JPS5910351B2 - Method for producing 3-oxy-1,2,4-triazole derivative - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention is based on the following formula: -8 cycloalkyl group, R2 represents an alkyl group having 1 to 6 carbon atoms, an alkenyl group having 3 to 6 carbon atoms, an alkynyl group having 3 to 6 carbon atoms, a benzyl group or the following substituents: represents an alkyl, alkoxy or alkylthio group having 1 to 4 carbon atoms, a benzyl group mono- or di-substituted with a halogen atom, a trifluoromethyl group or a nitro group, and X is an oxygen atom, a sulfur atom or a group 〉N- R3 (in the group, R3 means an alkyl group having 1 to 6 carbon atoms);

The present invention relates to a method for producing a 3-oxy-1,2,4-triazole derivative represented by the following. The 3-oxy-1,2,4-triazole derivative represented by the above formula 1 is a useful intermediate in the production of phosphate esters that can be used as pest control agents, especially insecticides.

Such phosphoric acid esters are described, for example, in DE 2259960, DE 2259974 and DE 23
No. 30089.

1.5-monosubstituted 3-oxy-1. represented by formula 1 above
The 2,4-triazole is first reacted with an orthoformic acid ester with a semicarbazide substituted with the R1 group defined above, resulting in the initial 1-monosubstituted 3-oxy-1.
The 5-position of the 2,4-triazole is subsequently chlorinated and the chlorine atom is replaced by an R2-X group in which R2 and X have the meaning given in formula 1.

) is known to be obtained by substitution.
However, this conventional method requires many reaction steps and is also unsatisfactory in terms of yield. The loss in yield is mainly due to 3-oxy-1, which occurs as an intermediate.
Chlorination of 2,4-triazole and R
The purpose is to replace the introduced chlorine atom with one 2-X group.
The 3-oxy-1,2,4-triazole derivative represented by formula 1 has the following formula: R1--COOR() (wherein R1 has the meaning shown in formula 1 above, and R is carbon A hydrazine carboxylic acid ester represented by the formula (representing an alkyl group having 1 to 4 atoms) is first reacted with cyanogen chloride to form a compound of the following formula: (wherein R1 and R have the meanings given in formula 1 above). ) and found that it can be easily produced by obtaining the corresponding 2-monosubstituted 2-cyanohydrazinecarboxylic acid ester represented by Ta.

The process according to the invention is carried out with particular advantage in inert solvents.

Suitable solvents for reacting the hydrazine carboxylic acid ester of the formula with cyanogen chloride are preferably halogenated hydrocarbons, such as methylene chloride, chloroform,
carbon tetrachloride, chlorobenzene, or aromatic hydrocarbons,
Examples include benzene and toluene, or ketones, especially methyl ethyl ketone, or esters, especially ethyl acetate, or ethers and ethereal liquids, such as diethyl ether, tetrahydrofuran and dioxane. Suitable solvents for terminating the cyclization reaction are in particular water and alcohols, suitable alcohols being lower alkanols having 1 to 4 carbon atoms. However, the cyclization reaction can also be carried out in the absence of the solvent. The reaction of the hydrazine carboxylic ester of the formula with cyanogen chloride is advantageously carried out in the presence of an acid binder at a temperature of 0 to 30°C.

Suitable acid binders are especially alkali metal hydroxides, alkali metal carbonates and especially alkali metal bicarbonates. Furthermore, it is very advantageous to carry out the reaction of the hydrazine carboxylic ester of the formula with cyanogen chloride in a two-phase reaction solvent consisting of water and one of the water-immiscible solvents mentioned above. The cyclization reaction is carried out at 0 to 140°C, preferably 40 to 8°C.
It is carried out at a temperature of 0°C.

The reaction can be carried out at normal pressure or, if necessary, in an autoclave overpressured to 50 atmospheres. When the cyclization reaction is carried out in lower alcohols, it is advantageous to carry out the reaction in the presence of the corresponding sodium or potassium alcoholade. The above cyclization reaction in a lower alcohol can also be carried out in the presence of sodium hydroxide or sodium hydroxide. If the cyclization reaction is carried out in water, it is advantageous to carry out it in the presence of sodium or potassium hydroxide. The groups R1 and R2 have 1 carbon atom as an alkyl group.
Contains straight or branched chain alkyl groups having ~6.

