature of benzene. Ta. After the reaction was completed, water was added to the reaction solution to dissolve the precipitated salt, and the benzene layer was separated. The benzene layer was washed with 5% hydrochloric acid, 5% sodium hydroxide solution and water, dried over anhydrous sodium sulfate, and the benzene was distilled off under reduced pressure to yield 4.2 g of the desired compound as a brown oil (13% yield). )
obtained in the amount of When this product was purified by silica gel column chromatography in the same manner as in Examples 1 to 3, it showed a refractive index n ²³ _D =1.5744.

Comparative Example 3 (By method [C] described in JP-A-54-160344) 27.9 g of O-methyl S-phenyl N-phenylthiophosphoroamidate and n-propyl iodide
22.1 g was dissolved in 100 ml of acetone, 15.2 g of potassium carbonate was added thereto, and the mixture was reacted for 3 hours at the reflux temperature of acetone. After the reaction is completed, acetone is distilled off under reduced pressure, benzene and water are added to the reaction mixture, and the benzene layer is separated. The benzene layer was washed with 5% hydrochloric acid, 5% sodium hydroxide solution, and water, dried over anhydrous sodium sulfate, and the benzene was distilled off under reduced pressure to obtain 6.7 g of the desired compound as a brown oil (yield 21%). ) was obtained in an amount of When this product was purified by silica gel column chromatography in the same manner as in Examples 1 to 3, it became a colorless oil with a refractive index n ²³ _D =1.5747.

Next, Reference Examples 1 and 2 are listed regarding the production mode of the starting materials used in the method of the present invention.

Reference example 1 S-phenylthiophosphorodichloridate 22.7
To this was added a solution of 35.2 g of N-normal propylaniline dissolved in 30 ml of benzene with stirring at room temperature, and the mixture was reacted for 1 hour at the reflux temperature of benzene. After cooling, the precipitated N-n-propylaniline hydrochloride was separated, and the liquid was washed with 5% hydrochloric acid, 5% sodium carbonate solution and water, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure to obtain S-phenyl. 31.9 g (98% yield) of N-normal propyl N-phenylthiophosphoroamide chloridate was obtained as a yellow oil. When this substance is vacuum distilled, the boiling point is 170.
~177℃/0.04mmHg pale yellow oil with refractive index
It showed n ¹⁸ _D = 1.6009. Its elemental analysis values are as follows.

N (%) P (%) S (%) Calculated value: 4.30 9.51 9.84 Actual value: 4.32 9.50 9.86 Reference example 2 15.2 g of N-normal propyl N-phenyl phosphoroamide dichloridate was dissolved in 100 ml of benzene, A solution of 11.0 g of thiophenol and 8.3 g of pyridine dissolved in 50 ml of benzene was added to this while stirring under ice cooling, and the mixture was gradually heated to the reflux temperature of benzene. The reaction was carried out at reflux temperature for 15 minutes, and after cooling, the precipitated pyridine hydrochloride was separated, and the liquid was
% hydrochloric acid, 5% sodium carbonate solution and water, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure to yield S-phenyl N-n-propyl N.
-Phenylthiophosphoroamide chloridate 28.7
g (88% yield) was obtained as a yellow oil. When this substance is vacuum distilled, the boiling point is 172-178℃/0.04mm
It became a pale yellow oil of Hg and showed a refractive index n ¹⁸ _D = 1.6008.

Claims (1)

[Claims] 1. General formula (wherein X represents a halogen atom) is reacted with methanol in activated form. A method for producing the compound.