Radical R as cycloalkyl group having 3 to 8 carbon atoms
1 also includes a cycloalkyl group whose ring is substituted with a lower alkyl group. Additionally, the cycloalkyl group may be bonded to the nitrogen atom via 1 to 3 methylene groups. R2 groups as benzyl groups each have 1 carbon atom
The benzene nucleus may be mono- or di-substituted with an alkyl, alkoxy or alkylthio group having -4, a halogen atom, especially a chlorine or bromine atom, a nitrogen atom, or a thiofluoromethyl group. The method according to the invention is further illustrated in the following examples.

Example 1 73.0 t of 2-isopropylhydrazinecarboxylic acid ethyl ester and 42.0 t of sodium bicarbonate are stirred in 200 ml of methylene chloride and 400 ml of water.

30.8 t of gaseous cyanogen chloride is then passed through the solution at room temperature for 20 minutes with stirring. After continued stirring for 1 hour, the basic methylene chloride is separated off, dried over sodium sulphate and the solvent is removed under reduced pressure.

Colorless oily 2-isopropyl-2-cyanohydrazinecarboxylic acid ethyl ester 75.07 (theoretical value 87.5
%) is obtained as a residue. 1370 tons of 2-isopropyl-2-cyanohydrazinecarboxylic acid ethyl ester was placed in an autoclave, and 423V of methyl mercaptan was added.
inject.

The temperature is maintained at 40°C for 24 hours. The resulting crystal mass was then transferred to a 2.51 sulfonation flask and heated to 120°C.
, on an oil bath for 2 hours. Then 90℃
The reaction mixture, cooled to 1.2 mL, is added to 1.21 g of water, with crystals precipitating as the reaction product. The crude crystals of 1-isopropyl-5methylthio-3-oxy-1,2,4-triazole were separated, and 11? Recrystallize from acetonitrile. 730t of pure 1-isopropyl-5-methylthio-3-oxy-1,2,4-triazole (
52% of theory) is obtained: melting point 88-93°C. Purity: 98%, Yield: 45.5% from 2-isopropylhydrazinecarboxylic acid ethyl ester. Example 960 t of 2-methyl mercaptan was introduced into a solution of 800 t of sodium hydroxide in 5000 ml of water, and then 2- 3024 t of isopropyl-2-cyanohydrazinecarboxylic acid ethyl ester are added dropwise.

The temperature is increased to 80° C. during the addition and then maintained at the same temperature for 2 hours. Continue stirring at 20° C. for 15 hours.

Addition of a further 1200 t of glacial acetic acid precipitates 2872 t of 1-isopropyl-5-methylthio-3-oxy-1,2,4-triazole: melting point 93-96°C. Extraction of the sap with ethyl acetate yields an additional 175 tons of 1-isopropyl 5-methylthio-3-oxy-1,2,4-triazole. The total yield is therefore 3047
t (87.5% of the theoretical value). Purity: 95% o Example 3 2-Ethylhydrazinecarboxylic acid ethyl ester 66.
0y and 42.0t of sodium bicarbonate, methylene chloride 2
00 ml and 400 ml of water.

Thereafter, 30.8 t of gaseous cyanogen chloride was passed through the mixture at room temperature while stirring for 20 minutes. After subsequent stirring for 1 hour, the methylene chloride layer is separated, dried over sodium sulfate and the solvent is distilled off under reduced pressure. Colorless oily 2-ethyl-2-cyanohydrazinecarboxylic acid ethyl ester 69
．． 0t (88% of theory) is obtained as residue. 31.4 t of 2-ethyl-2-cyanohydrazinecarboxylic acid ethyl ester is added dropwise to a solution of 4.6 V of sodium dissolved in 150 ml of absolute ethanol at 60°C.

The solution is then refluxed for 4 hours. Addition of glacial acetic acid and 12v of sodium acetate from the cooled solution produces a precipitate,
The substance is separated by ▲. The filtrate is concentrated to dryness under reduced pressure and the residue is extracted with 200 ml of chloroform. The extract is concentrated again to dryness and the residue is recrystallized from cyclohexane. l-ethyl-5-ethoxy-3
-Oxy-1,2,4-triazole 18.8t (60% of theory) obtained: 64-67℃, purity: 97%, yield: 85% from 2-isopropyl-2-cyanohydrazinecarboxylic acid ethyl ester .3% o Example 4 35.0 t of 2-isopropyl-2-cyanohydrazinecarboxylic acid ethyl ester was dissolved at 33% in absolute ethanol.
Add dropwise to a solution of 100 ml of dimethylamine.

The solution was first heated at room temperature for 15 hours and then at reflux temperature (65
℃) for 11 hours. Evaporation and concentration to dryness yields an oily residue, which slowly crystallizes on standing. The semisolid product obtained is washed with ethyl acetate. 1-isopropyl-5-dimethylamino-3-oxy-1,2,4-triazole 15.5r (
44% of theory) is obtained: melting point 111-112°C o
Purity: 98%.

Example 5 48 V of methyl mercaptan are mixed into a solution of 401 sodium hydroxide in 300 d of water, followed by dropwise addition of 185 f of 2-sec-butyl-2-cyanohydrazinecarboxylic acid.

During the addition the temperature is increased to 90°C. Cool the mixture to room temperature. When 60 tons of glacial acetic acid is added, 1-secondary butyl-
148.91 (79.5% of theory) of 5-methylthio-3-oxy-1,2,4-triazole precipitates: mp 104-106°C. Purity: 97% o 2-Second-butyl-2-cyanohydrazinecarboxylic acid ethyl ester used as starting material was as performed in Examples 1 and 3.

It is produced in a similar manner to the method in which 2-secondary butylhydrazine carboxylic acid ethyl ester is reacted with cyanogen chloride.

Purity: 89%, total process yield: 70.75% o Example 6
Methyl mercaptan 905f is introduced into an ethanolic solution of sodium ethylate prepared from sodium 361f and absolute ethanol 91, and subsequently 2-ethyl-2-cyanohydrazinecarboxylic acid ethyl ester 2
Add 470f.

The solution obtained is first kept at room temperature for 15 hours and then at reflux temperature (80° C.) for 3 hours. Upon addition of 942f of glacial acetic acid, a precipitate forms from the cooled sodium acetate solution and is separated. ▲ Concentrate the liquid under reduced pressure to dryness; 1 residue is taken up in chloroform 71, ▲
complete the process. The P solution is concentrated by evaporation at normal pressure and toluene is added. Perform a filtration and add 11 cyclohexane to the sap. 1-Ethyl-5-methyl-thio-3-oxy-1,2,4-triazole 1890y (75.5% of theory) is obtained: mp 83-87°C.

Purity: 95% o Example 7 To an ethanolic solution of sodium ethylate obtained from 4.6 V of sodium and 100 ml of absolute ethanol, first 14.9 f of ethyl mercaptan was added dropwise, followed by the addition of 2
-Ethyl-2-cyanohydrazinecarboxylic acid ethyl ester is added dropwise.

A crystalline precipitate forms, which is refluxed for 3 hours.
After addition of 12 tons of glacial acetic acid and filtration, the precipitated sodium acetate and the cooled suspension are separated, and the liquid f is concentrated to dryness under reduced pressure. Add 200 ml of chloroform to the residue and then separate. ▲ Concentrate the liquid again for drying.
The residue is recrystallized in cyclohexane. 1-ethyl-5
-Ethylthio-3-oxy-1,2,4-triazole 26y (75% of theory) is obtained; mp 65-68°C.

Purity: 98 ml Example 8 51.5 f of ethyl mercaptan followed by 163 t of 2-cyclopentyl-2-cyanohydrazinecarboxylic acid ethyl ester in 190 ml of water with 33.5 f of sodium hydroxide.
Add 2t dropwise to the solution at room temperature.

The solution is subsequently refluxed for 1 hour. After adding 50 y of glacial acetic acid, 1-cyclopentyl-5-methylthio-3-oxy-1,2,4-triazole 167
Obtain f7 (94% of theory): melting point 93-95°C. Purity: 92%. The 2-cyclopentyl-2-cyanohydrazinecarboxylic acid ethyl ester used as the starting material was
It is obtained by reacting 2-cyanocyclopentylhydrazinecarboxylic acid ethyl ester and cyanogen chloride in the same manner as described in Examples 1 and 3. Yield: 90% o Overall yield: 84.6% 0 Example 9 Allyl mercaptan 244r was added to a solution of sodium hydroxide 132f in 750 ml of water, followed by 2-ethyl-2-cyano at room temperature. 514 t of hydrazine carboxylic acid ethyl ester are added dropwise.

After refluxing for 1 hour, a cooled solution of 198 t of glacial acetic acid is added to the solution.

The oil layer is separated and concentrated under reduced pressure to dryness. 1-
Ethyl-5-allylthio-3-oxy-1,2,4-triazole 260y (43% of theory) is obtained: melting point 7
4-76°C o Purity: 90% o Example 10 31.7y of 4-chlorobenzyl mercaptan was added to 10% of water.
8t of sodium hydroxide in 0ml and 50d of alcohol
was added to the solution containing 2-isopropyl-2-
Cyanohydrazine carboxylic acid ethyl ester 34.2t
Add dropwise.

The temperature of the solution is increased to 38° C. throughout the dropwise addition. The temperature was then maintained at 85°C for 2 hours, then cooled to 20°C and 12t of glacial acetic acid was added dropwise to give white crystals of 1-isopropyl-3-oxy-5-(4chlorobenzyl-thio)-1. - 2,4-triazole precipitates. The precipitate is recrystallized from 400 ml of methanol. The yield of the product obtained is 42t (74% of theory); melting point 140-141°C. Purity: 99% o Example 11 To a solution of 8 V of sodium hydroxide in 100 ml of water and 50 ml of alcohol, first 24.8 V of benzyl mercaptan and then 34.2 t of 2-isopropyl 2-cyanohydrazinecarboxylic acid ethyl ester are added. .

The temperature of the solution is increased to 38°C during the dropwise addition and kept at 85°C for 2 hours after the dropwise addition is complete. The temperature is 20℃
After cooling to , 12 tons of glacial acetic acid are added to give 31 tons of 1-J■■1,2,4-triazole (62% of theory) in the form of white crystals; melting point 134-135°C. Purity: 97
．． 5%. Example 12 24.05 y of methyl mercaptan was added to 3 y of absolute ethanol.
11.5 t of sodium is dissolved in 0.00 ml of sodium ethylate solution.

71.5 V of 2-cyano-2-methyl-hydrazinecarboxylic acid ester is then added dropwise to the solution at 60°C, where the temperature of the solution is raised to 75°C. After the addition is complete, the reaction mixture is refluxed for 5 hours. followed by 30 ml of glacial acetic acid
t is added dropwise to the above solution cooled to room temperature. As a result, the resulting precipitate is separated by filtration, and the solvent in the solution is removed under reduced pressure. After cooling the residue with dry ice, methanol 14077! Recrystallize with l. 1-methyl-5
-Methylthio-3-oxy-1,2,4-triazole 21.8 V (30% of theory) is obtained; melting point 128
~130℃.

Purity: 98%. 2-cyano- required as starting material
2-Methylhydrazinecarboxylic acid ethyl ester is prepared by reacting 2-methylhydrazinecarboxylic acid ethyl ester with cyanogen chloride in a manner similar to that described in Examples 1 and 3.

Claims (1)

[Claims] Primary formula II: R_1-NH-NH-COOR(II) (wherein R_1 has the meaning shown in the following formula I, and R represents an alkyl group having 1 to 4 carbon atoms. The hydrazine carboxylic acid ester represented by (represented by) is first reacted with cyanogen chloride to form the following formula III: ▲ Numerical formula, chemical formula, table, etc. 2-substituted, 2-cyanohydrazinecarboxylic acid ester corresponding to the intermediate product of formula The following formula I, which is characterized by cyclization in an alkaline state in the presence of a compound: ▲ Numerical formulas, chemical formulas, tables, etc. ▼ (I) [In the formula, R_1 is an alkyl group having 1 to 6 carbon atoms or carbon represents a cycloalkyl group having 3 to 8 atoms, R_2
is an alkyl group having 1 to 6 carbon atoms, 3 to 6 carbon atoms
an alkenyl group, a benzyl group or the following substituents:
represents an alkyl, alkoxy or alkylthio group having 1 to 4 carbon atoms, a benzyl group mono- or di-substituted with a halogen atom, a trifluoromethyl group or a nitro group, and X is an oxygen atom, a sulfur atom or a group ▲mathematical formula, chemical formula , tables, etc. ▼ (In the group, R_3 is a carbon atom of 1 to
represents an alkyl group having 6. ). ] 3-oxy-1,2,4-
A method for producing a triazole derivative.